10q26 deletion syndrome https://medlineplus.gov/genetics/condition/10q26-deletion-syndrome description10q26 deletion syndrome is a condition that results from the loss (deletion) of a small piece of chromosome 10 in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated 10q26.The signs and symptoms of 10q26 deletion syndrome vary widely, even among affected members of the same family. Among the more common features associated with this chromosomal change are distinctive facial features, mild to moderate intellectual disability, growth problems, and developmental delay. People with 10q26 deletion syndrome often have delayed development of speech and of motor skills such as sitting, crawling, and walking. Some have limited speech throughout life. Affected individuals may experience seizures, attention-deficit/hyperactivity disorder (ADHD), poor impulse control (impulsivity), or exhibit autistic behaviors that affect communication and social interaction.A range of facial features is seen in people with 10q26 deletion syndrome, but not all affected individuals have these features. Facial features of people with 10q26 deletion syndrome may include a prominent or beaked nose, a broad nasal bridge, a small jaw (micrognathia), malformed ears that are low set, a thin upper lip, and an unusually small head size (microcephaly). Many affected individuals have widely spaced eyes (hypertelorism) that do not look in the same direction (strabismus). Some people with this condition have a short neck with extra folds of skin (webbed neck).Less common signs and symptoms can occur in 10q26 deletion syndrome. Skeletal problems include a spine that curves to the side (scoliosis), limited movement in the elbows or other joints, or curved fifth fingers and toes (clinodactyly). Slow growth before and after birth can also occur in affected individuals. Males with this condition may have genital abnormalities, such as a small penis (micropenis), undescended testes (cryptorchidism), or the urethra opening on the underside of the penis (hypospadias). Some people with 10q26 deletion syndrome have kidney abnormalities, heart defects, breathing problems, recurrent infections, or hearing or vision problems. ad Autosomal dominant 10 https://medlineplus.gov/genetics/chromosome/10 10qter deletion Chromosome 10q26 deletion syndrome Distal 10q deletion syndrome Distal deletion 10q Distal monosomy 10q Monosomy 10qter Telomeric deletion 10 Terminal chromosome 10q26 deletion syndrome GTR C2674937 MeSH D002872 OMIM 609625 SNOMED CT 16129004 SNOMED CT 718687003 2019-09 2020-09-08 15q11-q13 duplication syndrome https://medlineplus.gov/genetics/condition/15q11-q13-duplication-syndrome description15q11-q13 duplication syndrome (dup15q syndrome) is a developmental disorder; its signs and symptoms vary among affected individuals.Poor muscle tone (hypotonia) is common in individuals with dup15q syndrome and contributes to delayed development and impairment of motor skills, including sitting and walking. Most affected children develop the ability to walk independently after age 2 or 3, and they typically have a wide-based or uncoordinated (ataxic) pattern of walking (gait). Babies with dup15q syndrome often have trouble feeding due to weak facial muscles that impair sucking and swallowing.Intellectual disability also occurs in people with dup15q syndrome and can range from mild to profound; however, it is usually in the moderate to severe range. Speech and language development are particularly affected, with some individuals never developing functional speech. Most individuals with this disorder have autism spectrum disorder (ASD), and many have language problems associated with ASD such as repeating the words of others (echolalia) or repeating particular phrases (stereotypical utterances).Behavioral difficulties are also associated with dup15q syndrome, including other features of ASD such as difficulty with changes in routine and problems with social interaction. Affected individuals may also experience hyperactivity, anxiety, and frustration leading to tantrums. Mood disorders and psychosis occur in some affected individuals.More than half of people with dup15q syndrome have recurrent seizures (epilepsy). The seizures usually develop between the ages of 6 months and 9 years. Some people with dup15q syndrome have only focal seizures, which affect one part of the brain and usually do not cause a loss of consciousness. In other affected individuals, seizures begin with a type called infantile spasms (seizures that usually appear before the age of 1 and involve recurrent muscle contractions) and later include other types of seizures. In addition to focal seizures, these can include rapid uncontrolled muscle jerks (myotonic seizures); tonic-clonic (also called grand mal) seizures, which involve rigidity, convulsions, and loss of consciousness; and absence (also known as petit mal) seizures, which are brief episodes of impaired consciousness that look like staring spells. Affected individuals may develop complex, difficult-to-treat (intractable) seizure patterns such as Lennox-Gastaut syndrome. Seizures can lead to falls, loss of developmental milestones (developmental regression), and in a small minority of cases, sudden death during sleep (called sudden unexpected death in epilepsy, or SUDEP).Hearing loss in childhood is common in dup15q syndrome and usually results from ear infections that cause fluid buildup in the middle ear. This hearing loss is often temporary. However, if ear infections are left untreated during early childhood, the hearing loss can interfere with language development and worsen the speech problems associated with dup15q syndrome.About 30 percent of individuals with dup15q syndrome are born with eyes that do not look in the same direction (strabismus). Other unusual facial features that can occur in this condition include a low forehead; outside corners of the eyes that point downward (downslanting palpebral fissures); a flattened nasal bridge with a short, upturned nose; nostrils that open to the front rather than downward (anteverted nares); a long space between the nose and the upper lip (philtrum); a small lower jaw (micrognathia); a high-arched roof of the mouth (palate); full lips; low-set ears; and a flat back of the head (occiput). These features are typically subtle and may not be noticed during infancy.Other problems associated with dup15q syndrome in some affected individuals include a reduced ability to feel pain; a spine that curves to the side (scoliosis); recurrent respiratory infections in childhood; a skin condition called eczema; early (precocious) puberty and, in females, menstrual irregularities; minor genital abnormalities in males such as undescended testes (cryptorchidism); overeating; and excessive weight gain. n Not inherited 15 https://medlineplus.gov/genetics/chromosome/15 Dup15q syndrome Duplication/inversion 15q11 Idic(15) Inv dup(15) Inverted duplication 15 Isodicentric chromosome 15 Isodicentric chromosome 15 syndrome Non-distal tetrasomy 15q GTR C2675336 MeSH D025063 OMIM 608636 SNOMED CT 723332005 2012-09 2020-09-08 15q13.3 microdeletion https://medlineplus.gov/genetics/condition/15q133-microdeletion description15q13.3 microdeletion is a chromosomal change in which a small piece of chromosome 15 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q13.3. This chromosomal change increases the risk of intellectual disability, seizures, behavioral problems, and psychiatric disorders. However, some people with a 15q13.3 microdeletion do not appear to have any associated features.About half of all people with a 15q13.3 microdeletion have learning difficulties or intellectual disability, which is usually mild or moderate. Many of these individuals have delayed speech and language skills. 15q13.3 microdeletion also appears to be a major risk factor for recurrent seizures (epilepsy); about one-third of people with this chromosomal change have epilepsy.15q13.3 microdeletion has also been associated with behavioral problems, including a short attention span, aggression, impulsive behavior, and hyperactivity. Some people with a 15q13.3 microdeletion have been diagnosed with developmental disorders that affect communication and social interaction (autism spectrum disorders). This chromosomal change may also be associated with an increased risk of psychiatric disorders, particularly schizophrenia. Other signs and symptoms of 15q13.3 microdeletion can include heart defects, minor abnormalities involving the hands and arms, and subtle differences in facial features.Some people with a 15q13.3 microdeletion do not have any of the intellectual, behavioral, or physical features described above. In these individuals, the microdeletion is often detected when they undergo genetic testing because they have an affected relative. It is unknown why a 15q13.3 microdeletion causes cognitive and behavioral problems in some individuals but few or no health problems in others. ad Autosomal dominant 15 https://medlineplus.gov/genetics/chromosome/15 15q13.3 microdeletion syndrome Chromosome 15q13.3 deletion syndrome GTR C2677613 MeSH D025063 OMIM 612001 SNOMED CT 699254009 2011-05 2020-09-08 15q24 microdeletion https://medlineplus.gov/genetics/condition/15q24-microdeletion description15q24 microdeletion is a chromosomal change in which a small piece of chromosome 15 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q24.15q24 microdeletion is associated with mild to moderate intellectual disability and delayed speech development. Other common signs and symptoms include short stature, weak muscle tone (hypotonia), and skeletal abnormalities including loose (lax) joints. Affected males may have genital abnormalities, which can include an unusually small penis (micropenis) and the opening of the urethra on the underside of the penis (hypospadias). Affected individuals also have distinctive facial features such as a high front hairline, broad eyebrows, widely set eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), a broad nasal bridge, a full lower lip, and a long, smooth space between the upper lip and nose (philtrum). n Not inherited 15 https://medlineplus.gov/genetics/chromosome/15 15q24 deletion 15q24 microdeletion syndrome Interstitial deletion of chromosome 15q24 GTR C4310804 MeSH D025063 OMIM 613406 SNOMED CT 699308002 2011-09 2020-09-08 16p11.2 deletion syndrome https://medlineplus.gov/genetics/condition/16p112-deletion-syndrome description16p11.2 deletion syndrome is a disorder caused by a deletion of a small piece of chromosome 16. The deletion occurs near the middle of the chromosome at a location designated p11.2.People with 16p11.2 deletion syndrome usually have developmental delay and intellectual disability. Most also have at least some features of autism spectrum disorders. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. In 16p11.2 deletion syndrome, expressive language skills (vocabulary and the production of speech) are generally more severely affected than receptive language skills (the ability to understand speech). Some people with this disorder have recurrent seizures (epilepsy).Some affected individuals have minor physical abnormalities such as low-set ears or partially webbed toes (partial syndactyly). People with this disorder are also at increased risk of obesity compared with the general population. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 deletion syndrome. Signs and symptoms of the disorder vary even among affected members of the same family. Some people with the deletion have no identified physical, intellectual, or behavioral abnormalities. ad Autosomal dominant 16 https://medlineplus.gov/genetics/chromosome/16 Autism, susceptibility to, 14A AUTS14A GTR C3150154 MeSH D025063 OMIM 611913 SNOMED CT 699307007 2009-10 2023-07-13 16p11.2 duplication https://medlineplus.gov/genetics/condition/16p112-duplication description16p11.2 duplication is a chromosomal change in which a small amount of genetic material within chromosome 16 is abnormally copied (duplicated). The duplication occurs near the middle of the chromosome at a location designated p11.2. This duplication can have a variety of effects. Common characteristics that occur in people with a 16p11.2 duplication include a low weight; a small head size (microcephaly); and developmental delay, especially in speech and language. Affected individuals also have an increased risk of behavioral problems. However, some people with the duplication have no identified physical or behavioral abnormalities.Developmental delay and intellectual disability can occur in people with a 16p11.2 duplication. Approximately one-third of children with this condition have delays in developing physical skills such as sitting, crawling, or walking. The average IQ of affected individuals is about 26 points lower than that of their parents without the duplication. About 80 percent of people with a 16p11.2 duplication have problems related to speech or language. Both expressive language skills (vocabulary and the production of speech) and receptive language skills (the ability to understand speech) can be affected.One of the most common behavioral problems associated with this chromosomal change is attention-deficit/hyperactivity disorder (ADHD). Autism spectrum disorder, which affects communication and social skills, is diagnosed in about one in five people with a 16p11.2 duplication. Affected individuals also have an increased risk of mental health problems, including schizophrenia, anxiety, and depression. Recurrent seizures are possible in this condition, although they do not occur in most affected individuals.Other abnormalities that can occur with a 16p11.2 duplication include malformations of the kidneys and urinary tract. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 duplications; signs and symptoms related to the chromosomal change vary even among affected members of the same family. ad Autosomal dominant 16 https://medlineplus.gov/genetics/chromosome/16 16p11.2 duplication syndrome 16p11.2 microduplication Autism, susceptibility to, 14B AUTS14B GTR C3553407 MeSH D025063 OMIM 614671 SNOMED CT 88326002 2014-10 2023-03-23 16p12.2 microdeletion https://medlineplus.gov/genetics/condition/16p122-microdeletion description16p12.2 microdeletion is a chromosomal change in which a small amount of genetic material on chromosome 16 is deleted. The deletion occurs on the short (p) arm of the chromosome at a location designated p12.2. Common characteristics that have been described in people with a 16p12.2 microdeletion include developmental delay, delayed speech, intellectual disability that ranges from mild to profound, weak muscle tone (hypotonia), slow growth resulting in short stature, an usually small head (microcephaly), malformations of the heart, recurrent seizures (epilepsy), and psychiatric and behavioral problems.Less common features that can occur in people with a 16p12.2 microdeletion can include hearing loss, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), dental abnormalities, malformed kidneys, and genital abnormalities in males. However, there is no particular pattern of physical abnormalities that characterizes individuals with a 16p12.2 microdeletion. Signs and symptoms related to the chromosomal change vary even among affected members of the same family, and some people with the deletion have no identified physical or behavioral abnormalities. ad Autosomal dominant 16 https://medlineplus.gov/genetics/chromosome/16 16p12.1 microdeletion Chromosome 16p12.1 deletion syndrome, 520-kb GTR C3149276 MeSH D025063 OMIM 136570 2017-08 2020-09-08 17 alpha-hydroxylase/17,20-lyase deficiency https://medlineplus.gov/genetics/condition/17-alpha-hydroxylase-17-20-lyase-deficiency description17 alpha(α)-hydroxylase/17,20-lyase deficiency is a condition that affects the function of certain hormone-producing glands called the gonads (ovaries in females and testes in males) and the adrenal glands. The gonads direct sexual development before birth and during puberty and are important for reproduction. The adrenal glands, which are located on top of the kidneys, regulate the production of certain hormones, including those that control salt levels in the body. People with 17α-hydroxylase/17,20-lyase deficiency have an imbalance of many of the hormones that are made in these glands. 17α-hydroxylase/17,20-lyase deficiency is one of a group of disorders, known as congenital adrenal hyperplasias, that impair hormone production and disrupt sexual development and maturation.Hormone imbalances lead to the characteristic signs and symptoms of 17α-hydroxylase/17,20-lyase deficiency, which include high blood pressure (hypertension), low levels of potassium in the blood (hypokalemia), and abnormal sexual development. The severity of the features varies. Two forms of the condition are recognized: complete 17α-hydroxylase/17,20-lyase deficiency, which is more severe, and partial 17α-hydroxylase/17,20-lyase deficiency, which is typically less so.Males and females are affected by disruptions to sexual development differently. Females (who have two X chromosomes) with 17α-hydroxylase/17,20-lyase deficiency are born with normal external female genitalia; however, the internal reproductive organs, including the uterus and ovaries, may be underdeveloped. Women with complete 17α-hydroxylase/17,20-lyase deficiency do not develop secondary sex characteristics, such as breasts and pubic hair, and do not menstruate (amenorrhea). Women with partial 17α-hydroxylase/17,20-lyase deficiency may develop some secondary sex characteristics; menstruation is typically irregular or absent. Either form of the disorder results in an inability to conceive a baby (infertility).In affected individuals who are chromosomally male (having an X and a Y chromosome), problems with sexual development lead to abnormalities of the external genitalia. The most severely affected are born with characteristically female external genitalia and are generally raised as females. However, because they do not have female internal reproductive organs, these individuals have amenorrhea and do not develop female secondary sex characteristics. These individuals have testes, but they are abnormally located in the abdomen (undescended). Sometimes, complete 17α-hydroxylase/17,20-lyase deficiency leads to external genitalia that do not look clearly male or clearly female. Males with partial 17α-hydroxylase/17,20-lyase deficiency may have a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), or a scrotum divided into two lobes (bifid scrotum). Males with either complete or partial 17α-hydroxylase/17,20-lyase deficiency are also infertile. ar Autosomal recessive CYP17A1 https://medlineplus.gov/genetics/gene/cyp17a1 17-alpha-hydroxylase deficiency 17-alpha-hydroxylase-deficient congenital adrenal hyperplasia Adrenal hyperplasia V Combined 17 alpha-hydroxylase/17,20-lyase deficiency Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency Congenital adrenal hyperplasia type 5 Deficiency of steroid 17-alpha-monooxygenase GTR C0268285 ICD-10-CM MeSH D000312 OMIM 202110 SNOMED CT 124220008 2016-02 2023-10-27 17-beta hydroxysteroid dehydrogenase 3 deficiency https://medlineplus.gov/genetics/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency description17-beta hydroxysteroid dehydrogenase 3 deficiency is a condition that affects male sexual development. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a male sex hormone (androgen) called testosterone. Testosterone has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth.Most people with 17-beta hydroxysteroid dehydrogenase 3 deficiency are born with external genitalia that appear female. In some cases, the external genitalia do not look clearly male or clearly female. Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis (micropenis) or the urethra opening on the underside of the penis (hypospadias).During puberty, people with this condition develop some male secondary sex characteristics, such as increased muscle mass, deepening of the voice, and development of male pattern facial and body hair. In addition to these changes typical of adolescent boys, some affected individuals may also experience breast enlargement (gynecomastia). Despite having testes, people with this disorder are generally unable to father children (infertile). ar Autosomal recessive HSD17B3 https://medlineplus.gov/genetics/gene/hsd17b3 17-beta hydroxysteroid dehydrogenase III deficiency 17-ketosteroid reductase deficiency of testis 17-KSR deficiency Neutral 17-beta-hydroxysteroid oxidoreductase deficiency Pseudohermaphroditism, male, with gynecomastia Testosterone 17-beta-dehydrogenase deficiency ICD-10-CM MeSH D058490 OMIM 264300 SNOMED CT 50658006 2008-11 2025-01-31 17q12 deletion syndrome https://medlineplus.gov/genetics/condition/17q12-deletion-syndrome description17q12 deletion syndrome is a condition that results from the deletion of a small piece of chromosome 17 in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q12.The signs and symptoms of 17q12 deletion syndrome vary widely, even among affected members of the same family. Among the more common features associated with this chromosomal change are problems with development or function of the kidneys and urinary system. These abnormalities range from very severe malformations, leading to kidney failure before birth, to mild or no problems with kidney and urinary tract function. Fluid-filled sacs (cysts) in the kidneys are particularly common. Many affected individuals also develop a form of diabetes called maturity-onset diabetes of the young type 5 (MODY5), which is caused by a malfunction of certain cells in the pancreas. MODY5 usually appears in adolescence or early adulthood, most often before age 25. The combination of kidney cysts and MODY5 is sometimes referred to as renal cysts and diabetes (RCAD) syndrome.About half of people with 17q12 deletion syndrome have delayed development (particularly speech and language delays), intellectual disability, or behavioral or psychiatric disorders. Neurodevelopmental and psychiatric conditions that have been reported in people with 17q12 deletion syndrome include autism spectrum disorder (which affects social interaction and communication), schizophrenia, anxiety, and bipolar disorder.Less commonly, 17q12 deletion syndrome also causes abnormalities of the eyes, liver, brain, genitalia, and other body systems. Some females with this chromosomal change have Mayer-Rokitansky-Küster-Hauser syndrome, which is characterized by underdevelopment or absence of the vagina and uterus. 17q12 deletion syndrome is also sometimes associated with subtle differences in facial features. ad Autosomal dominant HNF1B https://medlineplus.gov/genetics/gene/hnf1b LHX1 https://medlineplus.gov/genetics/gene/lhx1 17 https://medlineplus.gov/genetics/chromosome/17 17q12 chromosomal microdeletion 17q12 microdeletion 17q12 recurrent deletion syndrome Deletion 17q12 Recurrent genomic rearrangement in chromosome 17q12 GTR C3281138 MeSH D001523 MeSH D002872 MeSH D003920 MeSH D007674 OMIM 614527 SNOMED CT 733519008 2017-04 2023-11-10 17q12 duplication https://medlineplus.gov/genetics/condition/17q12-duplication description17q12 duplication is a chromosomal change in which a small piece of chromosome 17 is copied (duplicated) abnormally in each cell. The duplication occurs on the long (q) arm of the chromosome at a position designated q12.Signs and symptoms related to 17q12 duplications vary significantly, even among members of the same family. Some individuals with the duplication have no apparent signs or symptoms, or the features are very mild. Other individuals can have intellectual disability, delayed development, and a wide range of physical abnormalities.Intellectual and learning ability in people with 17q12 duplications ranges from normal to severely impaired. Many affected individuals have delayed development, particularly involving speech and language skills and gross motor skills such sitting, standing, and walking. Seizures are also common. Neurodevelopmental and psychiatric conditions that have been reported in people with 17q12 duplications include autism spectrum disorder (which affects social interaction and communication), schizophrenia, aggression, and self-injury. About half of affected individuals have an unusually small head (microcephaly).Less commonly, 17q12 duplications have been associated with abnormalities of the eyes, heart, kidneys, and brain. Some individuals with this chromosomal change have subtle differences in facial features, although these are not consistent. ad Autosomal dominant 17 https://medlineplus.gov/genetics/chromosome/17 17q12 duplication syndrome 17q12 microduplication 17q12 microduplication syndrome 17q12 recurrent duplication Chromosome 17q12 duplication syndrome Recurrent duplication of 17q12 GTR C3281137 MeSH D002658 MeSH D008607 MeSH D012640 MeSH D058674 OMIM 614526 2017-04 2023-11-10 19p13.13 deletion syndrome https://medlineplus.gov/genetics/condition/19p1313-deletion-syndrome description19p13.13 deletion syndrome is a condition that results from a chromosomal change in which a small piece of chromosome 19 is deleted in each cell. The deletion occurs on the short (p) arm of the chromosome at a position designated p13.13.Features commonly associated with this chromosomal change include an unusually large head size (macrocephaly), tall stature, and intellectual disability that is usually moderate in severity. Many affected individuals have significantly delayed development, including speech, and children may speak few or no words. Weak muscle tone (hypotonia) and problems with coordinating muscle movement (ataxia) contribute to delays in gross motor skills (such as sitting and walking) and fine motor skills (such as holding a pencil).Other signs and symptoms that can occur with 19p13.13 deletion syndrome include seizures, abnormalities of brain structure, and mild differences in facial features (such as a prominent forehead). Many affected individuals have problems with feeding and digestion, including constipation, diarrhea, vomiting, and abdominal pain. Eye problems that can impair vision are also common. These include eyes that do not point in the same direction (strabismus) and underdevelopment of the optic nerves, which carry visual information from the eyes to the brain.The signs and symptoms of 19p13.13 deletion syndrome vary among affected individuals. In part, this variation occurs because the size of the deletion, and the number of genes it affects, varies from person to person. n Not inherited CACNA1A https://medlineplus.gov/genetics/gene/cacna1a CALR https://medlineplus.gov/genetics/gene/calr NFIX https://www.ncbi.nlm.nih.gov/gene/4784 MAST1 https://www.ncbi.nlm.nih.gov/gene/22983 BEST2 https://www.ncbi.nlm.nih.gov/gene/54831 19 https://medlineplus.gov/genetics/chromosome/19 19p13.13 microdeletion 19p13.13 microdeletion syndrome Chromosome 19p13.13 deletion syndrome GTR C3150894 MeSH D025063 OMIM 613638 2016-06 2020-09-08 1p36 deletion syndrome https://medlineplus.gov/genetics/condition/1p36-deletion-syndrome description1p36 deletion syndrome is a disorder that typically causes intellectual disabilities. Most affected individuals do not speak or speak only a few words. They may have temper tantrums, bite themselves, or exhibit other behavior problems. Most have structural abnormalities of the brain, and seizures occur in more than half of individuals with this disorder. Affected individuals usually have weak muscle tone (hypotonia) and difficulty swallowing (dysphagia).People with 1p36 deletion syndrome have a small head that is also unusually short and wide in proportion to its size (microbrachycephaly). Affected individuals also have distinctive facial features, including deep-set eyes with straight eyebrows; a sunken appearance of the middle of the face (midface hypoplasia); a broad, flat nose; a long area between the nose and mouth (philtrum); a pointed chin; and ears that are low-set, rotated backwards, and abnormally shaped.People with 1p36 deletion syndrome often have unusually short fingers and toes (brachydactyly), permanently bent fingers and toes (camptodactyly), and short feet. They may also have vision or hearing problems. Some affected individuals have abnormalities of the skeleton, heart, gastrointestinal system, kidneys, or genitalia. Life expectancy varies in people with 1p36 deletion syndrome, but affected individuals can survive into early adulthood. n Not inherited SKI https://medlineplus.gov/genetics/gene/ski MTOR https://medlineplus.gov/genetics/gene/mtor RERE https://www.ncbi.nlm.nih.gov/gene/473 CDC42 https://www.ncbi.nlm.nih.gov/gene/998 ECE1 https://www.ncbi.nlm.nih.gov/gene/1889 GABRD https://www.ncbi.nlm.nih.gov/gene/2563 GNB1 https://www.ncbi.nlm.nih.gov/gene/2782 KCNAB2 https://www.ncbi.nlm.nih.gov/gene/8514 PRDM16 https://www.ncbi.nlm.nih.gov/gene/63976 1 https://medlineplus.gov/genetics/chromosome/1 Chromosome 1p36 deletion syndrome Distal monosomy 1p36 Monosomy 1p36 syndrome GTR C1842870 MeSH D025063 OMIM 607872 SNOMED CT 699306003 2024-03 2024-03-15 1q21.1 microdeletion https://medlineplus.gov/genetics/condition/1q211-microdeletion description1q21.1 microdeletion is a chromosomal change in which a small piece of chromosome 1 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome in a region designated q21.1. This chromosomal change increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems. However, some people with a 1q21.1 microdeletion do not appear to have any associated features.About 75 percent of all children with a 1q21.1 microdeletion have delayed development, particularly affecting the development of motor skills such as sitting, standing, and walking. The intellectual disability and learning problems associated with this genetic change are usually mild.Distinctive facial features can also be associated with 1q21.1 microdeletions. The changes are usually subtle and can include a prominent forehead; a large, rounded nasal tip; a long space between the nose and upper lip (philtrum); and a high, arched roof of the mouth (palate). Other common signs and symptoms of 1q21.1 microdeletions include an unusually small head (microcephaly), short stature, and eye problems such as clouding of the lenses (cataracts). Less frequently, 1q21.1 microdeletions are associated with heart defects, abnormalities of the genitalia or urinary system, bone abnormalities (particularly in the hands and feet), and hearing loss.Neurological problems that have been reported in people with a 1q21.1 microdeletion include seizures and weak muscle tone (hypotonia). Psychiatric or behavioral problems affect a small percentage of people with this genetic change. These include developmental conditions called autism spectrum disorders that affect communication and social interaction, attention-deficit/hyperactivity disorder (ADHD), and sleep disturbances. Studies suggest that deletions of genetic material from the 1q21.1 region may also be risk factors for schizophrenia.Some people with a 1q21.1 microdeletion do not have any of the intellectual, physical, or psychiatric features described above. In these individuals, the microdeletion is often detected when they undergo genetic testing because they have a relative with the chromosomal change. It is unknown why 1q21.1 microdeletions cause cognitive and physical changes in some individuals but few or no health problems in others, even within the same family. ad Autosomal dominant 1 https://medlineplus.gov/genetics/chromosome/1 BCL9 https://www.ncbi.nlm.nih.gov/gene/607 FMO5 https://www.ncbi.nlm.nih.gov/gene/2330 GJA5 https://www.ncbi.nlm.nih.gov/gene/2702 GJA8 https://www.ncbi.nlm.nih.gov/gene/2703 PRKAB2 https://www.ncbi.nlm.nih.gov/gene/5565 CHD1L https://www.ncbi.nlm.nih.gov/gene/9557 ACP6 https://www.ncbi.nlm.nih.gov/gene/51205 GPHRB https://www.ncbi.nlm.nih.gov/gene/51463 HYDIN https://www.ncbi.nlm.nih.gov/gene/54768 1q21.1 contiguous gene deletion 1q21.1 deletion Chromosome 1q21.1 deletion syndrome Chromosome 1q21.1 deletion syndrome, 1.35-Mb GTR C2675897 MeSH D025063 OMIM 612474 SNOMED CT 699305004 2012-10 2020-09-08 1q21.1 microduplication https://medlineplus.gov/genetics/condition/1q211-microduplication description1q21.1 microduplication is a chromosomal change in which a small amount of genetic material on chromosome 1 is abnormally copied (duplicated). The duplication occurs on the long (q) arm of the chromosome at a location designated q21.1.Some people with a 1q21.1 microduplication have developmental delay and intellectual disability that is typically mild to moderate. Individuals with this condition can also have features of autism spectrum disorder. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. Expressive language skills (vocabulary and the production of speech) tend to be more impaired than receptive language skills (the ability to understand speech) in affected individuals. In childhood, 1q21.1 microduplications may also be associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) and other behavioral problems. Psychiatric disorders such as schizophrenia or mood disorders such as anxiety or depression occur in some affected individuals, usually during adulthood. Rarely, recurrent seizures (epilepsy) occur in people with a 1q21.1 microduplication.Some individuals with a 1q21.1 microduplication are born with malformations of the heart, including a particular combination of heart defects known as tetralogy of Fallot. Less commonly, other physical malformations such as the urethra opening on the underside of the penis (hypospadias) in males, inward- and upward-turning feet (clubfeet), or misalignment of the hip joint (hip dysplasia) are present at birth. Individuals with a 1q21.1 microduplication may also have a larger than average head size or taller than average adult stature. Some have slightly unusual facial features such as wide-set eyes or low-set ears. As adults, individuals with a 1q21.1 microduplication may be prone to develop cysts, swollen and knotted (varicose) veins, or carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. However, there is no particular pattern of physical abnormalities that characterizes 1q21.1 microduplications. Signs and symptoms related to the chromosomal change vary even among affected members of the same family. Some people with the duplication have no identified physical, intellectual, or behavioral abnormalities. ad Autosomal dominant 1 https://medlineplus.gov/genetics/chromosome/1 1q21.1 duplication 1q21.1 duplication syndrome GTR C2675891 MeSH D025063 OMIM 612475 SNOMED CT 79649006 2014-11 2023-02-01 2-hydroxyglutaric aciduria https://medlineplus.gov/genetics/condition/2-hydroxyglutaric-aciduria description2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA).The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. Researchers have described two subtypes of D-2-HGA, type I and type II. The two subtypes are distinguished by their genetic cause and pattern of inheritance, although they also have some differences in signs and symptoms. Type II tends to begin earlier and often causes more severe health problems than type I. Type II may also be associated with a weakened and enlarged heart (cardiomyopathy), a feature that is typically not found with type I.L-2-HGA particularly affects a region of the brain called the cerebellum, which is involved in coordinating movements. As a result, many affected individuals have problems with balance and muscle coordination (ataxia). Additional features of L-2-HGA can include delayed development, seizures, speech difficulties, and an unusually large head (macrocephaly). Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood.Combined D,L-2-HGA causes severe brain abnormalities that become apparent in early infancy. Affected infants have severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. They usually survive only into infancy or early childhood. ar Autosomal recessive ad Autosomal dominant L2HGDH https://medlineplus.gov/genetics/gene/l2hgdh D2HGDH https://medlineplus.gov/genetics/gene/d2hgdh IDH2 https://medlineplus.gov/genetics/gene/idh2 SLC25A1 https://medlineplus.gov/genetics/gene/slc25a1 2-HGA GTR C1855995 GTR C2746066 GTR C3150909 GTR C3152055 MeSH D020739 OMIM 236792 OMIM 600721 OMIM 613657 OMIM 615182 SNOMED CT 237960000 SNOMED CT 237961001 SNOMED CT 698870008 2013-08 2020-08-18 21-hydroxylase deficiency https://medlineplus.gov/genetics/condition/21-hydroxylase-deficiency description21-hydroxylase deficiency is an inherited disorder that affects the adrenal glands. The adrenal glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with 21-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones.There are three types of 21-hydroxylase deficiency. Two types are classic forms, known as the salt-wasting and simple virilizing types. The third type is called the non-classic type. The salt-wasting type is the most severe, the simple virilizing type is less severe, and the non-classic type is the least severe form.Males and females with either classic form of 21-hydroxylase deficiency tend to have an early growth spurt, but their final adult height is usually shorter than others in their family. Additionally, affected individuals may have a reduced ability to have biological children (decreased fertility). Females may also develop excessive body hair growth (hirsutism), male pattern baldness, and irregular menstruation.Approximately 75 percent of individuals with classic 21-hydroxylase deficiency have the salt-wasting type. Hormone production is extremely low in this form of the disorder. Affected individuals lose large amounts of sodium in their urine, which can be life-threatening in early infancy. Babies with the salt-wasting type can experience poor feeding, weight loss, dehydration, and vomiting. Individuals with the simple virilizing form do not experience salt loss.In both the salt-wasting and simple virilizing forms of this disorder, females typically have external genitalia that do not look clearly male or female. Males usually have male-typical genitalia but the testes may be small.Females with the non-classic type of 21-hydroxylase deficiency have female-typical genitalia. As affected females get older, they may experience hirsutism, male pattern baldness, irregular menstruation, and decreased fertility. Males with the non-classic type may have early beard growth and small testes. Some individuals with this type of 21-hydroxylase deficiency have no symptoms of the disorder. ar Autosomal recessive CYP21A2 https://medlineplus.gov/genetics/gene/cyp21a2 CAH1 Congenital adrenal hyperplasia 1 Congenital adrenal hyperplasia due to 21 hydroxylase deficiency CYP21 deficiency GTR C1859995 GTR C2936858 ICD-10-CM E25.0 MeSH D000312 OMIM 201910 SNOMED CT 124221007 SNOMED CT 237753002 SNOMED CT 52604008 SNOMED CT 71578002 SNOMED CT 717261006 SNOMED CT 840509001 2010-01 2024-10-02 22q11.2 deletion syndrome https://medlineplus.gov/genetics/condition/22q112-deletion-syndrome description22q11.2 deletion syndrome (which is also known by several other names, listed below) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2.22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. The features of this syndrome vary widely, even among affected members of the same family. People with 22q11.2 deletion syndrome commonly have heart abnormalities that are often present from birth, recurrent infections caused by problems with the immune system, and distinctive facial features. In affected individuals, the muscles that form the roof of the mouth (palate) may not close completely, even though the tissue covering them does, resulting in a condition called submucosal cleft palate. The abnormal palate is often highly arched and there may be a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula). Submucosal cleft palate can also interfere with normal speech by causing air to come out of the nose during speech, leading to nasal-sounding speech. Affected individuals may also have breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild short stature and, less frequently, abnormalities of the spinal bones.Many children with 22q11.2 deletion syndrome have developmental delays, including delayed growth and speech development, and some have mild intellectual disability or learning disabilities. Older affected individuals have difficulty reading, performing tasks involving math, and problem solving. Children with this condition often need help changing and adapting their behaviors when responding to situations. Additionally, affected children are more likely than children without 22q11.2 deletion syndrome to have attention-deficit/hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorder that affect communication and social interaction.Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with the autosomal dominant form of Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause. ad Autosomal dominant TBX1 https://medlineplus.gov/genetics/gene/tbx1 COMT https://medlineplus.gov/genetics/gene/comt 22 https://medlineplus.gov/genetics/chromosome/22 22q11.2DS Autosomal dominant Opitz G/BBB syndrome CATCH22 Cayler cardiofacial syndrome Conotruncal anomaly face syndrome (CTAF) Deletion 22q11.2 syndrome DiGeorge syndrome Sedlackova syndrome Shprintzen syndrome VCFS Velo-cardio-facial syndrome Velocardiofacial syndrome GTR C0012236 GTR C0220704 GTR CN032444 ICD-10-CM D82.1 ICD-10-CM Q93.81 MeSH D004062 OMIM 145420 OMIM 188400 OMIM 192430 SNOMED CT 449818005 SNOMED CT 77128003 SNOMED CT 83092002 2007-09 2023-08-23 22q11.2 duplication https://medlineplus.gov/genetics/condition/22q112-duplication description22q11.2 duplication is a condition caused by an extra copy of a small piece of chromosome 22. The duplication occurs near the middle of the chromosome at a location designated q11.2.The features of this condition vary widely, even among members of the same family. Affected individuals may have developmental delay, intellectual disability, slow growth leading to short stature, and weak muscle tone (hypotonia). Many people with the duplication have no apparent physical or intellectual disabilities. ad Autosomal dominant 22 https://medlineplus.gov/genetics/chromosome/22 Chromosome 22q11.2 duplication syndrome Chromosome 22q11.2 microduplication syndrome GTR C2675369 MeSH D025063 OMIM 608363 SNOMED CT 699311001 2009-11 2020-09-08 22q13.3 deletion syndrome https://medlineplus.gov/genetics/condition/22q133-deletion-syndrome description22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome, is a disorder caused by the loss of a small piece of chromosome 22. The deletion occurs near the end of the chromosome at a location designated q13.3.The features of 22q13.3 deletion syndrome vary widely and involve many parts of the body. Characteristic signs and symptoms include developmental delay, moderate to profound intellectual disability, decreased muscle tone (hypotonia), and absent or delayed speech. Some people with this condition have autism spectrum disorder or autistic-like characteristics that affects communication and social interaction, such as poor eye contact, sensitivity to touch, and aggression. They may also chew on non-food items such as clothing. Less frequently, people with this condition have seizures or lose skills they had already acquired (developmental regression).Individuals with 22q13.3 deletion syndrome tend to have a decreased sensitivity to pain. Many also have a reduced ability to sweat, which can lead to a greater risk of overheating and dehydration. Some people with this condition have episodes of frequent vomiting and nausea (cyclic vomiting) and backflow of stomach acids into the esophagus (gastroesophageal reflux).People with 22q13.3 deletion syndrome typically have distinctive facial features, including a long, narrow head; prominent ears; a pointed chin; droopy eyelids (ptosis); and deep-set eyes. Other physical features seen with this condition include large and fleshy hands and/or feet, a fusion of the second and third toes (syndactyly), and small or abnormal toenails. Some affected individuals have rapid (accelerated) growth. ad Autosomal dominant SHANK3 https://medlineplus.gov/genetics/gene/shank3 22 https://medlineplus.gov/genetics/chromosome/22 22q13 deletion syndrome Deletion 22q13 syndrome Deletion 22q13.3 syndrome Monosomy 22q13 Phelan-McDermid syndrome GTR C1853490 MeSH D025063 OMIM 606232 SNOMED CT 699310000 2009-09 2023-07-13 2q37 deletion syndrome https://medlineplus.gov/genetics/condition/2q37-deletion-syndrome description2q37 deletion syndrome is a condition that can affect many parts of the body. Most babies with 2q37 deletion syndrome are born with weak muscle tone (hypotonia), which usually improves with age. Other neurological abnormalities that are common in affected individuals include mild to severe intellectual disability; delayed development of motor skills, such as sitting and walking; and behavioral problems. About 25 percent of people with this condition have autism spectrum disorder, a developmental condition that affects communication and social interaction.Unusual physical features are also common in people with 2q37 deletion syndrome. About half of affected individuals have unusually short fingers and toes (brachydactyly), often with abnormally short fourth toes that may overlap the other toes. Additional features of this condition may include short stature, obesity, or sparse hair. Many people with 2q37 deletion syndrome have characteristic facial features that can include a prominent forehead, a low frontal hairline, thin eyelids, skin folds covering the inner corner of the eyes (epicanthal folds), outside corners of the eyes that point upward (upslanting palpebral fissures), a small nose, a small mouth with thin lips, a smooth space between the upper lip and nose (smooth philtrum), prominent cheekbones, a large chin, and minor ear abnormalities.Other features of 2q37 deletion syndrome can include seizures and an inflammatory skin disorder called eczema. Some affected individuals have malformations of the brain, heart, gastrointestinal system, kidneys, or genitalia. A few people with 2q37 deletion syndrome develop a rare form of kidney cancer called Wilms tumor. n Not inherited ad Autosomal dominant HDAC4 https://medlineplus.gov/genetics/gene/hdac4 2 https://medlineplus.gov/genetics/chromosome/2 2q37 microdeletion syndrome Albright hereditary osteodystrophy-like syndrome Brachydactyly-mental retardation syndrome Chromosome 2q37 deletion syndrome (disorder) Deletion 2q37 Monosomy 2q37 GTR C2931817 MeSH D025063 OMIM 600430 SNOMED CT 702357000 2018-10 2020-09-08 3-M syndrome https://medlineplus.gov/genetics/condition/3-m-syndrome description3-M syndrome is a disorder that causes skeletal abnormalities including short stature (dwarfism) and unusual facial features. The name of this condition comes from the initials of three researchers who first identified it: Miller, McKusick, and Malvaux.Individuals with 3-M syndrome grow extremely slowly before birth, and this slow growth continues throughout childhood and adolescence. They have low birth weight and length and remain much smaller than others in their family, growing to an adult height of approximately 4 feet to 4 feet 6 inches (120 centimeters to 130 centimeters). In some affected individuals, the head is normal-sized but looks disproportionately large in comparison with the body. In other people with this disorder, the head has an unusually long and narrow shape (dolichocephaly). Intelligence is unaffected by 3-M syndrome, and life expectancy is generally normal.In addition to short stature, people with 3-M syndrome have a triangle-shaped face with a broad, prominent forehead (frontal bossing) and a pointed chin; the middle of the face is less prominent (hypoplastic midface). Other common features include large ears, full eyebrows, an upturned nose with a fleshy tip, a long area between the nose and mouth (philtrum), a prominent mouth, and full lips.Other skeletal abnormalities that often occur in this disorder include a short, broad neck and chest; prominent shoulder blades; and shoulders that slope less than usual (square shoulders). Affected individuals may have abnormal spinal curvature such as a rounded upper back that also curves to the side (kyphoscoliosis) or exaggerated curvature of the lower back (hyperlordosis). People with 3-M syndrome can also have unusual curving of the fingers (clinodactyly), short fifth (pinky) fingers, prominent heels, and loose joints. Additional skeletal abnormalities, such as unusually slender long bones in the arms and legs; tall, narrow spinal bones (vertebrae); or slightly delayed bone age may be apparent in x-ray images.A variant of 3-M syndrome called Yakut short stature syndrome has been identified in the isolated Yakut population in the Russian province of Siberia. In addition to having most of the physical features characteristic of 3-M syndrome, people with this form of the disorder are often born with breathing problems that can be life-threatening in infancy. ar Autosomal recessive CUL7 https://medlineplus.gov/genetics/gene/cul7 OBSL1 https://medlineplus.gov/genetics/gene/obsl1 CCDC8 https://www.ncbi.nlm.nih.gov/gene/83987 3-MSBN Dolichospondylic dysplasia Le Merrer syndrome Three M syndrome Three-M slender-boned nanism Yakut short stature syndrome GTR C1848862 MeSH D004392 OMIM 273750 OMIM 612921 OMIM 614205 SNOMED CT 702342007 2018-06 2023-08-17 3-beta-hydroxysteroid dehydrogenase deficiency https://medlineplus.gov/genetics/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency description3-beta (β)-hydroxysteroid dehydrogenase (HSD) deficiency is an inherited disorder that affects hormone-producing glands including the gonads (ovaries in females and testes in males) and the adrenal glands. The gonads direct sexual development before birth and during puberty. The adrenal glands, which are located on top of the kidneys, regulate the production of certain hormones and control salt levels in the body. People with 3β-HSD deficiency lack many of the hormones that are made in these glands. 3β-HSD deficiency is one of a group of disorders known as congenital adrenal hyperplasias that impair hormone production and disrupt sexual development and maturation.There are three types of 3β-HSD deficiency: the salt-wasting, non-salt-wasting, and non-classic types. In the salt-wasting type, hormone production is extremely low. Individuals with this type lose large amounts of sodium in their urine, which can be life-threatening. Individuals affected with the salt-wasting type are usually diagnosed soon after birth due to complications related to a lack of salt reabsorption, including dehydration, poor feeding, and vomiting. People with the non-salt-wasting type of 3β-HSD deficiency produce enough hormone to allow sodium reabsorption in the kidneys. Individuals with the non-classic type have the mildest symptoms and do not experience salt wasting.In males with any type of 3β-HSD deficiency, problems with male sex hormones lead to abnormalities of the external genitalia. These abnormalities range from having the opening of the urethra on the underside of the penis (hypospadias) to having external genitalia that do not look clearly male or female. The severity of the genital abnormality does not consistently depend on the type of the condition. Because of the hormone dysfunction in the testes, males with 3β-HSD deficiency are frequently unable to have biological children (infertile).Females with 3β-HSD deficiency may have slight abnormalities of the external genitalia at birth. Females affected with the non-salt-wasting or non-classic types are typically not diagnosed until mid-childhood or puberty, when they may experience irregular menstruation, premature pubic hair growth, and excessive body hair growth (hirsutism). Females with 3β-HSD deficiency have difficulty conceiving a child (impaired fertility). ar Autosomal recessive HSD3B2 https://medlineplus.gov/genetics/gene/hsd3b2 3 beta-HSD deficiency 3 beta-ol dehydrogenase deficiency 3-beta–hydroxysteroid dehydrogenase deficiency 3b-hydroxysteroid dehydrogenase deficiency 3β-HSD deficiency 3β-HSD deficiency congenital adrenal hyperplasia 3β-hydroxysteroid dehydrogenase deficiency Type II 3β-hydroxysteroid dehydrogenase deficiency GTR C0342471 ICD-10-CM E25.0 MeSH D000312 OMIM 201810 SNOMED CT 124136000 SNOMED CT 54470008 2010-02 2023-10-27 3-hydroxy-3-methylglutaryl-CoA lyase deficiency https://medlineplus.gov/genetics/condition/3-hydroxy-3-methylglutaryl-coa-lyase-deficiency description3-hydroxy-3-methylglutaryl-CoA lyase deficiency (also known as HMG-CoA lyase deficiency) is an uncommon inherited disorder in which the body cannot process a particular protein building block (amino acid) called leucine. Additionally, the disorder prevents the body from making ketones, which are compounds that are used for energy during periods without food (fasting).The signs and symptoms of HMG-CoA lyase deficiency usually appear within the first year of life. The condition causes episodes of vomiting, diarrhea, dehydration, extreme tiredness (lethargy), and weak muscle tone (hypotonia). During an episode, blood sugar (glucose) levels can become dangerously low (hypoglycemia), and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If untreated, the disorder can lead to breathing problems, convulsions, coma, and death. Episodes are often triggered by an infection, fasting, strenuous exercise, or other types of stress.HMG-CoA lyase deficiency is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. ar Autosomal recessive HMGCL https://medlineplus.gov/genetics/gene/hmgcl 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency 3-OH 3-CH3 glutaric aciduria 3-OH 3-methyl glutaric aciduria 3HMG Deficiency of hydroxymethylglutaryl-CoA lyase HMG HMG-CoA lyase deficiency Hydroxymethylglutaric aciduria GTR C1533587 MeSH D000592 OMIM 246450 SNOMED CT 124611007 SNOMED CT 410059004 2008-10 2023-07-26 3-hydroxyacyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/3-hydroxyacyl-coa-dehydrogenase-deficiency description3-hydroxyacyl-CoA dehydrogenase deficiency is an inherited condition that prevents the body from converting certain fats to energy, particularly during prolonged periods without food (fasting).Initial signs and symptoms of this disorder typically occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, and lack of energy (lethargy). Affected individuals can also have muscle weakness (hypotonia), liver problems, low blood glucose (hypoglycemia), and abnormally high levels of insulin (hyperinsulinism). Insulin controls the amount of glucose that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-CoA dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden death. This condition may explain some cases of sudden infant death syndrome (SIDS), which is defined as unexplained death in babies younger than 1 year.Problems related to 3-hydroxyacyl-CoA dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. ar Autosomal recessive HADH https://medlineplus.gov/genetics/gene/hadh 3-alpha-hydroxyacyl-coenzyme A dehydrogenase deficiency 3-hydroxyacyl-coenzyme A dehydrogenase deficiency Deficiency of 3-hydroxyacyl-CoA dehydrogenase HAD deficiency HADH deficiency HADHSC deficiency L-3-alpha-hydroxyacyl-CoA dehydrogenase, short chain, deficiency M/SCHAD deficiency SCHAD deficiency GTR C1291230 MeSH D008052 OMIM 231530 SNOMED CT 124122005 2010-04 2023-07-26 3-methylcrotonyl-CoA carboxylase deficiency https://medlineplus.gov/genetics/condition/3-methylcrotonyl-coa-carboxylase-deficiency description3-methylcrotonyl-CoA carboxylase deficiency (also called MCC deficiency) is an inherited disorder in which the body is unable to process certain proteins. People with this disorder have a shortage of an enzyme that helps break down proteins that contain a particular building block (amino acid) called leucine.The signs and symptoms of MCC deficiency can vary among individuals, even among individuals in the same family. Some people with the genetic changes that cause MCC deficiency will not develop symptoms until adulthood, while many will never develop signs or symptoms.Some affected individuals develop signs and symptoms in infancy or early childhood after an event such as an infection, a long period without food, or the introduction of a high-protein diet. Features of MCC deficiency may include feeding difficulties, delayed development, vomiting, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, MCC deficiency can lead to seizures; breathing difficulties; and comas, which can be life-threatening. ar Autosomal recessive MCCC1 https://medlineplus.gov/genetics/gene/mccc1 MCCC2 https://medlineplus.gov/genetics/gene/mccc2 3-MCC deficiency 3-methylcrotonylglycinuria BMCC deficiency Deficiency of methylcrotonoyl-CoA carboxylase MCC deficiency MCCD Methylcrotonyl-CoA carboxylase deficiency Methylcrotonyl-coenzyme A carboxylase deficiency GTR C1859499 GTR No longer reported ICD-10-CM MeSH D008661 OMIM 210200 OMIM 210210 SNOMED CT 13144005 2024-03 2024-04-01 3-methylglutaconyl-CoA hydratase deficiency https://medlineplus.gov/genetics/condition/3-methylglutaconyl-coa-hydratase-deficiency description3-methylglutaconyl-CoA hydratase deficiency is an inherited condition that causes neurological problems. Beginning in infancy to early childhood, children with this condition often have delayed development of mental and motor skills (psychomotor delay), speech delay, involuntary muscle cramping (dystonia), and spasms and weakness of the arms and legs (spastic quadriparesis). Affected individuals can also have optic atrophy, which is the breakdown (atrophy) of nerve cells that carry visual information from the eyes to the brain.In some cases, signs and symptoms of 3-methylglutaconyl-CoA hydratase deficiency begin in adulthood, often in a person's twenties or thirties. These individuals have damage to a type of brain tissue called white matter (leukoencephalopathy). This damage likely contributes to progressive problems with speech (dysarthria), difficulty coordinating movements (ataxia), stiffness (spasticity), optic atrophy, and a decline in intellectual function (dementia).Affected individuals who show symptoms of 3-methylglutaconyl-CoA hydratase deficiency in childhood often go on to develop leukoencephalopathy and other neurological problems in adulthood.All people with 3-methylglutaconyl-CoA hydratase deficiency accumulate large amounts of a substance called 3-methylglutaconic acid in their body fluids. As a result, they have elevated levels of acid in their blood (metabolic acidosis) and excrete large amounts of acid in their urine (aciduria). 3-methylglutaconyl-CoA hydratase deficiency is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with 3-methylglutaconyl-CoA hydratase deficiency also have high urine levels of another acid called 3-methylglutaric acid. ar Autosomal recessive AUH https://medlineplus.gov/genetics/gene/auh 3-methylglutaconic aciduria, type I 3-MG-CoA-hydratase deficiency AUH defect MGA, type I MGA1 MGCA1 Primary 3-methylglutaconic aciduria GTR C0342727 ICD-10-CM E71.111 MeSH D000592 OMIM 250950 SNOMED CT 237951008 2014-06 2021-05-17 3MC syndrome https://medlineplus.gov/genetics/condition/3mc-syndrome description3MC syndrome is a disorder characterized by unusual facial features and problems affecting other tissues and organs.The distinctive facial features of people with 3MC syndrome include widely spaced eyes (hypertelorism), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), highly arched eyebrows, and an opening in the upper lip (cleft lip) with an opening in the roof of the mouth (cleft palate).Other common features of 3MC syndrome include developmental delay, intellectual disability, hearing loss, and slow growth after birth resulting in short stature. Less often, individuals with 3MC syndrome can have abnormal fusion of certain bones in the skull (craniosynostosis) or forearm (radioulnar synostosis); an outgrowth of the tailbone (caudal appendage); a soft out-pouching around the belly-button (an umbilical hernia); and abnormalities of the kidneys, bladder, or genitals.3MC syndrome encompasses four disorders that were formerly considered to be separate: Mingarelli, Malpeuch, Michels, and Carnevale syndromes. Researchers now generally consider these disorders to be part of the same condition, which is called 3MC based on the initials of the older condition names. ar Autosomal recessive COLEC11 https://medlineplus.gov/genetics/gene/colec11 MASP1 https://medlineplus.gov/genetics/gene/masp1 COLEC10 https://medlineplus.gov/genetics/gene/colec10 Carnevale syndrome Carnevale-Krajewska-Fischetto syndrome Craniofacial-ulnar-renal syndrome Craniosynostosis with lid anomalies Malpuech facial clefting syndrome Malpuech syndrome Michels syndrome Mingarelli syndrome Oculo-skeletal-abdominal syndrome Oculopalatoskeletal syndrome OSA syndrome Ptosis of eyelids with diastasis recti and hip dysplasia Ptosis-strabismus-rectus abdominis diastasis GTR C0796032 GTR C0796059 GTR C0796279 MeSH D019465 OMIM 248340 OMIM 257920 OMIM 265050 SNOMED CT 720756005 2018-07 2020-08-18 3p deletion syndrome https://medlineplus.gov/genetics/condition/3p-deletion-syndrome description3p deletion syndrome is a condition that results from a chromosomal change in which a small piece of chromosome 3 is deleted in each cell. The deletion occurs at the end of the short (p) arm of the chromosome. This chromosomal change often leads to intellectual disability, developmental delay, and abnormal physical features.Individuals with 3p deletion syndrome typically have severe to profound intellectual disability. Most have delayed development of language skills as well as motor skills such as crawling and walking. While affected individuals learn to walk in childhood, their language ability usually remains limited. Some individuals with 3p deletion syndrome have obsessive-compulsive disorder (OCD) or features of autism spectrum disorders, which are conditions characterized by impaired communication and social interaction.The physical signs and symptoms of 3p deletion syndrome vary greatly. Many affected individuals have slow growth, an abnormally small head (microcephaly), a small jaw (micrognathia), droopy eyelids (ptosis), malformed ears or nose, and widely spaced eyes (hypertelorism). Other frequent features include skin folds covering the inner corner of the eyes (epicanthal folds), extra fingers or toes (polydactyly), and an opening in the roof of the mouth (cleft palate). Additionally, individuals with 3p deletion syndrome may have seizures, weak muscle tone (hypotonia), intestinal abnormalities, or congenital heart defects. n Not inherited 3 https://medlineplus.gov/genetics/chromosome/3 3p partial monosomy syndrome 3p- syndrome Chromosome 3, deletion 3p Chromosome 3, monosomy 3p Chromosome 3p deletion syndrome Del(3p) syndrome Deletion 3p Monosomy 3p Partial monosomy 3p GTR C4706503 MeSH D002872 OMIM 613792 SNOMED CT 449819002 2016-06 2020-09-08 3q29 microdeletion syndrome https://medlineplus.gov/genetics/condition/3q29-microdeletion-syndrome description3q29 microdeletion syndrome (also known as 3q29 deletion syndrome) is a condition that results from the deletion of a small piece of chromosome 3 in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q29.The features associated with 3q29 microdeletion syndrome vary widely. Some individuals with this chromosomal change have very mild or no related signs and symptoms, and the deletion is discovered through genetic testing only after a family member is diagnosed. However, most people with a 3q29 microdeletion have delayed development (particularly speech delay) and mild or moderate intellectual disability. They also have an increased risk of neurodevelopmental or psychiatric disorders, including autism spectrum disorder (which affects social interaction and communication), anxiety, bipolar disorder, and schizophrenia.Infants with 3q29 microdeletion syndrome often have feeding difficulties and do not grow and gain weight at the expected rate (which is described as failure to thrive). Weak muscle tone (hypotonia), recurrent ear infections, an unusually small head (microcephaly), and yellowing of the skin and whites of the eyes (jaundice) can also occur. Some affected babies are born with a heart defect, most commonly an abnormal connection between two major arteries called patent ductus arteriosus (PDA).Other possible features of 3q29 microdeletion syndrome include gastrointestinal disorders, such as a backflow of acidic stomach contents into the esophagus (gastroesophageal reflux), and abnormalities of the teeth. There may also be a subtle pattern of characteristic facial features, including a long, narrow face; a narrow space between the nose and upper lip (short philtrum); a high bridge of the nose; and large ears. ad Autosomal dominant 3 https://medlineplus.gov/genetics/chromosome/3 3q subtelomere deletion syndrome 3q29 deletion syndrome 3q29 recurrent deletion Chromosome 3q29 deletion syndrome Microdeletion 3q29 syndrome Monosomy 3q29 GTR C2674949 MeSH D002872 MeSH D008607 OMIM 609425 SNOMED CT 716456000 2017-08 2023-08-02 3q29 microduplication syndrome https://medlineplus.gov/genetics/condition/3q29-microduplication-syndrome description3q29 microduplication syndrome (also known as 3q29 duplication syndrome) is a condition that results from the copying (duplication) of a small piece of chromosome 3 in each cell. The duplication occurs on the long (q) arm of the chromosome at a position designated q29.The features associated with 3q29 microduplication syndrome vary widely. Some individuals with this chromosomal change have very mild or no related signs and symptoms, and the duplication is discovered because they undergo genetic testing only after a family member is diagnosed. Other people with a 3q29 microduplication have delayed development (particularly speech delay) and intellectual disability or learning difficulties. Although most affected individuals have no major birth defects, eye abnormalities, heart defects, and an unusually small head (microcephaly) can occur. 3q29 microduplication syndrome may increase the likelihood of being overweight or having obesity, although it is hard to determine whether these weight issues are caused by the duplication. ad Autosomal dominant 3 https://medlineplus.gov/genetics/chromosome/3 3q29 interstitial microduplication 3q29 microduplication Chromosome 3q29 duplication syndrome Microduplication 3q29 syndrome Trisomy 3q29 GTR C2749873 MeSH D008607 MeSH D058674 OMIM 611936 SNOMED CT 717973004 2017-08 2022-05-16 46,XX testicular difference of sex development https://medlineplus.gov/genetics/condition/46xx-testicular-difference-of-sex-development description46,XX testicular difference of sex development is a condition in which individuals with two X chromosomes in each cell, the pattern typically found in females, have a male appearance. People with this condition have male external genitalia. They generally have small testes and may also have other features such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). A small number of affected people have external genitalia that do not look clearly male or clearly female.At puberty, most affected individuals require treatment with the male sex hormone testosterone to induce development of male secondary sex characteristics such as facial hair and deepening of the voice (masculinization). Hormone treatment can also help prevent breast enlargement (gynecomastia). Adults with this condition are usually shorter than average for males and are unable to have children (infertile). ad Autosomal dominant SRY https://medlineplus.gov/genetics/gene/sry NR5A1 https://medlineplus.gov/genetics/gene/nr5a1 WT1 https://medlineplus.gov/genetics/gene/wt1 SOX9 https://medlineplus.gov/genetics/gene/sox9 SOX3 https://www.ncbi.nlm.nih.gov/gene/6658 X https://medlineplus.gov/genetics/chromosome/x Y https://medlineplus.gov/genetics/chromosome/y 46,XX testicular disorder of sex development 46,XX testicular DSD nonsyndromic 46,XX testicular disorder/difference of sex development XX male syndrome GTR C2936419 ICD-10-CM MeSH D058531 OMIM 400045 SNOMED CT 74398009 2022-10 2025-01-31 47,XYY syndrome https://medlineplus.gov/genetics/condition/47xyy-syndrome description47,XYY syndrome is characterized by an extra copy of the Y chromosome in each of an individual's cells. Although many people with this condition are taller than average, the chromosomal change sometimes causes no unusual physical features. Most individuals with 47,XYY syndrome have normal production of the male sex hormone testosterone and normal male sexual development, and they are usually able to father children.47,XYY syndrome is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Affected children can have delayed development of motor skills (such as sitting and walking) or weak muscle tone (hypotonia). Other signs and symptoms of this condition include hand tremors or other involuntary movements (motor tics), seizures, and asthma. Individuals with 47,XYY syndrome have an increased risk of behavioral, social, and emotional difficulties compared with their unaffected peers. These problems include attention-deficit/hyperactivity disorder (ADHD); depression; anxiety; and autism spectrum disorder, which is a group of developmental conditions that affect communication and social interaction.Physical features related to 47,XYY syndrome can include increased belly fat, a large head (macrocephaly), unusually large teeth (macrodontia), flat feet (pes planus), fifth fingers that curve inward (clinodactyly), widely spaced eyes (ocular hypertelorism), and abnormal side-to-side curvature of the spine (scoliosis). These characteristics vary widely among people with this condition. n Not inherited Y https://medlineplus.gov/genetics/chromosome/y Jacob's syndrome XYY karyotype XYY syndrome YY syndrome GTR C3266843 ICD-10-CM Q98.5 MeSH D014997 SNOMED CT 50749006 2009-01 2022-03-02 48,XXXY syndrome https://medlineplus.gov/genetics/condition/48xxxy-syndrome description48,XXXY syndrome is a chromosomal condition in boys and men that causes intellectual disability, developmental delays, physical differences, and an inability to father biological children (infertility). Its signs and symptoms vary among affected individuals.Most boys and men with 48,XXXY syndrome have mild intellectual disability with learning difficulties. Speech and language development is particularly affected. Most affected boys and men can understand what other people say more easily than they themselves can speak. The problems with speech and communication can contribute to behavioral issues, including irritability and outbursts or temper tantrums. Boys and men with 48,XXXY syndrome tend to have anxiety, a short attention span, and impaired social skills.48,XXXY syndrome is also associated with weak muscle tone (hypotonia) and problems with coordination that delay the development of motor skills, such as sitting, standing, and walking. Affected boys and men tend to be taller than their peers, with an average adult height of over 6 feet.Other physical differences associated with 48,XXXY syndrome include abnormal fusion of certain bones in the forearm (radioulnar synostosis), an unusually large range of joint movement (hyperextensibility), elbow abnormalities, curved pinky fingers (fifth finger clinodactyly), and flat feet (pes planus). Affected individuals may have distinctive facial features, including widely spaced eyes (ocular hypertelorism), outside corners of the eyes that point upward (upslanting palpebral fissures), and skin folds covering the inner corner of the eyes (epicanthal folds). However, some boys and men with 48,XXXY syndrome do not have these differences in their facial features.48,XXXY syndrome disrupts male sexual development. The penis is shorter than usual, and the testes may be undescended, which means they are abnormally located inside the pelvis or abdomen. The testes are small and do not produce enough testosterone, which is the hormone that directs male sexual development. The shortage of testosterone often leads to incomplete puberty. Starting in adolescence, affected boys and men may have sparse body hair, and some experience breast enlargement (gynecomastia). Their testes typically do not produce sperm, so most men with this condition are infertile. n Not inherited X https://medlineplus.gov/genetics/chromosome/x XXXY males XXXY syndrome ICD-10-CM Q98.1 MeSH D007713 SNOMED CT 275263003 SNOMED CT 78317008 2018-09 2020-09-08 48,XXYY syndrome https://medlineplus.gov/genetics/condition/48xxyy-syndrome description48,XXYY syndrome is a chromosomal condition that affects male development. There is a lot of variability in symptoms between people with 48,XXYY syndrome. Almost all affected individuals have developmental delays in infancy and develop decreased testosterone levels (hypogonadism) during adolescence. People with 48,XXYY syndrome are also at risk for other health problems.Adolescents and adults with this condition usually have small testes that do not produce enough testosterone, which is the hormone that directs male sexual development. Without treatment, a shortage of testosterone during puberty can lead to reduced facial and body hair, poor muscle development, low energy levels, and an increased risk of breast enlargement (gynecomastia). Because their testes do not function normally, individuals with 48,XXYY syndrome have difficulty having biological children (a condition called infertility), but they may be able to have children using assisted reproductive technologies.48,XXYY syndrome can affect other parts of the body as well. Affected individuals are often taller than their peers, with an average adult height of 6 feet, 4 inches (193 cm). They may develop a mild to moderate hand tremor that typically starts in adolescence and may increase with age. Dental problems are frequently seen in people with this condition,  including delayed appearance of the primary (baby) or secondary (adult) teeth, thin tooth enamel, crowded or misaligned teeth, and multiple cavities.Additionally, individuals with 48,XXYY syndrome may have flat feet (pes planus), elbow abnormalities, abnormal fusion of certain bones in the forearm (radioulnar synostosis), allergies, asthma, type 2 diabetes, seizures, congenital heart defects, and an inflammatory condition in the throat (esophagus) called eosinophilic esophagitis. As people with 48,XXYY get older, they may develop a narrowing of the blood vessels in the legs called peripheral vascular disease. Peripheral vascular disease can cause skin ulcers to form. Affected individuals are also at risk of developing a type of clot called a deep vein thrombosis that occurs in the deep veins of the legs.Most individuals with 48,XXYY syndrome have an IQ score that ranges from 60 to 80 and have some degree of difficulty with speech and language development. The development of motor skills such as sitting, standing, and walking may be delayed in some children with 48,XXYY syndrome. They may also have poor coordination. Learning disabilities are very common in people with this disorder, especially in the areas of reading and written expression. People with 48,XXYY typically perform better at tasks focused on math, visual-spatial skills such as puzzles, and memorization of locations or directions. Affected individuals have higher-than-average rates of other neurodevelopmental and behavioral disorders, such as attention-deficit/hyperactivity disorder (ADHD); mood disorders, including anxiety and depression;and autism spectrum disorder, which affects communication and social interaction. n Not inherited X https://medlineplus.gov/genetics/chromosome/x Y https://medlineplus.gov/genetics/chromosome/y XXYY syndrome GTR C5979882 MeSH D007713 SNOMED CT 403760006 2023-07 2025-03-06 49,XXXXY syndrome https://medlineplus.gov/genetics/condition/49xxxxy-syndrome description49,XXXXY syndrome is a chromosomal condition that causes intellectual disabilities, developmental delays, changes in sex characteristics and other physical features, and an inability to have biological children (infertility). Some of these signs and symptoms vary among affected individuals. People with 49,XXXXY syndrome have mild or moderate intellectual disabilities with learning difficulties. Speech and language development are particularly affected. Most affected individuals are better at understanding what other people say (receptive language) than producing speech (expressive language). Because many individuals with 49,XXXXY have difficulty making the mouth movements needed to speak, they are often diagnosed with a condition called childhood apraxia of speech.People with 49,XXXXY syndrome tend to be shy and friendly, but problems with speech and communication can contribute to behavioral issues, including irritability, difficulty tolerating frustration, defiant behavior, and outbursts or temper tantrums.49,XXXXY syndrome is also associated with weak muscle tone (hypotonia) and problems with coordination that delay the development of motor skills, such as sitting, standing, and walking. Some people with 49,XXXXY have involuntary tensing of the neck, which causes the head to tilt or turn (torticollis).Affected infants and children are often shorter than their peers, but some catch up in height later in childhood or adolescence.The physical differences that are associated with 49,XXXXY syndrome include the fusion of bones in the forearm (radioulnar synostosis), an unusually large range of joint movement (hyperextensibility), elbow abnormalities, curved pinky fingers (fifth finger clinodactyly), and flat feet (pes planus). Affected individuals have distinctive facial features that can include widely spaced eyes (ocular hypertelorism), an upward tilt to the outside corners of the eyes (upslanting palpebral fissures), skin folds that cover the inner corner of the eyes (epicanthal folds), and a flat bridge of the nose. Dental abnormalities are also common in people with 49,XXXXY syndrome.49,XXXXY syndrome disrupts the development of typically male sex characteristics. The penis is often short and underdeveloped, and the testes may be undescended, which means they are located inside the pelvis or abdomen instead of outside of the body. The testes are small and do not produce sperm, so all individuals with 49,XXXXY syndrome are infertile. 49,XXXXY syndrome reduces the production of testosterone, which is the hormone that directs male sexual development. Without treatment, the shortage of testosterone often leads to incomplete puberty. Starting in adolescence, affected individuals may have sparse body hair, and some experience breast enlargement (gynecomastia).  n Not inherited X https://medlineplus.gov/genetics/chromosome/x 49,XXXXY chromosomal anomaly Chromosome XXXXY syndrome XXXXY aneuploidy XXXXY syndrome GTR C0265499 ICD-10-CM Q98.1 MeSH D007713 SNOMED CT 275264009 SNOMED CT 38847009 2024-04 2024-04-03 5-alpha reductase deficiency https://medlineplus.gov/genetics/condition/5-alpha-reductase-deficiency description5-alpha reductase deficiency is a condition that affects sexual development before birth and during puberty. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a hormone called dihydrotestosterone (DHT). DHT has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth.Many people with 5-alpha reductase deficiency have external genitalia that appears female. In other cases, affected infants have male-typical external genitalia, often an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias). Still other affected infants have external genitalia do not look clearly male or clearly female.During puberty, an increase in the levels of male sex hormones leads to the development of some secondary sex characteristics, such as increased muscle mass, deepening of the voice, development of pubic hair, and a growth spurt. The penis and scrotum (the sac of skin that holds the testes) may grow larger. People with 5-alpha reductase deficiency do not develop much facial or body hair. Most affected individuals are unable to have biological children (infertile) without assisted reproduction. ar Autosomal recessive SRD5A2 https://medlineplus.gov/genetics/gene/srd5a2 PPSH Pseudovaginal perineoscrotal hypospadias Steroid 5-alpha-reductase deficiency GTR C0268297 ICD-10-CM MeSH D058490 OMIM 264600 SNOMED CT 57514000 SNOMED CT 738771004 2008-04 2025-03-06 5q minus syndrome https://medlineplus.gov/genetics/condition/5q-minus-syndrome description5q minus (5q-) syndrome is a type of bone marrow disorder called myelodysplastic syndrome (MDS). MDS comprises a group of conditions in which immature blood cells fail to develop normally, resulting in too many immature cells and too few normal mature blood cells. In 5q- syndrome, development of red blood cells is particularly affected, leading to a shortage of these cells (anemia). In addition, the red blood cells that are present are unusually large (macrocytic). Although many people with 5q- syndrome have no symptoms related to anemia, especially in the early stages of the condition, some affected individuals develop extreme tiredness (fatigue), weakness, and an abnormally pale appearance (pallor) as the condition worsens. Individuals with 5q- syndrome also have abnormal development of bone marrow cells called megakaryocytes, which produce platelets, the cells involved in blood clotting. A common finding in people with 5q- syndrome is abnormal cells described as hypolobated megakaryocytes. In addition, some individuals with 5q- syndrome have an excess of platelets, while others have normal numbers of platelets.MDS is considered a slow-growing (chronic) blood cancer. It can progress to a fast-growing blood cancer called acute myeloid leukemia (AML). Progression to AML occurs less commonly in people with 5q- syndrome than in those with other forms of MDS. n Not inherited RPS14 https://medlineplus.gov/genetics/gene/rps14 MIR145 https://medlineplus.gov/genetics/gene/mir145 MIR146A https://medlineplus.gov/genetics/gene/mir146a 5 https://medlineplus.gov/genetics/chromosome/5 5q- syndrome Chromosome 5q deletion syndrome Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality Myelodysplastic syndrome with 5q deletion Myelodysplastic syndrome with 5q deletion syndrome Refractory macrocytic anemia due to 5q deletion GTR C1292779 ICD-10-CM D46.C MeSH D009190 OMIM 153550 SNOMED CT 277597005 2015-11 2020-09-08 5q31.3 microdeletion syndrome https://medlineplus.gov/genetics/condition/5q313-microdeletion-syndrome description5q31.3 microdeletion syndrome is a condition characterized by severely delayed development of speech and motor skills, such as walking. Beginning in infancy, affected individuals also have weak muscle tone (hypotonia), feeding difficulties, and breathing problems. Breathing problems and difficulty swallowing (dysphagia) can be life-threatening.5q31.3 microdeletion syndrome is also characterized by distinctive facial features. Such features include a narrow forehead, widely spaced eyes (hypertelorism), an open mouth with an upper lip that points outward (called a tented lip), a high arch in the roof of the mouth (high-arched palate), a small lower jaw (micrognathia), and a lack of facial expression. Some of these features, such as an open mouth with a tented lip and an expressionless face, are thought to be due to hypotonia.Recurrent seizures (epilepsy) and seizure-like episodes (which can include muscle jerking, twitching, and stiffening), are common in 5q31.3 microdeletion syndrome. Many individuals with 5q31.3 microdeletion syndrome have brain abnormalities, several of which are caused by reduced production of myelin or delayed maturation of myelin. Myelin is the protective covering that insulates nerves and ensures the rapid transmission of nerve impulses. ad Autosomal dominant PURA https://medlineplus.gov/genetics/gene/pura NRG2 https://www.ncbi.nlm.nih.gov/gene/9542 5 https://medlineplus.gov/genetics/chromosome/5 Severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion GTR C4015357 MeSH D065886 2017-08 2020-09-08 6q24-related transient neonatal diabetes mellitus https://medlineplus.gov/genetics/condition/6q24-related-transient-neonatal-diabetes-mellitus description6q24-related transient neonatal diabetes mellitus is a type of diabetes that occurs in infants. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy.People with 6q24-related transient neonatal diabetes mellitus experience very slow growth before birth (severe intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration), usually beginning in the first week of life. Signs and symptoms of this form of diabetes are transient, which means that they gradually lessen over time and generally disappear between the ages of 3 months and 18 months. Diabetes may recur, however, especially during childhood illnesses or pregnancy. Up to half of individuals with 6q24-related transient neonatal diabetes mellitus develop permanent diabetes mellitus later in life.Other features of 6q24-related transient neonatal diabetes mellitus that occur in some affected individuals include an unusually large tongue (macroglossia); a soft out-pouching around the belly-button (an umbilical hernia); malformations of the brain, heart, or kidneys; weak muscle tone (hypotonia); deafness; and developmental delay. ar Autosomal recessive PLAGL1 https://medlineplus.gov/genetics/gene/plagl1 ZFP57 https://medlineplus.gov/genetics/gene/zfp57 HYMAI https://www.ncbi.nlm.nih.gov/gene/57061 6 https://medlineplus.gov/genetics/chromosome/6 6q24-TNDM TNDM type 1 Transient neonatal diabetes mellitus 1 GTR C1832386 MeSH D003920 OMIM 601410 SNOMED CT 609579009 2011-02 2020-09-08 7q11.23 duplication syndrome https://medlineplus.gov/genetics/condition/7q1123-duplication-syndrome description7q11.23 duplication syndrome is a condition that can cause a variety of neurological and behavioral problems as well as other abnormalities.People with 7q11.23 duplication syndrome typically have delayed development of speech and motor skills such as crawling and walking. Speech problems and abnormalities in the way affected individuals walk and stand may persist throughout life. People with this condition may also have weak muscle tone (hypotonia) and abnormal movements, such as involuntary movements of one side of the body that mirror intentional movements of the other side. About one-fifth of people with 7q11.23 duplication syndrome experience seizures.Intellectual development varies widely in 7q11.23 duplication syndrome. The majority of people with this condition have low-average to average intelligence. Intellectual disability or borderline intellectual ability occur in about one-third of affected individuals. Rarely, people with this disorder have above-average intelligence.Neurodevelopmental problems associated with this condition include anxiety disorders (such as social phobias and selective mutism, which is an inability to speak in certain circumstances), attention-deficit/hyperactivity disorder (ADHD), physical aggression, excessively defiant behavior (oppositional disorder), and autism spectrum disorder that affect communication and social interaction.Approximately half of individuals with 7q11.23 duplication syndrome have enlargement (dilatation) of the blood vessel that carries blood from the heart to the rest of the body (the aorta); this enlargement can get worse over time. Aortic dilatation can lead to life-threatening complications if the wall of the aorta separates into layers (aortic dissection) or breaks open (ruptures).People with 7q11.23 duplication syndrome can have characteristic features of the head and face, including a large head (macrocephaly) that is flattened in the back (brachycephaly), a broad forehead, straight eyebrows, and deep-set eyes with long eyelashes. The nose may be broad at the tip with the area separating the nostrils attaching lower than usual on the face (low insertion of the columella), resulting in a shortened area between the nose and the upper lip (philtrum). A high arch in the roof of the mouth (high-arched palate) and ear abnormalities may also occur. These features may be mild and not recognized in some affected individuals. ad Autosomal dominant ELN https://medlineplus.gov/genetics/gene/eln GTF2I https://medlineplus.gov/genetics/gene/gtf2i 7 https://medlineplus.gov/genetics/chromosome/7 7q11.23 microduplication syndrome Chromosome 7q11.23 duplication Chromosome 7q11.23 duplication syndrome Dup(7)(q11.23) Somerville-Van der Aa syndrome Trisomy 7q11.23 WBS duplication syndrome Williams-Beuren region duplication syndrome GTR C1857844 MeSH D058674 OMIM 609757 SNOMED CT 726707004 2016-04 2023-08-02 8p11 myeloproliferative syndrome https://medlineplus.gov/genetics/condition/8p11-myeloproliferative-syndrome description8p11 myeloproliferative syndrome is a blood cancer that involves different types of blood cells. Blood cells are divided into several groups (lineages) based on the type of early cell from which they are descended. Two of these lineages are myeloid cells and lymphoid cells. Individuals with 8p11 myeloproliferative syndrome can develop both myeloid cell cancer and lymphoid cell cancer.The condition can occur at any age. It usually begins as a myeloproliferative disorder, which is characterized by a high number of white blood cells (leukocytes). Most affected individuals also have an excess of myeloid cells known as eosinophils (eosinophilia).In addition to a myeloproliferative disorder, many people with 8p11 myeloproliferative syndrome develop lymphoma, which is a form of blood cancer that involves lymphoid cells. The cancerous lymphoid cells grow and divide in lymph nodes, forming a tumor that enlarges the lymph nodes. In most cases of 8p11 myeloproliferative syndrome, the cancerous cells are lymphoid cells called T cells. Lymphoma can develop at the same time as the myeloproliferative disorder or later.In most people with 8p11 myeloproliferative syndrome, the myeloproliferative disorder develops into a fast-growing blood cancer called acute myeloid leukemia.The rapid myeloid and lymphoid cell production caused by these cancers results in enlargement of the spleen and liver (splenomegaly and hepatomegaly, respectively). Most people with 8p11 myeloproliferative syndrome have symptoms such as fatigue or night sweats. Some affected individuals have no symptoms, and the condition is discovered through routine blood tests. n Not inherited FGFR1 https://medlineplus.gov/genetics/gene/fgfr1 ZMYM2 https://medlineplus.gov/genetics/gene/zmym2 8 https://medlineplus.gov/genetics/chromosome/8 13 https://medlineplus.gov/genetics/chromosome/13 8p11 stem cell leukemia/lymphoma syndrome 8p11 stem cell syndrome Myeloid and lymphoid neoplasms with FGFR1 abnormalities Stem cell leukemia/lymphoma GTR C3150773 MeSH D009196 OMIM 613523 SNOMED CT 450942006 2013-07 2020-09-08 9q22.3 microdeletion https://medlineplus.gov/genetics/condition/9q223-microdeletion description9q22.3 microdeletion is a chromosomal change in which a small piece of chromosome 9 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome in a region designated q22.3. This chromosomal change is associated with delayed development, intellectual disability, certain physical abnormalities, and the characteristic features of a genetic condition called Gorlin syndrome.Many individuals with a 9q22.3 microdeletion have delayed development, particularly affecting the development of motor skills such as sitting, standing, and walking. In some people, the delays are temporary and improve in childhood. More severely affected individuals have permanent developmental disabilities along with intellectual impairment and learning problems. Rarely, seizures have been reported in people with a 9q22.3 microdeletion.About 20 percent of people with a 9q22.3 microdeletion experience overgrowth (macrosomia), which results in increased height and weight compared to unaffected peers. The macrosomia often begins before birth and continues into childhood. Other physical changes that are sometimes associated with a 9q22.3 microdeletion include the premature fusion of certain bones in the skull (metopic craniosynostosis) and a buildup of fluid in the brain (hydrocephalus). Affected individuals can also have distinctive facial features such as a prominent forehead with vertical skin creases, upward- or downward-slanting eyes, a short nose, and a long space between the nose and upper lip (philtrum).9q22.3 microdeletions also cause the characteristic features of Gorlin syndrome (also known as nevoid basal cell carcinoma syndrome). This genetic condition affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors. In people with Gorlin syndrome, the type of cancer diagnosed most often is basal cell carcinoma, which is the most common form of skin cancer. Most people with this condition also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors, which can cause facial swelling and tooth displacement. Other types of tumors that occur in some people with Gorlin syndrome include a form of childhood brain cancer called a medulloblastoma and a type of benign tumor called a fibroma that occurs in the heart or in a woman's ovaries. Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull. ad Autosomal dominant PTCH1 https://medlineplus.gov/genetics/gene/ptch1 9 https://medlineplus.gov/genetics/chromosome/9 9q22 deletion syndrome 9q22.3 deletion Microdeletion 9q22.3 syndrome GTR C0004779 GTR C3711390 MeSH D025063 OMIM 109400 SNOMED CT 711489004 2012-09 2023-02-01 ACAD9 deficiency https://medlineplus.gov/genetics/condition/acad9-deficiency descriptionACAD9 deficiency is a condition that varies in severity and can cause muscle weakness (myopathy), heart problems, and intellectual disability. Nearly all affected individuals have a buildup of a chemical called lactic acid in the body (lactic acidosis). Additional signs and symptoms that affect other body systems occur in rare cases.Mildly affected individuals with ACAD9 deficiency usually experience nausea and extreme fatigue in response to physical activity (exercise intolerance). People with ACAD9 deficiency who are moderately affected have low muscle tone (hypotonia) and weakness in the muscles used for movement (skeletal muscles). Severely affected individuals have brain dysfunction combined with myopathy (encephalomyopathy); these individuals usually also have an enlarged and weakened heart muscle (hypertrophic cardiomyopathy), which is typically fatal in infancy or childhood.Individuals with ACAD9 deficiency who survive past early childhood often have intellectual disability and may develop seizures. Rare signs and symptoms of ACAD9 deficiency include movement disorders and problems with liver and kidney function.Some individuals with ACAD9 deficiency have had improvement in muscle strength and a reduction in lactic acid levels with treatment. ar Autosomal recessive ACAD9 https://medlineplus.gov/genetics/gene/acad9 Acyl-CoA dehydrogenase 9 deficiency Deficiency of acyl-CoA dehydrogenase family member 9 Mitochondrial complex I deficiency due to ACAD9 deficiency GTR C4747517 MeSH D028361 OMIM 611126 SNOMED CT 725046003 2017-04 2020-08-18 ADCY5-related dyskinesia https://medlineplus.gov/genetics/condition/adcy5-related-dyskinesia descriptionADCY5-related dyskinesia is a movement disorder; the term "dyskinesia" refers to abnormal involuntary movements. The abnormal movements that occur in ADCY5-related dyskinesia typically appear as sudden (paroxysmal) jerks, twitches, tremors, muscle tensing (dystonia), or writhing (choreiform) movements, and can affect the limbs, neck, and face.The abnormal movements associated with ADCY5-related dyskinesia usually begin between infancy and late adolescence. They can occur continually during waking hours, and frequently also disturb sleep. The involuntary movements often occur when changing position, such as from sitting to standing, or when deliberately making other movements.Severely affected infants may experience weak muscle tone (hypotonia) and delay in development of motor skills such as crawling and walking; later, these individuals may have difficulties with activities of daily living and may eventually require a wheelchair. In more mildly affected individuals, the condition has little impact on walking and other motor skills, although the abnormal movements can lead to clumsiness or difficulty with social acceptance in school or other situations.In some people with ADCY5-related dyskinesia, the disorder is generally stable throughout their lifetime. In others, it slowly gets worse (progresses) in both frequency and severity before stabilizing or even improving in middle age. Anxiety, fatigue, and other stress can temporarily increase the severity of the signs and symptoms of ADCY5-related dyskinesia, while some affected individuals may experience remission periods of days or weeks without abnormal movements. Life expectancy is not usually affected by ADCY5-related dyskinesia, and most people with this condition have normal intelligence. ad Autosomal dominant ADCY5 https://medlineplus.gov/genetics/gene/adcy5 Familial dyskinesia with facial myokymia FDFM GTR C1847627 MeSH D020820 OMIM 606703 SNOMED CT 9748009 2015-07 2023-08-18 ADNP syndrome https://medlineplus.gov/genetics/condition/adnp-syndrome descriptionADNP syndrome is a condition that causes a wide variety of signs and symptoms. Its hallmark features are intellectual disability and autism spectrum disorder, which is characterized by impaired communication and social interaction. Affected individuals also have distinctive facial features and abnormalities of multiple body systems.Individuals with ADNP syndrome have mild to severe intellectual disability and delayed development of speech and motor skills such as sitting and walking. Some affected individuals are never able to speak. People with this disorder exhibit characteristics typical of autism spectrum disorder, including repetitive behaviors and difficulty with social interactions. ADNP syndrome is also associated with mood disorders or behavioral problems, such as anxiety, temper tantrums, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder, or sleep problems.Many people with ADNP syndrome have distinctive facial features, which most commonly include a prominent forehead, a high hairline, outside corners of the eyes that point upward or downward (upslanting or downslanting palpebral fissures), droopy eyelids (ptosis), a broad nasal bridge, and a thin upper lip. These individuals may also have unusually shaped ears or hand and finger abnormalities. Eye and vision abnormalities, such as eyes that do not point in the same direction (strabismus) and farsightedness (hyperopia), also occur in ADNP syndrome. Some people with this condition have early appearance (eruption) of primary (baby) teeth.Some people with ADNP syndrome have weak muscle tone (hypotonia) and feeding difficulties in infancy. They may also have digestive system problems, such as backflow of stomach acids into the esophagus (gastroesophageal reflux), vomiting, and constipation. Other features that occur in ADNP syndrome include obesity, seizures, and heart abnormalities. n Not inherited ADNP https://medlineplus.gov/genetics/gene/adnp ADNP-related intellectual disability and autism spectrum disorder ADNP-related multiple congenital anomalies-intellectual disability-autism spectrum disorder Helsmoortel-van der Aa syndrome HVDAS Mental retardation, autosomal dominant 28 MRD28 GTR C4014538 MeSH D065886 OMIM 615873 2017-03 2023-07-13 ALG1-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/alg1-congenital-disorder-of-glycosylation descriptionALG1-congenital disorder of glycosylation (ALG1-CDG, also known as congenital disorder of glycosylation type Ik) is an inherited disorder with varying signs and symptoms that typically develop during infancy and can affect several body systems.Individuals with ALG1-CDG often have intellectual disability, delayed development, and weak muscle tone (hypotonia). Many affected individuals develop seizures that can be difficult to treat. Individuals with ALG1-CDG may also have movement problems such as involuntary rhythmic shaking (tremor) or difficulties with movement and balance (ataxia).People with ALG1-CDG often have problems with blood clotting, which can lead to abnormal clotting or bleeding episodes. Additionally, affected individuals may produce abnormally low levels of proteins called antibodies (or immunoglobulins), particularly immunoglobulin G (IgG). Antibodies help protect the body against infection by foreign particles and germs. A reduction in antibodies can make it difficult for affected individuals to fight infections.Some people with ALG1-CDG have physical abnormalities such as a small head size (microcephaly); unusual facial features; joint deformities called contractures; long, slender fingers and toes (arachnodactyly); or unusually fleshy pads at the tips of the fingers and toes. Eye problems that may occur in people with this condition include eyes that do not point in the same direction (strabismus) or involuntary eye movements (nystagmus). Rarely, affected individuals develop vision loss.Less common abnormalities that occur in people with ALG1-CDG include respiratory problems, reduced sensation in their arms and legs (peripheral neuropathy), swelling (edema), and gastrointestinal difficulties.The signs and symptoms of ALG1-CDG are often severe, with affected individuals surviving only into infancy or childhood. However, some people with this condition are more mildly affected and survive into adulthood. ar Autosomal recessive ALG1 https://medlineplus.gov/genetics/gene/alg1 ALG1-CDG Carbohydrate deficient glycoprotein syndrome type Ik CDG1K CDGIk Congenital disorder of glycosylation type 1K Mannosyltransferase 1 deficiency GTR C2931005 MeSH D018981 OMIM 608540 SNOMED CT 720941007 2016-01 2021-11-26 ALG12-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/alg12-congenital-disorder-of-glycosylation descriptionALG12-congenital disorder of glycosylation (ALG12-CDG, also known as congenital disorder of glycosylation type Ig) is an inherited disorder with varying signs and symptoms that can affect several body systems. Individuals with ALG12-CDG typically develop signs and symptoms of the condition during infancy. They may have problems feeding and difficulty growing and gaining weight at the expected rate (failure to thrive). In addition, affected individuals often have intellectual disability, delayed development, and weak muscle tone (hypotonia), and some develop seizures.Some people with ALG12-CDG have physical abnormalities such as a small head size (microcephaly) and unusual facial features. These features can include folds of skin that cover the inner corners of the eyes (epicanthal folds), a prominent nasal bridge, and abnormally shaped ears. Some males with ALG12-CDG have abnormal genitalia, such as a small penis (micropenis) and undescended testes.People with ALG12-CDG often produce abnormally low levels of proteins called antibodies (or immunoglobulins), particularly immunoglobulin G (IgG). Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. A reduction in antibodies can make it difficult for affected individuals to fight infections.Less common abnormalities seen in people with ALG12-CDG include a weakened heart muscle (cardiomyopathy) and poor bone development, which can lead to skeletal abnormalities. ar Autosomal recessive ALG12 https://medlineplus.gov/genetics/gene/alg12 ALG12-CDG CDG Ig CDG1G Congenital disorder of glycosylation type 1G Congenital disorder of glycosylation type Ig GTR C2931001 MeSH D018981 OMIM 607143 SNOMED CT 711155008 2015-01 2021-11-26 ALG6-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/alg6-congenital-disorder-of-glycosylation descriptionALG6-congenital disorder of glycosylation (ALG6-CDG, also known as congenital disorder of glycosylation type Ic) is an inherited condition that affects many parts of the body. The signs and symptoms of ALG6-CDG vary widely among people with the condition.Individuals with ALG6-CDG typically develop signs and symptoms of the condition during infancy. They may have difficulty gaining weight and growing at the expected rate (failure to thrive). Affected infants often have weak muscle tone (hypotonia) and developmental delay.People with ALG6-CDG may have seizures, problems with coordination and balance (ataxia), or stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. They may also develop blood clotting disorders. Some individuals with ALG6-CDG have eye abnormalities including eyes that do not look in the same direction (strabismus) and an eye disorder called retinitis pigmentosa, which causes vision loss. Females with ALG6-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, most females with ALG6-CDG do not go through puberty. ar Autosomal recessive ALG6 https://medlineplus.gov/genetics/gene/alg6 ALG6-CDG Carbohydrate-deficient glycoprotein syndrome type Ic Carbohydrate-deficient glycoprotein syndrome type V CDG syndrome type Ic CDG1C CDGIc Congenital disorder of glycosylation type Ic Glucosyltransferase 1 deficiency GTR C2930997 MeSH D018981 OMIM 603147 SNOMED CT 709412006 2014-05 2020-08-18 Aarskog-Scott syndrome https://medlineplus.gov/genetics/condition/aarskog-scott-syndrome descriptionAarskog-Scott syndrome is a genetic disorder that affects the development of many parts of the body, most commonly the head and face, the hands and feet, and the genitals and urinary system (genitourinary tract). This condition mainly affects males, although females may have mild features of the syndrome.People with Aarskog-Scott syndrome often have distinctive facial features, such as widely spaced eyes (hypertelorism), a small nose, a long area between the nose and mouth (philtrum), and a widow's peak hairline. They frequently have mild to moderate short stature during childhood, but their growth usually catches up with that of their peers during puberty. Hand abnormalities are common in this syndrome and include short fingers (brachydactyly), curved pinky fingers (fifth finger clinodactyly), webbing of the skin between some fingers (cutaneous syndactyly), and a single crease across the palm. Affected individuals can also have wide, flat feet with broad, rounded toes. Other abnormalities in people with Aarskog-Scott syndrome include heart defects and a split in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).Most males with Aarskog-Scott syndrome have a shawl scrotum, in which the scrotum surrounds the penis instead of hanging below. Less often, they have undescended testes (cryptorchidism) or a soft out-pouching around the belly-button (umbilical hernia) or in the lower abdomen (inguinal hernia).The intellectual development of people with Aarskog-Scott syndrome varies widely. Most individuals with Aarskog-Scott syndrome have normal intelligence; however, some may have mild learning and behavior problems, and in rare cases, severe intellectual disability has been reported. ad Autosomal dominant xr X-linked recessive ar Autosomal recessive FGD1 https://medlineplus.gov/genetics/gene/fgd1 Aarskog syndrome AAS Facio-digito-genital dysplasia Faciodigitogenital syndrome Faciogenital dysplasia FGDY GTR C0175701 MeSH D040181 OMIM 305400 SNOMED CT 14921002 2022-06 2022-05-27 Abdominal wall defect https://medlineplus.gov/genetics/condition/abdominal-wall-defect descriptionAn abdominal wall defect is an opening in the abdomen through which various abdominal organs can protrude. This opening varies in size and can usually be diagnosed early in fetal development, typically between the tenth and fourteenth weeks of pregnancy. There are two main types of abdominal wall defects: omphalocele and gastroschisis. Omphalocele is an opening in the center of the abdominal wall where the umbilical cord meets the abdomen. Organs (typically the intestines, stomach, and liver) protrude through the opening into the umbilical cord and are covered by the same protective membrane that covers the umbilical cord. Gastroschisis is a defect in the abdominal wall, usually to the right of the umbilical cord, through which the large and small intestines protrude (although other organs may sometimes bulge out). There is no membrane covering the exposed organs in gastroschisis.Fetuses with omphalocele may grow slowly before birth (intrauterine growth retardation) and they may be born prematurely. Individuals with omphalocele frequently have multiple birth defects, such as a congenital heart defect. Additionally, underdevelopment of the lungs is often associated with omphalocele because the abdominal organs normally provide a framework for chest wall growth. When those organs are misplaced, the chest wall does not form properly, providing a smaller than normal space for the lungs to develop. As a result, many infants with omphalocele have respiratory insufficiency and may need to be supported with a machine to help them breathe (mechanical ventilation). Rarely, affected individuals who have breathing problems in infancy experience recurrent lung infections or asthma later in life. Affected infants often have gastrointestinal problems including a backflow of stomach acids into the esophagus (gastroesophageal reflux) and feeding difficulty; these problems can persist even after treatment of omphalocele. Large omphaloceles or those associated with multiple additional health problems are more often associated with fetal death than cases in which omphalocele occurs alone (isolated).Omphalocele is a feature of many genetic syndromes. Nearly half of individuals with omphalocele have a condition caused by an extra copy of one of the chromosomes in each of their cells (trisomy). Up to one-third of people born with omphalocele have a genetic condition called Beckwith-Wiedemann syndrome. Affected individuals may have additional signs and symptoms associated with these genetic conditions.Individuals who have gastroschisis rarely have other birth defects and seldom have chromosome abnormalities or a genetic condition. Most affected individuals experience intrauterine growth retardation and are small at birth; many affected infants are born prematurely.With gastroschisis, the protruding organs are not covered by a protective membrane and are susceptible to damage due to direct contact with amniotic fluid in the womb. Components of the amniotic fluid may trigger immune responses and inflammatory reactions against the intestines that can damage the tissue. Constriction around exposed organs at the abdominal wall opening late in fetal development may also contribute to organ injury. Intestinal damage causes impairment of the muscle contractions that move food through the digestive tract (peristalsis) in most children with gastroschisis. In these individuals, peristalsis usually improves in a few months and intestinal muscle contractions normalize. Rarely, children with gastroschisis have a narrowing or absence of a portion of intestine (intestinal atresia) or twisting of the intestine. After birth, these intestinal malformations can lead to problems with digestive function, further loss of intestinal tissue, and a condition called short bowel syndrome that occurs when areas of the small intestine are missing, causing dehydration and poor absorption of nutrients. Depending on the severity of the condition, intravenous feedings (parenteral nutrition) may be required.The health of an individual with gastroschisis depends largely on how damaged his or her intestine was before birth. When the abdominal wall defect is repaired and normal intestinal function is recovered, the vast majority of affected individuals have no health problems related to the repaired defect later in life. u Pattern unknown Abdominal hernia Gastroschisis Hernia, abdominal Omphalocele GTR C0795690 ICD-10-CM Q79.2 ICD-10-CM Q79.3 MeSH D046449 OMIM 164750 OMIM 230750 OMIM 310980 SNOMED CT 1542009 SNOMED CT 18735004 SNOMED CT 196864001 SNOMED CT 196868003 SNOMED CT 36631002 SNOMED CT 72951007 2012-08 2020-08-18 Abetalipoproteinemia https://medlineplus.gov/genetics/condition/abetalipoproteinemia descriptionAbetalipoproteinemia is an inherited disorder that impairs the normal absorption of fats and certain vitamins from the diet. Many of the signs and symptoms of abetalipoproteinemia result from a severe shortage (deficiency) of fat-soluble vitamins (vitamins A, E, and K). The signs and symptoms of this condition primarily affect the gastrointestinal system, eyes, nervous system, and blood.The first signs and symptoms of abetalipoproteinemia appear in infancy. They often include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; and fatty, foul-smelling stools (steatorrhea).As an individual with this condition ages, additional signs and symptoms include disturbances in nerve function that may lead to poor muscle coordination and difficulty with balance and movement (ataxia). They can also experience a loss of certain reflexes, impaired speech (dysarthria), tremors or other involuntary movements (motor tics), a loss of sensation in the extremities (peripheral neuropathy), or muscle weakness. The muscle problems can disrupt skeletal development, leading to an abnormally curved lower back (lordosis), a rounded upper back that also curves to the side (kyphoscoliosis), high-arched feet (pes cavus), or an inward- and upward-turning foot (clubfoot).Individuals with this condition may also develop an eye disorder called retinitis pigmentosa, in which breakdown of the light-sensitive layer (retina) at the back of the eye can cause vision loss. In individuals with abetalipoproteinemia, the retinitis pigmentosa can result in complete vision loss. People with abetalipoproteinemia may also have other eye problems, including involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and weakness of the external muscles of the eye (ophthalmoplegia).Individuals with abetalipoproteinemia usually have a low number of red blood cells (anemia) with abnormally star-shaped red blood cells (acanthocytosis) and have difficulty forming blood clots, which can cause abnormal bleeding. In some cases, a condition called fatty liver develops, which can cause liver damage. ar Autosomal recessive MTTP https://medlineplus.gov/genetics/gene/mttp Abetalipoproteinaemia Abetalipoproteinemia neuropathy ABL Acanthocytosis Apolipoprotein B deficiency Bassen-Kornzweig disease Bassen-Kornzweig syndrome Betalipoprotein deficiency disease Congenital betalipoprotein deficiency syndrome Microsomal triglyceride transfer protein deficiency disease MTP deficiency ICD-10-CM E78.6 MeSH D000012 OMIM 200100 SNOMED CT 190787008 2018-02 2023-11-24 Acatalasemia https://medlineplus.gov/genetics/condition/acatalasemia descriptionAcatalasemia is a condition characterized by very low levels of an enzyme called catalase. Many people with acatalasemia never have any health problems related to the condition and are diagnosed because they have affected family members.Some of the first reported individuals with acatalasemia developed open sores (ulcers) inside the mouth that led to the death of soft tissue (gangrene). When mouth ulcers and gangrene occur with acatalasemia, the condition is known as Takahara disease. These complications are rarely seen in more recent cases of acatalasemia, probably because of improvements in oral hygiene.Studies suggest that people with acatalasemia have an increased risk of developing type 2 diabetes, which is the most common form of diabetes. A higher percentage of people with acatalasemia have type 2 diabetes than in the general population, and the disease tends to develop at an earlier age (in a person's thirties or forties, on average). Researchers speculate that acatalasemia could also be a risk factor for other common, complex diseases; however, only a small number of cases have been studied. ar Autosomal recessive CAT https://medlineplus.gov/genetics/gene/cat Acatalasia Catalase deficiency GTR C0268419 ICD-10-CM E80.3 MeSH D020642 OMIM 614097 SNOMED CT 267454002 2014-09 2023-07-26 Aceruloplasminemia https://medlineplus.gov/genetics/condition/aceruloplasminemia descriptionAceruloplasminemia is a disorder in which iron gradually accumulates in the brain and other organs. Iron accumulation in the brain results in neurological problems that generally appear in adulthood and worsen over time.People with aceruloplasminemia develop a variety of movement problems. They may experience involuntary muscle contractions (dystonia) of the head and neck, resulting in repetitive movements and contortions. Other involuntary movements may also occur, such as rhythmic shaking (tremors), jerking movements (chorea), eyelid twitching (blepharospasm), and grimacing. Affected individuals may also have difficulty with coordination (ataxia). Some develop psychiatric problems and a decline of intellectual function (dementia) in their forties or fifties.In addition to neurological problems, affected individuals may have diabetes mellitus caused by iron damage to cells in the pancreas that make insulin, a hormone that helps control levels of blood sugar, also called blood glucose. Iron accumulation in the pancreas reduces the cells' ability to make insulin, which impairs blood glucose regulation and leads to the signs and symptoms of diabetes.Iron accumulation in the tissues and organs results in a corresponding shortage (deficiency) of iron in the blood, leading to a shortage of red blood cells (anemia). Anemia and diabetes usually occur by the time an affected person is in his or her twenties.Affected individuals also have changes in the light-sensitive tissue at the back of the eye (retina) caused by excess iron. The changes result in small opaque spots and areas of tissue degeneration (atrophy) around the edges of the retina. These abnormalities usually do not affect vision but can be observed during an eye examination.The specific features of aceruloplasminemia and their severity may vary, even within the same family. ar Autosomal recessive CP https://medlineplus.gov/genetics/gene/cp Deficiency of ferroxidase Familial apoceruloplasmin deficiency Hereditary ceruloplasmin deficiency Hypoceruloplasminemia Systemic hemosiderosis due to aceruloplasminemia GTR C0878682 MeSH D019189 OMIM 604290 SNOMED CT 124224004 2008-04 2023-07-25 Achondrogenesis https://medlineplus.gov/genetics/condition/achondrogenesis descriptionAchondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by skeletal abnormalities that cause serious health problems. As a result, most infants with achondrogenesis die before birth or soon after, often due to respiratory failure. Researchers have described three main types of achondrogenesis: type 1A, type 1B, and type 2. While these types differ in their genetic causes and inheritance patterns, they often have overlapping signs and symptoms. Genetic testing and medical imaging are often needed to tell them apart. All forms of achondrogenesis feature short arms and legs, a narrow chest, and underdeveloped lungs. Infants with achondrogenesis type 1A, which is also called TRIP11-related achondrogenesis, typically have ribs that fracture easily. Bone formation (ossification) is also severely reduced in the skull and spine.Infants with achondrogenesis type 1B, which is also called SLC26A2-related achondrogenesis, often have short fingers and toes and feet that may turn inward and upward (clubfeet). Infants with achondrogenesis type 1B may also have a sac (pouch) formed from the inner lining of the abdominal cavity that pushes through a hole in the abdominal wall around the belly-button (umbilical hernia) or near the groin (inguinal hernia).The ossification of the spine and pelvis may be severely reduced in infants with achondrogenesis type 2, which is also called COL2A1-related achondrogenesis. The distinctive facial features seen in infants with achondrogenesis type 2 include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (cleft palate). Achondrogenesis type 2 and a similar skeletal disorder called hypochondrogenesis were once thought to be distinct conditions. However, because these conditions have overlapping features and a shared genetic cause, they are now considered to be part of the same disease spectrum.  ar Autosomal recessive ad Autosomal dominant+New variant COL2A1 https://medlineplus.gov/genetics/gene/col2a1 SLC26A2 https://medlineplus.gov/genetics/gene/slc26a2 TRIP11 https://medlineplus.gov/genetics/gene/trip11 achondrogenesis type IA (Houston-Harris type) achondrogenesis type IB (Fraccaro type) achondrogenesis type II (Langer-Saldino type) GTR C0220685 GTR C0265273 GTR C0265274 ICD-10-CM Q77.0 MeSH D010009 OMIM 200600 OMIM 200610 OMIM 600972 SNOMED CT 14870002 SNOMED CT 2391001 SNOMED CT 254061001 2024-12 2024-12-19 Achondroplasia https://medlineplus.gov/genetics/condition/achondroplasia descriptionAchondroplasia is the most common form of short-limbed dwarfism. The word achondroplasia means "without cartilage formation." Cartilage is a tough but flexible tissue that makes up much of the skeleton during early development. However, in people with achondroplasia the problem is not  forming cartilage but  converting it to bone (a process called ossification), particularly in the long bones of the arms and legs. Achondroplasia is similar to another skeletal disorder called hypochondroplasia, but the features of achondroplasia tend to be more severe.All people with achondroplasia have short stature. Without treatment, the average height of an adult male with achondroplasia is 131 centimeters (4 feet, 4 inches), and the average height for adult females is 124 centimeters (4 feet, 1 inch). Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. Health problems commonly associated with achondroplasia include obesity and recurrent ear infections. People with achondroplasia are generally of normal intelligence. In childhood, individuals with the condition usually develop a pronounced and permanent sway of the lower back (lordosis) and bowed legs. Some affected people also develop abnormal front-to-back curvature of the spine (kyphosis) and back pain. As affected individuals age, they may experience a potentially serious complication of achondroplasia called spinal stenosis. Spinal stenosis is a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord. Spinal stenosis causes with pain, tingling, and weakness in the legs that can make walking difficult. An uncommon but serious complication of achondroplasia in early childhood is stenosis of the hole at the base of the skull where the spinal cord comes out of brain (foramen magnum). This complication can cause compression of the brain stem, which can lead to pauses in breathing during sleep (sleep apnea) or a condition known as hydrocephalus. Hydrocephalus is a buildup of fluid in the brain that can lead to increased head size and related brain abnormalities. ad Autosomal dominant FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 ACH Achondroplastic dwarfism Dwarf, achondroplastic GTR C0001080 ICD-10-CM Q77.4 MeSH D000130 OMIM 100800 SNOMED CT 86268005 2023-06 2023-05-29 Achromatopsia https://medlineplus.gov/genetics/condition/achromatopsia descriptionAchromatopsia is a disorder that causes problems with color vision. The retina, which is the light-sensitive tissue at the back of the eye, contains two types of light receptor cells called rods and cones. Rods provide vision in low light (night vision), while cones provide vision in bright light (daytime vision). Cones are also responsible for color vision. There are two types of achromatopsia: complete and incomplete. People with complete achromatopsia cannot perceive any color; they see only black, white, and shades of gray. People with incomplete achromatopsia can see some color.People with achromatopsia may have additional problems with their vision, including an increased sensitivity to light and glare (photophobia), involuntary back-and-forth eye movements (nystagmus), and significantly reduced sharpness of vision (low visual acuity). Affected individuals may also have a small visual blind spot (scotoma), farsightedness (hyperopia), or nearsightedness (myopia). Achromatopsia is different from the more common forms of color vision deficiency (also called color blindness), in which people can perceive color but have difficulty distinguishing between certain colors, such as red and green. One form of color blindness, called blue cone monochromacy (BCM), is sometimes considered a form of incomplete achromatopsia.  ar Autosomal recessive CNGA3 https://medlineplus.gov/genetics/gene/cnga3 CNGB3 https://medlineplus.gov/genetics/gene/cngb3 GNAT2 https://medlineplus.gov/genetics/gene/gnat2 PDE6C https://medlineplus.gov/genetics/gene/pde6c PDE6H https://medlineplus.gov/genetics/gene/pde6h ATF6 https://www.ncbi.nlm.nih.gov/gene/22926 ACHM Achromatism Rod monochromatism GTR C0152200 GTR C1841721 GTR C1849792 GTR C1857618 GTR C1864900 GTR C2751309 ICD-10-CM H53.51 MeSH D003117 OMIM 216900 OMIM 262300 OMIM 610024 OMIM 613093 OMIM 613856 SNOMED CT 56852002 2025-08 2026-02-12 Acrocallosal syndrome https://medlineplus.gov/genetics/condition/acrocallosal-syndrome descriptionAcrocallosal syndrome is a rare condition characterized by a brain abnormality called agenesis of the corpus callosum, the presence of extra fingers and toes (polydactyly), and distinctive facial features. The signs and symptoms of this disorder are present at birth, and their severity varies widely among affected individuals.Agenesis of the corpus callosum occurs when the tissue that connects the left and right halves of the brain (the corpus callosum) fails to form normally during the early stages of development before birth. Other brain abnormalities, including the growth of large cysts in brain tissue, have also been reported in people with acrocallosal syndrome. The changes in brain structure associated with this condition lead to delayed development and intellectual disability, which is most often moderate to severe. Some affected individuals also experience seizures.Extra fingers and toes are common in people with acrocallosal syndrome. The extra digits can be on the same side of the hand or foot as the pinky or little toe (postaxial polydactyly) or on the same side as the thumb or great toe (preaxial polydactyly). Some affected individuals also have webbed or fused skin between the fingers or toes (syndactyly).Distinctive facial features that can occur with acrocallosal syndrome include widely spaced eyes (hypertelorism) and a high, prominent forehead. Many affected individuals also have an unusually large head size (macrocephaly). ar Autosomal recessive ad Autosomal dominant GLI3 https://medlineplus.gov/genetics/gene/gli3 KIF7 https://medlineplus.gov/genetics/gene/kif7 ACLS Hallux duplication, postaxial polydactyly, and absence of corpus callosum Schinzel acrocallosal syndrome Schinzel syndrome 1 GTR C0796147 MeSH D055673 OMIM 200990 SNOMED CT 715951007 2017-01 2020-08-18 Acromicric dysplasia https://medlineplus.gov/genetics/condition/acromicric-dysplasia descriptionAcromicric dysplasia is a condition characterized by severely short stature, short limbs, stiff joints, and distinctive facial features.Newborns with acromicric dysplasia are of normal size, but slow growth over time results in short stature. The average height of adults with this disorder is about 4 feet, 2 inches for women and 4 feet, 5 inches for men. The long bones of the arms and legs, and the bones in the hands and feet, are shorter than would be expected for the individual's height. Other skeletal features that occur in this disorder include slowed mineralization of bone (delayed bone age), abnormally shaped bones of the spine (vertebrae), and constrained movement of joints. Affected individuals often develop carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. A misalignment of the hip joints (hip dysplasia) can also occur in this disorder. These skeletal and joint problems may require treatment, but most affected individuals have few limitations in their activities.Children with acromicric dysplasia may have a round face, sharply defined eyebrows, long eyelashes, a bulbous nose with upturned nostrils, a long space between the nose and upper lip (long philtrum), and a small mouth with thick lips. These facial differences become less apparent in adulthood. Intelligence is unaffected in this disorder, and life expectancy is generally normal. ad Autosomal dominant FBN1 https://medlineplus.gov/genetics/gene/fbn1 ACMICD GTR C0265287 MeSH D010009 OMIM 102370 SNOMED CT 254090007 2014-12 2020-08-18 Actin-accumulation myopathy https://medlineplus.gov/genetics/condition/actin-accumulation-myopathy descriptionActin-accumulation myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with actin-accumulation myopathy have severe muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body. Signs and symptoms of this condition are apparent in infancy and include feeding and swallowing difficulties, a weak cry, and difficulty with controlling head movements. Affected babies are sometimes described as "floppy" and may be unable to move on their own.The severe muscle weakness that occurs in actin-accumulation myopathy also affects the muscles used for breathing. Individuals with this disorder may take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Frequent respiratory infections and life-threatening breathing difficulties can occur. Because of the respiratory problems, most affected individuals do not survive past infancy. Those who do survive have delayed development of motor skills such as sitting, crawling, standing, and walking.The name actin-accumulation myopathy derives from characteristic accumulations in muscle cells of filaments composed of a protein called actin. These filaments can be seen when muscle tissue is viewed under a microscope. ad Autosomal dominant n Not inherited ACTA1 https://medlineplus.gov/genetics/gene/acta1 Actin filament aggregate myopathy Actin myopathy Congenital myopathy with excess of thin filaments Nemaline myopathy 3 GTR C3711389 MeSH D017696 OMIM 161800 SNOMED CT 702349003 2012-04 2020-08-18 Action myoclonus–renal failure syndrome https://medlineplus.gov/genetics/condition/action-myoclonus-renal-failure-syndrome descriptionAction myoclonus–renal failure (AMRF) syndrome causes episodes of involuntary muscle jerking or twitching (myoclonus) and, often, kidney (renal) disease. Although the condition name refers to kidney disease, not everyone with the condition has problems with kidney function.The movement problems associated with AMRF syndrome typically begin with involuntary rhythmic shaking (tremor) in the fingers and hands that occurs at rest and is most noticeable when trying to make small movements, such as writing. Over time, tremors can affect other parts of the body, such as the head, torso, legs, and tongue. Eventually, the tremors worsen to become myoclonic jerks, which can be triggered by voluntary movements or the intention to move (action myoclonus). These myoclonic jerks typically occur in the torso; upper and lower limbs; and face, particularly the muscles around the mouth and the eyelids. Anxiety, excitement, stress, or extreme tiredness (fatigue) can worsen the myoclonus. Some affected individuals develop seizures, a loss of sensation and weakness in the limbs (peripheral neuropathy), or hearing loss caused by abnormalities in the inner ear (sensorineural hearing loss). Severe seizures or myoclonus can be life-threatening.When kidney problems occur, an early sign is excess protein in the urine (proteinuria). Kidney function worsens over time, until the kidneys are no longer able to filter fluids and waste products from the body effectively (end-stage renal disease).AMRF syndrome typically begins causing symptoms between ages 15 and 25, but it can appear at younger or older ages. The age of onset and the course of the condition vary, even among members of the same family. Either the movement problems or kidney disease can occur first, or they can begin at the same time. Most people survive 7 to 15 years after the symptoms appear. ar Autosomal recessive SCARB2 https://medlineplus.gov/genetics/gene/scarb2 Action myoclonus-renal failure syndrome Action myoclonus–renal failure syndrome AMRF Epilepsy, progressive myoclonic 4, with or without renal failure EPM4 Familial myoclonus with renal failure Myoclonus-nephropathy syndrome Progressive myoclonus epilepsy with renal failure GTR C0751779 MeSH D020191 OMIM 254900 2016-06 2020-08-18 Activated PI3K-delta syndrome https://medlineplus.gov/genetics/condition/activated-pi3k-delta-syndrome descriptionActivated PI3K-delta syndrome (also known as APDS) is a disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells (lymphopenia), particularly B cells and T cells. Normally, these cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The severity of activated PI3K-delta syndrome varies widely. Some people may have multiple, severe infections while others show mild symptoms to none at all.Most commonly, people with activated PI3K-delta syndrome develop recurrent infections that begin in childhood, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with activated PI3K-delta syndrome may also have chronic active viral infections, such as Epstein-Barr virus, herpes simplex virus, or cytomegalovirus infections.Another possible feature of activated PI3K-delta syndrome is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly). The white blood cells can also build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While nodular lymphoid hyperplasia is not cancerous (benign), activated PI3K-delta syndrome increases the risk of developing forms of blood cancer called Hodgkin lymphoma and non-Hodgkin lymphoma.Some people with activated PI3K-delta syndrome develop autoimmunity, which occurs when the body attacks its own tissues and organs by mistake.There are two types of activated PI3K-delta syndrome, each with different genetic causes. ad Autosomal dominant PIK3R1 https://medlineplus.gov/genetics/gene/pik3r1 PIK3CD https://medlineplus.gov/genetics/gene/pik3cd APDS Immunodeficiency 14 Immunodeficiency 36 P110δ-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency PASLI GTR C3714976 GTR C4014934 ICD-10-CM MeSH D007153 OMIM 615513 OMIM 616005 SNOMED CT 711480000 2023-08 2023-11-10 Acute necrotizing encephalopathy type 1 https://medlineplus.gov/genetics/condition/acute-necrotizing-encephalopathy-type-1 descriptionAcute necrotizing encephalopathy type 1, also known as susceptibility to infection-induced acute encephalopathy 3 or IIAE3, is a rare type of brain disease (encephalopathy) that occurs following a viral infection such as the flu.Acute necrotizing encephalopathy type 1 typically appears in infancy or early childhood, although some people do not develop the condition until adolescence or adulthood. People with this condition usually show typical symptoms of an infection, such as fever, cough, congestion, vomiting, and diarrhea, for a few days. Following these flu-like symptoms, affected individuals develop neurological problems, such as seizures, hallucinations, difficulty coordinating movements (ataxia), or abnormal muscle tone. Eventually, most affected individuals go into a coma, which usually lasts for a number of weeks. The condition is described as "acute" because the episodes of illness are time-limited.People with acute necrotizing encephalopathy type 1 develop areas of damage (lesions) in certain regions of the brain. As the condition progresses, these brain regions develop swelling (edema), bleeding (hemorrhage), and then tissue death (necrosis). The progressive brain damage and tissue loss results in encephalopathy.Approximately one-third of individuals with acute necrotizing encephalopathy type 1 do not survive their illness and subsequent neurological decline. Of those who do survive, about half have permanent brain damage due to tissue necrosis, resulting in impairments in walking, speech, and other basic functions. Over time, many of these skills may be regained, but the loss of brain tissue is permanent. Other individuals who survive their illness appear to recover completely.It is estimated that half of individuals with acute necrotizing encephalopathy type 1 are susceptible to recurrent episodes and will have another infection that results in neurological decline; some people may have numerous episodes throughout their lives. Neurological function worsens following each episode as more brain tissue is damaged. ad Autosomal dominant RANBP2 https://medlineplus.gov/genetics/gene/ranbp2 Acute necrotizing encephalitis ADANE ANE1 Autosomal dominant acute necrotizing encephalopathy IIAE3 Postinfectious acute necrotizing hemorrhagic encephalopathy Susceptibility to acute necrotizing encephalopathy Susceptibility to infection-induced acute encephalopathy Susceptibility to infection-induced acute encephalopathy 3 GTR C2675556 ICD-10-CM G04.31 MeSH D001930 OMIM 608033 SNOMED CT 111897007 2016-07 2023-11-10 Acute promyelocytic leukemia https://medlineplus.gov/genetics/condition/acute-promyelocytic-leukemia descriptionAcute promyelocytic leukemia is a form of acute myeloid leukemia, a cancer of the blood-forming tissue (bone marrow). In normal bone marrow, hematopoietic stem cells produce red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting. In acute promyelocytic leukemia, immature white blood cells called promyelocytes accumulate in the bone marrow. The overgrowth of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body, which causes many of the signs and symptoms of the condition.People with acute promyelocytic leukemia are especially susceptible to developing bruises, small red dots under the skin (petechiae), nosebleeds, bleeding from the gums, blood in the urine (hematuria), or excessive menstrual bleeding. The abnormal bleeding and bruising occur in part because of the low number of platelets in the blood (thrombocytopenia) and also because the cancerous cells release substances that cause excessive bleeding.The low number of red blood cells (anemia) can cause people with acute promyelocytic leukemia to have pale skin (pallor) or excessive tiredness (fatigue). In addition, affected individuals may heal slowly from injuries or have frequent infections due to the loss of normal white blood cells that fight infection. Furthermore, the leukemic cells can spread to the bones and joints, which may cause pain in those areas. Other general signs and symptoms may occur as well, such as fever, loss of appetite, and weight loss.Acute promyelocytic leukemia is most often diagnosed around age 40, although it can be diagnosed at any age. n Not inherited RARA https://medlineplus.gov/genetics/gene/rara PML https://medlineplus.gov/genetics/gene/pml NPM1 https://medlineplus.gov/genetics/gene/npm1 NUMA1 https://www.ncbi.nlm.nih.gov/gene/4926 STAT5B https://www.ncbi.nlm.nih.gov/gene/6777 ZBTB16 https://www.ncbi.nlm.nih.gov/gene/7704 15 https://medlineplus.gov/genetics/chromosome/15 17 https://medlineplus.gov/genetics/chromosome/17 AML M3 APL Leukemia, acute promyelocytic M3 ANLL Myeloid leukemia, acute, M3 GTR C0023487 ICD-10-CM C92.4 ICD-10-CM C92.40 ICD-10-CM C92.41 ICD-10-CM C92.42 MeSH D015473 OMIM 612376 SNOMED CT 110004001 SNOMED CT 28950004 2011-04 2020-09-08 Adams-Oliver syndrome https://medlineplus.gov/genetics/condition/adams-oliver-syndrome descriptionAdams-Oliver syndrome is a rare condition that is present at birth. The primary features are an abnormality in skin development (called aplasia cutis congenita) and malformations of the limbs. A variety of other features can occur in people with Adams-Oliver syndrome.Most people with Adams-Oliver syndrome have aplasia cutis congenita, a condition characterized by localized areas of missing skin typically occurring on the top of the head (the skull vertex). In some cases, the bone under the skin is also underdeveloped. Individuals with this condition commonly have scarring and an absence of hair growth in the affected area.Abnormalities of the hands and feet are also common in people with Adams-Oliver syndrome. These most often involve the fingers and toes and can include abnormal nails, fingers or toes that are fused together (syndactyly), and abnormally short or missing fingers or toes (brachydactyly or oligodactyly). In some cases, other bones in the hands, feet, or lower limbs are malformed or missing.Some affected infants have a condition called cutis marmorata telangiectatica congenita. This disorder of the blood vessels causes a reddish or purplish net-like pattern on the skin. In addition, people with Adams-Oliver syndrome can develop high blood pressure in the blood vessels between the heart and the lungs (pulmonary hypertension), which can be life-threatening. Other blood vessel problems and heart defects can occur in affected individuals.In some cases, people with Adams-Oliver syndrome have neurological problems, such as developmental delay, learning disabilities, or abnormalities in the structure of the brain. ad Autosomal dominant ar Autosomal recessive ARHGAP31 https://medlineplus.gov/genetics/gene/arhgap31 DOCK6 https://medlineplus.gov/genetics/gene/dock6 EOGT https://medlineplus.gov/genetics/gene/eogt RBPJ https://medlineplus.gov/genetics/gene/rbpj NOTCH1 https://medlineplus.gov/genetics/gene/notch1 DLL4 https://medlineplus.gov/genetics/gene/dll4 Absence defect of limbs, scalp, and skull AOS Aplasia cutis congenita with terminal transverse limb defects Congenital scalp defects with distal limb reduction anomalies GTR C0265268 GTR C3280182 GTR C3553748 GTR C3809092 GTR C4014970 GTR C4225271 GTR C4551482 MeSH D004476 OMIM 100300 OMIM 614219 OMIM 614814 OMIM 615297 OMIM 616028 OMIM 616589 SNOMED CT 34748004 2015-11 2020-08-18 Adenine phosphoribosyltransferase deficiency https://medlineplus.gov/genetics/condition/adenine-phosphoribosyltransferase-deficiency descriptionAdenine phosphoribosyltransferase (APRT) deficiency is an inherited condition that affects the kidneys and urinary tract. The most common feature of this condition is recurrent kidney stones; urinary tract stones are also a frequent symptom. Kidney and urinary tract stones can create blockages in the urinary tract, causing pain during urination and difficulty releasing urine.Affected individuals can develop features of this condition anytime from infancy to late adulthood. When the condition appears in infancy, the first sign is usually the presence of tiny grains of reddish-brown material in the baby's diaper caused by the passing of stones. Later, recurrent kidney and urinary tract stones can lead to problems with kidney function beginning as early as mid- to late childhood. Approximately half of individuals with APRT deficiency first experience signs and symptoms of the condition in adulthood. The first features in affected adults are usually kidney stones and related urinary problems. Other signs and symptoms of APRT deficiency caused by kidney and urinary tract stones include fever, urinary tract infection, blood in the urine (hematuria), abdominal cramps, nausea, and vomiting.Without treatment, kidney function can decline, which may lead to end-stage renal disease (ESRD). ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.The features of this condition and their severity vary greatly among affected individuals, even among members of the same family. It is estimated that 15 to 20 percent of people with APRT deficiency do not have any signs or symptoms of the condition. ar Autosomal recessive APRT https://medlineplus.gov/genetics/gene/aprt 2,8-dihydroxyadenine urolithiasis 2,8-dihydroxyadeninuria APRT deficiency DHA crystalline nephropathy GTR C0268120 MeSH D011686 OMIM 614723 SNOMED CT 124274002 SNOMED CT 238009001 SNOMED CT 238010006 SNOMED CT 65791008 2012-10 2020-08-18 Adenosine deaminase 2 deficiency https://medlineplus.gov/genetics/condition/adenosine-deaminase-2-deficiency descriptionAdenosine deaminase 2 (ADA2) deficiency is a disorder characterized by abnormal inflammation of various tissues. Signs and symptoms can begin anytime from early childhood to adulthood. The severity of the disorder also varies, even among affected individuals in the same family.Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, ADA2 deficiency causes abnormal, unprovoked inflammation that can damage the body's tissues and organs, particularly blood vessels. (Inflammation of blood vessels is known as vasculitis.) Other tissues affected by abnormal inflammation can include the skin, gastrointestinal system, liver, kidneys, and nervous system. Depending on the severity and location of the inflammation, the disorder can cause disability or be life-threatening.Signs and symptoms that can occur with ADA2 deficiency include fevers that are intermittent, meaning they come and go; areas of net-like, mottled skin discoloration called livedo racemosa; an enlarged liver and spleen (hepatosplenomegaly); and recurrent strokes affecting structures deep in the brain that can start in the first few years of life. In some people, ADA2 deficiency causes additional immune system abnormalities that increase the risk of bacterial and viral infections.ADA2 deficiency is sometimes described as a form of polyarteritis nodosa (PAN), a disorder that causes inflammation of blood vessels throughout the body (systemic vasculitis). However, not all researchers classify ADA2 deficiency as a type of PAN. ar Autosomal recessive ADA2 https://medlineplus.gov/genetics/gene/ada2 ADA2 deficiency Childhood-onset polyarteritis nodosa DADA2 Deficiency of ADA2 Sneddon syndrome GTR C0282492 GTR C3887654 ICD-10-CM M30.0 MeSH D056647 OMIM 182410 OMIM 615688 SNOMED CT 155441006 2018-08 2020-08-18 Adenosine deaminase deficiency https://medlineplus.gov/genetics/condition/adenosine-deaminase-deficiency descriptionAdenosine deaminase (ADA) deficiency is a disorder that affects the immune system. Specifically, ADA deficiency impairs the development and function of immune cells called lymphocytes. Lymphocytes are white blood cells that help the body fight infections. As a result, people with ADA deficiency often develop pneumonia, chronic diarrhea, and widespread skin rashes. Additional signs and symptoms of ADA deficiency include slow growth and developmental delays.About 80 percent of individuals with ADA deficiency also have severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. People with ADA deficiency with SCID (ADA-SCID) typically develop health problems within the first 6 months of life. Without treatment, these babies usually do not survive past age 2.About 15 to 20 percent of people with ADA deficiency develop health problems that begin between 1 and 10 years of age (delayed onset) or in adulthood (late onset). In people with this form of ADA deficiency (known as delayed or late-onset combined immunodeficiency or ADA-CID), the immune deficiency tends to be less severe than in people with ADA-SCID. People with ADA-CID typically have recurrent upper respiratory and ear infections. Over time, affected individuals may develop chronic lung damage, malnutrition, and other health problems.In some individuals, ADA deficiency only impacts red blood cells. Since white blood cells are not affected, these individuals have normal immune systems. This form of the condition is known as partial ADA deficiency. Individuals with this form do not have any health problems related to the condition. They often only find out they have ADA deficiency when they undergo testing because of an affected relative or during a normal health screening. ar Autosomal recessive ADA https://medlineplus.gov/genetics/gene/ada ADA deficiency ADA-Related Immune Deficiency, Adenosine Deaminase 1 Deficiency ADA-SCID ADA1 Deficiency Adenosine deaminase deficient severe combined immunodeficiency SCID due to ADA deficiency Severe combined immunodeficiency due to ADA deficiency Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency GTR C0392607 ICD-10-CM D81.3 MeSH D016511 OMIM 102700 SNOMED CT 44940001 2024-05 2024-05-21 Adenosine monophosphate deaminase deficiency https://medlineplus.gov/genetics/condition/adenosine-monophosphate-deaminase-deficiency descriptionAdenosine monophosphate (AMP) deaminase deficiency is a condition that can affect the muscles used for movement (skeletal muscles). In many affected individuals, AMP deaminase deficiency does not cause any symptoms. People who do experience symptoms typically have fatigue, muscle pain (myalgia), or cramps after exercise or prolonged physical activity (exercise intolerance). Following strenuous activity, they often get tired more quickly and stay tired longer than would normally be expected. In rare cases, affected individuals have more severe symptoms including severe muscle weakness, low muscle tone (hypotonia), and muscle wasting (atrophy), but it is unclear whether these symptoms are due solely to AMP deaminase deficiency or additional health conditions. Exercise intolerance associated with AMP deaminase deficiency usually becomes apparent in childhood or early adulthood. ar Autosomal recessive AMPD1 https://medlineplus.gov/genetics/gene/ampd1 AMP deaminase deficiency Exercise-induced myopathy MAD deficiency MADA deficiency Muscle AMP deaminase deficiency Myoadenylate deaminase deficiency GTR C3714933 ICD-10-CM E79.2 MeSH D011686 OMIM 615511 SNOMED CT 124525004 SNOMED CT 9105005 2008-07 2020-08-18 Adenylosuccinate lyase deficiency https://medlineplus.gov/genetics/condition/adenylosuccinate-lyase-deficiency descriptionAdenylosuccinate lyase deficiency is a neurological disorder that causes brain dysfunction (encephalopathy) leading to delayed development of mental and movement abilities (psychomotor delay), autistic characteristics that affect communication and social interaction, and seizures. A key feature that can help with diagnosis of this condition is the presence of chemicals called succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in body fluids.Adenylosuccinate lyase deficiency is classified into three forms based on the severity of the signs and symptoms. The most severe is the neonatal form. Signs and symptoms of this form can be detected at or before birth and can include impaired growth during fetal development and a small head size (microcephaly). Affected newborns have severe encephalopathy, which leads to a lack of movement, difficulty feeding, and life-threatening respiratory problems. Some affected babies develop seizures that do not improve with treatment. Because of the severity of the encephalopathy, infants with this form of the condition generally do not survive more than a few weeks after birth.Adenylosuccinate lyase deficiency type I (also known as the severe form) is the most common. The signs and symptoms of this form begin in the first months of life. Affected babies have severe psychomotor delay, weak muscle tone (hypotonia), and microcephaly. Many affected infants develop recurrent seizures that are difficult to treat, and some exhibit autistic traits, such as repetitive actions and a lack of eye contact.In individuals with adenylosuccinate lyase deficiency type II (also known as the moderate or mild form), development is typically normal for the first few years of life but then slows. Psychomotor delay is considered mild or moderate. Some children with this form of the condition develop seizures and autistic traits. ar Autosomal recessive ADSL https://medlineplus.gov/genetics/gene/adsl Adenylosuccinase deficiency ADSL deficiency Succinylpurinemic autism GTR C0268126 MeSH D011686 OMIM 103050 SNOMED CT 15285008 2014-12 2023-07-13 Adermatoglyphia https://medlineplus.gov/genetics/condition/adermatoglyphia descriptionAdermatoglyphia is the absence of ridges on the skin on the pads of the fingers and toes, as well as on the palms of the hands and soles of the feet. The patterns of these ridges (called dermatoglyphs) form whorls, arches, and loops that are the basis for each person's unique fingerprints. Because no two people have the same patterns, fingerprints have long been used as a way to identify individuals. However, people with adermatoglyphia do not have these ridges, and so they cannot be identified by their fingerprints. Adermatoglyphia has been called the "immigration delay disease" because affected individuals have had difficulty entering countries that require fingerprinting for identification.In some families, adermatoglyphia occurs without any related signs and symptoms. In others, a lack of dermatoglyphs is associated with other features, typically affecting the skin. These can include small white bumps called milia on the face, blistering of the skin in areas exposed to heat or friction, and a reduced number of sweat glands on the hands and feet. Adermatoglyphia is also a feature of several rare syndromes classified as ectodermal dysplasias, including a condition called Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis that affects the skin, hair, sweat glands, and teeth. ad Autosomal dominant SMARCAD1 https://medlineplus.gov/genetics/gene/smarcad1 Absence of fingerprints ADERM ADG Immigration delay disease MeSH D003878 OMIM 129200 OMIM 136000 SNOMED CT 83145004 2015-04 2020-08-18 Adiposis dolorosa https://medlineplus.gov/genetics/condition/adiposis-dolorosa descriptionAdiposis dolorosa is a condition that is characterized by painful fatty (adipose) tissue just underneath the skin (subcutaneous). The pain is often associated with multiple noncancerous (benign) tumors called lipomas. Adiposis dolorosa occurs most often in women between the ages of 35 and 50 who are overweight or have obesity.Adiposis dolorosa affects the adipose tissue. Adipose tissue is found in many parts of the body. It stores fat for energy and provides support for the body’s structures. In some individuals, lipomas develop within the adipose tissue. These lipomas can occur anywhere on the body, but they are most often found on the torso, buttocks, or the upper arms and legs. The lipomas in people with adiposis dolorosa usually feel like firm bumps (nodules) underneath the skin and tend to be painful. The pain can be severe, particularly if the lipomas are pressing on a nearby nerve. In some people, the pain is disabling.People with adiposis dolorosa may experience additional signs and symptoms. However, these features do not occur in all people with adiposis dolorosa, and it is unclear whether they are directly related to the condition. Researchers are working to learn more about the signs and symptoms of this condition. ad Autosomal dominant Adiposalgia Adipose tissue rheumatism Dercum disease Lipomatosis dolorosa Morbus Dercum MeSH D000274 OMIM 103200 SNOMED CT 71404003 2026-02 2026-02-12 Adolescent idiopathic scoliosis https://medlineplus.gov/genetics/condition/adolescent-idiopathic-scoliosis descriptionAdolescent idiopathic scoliosis is an abnormal curvature of the spine that appears in late childhood or adolescence. Instead of growing straight, the spine develops a side-to-side curvature, usually in an elongated "S" or "C" shape; the bones of the spine are also slightly twisted or rotated.Adolescent idiopathic scoliosis appears during the adolescent growth spurt, a time when children are growing rapidly. In many cases the abnormal spinal curve is stable, although in some children the curve is progressive (meaning it becomes more severe over time). For unknown reasons, severe and progressive curves occur more frequently in girls than in boys. However, mild spinal curvature is equally common in girls and boys.Mild scoliosis generally does not cause pain, problems with movement, or difficulty breathing. It may only be diagnosed if it is noticed during a regular physical examination or a scoliosis screening at school. The most common signs of the condition include a tilt or unevenness (asymmetry) in the shoulders, hips, or waist, or having one leg that appears longer than the other. A small percentage of affected children develop more severe, pronounced spinal curvature.Scoliosis can occur as a feature of other conditions, including a variety of genetic syndromes. However, adolescent idiopathic scoliosis typically occurs by itself, without signs and symptoms affecting other parts of the body. u Pattern unknown AIS Late onset idiopathic scoliosis ICD-10-CM M41.12 ICD-10-CM M41.122 ICD-10-CM M41.123 ICD-10-CM M41.124 ICD-10-CM M41.125 ICD-10-CM M41.126 ICD-10-CM M41.127 ICD-10-CM M41.129 MeSH D012600 OMIM 181800 OMIM 607354 OMIM 608765 OMIM 612238 OMIM 612239 SNOMED CT 203646004 2013-09 2023-11-07 Adult polyglucosan body disease https://medlineplus.gov/genetics/condition/adult-polyglucosan-body-disease descriptionAdult polyglucosan body disease (APBD) is a condition that affects the nervous system. People with APBD typically first experience signs and symptoms related to the condition between ages 35 and 60. Initial symptoms of the disorder include numbness and tingling in the legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). As a result, affected individuals can have an unsteady gait, poor balance, and an increased risk of falling.Damage to the nerves that control bladder function, a condition called neurogenic bladder, is another feature that often occurs early in the course of APBD. Affected individuals have increasing difficulty starting or stopping the flow of urine.Eventually, most people with APBD lose the ability to control their bladder and bowel functions and their limbs. Damage to the autonomic nervous system, which controls body functions that are mostly involuntary, leads to problems with blood pressure, heart rate, breathing rate, digestion, temperature regulation, and sexual response, and results in daily bouts of exhaustion. About half of people with APBD experience a decline in intellectual function (dementia). ar Autosomal recessive GBE1 https://medlineplus.gov/genetics/gene/gbe1 APBD Polyglucosan body disease, adult form GTR C1849722 MeSH D002493 MeSH D006008 OMIM 263570 SNOMED CT 721099001 2013-02 2020-08-18 Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia https://medlineplus.gov/genetics/condition/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia descriptionAdult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a neurological condition characterized by changes to certain areas of the brain. A hallmark of ALSP is leukoencephalopathy, which is the alteration of a type of brain tissue called white matter. White matter consists of nerve fibers (axons) covered by a substance called myelin that insulates and protects them. The axons extend from nerve cells (neurons) and transmit nerve impulses throughout the body. Areas of damage to this brain tissue (white matter lesions) can be seen with magnetic resonance imaging (MRI). Another feature of ALSP is swellings called spheroids in the axons of the brain, which are a sign of axon damage. Also common in ALSP are abnormally pigmented glial cells. Glial cells are specialized brain cells that protect and maintain neurons. Damage to myelin and neurons is thought to contribute to many of the neurological signs and symptoms in people with ALSP.Symptoms of ALSP usually begin in a person's forties and worsen over time. Personality changes, including depression and a loss of social inhibitions, are among the earliest symptoms of ALSP. Affected individuals may develop memory loss and loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Loss of this function impairs skills such as impulse control, self-monitoring, and focusing attention appropriately. Some people with ALSP have mild seizures, usually only when the condition begins. As ALSP progresses, it causes a severe decline in thinking and reasoning abilities (dementia).Over time, motor skills are affected, and people with ALSP may have difficulty walking. Many develop a pattern of movement abnormalities known as parkinsonism, which includes unusually slow movement (bradykinesia), involuntary trembling (tremor), and muscle stiffness (rigidity). The pattern of cognitive and motor problems are variable, even among individuals in the same family, although almost all affected individuals ultimately become unable to walk, speak, and care for themselves.ALSP was previously thought to be two separate conditions, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD), both of which cause very similar white matter damage and cognitive and movement problems. POLD was thought to be distinguished by the presence of pigmented glial cells and an absence of spheroids; however, people with HDLS can have pigmented cells, too, and people with POLD can have spheroids. HDLS and POLD are now considered to be part of the same disease spectrum, which researchers have recommended calling ALSP. ad Autosomal dominant CSF1R https://medlineplus.gov/genetics/gene/csf1r ALSP Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia GTR C3711381 MeSH D056784 OMIM 221820 SNOMED CT 702427005 2012-12 2020-08-18 African iron overload https://medlineplus.gov/genetics/condition/african-iron-overload descriptionAfrican iron overload is a condition that involves absorption of too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the liver, bone marrow, and spleen. Humans cannot increase the excretion of iron, although some iron is lost through bleeding or when cells of the intestine (enterocytes) are shed at the end of the cells' lifespan. Iron levels in the body are primarily regulated through control of how much iron is absorbed from the diet.African iron overload results from a diet high in iron. It is particularly associated with consumption of a traditional African beer that contains dissolved iron from the metal drums in which it is brewed. Some evidence suggests that a genetic predisposition to absorbing too much iron may also be involved.In African iron overload, excess iron typically accumulates primarily in certain immune cells called reticuloendothelial cells. Reticuloendothelial cells include macrophages in the bone marrow and spleen and Kupffer cells, which are specialized macrophages found in the liver that help protect the body against foreign invaders such as viruses and bacteria. Later in the course of the condition, iron also accumulates in liver cells (hepatocytes). This pattern differs from that seen in a similar iron overload disorder called hereditary hemochromatosis, in which the excess iron accumulates primarily in the hepatocytes.When too much iron is absorbed, the resulting iron overload can eventually damage tissues and organs. Iron overload in the liver can lead to chronic liver disease (cirrhosis). Cirrhosis increases the risk of developing a type of liver cancer called hepatocellular carcinoma. Iron overload in immune cells may affect their ability to fight infections. African iron overload is associated with an increased risk of developing infections such as tuberculosis. The excess iron also leads to a faster-than-normal breakdown of vitamin C in the body, so affected individuals are at increased risk of vitamin C deficiency problems such as scurvy.People with African iron overload may have a slightly low number of red blood cells (mild anemia), possibly because the iron that accumulates in the liver, bone marrow, and spleen is less available for production of red blood cells. Affected individuals also have high levels of a protein called ferritin in their blood, which can be detected with a blood test. Ferritin stores and releases iron in cells, and cells produce more ferritin in response to excess amounts of iron. u Pattern unknown SLC40A1 https://medlineplus.gov/genetics/gene/slc40a1 African hemochromatosis African nutritional hemochromatosis African siderosis MeSH D012806 OMIM 601195 SNOMED CT 66576001 2011-12 2023-11-10 Age-related hearing loss https://medlineplus.gov/genetics/condition/age-related-hearing-loss descriptionAge-related hearing loss (also known as presbycusis) is a decrease in hearing ability that happens with age. In most cases, the hearing loss affects both ears. It can begin as early as a person's thirties or forties and worsens gradually over time.Age-related hearing loss first affects the ability to hear high-frequency sounds, such as speech. Affected people find it increasingly difficult to understand what others are saying, particularly when there is background noise (such as at a party). However, because the hearing loss is gradual, many people do not realize they cannot hear as well as they used to. They may turn up the television volume or start speaking louder without being aware of it.As the hearing loss worsens, it affects more frequencies of sound, making it difficult to hear more than just speech. Determining where a sound is coming from (localization) and identifying its source become more challenging. Some affected individuals also experience a ringing sensation in the ears (tinnitus) or dizziness and problems with balance (presbystasis).Age-related hearing loss often impacts a person's quality of life. Because affected individuals have trouble understanding speech, the condition affects their ability to communicate. It can contribute to social isolation, depression, and loss of self-esteem. Age-related hearing loss also causes safety issues if individuals become unable to hear smoke alarms, car horns, and other sounds that alert people to dangerous situations. u Pattern unknown APOE https://medlineplus.gov/genetics/gene/apoe MYO7A https://medlineplus.gov/genetics/gene/myo7a CDH23 https://medlineplus.gov/genetics/gene/cdh23 KCNQ4 https://medlineplus.gov/genetics/gene/kcnq4 SLC26A4 https://medlineplus.gov/genetics/gene/slc26a4 MTHFR https://medlineplus.gov/genetics/gene/mthfr NAT2 https://www.ncbi.nlm.nih.gov/gene/10 EDN1 https://www.ncbi.nlm.nih.gov/gene/1906 ESRRG https://www.ncbi.nlm.nih.gov/gene/2104 GRM7 https://www.ncbi.nlm.nih.gov/gene/2917 GRM8 https://www.ncbi.nlm.nih.gov/gene/2918 MYO6 https://www.ncbi.nlm.nih.gov/gene/4646 UCP2 https://www.ncbi.nlm.nih.gov/gene/7351 GRHL2 https://www.ncbi.nlm.nih.gov/gene/79977 GIPC3 https://www.ncbi.nlm.nih.gov/gene/126326 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Age-related hearing impairment Deafness due to old age Hearing loss, age-related Old-aged sensorineural hearing impairment Presbyacusia Presbycusis ICD-10-CM H91.1 ICD-10-CM H91.10 ICD-10-CM H91.11 ICD-10-CM H91.12 ICD-10-CM H91.13 MeSH D011304 OMIM 612448 OMIM 612976 SNOMED CT 49526009 2017-10 2020-09-08 Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration descriptionAge-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. Subtle abnormalities indicating changes in vision may occur in a person's forties or fifties. Distorted vision and vision loss usually become noticeable in a person's sixties or seventies and tend to worsen over time.Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected, but slow adjustment of vision to darkness (dark adaptation) and reduced dim light (scotopic) vision often occur in the early stages of the disease.Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and vision loss that worsens slowly over time. The most advanced stage of dry age-related macular degeneration is known as geographic atrophy, in which areas of the macula waste away (atrophy), resulting in severe vision loss. Dry age-related macular degeneration typically affects vision in both eyes, although vision loss often occurs in one eye before the other.In 10 to 15 percent of affected individuals, the dry form progresses to the wet form of age-related macular degeneration. The wet form is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted. The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly. u Pattern unknown APOE https://medlineplus.gov/genetics/gene/apoe ERCC6 https://medlineplus.gov/genetics/gene/ercc6 BEST1 https://medlineplus.gov/genetics/gene/best1 FBLN5 https://medlineplus.gov/genetics/gene/fbln5 CFH https://medlineplus.gov/genetics/gene/cfh CFI https://medlineplus.gov/genetics/gene/cfi ABCA4 https://medlineplus.gov/genetics/gene/abca4 ELOVL4 https://medlineplus.gov/genetics/gene/elovl4 C3 https://medlineplus.gov/genetics/gene/c3 CFHR5 https://medlineplus.gov/genetics/gene/cfhr5 ARMS2 https://medlineplus.gov/genetics/gene/arms2 HTRA1 https://medlineplus.gov/genetics/gene/htra1 ASPM https://medlineplus.gov/genetics/gene/aspm CST3 https://medlineplus.gov/genetics/gene/cst3 C2 https://medlineplus.gov/genetics/gene/c2 F13B https://medlineplus.gov/genetics/gene/f13b LIPC https://medlineplus.gov/genetics/gene/lipc CFB https://www.ncbi.nlm.nih.gov/gene/629 C9 https://www.ncbi.nlm.nih.gov/gene/735 CETP https://www.ncbi.nlm.nih.gov/gene/1071 COL8A1 https://www.ncbi.nlm.nih.gov/gene/1295 COL10A1 https://www.ncbi.nlm.nih.gov/gene/1300 CX3CR1 https://www.ncbi.nlm.nih.gov/gene/1524 FRK https://www.ncbi.nlm.nih.gov/gene/2444 CFHR1 https://www.ncbi.nlm.nih.gov/gene/3078 CFHR2 https://www.ncbi.nlm.nih.gov/gene/3080 MAP2 https://www.ncbi.nlm.nih.gov/gene/4133 TIMP3 https://www.ncbi.nlm.nih.gov/gene/7078 VEGFA https://www.ncbi.nlm.nih.gov/gene/7422 TNFRSF10A https://www.ncbi.nlm.nih.gov/gene/8797 CFHR4 https://www.ncbi.nlm.nih.gov/gene/10877 CFHR3 https://www.ncbi.nlm.nih.gov/gene/10878 FILIP1L https://www.ncbi.nlm.nih.gov/gene/11259 HMCN1 https://www.ncbi.nlm.nih.gov/gene/83872 Age-related maculopathy AMD ARMD Macular degeneration, age-related GTR C0242383 GTR C1853147 GTR C1857813 GTR C1864205 GTR C1969108 GTR C1969651 GTR C2677774 GTR C3151060 GTR C3151063 GTR C3151070 GTR C3151079 GTR C3495438 GTR C3809523 GTR C3809653 GTR C3810042 ICD-10-CM H35.30 ICD-10-CM H35.31 ICD-10-CM H35.32 MeSH D008268 OMIM 153800 OMIM 603075 OMIM 608895 OMIM 610149 OMIM 610698 OMIM 611378 OMIM 611488 OMIM 611953 OMIM 613757 OMIM 613761 OMIM 613778 OMIM 613784 OMIM 615439 OMIM 615489 OMIM 615591 SNOMED CT 267718000 2011-06 2025-04-03 Aicardi syndrome https://medlineplus.gov/genetics/condition/aicardi-syndrome descriptionAicardi syndrome is a disorder that occurs almost exclusively in females. It is characterized by three main features that occur together in most affected individuals. People with Aicardi syndrome have absent or underdeveloped tissue connecting the left and right halves of the brain (agenesis or dysgenesis of the corpus callosum). They have seizures beginning in infancy (infantile spasms), which tend to progress to recurrent seizures (epilepsy) that can be difficult to treat. Affected individuals also have chorioretinal lacunae, which are defects in the light-sensitive tissue at the back of the eye (retina).People with Aicardi syndrome often have additional brain abnormalities, including asymmetry between the two sides of the brain, brain folds and grooves that are small in size or reduced in number, cysts, and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. Some have an unusually small head (microcephaly). Most affected individuals have moderate to severe developmental delay and intellectual disability, although some people with this disorder have milder disability.In addition to chorioretinal lacunae, people with Aicardi syndrome may have other eye abnormalities such as small or poorly developed eyes (microphthalmia) or a gap or hole (coloboma) in the optic nerve, a structure that carries information from the eye to the brain. These eye abnormalities may cause blindness in affected individuals.Some people with Aicardi syndrome have unusual facial features including a short area between the upper lip and the nose (philtrum), a flat nose with an upturned tip, large ears, and sparse eyebrows. Other features of this condition include small hands, hand malformations, and spinal and rib abnormalities leading to progressive abnormal curvature of the spine (scoliosis). They often have gastrointestinal problems such as constipation or diarrhea, gastroesophageal reflux, and difficulty feeding.The severity of Aicardi syndrome varies. Some people with this disorder have very severe epilepsy and may not survive past childhood. Less severely affected individuals may live into adulthood with milder signs and symptoms. xd X-linked dominant Agenesis of corpus callosum with chorioretinal abnormality Agenesis of corpus callosum with infantile spasms and ocular abnormalities Aicardi's syndrome Callosal agenesis and ocular abnormalities Chorioretinal anomalies with ACC GTR C0175713 MeSH D058540 OMIM 304050 SNOMED CT 80651009 2010-06 2024-10-02 Aicardi-Goutières syndrome https://medlineplus.gov/genetics/condition/aicardi-goutieres-syndrome descriptionAicardi-Goutières syndrome is a disorder with variable signs and symptoms, but it primarily affects the brain, the immune system, and the skin.Aicardi-Goutières syndrome is often divided into two types, which are distinguished by the severity of features and the age at which they begin: the early-onset form (sometimes called the classic form) and the later-onset form. Individuals with the early-onset form of Aicardi-Goutières syndrome can experience severe brain dysfunction (encephalopathy) within the first months of life. This encephalopathic phase of the disorder can last for weeks or months. Affected infants stop developing new skills and begin losing skills they had already acquired (developmental regression). Infants with this form can have seizures. Medical imaging reveals loss of white matter in the brain (leukodystrophy). White matter consists of nerve cells covered by myelin, which is a substance that protects nerves and allows them to rapidly transmit nerve impulses. Growth of the brain and skull slows down, resulting in an abnormally small head size (microcephaly). Affected individuals may have abnormal deposits of calcium (calcification) in the brain. As a result of this neurological damage, most people with Aicardi-Goutières syndrome have profound intellectual disabilities.Affected babies are usually extremely irritable and do not feed well. They also have muscle stiffness (spasticity), involuntary tensing of various muscles (dystonia), and weak muscle tone (hypotonia). They can have vision problems including vision loss and increased pressure in the eye (glaucoma).Some newborns have a combination of features that include an enlarged liver and spleen (hepatosplenomegaly), elevated blood levels of liver enzymes, and a shortage of blood cells called platelets that are needed for normal blood clotting (thrombocytopenia). They may develop intermittent fevers in the absence of infection (sterile pyrexias). While this combination of signs and symptoms is typically associated with the immune system's response to a viral infection that is present at birth (congenital), no actual infection is found in these infants. For this reason, Aicardi-Goutières syndrome is sometimes referred to as a "mimic of congenital infection."In some affected newborns, white blood cells, interferon proteins, and other immune system molecules can be detected in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). These findings are consistent with inflammation and tissue damage in the central nervous system.About 40 percent of people with the early-onset form of Aicardi-Goutières syndrome develop a skin problem called chilblains. Chilblains are painful, itchy skin lesions that are puffy and red, and they usually appear on the fingers, toes, nose, and ears. They are caused by inflammation of small blood vessels and may be brought on or made worse by exposure to cold temperatures. In about 20 percent of cases, the early-onset form of Aicardi-Goutières syndrome begins prenatally. Slow growth (intrauterine growth retardation) and brain abnormalities, especially brain calcification, may be seen on ultrasound imaging. These individuals have the most severe neurological problems and the highest risk for early death.People with the later-onset form of Aicardi-Goutières syndrome typically have normal development in infancy. In these individuals, encephalopathy typically occurs after 1 year of age. Similar to those with the early-onset form, babies with the later-onset form experience irritability, poor feeding, and sterile pyrexias. Over time, affected individuals show developmental delays and regression. They may also have spasticity and hypotonia, and the growth of the brain and head may slow leading to microcephaly. The health and developmental problems in people with the later-onset form are typically not as severe as those in individuals with the early-onset form, though the severity can vary among affected individuals.As a result of the severe neurological problems that are usually associated with Aicardi-Goutières syndrome, most people with this disorder do not survive past childhood. However, some affected individuals with the later-onset form of the condition and milder neurological problems can live into adolescence or adulthood. ar Autosomal recessive ad Autosomal dominant TREX1 https://medlineplus.gov/genetics/gene/trex1 RNASEH2A https://medlineplus.gov/genetics/gene/rnaseh2a RNASEH2B https://medlineplus.gov/genetics/gene/rnaseh2b RNASEH2C https://medlineplus.gov/genetics/gene/rnaseh2c SAMHD1 https://medlineplus.gov/genetics/gene/samhd1 IFIH1 https://medlineplus.gov/genetics/gene/ifih1 ADAR https://medlineplus.gov/genetics/gene/adar RNU7-1 https://medlineplus.gov/genetics/gene/rnu7-1 LSM11 https://medlineplus.gov/genetics/gene/lsm11 AGS Aicardi Goutieres syndrome Cree encephalitis Encephalopathy with basal ganglia calcification Familial infantile encephalopathy with intracranial calcification and chronic cerebrospinal fluid lymphocytosis Pseudotoxoplasmosis syndrome GTR C0393591 GTR C0796126 GTR C1835912 GTR C1835916 GTR C2749659 GTR C3489724 GTR C3539013 GTR C3888244 MeSH D020279 OMIM 225750 OMIM 610181 OMIM 610329 OMIM 610333 OMIM 612952 OMIM 615010 OMIM 615846 OMIM 619486 OMIM 619487 SNOMED CT 230312006 2024-09 2026-03-04 Alagille syndrome https://medlineplus.gov/genetics/condition/alagille-syndrome descriptionAlagille syndrome is a genetic disorder that can affect the liver, heart, and other parts of the body.One of the major features of Alagille syndrome is liver damage caused by abnormalities in the bile ducts. These ducts carry bile (which helps to digest fats) from the liver to the gallbladder and small intestine. In Alagille syndrome, the bile ducts may be narrow, malformed, and reduced in number (bile duct paucity). As a result, bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream. Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itchy skin, and deposits of cholesterol in the skin (xanthomas).Alagille syndrome is also associated with several heart problems, including impaired blood flow from the heart into the lungs (pulmonic stenosis). Pulmonic stenosis may occur along with a hole between the two lower chambers of the heart (ventricular septal defect) and other heart abnormalities. This combination of heart defects is called tetralogy of Fallot.People with Alagille syndrome may have distinctive facial features including a broad, prominent forehead; deep-set eyes; and a small, pointed chin. The disorder may also affect the blood vessels within the brain and spinal cord (central nervous system) and the kidneys. Affected individuals may have an unusual butterfly shape of the bones of the spinal column (vertebrae) that can be seen in an x-ray.Problems associated with Alagille syndrome generally become evident in infancy or early childhood. The severity of the disorder varies among affected individuals, even within the same family. Symptoms range from so mild as to go unnoticed to severe heart and/or liver disease requiring transplantation.Some people with Alagille syndrome may have isolated signs of the disorder, such as a heart defect like tetralogy of Fallot, or a characteristic facial appearance. These individuals do not have liver disease or other features typical of the disorder. ad Autosomal dominant JAG1 https://medlineplus.gov/genetics/gene/jag1 NOTCH2 https://medlineplus.gov/genetics/gene/notch2 20 https://medlineplus.gov/genetics/chromosome/20 Alagille's syndrome Alagille-Watson syndrome Arteriohepatic dysplasia (AHD) Cardiovertebral syndrome Cholestasis with peripheral pulmonary stenosis Hepatic ductular hypoplasia Hepatofacioneurocardiovertebral syndrome Paucity of interlobular bile ducts Watson-Miller syndrome GTR C1857761 GTR C1956125 MeSH D016738 OMIM 118450 OMIM 610205 SNOMED CT 31742004 2010-03 2021-04-07 Alcohol use disorder https://medlineplus.gov/genetics/condition/alcohol-use-disorder descriptionAlcohol use disorder is a diagnosis made when an individual has severe problems related to drinking alcohol. Alcohol use disorder can cause major health, social, and economic problems, and can endanger affected individuals and others through behaviors prompted by impaired decision-making and lowered inhibitions, such as aggression, unprotected sex, or driving while intoxicated.Alcohol use disorder is a broad diagnosis that encompasses several commonly used terms describing problems with drinking. It includes alcoholism, also called alcohol addiction, which is a long-lasting (chronic) condition characterized by a powerful, compulsive urge to drink alcohol and the inability to stop drinking after starting. In addition to alcoholism, alcohol use disorder includes alcohol abuse, which involves problem drinking without addiction.Habitual excessive use of alcohol changes the chemistry of the brain and leads to tolerance, which means that over time the amount of alcohol ingested needs to be increased to achieve the same effect. Long-term excessive use of alcohol may also produce dependence, which means that when people stop drinking, they have physical and psychological symptoms of withdrawal, such as sleep problems, irritability, jumpiness, shakiness, restlessness, headache, nausea, sweating, anxiety, and depression. In severe cases, agitation, fever, seizures, and hallucinations can occur; this pattern of severe withdrawal symptoms is called delirium tremens.The heavy drinking that often occurs in alcohol use disorder, and can also occur in short-term episodes called binge drinking, can lead to a life-threatening overdose known as alcohol poisoning. Alcohol poisoning occurs when a large quantity of alcohol consumed over a short time causes problems with breathing, heart rate, body temperature, and the gag reflex. Signs and symptoms can include vomiting, choking, confusion, slow or irregular breathing, pale or blue-tinged skin, seizures, a low body temperature, a toxic buildup of substances called ketones in the blood (alcoholic ketoacidosis), and passing out (unconsciousness). Coma, brain damage, and death can occur if alcohol poisoning is not treated immediately.Chronic heavy alcohol use can also cause long-term problems affecting many organs and systems of the body. These health problems include irreversible liver disease (cirrhosis), inflammation of the pancreas (pancreatitis), brain dysfunction (encephalopathy), nerve damage (neuropathy), high blood pressure (hypertension), stroke, weakening of the heart muscle (cardiomyopathy), irregular heartbeats (arrhythmia), and immune system problems. Long-term overuse of alcohol also increases the risk of certain cancers, including cancers of the mouth, throat, esophagus, liver, and breast. Alcohol use in pregnant women can cause birth defects and fetal alcohol syndrome, which can lead to lifelong physical and behavioral problems in the affected child. u Pattern unknown COMT https://medlineplus.gov/genetics/gene/comt SLC6A3 https://medlineplus.gov/genetics/gene/slc6a3 OPRM1 https://medlineplus.gov/genetics/gene/oprm1 ADH1B https://www.ncbi.nlm.nih.gov/gene/125 ADH1C https://www.ncbi.nlm.nih.gov/gene/126 ADH4 https://www.ncbi.nlm.nih.gov/gene/127 ALDH2 https://www.ncbi.nlm.nih.gov/gene/217 CHRM2 https://www.ncbi.nlm.nih.gov/gene/1129 DRD2 https://www.ncbi.nlm.nih.gov/gene/1813 DRD3 https://www.ncbi.nlm.nih.gov/gene/1814 GABRA2 https://www.ncbi.nlm.nih.gov/gene/2555 GABRG3 https://www.ncbi.nlm.nih.gov/gene/2567 HTR2A https://www.ncbi.nlm.nih.gov/gene/3356 SLC6A4 https://www.ncbi.nlm.nih.gov/gene/6532 TAS2R16 https://www.ncbi.nlm.nih.gov/gene/50833 Alcohol addiction Alcohol dependence Alcoholism GTR C0001973 ICD-10-CM F10.2 ICD-10-CM F10.20 ICD-10-CM F10.21 ICD-10-CM F10.22 ICD-10-CM F10.220 ICD-10-CM F10.221 ICD-10-CM F10.229 ICD-10-CM F10.23 ICD-10-CM F10.230 ICD-10-CM F10.231 ICD-10-CM F10.232 ICD-10-CM F10.239 ICD-10-CM F10.24 ICD-10-CM F10.25 ICD-10-CM F10.250 ICD-10-CM F10.251 ICD-10-CM F10.259 ICD-10-CM F10.26 ICD-10-CM F10.27 ICD-10-CM F10.28 ICD-10-CM F10.280 ICD-10-CM F10.281 ICD-10-CM F10.282 ICD-10-CM F10.288 ICD-10-CM F10.29 ICD-10-CM F10.94 MeSH D000437 OMIM 103780 SNOMED CT 7200002 2018-01 2020-08-18 Aldosterone-producing adenoma https://medlineplus.gov/genetics/condition/aldosterone-producing-adenoma descriptionAn aldosterone-producing adenoma is a noncancerous (benign) tumor that develops in an adrenal gland, which is a small hormone-producing gland located on top of each kidney. In most cases, individuals develop a single tumor in one of the adrenal glands. The adrenal tumor produces too much of the hormone aldosterone, which is a condition known as primary hyperaldosteronism. Aldosterone helps regulate the body's fluid levels and blood pressure by controlling the amount of salt retained by the kidneys. Excess aldosterone causes the kidneys to retain more salt than normal, which increases the body's fluid levels and blood pressure. People with an aldosterone-producing adenoma may develop severe high blood pressure (hypertension), and they have an increased risk of heart attack, stroke, or an irregular heart beat (atrial fibrillation). n Not inherited CTNNB1 https://medlineplus.gov/genetics/gene/ctnnb1 KCNJ5 https://medlineplus.gov/genetics/gene/kcnj5 CACNA1D https://medlineplus.gov/genetics/gene/cacna1d ATP1A1 https://medlineplus.gov/genetics/gene/atp1a1 ATP2B3 https://www.ncbi.nlm.nih.gov/gene/492 Aldosterone-secreting adenoma Aldosteronoma Conn adenoma Primary aldosteronism due to Conn adenoma GTR C1706762 MeSH D000236 2017-07 2023-02-01 Alexander disease https://medlineplus.gov/genetics/condition/alexander-disease descriptionAlexander disease is a rare disorder of the nervous system. It is one of a group of disorders, called leukodystrophies, that involve the destruction of myelin. Myelin is the fatty covering that insulates nerve fibers and promotes the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses could be disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), intellectual disability, and developmental delay. Less frequently, onset occurs later in childhood (the juvenile form) or in adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, seizures, and poor coordination (ataxia). Rarely, a neonatal form of Alexander disease occurs within the first month of life and is associated with severe intellectual disability and developmental delay, a buildup of fluid in the brain (hydrocephalus), and seizures.Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the brain and spinal cord (central nervous system). ad Autosomal dominant GFAP https://medlineplus.gov/genetics/gene/gfap Alexander's disease ALX AxD Demyelinogenic leukodystrophy Dysmyelinogenic leukodystrophy Fibrinoid degeneration of astrocytes Leukodystrophy with Rosenthal fibers GTR C0270726 MeSH D038261 OMIM 203450 SNOMED CT 81854007 2008-11 2020-08-18 Alkaptonuria https://medlineplus.gov/genetics/condition/alkaptonuria descriptionAlkaptonuria is an inherited condition that causes arthritis, kidney stones, spots of dark pigmentation, and dark urine. Ochronosis, a buildup of dark (blue-black) pigment in certain tissues, is a characteristic feature of alkaptonuria. The first symptom of alkaptonuria is often urine that turns black or very dark when it is exposed to air (oxidation). However, this color change may not occur immediately after urination.Ochronosis occurs in connective tissues throughout the body, such as the joints, tendons, and ligaments. Pigment changes can be easily seen in the whites of the eyes (sclera), the outer ears, and the hands. Dark pigment can also be found in earwax and in body sweat (perspiration). These pigment changes are usually evident after age 30.Ochronosis in the joints causes people with alkaptonuria to develop arthritis, typically in early adulthood. Arthritis usually affects the spine and large joints (such as the hips and knees). Many affected individuals require joint replacements later in life.Over time, the deposits of pigment can harden (calcify). Calcification in joints or ligaments causes them to become rigid and brittle, decreasing their flexibility and making them prone to damage. Calcification of the discs that separate the bones of the spine can cause further back pain. This calcification can also affect the cartilage that makes up the valves of the heart, which allow blood to move through the heart and prevent blood from flowing backward. As a result, the heart valves narrow (stenosis), which can cause the valves to leak (regurgitation).The body removes the excess pigment in urine. However, removing the large pigment deposits found in people with alkaptonuria can put strain on the kidneys, and this can lead to kidney (renal) failure. Similarly, a buildup of these substances in the kidneys or prostate gland can cause calcium stones to develop. If the body cannot effectively process and remove the pigment and related substances, these products substances can continue to build up in the body, worsening ochronosis, arthritis, and other features of alkaptonuria.With appropriate medical management, people with alkaptonuria generally have a normal life expectancy. ar Autosomal recessive HGD https://medlineplus.gov/genetics/gene/hgd AKU Alcaptonuria Homogentisic acid oxidase deficiency Homogentisic acidura GTR C0002066 ICD-10-CM E70.29 MeSH D000474 OMIM 203500 SNOMED CT 360381004 2025-03 2025-03-10 Allan-Herndon-Dudley syndrome https://medlineplus.gov/genetics/condition/allan-herndon-dudley-syndrome descriptionAllan-Herndon-Dudley syndrome is a rare disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs exclusively in males, disrupts development from before birth. Although affected males have impaired speech and a limited ability to communicate, they seem to enjoy interaction with other people.Most children with Allan-Herndon-Dudley syndrome have weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contractures, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan-Herndon-Dudley syndrome are unable to walk independently and become wheelchair-bound by adulthood. xr X-linked recessive SLC16A2 https://medlineplus.gov/genetics/gene/slc16a2 Allan-Herndon syndrome MCT8 (SLC16A2)-specific thyroid hormone cell transporter deficiency Mental retardation, X-linked, with hypotonia Monocarboxylate transporter 8 (MCT8) deficiency GTR C0795889 MeSH D009123 MeSH D038901 OMIM 300523 SNOMED CT 702327009 2007-05 2020-08-18 Allergic asthma https://medlineplus.gov/genetics/condition/allergic-asthma descriptionAsthma is a breathing disorder characterized by inflammation of the airways and recurrent episodes of breathing difficulty. These episodes, sometimes referred to as asthma attacks, are triggered by irritation of the inflamed airways. In allergic asthma, the attacks occur when substances known as allergens are inhaled, causing an allergic reaction. Allergens are harmless substances that the body's immune system mistakenly reacts to as though they are harmful. Common allergens include pollen, dust, animal dander, and mold. The immune response leads to the symptoms of asthma. Allergic asthma is the most common form of the disorder.A hallmark of asthma is bronchial hyperresponsiveness, which means the airways are especially sensitive to irritants and respond excessively. Because of this hyperresponsiveness, attacks can be triggered by irritants other than allergens, such as physical activity, respiratory infections, or exposure to tobacco smoke, in people with allergic asthma.An asthma attack is characterized by tightening of the muscles around the airways (bronchoconstriction), which narrows the airway and makes breathing difficult. Additionally, the immune reaction can lead to swelling of the airways and overproduction of mucus. During an attack, an affected individual can experience chest tightness, wheezing, shortness of breath, and coughing. Over time, the muscles around the airways can become enlarged (hypertrophied), further narrowing the airways.Some people with allergic asthma have another allergic disorder, such as hay fever (allergic rhinitis) or food allergies. Asthma is sometimes part of a series of allergic disorders, referred to as the atopic march. Development of these conditions typically follows a pattern, beginning with eczema (atopic dermatitis), followed by food allergies, then hay fever, and finally asthma. However, not all individuals with asthma have progressed through the atopic march, and not all individuals with one allergic disease will develop others. u Pattern unknown Extrinsic asthma GTR C1869116 ICD-10-CM J45 MeSH D001249 OMIM 600807 SNOMED CT 389145006 2015-12 2024-10-02 Alopecia areata https://medlineplus.gov/genetics/condition/alopecia-areata descriptionAlopecia areata is a common disorder that causes hair loss. "Alopecia" is a Latin term that means baldness, and "areata" refers to the patchy nature of the hair loss that is typically seen with this condition.In most people with alopecia areata, hair falls out in small, round patches, leaving coin-sized areas of bare skin. This patchy hair loss occurs most often on the scalp but can affect other parts of the body as well. Uncommonly, the hair loss involves the entire scalp (in which case the condition is known as alopecia totalis) or the whole body (alopecia universalis). Other rare forms of alopecia areata, which have different patterns of hair loss, have also been reported.Alopecia areata affects people of all ages, although it most commonly appears in adolescence or early adulthood. Hair loss occurs over a period of weeks. The hair usually grows back after several months, although it may fall out again. In some cases, unpredictable cycles of hair loss followed by regrowth can last for years. In addition to hair loss, some affected individuals have fingernail and toenail abnormalities, such as pits on the surface of the nails.The hair loss associated with alopecia areata is not painful or disabling. However, it causes changes in a person's appearance that can profoundly affect quality of life and self-esteem. In some people, the condition can lead to depression, anxiety, and other emotional or psychological issues. u Pattern unknown MTHFR https://medlineplus.gov/genetics/gene/mthfr AIRE https://medlineplus.gov/genetics/gene/aire PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 HLA-DQB1 https://medlineplus.gov/genetics/gene/hla-dqb1 HLA-DQA1 https://medlineplus.gov/genetics/gene/hla-dqa1 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 FLG https://medlineplus.gov/genetics/gene/flg CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 ERBB3 https://www.ncbi.nlm.nih.gov/gene/2065 HLA-A https://www.ncbi.nlm.nih.gov/gene/3105 HLA-C https://www.ncbi.nlm.nih.gov/gene/3107 HLA-DMB https://www.ncbi.nlm.nih.gov/gene/3109 HLA-DQA2 https://www.ncbi.nlm.nih.gov/gene/3118 HLA-DQB2 https://www.ncbi.nlm.nih.gov/gene/3120 HLA-DRA https://www.ncbi.nlm.nih.gov/gene/3122 HLA-DRB5 https://www.ncbi.nlm.nih.gov/gene/3127 HSPA1B https://www.ncbi.nlm.nih.gov/gene/3304 IFNG https://www.ncbi.nlm.nih.gov/gene/3458 IL1B https://www.ncbi.nlm.nih.gov/gene/3553 IL1RN https://www.ncbi.nlm.nih.gov/gene/3557 IL2 https://www.ncbi.nlm.nih.gov/gene/3558 IL2RA https://www.ncbi.nlm.nih.gov/gene/3559 IL4 https://www.ncbi.nlm.nih.gov/gene/3565 IL13 https://www.ncbi.nlm.nih.gov/gene/3596 IL16 https://www.ncbi.nlm.nih.gov/gene/3603 LTA https://www.ncbi.nlm.nih.gov/gene/4049 MICA https://www.ncbi.nlm.nih.gov/gene/4276 MIF https://www.ncbi.nlm.nih.gov/gene/4282 NOS3 https://www.ncbi.nlm.nih.gov/gene/4846 NOTCH4 https://www.ncbi.nlm.nih.gov/gene/4855 CCL2 https://www.ncbi.nlm.nih.gov/gene/6347 TLR1 https://www.ncbi.nlm.nih.gov/gene/7096 TNF https://www.ncbi.nlm.nih.gov/gene/7124 TRAF1 https://www.ncbi.nlm.nih.gov/gene/7185 STX17 https://www.ncbi.nlm.nih.gov/gene/9485 TSBP1 https://www.ncbi.nlm.nih.gov/gene/10665 KLRK1 https://www.ncbi.nlm.nih.gov/gene/22914 CLEC16A https://www.ncbi.nlm.nih.gov/gene/23274 PRDX5 https://www.ncbi.nlm.nih.gov/gene/25824 ICOS https://www.ncbi.nlm.nih.gov/gene/29851 BTNL2 https://www.ncbi.nlm.nih.gov/gene/56244 IKZF4 https://www.ncbi.nlm.nih.gov/gene/64375 ULBP3 https://www.ncbi.nlm.nih.gov/gene/79465 RAET1L https://www.ncbi.nlm.nih.gov/gene/154064 AFG2A https://www.ncbi.nlm.nih.gov/gene/166378 AA Alopecia circumscripta GTR C0263505 ICD-10-CM L63.0 ICD-10-CM L63.1 ICD-10-CM L63.2 ICD-10-CM L63.8 ICD-10-CM L63.9 MeSH D000506 OMIM 104000 OMIM 610753 SNOMED CT 19754005 SNOMED CT 68225006 2018-06 2026-03-16 Alpers-Huttenlocher syndrome https://medlineplus.gov/genetics/condition/alpers-huttenlocher-syndrome descriptionAlpers-Huttenlocher syndrome is one of the most severe of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Alpers-Huttenlocher syndrome typically becomes apparent in children between ages 2 and 4. People with this condition usually have three characteristic features: recurrent seizures that do not improve with treatment (intractable epilepsy), loss of mental and movement abilities (psychomotor regression), and liver disease.People with Alpers-Huttenlocher syndrome usually have additional signs and symptoms. Most have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). Neuropathy can lead to abnormal or absent reflexes (areflexia). In addition, affected individuals may develop weak muscle tone (hypotonia) that worsens until they lose the ability to control their muscles and movement. Some people with Alpers-Huttenlocher syndrome lose the ability to walk, sit, or feed themselves. Other movement-related symptoms in affected individuals can include involuntary muscle twitches (myoclonus), uncontrollable movements of the limbs (choreoathetosis), or a pattern of movement abnormalities known as parkinsonism.Affected individuals may have other brain-related signs and symptoms. Migraine headaches, often with visual sensations or auras, are common. Additionally, people with this condition may have decreased brain function that is demonstrated as sleepiness, inability to concentrate, irritability, or loss of language skills or memory. Some people with the condition may lose their eyesight or hearing. People with Alpers-Huttenlocher syndrome can survive from a few months to more than 10 years after the condition first appears. ar Autosomal recessive POLG https://medlineplus.gov/genetics/gene/polg Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis Alpers disease Alpers progressive infantile poliodystrophy Alpers syndrome Diffuse cerebral sclerosis of Schilder Progressive sclerosing poliodystrophy GTR C0205710 ICD-10-CM G31.81 MeSH D002549 OMIM 203700 SNOMED CT 20415001 2011-06 2023-02-06 Alpha thalassemia https://medlineplus.gov/genetics/condition/alpha-thalassemia descriptionAlpha thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body.In people with the characteristic features of alpha thalassemia, a reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications.Two types of alpha thalassemia can cause health problems. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome, which is also called Hb Bart syndrome or alpha thalassemia major. The milder form is called HbH disease.Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. Without treatment, most babies with this condition are stillborn or die soon after birth because of these serious health problems. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (preeclampsia), premature delivery, and abnormal bleeding.HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice). The features of HbH disease usually appear in early childhood, and affected individuals typically live into adulthood. u Pattern unknown HBA1 https://medlineplus.gov/genetics/gene/hba1 HBA2 https://medlineplus.gov/genetics/gene/hba2 Alpha-thalassemia Α-thalassemia GTR C0002312 ICD-10-CM D56.0 ICD-10-CM D56.3 MeSH D017085 OMIM 141800 OMIM 141850 OMIM 604131 SNOMED CT 68913001 2022-12 2024-06-17 Alpha thalassemia X-linked intellectual disability syndrome https://medlineplus.gov/genetics/condition/alpha-thalassemia-x-linked-intellectual-disability-syndrome descriptionAlpha thalassemia X-linked intellectual disability syndrome is an inherited disorder that affects many parts of the body. This condition occurs almost exclusively in males.Males with alpha thalassemia X-linked intellectual disability syndrome have intellectual disability and delayed development. Their speech is significantly delayed, and most never speak or sign more than a few words. Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with this disorder are never able to walk independently.Almost everyone with alpha thalassemia X-linked intellectual disability syndrome has distinctive facial features, including widely spaced eyes, a small nose with upturned nostrils, and low-set ears. The upper lip is shaped like an upside-down "V," and the lower lip tends to be prominent. These facial characteristics are most apparent in early childhood. Over time, the facial features become coarser, including a flatter face with a shortened nose.Most affected individuals have mild signs of a blood disorder called alpha thalassemia. This disorder reduces the production of hemoglobin, which is the protein in red blood cells that carries oxygen to cells throughout the body. A reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Rarely, affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue.Additional features of alpha thalassemia X-linked intellectual disability syndrome include an unusually small head size (microcephaly), short stature, and skeletal abnormalities. Many affected individuals have problems with the digestive system, such as a backflow of stomach acids into the esophagus (gastroesophageal reflux) and chronic constipation. Genital abnormalities are also common; affected males may have undescended testes and the opening of the urethra on the underside of the penis (hypospadias). In more severe cases, the external genitalia do not look clearly male or female. xr X-linked recessive ATRX https://medlineplus.gov/genetics/gene/atrx Alpha thalassemia X-linked mental retardation syndrome Alpha thalassemia/mental retardation, X-linked Alpha-thalassemia X-linked mental retardation syndrome Alpha-thalassemia/mental retardation syndrome, nondeletion type ATR-X syndrome ATRX syndrome X-linked alpha-thalassemia/mental retardation syndrome XLMR-hypotonic face syndrome GTR C1845055 ICD-10-CM D56.0 MeSH D038901 OMIM 301040 SNOMED CT 715342005 2009-08 2023-10-27 Alpha-1 antitrypsin deficiency https://medlineplus.gov/genetics/condition/alpha-1-antitrypsin-deficiency descriptionAlpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals.People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 25 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, and fatigue. Affected individuals often develop emphysema, which is a lung disease caused by damage to the small air sacs in the lungs (alveoli). Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and whites of the eyes (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk of developing a type of liver cancer called hepatocellular carcinoma.In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age. ar Autosomal recessive SERPINA1 https://medlineplus.gov/genetics/gene/serpina1 AAT AATD Alpha-1 protease inhibitor deficiency Alpha-1 related emphysema Genetic emphysema Hereditary pulmonary emphysema Inherited emphysema GTR C0221757 ICD-10-CM E88.01 MeSH D019896 OMIM 613490 SNOMED CT 30188007 2009-08 2025-04-03 Alpha-N-acetylgalactosaminidase deficiency https://medlineplus.gov/genetics/condition/alpha-n-acetylgalactosaminidase-deficiency descriptionAlpha-N-acetylgalactosaminidase deficiency, also known as Schindler disease, is an inherited disorder that can affect the development of the nervous system. People with alpha-N-acetylgalactosaminidase deficiency often have distinctive facial features that can be described as "coarse" and tooth abnormalities such as widely-spaced teeth and missing teeth (hypodontia). The three types of alpha-N-acetylgalactosaminidase deficiency differ in the severity of their signs and symptoms and the age at which they first appear. The signs and symptoms of alpha-N-acetylgalactosaminidase deficiency can vary, even among members of the same family. Type I is the most severe form of this condition. Babies with alpha-N-acetylgalactosaminidase deficiency type I appear healthy at birth. However, by late infancy, these babies typically have trouble meeting normal developmental milestones. By the age of 2 years, individuals with type I begin to lose skills that they had already acquired (developmental regression). Individuals with type I often experience weak muscle tone (hypotonia), vision and hearing loss, and seizures. During early childhood, children with type I typically lose awareness of their surroundings and eventually become unresponsive.Alpha-N-acetylgalactosaminidase deficiency type II is the least severe form. Type II is typically diagnosed in adulthood. Affected individuals may have mild cognitive impairment and hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). They may also experience a loss of sensation or muscle weakness in the extremities (peripheral neuropathy). Clusters of enlarged blood vessels that form small, dark red spots on the skin (angiokeratomas) are a characteristic feature of alpha-N-acetylgalactosaminidase deficiency type II.Type III is the intermediate form of alpha-N-acetylgalactosaminidase deficiency. People with type III may show a variety of signs and symptoms, including developmental, speech, and language delays; seizures that begin in infancy; and features of autism spectrum disorder that appear in childhood. Autism spectrum disorder is characterized by impaired communication and socialization skills. People with type III may also have skeletal signs and symptoms, such as pain in the lower back, hips, and knees. Wear on the cartilage (disks) and bones of the neck (cervical spondylosis) and a cyst-like collection of cerebrospinal fluid that forms in the spinal cord (syringohydromyelia) have also been reported. ar Autosomal recessive NAGA https://medlineplus.gov/genetics/gene/naga Alpha-galactosidase B deficiency Alpha-galNAc deficiency, Schindler type Alpha-N-acetylgalactosaminidase deficiency Alpha-NAGA deficiency Angiokeratoma corporis diffusum-glycopeptiduria GALB deficiency Kanzaki disease Lysosomal glycoaminoacid storage disease-angiokeratoma corporis diffusum NAGA deficiency type I NAGA deficiency type II NAGA deficiency type III Neuroaxonal dystrophy, Schindler type Neuronal axonal dystrophy, Schindler type Schindler disease type I Schindler disease type II Schindler disease type III GTR C1836522 GTR C1836544 MeSH D016464 OMIM 609241 OMIM 609242 SNOMED CT 238048001 2025-03 2025-03-14 Alpha-mannosidosis https://medlineplus.gov/genetics/condition/alpha-mannosidosis descriptionAlpha-mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. Affected individuals may have intellectual disability, distinctive facial features, and skeletal abnormalities. Characteristic facial features can include a large head, prominent forehead, low hairline, rounded eyebrows, large ears, flattened bridge of the nose, protruding jaw, widely spaced teeth, overgrown gums, and large tongue. The skeletal abnormalities that can occur in this disorder include reduced bone density (osteopenia), thickening of the bones at the top of the skull (calvaria), deformations of the bones in the spine (vertebrae), knock knees, and deterioration of the bones and joints.Affected individuals may also experience difficulty in coordinating movements (ataxia); muscle weakness (myopathy); delay in developing motor skills such as sitting and walking; speech impairments; increased risk of infections; enlargement of the liver and spleen (hepatosplenomegaly); a buildup of fluid in the brain (hydrocephalus); hearing loss; and a clouding of the lens of the eye (cataract). Some people with alpha-mannosidosis experience psychiatric symptoms such as depression, anxiety, or hallucinations; episodes of psychiatric disturbance may be triggered by stressors such as having undergone surgery, emotional upset, or changes in routine.The signs and symptoms of alpha-mannosidosis can range from mild to severe. The disorder may appear in infancy with rapid progression and severe neurological deterioration. Individuals with this early-onset form of alpha-mannosidosis often do not survive past childhood. In the most severe cases, an affected fetus may die before birth. Other individuals with alpha-mannosidosis experience milder signs and symptoms that appear later and progress more slowly. People with later-onset alpha-mannosidosis may survive into their fifties. The mildest cases may be detected only through laboratory testing and result in few if any symptoms. ar Autosomal recessive MAN2B1 https://medlineplus.gov/genetics/gene/man2b1 Alpha-D-mannosidosis Alpha-mannosidase B deficiency Alpha-mannosidase deficiency Deficiency of alpha-mannosidase Lysosomal alpha B mannosidosis Lysosomal alpha-D-mannosidase deficiency Mannosidosis GTR C0024748 MeSH D008363 OMIM 248500 SNOMED CT 124466001 2007-12 2023-11-10 Alpha-methylacyl-CoA racemase deficiency https://medlineplus.gov/genetics/condition/alpha-methylacyl-coa-racemase-deficiency descriptionAlpha-methylacyl-CoA racemase (AMACR) deficiency is a disorder that causes a variety of neurological problems that begin in adulthood and slowly get worse. People with AMACR deficiency may have a gradual loss in intellectual functioning (cognitive decline), seizures, and migraines. They may also have acute episodes of brain dysfunction (encephalopathy) similar to stroke, involving altered consciousness and areas of damage (lesions) in the brain. Other features of AMACR deficiency may include weakness and loss of sensation in the limbs due to nerve damage (sensorimotor neuropathy), muscle stiffness (spasticity), and difficulty coordinating movements (ataxia). Vision problems caused by deterioration of the light-sensitive layer at the back of the eye (the retina) can also occur in this disorder. ar Autosomal recessive AMACR https://medlineplus.gov/genetics/gene/amacr AMACR deficiency GTR C3280428 MeSH D018901 OMIM 614307 SNOMED CT 700463002 2013-12 2020-08-18 Alport syndrome https://medlineplus.gov/genetics/condition/alport-syndrome descriptionAlport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys gradually lose their ability to efficiently remove waste products from the body, resulting in end-stage kidney disease (ESKD).In late childhood or early adolescence, many people with Alport syndrome develop sensorineural hearing loss, which is caused by abnormalities of the inner ear. Affected individuals may also have misshapen lenses in their eyes (anterior lenticonus) and abnormal coloration of the retina, which is the light-sensitive tissue at the back of the eye. These eye abnormalities seldom lead to vision loss. ar Autosomal recessive ad Autosomal dominant x X-linked COL4A5 https://medlineplus.gov/genetics/gene/col4a5 COL4A3 https://medlineplus.gov/genetics/gene/col4a3 COL4A4 https://medlineplus.gov/genetics/gene/col4a4 Congenital hereditary hematuria Hematuria-nephropathy-deafness syndrome Hematuric hereditary nephritis Hemorrhagic familial nephritis Hemorrhagic hereditary nephritis Hereditary familial congenital hemorrhagic nephritis Hereditary hematuria syndrome Hereditary interstitial pyelonephritis Hereditary nephritis GTR C1567741 GTR C4746745 GTR C4746986 GTR C5882663 ICD-10-CM Q87.81 MeSH D009394 OMIM 104200 OMIM 203780 OMIM 301050 SNOMED CT 717766000 SNOMED CT 717767009 SNOMED CT 717768004 2023-09 2025-03-10 Alström syndrome https://medlineplus.gov/genetics/condition/alstrom-syndrome descriptionAlström syndrome is a rare condition that affects many body systems. Many of the signs and symptoms of this condition begin in infancy or early childhood, although some appear later in life.Alström syndrome is characterized by a progressive loss of vision and hearing, a form of heart disease that enlarges and weakens the heart muscle (dilated cardiomyopathy), obesity, type 2 diabetes (the most common form of diabetes), and short stature. This disorder can also cause serious or life-threatening medical problems involving the liver, kidneys, bladder, and lungs. Some individuals with Alström syndrome have a skin condition called acanthosis nigricans, which causes the skin in body folds and creases to become thick, dark, and velvety. The signs and symptoms of Alström syndrome vary in severity, and not all affected individuals have all of the characteristic features of the disorder. ar Autosomal recessive ALMS1 https://medlineplus.gov/genetics/gene/alms1 ALMS Alstrom syndrome Alstrom-Hallgren syndrome GTR C0268425 MeSH D056769 OMIM 203800 SNOMED CT 63702009 2008-08 2020-08-18 Alternating hemiplegia of childhood https://medlineplus.gov/genetics/condition/alternating-hemiplegia-of-childhood descriptionAlternating hemiplegia of childhood is a neurological condition characterized by recurrent episodes of temporary paralysis, often affecting one side of the body (hemiplegia). During some episodes, the paralysis alternates from one side of the body to the other or affects both sides at the same time. These episodes begin in infancy or early childhood, usually before 18 months of age, and the paralysis lasts from minutes to days.In addition to paralysis, affected individuals can have sudden attacks of uncontrollable muscle activity; these can cause involuntary limb movements (choreoathetosis), muscle tensing (dystonia), movement of the eyes (nystagmus), or shortness of breath (dyspnea). People with alternating hemiplegia of childhood may also experience sudden redness and warmth (flushing) or unusual paleness (pallor) of the skin. These attacks can occur during or separately from episodes of hemiplegia.The episodes of hemiplegia or uncontrolled movements can be triggered by certain factors, such as stress, extreme tiredness, cold temperatures, or bathing, although the trigger is not always known. A characteristic feature of alternating hemiplegia of childhood is that all symptoms disappear while the affected person is sleeping but can reappear shortly after awakening. The number and length of the episodes initially worsen throughout childhood but then begin to decrease over time. The uncontrollable muscle movements may disappear entirely, but the episodes of hemiplegia occur throughout life.Alternating hemiplegia of childhood also causes mild to severe cognitive problems. Almost all affected individuals have some level of developmental delay and intellectual disability. Their cognitive functioning typically declines over time. ad Autosomal dominant ATP1A2 https://medlineplus.gov/genetics/gene/atp1a2 ATP1A3 https://medlineplus.gov/genetics/gene/atp1a3 Alternating hemiplegia syndrome GTR C3549447 GTR C3553788 MeSH D006429 OMIM 104290 OMIM 614820 SNOMED CT 230466004 2014-02 2020-08-18 Alveolar capillary dysplasia with misalignment of pulmonary veins https://medlineplus.gov/genetics/condition/alveolar-capillary-dysplasia-with-misalignment-of-pulmonary-veins descriptionAlveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a disorder affecting the development of the lungs and their blood vessels. The disorder affects the millions of small air sacs (alveoli) in the lungs and the tiny blood vessels (capillaries) in the alveoli. It is through these alveolar capillaries that inhaled oxygen enters the bloodstream for distribution throughout the body and carbon dioxide leaves the bloodstream to be exhaled.In ACD/MPV, the alveolar capillaries fail to develop normally. The number of capillaries is drastically reduced, and existing capillaries are improperly positioned within the walls of the alveoli. These abnormalities in capillary number and location impede the exchange of oxygen and carbon dioxide.Other abnormalities of the blood vessels in the lungs also occur in ACD/MPV. The veins that carry blood from the lungs into the heart (pulmonary veins) are improperly positioned and may be abnormally bundled together with arteries that carry blood from the heart to the lungs (pulmonary arteries). The muscle tissue in the walls of the pulmonary arteries may be overgrown, resulting in thicker artery walls and a narrower channel. These changes restrict normal blood flow, which causes high blood pressure in the pulmonary arteries (pulmonary hypertension) and requires the heart to pump harder.Most infants with ACD/MPV are born with additional abnormalities. These may include abnormal twisting (malrotation) of the large intestine or other malformations of the gastrointestinal tract. Cardiovascular and genitourinary abnormalities are also common in affected individuals.Infants with ACD/MPV typically develop respiratory distress within a few minutes to a few hours after birth. They experience shortness of breath and cyanosis, which is a bluish appearance of the skin, mucous membranes, or the area underneath the fingernails caused by a lack of oxygen in the blood. Without lung transplantation, infants with ACD/MPV have not been known to survive past one year of age, and most affected infants live only a few weeks. ar Autosomal recessive ad Autosomal dominant FOXF1 https://medlineplus.gov/genetics/gene/foxf1 16 https://medlineplus.gov/genetics/chromosome/16 ACD ACD/MPV ACDMPV Alveolar capillary dysplasia Congenital alveolar capillary dysplasia Familial persistent pulmonary hypertension of the newborn Misalignment of the pulmonary vessels GTR C0031190 MeSH D010547 OMIM 265380 SNOMED CT 206597007 2010-04 2020-09-08 Alzheimer's disease https://medlineplus.gov/genetics/condition/alzheimers-disease descriptionAlzheimer's disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. This disorder usually appears in people older than age 65, but less common forms of the disease appear earlier in adulthood.Memory loss is the most common sign of Alzheimer's disease. Forgetfulness may be subtle at first, but the loss of memory worsens over time until it interferes with most aspects of daily living. Even in familiar settings, a person with Alzheimer's disease may get lost or become confused. Routine tasks such as preparing meals, doing laundry, and performing other household chores can be challenging. Additionally, it may become difficult to recognize people and name objects. Affected people increasingly require help with dressing, eating, and personal care.As the disorder progresses, some people with Alzheimer's disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner. Other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. People with Alzheimer's disease usually require total care during the advanced stages of the disease.Individuals with Alzheimer's disease usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Survival is usually shorter in individuals diagnosed after age 80 than in those diagnosed at a younger age. In Alzheimer's disease, death usually results from pneumonia, malnutrition, or general body wasting (inanition).Alzheimer's disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear between a person's thirties and mid-sixties, while the late-onset form appears during or after a person's mid-sixties. The early-onset form of Alzheimer's disease is much less common than the late-onset form, accounting for less than 10 percent of all cases of Alzheimer's disease. u Pattern unknown ad Autosomal dominant+1 affected parent APP https://medlineplus.gov/genetics/gene/app APOE https://medlineplus.gov/genetics/gene/apoe PSEN1 https://medlineplus.gov/genetics/gene/psen1 PSEN2 https://medlineplus.gov/genetics/gene/psen2 AD Alzheimer dementia (AD) Alzheimer disease Alzheimer sclerosis Alzheimer syndrome Alzheimer-type dementia (ATD) DAT Familial Alzheimer disease (FAD) Presenile and senile dementia Primary senile degenerative dementia SDAT GTR C0002395 GTR C1843013 GTR C1847200 GTR C1863051 ICD-10-CM G30 ICD-10-CM G30.0 ICD-10-CM G30.1 ICD-10-CM G30.8 ICD-10-CM G30.9 MeSH D000544 OMIM 104300 OMIM 104310 OMIM 606889 OMIM 607822 SNOMED CT 10532003 SNOMED CT 26929004 SNOMED CT 416780008 SNOMED CT 416975007 SNOMED CT 65096006 2008-12 2024-10-02 Amelogenesis imperfecta https://medlineplus.gov/genetics/condition/amelogenesis-imperfecta descriptionAmelogenesis imperfecta is a group of disorders of tooth development. In people with this condition, tooth enamel does not form properly. Tooth enamel is the hard, white material that is mainly made of mineral crystals and forms the protective outer layer of each tooth. People with amelogenesis imperfecta may have teeth that appear (erupt) later than normal, and their teeth may be unusually small, discolored, pitted, or grooved. Affected individuals can also have misalignment of the top and bottom teeth (malocclusion). Because of these teeth problems, people with amelogenesis imperfecta often have difficulty eating, sensitivity to certain foods and drinks, and pain when brushing their teeth. Their teeth are also prone to rapid wear, frequent cavities, and breakage. Other dental abnormalities are also possible. These problems can affect both primary (baby) teeth and permanent (adult) teeth.Because amelogenesis imperfecta causes changes in a person's appearance, the condition can profoundly affect quality of life and self-esteem if not treated. In some people, the condition can lead to avoidance of social activities, anxiety, and other emotional or psychological issues.Researchers have described at least four forms of amelogenesis imperfecta: hypoplastic (also referred to as type I), hypomaturation (type II), hypocalcified (type III), and hypomaturation and hypocalcified with taurodontism (type IV). These types are generally distinguished by their specific enamel abnormalities. The hypoplastic type is defined by thin enamel, the hypomaturation type is defined by weak or brittle enamel, and the hypocalcified type is defined by soft enamel. The hypomaturation and hypocalcified with taurodontism type involves weak and soft enamel and teeth that are too large for the size of their roots, which are small (this combination is known as taurodontism). These four types of amelogenesis imperfecta are further divided into subtypes according to their pattern of inheritance and their genetic cause.Some doctors simplify the classification of amelogenesis imperfecta by grouping structural problems with enamel into one group (quantitative enamel defect) and strength or hardness issues with enamel into a second group (qualitative enamel defect).Amelogenesis imperfecta can occur without any other signs and symptoms (isolated) or it can occur as part of a syndrome that affects multiple parts of the body (syndromic). A subtype of type I, known as amelogenesis imperfecta type IG, can affect the kidneys and is called enamel-renal syndrome. People with this condition may develop calcium deposits in the kidneys (nephrocalcinosis) later in life. ad Autosomal dominant ar Autosomal recessive x X-linked AMELX https://medlineplus.gov/genetics/gene/amelx ENAM https://medlineplus.gov/genetics/gene/enam MMP20 https://medlineplus.gov/genetics/gene/mmp20 COL7A1 https://medlineplus.gov/genetics/gene/col7a1 LAMB3 https://medlineplus.gov/genetics/gene/lamb3 LAMC2 https://medlineplus.gov/genetics/gene/lamc2 LAMA3 https://medlineplus.gov/genetics/gene/lama3 COL17A1 https://medlineplus.gov/genetics/gene/col17a1 SACK1H https://medlineplus.gov/genetics/gene/sack1h FAM20A https://medlineplus.gov/genetics/gene/fam20a AMBN https://www.ncbi.nlm.nih.gov/gene/258 ARHGAP6 https://www.ncbi.nlm.nih.gov/gene/395 DLX3 https://www.ncbi.nlm.nih.gov/gene/1747 ITGB6 https://www.ncbi.nlm.nih.gov/gene/3694 GPR68 https://www.ncbi.nlm.nih.gov/gene/8111 KLK4 https://www.ncbi.nlm.nih.gov/gene/9622 SLC24A4 https://www.ncbi.nlm.nih.gov/gene/56796 SP6 https://www.ncbi.nlm.nih.gov/gene/80320 RELT https://www.ncbi.nlm.nih.gov/gene/84957 ACP4 https://www.ncbi.nlm.nih.gov/gene/93650 KLF14 https://www.ncbi.nlm.nih.gov/gene/136259 ODAPH https://www.ncbi.nlm.nih.gov/gene/152816 WDR72 https://www.ncbi.nlm.nih.gov/gene/256764 AMTN https://www.ncbi.nlm.nih.gov/gene/401138 AI Congenital enamel hypoplasia GTR C0002452 MeSH D000567 OMIM 104500 OMIM 104510 OMIM 104530 OMIM 130900 OMIM 204650 OMIM 204690 OMIM 204700 OMIM 301200 OMIM 612529 OMIM 613211 OMIM 614832 OMIM 615887 OMIM 616221 OMIM 616270 OMIM 617217 OMIM 617297 OMIM 617607 OMIM 618386 OMIM 620104 SNOMED CT 234961008 SNOMED CT 78494001 2025-12 2026-03-02 Aminoacylase 1 deficiency https://medlineplus.gov/genetics/condition/aminoacylase-1-deficiency descriptionAminoacylase 1 deficiency is an inherited disorder that can cause neurological problems; the pattern and severity of signs and symptoms vary widely among affected individuals. Individuals with this condition typically have delayed development of mental and motor skills (psychomotor delay). They can have movement problems, reduced muscle tone (hypotonia), mild intellectual disability, and seizures. However, some people with aminoacylase 1 deficiency have no health problems related to the condition. A key feature common to all people with aminoacylase 1 deficiency is high levels of modified protein building blocks (amino acids), called N-acetylated amino acids, in the urine. ar Autosomal recessive ACY1 https://medlineplus.gov/genetics/gene/acy1 ACY1D Deficiency of the aminoacylase-1 enzyme GTR C1835922 MeSH D008661 OMIM 609924 SNOMED CT 709282004 2014-05 2020-08-18 Amish lethal microcephaly https://medlineplus.gov/genetics/condition/amish-lethal-microcephaly descriptionAmish lethal microcephaly is a disorder in which infants are born with an usually small head (microcephaly) and underdeveloped brain.Infants with Amish lethal microcephaly have a sloping forehead and an extremely small head size. They may also have an unusually small lower jaw and chin (micrognathia) and an enlarged liver (hepatomegaly).Affected infants may have seizures and difficulty maintaining their body temperature. Often they become very irritable starting in the second or third month of life. A compound called alpha-ketoglutaric acid can be detected in their urine (alpha-ketoglutaric aciduria), and during episodes of viral illness they tend to develop elevated levels of acid in the blood and tissues (metabolic acidosis). Infants with this disorder typically feed adequately but do not develop skills such as purposeful movement or the ability to track faces and sounds. Affected infants live only about six months. ar Autosomal recessive SLC25A19 https://medlineplus.gov/genetics/gene/slc25a19 Amish microcephaly MCPHA Microcephaly, Amish type GTR C1846648 MeSH D008831 OMIM 607196 SNOMED CT 702437000 2007-11 2024-05-24 Amyotrophic lateral sclerosis https://medlineplus.gov/genetics/condition/amyotrophic-lateral-sclerosis descriptionAmyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die (atrophy) over time, leading to muscle weakness, a loss of muscle mass, and an inability to control movement.There are many different types of ALS; these types are distinguished by their signs and symptoms and their genetic cause or lack of clear genetic association. Most people with ALS have a form of the condition that is described as sporadic, which means it occurs in people with no apparent history of the disorder in their family. People with sporadic ALS usually first develop features of the condition in their late fifties or early sixties. A small proportion of people with ALS, estimated at 5 to 10 percent, have a family history of ALS or a related condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. The signs and symptoms of familial ALS typically first appear in one's late forties or early fifties. Rarely, people with familial ALS develop symptoms in childhood or their teenage years. These individuals have a rare form of the disorder known as juvenile ALS.The first signs and symptoms of ALS may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Affected individuals may develop slurred speech (dysarthria) and, later, difficulty chewing or swallowing (dysphagia). Many people with ALS experience malnutrition because of reduced food intake due to dysphagia and an increase in their body's energy demands (metabolism) due to prolonged illness. Muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue atrophies. Individuals with ALS eventually lose muscle strength and the ability to walk. Affected individuals eventually become wheelchair-dependent and increasingly require help with personal care and other activities of daily living. Over time, muscle weakness causes affected individuals to lose the use of their hands and arms. Breathing becomes difficult because the muscles of the respiratory system weaken. Most people with ALS die from respiratory failure within 2 to 10 years after the signs and symptoms of ALS first appear; however, disease progression varies widely among affected individuals.Approximately 20 percent of individuals with ALS also develop FTD. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. Communication skills worsen as the disease progresses. It is unclear how the development of ALS and FTD are related. Individuals who develop both conditions are diagnosed as having ALS-FTD.A rare form of ALS that often runs in families is known as ALS-parkinsonism-dementia complex (ALS-PDC). This disorder is characterized by the signs and symptoms of ALS, in addition to a pattern of movement abnormalities known as parkinsonism, and a progressive loss of intellectual function (dementia). Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. Affected members of the same family can have different combinations of signs and symptoms. xd X-linked dominant n Not inherited ad Autosomal dominant ar Autosomal recessive SOD1 https://medlineplus.gov/genetics/gene/sod1 ALS2 https://medlineplus.gov/genetics/gene/als2 SMN1 https://medlineplus.gov/genetics/gene/smn1 SETX https://medlineplus.gov/genetics/gene/setx DCTN1 https://medlineplus.gov/genetics/gene/dctn1 VCP https://medlineplus.gov/genetics/gene/vcp SPG11 https://medlineplus.gov/genetics/gene/spg11 SQSTM1 https://medlineplus.gov/genetics/gene/sqstm1 CHMP2B https://medlineplus.gov/genetics/gene/chmp2b ATXN2 https://medlineplus.gov/genetics/gene/atxn2 MATR3 https://medlineplus.gov/genetics/gene/matr3 TARDBP https://medlineplus.gov/genetics/gene/tardbp FUS https://medlineplus.gov/genetics/gene/fus C9orf72 https://medlineplus.gov/genetics/gene/c9orf72 ANG https://www.ncbi.nlm.nih.gov/gene/283 ERBB4 https://www.ncbi.nlm.nih.gov/gene/2066 HNRNPA1 https://www.ncbi.nlm.nih.gov/gene/3178 NEFH https://www.ncbi.nlm.nih.gov/gene/4744 PFN1 https://www.ncbi.nlm.nih.gov/gene/5216 PRPH https://www.ncbi.nlm.nih.gov/gene/5630 TUBA4A https://www.ncbi.nlm.nih.gov/gene/7277 VAPB https://www.ncbi.nlm.nih.gov/gene/9217 FIG4 https://www.ncbi.nlm.nih.gov/gene/9896 OPTN https://www.ncbi.nlm.nih.gov/gene/10133 SIGMAR1 https://www.ncbi.nlm.nih.gov/gene/10280 TBK1 https://www.ncbi.nlm.nih.gov/gene/29110 UBQLN2 https://www.ncbi.nlm.nih.gov/gene/29978 TRPM7 https://www.ncbi.nlm.nih.gov/gene/54822 CHCHD10 https://www.ncbi.nlm.nih.gov/gene/400916 ALS Amyotrophic lateral sclerosis with dementia Charcot disease Dementia with amyotrophic lateral sclerosis Lou Gehrig disease Motor neuron disease, amyotrophic lateral sclerosis GTR C0002736 ICD-10-CM G12.21 MeSH D000690 OMIM 105400 OMIM 105500 OMIM 105550 OMIM 205100 OMIM 300857 OMIM 600795 OMIM 602099 OMIM 602433 OMIM 606640 OMIM 608030 OMIM 608031 OMIM 608627 OMIM 611895 OMIM 612069 OMIM 612577 OMIM 613435 OMIM 613954 OMIM 614373 OMIM 614808 OMIM 615426 OMIM 615515 OMIM 615911 OMIM 616208 OMIM 616437 OMIM 616439 SNOMED CT 230258005 SNOMED CT 86044005 2016-02 2023-08-18 Anauxetic dysplasia https://medlineplus.gov/genetics/condition/anauxetic-dysplasia descriptionAnauxetic dysplasia is a disorder characterized by extremely short stature (dwarfism) and other skeletal abnormalities, an unusually large range of joint movement (hypermobility), dental problems, and distinctive facial features. Mild intellectual disability can also occur in this disorder.People with anauxetic dysplasia have dwarfism with unusually short limbs for their height (disproportionate short stature) beginning before birth. Dislocation of the bones at the top of the spine (atlantoaxial subluxation) can also occur in this disorder, and may cause pinching (compression) of the spinal cord. As a result, affected individuals may experience neurological symptoms including pain, tingling, numbness, coordination problems, weakness, and paralysis. In severe cases, the spinal cord compression may lead to paralysis of the muscles needed for breathing, which can be life-threatening during early childhood.Other skeletal abnormalities in anauxetic dysplasia include a barrel-shaped chest and a rounded upper back that also curves to the side (kyphoscoliosis). Without surgical correction, the kyphoscoliosis can constrict the lungs and cause difficulty breathing. People with anauxetic dysplasia can also have an exaggerated curvature of the lower back (hyperlordosis), dislocation of the hips, and soles of the feet that are rounded outward (rocker-bottom feet).Typical facial features in anauxetic dysplasia include closely spaced eyes (hypotelorism), a flat or sunken appearance of the middle of the face (midface hypoplasia), an unusually large tongue (macroglossia), and a protruding chin (prognathism). Affected individuals can also have fewer teeth than normal (hypodontia). ar Autosomal recessive RMRP https://medlineplus.gov/genetics/gene/rmrp POP1 https://www.ncbi.nlm.nih.gov/gene/10940 AD Spondylometaepiphyseal dysplasia, anauxetic type Spondylometaepiphyseal dysplasia, Menger type MeSH D004392 OMIM 607095 OMIM 617396 2017-07 2020-08-18 Andermann syndrome https://medlineplus.gov/genetics/condition/andermann-syndrome descriptionAndermann syndrome is a disorder that damages the nerves used for muscle movement and sensation (motor and sensory neuropathy). The neuropathy in this condition is due to poor development of nerves, particularly nerves that control movement, which are half their normal size. Absence (agenesis) or malformation of the tissue connecting the left and right halves of the brain (corpus callosum) occurs in most people with this disorder. Because of these features, Andermann syndrome is sometimes referred to as hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC).People affected by Andermann syndrome have abnormal or absent reflexes (areflexia) and weak muscle tone (hypotonia). They experience muscle wasting (amyotrophy), severe progressive weakness and loss of sensation in the limbs, and rhythmic shaking (tremors). People with Andermann syndrome typically begin walking between ages 3 and 4, and worsening neuropathy causes them to lose this ability by their teenage years. As they get older, people with this disorder frequently develop joint deformities called contractures, which restrict the movement of certain joints. Most affected individuals also develop abnormal curvature of the spine (scoliosis), which may require surgery.Andermann syndrome also results in abnormal function of certain cranial nerves, which emerge directly from the brain and extend to various areas of the head and neck. Cranial nerve problems may result in facial muscle weakness, drooping eyelids (ptosis), and difficulty following movements with the eyes (gaze palsy).Individuals with Andermann syndrome usually have intellectual disability, which may be mild to severe, and some experience seizures. They may also develop psychiatric symptoms such as depression, anxiety, agitation, paranoia, and hallucinations, which usually appear in adolescence.Some people with Andermann syndrome have atypical physical features such as widely spaced eyes (ocular hypertelorism); a wide, short skull (brachycephaly); a high arch of the hard palate at the roof of the mouth; a big toe that crosses over the other toes; and partial fusion (syndactyly) of the second and third toes.Andermann syndrome is associated with a shortened life expectancy related to respiratory insufficiency, but affected individuals typically live into adulthood. ar Autosomal recessive SLC12A6 https://medlineplus.gov/genetics/gene/slc12a6 ACCPN Agenesis of corpus callosum with neuronopathy Agenesis of corpus callosum with peripheral neuropathy Agenesis of corpus callosum with polyneuropathy Charlevoix disease Hereditary motor and sensory neuropathy with agenesis of the corpus callosum HMSN/ACC GTR C0795950 MeSH D006211 MeSH D015417 OMIM 218000 SNOMED CT 702439002 2022-09 2025-04-03 Andersen-Tawil syndrome https://medlineplus.gov/genetics/condition/andersen-tawil-syndrome descriptionAndersen-Tawil syndrome is a disorder that causes episodes of muscle weakness (periodic paralysis), changes in heart rhythm (arrhythmia), and developmental abnormalities. Periodic paralysis begins early in life, and episodes last from hours to days. These episodes may occur after exercise or long periods of rest, but they often have no obvious trigger. Muscle strength usually returns to normal between episodes. However, mild muscle weakness may eventually become permanent.In people with Andersen-Tawil syndrome, the most common changes affecting the heart are ventricular arrhythmia, which is a disruption in the rhythm of the heart's lower chambers (the ventricles), and long QT syndrome. Long QT syndrome is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. The irregular heartbeats can lead to discomfort, such as the feeling that the heart is skipping beats (palpitations). Uncommonly, the irregular heartbeats can cause fainting (syncope), and even more rarely, sudden death.Physical abnormalities associated with Andersen-Tawil syndrome typically affect the face, other parts of the head, and the limbs. These features often include a very small lower jaw (micrognathia), dental abnormalities (such as crowded teeth), low-set ears, widely spaced eyes, fusion (syndactyly) of the second and third toes, and unusual curving of the fingers or toes (clinodactyly). Some affected people also have short stature and an abnormal side-to-side curvature of the spine (scoliosis).The signs and symptoms of Andersen-Tawil syndrome vary widely, and they can be different even among affected members of the same family. About 60 percent of affected individuals have all three major features (periodic paralysis, cardiac arrhythmia, and physical abnormalities). ad Autosomal dominant KCNJ2 https://medlineplus.gov/genetics/gene/kcnj2 KCNJ5 https://medlineplus.gov/genetics/gene/kcnj5 Andersen syndrome ATS Long QT syndrome 7 LQT7 GTR C1563715 MeSH D050030 OMIM 170390 SNOMED CT 422348008 2018-04 2020-08-18 Androgen insensitivity syndrome https://medlineplus.gov/genetics/condition/androgen-insensitivity-syndrome descriptionAndrogen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this condition have one X chromosome and one Y chromosome in each cell. In people with androgen insensitivity syndrome, the body's cells and tissues are unable to respond to certain male sex hormones (called androgens) that are important for normal male sexual development before birth and during puberty. As a result, affected individuals may have external sex characteristics that are typical for females or have features of both male and female sexual development.There are three forms of androgen insensitivity syndrome: complete, partial, and mild.Complete androgen insensitivity syndrome occurs when the body does not respond to androgens at all. People with this form of the condition have external sex characteristics that are typical of females. Affected individuals do not have a uterus. They have male internal sex organs (testes) that are undescended, which means they are located in the pelvis or abdomen instead of outside the body. As such, affected individuals do not menstruate and are unable to conceive a child (infertile). People with complete androgen insensitivity syndrome also have sparse or absent hair in the pubic area and under the arms.The partial and mild forms of androgen insensitivity syndrome occur when the body's tissues are partially sensitive to the effects of androgens. People with partial androgen insensitivity can have genitalia that look typical for females, genitalia that have both male and female characteristics, or genitalia that look typical for males.  People with mild androgen insensitivity are born with male-typical sex characteristics, but they are often infertile and tend to experience breast enlargement at puberty. xr X-linked recessive AR https://medlineplus.gov/genetics/gene/ar AIS Androgen receptor deficiency Androgen resistance syndrome AR deficiency DHTR deficiency Dihydrotestosterone receptor deficiency GTR C0039585 GTR C0268301 ICD-10-CM E34.5 ICD-10-CM E34.50 ICD-10-CM E34.51 ICD-10-CM E34.52 MeSH D013734 OMIM 300068 SNOMED CT 12313004 SNOMED CT 52832001 SNOMED CT 58672003 2024-04 2025-03-06 Androgenetic alopecia https://medlineplus.gov/genetics/condition/androgenetic-alopecia descriptionAndrogenetic alopecia is a common form of hair loss in both men and women. In men, it is also known as male pattern baldness, and in women, it is also known as female pattern hair loss.In men, hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline moves back (recedes) to form a characteristic "M" shape. Hair also thins at the top of the head (vertex or crown), often progressing to partial or complete baldness.The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner at the top of the head, and the middle part widens. The hairline does not typically recede.  Androgenetic alopecia in women rarely leads to total baldness.Androgenetic alopecia in men has been associated with several other medical conditions, including coronary heart disease and enlargement of the prostate. Additionally, prostate cancer, disorders of insulin resistance (such as diabetes and obesity), and high blood pressure (hypertension) have been related to androgenetic alopecia. In women, this form of hair loss is associated with an increased risk of polycystic ovary syndrome (PCOS). PCOS is characterized by a hormonal imbalance that can lead to irregular menstruation, acne, excess hair elsewhere on the body (hirsutism), and weight gain. u Pattern unknown AR https://medlineplus.gov/genetics/gene/ar Androgenic alopecia Female pattern baldness Female-pattern hair loss Male pattern alopecia Male pattern hair loss Male-pattern baldness Pattern baldness ICD-10-CM L64 ICD-10-CM L64.8 ICD-10-CM L64.9 MeSH D000505 OMIM 109200 OMIM 300710 OMIM 612421 SNOMED CT 1108009 SNOMED CT 201144006 SNOMED CT 87872006 2023-07 2023-07-27 Anencephaly https://medlineplus.gov/genetics/condition/anencephaly descriptionAnencephaly is a condition that prevents the normal development of the brain and the bones of the skull. This condition results when a structure called the neural tube fails to close during the first few weeks of embryonic development. The neural tube is a layer of cells that ultimately develops into the brain and spinal cord. Because anencephaly is caused by abnormalities of the neural tube, it is classified as a neural tube defect.Because the neural tube fails to close properly, the developing brain and spinal cord are exposed to the amniotic fluid that surrounds the fetus in the womb. This exposure causes the nervous system tissue to break down (degenerate). As a result, people with anencephaly are missing large parts of the brain called the cerebrum and cerebellum. These brain regions are necessary for thinking, hearing, vision, emotion, and coordinating movement. The bones of the skull are also missing or incompletely formed.Because these nervous system abnormalities are so severe, almost all babies with anencephaly die before birth or within a few hours or days after birth. u Pattern unknown MTHFR https://medlineplus.gov/genetics/gene/mthfr Anencephalia Anencephalus Aprosencephaly Congenital absence of brain GTR C0002902 GTR C0027794 GTR C1866558 ICD-10-CM Q00.0 MeSH D000757 OMIM 182940 OMIM 206500 OMIM 601634 SNOMED CT 277922001 SNOMED CT 85641006 SNOMED CT 89369001 2014-11 2023-08-22 Angelman syndrome https://medlineplus.gov/genetics/condition/angelman-syndrome descriptionAngelman syndrome is a complex genetic disorder that primarily affects the nervous system. Characteristic features of this condition include delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy) and a small head size (microcephaly). Delayed development becomes noticeable by the age of 6 to 12 months, and other common signs and symptoms usually appear in early childhood.Children with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. Hyperactivity and a short attention span are common. Most affected children also have difficulty sleeping and need less sleep than usual.With age, people with Angelman syndrome become less excitable, and the sleeping problems tend to improve. However, affected individuals continue to have intellectual disability, severe speech impairment, and seizures throughout their lives. Adults with Angelman syndrome have distinctive facial features that may be described as "coarse." Other common features include unusually fair skin with light-colored hair and an abnormal side-to-side curvature of the spine (scoliosis). The life expectancy of people with this condition appears to be nearly normal. n Not inherited UBE3A https://medlineplus.gov/genetics/gene/ube3a OCA2 https://medlineplus.gov/genetics/gene/oca2 15 https://medlineplus.gov/genetics/chromosome/15 AS GTR C0162635 MeSH D017204 OMIM 105830 SNOMED CT 76880004 2022-05 2022-05-17 Anhidrotic ectodermal dysplasia with immune deficiency https://medlineplus.gov/genetics/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency descriptionAnhidrotic ectodermal dysplasia with immune deficiency (EDA-ID) is a form of ectodermal dysplasia, which is a group of conditions characterized by abnormal development of ectodermal tissues including the skin, hair, teeth, and sweat glands. In addition, immune system function is reduced in people with EDA-ID. The signs and symptoms of EDA-ID are evident soon after birth, and due to the severity of the immune system problems, most people with this condition survive only into childhood.Skin abnormalities in children with EDA-ID include areas that are dry, wrinkled, or darker in color than the surrounding skin. Affected individuals tend to have sparse scalp and body hair (hypotrichosis). EDA-ID is also characterized by missing teeth (hypodontia) or teeth that are small and pointed. Most children with EDA-ID have a reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly. An inability to sweat (anhidrosis) can lead to a dangerously high body temperature (hyperthermia), particularly in hot weather and during exercise, because the body cannot cool itself by evaporating sweat.The immune deficiency in EDA-ID varies among individuals with this condition. Children with EDA-ID often produce abnormally low levels of proteins called antibodies or immunoglobulins. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. A reduction in antibodies makes it difficult for children with this disorder to fight off infections. In EDA-ID, immune system cells called T cells and B cells have a decreased ability to recognize and respond to foreign invaders (such as bacteria, viruses, and yeast) that have sugar molecules attached to their surface (glycan antigens). Other key aspects of the immune system may also be impaired, leading to recurrent infections.Children with EDA-ID commonly get infections in the lungs (pneumonia), ears (otitis media), sinuses (sinusitis), lymph nodes (lymphadenitis), skin, bones, and gastrointestinal tract. Approximately one quarter of individuals with EDA-ID have disorders involving abnormal inflammation, such as inflammatory bowel disease or rheumatoid arthritis.There are two forms of EDA-ID that have similar signs and symptoms and are distinguished by the modes of inheritance: X-linked recessive or autosomal dominant. ad Autosomal dominant xr X-linked recessive IKBKG https://medlineplus.gov/genetics/gene/ikbkg NFKBIA https://medlineplus.gov/genetics/gene/nfkbia Ectodermal dysplasia, hypohidrotic, with immune deficiency EDA-ID HED-ID Hyper-IgM immunodeficiency with hypohidrotic ectodermal dysplasia Hypohidrotic ectodermal dysplasia with immune deficiency GTR C1846006 ICD-10-CM Q82.4 MeSH D053358 OMIM 300291 SNOMED CT 703525006 2013-08 2022-06-22 Aniridia https://medlineplus.gov/genetics/condition/aniridia descriptionAniridia is an eye disorder that is characterized by a complete or partial absence of the colored part of the eye (the iris). Aniridia is typically present from birth (congenital) and affects both eyes. The pupils may also be abnormal or misshapen.People with aniridia can have other eye problems that may be congenital or develop later in life. Clouding of the lenses of the eyes (cataracts) occurs in most people with aniridia. Affected individuals often have involuntary eye movements (nystagmus) or an increased sensitivity to light (photophobia). Underdevelopment of a specific region at the back of the eye (foveal hypoplasia) can reduce the sharpness of vision (visual acuity).Additional signs and symptoms of aniridia may include problems with the cornea (aniridia-associated keratopathy). The cornea is the clear outer covering of the eye. Aniridia can also cause increased pressure in the eye (glaucoma) in late childhood through early adulthood. In some affected individuals, the structures that carry information from the eyes to the brain are underdeveloped (optic nerve hypoplasia). Many of these eye problems contribute to vision loss that worsens over time. The severity of symptoms is typically the same in both eyes.In rare cases, individuals with aniridia have additional health problems, which can include behavioral issues, metabolic disorders, and problems detecting odors.Aniridia can affect the eyes alone (isolated) or it can occur with other features as part of a syndrome. Aniridia is a common feature of certain genetic conditions including Gillespie syndrome and WAGR syndrome.Injuries to the head or eyes can also cause aniridia. This type of aniridia is not genetic and can occur at any age. ad Autosomal dominant+Inherited or new variant PAX6 https://medlineplus.gov/genetics/gene/pax6 ELP4 https://www.ncbi.nlm.nih.gov/gene/26610 TRIM44 https://www.ncbi.nlm.nih.gov/gene/54765 Absent iris Congenital aniridia Irideremia GTR C0344542 GTR C0344543 GTR C4310695 ICD-10-CM Q13.1 MeSH D015783 OMIM 106210 OMIM 617141 OMIM 617142 SNOMED CT 15986951000119103 SNOMED CT 15986991000119108 SNOMED CT 15987031000119108 SNOMED CT 253231007 SNOMED CT 253232000 SNOMED CT 69278003 2026-04 2026-04-09 Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome https://medlineplus.gov/genetics/condition/ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome descriptionAnkyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a form of ectodermal dysplasia, a group of about 180 conditions characterized by abnormal development of ectodermal tissues including the skin, hair, nails, teeth, eyes, ears, and sweat glands.Among the most common features of AEC syndrome are missing patches of skin (erosion). In affected infants, skin erosion most commonly occurs on the scalp. It tends to recur throughout childhood and into adulthood, frequently affecting the scalp, neck, hands, and feet. Skin erosion ranges from mild to severe and can lead to life-threatening infection in infancy, scarring, and hair loss. Other ectodermal abnormalities in AEC syndrome include changes in skin coloring; brittle, sparse, or missing hair; misshapen or absent fingernails and toenails; and malformed or missing teeth. Affected individuals may also have an inability to control their body temperature because of missing or nonfunctioning sweat glands causing overheating or hypothermia. Many infants with AEC syndrome are born with an eyelid condition known as ankyloblepharon filiforme adnatum, in which strands of tissue partially or completely fuse the upper and lower eyelids. Most people with AEC syndrome are also born with an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both. Cleft lip or cleft palate can make it difficult for affected infants to suck, so these infants often have trouble feeding and do not grow and gain weight at the expected rate (failure to thrive).Additional features of AEC syndrome can include limb abnormalities, most commonly fused fingers and toes (syndactyly). Less often, affected individuals have permanently bent fingers and toes (camptodactyly) or a deep split in the hands or feet with missing fingers or toes and fusion of the remaining digits (ectrodactyly). Hearing loss is common, occurring in more than 90 percent of children with AEC syndrome. Some affected individuals have distinctive facial features, such as small jaws that cannot open fully and a narrow space between the upper lip and nose (philtrum). Other signs and symptoms can include the opening of the urethra on the underside of the penis (hypospadias) in affected males, digestive problems, absent tear duct openings in the eyes, and chronic sinus or ear infections.A condition known as Rapp-Hodgkin syndrome has signs and symptoms that overlap considerably with those of AEC syndrome. These two syndromes were classified as separate disorders until it was discovered that they both result from mutations in the same part of the same gene. Most researchers now consider Rapp-Hodgkin syndrome and AEC syndrome to be part of the same disease spectrum. ad Autosomal dominant TP63 https://medlineplus.gov/genetics/gene/tp63 AEC syndrome Ankyloblepharon-ectodermal defects-cleft lip and palate syndrome Hay-Wells syndrome GTR C0406709 GTR C1785148 MeSH D004476 OMIM 106260 OMIM 129400 SNOMED CT 55821006 2011-06 2022-07-19 Ankylosing spondylitis https://medlineplus.gov/genetics/condition/ankylosing-spondylitis descriptionAnkylosing spondylitis is a form of painful, ongoing joint inflammation (chronic inflammatory arthritis) that primarily affects the spine.  Early symptoms of ankylosing spondylitis typically begin between the ages of 15 and 30. Most commonly, affected individuals first experience chronic back pain and stiffness. This pain worsens with rest or inactivity, and tends to be relieved with physical activity or exercise. Pain in ankylosing spondylitis results from inflammation of the joints between the pelvic bones (the ilia) and the base of the spine (the sacrum). These joints are called sacroiliac joints, and inflammation of these joints is known as sacroiliitis. The inflammation gradually spreads to the joints between the vertebrae, eventually involving the whole spine, causing a condition called spondylitis. Over time, back movement gradually becomes limited as the bones of the spine (vertebrae) fuse together. This progressive bony fusion is called ankylosis. These fused bones are prone to fracture.Ankylosing spondylitis can involve other joints as well, including the shoulders, hips, and, less often, the knees. As the disease progresses, it can affect the joints between the spine and ribs, restricting movement of the chest and making it difficult to breathe deeply. Ankylosing spondylitis affects the eyes in more than 30 percent of cases, leading to episodes of eye inflammation called acute iritis. Acute iritis typically affects one eye at a time and causes eye pain and increased sensitivity to light (photophobia). Rarely, ankylosing spondylitis can also cause serious complications involving the heart, lungs, and nervous system. Six to 10 percent of people with ankylosing spondylitis have additional inflammatory disorders such as psoriasis, which affects the skin, or ulcerative colitis or Crohn's disease, which both affect the digestive tract. u Pattern unknown HLA-B https://medlineplus.gov/genetics/gene/hla-b IL23R https://medlineplus.gov/genetics/gene/il23r STAT3 https://medlineplus.gov/genetics/gene/stat3 IL1A https://medlineplus.gov/genetics/gene/il1a ERAP1 https://medlineplus.gov/genetics/gene/erap1 CARD9 https://medlineplus.gov/genetics/gene/card9 IL1R1 https://www.ncbi.nlm.nih.gov/gene/3554 IL6R https://www.ncbi.nlm.nih.gov/gene/3570 IL12B https://www.ncbi.nlm.nih.gov/gene/3593 IL17A https://www.ncbi.nlm.nih.gov/gene/3605 PTGER4 https://www.ncbi.nlm.nih.gov/gene/5734 TYK2 https://www.ncbi.nlm.nih.gov/gene/7297 IL1R2 https://www.ncbi.nlm.nih.gov/gene/7850 ERAP2 https://www.ncbi.nlm.nih.gov/gene/64167 IL27 https://www.ncbi.nlm.nih.gov/gene/246778 axial spondylarthritis Bechterew disease Marie-Struempell disease SpA Spondylarthritis ankylopoietica Spondylitis ankylopoietica spondyloarthritis Spondyloarthritis ankylopoietica GTR C1862852 ICD-10-CM M08.1 ICD-10-CM M45 ICD-10-CM M45.0 ICD-10-CM M45.1 ICD-10-CM M45.2 ICD-10-CM M45.3 ICD-10-CM M45.4 ICD-10-CM M45.5 ICD-10-CM M45.6 ICD-10-CM M45.7 ICD-10-CM M45.8 ICD-10-CM M45.9 MeSH D013167 OMIM 106300 OMIM 183840 OMIM 613238 SNOMED CT 838436001 SNOMED CT 9631008 2022-03 2024-09-17 Ankyrin-B syndrome https://medlineplus.gov/genetics/condition/ankyrin-b-syndrome descriptionAnkyrin-B syndrome is associated with a variety of heart problems related to disruption of the heart's normal rhythm (arrhythmia). Heart rhythm is controlled by electrical signals that move through the heart in a highly coordinated way. In ankyrin-B syndrome, disruption of different steps of electrical signaling can lead to arrhythmia, and the resulting heart problems vary among affected individuals.Individuals with ankyrin-B syndrome may have problems with the sinoatrial (SA) node, which generates the electrical impulses that start each heartbeat. If the SA node is not functioning properly, the heartbeat can be too slow (bradycardia). In a small number of people with ankyrin-B syndrome, the heart takes longer than usual to recharge between beats, which is known as a prolonged QT interval (long QT). Some affected individuals have impaired progression (conduction) of electrical impulses between the chambers of the heart, which can cause a problem called heart block. Other heart problems that occur in ankyrin-B syndrome include irregular and uncoordinated electrical activity in the heart's upper chambers (atrial fibrillation) or lower chambers (ventricular fibrillation) and an abnormality called catecholaminergic polymorphic ventricular tachycardia (CPVT), in which an increase in the heart rate can trigger an abnormally fast and irregular heartbeat called ventricular tachycardia. In people with ankyrin-B syndrome, arrhythmia can lead to fainting (syncope) or cardiac arrest and sudden death.When associated with a prolonged QT interval, the condition is sometimes classified as long QT syndrome 4. However, because additional heart problems can result from changes in the same gene, long QT syndrome 4 is usually considered part of ankyrin-B syndrome. ad Autosomal dominant ANK2 https://medlineplus.gov/genetics/gene/ank2 Cardiac arrhythmia, ankyrin-B-related GTR C1970119 MeSH D001145 OMIM 600919 2017-03 2020-08-18 Anonychia congenita https://medlineplus.gov/genetics/condition/anonychia-congenita descriptionAnonychia congenita is a condition that affects the fingernails and toenails. Individuals with this condition are typically missing all of their fingernails and toenails (anonychia). This absence of nails is noticeable from birth (congenital). In some cases, only part of the nail is missing (hyponychia) or not all fingers and toes are affected. All of the other tissues at the tips of the fingers and toes, including structures that usually support the nail and its growth (such as the nail bed), are normal.Individuals with anonychia congenita do not have any other health problems related to the condition. ar Autosomal recessive RSPO4 https://medlineplus.gov/genetics/gene/rspo4 Absent nails Anonychia Aplastic nails Congenital absence of nails Hyponychia congenita GTR C0265998 ICD-10-CM Q84.3 MeSH D009264 OMIM 206800 SNOMED CT 23610003 2017-05 2024-09-17 Anophthalmia/Microphthalmia https://medlineplus.gov/genetics/condition/anophthalmia-microphthalmia descriptionAnophthalmia and microphthalmia are disorders that affect eye development before birth. Microphthalmia is a birth defect in which one or both eyes do not develop fully and are abnormally small. Anophthalmia is a more severe birth defect in which one or both eyes do not form at all. While people who have anophthalmia have no vision in the affected eye, people who have microphthalmia may or may not have significant vision loss. Because both conditions are characterized by impaired eye development, anophthalmia and microphthalmia are often considered to be related disorders (anophthalmia/microphthalmia).Anophthalmia and microphthalmia can occur along with other eye abnormalities. People who have one missing eye (unilateral anophthalmia) can have additional eye abnormalities in the unaffected eye, while people who have microphthalmia can have additional eye abnormalities in one or both eyes (complex microphthalmia). The presence of other eye problems can worsen vision. Additional eye abnormalities can include a missing piece of tissue that may appear as a notch or gap in one of several parts of the eye (coloboma); a clouding of the lens of the eye (cataract); abnormal development of the cells in the retina (retinal dysplasia);  or microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.Some individuals have anophthalmia or microphthalmia as part of a syndrome that affects multiple parts of the body (syndromic anophthalmia or microphthalmia). As many as 45 percent of people with anophthalmia or microphthalmia have the condition as part of a recognized syndrome, such as CHARGE syndrome, Fraser syndrome type 1 or 2, and oculofaciocardiodental syndrome. When people have anophthalmia or microphthalmia but do not have additional abnormalities of the eye or other body systems, this is known as isolated anophthalmia or microphthalmia. xr X-linked recessive ad Autosomal dominant+New variant ar Autosomal recessive x X-linked MITF https://medlineplus.gov/genetics/gene/mitf NDP https://medlineplus.gov/genetics/gene/ndp SALL4 https://medlineplus.gov/genetics/gene/sall4 SALL1 https://medlineplus.gov/genetics/gene/sall1 CHD7 https://medlineplus.gov/genetics/gene/chd7 BCOR https://medlineplus.gov/genetics/gene/bcor SOX2 https://medlineplus.gov/genetics/gene/sox2 LRP5 https://medlineplus.gov/genetics/gene/lrp5 GJA1 https://medlineplus.gov/genetics/gene/gja1 PAX6 https://medlineplus.gov/genetics/gene/pax6 PORCN https://medlineplus.gov/genetics/gene/porcn HCCS https://medlineplus.gov/genetics/gene/hccs OTX2 https://medlineplus.gov/genetics/gene/otx2 SHH https://medlineplus.gov/genetics/gene/shh KMT2D https://medlineplus.gov/genetics/gene/kmt2d COL4A1 https://medlineplus.gov/genetics/gene/col4a1 GDF6 https://medlineplus.gov/genetics/gene/gdf6 GDF3 https://medlineplus.gov/genetics/gene/gdf3 PQBP1 https://medlineplus.gov/genetics/gene/pqbp1 TFAP2A https://medlineplus.gov/genetics/gene/tfap2a SMOC1 https://medlineplus.gov/genetics/gene/smoc1 ALX1 https://medlineplus.gov/genetics/gene/alx1 FRAS1 https://medlineplus.gov/genetics/gene/fras1 SMCHD1 https://medlineplus.gov/genetics/gene/smchd1 RERE https://medlineplus.gov/genetics/gene/rere ALDH1A3 https://www.ncbi.nlm.nih.gov/gene/220 BMP4 https://www.ncbi.nlm.nih.gov/gene/652 BMP7 https://www.ncbi.nlm.nih.gov/gene/655 COX7B https://www.ncbi.nlm.nih.gov/gene/1349 CRYAA https://www.ncbi.nlm.nih.gov/gene/1409 CRYBA4 https://www.ncbi.nlm.nih.gov/gene/1413 FOXE3 https://www.ncbi.nlm.nih.gov/gene/2301 GJA8 https://www.ncbi.nlm.nih.gov/gene/2703 GLI2 https://www.ncbi.nlm.nih.gov/gene/2736 HMGB3 https://www.ncbi.nlm.nih.gov/gene/3149 HMX1 https://www.ncbi.nlm.nih.gov/gene/3166 MAF https://www.ncbi.nlm.nih.gov/gene/4094 NHS https://www.ncbi.nlm.nih.gov/gene/4810 SIX6 https://www.ncbi.nlm.nih.gov/gene/4990 PITX3 https://www.ncbi.nlm.nih.gov/gene/5309 RARB https://www.ncbi.nlm.nih.gov/gene/5915 RBP4 https://www.ncbi.nlm.nih.gov/gene/5950 PXDN https://www.ncbi.nlm.nih.gov/gene/7837 NAA10 https://www.ncbi.nlm.nih.gov/gene/8260 ABCB6 https://www.ncbi.nlm.nih.gov/gene/10058 YAP1 https://www.ncbi.nlm.nih.gov/gene/10413 MAB21L2 https://www.ncbi.nlm.nih.gov/gene/10586 VAX1 https://www.ncbi.nlm.nih.gov/gene/11023 RAB3GAP1 https://www.ncbi.nlm.nih.gov/gene/22930 RPGRIP1L https://www.ncbi.nlm.nih.gov/gene/23322 FNBP4 https://www.ncbi.nlm.nih.gov/gene/23360 RAX https://www.ncbi.nlm.nih.gov/gene/30062 TMX3 https://www.ncbi.nlm.nih.gov/gene/54495 NDUFB11 https://www.ncbi.nlm.nih.gov/gene/54539 TENM3 https://www.ncbi.nlm.nih.gov/gene/55714 STRA6 https://www.ncbi.nlm.nih.gov/gene/64220 MFRP https://www.ncbi.nlm.nih.gov/gene/83552 C12orf57 https://www.ncbi.nlm.nih.gov/gene/113246 ATOH7 https://www.ncbi.nlm.nih.gov/gene/220202 TBC1D32 https://www.ncbi.nlm.nih.gov/gene/221322 VSX2 https://www.ncbi.nlm.nih.gov/gene/338917 PRSS56 https://www.ncbi.nlm.nih.gov/gene/646960 A/M Anophthalmia Anophthalmos Microphthalmia Microphthalmos GTR C0003119 GTR C0026010 ICD-10-CM Q11.2 MeSH D008850 OMIM 206900 OMIM 251600 OMIM 300166 OMIM 300915 OMIM 309800 OMIM 601186 OMIM 601349 OMIM 607932 OMIM 610093 OMIM 610125 OMIM 611038 OMIM 611040 OMIM 611222 OMIM 613094 OMIM 613517 OMIM 613704 OMIM 614402 OMIM 615113 OMIM 615524 SNOMED CT 15987151000119103 SNOMED CT 61142002 2025-07 2026-02-12 Anophthalmia/microphthalmia-esophageal atresia syndrome https://medlineplus.gov/genetics/condition/anophthalmia-microphthalmia-esophageal-atresia-syndrome descriptionAnophthalmia/microphthalmia-esophageal atresia (AEG) syndrome is a rare disorder that is characterized by the abnormal development of the eyes and other parts of the body, including the tube that carries food from the mouth to the stomach (esophagus).People who have AEG syndrome are usually born without one or both eyes (anophthalmia), although some individuals have underdeveloped and abnormally small eyes (microphthalmia). People who have anophthalmia have no vision in the affected eye, but people who have microphthalmia may or may not have significant vision loss. Affected individuals who have some remaining eye tissue can have additional eye abnormalities. Some people may be missing pieces of tissue in the structures that form the eye (coloboma), or the nerves that carry signals between the eyes and the brain may be underdeveloped (optic nerve hypoplasia). The presence of other eye problems can worsen an affected person's vision.Some people with AEG syndrome are born with a blocked esophagus (esophageal atresia), which is often accompanied by an abnormal connection between the windpipe (trachea) and the esophagus (tracheoesophageal fistula). Additional features of AEG syndrome can include brain abnormalities, slow growth, delayed development of motor skills (such as walking), and intellectual disabilities. Affected individuals may also have genital abnormalities, which can include undescended testes (cryptorchidism) and an unusually small penis. ad Autosomal dominant+New variant SOX2 https://medlineplus.gov/genetics/gene/sox2 AEG syndrome Anophthalmia-esophageal-genital syndrome MCOPS3 SOX2 anophthalmia syndrome SOX2 disorder SOX2 syndrome SOX2-related eye disorders Syndromic microphthalmia type 3 GTR C1859773 MeSH D000853 OMIM 206900 SNOMED CT 698851003 2025-07 2025-07-08 Antiphospholipid syndrome https://medlineplus.gov/genetics/condition/antiphospholipid-syndrome descriptionAntiphospholipid syndrome is a disorder characterized by an increased tendency to form abnormal blood clots (thromboses) that can block blood vessels. This clotting tendency is known as thrombophilia. In antiphospholipid syndrome, the thromboses can develop in nearly any blood vessel in the body. If a blood clot forms in the vessels in the brain, blood flow is impaired and can lead to stroke. Antiphospholipid syndrome is an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs.Women with antiphospholipid syndrome are at increased risk of complications during pregnancy. These complications include pregnancy-induced high blood pressure (preeclampsia), an underdeveloped placenta (placental insufficiency), early delivery, or pregnancy loss (miscarriage). In addition, women with antiphospholipid syndrome are at greater risk of having a thrombosis during pregnancy than at other times during their lives. At birth, infants of mothers with antiphospholipid syndrome may be small and underweight.A thrombosis or pregnancy complication is typically the first sign of antiphospholipid syndrome. This condition usually appears in early to mid-adulthood but can begin at any age.Other signs and symptoms of antiphospholipid syndrome that affect blood cells and vessels include a reduced amount of cells involved in blood clotting called platelets (thrombocytopenia), a shortage of red blood cells (anemia) due to their premature breakdown (hemolysis), and a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin. In addition, affected individuals may have open sores (ulcers) on the skin, migraine headaches, or heart disease. Many people with antiphospholipid syndrome also have other autoimmune disorders such as systemic lupus erythematosus.Rarely, people with antiphospholipid syndrome develop thromboses in multiple blood vessels throughout their body. These thromboses block blood flow in affected organs, which impairs their function and ultimately causes organ failure. These individuals are said to have catastrophic antiphospholipid syndrome (CAPS). CAPS typically affects the kidneys, lungs, brain, heart, and liver, and is fatal in over half of affected individuals. Less than 1 percent of individuals with antiphospholipid syndrome develop CAPS. u Pattern unknown Anti-phospholipid syndrome Antiphospholipid antibody syndrome Hughes syndrome ICD-10-CM D68.61 MeSH D016736 OMIM 107320 SNOMED CT 19267009 SNOMED CT 239892009 SNOMED CT 239895006 SNOMED CT 26843008 SNOMED CT 72161000119100 2013-06 2023-03-21 Apert syndrome https://medlineplus.gov/genetics/condition/apert-syndrome descriptionApert syndrome is a genetic disorder characterized by skeletal abnormalities. A key feature of Apert syndrome is the premature closure of the bones of the skull (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. In addition, a varied number of fingers and toes are fused together (syndactyly).Craniosynostosis causes many of the characteristic facial features of Apert syndrome. Premature fusion of the skull bones prevents the head from growing normally, which leads to a sunken appearance in the middle of the face (midface hypoplasia), a beaked nose, a wrinkled forehead, and an opening in the roof of the mouth (a cleft palate). In individuals with Apert syndrome, an underdeveloped upper jaw can lead to dental problems, such as missing teeth, irregular tooth enamel, and crowded teeth.Many individuals with Apert syndrome have vision problems due to eye abnormalities, which can include bulging eyes (exophthalmos), wide-set eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), eyes that do not look in the same direction (strabismus), and shallow eye sockets (ocular proptosis). Some people with Apert syndrome have hearing loss or recurrent ear infections due to malformed ear structures.Abnormal development of structures in the face and head can also cause partial blockage of the airways and lead to breathing difficulties in people with Apert syndrome. Craniosynostosis also affects development of the brain, which can disrupt intellectual development. Cognitive abilities in people with Apert syndrome range from normal to mild or moderate intellectual disability.Individuals with Apert syndrome have syndactyly of the fingers and toes. The severity of the fusion varies, although the hands tend to be more severely affected than the feet. Most commonly, three digits on each hand and foot are fused together. In the most severe cases, all of the fingers and toes are fused. Rarely, people with Apert syndrome may have extra fingers or toes (polydactyly). Some people with Apert syndrome have abnormalities in the bones of the elbows or shoulders. These bone problems can restrict movement and impede everyday activities. In some people, abnormalities occur in both sides of the body, but in others, only one side is affected.Additional signs and symptoms of Apert syndrome can include unusually heavy sweating (hyperhidrosis), oily skin with severe acne, or patches of missing hair in the eyebrows. ad Autosomal dominant FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 Acrocephalosyndactyly Acrocephalosyndactyly type I Apert's syndrome Type I acrocephalosyndactyly GTR C0001193 MeSH D000168 OMIM 101200 SNOMED CT 205258009 2019-08 2020-08-18 Arginase deficiency https://medlineplus.gov/genetics/condition/arginase-deficiency descriptionArginase deficiency is an inherited disorder that causes the amino acid arginine (a building block of proteins) and ammonia to accumulate gradually in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.Arginase deficiency usually becomes evident by about the age of 3. It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity). Other symptoms may include slower than normal growth, developmental delays and eventual loss of developmental milestones, intellectual disabilities, seizures, tremors, and difficulty with balance and coordination (ataxia). Occasionally, high-protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting.In some affected individuals, the signs and symptoms of arginase deficiency may be less severe and may not appear until later in life. ar Autosomal recessive ARG1 https://medlineplus.gov/genetics/gene/arg1 ARG1 deficiency Arginase deficiency disease Argininemia Hyperargininemia GTR C0268548 ICD-10-CM E72.21 MeSH D020162 OMIM 207800 SNOMED CT 23501004 2024-02 2024-02-13 Arginine vasopressin deficiency https://medlineplus.gov/genetics/condition/arginine-vasopressin-deficiency descriptionArginine vasopressin deficiency (previously called neurohypophyseal diabetes insipidus) is a disorder of water balance. The body normally balances fluid intake by releasing fluid in urine. However, people with arginine vasopressin deficiency produce an excessive amount of urine (polyuria), which depletes the amount of water in the body. This water loss also leads to excessive thirst (polydipsia).People with arginine vasopressin deficiency can quickly become dehydrated if they do not drink enough water. Dehydration can cause dizziness and fatigue. Prolonged dehydration can lead to confusion, low blood pressure, seizures, and coma. People with this condition often develop high levels of sodium in the blood (hypernatremia) due to dehydration. Repeated cycles of dehydration can cause long-term health problems, particularly in children. Arginine vasopressin deficiency can be either acquired or familial. The acquired form occurs when the brain is damaged due to head injuries, brain tumors, or other events, and this form can occur at any time during life. The familial form is caused by genetic changes; its signs and symptoms usually become apparent in childhood and worsen over time.Researchers have recommended using the condition name arginine vasopressin deficiency because the previous name, neurohypophyseal diabetes insipidus, was often confused with a much more common disorder called diabetes mellitus. Arginine vasopressin deficiency and diabetes mellitus are separate disorders with different features, causes, and treatment. ar Autosomal recessive ad Autosomal dominant AVP https://medlineplus.gov/genetics/gene/avp Central diabetes insipidus Diabetes insipidus secondary to vasopressin deficiency Diabetes insipidus, central Diabetes insipidus, neurogenic Diabetes insipidus, neurohypophyseal Diabetes insipidus, pituitary Neurohypophyseal diabetes insipidus Pituitary diabetes insipidus Vasopressin defective diabetes insipidus Vasopressin deficiency GTR C0342394 ICD-10-CM E23.2 MeSH D020790 OMIM 125700 SNOMED CT 45369008 2024-07 2024-07-19 Arginine vasopressin resistance https://medlineplus.gov/genetics/condition/arginine-vasopressin-resistance descriptionArginine vasopressin resistance (previously called nephrogenic diabetes insipidus) is a disorder of water balance. The body normally balances fluid intake by releasing excess fluid in urine. However, people with arginine vasopressin resistance produce an excessive amount of urine (polyuria), which depletes the amount of water in the body. This water loss also leads to excessive thirst (polydipsia). Affected individuals can quickly become dehydrated if they do not drink enough water. Dehydration can cause dizziness and fatigue. Prolonged dehydration can lead to confusion, low blood pressure, seizures, and coma. People with arginine vasopressin resistance often develop high levels of sodium in the blood (hypernatremia) due to dehydration. Repeated cycles of dehydration can cause long-term health problems, particularly in children. Arginine vasopressin resistance can be either acquired or familial. The acquired form can occur at any time during life. The familial form usually become apparent within the first year of life, though in some cases they develop in adolescence or early adulthood.Infants with familial arginine vasopressin resistance tend to have problems feeding and gaining weight (failure to thrive). They may also be irritable and experience fevers, diarrhea, and vomiting. Recurrent episodes of dehydration can lead to slow growth and delayed development. If the condition is not well-managed, it can damage the bladder and kidneys leading to pain, infections, and kidney failure. With appropriate treatment, affected individuals usually have few complications and a normal lifespan.Researchers have recommended using the condition name arginine vasopressin resistance because the previous name, nephrogenic diabetes insipidus, was often confused with a much more common disorder called diabetes mellitus. Arginine vasopressin resistance and diabetes mellitus are separate disorders with different features, causes, and treatment. ad Autosomal dominant ar Autosomal recessive x X-linked AVPR2 https://medlineplus.gov/genetics/gene/avpr2 AQP2 https://medlineplus.gov/genetics/gene/aqp2 ADH-resistant diabetes insipidus Congenital nephrogenic diabetes insipidus Diabetes insipidus renalis Diabetes insipidus, nephrogenic NDI Nephrogenic diabetes insipidus Vasopressin-resistant diabetes insipidus GTR C0162283 GTR C1563705 GTR C1563706 ICD-10-CM N25.1 MeSH D018500 OMIM 125800 OMIM 304800 SNOMED CT 111395007 SNOMED CT 61165007 SNOMED CT 81475007 2024-08 2025-03-06 Arginine:glycine amidinotransferase deficiency https://medlineplus.gov/genetics/condition/arginineglycine-amidinotransferase-deficiency descriptionArginine:glycine amidinotransferase deficiency is an inherited disorder that primarily affects the brain. People with this disorder have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviors that affect communication and social interaction. They may experience seizures, especially when they have a fever.Children with arginine:glycine amidinotransferase deficiency may not gain weight and grow at the expected rate (failure to thrive), and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily. ar Autosomal recessive GATM https://medlineplus.gov/genetics/gene/gatm AGAT deficiency Cerebral creatine deficiency syndrome 3 Creatine deficiency syndrome due to AGAT deficiency GATM deficiency L-arginine:glycine amidinotransferase deficiency L-arginine:glycine aminidotransferase deficiency GTR C2675179 MeSH D020739 OMIM 612718 SNOMED CT 702440000 2011-06 2021-04-19 Argininosuccinic aciduria https://medlineplus.gov/genetics/condition/argininosuccinic-aciduria descriptionArgininosuccinic aciduria is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.Argininosuccinic aciduria usually becomes evident in the first few days of life. An infant with argininosuccinic aciduria may be lacking in energy (lethargic) or unwilling to eat, and have a poorly controlled breathing rate or body temperature. Some babies with this disorder experience seizures or unusual body movements, or go into a coma. Complications from argininosuccinic aciduria may include developmental delay and intellectual disability. Progressive liver damage, high blood pressure (hypertension), skin lesions, and brittle hair may also be seen.Occasionally, individuals may inherit a mild form of the disorder. These individuals can have an accumulation of ammonia in the bloodstream only during periods of illness or other stress, or mild intellectual disability or learning disabilities with no evidence of elevated ammonia levels. ar Autosomal recessive ASL https://medlineplus.gov/genetics/gene/asl Argininosuccinate lyase deficiency Argininosuccinic acidemia Argininosuccinicaciduria Argininosuccinyl-CoA lyase deficiency Arginosuccinase deficiency ASA ASAuria ASL deficiency GTR C0268547 ICD-10-CM E72.22 MeSH D056807 OMIM 207900 SNOMED CT 41013004 2020-03 2020-08-18 Aromatase deficiency https://medlineplus.gov/genetics/condition/aromatase-deficiency descriptionAromatase deficiency is a condition characterized by reduced levels of the female sex hormone estrogen and increased levels of the male sex hormone testosterone.Females with aromatase deficiency have a typical female chromosome pattern (46,XX) but are born with external genitalia that do not appear clearly female or male. These individuals typically have normal internal reproductive organs, but develop ovarian cysts early in childhood, which impair the release of egg cells from the ovaries (ovulation). In adolescence, most affected females do not develop secondary sexual characteristics, such as breast growth and menstrual periods. They tend to develop acne and excessive body hair growth (hirsutism).Men with this condition have a typical male chromosome pattern (46,XY) and are born with male external genitalia. Some men with this condition have decreased sex drive, abnormal sperm production, or testes that are small or undescended (cryptorchidism).There are other features associated with aromatase deficiency that can affect both males and females. Affected individuals are abnormally tall because of excessive growth of long bones in the arms and legs. The abnormal bone growth results in slowed mineralization of bones (delayed bone age) and thinning of the bones (osteoporosis), which can lead to bone fractures with little trauma. In affected individuals, the body does not respond correctly to the hormone insulin, so people with aromatase deficiency can have abnormally high blood sugar (glucose), a condition known as hyperglycemia. In addition, people with armoatase deficiency can have excessive weight gain and a fatty liver.Women who are pregnant with fetuses that have aromatase deficiency often experience mild symptoms of the disorder even though they themselves do not have the disorder. These women may develop hirsutism, acne, an enlarged clitoris (clitoromegaly), and a deep voice. These features can appear as early as 12 weeks of pregnancy and go away soon after delivery. ar Autosomal recessive CYP19A1 https://medlineplus.gov/genetics/gene/cyp19a1 46,XX disorder of sex development (DSD) due to placental aromatase deficiency Estrogen synthetase deficiency Oestrogen synthetase deficiency Placental aromatase deficiency GTR C1960539 ICD-10-CM MeSH D017588 OMIM 613546 SNOMED CT 425708006 SNOMED CT 427627006 2014-04 2023-10-26 Aromatase excess syndrome https://medlineplus.gov/genetics/condition/aromatase-excess-syndrome descriptionAromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females. Males with aromatase excess syndrome experience breast enlargement (gynecomastia) in late childhood or adolescence. The bones of affected males grow and develop more quickly and stop growing sooner than usual (advanced bone age). As a result males have an early growth spurt, typically during late childhood, with short stature as an adult. Affected females rarely show signs and symptoms of the condition, but they may have increased breast growth (macromastia), irregular menstrual periods, and short stature. The ability to have children (fertility) is usually normal in both males and females with aromatase excess syndrome. ad Autosomal dominant CYP19A1 https://medlineplus.gov/genetics/gene/cyp19a1 AEXS Familial gynecomastia due to increased aromatase activity Hereditary gynecomastia Increased aromatase activity GTR C1970109 MeSH D012734 OMIM 139300 SNOMED CT 709075008 2014-04 2020-08-18 Aromatic l-amino acid decarboxylase deficiency https://medlineplus.gov/genetics/condition/aromatic-l-amino-acid-decarboxylase-deficiency descriptionAromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disorder that affects the way nerve cells (neurons) transmit information to other cells.Signs and symptoms of AADC deficiency typically appear in the first six months of life. Affected infants may have feeding problems, weak muscle tone (hypotonia), and sleep disturbances. Most children with AADC deficiency experience episodes called oculogyric crises that involve involuntary upward-rolling movements of the eyes. Additional signs and symptoms typically include developmental delays and intellectual disabilities. Movement disorders are common in people with AADC deficiency. Involuntary movements that can occur in people with AADC deficiency include muscle contractions that may cause unusual body positions (dystonia) and writhing movements of the limbs (athetosis). Dystonia tends to become worse when the individual is tired, but it usually improves after sleep. Affected individuals may also experience slow or diminished movements (hypokinesia). AADC deficiency may also affect the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. This can lead to signs and symptoms such as droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, poor control of body temperature, low blood pressure (hypotension), low blood glucose (hypoglycemia), and abnormal heart rhythms.People with AADC deficiency have an increased risk of infection, which can lead to life-threatening complications.  ar Autosomal recessive DDC https://medlineplus.gov/genetics/gene/ddc AADC deficiency AADCD DDC deficiency Dopa decarboxylase deficiency GTR C1291564 ICD-10-CM MeSH D000592 OMIM 608643 SNOMED CT 124600004 2024-05 2024-11-14 Arrhythmogenic right ventricular cardiomyopathy https://medlineplus.gov/genetics/condition/arrhythmogenic-right-ventricular-cardiomyopathy descriptionArrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of heart disease that usually appears in adulthood. ARVC is a disorder of the myocardium, which is the muscular wall of the heart. This condition causes part of the myocardium to break down over time, increasing the risk of an abnormal heartbeat (arrhythmia) and sudden death.ARVC may not cause any symptoms in its early stages. However, affected individuals may still be at risk of sudden death, especially during strenuous exercise. When symptoms occur, they most commonly include a sensation of fluttering or pounding in the chest (palpitations), light-headedness, and fainting (syncope). Over time, ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen. If the myocardium becomes severely damaged in the later stages of the disease, it can lead to heart failure. ad Autosomal dominant ar Autosomal recessive LMNA https://medlineplus.gov/genetics/gene/lmna TTN https://medlineplus.gov/genetics/gene/ttn RYR2 https://medlineplus.gov/genetics/gene/ryr2 PKP2 https://medlineplus.gov/genetics/gene/pkp2 DES https://medlineplus.gov/genetics/gene/des DSC2 https://medlineplus.gov/genetics/gene/dsc2 DSP https://medlineplus.gov/genetics/gene/dsp JUP https://medlineplus.gov/genetics/gene/jup TGFB3 https://medlineplus.gov/genetics/gene/tgfb3 DSG2 https://www.ncbi.nlm.nih.gov/gene/1829 PLN https://www.ncbi.nlm.nih.gov/gene/5350 CTNNA3 https://www.ncbi.nlm.nih.gov/gene/29119 TMEM43 https://www.ncbi.nlm.nih.gov/gene/79188 Arrhythmogenic right ventricular cardiomyopathy-dysplasia Arrhythmogenic right ventricular dysplasia Arrhythmogenic right ventricular dysplasia/cardiomyopathy ARVC ARVD ARVD/C Right ventricular dysplasia, arrhythmogenic Ventricular dysplasia, right, arrhythmogenic GTR C0349788 GTR C1832931 GTR C1836704 GTR C1836906 GTR C1843896 GTR C1857777 GTR C1858378 GTR C1858379 GTR C1862511 GTR C1864850 GTR C1865881 GTR C1865882 GTR C1969081 GTR C3552311 GTR C3810138 MeSH D019571 OMIM 107970 OMIM 602086 OMIM 602087 OMIM 604400 OMIM 604401 OMIM 604772 OMIM 607450 OMIM 609040 OMIM 610193 OMIM 610476 OMIM 611528 OMIM 615616 SNOMED CT 253528005 SNOMED CT 281170005 2010-05 2020-08-18 Arterial tortuosity syndrome https://medlineplus.gov/genetics/condition/arterial-tortuosity-syndrome descriptionArterial tortuosity syndrome is a disorder that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the body, including blood vessels, skin, joints, and the gastrointestinal tract.As its name suggests, arterial tortuosity syndrome is characterized by blood vessel abnormalities, particularly abnormal twists and turns (tortuosity) of the blood vessels that carry blood from the heart to the rest of the body (the arteries). Tortuosity arises from abnormal elongation of the arteries; since the end points of the arteries are fixed, the extra length twists and curves. Other blood vessel abnormalities that may occur in this disorder include constriction (stenosis) and abnormal bulging (aneurysm) of vessels, as well as small clusters of enlarged blood vessels just under the skin (telangiectasia).Complications resulting from the abnormal arteries can be life-threatening. Rupture of an aneurysm or sudden tearing (dissection) of the layers in an arterial wall can result in massive loss of blood from the circulatory system. Blockage of blood flow to vital organs such as the heart, lungs, or brain can lead to heart attacks, respiratory problems, and strokes. Stenosis of the arteries forces the heart to work harder to pump blood and may lead to heart failure. As a result of these complications, arterial tortuosity syndrome is often fatal in childhood, although some individuals with mild cases of the disorder live into adulthood.Features of arterial tortuosity syndrome outside the circulatory system are caused by abnormal connective tissue in other parts of the body. These features include joints that are either loose and very flexible (hypermobile) or that have deformities limiting movement (contractures), and unusually soft and stretchable skin. Some affected individuals have long, slender fingers and toes (arachnodactyly); curvature of the spine (scoliosis); or a chest that is either sunken (pectus excavatum) or protruding (pectus carinatum). They may have protrusion of organs through gaps in muscles (hernias), elongation of the intestines, or pouches called diverticula in the intestinal walls.People with arterial tortuosity syndrome often look older than their age and have distinctive facial features including a long, narrow face with droopy cheeks; eye openings that are narrowed (blepharophimosis) with outside corners that point downward (downslanting palpebral fissures); a beaked nose with soft cartilage; a high, arched roof of the mouth (palate); a small lower jaw (micrognathia); and large ears. The cornea, which is the clear front covering of the eye, may be cone-shaped and abnormally thin (keratoconus). ar Autosomal recessive SLC2A10 https://medlineplus.gov/genetics/gene/slc2a10 Arterial tortuosity ATS GTR C1859726 ICD-10-CM Q87.82 MeSH D054079 OMIM 208050 SNOMED CT 458432002 2013-01 2020-08-18 Arts syndrome https://medlineplus.gov/genetics/condition/arts-syndrome descriptionArts syndrome is a disorder that causes serious neurological problems in males. Females can also be affected by this condition, but they typically have much milder symptoms.Boys with Arts syndrome have profound sensorineural hearing loss, which is a complete or almost complete loss of hearing caused by abnormalities in the inner ear. Other features of the disorder include weak muscle tone (hypotonia), impaired muscle coordination (ataxia), developmental delay, and intellectual disability. In early childhood, affected boys develop vision loss caused by degeneration of nerves that carry information from the eyes to the brain (optic nerve atrophy). They also experience loss of sensation and weakness in the limbs (peripheral neuropathy).Boys with Arts syndrome also usually have recurrent infections, especially involving the respiratory system. Because of these infections and their complications, affected boys often do not survive past early childhood.In females with Arts syndrome, hearing loss that begins in adulthood may be the only symptom. xd X-linked dominant PRPS1 https://medlineplus.gov/genetics/gene/prps1 Ataxia, fatal X-linked, with deafness and loss of vision Ataxia-deafness-optic atrophy, lethal GTR C0796028 MeSH D009422 OMIM 301835 SNOMED CT 702441001 2009-08 2020-08-18 Asparagine synthetase deficiency https://medlineplus.gov/genetics/condition/asparagine-synthetase-deficiency descriptionAsparagine synthetase deficiency is a condition that causes neurological problems in affected individuals starting soon after birth. Most people with this condition have an unusually small head size (microcephaly) that worsens over time due to loss (atrophy) of brain tissue. They also have severe developmental delay that affects both mental and motor skills (psychomotor delay). Affected individuals cannot sit, crawl, or walk and are unable to communicate verbally or nonverbally. The few affected children who achieve developmental milestones often lose these skills over time (developmental regression).Most individuals with asparagine synthetase deficiency have exaggerated reflexes (hyperreflexia) and weak muscle tone (hypotonia). The muscle problems worsen through childhood and lead to muscle stiffness, uncontrolled movements, and ultimately, paralysis of the arms and legs (spastic quadriplegia). Many affected individuals also have recurrent seizures (epilepsy). Not all affected people experience the same type of seizure. The most common types involve a loss of consciousness, muscle rigidity, and convulsions (tonic-clonic); involuntary muscle twitches (myoclonic); or abnormal muscle contraction (tonic). People with asparagine synthetase deficiency may have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli. Some affected individuals have blindness due to impairment of the area of the brain responsible for processing vision, called the occipital cortex (cortical blindness).People with asparagine synthetase deficiency typically do not survive past childhood. ar Autosomal recessive ASNS https://medlineplus.gov/genetics/gene/asns ASNS deficiency ASNSD Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome Disorder of asparagine metabolism GTR C3809971 MeSH D000592 OMIM 615574 2018-11 2020-08-18 Aspartylglucosaminuria https://medlineplus.gov/genetics/condition/aspartylglucosaminuria descriptionAspartylglucosaminuria is a condition that primarily affects mental functioning and movement. This conditions worsens over time. Infants with aspartylglucosaminuria appear healthy at birth, and development is typically normal throughout early childhood. Around the age of 2 or 3, affected children usually begin to have delayed speech, mild intellectual disability, and problems coordinating movements. Other features that develop in childhood include respiratory infections, a protrusion of organs through gaps in muscles (hernia), and a growth spurt resulting in a large head size (macrocephaly).Intellectual disability and movement problems worsen in adolescence. Most people with this disorder lose much of the speech they have learned, and affected adults usually have only a few words in their vocabulary. Adults with aspartylglucosaminuria often have psychological disorders and may develop seizures.People with aspartylglucosaminuria may also have bones that become progressively weak and prone to fracture (osteoporosis), an unusually large range of joint movement (hypermobility), and loose skin. Affected individuals tend to have a characteristic facial appearance that includes widely spaced eyes (ocular hypertelorism), small ears, and full lips. The nose is short and broad and the face is usually square-shaped. They often have poor oral health, including infections and gum disease (gingivitis). Children with this condition may be tall for their age, but lack of a growth spurt in puberty typically causes adults to be short with a small head size (microcephaly). Individuals with aspartylglucosaminuria usually survive into mid-adulthood. ar Autosomal recessive AGA https://medlineplus.gov/genetics/gene/aga AGA deficiency Aspartylglucosamidase deficiency Aspartylglucosaminidase deficiency Aspartylglycosaminuria Glycosylasparaginase deficiency GTR C0268225 ICD-10-CM E77.1 MeSH D054880 OMIM 208400 SNOMED CT 54954004 2008-12 2022-01-19 Asphyxiating thoracic dystrophy https://medlineplus.gov/genetics/condition/asphyxiating-thoracic-dystrophy descriptionAsphyxiating thoracic dystrophy, also known as Jeune syndrome, is an inherited disorder of bone growth characterized by a narrow chest, short ribs, shortened bones in the arms and legs, short stature, and extra fingers and toes (polydactyly). Additional skeletal abnormalities can include unusually shaped collarbones (clavicles) and pelvic bones, and and cone-shaped ends of the long bones in the arms and legs. Many infants with this condition are born with an extremely narrow, bell-shaped chest that can restrict the growth and expansion of the lungs. Life-threatening problems with breathing result, and people with asphyxiating thoracic dystrophy may live only into infancy or early childhood. However, in people who survive beyond the first few years, the narrow chest and related breathing problems can improve with age.Some people with asphyxiating thoracic dystrophy are born with less severe skeletal abnormalities and have only mild breathing difficulties, such as rapid breathing or shortness of breath. These individuals may live into adolescence or adulthood. After infancy, people with this condition may develop life-threatening kidney (renal) abnormalities that cause the kidneys to malfunction or fail. Heart defects and a narrowing of the airway (subglottic stenosis) are also possible. Other, less common features of asphyxiating thoracic dystrophy include liver disease, fluid-filled sacs (cysts) in the pancreas, dental abnormalities, and an eye disease called retinal dystrophy that can lead to vision loss. ar Autosomal recessive IFT80 https://medlineplus.gov/genetics/gene/ift80 IFT140 https://medlineplus.gov/genetics/gene/ift140 WDR19 https://medlineplus.gov/genetics/gene/wdr19 WDR35 https://medlineplus.gov/genetics/gene/wdr35 DYNC2H1 https://medlineplus.gov/genetics/gene/dync2h1 IFT172 https://www.ncbi.nlm.nih.gov/gene/26160 DYNC2I1 https://www.ncbi.nlm.nih.gov/gene/55112 TTC21B https://www.ncbi.nlm.nih.gov/gene/79809 CSPP1 https://www.ncbi.nlm.nih.gov/gene/79848 DYNC2I2 https://www.ncbi.nlm.nih.gov/gene/89891 CEP120 https://www.ncbi.nlm.nih.gov/gene/153241 Asphyxiating thoracic chondrodystrophy Asphyxiating thoracic dysplasia ATD Chondroectodermal dysplasia-like syndrome Infantile thoracic dystrophy Jeune syndrome Jeune thoracic dysplasia Jeune thoracic dystrophy Thoracic asphyxiant dystrophy Thoracic-pelvic-phalangeal dystrophy GTR C0265275 GTR C1970005 GTR C3151185 GTR C3280598 GTR C4551856 ICD-10-CM Q77.2 MeSH D010009 OMIM 208500 OMIM 263520 OMIM 266920 OMIM 611263 OMIM 613091 OMIM 613819 OMIM 614091 OMIM 614376 OMIM 615503 OMIM 615630 OMIM 615633 SNOMED CT 75049004 2015-05 2020-08-18 Ataxia neuropathy spectrum https://medlineplus.gov/genetics/condition/ataxia-neuropathy-spectrum descriptionAtaxia neuropathy spectrum is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Ataxia neuropathy spectrum now includes the conditions previously called mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO).As the name implies, people with ataxia neuropathy spectrum typically have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). The neuropathy can be classified as sensory, motor, or a combination of the two (mixed). Sensory neuropathy causes numbness, tingling, or pain in the arms and legs, and motor neuropathy refers to disturbance in the nerves used for muscle movement.Most people with ataxia neuropathy spectrum also have severe brain dysfunction (encephalopathy) and seizures. Some affected individuals have weakness of the external muscles of the eye (ophthalmoplegia), which leads to drooping eyelids (ptosis). Other signs and symptoms can include involuntary muscle twitches (myoclonus), liver disease, depression, migraine headaches, or blindness. ad Autosomal dominant ar Autosomal recessive TWNK https://medlineplus.gov/genetics/gene/twnk POLG https://medlineplus.gov/genetics/gene/polg ANS MIRAS Mitochondrial recessive ataxia syndrome SANDO Sensory ataxia neuropathy dysarthria and ophthalmoplegia GTR C1843851 MeSH D028361 OMIM 607459 SNOMED CT 193165008 2011-06 2020-08-18 Ataxia with oculomotor apraxia https://medlineplus.gov/genetics/condition/ataxia-with-oculomotor-apraxia descriptionAtaxia with oculomotor apraxia is a condition characterized by problems with movement that worsen over time. The hallmark of this condition is poor coordination and balance (ataxia), which is often the first symptom. Most affected people also have oculomotor apraxia, which makes it difficult to move their eyes side-to-side. People with oculomotor apraxia have to turn their head to see things in their side (peripheral) vision.There are several types of ataxia with oculomotor apraxia, the most common of which are types 1, 2, and 4. The types are very similar but are caused by mutations in different genes.Type 1 begins around age 4. In addition to ataxia and oculomotor apraxia, affected individuals can have involuntary jerking movements (chorea) or muscle twitches (myoclonus); these movement problems tend to disappear over time. Individuals with this type may also develop muscle wasting in their hands and feet, which further impairs movement. As in all forms of ataxia with oculomotor apraxia, nearly all people with type 1 develop nerve abnormalities (neuropathy). Neuropathy impairs reflexes and leads to limb weakness and an inability to sense vibrations. Many individuals with ataxia with oculomotor apraxia require wheelchair assistance, typically 10 to 15 years after the start of movement problems.People with some types of ataxia with oculomotor apraxia may have characteristic blood abnormalities. Individuals with type 1 tend to have reduced amounts of a protein called albumin, which transports molecules in the blood. The shortage of albumin likely results in elevated levels of cholesterol circulating in the bloodstream. Increased cholesterol levels raise a person's risk of developing heart disease.Ataxia with oculomotor apraxia type 2 usually begins around age 15. As in type 1, affected individuals may have chorea or myoclonus, although these movement problems persist throughout life in type 2. Neuropathy is also common in this type.A key feature of ataxia with oculomotor apraxia type 2 is high amounts of a protein called alpha-fetoprotein (AFP) in the blood. (Raised levels of this protein are normally seen in the bloodstream of pregnant women.) Individuals with type 2 may also have high amounts of a protein called creatine phosphokinase (CPK) in their blood. This protein is normally found primarily in muscle tissue. The effect of abnormally high levels of AFP or CPK in people with ataxia with oculomotor apraxia type 2 is unknown. Although individuals with type 2 usually have normal albumin levels, cholesterol may be elevated.Ataxia with oculomotor apraxia type 4 begins around age 4. In addition to ataxia and oculomotor apraxia, individuals with this type typically develop dystonia, which is involuntary, sustained muscle tensing that causes unusual positioning of body parts. Dystonia can be the first feature of the condition, and it tends to disappear gradually over time. Muscle wasting in the hands and feet and neuropathy are also common in individuals with type 4.In ataxia with oculomotor apraxia type 4, albumin levels can be low, and cholesterol or AFP can be elevated. However, the amounts of these molecules are normal in many affected individuals.Intelligence is usually not affected by ataxia with oculomotor apraxia, but some people with the condition have intellectual disability. ar Autosomal recessive SETX https://medlineplus.gov/genetics/gene/setx APTX https://medlineplus.gov/genetics/gene/aptx PNKP https://medlineplus.gov/genetics/gene/pnkp XRCC1 https://www.ncbi.nlm.nih.gov/gene/7515 PIK3R5 https://www.ncbi.nlm.nih.gov/gene/23533 Adult onset ataxia with oculomotor apraxia EAOH Early-onset ataxia with ocular motor apraxia and hypoalbuminemia SCAN2 SCAR1 Spinocerebellar ataxia with axonal neuropathy type 2 Spinocerebellar ataxia, recessive, non-Friedreich type 1 GTR C1853761 GTR C1859598 GTR C3554690 GTR C4225397 MeSH D002524 OMIM 208920 OMIM 606002 OMIM 615217 OMIM 616267 SNOMED CT 715366004 SNOMED CT 725408001 2018-06 2020-08-18 Ataxia with vitamin E deficiency https://medlineplus.gov/genetics/condition/ataxia-with-vitamin-e-deficiency descriptionAtaxia with vitamin E deficiency is a disorder that impairs the body's ability to use vitamin E obtained from the diet. Vitamin E is an antioxidant, which means that it protects cells in the body from the damaging effects of unstable molecules called free radicals. A shortage (deficiency) of vitamin E can lead to neurological problems, such as difficulty coordinating movements (ataxia) and speech (dysarthria), loss of reflexes in the legs (lower limb areflexia), and a loss of sensation in the extremities (peripheral neuropathy). Some people with this condition have developed an eye disorder called retinitis pigmentosa that causes vision loss. Most people who have ataxia with vitamin E deficiency start to experience problems with movement between the ages of 5 and 15 years. The movement problems tend to worsen with age. ar Autosomal recessive TTPA https://medlineplus.gov/genetics/gene/ttpa Ataxia with isolated vitamin E deficiency AVED Familial isolated vitamin E deficiency FIVE Friedreich ataxia phenotype with selective vitamin E deficiency Friedreich-like ataxia GTR C1848533 MeSH D014811 OMIM 277460 SNOMED CT 702442008 2008-04 2020-08-18 Ataxia-pancytopenia syndrome https://medlineplus.gov/genetics/condition/ataxia-pancytopenia-syndrome descriptionAtaxia-pancytopenia syndrome is a rare condition that affects the part of the brain that coordinates movement (the cerebellum) and blood-forming cells in the bone marrow. The age when signs and symptoms begin, the severity of the condition, and the rate at which it worsens all vary among affected individuals.People with ataxia-pancytopenia syndrome have neurological problems associated with a loss of tissue (atrophy) and other changes in the cerebellum. These problems include poor coordination and balance (ataxia), difficulty with movements that involve judging distance or scale (dysmetria), uncontrollable muscle contractions (clonus), and involuntary back-and-forth eye movements (nystagmus). These neurological issues worsen over time, making walking and other movements challenging. Some affected individuals eventually require wheelchair assistance.Ataxia-pancytopenia syndrome also causes a shortage of one or more types of normal blood cells: red blood cells, white blood cells, and platelets. A shortage of all three of these cell types is known as pancytopenia. Pancytopenia can result in extreme tiredness (fatigue) due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and abnormal bleeding due to low numbers of platelets (thrombocytopenia). Ataxia-pancytopenia syndrome is also associated with an increased risk of certain cancerous conditions of the blood, particularly myelodysplastic syndrome and acute myeloid leukemia. ad Autosomal dominant SAMD9L https://medlineplus.gov/genetics/gene/samd9l ATXPC Myelocerebellar disorder GTR C1327919 MeSH D001259 MeSH D010198 OMIM 159550 OMIM 252270 2017-09 2020-08-18 Ataxia-telangiectasia https://medlineplus.gov/genetics/condition/ataxia-telangiectasia descriptionAtaxia-telangiectasia is a rare inherited disorder that affects the nervous system, immune system, and other body systems.  This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood, usually before age 5. Affected children typically develop difficulty walking, problems with balance and hand coordination, involuntary jerking movements (chorea), muscle twitches (myoclonus), and disturbances in nerve function (neuropathy).  The movement problems typically cause people to require wheelchair assistance by adolescence. People with this disorder also have slurred speech and trouble moving their eyes to look side-to-side (oculomotor apraxia). Small clusters of enlarged blood vessels called telangiectases, which occur in the eyes and on the surface of the skin, are also characteristic of this condition.Affected individuals tend to have high amounts of a protein called alpha-fetoprotein (AFP) in their blood. The level of this protein is normally increased in the bloodstream of pregnant women, but it is unknown why individuals with ataxia-telangiectasia have elevated AFP or what effects it has in these individuals.People with ataxia-telangiectasia often have a weakened immune system, and many develop chronic lung infections. They also have an increased risk of developing cancer, particularly cancer of blood-forming cells (leukemia) and cancer of immune system cells (lymphoma). Affected individuals are very sensitive to the effects of radiation exposure, including medical x-rays. Ataxia-telangiectasia has no cure, though treatments might improve some symptoms. These treatments include physical and speech therapy and improving deficits in the immune system and nutrition. The life expectancy of people with ataxia-telangiectasia varies greatly, but affected individuals typically live into early adulthood. ar Autosomal recessive ATM https://medlineplus.gov/genetics/gene/atm A-T Ataxia telangiectasia syndrome ATM Louis-Bar syndrome Telangiectasia, cerebello-oculocutaneous GTR C0004135 MeSH D001260 OMIM 208900 SNOMED CT 68504005 2022-09 2022-09-19 Atelosteogenesis type 1 https://medlineplus.gov/genetics/condition/atelosteogenesis-type-1 descriptionAtelosteogenesis type 1 is a disorder that affects the development of bones throughout the body. Affected individuals are born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. Bones in the spine, rib cage, pelvis, and limbs may be underdeveloped or in some cases absent. As a result of the limb bone abnormalities, individuals with this condition have very short arms and legs. Characteristic facial features include a prominent forehead, wide-set eyes (hypertelorism), an upturned nose with a grooved tip, and a very small lower jaw and chin (micrognathia). Affected individuals may also have an opening in the roof of the mouth (a cleft palate). Males with this condition can have undescended testes.Individuals with atelosteogenesis type 1 typically have an underdeveloped rib cage that affects the development and functioning of the lungs. As a result, affected individuals are usually stillborn or die shortly after birth from respiratory failure. ad Autosomal dominant FLNB https://medlineplus.gov/genetics/gene/flnb AOI Atelosteogenesis type I Giant cell chondrodysplasia Spondylohumerofemoral hypoplasia GTR C0265283 MeSH D010009 OMIM 108720 SNOMED CT 725141006 2011-09 2020-08-18 Atelosteogenesis type 2 https://medlineplus.gov/genetics/condition/atelosteogenesis-type-2 descriptionAtelosteogenesis type 2 is a severe disorder of cartilage and bone development. Infants born with this condition have very short arms and legs, a narrow chest, and a prominent, rounded abdomen. This disorder is also characterized by an opening in the roof of the mouth (a cleft palate), distinctive facial features, an inward- and upward-turning foot (clubfoot), and unusually positioned thumbs (hitchhiker thumbs).The signs and symptoms of atelosteogenesis type 2 are similar to those of another skeletal disorder called diastrophic dysplasia; however, atelosteogenesis type 2 is typically more severe. As a result of serious health problems, infants with this disorder are usually stillborn or die soon after birth from respiratory failure. Some infants, however, have lived for a short time with intensive medical support. ar Autosomal recessive SLC26A2 https://medlineplus.gov/genetics/gene/slc26a2 AO2 Atelosteogenesis de la Chapelle type Atelosteogenesis, type 2 De la Chapelle dysplasia McAlister dysplasia Neonatal osseous dysplasia 1 GTR C1850554 MeSH D010009 OMIM 256050 SNOMED CT 254055004 2020-05 2020-08-18 Atelosteogenesis type 3 https://medlineplus.gov/genetics/condition/atelosteogenesis-type-3 descriptionAtelosteogenesis type 3 is a disorder that affects the development of bones throughout the body. Affected individuals are born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. Bones in the spine, rib cage, pelvis, and limbs may be underdeveloped or in some cases absent. As a result of the limb bone abnormalities, individuals with this condition have very short arms and legs. Their hands and feet are wide, with broad fingers and toes that may be permanently bent (camptodactyly) or fused together (syndactyly). Characteristic facial features include a broad forehead, wide-set eyes (hypertelorism), and an underdeveloped nose. About half of affected individuals have an opening in the roof of the mouth (a cleft palate.)Individuals with atelosteogenesis type 3 typically have an underdeveloped rib cage that affects the development and functioning of the lungs. As a result, affected individuals are usually stillborn or die shortly after birth from respiratory failure. Some affected individuals survive longer, usually with intensive medical support. They typically experience further respiratory problems as a result of weakness of the airways that can lead to partial closing, short pauses in breathing (apnea), or frequent infections. People with atelosteogenesis type 3 who survive past the newborn period may have learning disabilities and delayed language skills, which are probably caused by low levels of oxygen in the brain due to respiratory problems. As a result of their orthopedic abnormalities, they also have delayed development of motor skills such as standing and walking. ad Autosomal dominant FLNB https://medlineplus.gov/genetics/gene/flnb AOIII Atelosteogenesis type III GTR C3668942 MeSH D010009 OMIM 108721 SNOMED CT 725142004 2011-09 2020-08-18 Atopic dermatitis https://medlineplus.gov/genetics/condition/atopic-dermatitis descriptionAtopic dermatitis (also known as atopic eczema) is a disorder characterized by inflammation of the skin (dermatitis). The condition usually begins in early infancy, and it often disappears before adolescence. However, in some affected individuals the condition continues into adulthood; in others, it does not begin until adulthood. Hallmarks of atopic dermatitis include dry, itchy skin and red rashes that come and go. The rashes can occur on any part of the body, although the pattern tends to be different at different ages. In affected infants, the rashes commonly occur on the face, scalp, hands, and feet. In children, the rashes are usually found in the bend of the elbows and knees and on the front of the neck. In adolescents and adults, the rashes typically occur on the wrists, ankles, and eyelids in addition to the bend of the elbows and knees. Scratching the itchy skin can lead to oozing and crusting of the rashes and thickening and hardening (lichenification) of the skin. The itchiness can be so severe as to disturb sleep and impair a person's quality of life.The word "atopic" indicates an association with allergies. While atopic dermatitis is not always due to an allergic reaction, it is commonly associated with other allergic disorders: up to 60 percent of people with atopic dermatitis develop asthma or hay fever (allergic rhinitis) later in life, and up to 30 percent have food allergies. Atopic dermatitis is often the beginning of a series of allergic disorders, referred to as the "atopic march." Development of these disorders typically follows a pattern, beginning with atopic dermatitis, followed by food allergies, then hay fever, and finally asthma. However, not all individuals with atopic dermatitis will progress through the atopic march, and not all individuals with one allergic disease will develop others.Individuals with atopic dermatitis have an increased risk of developing other conditions related to inflammation, such as inflammatory bowel disease, rheumatoid arthritis, and hair loss caused by a malfunctioning immune reaction (alopecia areata). They also have an increased risk of having a behavioral or psychiatric disorder, such as attention-deficit/hyperactivity disorder (ADHD) or depression.In a particular subset of individuals with atopic dermatitis, the immune system is unable to protect the body from foreign invaders such as bacteria and fungi (which is known as immunodeficiency). These individuals are prone to recurrent infections. Most also have other allergic disorders, such as asthma, hay fever, and food allergies.Atopic dermatitis can also be a feature of separate disorders that have a number of signs and symptoms, which can include skin abnormalities and immunodeficiency. Some such disorders are Netherton syndrome; immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome; and severe dermatitis, multiple allergies, metabolic wasting (SAM) syndrome. ad Autosomal dominant FLG https://medlineplus.gov/genetics/gene/flg CARD11 https://medlineplus.gov/genetics/gene/card11 Atopic eczema GTR C1853965 ICD-10-CM L20.82 ICD-10-CM L20.83 ICD-10-CM L20.84 ICD-10-CM L20.89 ICD-10-CM L20.9 MeSH D003876 OMIM 603165 OMIM 605803 OMIM 617638 SNOMED CT 24079001 SNOMED CT 402189008 SNOMED CT 402194008 2017-10 2020-08-18 Attention-deficit/hyperactivity disorder https://medlineplus.gov/genetics/condition/attention-deficit-hyperactivity-disorder descriptionAttention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.In people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.Hyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.Impulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.More than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.In most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood. u Pattern unknown ADD ADDH ADHD Attention deficit Attention deficit disorder Attention deficit disorder of childhood with hyperactivity Attention deficit disorder with hyperactivity Attention deficit disorder with hyperactivity syndrome Attention deficit hyperactivity disorder Hyperkinetic disorder Hyperkinetic syndrome GTR C1263846 GTR C1837153 GTR C2751802 ICD-10-CM F90.0 ICD-10-CM F90.1 ICD-10-CM F90.2 ICD-10-CM F90.8 ICD-10-CM F90.9 MeSH D001289 OMIM 143465 SNOMED CT 406506008 2019-06 2020-08-18 Atypical hemolytic-uremic syndrome https://medlineplus.gov/genetics/condition/atypical-hemolytic-uremic-syndrome descriptionAtypical hemolytic-uremic syndrome is a disease that primarily affects kidney function. This condition, which can occur at any age, causes abnormal blood clots (thrombi) to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow. Atypical hemolytic-uremic syndrome is characterized by three major features related to abnormal clotting: hemolytic anemia, thrombocytopenia, and kidney failure.Hemolytic anemia occurs when red blood cells break down (undergo hemolysis) prematurely. In atypical hemolytic-uremic syndrome, red blood cells can break apart as they squeeze past clots within small blood vessels. Anemia results if these cells are destroyed faster than the body can replace them. Anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.Thrombocytopenia is a reduced level of circulating platelets, which are cells that normally assist with blood clotting. In people with atypical hemolytic-uremic syndrome, fewer platelets are available in the bloodstream because a large number of platelets are used to make abnormal clots. Thrombocytopenia can cause easy bruising and abnormal bleeding.As a result of clot formation in small blood vessels, people with atypical hemolytic-uremic syndrome experience kidney damage and acute kidney failure that lead to end-stage renal disease (ESRD) in about half of all cases. These life-threatening complications prevent the kidneys from filtering fluids and waste products from the body effectively.Atypical hemolytic-uremic syndrome should be distinguished from a more common condition called typical hemolytic-uremic syndrome. The two disorders have different causes and different signs and symptoms. Unlike the atypical form, the typical form is caused by infection with certain strains of Escherichia coli bacteria that produce toxic substances called Shiga-like toxins. The typical form is characterized by severe diarrhea and most often affects children younger than 10. The typical form is less likely than the atypical form to involve recurrent attacks of kidney damage that lead to ESRD. ad Autosomal dominant ar Autosomal recessive CFH https://medlineplus.gov/genetics/gene/cfh CFI https://medlineplus.gov/genetics/gene/cfi C3 https://medlineplus.gov/genetics/gene/c3 CFHR5 https://medlineplus.gov/genetics/gene/cfhr5 CFB https://www.ncbi.nlm.nih.gov/gene/629 CD46 https://www.ncbi.nlm.nih.gov/gene/4179 THBD https://www.ncbi.nlm.nih.gov/gene/7056 AHUS Non-Shiga-like toxin-associated HUS Non-Stx-HUS Nonenteropathic HUS GTR C2749604 GTR C2752036 GTR C2752037 GTR C2752038 GTR C2752039 GTR C2752040 GTR C2931788 ICD-10-CM D59.3 MeSH D006463 OMIM 235400 OMIM 612922 OMIM 612923 OMIM 612924 OMIM 612925 OMIM 612926 SNOMED CT 373422007 2010-06 2020-08-18 Au-Kline syndrome https://medlineplus.gov/genetics/condition/au-kline-syndrome descriptionAu-Kline syndrome is a condition that affects many body systems. Individuals with this condition typically have weak muscle tone (hypotonia), intellectual disability, and delayed development. Speech is delayed in children with Au-Kline syndrome, and some are able to say only one or a few words or are never able to speak. In addition, affected children learn to walk later than usual, and some are never able to walk on their own.Individuals with Au-Kline syndrome can have distinctive facial features, including long openings of the eyelids (long palpebral fissures), drooping eyelids (ptosis), and shallow eye sockets. Other common facial features in this condition include a broad nasal bridge, a mouth with the outer corners turned downward and often held in an open position, and a deep groove down the middle of the tongue. Less common abnormalities include premature joining of certain skull bones (craniosynostosis) in affected infants, an opening or unusually high arch in the roof of the mouth (cleft or high-arched palate), a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula), and missing teeth (oligodontia).Malformations of the heart, blood vessels, kidneys, or bones can also occur in people with Au-Kline syndrome. For example, in some affected individuals, the large blood vessel that distributes blood from the heart to the rest of the body (the aorta) becomes weakened and stretched (aortic dilatation), which can be life-threatening. Some people with Au-Kline syndrome have an abnormal curvature of the spine (scoliosis). In addition, affected individuals may have difficulty feeding or poor vision.Au-Kline syndrome can sometimes affect the autonomic nervous system, which controls involuntary body functions, such as digestion and regulation of body temperature. In people with Au-Kline syndrome, abnormalities in this system can lead to digestive problems, difficulty feeling pain, abnormal sweating, and an inability to adjust to high heat in people with Au-Kline syndrome. ad Autosomal dominant HNRNPK https://medlineplus.gov/genetics/gene/hnrnpk Okamoto syndrome GTR C4225274 MeSH D002658 MeSH D008607 OMIM 616580 2019-10 2020-08-18 Auriculocondylar syndrome https://medlineplus.gov/genetics/condition/auriculo-condylar-syndrome descriptionAuriculocondylar syndrome is a condition that affects facial development, particularly the development of the ears and lower jaw (mandible). The features seen in people with this condition can vary, even among members of the same family. A hallmark of this condition is an ear abnormality called a question mark ear, in which the ears have a distinctive question mark shape that is caused by a split that separates the upper part of the ear from the earlobe. Other ear abnormalities that can occur in people with auriculocondylar syndrome include cupped ears, ears with fewer folds and grooves than usual, narrow ear canals, small skin tags in front of or behind the ears, and ears that are rotated backward. Some affected individuals also have hearing loss.Affected individuals often have a small lower jaw (micrognathia), which is caused by the underdevelopment of the upper portion of the mandible (condyle). These abnormalities can impair the function of the temporomandibular joint (TMJ), which connects the lower jaw to the skull. Problems with the TMJ affect how the upper and lower jaws fit together and can make it difficult to open and close the mouth. Because micrognathia often causes problems with breathing, many infants with auriculocondylar syndrome will need a breathing tube.Other features of auriculocondylar syndrome can include prominent cheeks, an unusually small mouth (microstomia), a tongue that is placed further back in the mouth than normal (glossoptosis), differences in the size and shape of facial features between the right and left sides of the face (facial asymmetry), and an opening in the roof of the mouth (cleft palate). In rare cases, people with auriculocondylar syndrome have developmental delays and intellectual disabilities. ar Autosomal recessive ad Autosomal dominant+New variant GNAI3 https://medlineplus.gov/genetics/gene/gnai3 PLCB4 https://medlineplus.gov/genetics/gene/plcb4 EDN1 https://medlineplus.gov/genetics/gene/edn1 Auriculo-condylar syndrome Dysgnathia complex Question-mark ear syndrome GTR C1865295 GTR C3553404 GTR C3810332 GTR C4551996 GTR C5830664 MeSH D004427 OMIM 602483 OMIM 614669 OMIM 615706 OMIM 620458 SNOMED CT 702443003 2025-08 2025-08-18 Autism spectrum disorder https://medlineplus.gov/genetics/condition/autism-spectrum-disorder descriptionAutism spectrum disorder (ASD) is a condition that appears very early in childhood development, varies in severity, and is characterized by impaired social skills, communication problems, and repetitive actions. These difficulties can interfere with affected individuals' ability to function in social, academic, and employment settings. People with ASD also have an increased risk of psychiatric problems such as anxiety, depression, obsessive-compulsive disorder, and eating disorders.From as early as 1 to 2 years of age, people with ASD have an impaired ability to interact with other people; they are often more comfortable dealing with objects. Affected individuals have difficulty understanding and using non-verbal social cues such as eye contact, facial expressions, gestures, and body language. Inability to recognize and use these cues makes it hard for affected individuals to understand the feelings of others or communicate their own feelings appropriately. Signs of ASD, such as reduced eye contact and social interaction, can sometimes be detected before age 2. However, the condition is usually diagnosed between ages 2 and 4, when more advanced communication and social skills, such as learning to play with others, typically begin to develop.Repetitive actions in ASD can include simple actions such as rocking, hand-flapping, or repetition of words or noises (echolalia). Affected individuals often dwell on or repeatedly express particular thoughts; this trait is called perseveration. People with ASD tend to be rigid about their established routines and may strongly resist disruptions such as changes in schedule. They may also have difficulty tolerating sensory stimuli such as loud noises or bright lights.While social and communication difficulties and unusual actions define ASD, affected individuals can have a wide range of intellectual abilities and language skills. A majority of people with ASD have mild to moderate intellectual disability, while others have average to above-average intelligence. Some have particular cognitive abilities that greatly surpass their overall level of functioning, often in areas such as music, mathematics, or memory.Some people with ASD do not speak at all, while others use language fluently. However, fluent speakers with ASD often have problems associated with verbal communication. They might speak in a monotone voice, have unusual vocal mannerisms, or choose unusual topics of conversation.Several diagnoses that used to be classified as separate conditions are now grouped together under the diagnosis of ASD. For example, autistic disorder was a term that was used when affected individuals had limited or absent verbal communication, often in combination with intellectual disability. By contrast, Asperger syndrome was a diagnosis formerly applied to affected individuals of average or above-average intelligence who were not delayed in their language development. The broader diagnosis of ASD was established because many affected individuals fall outside of the strict definitions of the narrower diagnoses, and their intellectual and communication abilities may change over time. However, some individuals who were previously diagnosed with one of the subtypes now do not meet all the criteria of the new umbrella diagnosis. u Pattern unknown PTEN https://medlineplus.gov/genetics/gene/pten MECP2 https://medlineplus.gov/genetics/gene/mecp2 UBE3A https://medlineplus.gov/genetics/gene/ube3a ANK2 https://medlineplus.gov/genetics/gene/ank2 CTNND2 https://medlineplus.gov/genetics/gene/ctnnd2 SHANK3 https://medlineplus.gov/genetics/gene/shank3 KCNQ3 https://medlineplus.gov/genetics/gene/kcnq3 RELN https://medlineplus.gov/genetics/gene/reln ARID1B https://medlineplus.gov/genetics/gene/arid1b SYNGAP1 https://medlineplus.gov/genetics/gene/syngap1 CHD2 https://medlineplus.gov/genetics/gene/chd2 ADNP https://medlineplus.gov/genetics/gene/adnp CHD8 https://medlineplus.gov/genetics/gene/chd8 DYRK1A https://medlineplus.gov/genetics/gene/dyrk1a POGZ https://medlineplus.gov/genetics/gene/pogz ASH1L https://medlineplus.gov/genetics/gene/ash1l GRIN2B https://medlineplus.gov/genetics/gene/grin2b SCN2A https://medlineplus.gov/genetics/gene/scn2a DSCAM https://www.ncbi.nlm.nih.gov/gene/1826 EIF4E https://www.ncbi.nlm.nih.gov/gene/1977 GABRB3 https://www.ncbi.nlm.nih.gov/gene/2562 KDM5A https://www.ncbi.nlm.nih.gov/gene/5927 RPL10 https://www.ncbi.nlm.nih.gov/gene/6134 SYN1 https://www.ncbi.nlm.nih.gov/gene/6853 SYN2 https://www.ncbi.nlm.nih.gov/gene/6854 CACNA1H https://www.ncbi.nlm.nih.gov/gene/8912 NRXN1 https://www.ncbi.nlm.nih.gov/gene/9378 TBR1 https://www.ncbi.nlm.nih.gov/gene/10716 KDM5B https://www.ncbi.nlm.nih.gov/gene/10765 NLGN1 https://www.ncbi.nlm.nih.gov/gene/22871 SHANK2 https://www.ncbi.nlm.nih.gov/gene/22941 MYT1L https://www.ncbi.nlm.nih.gov/gene/23040 CNTNAP2 https://www.ncbi.nlm.nih.gov/gene/26047 CNTN4 https://www.ncbi.nlm.nih.gov/gene/53943 NLGN3 https://www.ncbi.nlm.nih.gov/gene/54413 TMLHE https://www.ncbi.nlm.nih.gov/gene/55217 KCNQ5 https://www.ncbi.nlm.nih.gov/gene/56479 ASXL3 https://www.ncbi.nlm.nih.gov/gene/80816 KATNAL2 https://www.ncbi.nlm.nih.gov/gene/83473 PTCHD1 https://www.ncbi.nlm.nih.gov/gene/139411 ASD Autistic continuum Pervasive developmental disorder GTR C1510586 ICD-10-CM F84.0 MeSH D000067877 OMIM 209850 SNOMED CT 408856003 2017-06 2025-08-18 Autoimmune Addison disease https://medlineplus.gov/genetics/condition/autoimmune-addison-disease descriptionAutoimmune Addison disease affects the function of the adrenal glands, which are small hormone-producing glands located on top of each kidney. It is classified as an autoimmune disorder because it results from a malfunctioning immune system that attacks the adrenal glands. As a result, the production of several hormones is disrupted, which affects many body systems.The signs and symptoms of autoimmune Addison disease can begin at any time, although they most commonly begin between ages 30 and 50. Common features of this condition include extreme tiredness (fatigue), nausea, decreased appetite, and weight loss. In addition, many affected individuals have low blood pressure (hypotension), which can lead to dizziness when standing up quickly; muscle cramps; and a craving for salty foods. A characteristic feature of autoimmune Addison disease is abnormally dark areas of skin (hyperpigmentation), especially in regions that experience a lot of friction, such as the armpits, elbows, knuckles, and palm creases. The lips and the inside lining of the mouth can also be unusually dark. Because of an imbalance of hormones involved in development of sexual characteristics, women with this condition may lose their underarm and pubic hair.Other signs and symptoms of autoimmune Addison disease include low levels of sugar (hypoglycemia) and sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood. Affected individuals may also have a shortage of red blood cells (anemia) and an increase in the number of white blood cells (lymphocytosis), particularly those known as eosinophils (eosinophilia).Autoimmune Addison disease can lead to a life-threatening adrenal crisis, characterized by vomiting, abdominal pain, back or leg cramps, and severe hypotension leading to shock. The adrenal crisis is often triggered by a stressor, such as surgery, trauma, or infection.Individuals with autoimmune Addison disease or their family members can have another autoimmune disorder, most commonly autoimmune thyroid disease or type 1 diabetes. u Pattern unknown NLRP1 https://medlineplus.gov/genetics/gene/nlrp1 PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 HLA-DQB1 https://medlineplus.gov/genetics/gene/hla-dqb1 HLA-DQA1 https://medlineplus.gov/genetics/gene/hla-dqa1 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 CIITA https://medlineplus.gov/genetics/gene/ciita CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 MICA https://www.ncbi.nlm.nih.gov/gene/4276 Autoimmune Addison's disease Autoimmune adrenalitis Classic Addison disease Primary Addison disease ICD-10-CM E27.1 ICD-10-CM E27.2 MeSH D000224 SNOMED CT 363732003 2014-06 2026-03-17 Autoimmune lymphoproliferative syndrome https://medlineplus.gov/genetics/condition/autoimmune-lymphoproliferative-syndrome descriptionAutoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which the body cannot properly regulate the number of immune system cells (lymphocytes). ALPS is characterized by the production of an abnormally large number of lymphocytes (lymphoproliferation). Accumulation of excess lymphocytes results in enlargement of the lymph nodes (lymphadenopathy), the liver (hepatomegaly), and the spleen (splenomegaly).Autoimmune disorders are also common in ALPS. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Most of the autoimmune disorders associated with ALPS target and damage blood cells. For example, the immune system may attack red blood cells (autoimmune hemolytic anemia), white blood cells (autoimmune neutropenia), or platelets (autoimmune thrombocytopenia). Less commonly, autoimmune disorders that affect other organs and tissues occur in people with ALPS. These disorders can damage the kidneys (glomerulonephritis), liver (autoimmune hepatitis), eyes (uveitis), or nerves (Guillain-Barre syndrome). Skin problems, usually rashes or hives (urticaria), can also occur in ALPS.ALPS can have varying patterns of signs and symptoms. Most commonly, lymphoproliferation becomes apparent during childhood. Enlargement of the lymph nodes and spleen frequently occur in affected individuals. Autoimmune disorders typically develop several years later, most frequently as a combination of hemolytic anemia and thrombocytopenia, also called Evans syndrome. People with this classic form of ALPS generally have a near-normal lifespan, but have a greatly increased risk of developing cancer of the immune system cells (lymphoma) compared with the general population.Some people have signs and symptoms that resemble those of ALPS, including lymphoproliferation, lymphadenopathy, splenomegaly, and low blood counts, but the specific pattern of these signs and symptoms or the genetic cause may be different. Researchers disagree whether individuals with these non-classic forms should be considered to have ALPS or a separate condition. ad Autosomal dominant ar Autosomal recessive KRAS https://medlineplus.gov/genetics/gene/kras STAT3 https://medlineplus.gov/genetics/gene/stat3 FAS https://medlineplus.gov/genetics/gene/fas NRAS https://medlineplus.gov/genetics/gene/nras MAGT1 https://medlineplus.gov/genetics/gene/magt1 PIK3CD https://medlineplus.gov/genetics/gene/pik3cd FASLG https://www.ncbi.nlm.nih.gov/gene/356 CASP10 https://www.ncbi.nlm.nih.gov/gene/843 CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 ALPS Canale-Smith syndrome GTR C1328840 ICD-10-CM D89.82 MeSH D056735 OMIM 601859 SNOMED CT 702444009 2018-12 2020-08-18 Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy https://medlineplus.gov/genetics/condition/autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy descriptionAutoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inherited condition that affects many of the body's organs. It is one of many autoimmune diseases, which are disorders that occur when the immune system malfunctions and attacks the body's own tissues and organs by mistake.In most cases, the signs and symptoms of APECED begin in childhood or adolescence. This condition commonly involves three characteristic features: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal gland insufficiency. Affected individuals typically have at least two of these features, and many have all three.CMC is a tendency to develop infections of the skin, the nails, and the moist lining of body cavities (mucous membranes) caused by a type of fungus called Candida. These infections, which are commonly known as yeast infections, are chronic, which means they recur and can last a long time. CMC is usually the first of the three characteristic features of APECED to become apparent in people with this disorder. Almost all affected individuals develop infections of the oral cavity (known as thrush). Infections of the tube that carries food from the mouth to the stomach (the esophagus) are also common, while the skin and nails are affected less often. In women, vaginal infections frequently occur.Other features of APECED result from the body's immune system attacking the network of hormone-producing glands (the endocrine system). The second characteristic feature of the disorder is hypoparathyroidism, which is a malfunction of the parathyroid glands. These glands secrete a hormone that regulates the body's use of calcium and phosphorus. Damage to the parathyroid glands leads to reduced parathyroid hormone production (hypoparathyroidism). Hypoparathyroidism can cause a tingling sensation in the lips, fingers, and toes; muscle pain and cramping; weakness; and fatigue. Serious effects of hypoparathyroidism, such spasms of the voicebox (larynx) leading to breathing problems and seizures, can be life-threatening.Damage to the small hormone-producing glands on top of each kidney (adrenal glands) results in a third major feature of APECED, adrenal gland insufficiency (autoimmune Addison disease). Reduced hormone production by the adrenal glands leads to signs and symptoms that can include fatigue, muscle weakness, loss of appetite, weight loss, low blood pressure, and changes in skin coloring. Other endocrine problems that can occur in APECED include type 1 diabetes resulting from impaired production of the hormone insulin; a shortage of growth hormone leading to short stature; problems affecting the internal reproductive organs (ovaries or testes) that can cause inability to conceive children (infertility); and dysfunction of the thyroid gland (a butterfly-shaped tissue in the lower neck), which can result in many symptoms including weight gain and fatigue.Autoimmune problems affecting non-endocrine tissues can lead to a variety of additional signs and symptoms in people with APECED. These features occur more often in North American populations than in European populations. Rashes that resemble hives (urticarial eruptions) are common and often occur in infancy and early childhood. Other early signs and symptoms may include thin enamel on the teeth (enamel hypoplasia) and chronic diarrhea or constipation associated with difficulty in absorbing nutrients from food. Additional features that occur in people with APECED, many of which can lead to permanent organ and tissue damage if left untreated, include stomach irritation (gastritis), liver inflammation (hepatitis), lung irritation (pneumonitis), dry mouth and dry eyes (Sjogren-like syndrome), inflammation of the eyes (keratitis), kidney problems (nephritis), vitamin B12 deficiency, hair loss (alopecia), loss of skin color in blotches (vitiligo), high blood pressure (hypertension), or a small (atrophic) or absent spleen (asplenia). ar Autosomal recessive AIRE https://medlineplus.gov/genetics/gene/aire AIRE deficiency APECED APS type 1 APS1 Autoimmune polyendocrinopathy syndrome type 1 Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy Autoimmune polyglandular syndrome, type 1 PGA I Polyglandular autoimmune syndrome, type 1 Polyglandular type I autoimmune syndrome GTR C0085859 GTR C2749602 ICD-10-CM E31.0 MeSH D016884 OMIM 240300 SNOMED CT 11244009 2016-10 2020-08-18 Autosomal dominant cerebellar ataxia, deafness, and narcolepsy https://medlineplus.gov/genetics/condition/autosomal-dominant-cerebellar-ataxia-deafness-and-narcolepsy descriptionAutosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCADN) is a nervous system disorder with signs and symptoms that usually begin in mid-adulthood and gradually get worse.People with ADCADN have difficulty coordinating movements (ataxia) and mild to moderate hearing loss caused by abnormalities of the inner ear (sensorineural deafness). Most have excessive daytime sleepiness (narcolepsy). Narcolepsy is typically accompanied by cataplexy, which is a sudden brief loss of muscle tone in response to strong emotion (such as excitement, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. These characteristic signs and symptoms of ADCADN typically begin in a person's thirties.Eventually, people with ADCADN also experience a decline of intellectual function (dementia). The cognitive problems often begin with impairment of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Other features that can occur as the condition worsens include degeneration of the nerves that carry information from the eyes to the brain (optic atrophy); clouding of the lenses of the eyes (cataracts); numbness, tingling, or pain in the arms and legs (sensory neuropathy); puffiness or swelling (lymphedema) of the limbs; an inability to control the bowels or the flow of urine (incontinence); depression; uncontrollable crying or laughing (pseudobulbar signs); or a distorted view of reality (psychosis). Affected individuals usually survive into their forties or fifties. ad Autosomal dominant DNMT1 https://medlineplus.gov/genetics/gene/dnmt1 ADCA-DN syndrome ADCADN Autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant GTR C4302668 MeSH D002524 OMIM 604121 SNOMED CT 722293005 2017-07 2020-08-18 Autosomal dominant congenital stationary night blindness https://medlineplus.gov/genetics/condition/autosomal-dominant-congenital-stationary-night-blindness descriptionAutosomal dominant congenital stationary night blindness is a disorder of the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing and distinguishing objects in low light (night blindness). For example, they are not able to identify road signs at night and some people cannot see stars in the night sky. Affected individuals have normal daytime vision and typically do not have other vision problems related to this disorder.The night blindness associated with this condition is congenital, which means it is present from birth. This vision impairment tends to remain stable (stationary); it does not worsen over time. ad Autosomal dominant RHO https://medlineplus.gov/genetics/gene/rho GNAT1 https://medlineplus.gov/genetics/gene/gnat1 PDE6B https://medlineplus.gov/genetics/gene/pde6b AdCSNB CSNBAD Night blindness, congenital stationary, autosomal dominant GTR C0339535 ICD-10-CM H53.63 MeSH D009755 OMIM 163500 OMIM 610444 OMIM 610445 SNOMED CT 232061009 2013-11 2020-08-18 Autosomal dominant epilepsy with auditory features https://medlineplus.gov/genetics/condition/autosomal-dominant-epilepsy-with-auditory-features descriptionAutosomal dominant epilepsy with auditory features (ADEAF) is an uncommon form of epilepsy that runs in families. People with this condition typically hear sounds (auditory features), such as buzzing, humming, or ringing, during seizures. Some people hear more complex sounds, like specific voices or music, or changes in the volume of sounds. Some people with ADEAF suddenly become unable to understand language before losing consciousness during a seizure. This inability to understand speech is known as receptive aphasia. Less commonly, seizures may cause visual hallucinations, a disturbance in the sense of smell, a feeling of dizziness or spinning (vertigo), or other symptoms that affect the senses.ADEAF is called a focal epilepsy because the seizures start in one part of the brain, rather than involving the entire brain from the beginning. Most people with ADEAF have focal aware seizures, which do not cause a loss of consciousness. These seizures are thought to begin in a part of the brain called the lateral temporal lobe. In some people, seizure activity may spread from the lateral temporal lobe to affect other regions of the brain. If seizure activity spreads to the entire brain, it causes a loss of consciousness, muscle stiffening, and rhythmic jerking. Episodes that begin as focal seizures and spread throughout the brain are known as secondarily generalized seizures.Seizures associated with ADEAF usually begin in adolescence or young adulthood. They may be triggered by specific sounds, such as a ringing telephone or speech, but in most cases the seizures do not have any recognized triggers. In most affected people, seizures are infrequent and effectively controlled with medication. ad Autosomal dominant LGI1 https://medlineplus.gov/genetics/gene/lgi1 RELN https://medlineplus.gov/genetics/gene/reln DEPDC5 https://medlineplus.gov/genetics/gene/depdc5 MICAL1 https://www.ncbi.nlm.nih.gov/gene/64780 ADEAF ADLTE ADPEAF Autosomal dominant lateral temporal lobe epilepsy Autosomal dominant partial epilepsy with auditory features Epilepsy, partial, with auditory features ETL1 GTR C1838062 ICD-10-CM MeSH D004828 OMIM 600512 SNOMED CT 72103000 2023-11 2025-08-01 Autosomal dominant hyper-IgE syndrome https://medlineplus.gov/genetics/condition/autosomal-dominant-hyper-ige-syndrome descriptionAutosomal dominant hyper-IgE syndrome (AD-HIES), formerly known as Job syndrome, is a condition that affects several body systems, particularly the immune system. Recurrent infections are common in people with this condition. Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, excessive inflammation can damage body tissues. Recurring pneumonia often results in the formation of air-filled cysts (pneumatoceles) in the lungs. Frequent skin infections and an inflammatory skin disorder called eczema are also very common in AD-HIES. These skin problems cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling.For unknown reasons, people with AD-HIES have abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood. IgE normally triggers an immune response against foreign invaders in the body, particularly parasitic worms, and is involved in allergies. However, IgE is not needed for these roles in people with AD-HIES, and it is unclear why affected individuals have such high levels of the protein without having allergies.AD-HIES also affects other parts of the body, including the bones and teeth. Many people with AD-HIES have skeletal abnormalities such as an unusually large range of joint movement (hyperextensibility), an abnormal curvature of the spine (scoliosis), reduced bone density (osteopenia), and a tendency for bones to fracture easily. A common dental abnormality in this condition is that the primary (baby) teeth do not fall out at the usual time during childhood but are retained as the adult teeth grow in. Other signs and symptoms of AD-HIES can include abnormalities of the arteries that supply blood to the heart muscle (coronary arteries), distinctive facial features, and structural abnormalities of the brain, which do not affect a person's intelligence. ar Autosomal recessive ad Autosomal dominant STAT3 https://medlineplus.gov/genetics/gene/stat3 ZNF341 https://medlineplus.gov/genetics/gene/znf341 AD-HIES Autosomal dominant HIES Autosomal dominant hyper-IgE recurrent infection syndrome Autosomal dominant hyperimmunoglobulin E recurrent infection syndrome Autosomal dominant Job syndrome Buckley syndrome Job syndrome Job's syndrome Job-Buckley syndrome STAT3 deficiency STAT3-deficient hyper IgE syndrome GTR C2936739 ICD-10-CM D82.4 MeSH D007589 OMIM 147060 SNOMED CT 50926003 2019-08 2024-12-05 Autosomal dominant hypocalcemia https://medlineplus.gov/genetics/condition/autosomal-dominant-hypocalcemia descriptionAutosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals can have an imbalance of other molecules in the blood as well, including too much phosphate (hyperphosphatemia) or too little magnesium (hypomagnesemia). Some people with autosomal dominant hypocalcemia also have low levels of a hormone called parathyroid hormone (hypoparathyroidism). This hormone is involved in the regulation of calcium levels in the blood. Abnormal levels of calcium and other molecules in the body can lead to a variety of signs and symptoms, although about half of affected individuals have no associated health problems.The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, prickling or tingling sensations (paresthesias), or twitching of the nerves and muscles (neuromuscular irritability) in various parts of the body. More severely affected individuals develop seizures, usually in infancy or childhood. Sometimes, these symptoms occur only during episodes of illness or fever.Some people with autosomal dominant hypocalcemia have high levels of calcium in their urine (hypercalciuria), which can lead to deposits of calcium in the kidneys (nephrocalcinosis) or the formation of kidney stones (nephrolithiasis). These conditions can damage the kidneys and impair their function. Sometimes, abnormal deposits of calcium form in the brain, typically in structures called basal ganglia, which help control movement.A small percentage of severely affected individuals have features of a kidney disorder called Bartter syndrome in addition to hypocalcemia. These features can include a shortage of potassium (hypokalemia) and magnesium and a buildup of the hormone aldosterone (hyperaldosteronism) in the blood. The abnormal balance of molecules can raise the pH of the blood, which is known as metabolic alkalosis. The combination of features of these two conditions is sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V.There are two types of autosomal dominant hypocalcemia distinguished by their genetic cause. The signs and symptoms of the two types are generally the same. ad Autosomal dominant CASR https://medlineplus.gov/genetics/gene/casr GNA11 https://medlineplus.gov/genetics/gene/gna11 ADH Autosomal dominant hypoparathyroidism Familial hypercalciuric hypocalcemia Familial hypocalcemia GTR C4048195 MeSH D006996 OMIM 601198 OMIM 615361 SNOMED CT 711152006 2015-02 2023-11-10 Autosomal dominant leukodystrophy with autonomic disease https://medlineplus.gov/genetics/condition/autosomal-dominant-leukodystrophy-with-autonomic-disease descriptionAutosomal dominant leukodystrophy with autonomic disease (ADLD) is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates and protects nerve fibers and promotes the rapid transmission of nerve impulses.People with ADLD develop signs and symptoms of the condition in adulthood, typically in their forties or fifties. The first signs of the condition often involve problems with the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. These problems include difficulty with bowel and bladder function, a sharp drop in blood pressure upon standing (orthostatic hypotension), and erectile dysfunction in men. Rarely, people experience an inability to sweat (anhidrosis), which can lead to a dangerously high body temperature.In ADLD, movement difficulties often develop after the autonomic nervous system problems. Affected individuals can have muscle stiffness (spasticity) or weakness and involuntary rhythmic shaking, called intention tremor because it worsens during movement. People with ADLD often have difficulty coordinating movements (ataxia), including movements that involve judging distance or scale (dysmetria), such as picking up a distant object, and rapidly alternating movements (dysdiadochokinesia), including hand clapping or foot stomping. These movement problems usually first affect the legs, but as the condition worsens, the arms and eventually the face become involved. In some people with ADLD, the symptoms worsen during episodes of fever, infection, or exposure to heat. Due to difficulty walking and an unsteady gait, many affected individuals need a cane, walker, or wheelchair for assistance.Intelligence is usually unaffected; however, people who have had ADLD for a long time may have a decline in intellectual function (dementia). ADLD worsens slowly, and affected individuals usually survive 10 to 20 years after the onset of symptoms. ad Autosomal dominant LMNB1 https://medlineplus.gov/genetics/gene/lmnb1 ADLD Adult-onset autosomal dominant leukodystrophy with autonomic symptoms Autosomal dominant adult-onset demyelinating leukodystrophy LMNB1-related adult-onset autosomal dominant leukodystrophy GTR C1868512 MeSH D020279 OMIM 169500 SNOMED CT 448054001 2016-09 2025-11-20 Autosomal dominant optic atrophy and cataract https://medlineplus.gov/genetics/condition/autosomal-dominant-optic-atrophy-and-cataract descriptionAutosomal dominant optic atrophy and cataract is an eye disorder that is characterized by impaired vision. Most affected individuals have decreased sharpness of vision (visual acuity) from birth, while others begin to experience vision problems in early childhood or later. In affected individuals, both eyes are usually affected equally. However, the severity of the vision loss varies widely, even among affected members of the same family, ranging from nearly normal vision to complete blindness.Several abnormalities contribute to impaired vision in people with autosomal dominant optic atrophy and cataract. In the early stages of the condition, affected individuals experience a progressive loss of certain cells within the retina, which is a specialized light-sensitive tissue that lines the back of the eye. The loss of these cells (known as retinal ganglion cells) is followed by the degeneration (atrophy) of the nerves that relay visual information from the eyes to the brain (optic nerves), which contributes to vision loss. Atrophy of these nerves causes an abnormally pale appearance (pallor) of the optic nerves, which can be seen only during an eye examination. Most people with this disorder also have clouding of the lenses of the eyes (cataracts). This eye abnormality can develop anytime but typically appears in childhood. Other common eye problems in autosomal dominant optic atrophy and cataract include involuntary movements of the eyes (nystagmus), or problems with color vision (color vision deficiency) that make it difficult or impossible to distinguish between shades of blue and green.Some people with autosomal dominant optic atrophy and cataract develop disturbances in the function of other nerves (neuropathy) besides the optic nerves. These disturbances can lead to problems with balance and coordination (cerebellar ataxia), an unsteady style of walking (gait), prickling or tingling sensations (paresthesias) in the arms and legs, progressive muscle stiffness (spasticity), or rhythmic shaking (tremors). In some cases, affected individuals have hearing loss caused by abnormalities of the inner ear (sensorineural deafness). ad Autosomal dominant OPA3 https://medlineplus.gov/genetics/gene/opa3 Autosomal dominant optic atrophy type 3 OPA3 OPA3, autosomal dominant Optic atrophy and cataract, autosomal dominant Optic atrophy type 3 Optic atrophy, cataract, and neurologic disorder GTR C1833809 ICD-10-CM H47.22 MeSH D015418 OMIM 165300 SNOMED CT 719517009 2019-02 2020-08-18 Autosomal dominant sleep-related hypermotor epilepsy https://medlineplus.gov/genetics/condition/autosomal-dominant-sleep-related-hypermotor-epilepsy descriptionSleep-related hypermotor epilepsy (SHE) is a form of epilepsy that is characterized by seizures that typically begin while a person is sleeping. The seizures often appear during childhood or adolescence and involve varying degrees of muscle (motor) activity, which can include large, complex, and repetitive movements (hyperkinetic seizures). Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is a form of SHE that runs in families. The specific features of ADSHE can vary, even among members of the same family.People with ADSHE typically have seizures that start in a specific region of the brain (focal seizures). The seizures often occur in clusters during a phase of sleep called nonrapid eye movement (non-REM) sleep. They typically begin and end abruptly, with each seizure lasting no more than 2 minutes. Some seizures are characterized by minor motor activity that may simply wake a person from sleep, while others are more complex and include repetitive motor activity, such as flinging or throwing motions of the arms and bicycling movements of the legs. Seizures may also include muscle stiffness or abnormal body positions. Some affected individuals may get out of bed and wander around during a seizure, which can be mistaken for sleepwalking. Rapid breathing (hyperventilation); a sense of breathlessness; and vocalizations, such as moaning or crying, can also occur.In some types of epilepsy, a pattern of unusual feelings or sensations (aura) occurs before the seizure. Upon waking from sleep, people with ADSHE may experience an aura that warns them of an oncoming seizure. Auras in people with ADSHE can be associated with a feeling of numbness, shivering, a sense of fear, dizziness (vertigo), and a feeling of falling or being pushed.People with ADSHE typically develop seizures before the age of 20 years. The episodes tend to become milder and less frequent over time. Although many people with ADSHE have seizures that can be effectively managed with medication, approximately 30 percent of affected individuals have seizures that become resistant to medication.Psychiatric disorders, behavioral problems, and intellectual disabilities have been reported in some individuals with ADSHE. It is unclear whether these additional features are directly related to the seizures or to the underlying genetic cause. ad Autosomal dominant+New variant CHRNA2 https://medlineplus.gov/genetics/gene/chrna2 CHRNA4 https://medlineplus.gov/genetics/gene/chrna4 CHRNB2 https://medlineplus.gov/genetics/gene/chrnb2 KCNT1 https://medlineplus.gov/genetics/gene/kcnt1 DEPDC5 https://medlineplus.gov/genetics/gene/depdc5 NPRL2 https://medlineplus.gov/genetics/gene/nprl2 NPRL3 https://medlineplus.gov/genetics/gene/nprl3 CRH https://www.ncbi.nlm.nih.gov/gene/1392 CABP4 https://www.ncbi.nlm.nih.gov/gene/57010 ADNFLE ADSHE Autosomal dominant nocturnal frontal lobe epilepsy Autosomal dominant sleep-related hypermotor (hyperkinetic) epilepsy ENFL Nocturnal frontal lobe epilepsy Sleep-related hypermotor epilepsy GTR C1835905 GTR C1838049 GTR C1854335 GTR C1864125 MeSH D017034 OMIM 600513 OMIM 603204 OMIM 605375 OMIM 610353 SNOMED CT 230445007 SNOMED CT 698021005 2025-08 2026-02-12 Autosomal dominant tubulointerstitial kidney disease-UMOD https://medlineplus.gov/genetics/condition/autosomal-dominant-tubulointerstitial-kidney-disease-umod descriptionAutosomal dominant tubulointerstitial kidney disease-UMOD (ADTKD-UMOD) is part of a group of disorders (collectively called autosomal dominant tubulointerstitial kidney disease or ADTKD) that cause a slow loss of kidney function. In people with ADTKD-UMOD, the signs and symptoms of kidney disease often begin in adolescence or early adulthood. Over time, the kidneys become less able to filter fluids and waste products from the body. People with ADTKD-UMOD eventually develop kidney failure, which requires either dialysis to remove waste from the blood or a kidney transplant. The age at which people with ADTKD-UMOD develop kidney failure can vary, though the average age is approximately 45 years. People with ADTKD-UMOD typically develop high levels of a waste product called uric acid in their blood. Normally, the kidneys transfer uric acid from the blood into urine, which then removes it from the body. People with ADTKD-UMOD are unable to remove uric acid from the blood effectively. In about 50 percent of people with ADTKD-UMOD, uric acid builds up in the joints and causes a form of arthritis called gout, typically in late adolescence or early adulthood. Gout is characterized by a sudden onset of severe joint pain and redness, often starting in the big toe. Untreated episodes of gout typically worsen over time. ad Autosomal dominant UMOD https://medlineplus.gov/genetics/gene/umod ADMCKD2 ADTKD-UMOD ADTKD1 Autosomal dominant medullary cystic kidney disease 2 Autosomal dominant tubulointerstitial kidney disease 1 Autosomal dominant tubulointerstitial kidney disease due to UMOD mutation Familial juvenile gouty nephropathy Familial juvenile hyperuricemic nephropathy 1 FJHN Glomerulocystic kidney disease with hyperuricemia and isosthenuria HNFJ1 MCKD2 Medullary cystic kidney disease type 2 UAKD UMOD kidney disease UMOD-related ADTKD UMOD-related autosomal dominant tubulointerstitial kidney disease Uromodulin-associated kidney disease GTR C4551496 MeSH D007674 OMIM 162000 SNOMED CT 46785007 SNOMED CT 723373006 2024-08 2024-08-02 Autosomal dominant vitreoretinochoroidopathy https://medlineplus.gov/genetics/condition/autosomal-dominant-vitreoretinochoroidopathy descriptionAutosomal dominant vitreoretinochoroidopathy (ADVIRC) is a disorder that affects several parts of the eyes, including the clear gel that fills the eye (the vitreous), the light-sensitive tissue that lines the back of the eye (the retina), and the network of blood vessels within the retina (the choroid). The eye abnormalities in ADVIRC can lead to varying degrees of vision impairment, from mild reduction to complete loss, although some people with the condition have normal vision.The signs and symptoms of ADVIRC vary, even among members of the same family. Many affected individuals have microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved. The area behind the cornea can also be abnormally small, which is described as a shallow anterior chamber. Individuals with ADVIRC can develop increased pressure in the eyes (glaucoma) or clouding of the lens of the eye (cataract). In addition, some people have breakdown (degeneration) of the vitreous or the choroid.A characteristic feature of ADVIRC, visible with a special eye exam, is a circular band of excess coloring (hyperpigmentation) in the retina. This feature can help physicians diagnose the disorder. Affected individuals may also have white spots on the retina. ad Autosomal dominant BEST1 https://medlineplus.gov/genetics/gene/best1 ADVIRC Vitreoretinochoroidopathy dominant Vitreoretinochoroidopathy with microcornea, glaucoma, and cataract Vitreoretinochoroidopathy, autosomal dominant, with nanophthalmos GTR C3888099 MeSH D015785 MeSH D058499 OMIM 193220 SNOMED CT 711162004 2014-11 2021-11-24 Autosomal recessive axonal neuropathy with neuromyotonia https://medlineplus.gov/genetics/condition/autosomal-recessive-axonal-neuropathy-with-neuromyotonia descriptionAutosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.Axonal neuropathy, a characteristic feature of this condition, is caused by damage to a particular part of peripheral nerves called axons, which are the extensions of nerve cells (neurons) that transmit nerve impulses. In people with autosomal recessive axonal neuropathy with neuromyotonia, the damage primarily causes progressive weakness and wasting (atrophy) of muscles in the feet, legs, and hands. Muscle weakness may be especially apparent during exercise (exercise intolerance) and can lead to an unusual walking style (gait), frequent falls, and joint deformities (contractures) in the hands and feet. In some affected individuals, axonal neuropathy also causes decreased sensitivity to touch, heat, or cold, particularly in the lower arms or legs.Another feature of this condition is neuromyotonia (also known as Isaac syndrome). Neuromyotonia results from overactivation (hyperexcitability) of peripheral nerves, which leads to delayed relaxation of muscles after voluntary tensing (contraction), muscle cramps, and involuntary rippling movement of the muscles (myokymia). ar Autosomal recessive HINT1 https://medlineplus.gov/genetics/gene/hint1 ARAN-NM Autosomal recessive Charcot-Marie-Tooth disease type 2 with neuromyotonia Autosomal recessive neuromyotonia and axonal neuropathy Gamstorp-Wohlfart syndrome Myokymia, myotonia, and muscle wasting NMAN GTR C5700127 MeSH D010523 OMIM 137200 SNOMED CT 711406009 2014-08 2023-08-21 Autosomal recessive cerebellar ataxia type 1 https://medlineplus.gov/genetics/condition/autosomal-recessive-cerebellar-ataxia-type-1 descriptionAutosomal recessive cerebellar ataxia type 1 (ARCA1) is a condition characterized by progressive problems with movement due to a loss (atrophy) of nerve cells in the part of the brain that coordinates movement (the cerebellum). Signs and symptoms of the disorder first appear in early to mid-adulthood. People with this condition initially experience impaired speech (dysarthria), problems with coordination and balance (ataxia), or both. They may also have difficulty with movements that involve judging distance or scale (dysmetria). Other features of ARCA1 include abnormal eye movements (nystagmus) and problems following the movements of objects with the eyes. The movement problems are slowly progressive, often resulting in the need for a cane, walker, or wheelchair. ar Autosomal recessive SYNE1 https://medlineplus.gov/genetics/gene/syne1 ARCA1 Autosomal recessive spinocerebellar ataxia 8 Recessive ataxia of Beauce GTR C1853116 MeSH D002524 OMIM 610743 SNOMED CT 230233000 2010-10 2020-08-18 Autosomal recessive congenital methemoglobinemia https://medlineplus.gov/genetics/condition/autosomal-recessive-congenital-methemoglobinemia descriptionAutosomal recessive congenital methemoglobinemia is an inherited condition that mainly affects the function of red blood cells. Specifically, it alters a molecule within these cells called hemoglobin. Hemoglobin carries oxygen to cells and tissues throughout the body. In people with autosomal recessive congenital methemoglobinemia, some of the normal hemoglobin is replaced by an abnormal form called methemoglobin, which is unable to deliver oxygen to the body's tissues. As a result, tissues in the body become oxygen deprived, leading to a bluish appearance of the skin, lips, and nails (cyanosis).There are two forms of autosomal recessive congenital methemoglobinemia: types I and II. People with type I have cyanosis from birth and may experience weakness or shortness of breath related to the shortage of oxygen in their tissues. People with type II have cyanosis as well as severe neurological problems. After a few months of apparently normal development, children with type II develop severe brain dysfunction (encephalopathy), uncontrolled muscle tensing (dystonia), and involuntary limb movements (choreoathetosis); also, the size of their head remains small and does not grow in proportion with their body (microcephaly). People with type II have severe intellectual disability; they can recognize faces and usually babble but speak no words. They can sit unassisted and grip objects but have impaired motor skills that leave them unable to walk. In type II, growth is often slowed. Abnormal facial muscle movements can interfere with swallowing, which can lead to feeding difficulties and further slow growth.People with autosomal recessive congenital methemoglobinemia type I have a normal life expectancy, but people with type II often do not survive past early adulthood. ar Autosomal recessive CYB5R3 https://medlineplus.gov/genetics/gene/cyb5r3 Chronic familial methemoglobin reductase deficiency Congenital methemoglobinemia due to NADH-cytochrome b5 reductase 3 deficiency Congenital NADH-methemoglobin reductase deficiency Cytochrome b5 reductase deficiency Deficiency of cytochrome-b5 reductase Diaphorase deficiency NADH-CYB5R deficiency NADH-cytochrome b5 reductase deficiency GTR C2749559 GTR C2749560 ICD-10-CM D74.0 MeSH D008708 OMIM 250800 SNOMED CT 234395000 2015-05 2023-11-13 Autosomal recessive congenital stationary night blindness https://medlineplus.gov/genetics/condition/autosomal-recessive-congenital-stationary-night-blindness descriptionAutosomal recessive congenital stationary night blindness is a disorder of the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing and distinguishing objects in low light (night blindness). For example, they may not be able to identify road signs at night or see stars in the night sky. They also often have other vision problems, including loss of sharpness (reduced acuity), nearsightedness (myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus).The vision problems associated with this condition are congenital, which means they are present from birth. They tend to remain stable (stationary) over time. ar Autosomal recessive TRPM1 https://medlineplus.gov/genetics/gene/trpm1 GRM6 https://medlineplus.gov/genetics/gene/grm6 SLC24A1 https://www.ncbi.nlm.nih.gov/gene/9187 CABP4 https://www.ncbi.nlm.nih.gov/gene/57010 LRIT3 https://www.ncbi.nlm.nih.gov/gene/345193 GPR179 https://www.ncbi.nlm.nih.gov/gene/440435 Autosomal recessive complete congenital stationary night blindness Autosomal recessive incomplete congenital stationary night blindness GTR C1850362 GTR C2750747 GTR C3151193 GTR C3281215 GTR C3554399 GTR C4041558 ICD-10-CM H53.63 MeSH D009755 OMIM 257270 OMIM 610427 OMIM 613216 OMIM 613830 OMIM 614565 OMIM 615058 SNOMED CT 232061009 2014-01 2020-08-18 Autosomal recessive hypotrichosis https://medlineplus.gov/genetics/condition/autosomal-recessive-hypotrichosis descriptionAutosomal recessive hypotrichosis is a condition that affects hair growth. People with this condition have sparse hair (hypotrichosis) on the scalp beginning in infancy. This hair is usually coarse, dry, and tightly curled (often described as woolly hair). Scalp hair may also be lighter in color than expected and is fragile and easily broken. Affected individuals often cannot grow hair longer than a few inches. The eyebrows, eyelashes, and other body hair may be sparse as well. Over time, the hair problems can remain stable or progress to complete scalp hair loss (alopecia) and a decrease in body hair.Rarely, people with autosomal recessive hypotrichosis have skin problems affecting areas with sparse hair, such as redness (erythema), itchiness (pruritus), or missing patches of skin (erosions) on the scalp. In areas of poor hair growth, they may also develop bumps called hyperkeratotic follicular papules that develop around hair follicles, which are specialized structures in the skin where hair growth occurs. ar Autosomal recessive DSG4 https://medlineplus.gov/genetics/gene/dsg4 LIPH https://medlineplus.gov/genetics/gene/liph LPAR6 https://medlineplus.gov/genetics/gene/lpar6 AH Autosomal recessive localized hypotrichosis Autosomal recessive woolly hair with or without hypotrichosis HTL Hypotrichoses Hypotrichosis LAH Total hypotrichosis, Mari type GTR C1836672 GTR C1842839 GTR C1848435 MeSH D007039 OMIM 278150 OMIM 604379 OMIM 607903 SNOMED CT 56558005 SNOMED CT 723362004 2013-04 2020-08-18 Autosomal recessive primary microcephaly https://medlineplus.gov/genetics/condition/autosomal-recessive-primary-microcephaly descriptionAutosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary") is a condition in which infants are born with a very small head and a small brain. The term "microcephaly" comes from the Greek words for "small head."Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal.MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed.People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems. ar Autosomal recessive ASPM https://medlineplus.gov/genetics/gene/aspm MCPH1 https://www.ncbi.nlm.nih.gov/gene/4180 STIL https://www.ncbi.nlm.nih.gov/gene/6491 CEP152 https://www.ncbi.nlm.nih.gov/gene/22995 CDK5RAP2 https://www.ncbi.nlm.nih.gov/gene/55755 CPAP https://www.ncbi.nlm.nih.gov/gene/55835 KNL1 https://www.ncbi.nlm.nih.gov/gene/57082 WDR62 https://www.ncbi.nlm.nih.gov/gene/284403 MCPH Microcephaly primary hereditary Primary autosomal recessive microcephaly True microcephaly GTR C1837501 GTR C1842109 GTR C1855081 GTR C1858108 GTR C1858516 GTR C1858535 GTR C2675187 ICD-10-CM Q02 MeSH D008831 OMIM 251200 OMIM 604317 OMIM 604321 OMIM 604804 OMIM 608393 OMIM 608716 OMIM 612703 SNOMED CT 715981004 2011-04 2020-08-18 Autosomal recessive spastic ataxia of Charlevoix-Saguenay https://medlineplus.gov/genetics/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay descriptionAutosomal recessive spastic ataxia of Charlevoix-Saguenay, more commonly known as ARSACS, is a condition affecting muscle movement. People with ARSACS typically have abnormal tensing of the muscles (spasticity), problems with balance and coordination (cerebellar ataxia), and reduced sensation and weakness in the arms and legs (peripheral neuropathy).Additional muscle problems that can occur in ARSACS include muscle wasting (amyotrophy), involuntary eye movements (nystagmus), and difficulty swallowing (dysphagia) and speaking (dysarthria). Other features of ARSACS involve high-arched feet (pes cavus), a spine that curves to the side (scoliosis), yellow streaks of fatty tissue in the light-sensitive tissue at the back of the eye (hypermyelination of the retina), urinary tract problems, intellectual disability, hearing loss, and recurrent seizures (epilepsy).An unsteady walking style (gait) is the first symptom of ARSACS. Walking problems usually begin between the ages of 12 months and 18 months, as toddlers are learning to walk. These movement problems worsen over time, with increased spasticity and ataxia of the arms and legs. In some cases spasticity goes away, but this apparent improvement is thought to be due to the wasting away (atrophy) of nerves in the arms and legs. Most affected individuals require wheelchair assistance by the time they are in their thirties or forties.While this condition was named after the area in which it was first seen, the Charlevoix-Saguenay region of Quebec, Canada, ARSACS has been identified in individuals worldwide. ar Autosomal recessive SACS https://medlineplus.gov/genetics/gene/sacs ARSACS Charlevoix-Saguenay spastic ataxia Spastic ataxia of Charlevoix-Saguenay Spastic ataxia, Charlevoix-Saguenay type GTR C1849140 MeSH D001259 OMIM 270550 SNOMED CT 702445005 2008-04 2025-04-03 Axenfeld-Rieger syndrome https://medlineplus.gov/genetics/condition/axenfeld-rieger-syndrome descriptionAxenfeld-Rieger syndrome is primarily an eye disorder, although it can also affect other parts of the body. This condition is characterized by abnormalities of the front part of the eye, an area known as the anterior segment. For example, the colored part of the eye (the iris), may be thin or poorly developed. The iris normally has a single central hole, called the pupil, through which light enters the eye. People with Axenfeld-Rieger syndrome often have a pupil that is off-center (corectopia) or extra holes in the iris that can look like multiple pupils (polycoria). This condition can also cause abnormalities of the cornea, which is the clear front covering of the eye.About half of affected individuals develop glaucoma, a serious condition that increases pressure inside the eye. When glaucoma occurs with Axenfeld-Rieger syndrome, it most often develops in late childhood or adolescence, although it can occur as early as infancy. Glaucoma can cause vision loss or blindness.The signs and symptoms of Axenfeld-Rieger syndrome can also affect other parts of the body. Many affected individuals have distinctive facial features such as widely spaced eyes (hypertelorism); a flattened mid-face with a broad, flat nasal bridge; and a prominent forehead. The condition is also associated with dental abnormalities including unusually small teeth (microdontia) or fewer than normal teeth (oligodontia). Some people with Axenfeld-Rieger syndrome have extra folds of skin around their belly button (redundant periumbilical skin). Other, less common features can include heart defects, the opening of the urethra on the underside of the penis (hypospadias), narrowing of the anus (anal stenosis), and abnormalities of the pituitary gland that can result in slow growth.Researchers have described at least three types of Axenfeld-Rieger syndrome. The types, which are numbered 1 through 3, are distinguished by their genetic cause. ad Autosomal dominant FOXC1 https://medlineplus.gov/genetics/gene/foxc1 PITX2 https://medlineplus.gov/genetics/gene/pitx2 ARS Axenfeld and Rieger anomaly Axenfeld anomaly Axenfeld syndrome AXRA AXRS Rieger anomaly Rieger syndrome GTR C0265341 GTR C1832229 GTR C2678503 GTR C3714873 ICD-10-CM Q13.81 MeSH D005124 OMIM 180500 OMIM 601499 OMIM 602482 SNOMED CT 204152008 SNOMED CT 417604002 2012-06 2020-08-18 BAP1 tumor predisposition syndrome https://medlineplus.gov/genetics/condition/bap1-tumor-predisposition-syndrome descriptionBAP1 tumor predisposition syndrome is an inherited disorder that increases the risk of a variety of cancerous (malignant) and noncancerous (benign) tumors, most commonly certain types of tumors that occur in the skin, eyes, kidneys, and the tissue that lines the chest, abdomen, and the outer surface of the internal organs (the mesothelium). Affected individuals can develop one or more types of tumor, and affected members of the same family can have different types.Some people with BAP1 tumor predisposition syndrome develop growths in the skin known as atypical Spitz tumors. People with this syndrome may have more than one of these tumors, and they can have dozens. Atypical Spitz tumors are generally considered benign, although it is unclear if they can become cancerous. Skin cancers are also associated with BAP1 tumor predisposition syndrome, including cutaneous melanoma and basal cell carcinoma.A type of eye cancer called uveal melanoma is the most common cancerous tumor in BAP1 tumor predisposition syndrome. Although uveal melanoma does not usually cause any symptoms, some people with this type of cancer have blurred vision; small, moving dots (floaters) or flashes of light in their vision; headaches; or a visible dark spot on the eye.People with BAP1 tumor predisposition syndrome are at risk of developing malignant mesothelioma, which is cancer of the mesothelium. When associated with BAP1 tumor predisposition syndrome, malignant mesothelioma most often occurs in the membrane that lines the abdomen and covers the abdominal organs (the peritoneum). It less commonly occurs in the outer covering of the lungs (the pleura).A form of kidney cancer called clear cell renal cell carcinoma is also associated with the condition. Researchers are still determining whether other forms of cancer are linked to BAP1 tumor predisposition syndrome.When they occur in people with BAP1 tumor predisposition syndrome, cancers tend to arise at a younger age and are often more aggressive than cancers in the general population. The cancerous tumors in BAP1 tumor predisposition syndrome tend to spread (metastasize) to other parts of the body. Survival of affected individuals with this syndrome is usually shorter than in other people who have one of these cancers. However, individuals with malignant mesothelioma as part of the BAP1 tumor predisposition syndrome appear to survive longer than those who have the cancer without the syndrome. ad Autosomal dominant BAP1 https://medlineplus.gov/genetics/gene/bap1 BAP1-related tumor predisposition syndrome BAP1-TPDS COMMON syndrome Cutaneous/ocular melanoma, atypical melanocytic proliferations, and other internal neoplasms GTR C3280492 MeSH D009386 OMIM 614327 2017-01 2023-03-27 Baller-Gerold syndrome https://medlineplus.gov/genetics/condition/baller-gerold-syndrome descriptionBaller-Gerold syndrome is a rare condition characterized by the premature fusion of certain skull bones (craniosynostosis) and abnormalities of bones in the arms and hands.People with Baller-Gerold syndrome have prematurely fused skull bones, most often along the coronal suture, the growth line that goes over the head from ear to ear. Other sutures of the skull may be fused as well. These changes result in an abnormally shaped head, a prominent forehead, and bulging eyes with shallow eye sockets (ocular proptosis). Other distinctive facial features can include widely spaced eyes (hypertelorism), a small mouth, and a saddle-shaped or underdeveloped nose.Bone abnormalities in the hands include missing fingers (oligodactyly) and malformed or absent thumbs. Partial or complete absence of bones in the forearm is also common. Together, these hand and arm abnormalities are called radial ray malformations.People with Baller-Gerold syndrome may have a variety of additional signs and symptoms including slow growth beginning in infancy, small stature, and malformed or missing kneecaps (patellae). A skin rash often appears on the arms and legs a few months after birth. This rash spreads over time, causing patchy changes in skin coloring, areas of thinning skin (atrophy), and small clusters of blood vessels just under the skin (telangiectases). These chronic skin problems are collectively known as poikiloderma.The varied signs and symptoms of Baller-Gerold syndrome overlap with features of other disorders, namely Rothmund-Thomson syndrome and RAPADILINO syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Baller-Gerold syndrome, Rothmund-Thomson syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms. ar Autosomal recessive RECQL4 https://medlineplus.gov/genetics/gene/recql4 BGS Craniosynostosis with radial defects Craniosynostosis-radial aplasia syndrome GTR C0265308 MeSH D019465 OMIM 218600 SNOMED CT 77608001 2013-08 2023-03-21 Bannayan-Riley-Ruvalcaba syndrome https://medlineplus.gov/genetics/condition/bannayan-riley-ruvalcaba-syndrome descriptionBannayan-Riley-Ruvalcaba syndrome is a genetic condition characterized by a large head size (macrocephaly), multiple noncancerous tumors and tumor-like growths called hamartomas, and dark freckles on the penis in males. The signs and symptoms of Bannayan-Riley-Ruvalcaba syndrome are present from birth or become apparent in early childhood.At least half of affected infants have macrocephaly, and many also have a high birth weight and a large body size (macrosomia). Growth usually slows during childhood, so affected adults are of normal height and body size. About half of all children with Bannayan-Riley-Ruvalcaba syndrome have intellectual disability or delayed development, particularly the development of speech and of motor skills such as sitting, crawling, and walking. These delays may improve with age.About half of all people with Bannayan-Riley-Ruvalcaba syndrome develop hamartomas in their intestines, known as hamartomatous polyps. Other noncancerous growths often associated with Bannayan-Riley-Ruvalcaba syndrome include fatty tumors called lipomas and angiolipomas that develop under the skin. Some affected individuals also develop hemangiomas, which are red or purplish growths that consist of tangles of abnormal blood vessels. People with Bannayan-Riley-Ruvalcaba syndrome may also have an increased risk of developing certain cancers, although researchers are still working to determine the cancer risks associated with this condition.Other signs and symptoms that have been reported in people with Bannayan-Riley-Ruvalcaba syndrome include weak muscle tone (hypotonia) and other muscle abnormalities, and seizures. Some affected individuals have thyroid problems, such as an enlargement of the thyroid gland, known as multinodular goiter, or a condition called Hashimoto thyroiditis. Skeletal abnormalities have also been described with this condition, including an unusually large range of joint movement (hyperextensibility), abnormal side-to-side curvature of the spine (scoliosis), and a sunken chest (pectus excavatum).The features of Bannayan-Riley-Ruvalcaba syndrome overlap with those of another disorder called Cowden syndrome. People with Cowden syndrome develop hamartomas and other noncancerous growths; they also have an increased risk of developing certain types of cancer. Both conditions can be caused by mutations in the PTEN gene. Some people with Bannayan-Riley-Ruvalcaba syndrome have had relatives diagnosed with Cowden syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions. ad Autosomal dominant PTEN https://medlineplus.gov/genetics/gene/pten Bannayan-Ruvalcaba-Riley syndrome Bannayan-Zonana syndrome BRRS BZS Myhre-Riley-Smith syndrome Riley-Smith syndrome Ruvalcaba-Myhre syndrome Ruvalcaba-Myhre-Smith syndrome GTR C0265326 ICD-10-CM E71.440 MeSH D006223 OMIM 158350 SNOMED CT 234138005 SNOMED CT 3073006 2012-09 2023-03-27 Baraitser-Winter syndrome https://medlineplus.gov/genetics/condition/baraitser-winter-syndrome descriptionBaraitser-Winter syndrome is a condition that affects the development of many parts of the body, particularly the face and the brain.An unusual facial appearance is the most common characteristic of Baraitser-Winter syndrome. Distinctive facial features can include widely spaced eyes (hypertelorism), large eyelid openings, droopy eyelids (ptosis), high-arched eyebrows, a broad nasal bridge and tip of the nose, a long space between the nose and upper lip (philtrum), full cheeks, and a pointed chin.Structural brain abnormalities are also present in most people with Baraitser-Winter syndrome. These abnormalities are related to impaired neuronal migration, a process by which nerve cells (neurons) move to their proper positions in the developing brain. The most frequent brain abnormality associated with Baraitser-Winter syndrome is pachygyria, which is an area of the brain that has an abnormally smooth surface with fewer folds and grooves. Less commonly, affected individuals have lissencephaly, which is similar to pachygyria but involves the entire brain surface. These structural changes can cause mild to severe intellectual disability, developmental delay, and seizures.Other features of Baraitser-Winter syndrome can include short stature, ear abnormalities and hearing loss, heart defects, presence of an extra (duplicated) thumb, and abnormalities of the kidneys and urinary system. Some affected individuals have limited movement of large joints, such as the elbows and knees, which may be present at birth or develop over time. Rarely, people with Baraitser-Winter syndrome have involuntary muscle tensing (dystonia). ad Autosomal dominant ACTG1 https://medlineplus.gov/genetics/gene/actg1 ACTB https://medlineplus.gov/genetics/gene/actb BRWS Cerebro-frontofacial syndrome, type 3 Fryns-Aftimos syndrome Iris coloboma with ptosis, hypertelorism, and mental retardation GTR C1855722 GTR C3281235 MeSH D054221 OMIM 243310 OMIM 614583 SNOMED CT 702410002 2013-04 2024-09-17 Bardet-Biedl syndrome https://medlineplus.gov/genetics/condition/bardet-biedl-syndrome descriptionBardet-Biedl syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.Vision loss is one of the major features of Bardet-Biedl syndrome. Loss of vision occurs as the light-sensing tissue at the back of the eye (the retina) gradually deteriorates. Problems with night vision become apparent by mid-childhood, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. Most people with Bardet-Biedl syndrome also develop blurred central vision (poor visual acuity) and become legally blind by adolescence or early adulthood.Obesity is another characteristic feature of Bardet-Biedl syndrome. Abnormal weight gain typically begins in early childhood and continues to be an issue throughout life. Complications of obesity can include type 2 diabetes, high blood pressure (hypertension), and abnormally high cholesterol levels (hypercholesterolemia).Other major signs and symptoms of Bardet-Biedl syndrome include the presence of extra fingers or toes (polydactyly), intellectual disability or learning problems, and abnormalities of the genitalia. Most affected males produce reduced amounts of sex hormones (hypogonadism), and they are usually unable to father biological children (infertile). Many people with Bardet-Biedl syndrome also have kidney abnormalities, which can be serious or life-threatening.Additional features of Bardet-Biedl syndrome can include impaired speech, delayed development of motor skills such as standing and walking, behavioral problems such as emotional immaturity and inappropriate outbursts, and clumsiness or poor coordination. Distinctive facial features, dental abnormalities, unusually short or fused fingers or toes, and a partial or complete loss of the sense of smell (anosmia) have also been reported in some people with Bardet-Biedl syndrome. Additionally, this condition can affect the heart, liver, and digestive system. ar Autosomal recessive MKKS https://medlineplus.gov/genetics/gene/mkks BBS1 https://medlineplus.gov/genetics/gene/bbs1 BBS10 https://medlineplus.gov/genetics/gene/bbs10 CEP290 https://medlineplus.gov/genetics/gene/cep290 BBS5 https://www.ncbi.nlm.nih.gov/gene/428 BBS2 https://www.ncbi.nlm.nih.gov/gene/583 BBS4 https://www.ncbi.nlm.nih.gov/gene/585 MKS1 https://www.ncbi.nlm.nih.gov/gene/4290 TRIM32 https://www.ncbi.nlm.nih.gov/gene/22954 BBS9 https://www.ncbi.nlm.nih.gov/gene/27241 BBS7 https://www.ncbi.nlm.nih.gov/gene/55212 ARL6 https://www.ncbi.nlm.nih.gov/gene/84100 TTC8 https://www.ncbi.nlm.nih.gov/gene/123016 BBS12 https://www.ncbi.nlm.nih.gov/gene/166379 BBS GTR C0752166 MeSH D020788 OMIM 209900 SNOMED CT 232059000 SNOMED CT 5619004 2010-05 2020-08-18 Bare lymphocyte syndrome type I https://medlineplus.gov/genetics/condition/bare-lymphocyte-syndrome-type-i descriptionBare lymphocyte syndrome type I (BLS I) is an inherited disorder of the immune system (primary immunodeficiency). Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria or viruses. Starting in childhood, most people with BLS I develop recurrent bacterial infections in the lungs and airways (respiratory tract). These recurrent infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems.Many people with BLS I also have open sores (ulcers) on their skin, usually on the face, arms, and legs. These ulcers typically develop in adolescence or young adulthood. Some people with BLS I have no symptoms of the condition.People with BLS I have a shortage of specialized immune proteins called major histocompatibility complex (MHC) class I proteins on cells, including infection-fighting white blood cells (lymphocytes), which is where the condition got its name. ar Autosomal recessive TAP1 https://medlineplus.gov/genetics/gene/tap1 TAP2 https://medlineplus.gov/genetics/gene/tap2 TAPBP https://www.ncbi.nlm.nih.gov/gene/6892 HLA class I deficiency GTR C1858266 ICD-10-CM D81.6 MeSH D007153 OMIM 604571 SNOMED CT 725136003 2017-08 2020-08-18 Bare lymphocyte syndrome type II https://medlineplus.gov/genetics/condition/bare-lymphocyte-syndrome-type-ii descriptionBare lymphocyte syndrome type II (BLS II) is an inherited disorder of the immune system categorized as a form of combined immunodeficiency (CID). People with BLS II lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system.BLS II is typically diagnosed in the first year of life. Most affected infants have persistent infections in the respiratory, gastrointestinal, and urinary tracts. Because of the infections, affected infants have difficulty absorbing nutrients (malabsorption), and they grow more slowly than their peers. Eventually, the persistent infections lead to organ failure. Without treatment, individuals with BLS II usually do not survive past early childhood.In people with BLS II, infection-fighting white blood cells (lymphocytes) are missing specialized proteins on their surface called major histocompatibility complex (MHC) class II proteins, which is where the condition got its name. Because BLS II is the most common and best studied form of a group of related conditions, it is often referred to as simply bare lymphocyte syndrome (BLS). ar Autosomal recessive CIITA https://medlineplus.gov/genetics/gene/ciita RFX5 https://medlineplus.gov/genetics/gene/rfx5 RFXANK https://medlineplus.gov/genetics/gene/rfxank RFXAP https://medlineplus.gov/genetics/gene/rfxap Bare lymphocyte syndrome type 2 BLS type II Major histocompatibility complex class II deficiency MHC class II deficiency SCID due to absence of class II HLA antigens SCID, HLA class 2-negative SCID, HLA class II-negative Severe combined immunodeficiency due to absent class II human leukocyte antigens Severe combined immunodeficiency, HLA class II-negative GTR C1859534 GTR C1859536 ICD-10-CM D81.7 MeSH D007153 OMIM 209920 SNOMED CT 71904008 2017-05 2020-08-18 Bart-Pumphrey syndrome https://medlineplus.gov/genetics/condition/bart-pumphrey-syndrome descriptionBart-Pumphrey syndrome is characterized by nail and skin abnormalities and hearing loss.People with Bart-Pumphrey syndrome typically have a white discoloration of the nails (leukonychia); the nails may also be thick and crumbly. Affected individuals often have wart-like (verrucous) skin growths called knuckle pads on the knuckles of the fingers and toes. They may also have thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). The skin abnormalities generally become noticeable during childhood.The hearing loss associated with Bart-Pumphrey syndrome ranges from moderate to profound and is typically present from birth (congenital).The signs and symptoms of this disorder may vary even within the same family; while almost all affected individuals have hearing loss, they may have different combinations of the other associated features. ad Autosomal dominant GJB2 https://medlineplus.gov/genetics/gene/gjb2 Knuckle pads, deafness, and leukonychia syndrome Knuckle pads, leukonychia, and sensorineural deafness GTR C0266004 MeSH D007645 OMIM 149200 SNOMED CT 1271009 2012-11 2020-08-18 Barth syndrome https://medlineplus.gov/genetics/condition/barth-syndrome descriptionBarth syndrome is a rare condition characterized by an enlarged and weakened heart (dilated cardiomyopathy), weakness in muscles used for movement (skeletal myopathy), recurrent infections due to small numbers of white blood cells (neutropenia), and short stature. Barth syndrome occurs almost exclusively in males.In males with Barth syndrome, dilated cardiomyopathy is often present at birth or develops within the first months of life. Over time, the heart muscle becomes increasingly weakened and is less able to pump blood. Individuals with Barth syndrome may have elastic fibers in place of muscle fibers in some areas of the heart muscle, which contributes to the cardiomyopathy. This condition is called endocardial fibroelastosis; it results in thickening of the muscle and impairs its ability to pump blood. In people with Barth syndrome, the heart problems can lead to heart failure. In rare cases, the cardiomyopathy gets better over time and affected individuals eventually have no symptoms of heart disease.In Barth syndrome, skeletal myopathy, particularly of the muscles closest to the center of the body (proximal muscles), is usually noticeable from birth and causes low muscle tone (hypotonia). The muscle weakness often causes delay of motor skills such as crawling and walking. Additionally, affected individuals tend to experience extreme tiredness (fatigue) during strenuous physical activity.Most males with Barth syndrome have neutropenia. The levels of white blood cells can be consistently low (persistent), can vary from normal to low (intermittent), or can cycle between regular episodes of normal and low (cyclical). Neutropenia makes it more difficult for the body to fight off foreign invaders such as bacteria and viruses, so affected individuals have an increased risk of recurrent infections.Newborns with Barth syndrome are often smaller than normal, and their growth continues to be slow throughout life. Some boys with this condition experience a growth spurt in puberty and are of average height as adults, but many men with Barth syndrome continue to have short stature in adulthood.Males with Barth syndrome often have distinctive facial features including prominent cheeks. Affected individuals typically have normal intelligence but often have difficulty performing tasks involving math or visual-spatial skills such as puzzles.Males with Barth syndrome have increased levels of a substance called 3-methylglutaconic acid in their blood and urine. The amount of the acid does not appear to influence the signs and symptoms of the condition. Barth syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria).Even though most features of Barth syndrome are present at birth or in infancy, affected individuals may not experience health problems until later in life. The age at which individuals with Barth syndrome display symptoms or are diagnosed varies greatly. The severity of signs and symptoms among affected individuals is also highly variable.Males with Barth syndrome have a reduced life expectancy. Many affected children die of heart failure or infection in infancy or early childhood, but those who live into adulthood can survive into their late forties. xr X-linked recessive TAFAZZIN https://medlineplus.gov/genetics/gene/tafazzin 3 methylglutaconic aciduria, type II 3-methylglutaconic aciduria type 2 BTHS Cardioskeletal myopathy with neutropenia and abnormal mitochondria DNAJC19 defect MGA type 2 MGA type II GTR C0574083 ICD-10-CM E78.71 MeSH D056889 OMIM 302060 SNOMED CT 297231002 2014-07 2021-11-24 Bartter syndrome https://medlineplus.gov/genetics/condition/bartter-syndrome descriptionBartter syndrome is a group of very similar kidney disorders that cause an imbalance of potassium, sodium, chloride, and related molecules in the body.In some cases, Bartter syndrome becomes apparent before birth. The disorder can cause polyhydramnios, which is an increased volume of fluid surrounding the fetus (amniotic fluid). Polyhydramnios increases the risk of premature birth.Beginning in infancy, affected individuals often fail to grow and gain weight at the expected rate (failure to thrive). They lose excess amounts of salt (sodium chloride) in their urine, which leads to dehydration, constipation, and increased urine production (polyuria). In addition, large amounts of calcium are lost through the urine (hypercalciuria), which can cause weakening of the bones (osteopenia). Some of the calcium is deposited in the kidneys as they are concentrating urine, leading to hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is also characterized by low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and fatigue. Rarely, affected children develop hearing loss caused by abnormalities in the inner ear (sensorineural deafness).Two major forms of Bartter syndrome are distinguished by their age of onset and severity. One form begins before birth (antenatal) and is often life-threatening. The other form, often called the classical form, begins in early childhood and tends to be less severe. Once the genetic causes of Bartter syndrome were identified, researchers also split the disorder into different types based on the genes involved. Types I, II, and IV have the features of antenatal Bartter syndrome. Because type IV is also associated with hearing loss, it is sometimes called antenatal Bartter syndrome with sensorineural deafness. Type III usually has the features of classical Bartter syndrome. ar Autosomal recessive SLC12A1 https://medlineplus.gov/genetics/gene/slc12a1 BSND https://medlineplus.gov/genetics/gene/bsnd CLCNKA https://medlineplus.gov/genetics/gene/clcnka CLCNKB https://medlineplus.gov/genetics/gene/clcnkb KCNJ1 https://medlineplus.gov/genetics/gene/kcnj1 Aldosteronism with hyperplasia of the adrenal cortex Bartter disease Bartter's syndrome Juxtaglomerular hyperplasia with secondary aldosteronism GTR C0004775 GTR C1846343 GTR C1865270 GTR C4310805 GTR CN239220 ICD-10-CM E26.81 MeSH D001477 OMIM 241200 OMIM 601678 OMIM 602522 OMIM 607364 OMIM 613090 SNOMED CT 69194003 SNOMED CT 707742001 2011-02 2020-08-18 Beare-Stevenson cutis gyrata syndrome https://medlineplus.gov/genetics/condition/beare-stevenson-cutis-gyrata-syndrome descriptionBeare-Stevenson cutis gyrata syndrome is a genetic disorder that typically features skin abnormalities and the premature fusion of certain bones of the skull (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.Many of the characteristic facial features of Beare-Stevenson cutis gyrata syndrome result from the premature fusion of the skull bones. The head is unable to grow normally, which leads to a cloverleaf-shaped skull, wide-set and bulging eyes, ear abnormalities, and an underdeveloped upper jaw. Early fusion of the skull bones also affects the growth of the brain, causing delayed development and intellectual disability.A skin abnormality called cutis gyrata is also characteristic of this disorder. The skin has a furrowed and wrinkled appearance, particularly on the face, near the ears, and on the palms and soles of the feet. Additionally, thick, dark, velvety areas of skin (acanthosis nigricans) are sometimes found on the hands and feet and in the genital region.Additional signs and symptoms of Beare-Stevenson cutis gyrata syndrome can include a blockage of the nasal passages (choanal atresia), a malformation of the airways (tracheal cartilaginous sleeve), overgrowth of the umbilical stump (tissue that normally falls off shortly after birth, leaving the belly button), and abnormalities of the genitalia and anus. The medical complications associated with this condition are often life-threatening in infancy or early childhood. ad Autosomal dominant FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 Cutis gyrata syndrome of Beare and Stevenson Cutis gyrata syndrome of Beare-Stevenson GTR C1852406 MeSH D003398 MeSH D012873 OMIM 123790 SNOMED CT 703528008 2020-06 2020-08-18 Beckwith-Wiedemann syndrome https://medlineplus.gov/genetics/condition/beckwith-wiedemann-syndrome descriptionBeckwith-Wiedemann syndrome is a condition that affects many parts of the body. It is classified as an overgrowth syndrome, which means that affected infants are larger than normal (macrosomia), and some may be taller than their peers during childhood. Growth begins to slow by about age 8, and adults with this condition are not unusually tall. In some children with Beckwith-Wiedemann syndrome, specific body parts may grow abnormally large on one side of the body, leading to an asymmetric or uneven appearance. This unusual growth pattern, which is known as hemihyperplasia, usually becomes less apparent over time.The signs and symptoms of Beckwith-Wiedemann syndrome vary among affected individuals. Some children with this condition are born with an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the belly-button. Other abdominal wall defects, such as a soft out-pouching around the belly-button (an umbilical hernia), are also common. Some infants with Beckwith-Wiedemann syndrome have an abnormally large tongue (macroglossia), which may interfere with breathing, swallowing, and speaking. Other major features of this condition include abnormally large abdominal organs (visceromegaly), creases or pits in the skin near the ears, low blood glucose (hypoglycemia) in infancy, and kidney abnormalities.Children with Beckwith-Wiedemann syndrome are at an increased risk of developing several types of cancerous and noncancerous tumors, particularly a form of kidney cancer called Wilms tumor and a form of liver cancer called hepatoblastoma. Tumors develop in about 10 percent of people with this condition and almost always appear in childhood.Most children and adults with Beckwith-Wiedemann syndrome do not have serious medical problems associated with the condition. Their life expectancy is usually normal. ad Autosomal dominant IGF2 https://medlineplus.gov/genetics/gene/igf2 CDKN1C https://medlineplus.gov/genetics/gene/cdkn1c KCNQ1OT1 https://medlineplus.gov/genetics/gene/kcnq1ot1 H19 https://medlineplus.gov/genetics/gene/h19 11 https://medlineplus.gov/genetics/chromosome/11 BWS Wiedemann-Beckwith syndrome (WBS) GTR C0004903 MeSH D001506 OMIM 130650 SNOMED CT 81780002 2022-02 2023-07-26 Behçet disease https://medlineplus.gov/genetics/condition/behcet-disease descriptionBehçet disease is an inflammatory condition that affects many parts of the body. The health problems associated with Behçet disease result from widespread inflammation of blood vessels (vasculitis). This inflammation most commonly affects small blood vessels in the mouth, genitals, skin, and eyes.Painful mouth sores called aphthous ulcers are usually the first sign of Behçet disease. These sores can occur on the lips, tongue, inside the cheeks, the roof of the mouth, the throat, and the tonsils. The ulcers look like common canker sores, and they typically heal within one to two weeks. About 75 percent of all people with Behçet disease develop similar ulcers on the genitals. These ulcers occur most frequently on the scrotum in men and on the labia in women.Behçet disease can also cause painful bumps and sores on the skin. Most affected individuals develop pus-filled bumps that resemble acne. These bumps can occur anywhere on the body. Some affected people also have red, tender nodules called erythema nodosum. These nodules usually develop on the legs but can also occur on the arms, face, and neck.An inflammation of the eye called uveitis is found in more than half of people with Behçet disease. Eye problems are more common in younger people with the disease and affect men more often than women. Uveitis can result in blurry vision and an extreme sensitivity to light (photophobia). Rarely, inflammation can also cause eye pain and redness. If untreated, the eye problems associated with Behçet disease can lead to blindness.Joint involvement is also common in Behçet disease. Often this affects one joint at a time, with each affected joint becoming swollen and painful and then getting better.Less commonly, Behçet disease can affect the brain and spinal cord (central nervous system), gastrointestinal tract, large blood vessels, heart, lungs, and kidneys. Central nervous system abnormalities can lead to headaches, confusion, personality changes, memory loss, impaired speech, and problems with balance and movement. Involvement of the gastrointestinal tract can lead to a hole in the wall of the intestine (intestinal perforation), which can cause serious infection and may be life-threatening.The signs and symptoms of Behçet disease usually begin in a person's twenties or thirties, although they can appear at any age. Some affected people have relatively mild symptoms that are limited to sores in the mouth and on the genitals. Others have more severe symptoms affecting various parts of the body, including the eyes and the vital organs. The features of Behçet disease typically come and go over a period of months or years. In most affected individuals, the health problems associated with this disorder improve with age. u Pattern unknown HLA-B https://medlineplus.gov/genetics/gene/hla-b Adamantiades-Behcet disease Behcet disease Behcet syndrome Behcet triple symptom complex Behcet's syndrome Malignant aphthosis Old Silk Route disease Triple symptom complex GTR C0004943 ICD-10-CM M35.2 MeSH D001528 OMIM 109650 SNOMED CT 310701003 2010-07 2026-03-04 Benign essential blepharospasm https://medlineplus.gov/genetics/condition/benign-essential-blepharospasm descriptionBenign essential blepharospasm is a condition characterized by abnormal blinking or spasms of the eyelids. This condition is a type of dystonia, which is a group of movement disorders that involve uncontrolled tensing of the muscles (muscle contractions), rhythmic shaking (tremors), and other involuntary movements. Benign essential blepharospasm is different from the common and temporary eyelid twitching that can be caused by fatigue, stress, or caffeine.The signs and symptoms of benign essential blepharospasm usually appear in mid- to late adulthood and gradually worsen. The first signs and symptoms of the condition include an increased frequency of blinking; dry eyes; and eye irritation that is aggravated by wind, air pollution, sunlight, and other irritants. These signs and symptoms may begin in one eye, but they ultimately affect both eyes. As the condition progresses, spasms in the muscles that surround the eyes cause involuntary blinking or squinting. Over time, affected individuals find it increasingly difficult to keep their eyes open, which can severely impair their vision.In some people with benign essential blepharospasm, the symptoms of dystonia spread beyond the eyes to affect other facial muscles. When people with benign essential blepharospasm also experience involuntary muscle spasms that affect the tongue and jaw (oromandibular dystonia), the combination of signs and symptoms is known as Meige syndrome. ad Autosomal dominant TOR1A https://medlineplus.gov/genetics/gene/tor1a DRD5 https://medlineplus.gov/genetics/gene/drd5 Essential blepharospasm Eyelid twitching Primary blepharospasm Spasm of eyelids ICD-10-CM G24.5 MeSH D001764 OMIM 606798 SNOMED CT 59026006 2024-11 2024-11-21 Benign familial neonatal seizures https://medlineplus.gov/genetics/condition/benign-familial-neonatal-seizures descriptionBenign familial neonatal seizures (BFNS) is a condition characterized by recurrent seizures in newborn babies. The seizures begin around day 3 of life and usually go away within 1 to 4 months. The seizures can involve only one side of the brain (focal seizures) or both sides (generalized seizures). This condition is often associated with generalized tonic-clonic seizures (also known as grand mal seizures). This type of seizure involves both sides of the brain and affects the entire body, causing a combination of seizure types: tonic seizures, which are characterized by uncontrolled muscle stiffness and rigidity, and clonic seizures, which are characterized by uncontrolled jerking of the muscles. Seizure episodes in infants with BFNS typically begin with tonic stiffness and pauses in breathing (apnea) followed by clonic jerking. A test called an electroencephalogram (EEG) is used to measure the electrical activity of the brain. Abnormalities on an EEG test, measured during no seizure activity, can indicate a risk for seizures. However, infants with BFNS usually have normal EEG readings. In some affected individuals, the EEG shows a specific abnormality called the theta pointu alternant pattern. By age 2, most affected individuals who had EEG abnormalities have a normal EEG reading.Typically, seizures are the only symptom of BFNS, and most people with this condition develop normally. However, some affected individuals develop intellectual disability that becomes noticeable in early childhood. A small percentage of people with BFNS also have a condition called myokymia, which is an involuntary rippling movement of the muscles. In addition, in about 15 percent of people with BFNS, recurrent seizures (epilepsy) will come back later in life after the seizures associated with BFNS have gone away. The age that epilepsy begins is variable. ad Autosomal dominant KCNQ2 https://medlineplus.gov/genetics/gene/kcnq2 KCNQ3 https://medlineplus.gov/genetics/gene/kcnq3 Benign familial neonatal convulsions Benign familial neonatal epilepsy Benign neonatal convulsions Benign neonatal epilepsy BFNE BFNS GTR C1852581 GTR C3149074 MeSH D020936 OMIM 121200 OMIM 121201 SNOMED CT 230410004 2011-05 2023-08-17 Benign recurrent intrahepatic cholestasis https://medlineplus.gov/genetics/condition/benign-recurrent-intrahepatic-cholestasis descriptionBenign recurrent intrahepatic cholestasis (BRIC) is characterized by episodes of liver dysfunction called cholestasis. During these episodes, the liver cells have a reduced ability to release a digestive fluid called bile. Because the problems with bile release occur within the liver (intrahepatic), the condition is described as intrahepatic cholestasis. Episodes of cholestasis can last from weeks to months, and the time between episodes, during which there are usually no symptoms, can vary from weeks to years.The first episode of cholestasis usually occurs in an affected person's teens or twenties. An attack typically begins with severe itchiness (pruritus), followed by yellowing of the skin and whites of the eyes (jaundice) a few weeks later. Other general signs and symptoms that occur during these episodes include a vague feeling of discomfort (malaise), irritability, nausea, vomiting, and a lack of appetite. A common feature of BRIC is the reduced absorption of fat in the body, which leads to excess fat in the feces (steatorrhea). Because of a lack of fat absorption and loss of appetite, affected individuals often lose weight during episodes of cholestasis.BRIC is divided into two types, BRIC1 and BRIC2, based on the genetic cause of the condition. The signs and symptoms are the same in both types.This condition is called benign because it does not cause lasting damage to the liver. However, episodes of liver dysfunction occasionally develop into a more severe, permanent form of liver disease known as progressive familial intrahepatic cholestasis (PFIC). BRIC and PFIC are sometimes considered to be part of a spectrum of intrahepatic cholestasis disorders of varying severity. ar Autosomal recessive ATP8B1 https://medlineplus.gov/genetics/gene/atp8b1 ABCB11 https://medlineplus.gov/genetics/gene/abcb11 ABCB11-related intrahepatic cholestasis ATP8B1-related intrahepatic cholestasis BRIC Low gamma-GT familial intrahepatic cholestasis Recurrent familial intrahepatic cholestasis GTR C2608083 MeSH D002780 OMIM 243300 OMIM 605479 SNOMED CT 31155007 SNOMED CT 838305005 2012-04 2020-08-18 Bernard-Soulier syndrome https://medlineplus.gov/genetics/condition/bernard-soulier-syndrome descriptionBernard-Soulier syndrome is a bleeding disorder associated with abnormal platelets, which are blood cells involved in blood clotting. In affected individuals, platelets are unusually large and fewer in number than usual (a combination known as macrothrombocytopenia). People with Bernard-Soulier syndrome tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or prolonged bleeding following minor injury or surgery or even without trauma (spontaneous bleeding). Rarely, bleeding under the skin causes tiny red or purple spots on the skin called petechiae. Women with Bernard-Soulier syndrome often have heavy or prolonged menstrual bleeding (menorrhagia). ar Autosomal recessive ad Autosomal dominant GP1BA https://medlineplus.gov/genetics/gene/gp1ba GP1BB https://medlineplus.gov/genetics/gene/gp1bb GP9 https://medlineplus.gov/genetics/gene/gp9 BDPLT1 Bleeding disorder, platelet-type, 1 BSS Deficiency of platelet glycoprotein 1b Giant platelet syndrome Glycoprotein Ib, platelet, deficiency of Hemorrhagioparous thrombocytic dystrophy Macrothrombocytopenia, familial Bernard-Soulier type Platelet glycoprotein Ib deficiency Von Willebrand factor receptor deficiency GTR C0005129 MeSH D001606 OMIM 153670 OMIM 231200 SNOMED CT 54569005 2016-06 2023-11-10 Beta thalassemia https://medlineplus.gov/genetics/condition/beta-thalassemia descriptionBeta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body.In people with beta thalassemia, low levels of hemoglobin reduce oxygen levels in the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots.Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia major (also known as transfusion-dependent thalassemia or Cooley's anemia) and thalassemia intermedia (which is a non-transfusion-dependent thalassemia). Of the two types, thalassemia major is more severe.The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight and grow at the expected rate (failure to thrive) and may develop yellowing of the skin and whites of the eyes (jaundice). Affected individuals may have an enlarged spleen, liver, and heart, and their bones may be misshapen. Puberty is delayed in some adolescents with thalassemia major. Many people with thalassemia major have such severe symptoms that they need frequent blood transfusions to replenish their red blood cell supply. Over time, an influx of iron-containing hemoglobin from chronic blood transfusions can lead to a buildup of iron in the body, resulting in liver, heart, and hormone problems.Thalassemia intermedia is milder than thalassemia major. The signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth, bone abnormalities, and an increased risk of developing abnormal blood clots. ar Autosomal recessive HBB https://medlineplus.gov/genetics/gene/hbb Erythroblastic anemia Mediterranean anemia Thalassemia, beta type GTR C0005283 GTR C1858990 ICD-10-CM D56.1 MeSH D017086 OMIM 603902 OMIM 613985 SNOMED CT 111572002 SNOMED CT 15326009 SNOMED CT 191189009 SNOMED CT 26682008 SNOMED CT 27080008 SNOMED CT 39586009 SNOMED CT 47084006 SNOMED CT 5967006 SNOMED CT 61395005 SNOMED CT 65959000 SNOMED CT 716682000 SNOMED CT 79592006 SNOMED CT 86715000 2022-12 2025-04-03 Beta-ketothiolase deficiency https://medlineplus.gov/genetics/condition/beta-ketothiolase-deficiency descriptionBeta-ketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block (amino acid) called isoleucine. This disorder also impairs the body's ability to process ketones, which are molecules produced during the breakdown of fats.The signs and symptoms of beta-ketothiolase deficiency typically appear between the ages of 6 months and 24 months. Affected children experience episodes of vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and, occasionally, seizures. These episodes, which are called ketoacidotic attacks, sometimes lead to coma. Ketoacidotic attacks are frequently triggered by infections or periods without food (fasting), and increased intake of protein-rich foods can also play a role. ar Autosomal recessive ACAT1 https://medlineplus.gov/genetics/gene/acat1 2-methyl-3-hydroxybutyricacidemia 2-methylacetoacetyl-coenzyme A thiolase deficiency 3-alpha-oxothiolase deficiency 3-ketothiolase deficiency 3-oxothiolase deficiency Alpha-methylacetoacetic aciduria MAT deficiency Methylacetoacetyl-coenzyme A thiolase deficiency Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency - potassium stimulated Mitochondrial acetoacetyl-CoA thiolase deficiency T2 deficiency Β-ketothiolase deficiency GTR C1536500 MeSH D018901 OMIM 203750 SNOMED CT 124258007 SNOMED CT 124265004 SNOMED CT 237953006 2020-06 2021-04-07 Beta-mannosidosis https://medlineplus.gov/genetics/condition/beta-mannosidosis descriptionBeta-mannosidosis is a rare inherited disorder affecting the way certain sugar molecules are processed in the body.Signs and symptoms of beta-mannosidosis vary widely in severity, and the age of onset ranges from infancy to adulthood. Almost all individuals with beta-mannosidosis experience intellectual disability, and some have delayed motor development and seizures. Affected individuals may be prone to depression or have behavioral problems such as hyperactivity, impulsivity or aggression. People with beta-mannosidosis are often extremely introverted.People with beta-mannosidosis may experience an increased risk of respiratory and ear infections, hearing loss, speech impairment, swallowing difficulties, poor muscle tone (hypotonia), and reduced sensation or other nervous system abnormalities in the extremities (peripheral neuropathy). They may also exhibit distinctive facial features and clusters of enlarged blood vessels forming small, dark red spots on the skin (angiokeratomas). ar Autosomal recessive MANBA https://medlineplus.gov/genetics/gene/manba Beta-D-mannosidosis Beta-mannosidase deficiency Lysosomal beta A mannosidosis Lysosomal beta-mannosidase deficiency GTR C4048196 MeSH D044905 OMIM 248510 SNOMED CT 238047006 2023-02 2023-02-01 Beta-propeller protein-associated neurodegeneration https://medlineplus.gov/genetics/condition/beta-propeller-protein-associated-neurodegeneration descriptionBeta-propeller protein-associated neurodegeneration (BPAN) is a disorder that damages the nervous system and is progressive, which means that it gradually gets worse. Affected individuals develop a buildup of iron in the brain that can be seen with medical imaging. For this reason, BPAN is classified as a type of disorder called neurodegeneration with brain iron accumulation (NBIA), although the iron accumulation may not occur until late in the disease.Many people with BPAN have recurrent seizures (epilepsy) beginning in infancy or early childhood. Several different types of seizures can occur in this disorder, even in the same individual. Often the first type to occur are febrile seizures, which are triggered by a high fever. Affected individuals can also experience generalized tonic-clonic seizures (also known as grand mal seizures). This type of seizure affects the entire body, causing muscle rigidity, convulsions, and loss of consciousness. Other seizure types that can occur in this disorder include short lapses in awareness that can have the appearance of staring spells or daydreaming (absence seizures, also called petit mal seizures), sudden episodes of weak muscle tone (atonic seizures), involuntary muscle twitches (myoclonic seizures), or more pronounced movements called epileptic spasms. Some individuals have seizure patterns that resemble those in epileptic syndromes, such as West syndrome or Lennox-Gastaut syndrome.Children with BPAN also have intellectual disability, delayed development including significant problems with vocabulary and producing speech (expressive language), and difficulty coordinating movements (ataxia). Ataxia can affect the ability to walk and perform fine motor skills such as using utensils. Affected individuals can have neurodevelopmental issues that are often compared to features of a disorder called Rett syndrome. These features include repeated hand wringing or clasping (stereotypic hand movements); teeth grinding (bruxism); sleep disturbances; and problems with communication and social interaction characteristic of autism spectrum disorder.In late adolescence or early adulthood, individuals with BPAN may begin to experience a gradual loss of intellectual functioning (cognitive decline) that can lead to a severe loss of thinking and reasoning abilities (dementia). Worsening problems with movement also occur, including dystonia and parkinsonism. Dystonia is a condition characterized by involuntary, sustained muscle contractions. In BPAN, the dystonia often starts in the arms. Parkinsonism can include unusually slow movement (bradykinesia), rigidity, tremors, an inability to hold the body upright and balanced (postural instability), and a shuffling walk that can cause recurrent falls.The lifespan of people with BPAN varies. With proper management of their signs and symptoms, affected individuals can live into middle age. Death may result from complications of dementia or movement problems, such as injuries from falls or swallowing difficulties (dysphagia) that can lead to a bacterial lung infection called aspiration pneumonia. xd X-linked dominant WDR45 https://medlineplus.gov/genetics/gene/wdr45 BPAN NBIA5 Neurodegeneration with brain iron accumulation 5 SENDA Static encephalopathy of childhood with neurodegeneration in adulthood GTR C3550973 MeSH D020271 OMIM 300894 SNOMED CT 732959007 2017-05 2023-08-22 Beta-ureidopropionase deficiency https://medlineplus.gov/genetics/condition/beta-ureidopropionase-deficiency descriptionBeta-ureidopropionase deficiency is a disorder that causes excessive amounts of molecules called N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine to be released in the urine. Neurological problems ranging from mild to severe also occur in some affected individuals.People with beta-ureidopropionase deficiency can have low muscle tone (hypotonia), seizures, speech difficulties, developmental delay, intellectual disability, and autistic behaviors that affect communication and social interaction. Some people with this condition have an abnormally small head size (microcephaly); they may also have brain abnormalities that can be seen with medical imaging. Deterioration of the optic nerve, which carries visual information from the eyes to the brain, can lead to vision loss in this condition.In some people with beta-ureidopropionase deficiency, the disease causes no neurological problems and can only be diagnosed by laboratory testing. ar Autosomal recessive UPB1 https://medlineplus.gov/genetics/gene/upb1 Beta-alanine synthase deficiency Deficiency of beta-ureidopropionase GTR C1291512 MeSH D011686 OMIM 613161 SNOMED CT 124511000 2014-08 2020-08-18 Bietti crystalline dystrophy https://medlineplus.gov/genetics/condition/bietti-crystalline-dystrophy descriptionBietti crystalline dystrophy is a disorder in which numerous small, yellow or white crystal-like deposits of fatty (lipid) compounds accumulate in the light-sensitive tissue that lines the back of the eye (the retina). The deposits damage the retina, resulting in progressive vision loss.People with Bietti crystalline dystrophy typically begin noticing vision problems in their teens or twenties. They experience a loss of sharp vision (reduction in visual acuity) and difficulty seeing in dim light (night blindness). They usually lose areas of vision (visual field loss), most often side (peripheral) vision. Color vision may also be impaired.The vision problems may worsen at different rates in each eye, and the severity and progression of symptoms varies widely among affected individuals, even within the same family. However, most people with this condition become legally blind by their forties or fifties. Most affected individuals retain some degree of vision, usually in the center of the visual field, although it is typically blurry and cannot be corrected by glasses or contact lenses. Vision impairment that cannot be improved with corrective lenses is called low vision. ar Autosomal recessive CYP4V2 https://medlineplus.gov/genetics/gene/cyp4v2 BCD Bietti crystalline corneoretinal dystrophy Bietti crystalline retinopathy Bietti tapetoretinal degeneration with marginal corneal dystrophy GTR C1859486 MeSH D012162 OMIM 210370 SNOMED CT 312927001 2012-11 2020-08-18 Biotin-thiamine-responsive basal ganglia disease https://medlineplus.gov/genetics/condition/biotin-thiamine-responsive-basal-ganglia-disease descriptionBiotin-thiamine-responsive basal ganglia disease is a disorder that affects the nervous system, including a group of structures in the brain called the basal ganglia, which help control movement. As its name suggests, the condition may improve if the vitamins biotin and thiamine are given as treatment. Without early and lifelong vitamin treatment, people with biotin-thiamine-responsive basal ganglia disease experience a variety of neurological problems that gradually get worse. The occurrence of specific neurological problems and their severity vary even among affected individuals within the same family.The signs and symptoms of biotin-thiamine-responsive basal ganglia disease usually begin between the ages of 3 and 10, but the disorder can appear at any age. Many of the neurological problems that can occur in biotin-thiamine-responsive basal ganglia disease affect movement, and can include involuntary tensing of various muscles (dystonia), muscle rigidity, muscle weakness on one or both sides of the body (hemiparesis or quadriparesis), problems coordinating movements (ataxia), and exaggerated reflexes (hyperreflexia). Movement problems can also affect the face, and may include the inability to move facial muscles due to facial nerve paralysis (supranuclear facial palsy), paralysis of the eye muscles (external ophthalmoplegia), difficulty chewing or swallowing (dysphagia), and slurred speech. Affected individuals may also experience confusion, loss of previously learned skills, intellectual disability, and seizures. Severe cases may result in coma and become life-threatening.Typically, the neurological symptoms occur as increasingly severe episodes, which may be triggered by fever, injury, or other stresses on the body. Less commonly, the signs and symptoms persist at the same level or slowly increase in severity over time rather than occurring as episodes that come and go. In these individuals, the neurological problems are usually limited to dystonia, seizure disorders, and delay in the development of mental and motor skills (psychomotor delay). ar Autosomal recessive SLC19A3 https://medlineplus.gov/genetics/gene/slc19a3 BBGD Biotin-responsive basal ganglia disease BTBGD Thiamine metabolism dysfunction syndrome 2 Thiamine transporter-2 deficiency Thiamine-responsive encephalopathy THMD2 GTR C1843807 MeSH D001480 OMIM 607483 SNOMED CT 703522009 2014-01 2020-08-18 Biotinidase deficiency https://medlineplus.gov/genetics/condition/biotinidase-deficiency descriptionBiotinidase deficiency is an inherited disorder in which the body is unable to recycle the vitamin biotin. If this condition is not recognized and treated, its signs and symptoms typically appear within the first few months of life, although it can also become apparent later in childhood.Profound biotinidase deficiency, the more severe form of the condition, can cause seizures, weak muscle tone (hypotonia), breathing problems, hearing and vision loss, problems with movement and balance (ataxia), skin rashes, hair loss (alopecia), and a fungal infection called candidiasis. Affected children also have delayed development. Lifelong treatment can prevent these complications from occurring or improve them if they have already developed.Partial biotinidase deficiency is a milder form of this condition. Without treatment, affected children may experience hypotonia, skin rashes, and hair loss, but these problems may appear only during illness, infection, or other times of stress. ar Autosomal recessive BTD https://medlineplus.gov/genetics/gene/btd BIOT BTD deficiency Carboxylase deficiency, multiple, late-onset Late-onset biotin-responsive multiple carboxylase deficiency Late-onset multiple carboxylase deficiency Multiple carboxylase deficiency, late-onset GTR C0220754 ICD-10-CM D81.810 MeSH D028921 OMIM 253260 SNOMED CT 8808004 2014-12 2021-05-20 Bipolar disorder https://medlineplus.gov/genetics/condition/bipolar-disorder descriptionBipolar disorder is a mental health condition that causes extreme shifts in mood, energy, and behavior. This disorder most often appears in late adolescence or early adulthood, although symptoms can begin at any time of life.People with bipolar disorder experience both dramatic "highs," called manic episodes, and "lows," called depressive episodes. These episodes can last from hours to weeks, and many people have no symptoms between episodes.Manic episodes are characterized by increased energy and activity, irritability, restlessness, an inability to sleep, and reckless behavior. Some people with bipolar disorder experience hypomanic episodes, which are similar to but less extreme than manic episodes.Depressive episodes are marked by low energy and activity, a feeling of hopelessness, and an inability to perform everyday tasks. People with bipolar disorder often have repeated thoughts of death and suicide, and they have a much greater risk of dying by suicide than the general population.Manic and depressive episodes can include psychotic symptoms, such as false perceptions (hallucinations) or strongly held false beliefs (delusions). Mixed episodes, which have features of manic and depressive episodes at the same time, also occur in some affected individuals.Bipolar disorder is classified into several types based on the mood changes that occur. Bipolar I involves manic episodes, which can be accompanied by psychotic symptoms, and hypomanic or depressive episodes. Bipolar II involves hypomanic episodes and depressive episodes. Cyclothymic disorder involves hypomanic episodes and depressive episodes that are typically less severe than those in bipolar I or bipolar II.Bipolar disorder often occurs with other mental health conditions, including anxiety disorders (such as panic attacks), behavioral disorders (such as attention-deficit/hyperactivity disorder), and substance abuse. u Pattern unknown Bipolar affective disorder Bipolar affective psychosis Bipolar spectrum disorder Depression, bipolar Manic depressive illness GTR C1852197 GTR C2700438 ICD-10-CM F31 ICD-10-CM F31.0 ICD-10-CM F31.1 ICD-10-CM F31.10 ICD-10-CM F31.11 ICD-10-CM F31.12 ICD-10-CM F31.13 ICD-10-CM F31.2 ICD-10-CM F31.3 ICD-10-CM F31.30 ICD-10-CM F31.31 ICD-10-CM F31.32 ICD-10-CM F31.4 ICD-10-CM F31.5 ICD-10-CM F31.6 ICD-10-CM F31.60 ICD-10-CM F31.61 ICD-10-CM F31.62 ICD-10-CM F31.63 ICD-10-CM F31.64 ICD-10-CM F31.7 ICD-10-CM F31.70 ICD-10-CM F31.71 ICD-10-CM F31.72 ICD-10-CM F31.73 ICD-10-CM F31.74 ICD-10-CM F31.75 ICD-10-CM F31.76 ICD-10-CM F31.77 ICD-10-CM F31.78 ICD-10-CM F31.8 ICD-10-CM F31.81 ICD-10-CM F31.89 ICD-10-CM F31.9 MeSH D001714 OMIM 125480 OMIM 309200 OMIM 609633 OMIM 611247 OMIM 611535 OMIM 611536 OMIM 612357 OMIM 612371 OMIM 612372 SNOMED CT 13746004 2016-10 2024-09-17 Birt-Hogg-Dubé syndrome https://medlineplus.gov/genetics/condition/birt-hogg-dube-syndrome descriptionBirt-Hogg-Dubé syndrome is a rare disorder that affects the skin and lungs and increases the risk of certain types of tumors. Its signs and symptoms vary among affected individuals.Birt-Hogg-Dubé syndrome is characterized by multiple noncancerous (benign) skin tumors, particularly on the face, neck, and upper chest. These growths typically first appear in a person's twenties or thirties and become larger and more numerous over time. Affected individuals also have an increased chance of developing cysts in the lungs and an abnormal accumulation of air in the chest cavity (pneumothorax) that may result in the collapse of a lung. Additionally, Birt-Hogg-Dubé syndrome is associated with an elevated risk of developing cancerous or noncancerous kidney tumors. Other types of cancer have also been reported in affected individuals, but it is unclear whether these tumors are actually a feature of Birt-Hogg-Dubé syndrome. ad Autosomal dominant FLCN https://medlineplus.gov/genetics/gene/flcn BHD Fibrofolliculomas with trichodiscomas and acrochordons Hornstein-Birt-Hogg-Dubé syndrome Hornstein-Knickenberg syndrome GTR C0346010 MeSH D058249 OMIM 135150 SNOMED CT 110985001 2006-03 2020-08-18 Björnstad syndrome https://medlineplus.gov/genetics/condition/bjornstad-syndrome descriptionBjörnstad syndrome is a rare disorder characterized by abnormal hair and hearing problems. Affected individuals have a condition known as pili torti, which means "twisted hair," so named because the strands appear twisted when viewed under a microscope. The hair is brittle and breaks easily, leading to short hair that grows slowly. In Björnstad syndrome, pili torti usually affects only the hair on the head; eyebrows, eyelashes, and hair on other parts of the body are normal. The proportion of hairs affected and the severity of brittleness and breakage can vary. This hair abnormality commonly begins before the age of 2. It may become milder with age, particularly after puberty.People with Björnstad syndrome also have hearing problems that become evident in early childhood. The hearing loss, which is caused by changes in the inner ear (sensorineural deafness), can range from mild to severe. Mildly affected individuals may be unable to hear sounds at certain frequencies, while severely affected individuals may not be able to hear at all. ar Autosomal recessive BCS1L https://medlineplus.gov/genetics/gene/bcs1l Bjornstad syndrome BJS Deafness and pili torti, Bjornstad type Pili torti and nerve deafness Pili torti-deafness syndrome Pili torti-sensorineural hearing loss PTD GTR C0266006 MeSH D028361 OMIM 262000 SNOMED CT 67817003 2014-03 2020-08-18 Bladder cancer https://medlineplus.gov/genetics/condition/bladder-cancer descriptionBladder cancer is a disease in which certain cells in the bladder become abnormal and multiply uncontrollably to form a tumor. The bladder is a muscular organ in the lower abdomen that stores urine until it can be removed (excreted) from the body.Bladder cancer may cause blood in the urine, pain during urination, frequent urination, the feeling of needing to urinate without being able to, or lower back pain. Many of these signs and symptoms are nonspecific, which means they may occur in multiple disorders. People who have one or more of these nonspecific health problems often do not have bladder cancer, but have another condition such as an infection.Bladder cancer develops when tumors form in the tissue that lines the bladder. There are several types of bladder cancer, categorized by the type of cell in the tissue that becomes cancerous. The most common type is transitional cell carcinoma (also known as urothelial carcinoma); others include squamous cell carcinoma and adenocarcinoma. If the tumor spreads  (metastasizes) beyond the lining of the bladder into nearby tissues or organs, it is known as invasive bladder cancer.  n Not inherited ad Autosomal dominant FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 HRAS https://medlineplus.gov/genetics/gene/hras RB1 https://medlineplus.gov/genetics/gene/rb1 TP53 https://medlineplus.gov/genetics/gene/tp53 PTEN https://medlineplus.gov/genetics/gene/pten ATM https://medlineplus.gov/genetics/gene/atm CREBBP https://medlineplus.gov/genetics/gene/crebbp EP300 https://medlineplus.gov/genetics/gene/ep300 RAF1 https://medlineplus.gov/genetics/gene/raf1 KMT2D https://medlineplus.gov/genetics/gene/kmt2d ARID1A https://medlineplus.gov/genetics/gene/arid1a KDM6A https://medlineplus.gov/genetics/gene/kdm6a PIK3CA https://medlineplus.gov/genetics/gene/pik3ca CDKN2A https://medlineplus.gov/genetics/gene/cdkn2a RHOB https://www.ncbi.nlm.nih.gov/gene/388 CCNE1 https://www.ncbi.nlm.nih.gov/gene/898 CDKN1A https://www.ncbi.nlm.nih.gov/gene/1026 ELF3 https://www.ncbi.nlm.nih.gov/gene/1999 ERBB2 https://www.ncbi.nlm.nih.gov/gene/2064 FAT1 https://www.ncbi.nlm.nih.gov/gene/2195 MDM2 https://www.ncbi.nlm.nih.gov/gene/4193 KMT2A https://www.ncbi.nlm.nih.gov/gene/4297 RAC1 https://www.ncbi.nlm.nih.gov/gene/5879 SPTAN1 https://www.ncbi.nlm.nih.gov/gene/6709 KMT2B https://www.ncbi.nlm.nih.gov/gene/9757 STAG2 https://www.ncbi.nlm.nih.gov/gene/10735 KMT2C https://www.ncbi.nlm.nih.gov/gene/58508 9 https://medlineplus.gov/genetics/chromosome/9 Bladder carcinoma urinary Bladder tumor Cancer of the urinary bladder Cancer, bladder Cancer, urinary bladder Malignant bladder neoplasm Malignant bladder tumor Neoplasm of the bladder Neoplasm of the urinary bladder Tumor of the urinary bladder Urinary bladder carcinoma Urinary bladder neoplasm GTR C0699885 ICD-10-CM C67 ICD-10-CM C67.0 ICD-10-CM C67.1 ICD-10-CM C67.2 ICD-10-CM C67.3 ICD-10-CM C67.4 ICD-10-CM C67.5 ICD-10-CM C67.6 ICD-10-CM C67.7 ICD-10-CM C67.8 ICD-10-CM C67.9 ICD-10-CM D09.0 MeSH D001749 OMIM 109800 SNOMED CT 126885006 SNOMED CT 255108000 SNOMED CT 399326009 2020-02 2024-09-17 Blau syndrome https://medlineplus.gov/genetics/condition/blau-syndrome descriptionBlau syndrome is an inflammatory disorder that primarily affects the skin, joints, and eyes. Signs and symptoms begin in childhood, usually before age 4.A form of skin inflammation called granulomatous dermatitis is typically the earliest sign of Blau syndrome. This skin condition causes a persistent rash that can be scaly or involve hard lumps (nodules) that can be felt under the skin. The rash is usually found on the torso, arms, and legs.Arthritis is another common feature of Blau syndrome. In affected individuals, arthritis is characterized by inflammation of the lining of the joints (the synovium). This inflammation, known as synovitis, is associated with swelling and joint pain. Synovitis usually begins in the joints of the hands, feet, wrists, and ankles. As the condition worsens, it can involve additional joints and restrict movement by decreasing the range of motion in many joints. In people with Blau syndrome, the tendons as well as the joints can be inflamed, causing tenosynovitis.Most people with Blau syndrome also develop uveitis, which is swelling and inflammation of the middle layer of the eye (the uvea). The uvea includes the colored portion of the eye (the iris) and related tissues that underlie the white part of the eye (the sclera). Uveitis can cause eye irritation and pain, increased sensitivity to bright light (photophobia), and blurred vision. Other structures in the eye can also become inflamed, including the outermost protective layer of the eye (the conjunctiva), the tear glands, the specialized light-sensitive tissue that lines the back of the eye (the retina), and the nerve that carries information from the eye to the brain (the optic nerve). While individuals with Blau syndrome may have normal vision, inflammation of any of these structures can lead to severe vision impairment or blindness.Some individuals with Blau syndrome develop kidney disease (nephritis) due to inflammation. They may also have deposits of calcium in the kidneys (nephrocalcinosis) and often develop chronic kidney failure. Inflammation of blood vessels (vasculitis) can cause scarring and tissue death in the vessels and impedes blood flow to tissues and organs.Less commonly, Blau syndrome can affect other parts of the body, including the liver, spleen, lymph nodes, brain, blood vessels, lungs, and heart. Inflammation involving these organs and tissues can impair their function and cause life-threatening complications. Rarely, affected individuals have disturbances in nerve function (neuropathy), episodes of fever, or high blood pressure in the blood vessels that carry blood from the heart to the lungs (pulmonary hypertension). ad Autosomal dominant NOD2 https://medlineplus.gov/genetics/gene/nod2 Arthrocutaneouveal granulomatosis Early-onset sarcoidosis Familial granulomatosis, Blau type Familial juvenile systemic granulomatosis Granulomatous inflammatory arthritis, dermatitis, and uveitis, familial Pediatric granulomatous arthritis MeSH D012507 OMIM 186580 SNOMED CT 699861000 2012-07 2026-03-04 Blepharocheilodontic syndrome https://medlineplus.gov/genetics/condition/blepharocheilodontic-syndrome descriptionBlepharocheilodontic (BCD) syndrome is a disorder that is present at birth. It mainly affects the eyelids (blepharo-), upper lip (-cheilo-), and teeth (-dontic).People with BCD syndrome have lower eyelids that turn out so that the inner surface is exposed (ectropion). The outside of the lower lid may sag away from the eye (euryblepharon), and the eyelids may not be able to close completely (lagophthalmia). There can be extra eyelashes (distichiasis) on the upper eyelids, ranging from a few extra eyelashes to a full extra set. These eyelashes do not grow along the edge of the eyelid with the normal lashes, but out of its inner lining. When the abnormal eyelashes touch the eyeball, they can cause damage to the clear covering of the eye (cornea). Affected individuals may also have widely spaced eyes (hypertelorism), a flat face, and a high forehead.Other features of BCD syndrome usually include openings on both sides of the upper lip (bilateral cleft lip) and an opening in the roof of the mouth (cleft palate). Affected individuals may have fewer teeth than normal (oligodontia) and their teeth are often smaller than usual and cone-shaped. The dental abnormalities affect both primary teeth (sometimes called "baby teeth") and secondary (permanent) teeth. Other frequent features include sparse, fine hair and abnormal nails.Occasionally people with BCD syndrome have additional features, including an obstruction of the anal opening (imperforate anus); malformation or absence of the butterfly-shaped gland in the lower neck called the thyroid, resulting in lack of thyroid gland function; or fused fingers or toes (syndactyly). Very rarely, affected individuals have incompletely formed arms or legs (limb reduction defects) or a spinal cord abnormality known as spina bifida. ad Autosomal dominant CDH1 https://medlineplus.gov/genetics/gene/cdh1 CTNND1 https://medlineplus.gov/genetics/gene/ctnnd1 BCD syndrome BCDS Blepharo-cheilo-dontic syndrome Blepharo-cheilo-odontic syndrome Clefting, ectropion, and conical teeth Ectropion, inferior, with cleft lip and/or palate Elschnig syndrome Lagophthalmia with bilateral cleft lip and palate GTR C4540127 GTR C4551988 MeSH D000015 OMIM 119580 OMIM 617681 SNOMED CT 717911008 2017-07 2020-08-18 Blepharophimosis, ptosis, and epicanthus inversus syndrome https://medlineplus.gov/genetics/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome descriptionBlepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a condition that mainly affects development of the eyelids. People with this condition have a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and an upward fold of the skin of the lower eyelid near the inner corner of the eye (epicanthus inversus). In addition, there is an increased distance between the inner corners of the eyes (telecanthus). Because of these eyelid abnormalities, the eyelids cannot open fully, and vision may be limited.Other structures in the eyes and face may be mildly affected by BPES. Affected individuals are at an increased risk of developing vision problems such as nearsightedness (myopia) or farsightedness (hyperopia) beginning in childhood. They may also have eyes that do not point in the same direction (strabismus) or "lazy eye" (amblyopia) affecting one or both eyes. People with BPES may also have distinctive facial features including a broad nasal bridge, low-set ears, or a shortened distance between the nose and upper lip (a short philtrum).There are two types of BPES, which are distinguished by their signs and symptoms. Both types I and II include the eyelid malformations and other facial features. Type I is also associated with an early loss of ovarian function (primary ovarian insufficiency) in women, which causes their menstrual periods to become less frequent and eventually stop before age 40. Primary ovarian insufficiency can lead to difficulty conceiving a child (subfertility) or a complete inability to conceive (infertility). ad Autosomal dominant FOXL2 https://medlineplus.gov/genetics/gene/foxl2 Blepharophimosis syndrome Blepharophimosis, ptosis, and epicanthus inversus BPES GTR C0220663 MeSH D005141 OMIM 110100 SNOMED CT 79833006 2013-10 2024-04-17 Bloom syndrome https://medlineplus.gov/genetics/condition/bloom-syndrome descriptionBloom syndrome is an inherited disorder characterized by short stature, a skin rash that develops after exposure to the sun, and a greatly increased risk of cancer.People with Bloom syndrome are usually smaller than 97 percent of the population in both height and weight from birth, and they rarely exceed 5 feet tall in adulthood.Affected individuals have skin that is sensitive to sun exposure, and they usually develop a butterfly-shaped patch of reddened skin across the nose and cheeks. A skin rash can also appear on other areas that are typically exposed to the sun, such as the back of the hands and the forearms. Small clusters of enlarged blood vessels (telangiectases) often appear in the rash; telangiectases can also occur in the eyes. Other skin features include patches of skin that are lighter or darker than the surrounding areas (hypopigmentation or hyperpigmentation respectively). These patches appear on areas of the skin that are not exposed to the sun, and their development is not related to the rashes.People with Bloom syndrome have an increased risk of cancer. They can develop any type of cancer, but the cancers arise earlier in life than they do in the general population, and affected individuals often develop more than one type of cancer.Individuals with Bloom syndrome have a high-pitched voice and distinctive facial features including a long, narrow face; a small lower jaw; and prominent nose and ears. Other features can include learning disabilities, an increased risk of diabetes, chronic obstructive pulmonary disease (COPD), and mild immune system abnormalities leading to recurrent infections of the upper respiratory tract, ears, and lungs during infancy. Men with Bloom syndrome usually do not produce sperm and as a result are unable to father children (infertile). Women with the disorder generally have reduced fertility and experience menopause at an earlier age than usual. ar Autosomal recessive BLM https://medlineplus.gov/genetics/gene/blm Bloom's syndrome Bloom-Torre-Machacek syndrome Congenital telangiectatic erythema GTR C0005859 MeSH D001816 OMIM 210900 SNOMED CT 4434006 2010-11 2025-04-03 Bohring-Opitz syndrome https://medlineplus.gov/genetics/condition/bohring-opitz-syndrome descriptionBohring-Opitz syndrome is a rare condition that affects the development of many parts of the body.Most individuals with Bohring-Opitz syndrome have profound to severe intellectual disability, developmental delay, and seizures. Most affected individuals have a normal head shape and size with no brain abnormalities; however, some have abnormal development of the head. Abnormal development can lead to a small head size (microcephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance. Structural brain abnormalities can occur with or without head abnormalities. For example, the fluid-filled spaces near the center of the brain (ventricles) may be usually large (ventriculomegaly) or the tissue that connects the left and right halves of the brain (the corpus callosum) can be abnormally thin.Eye problems that can affect vision also occur in people with Bohring-Opitz syndrome. People with this disorder may have protruding eyes (exophthalmos), eyes that do not point in the same direction (strabismus), widely spaced eyes (hypertelorism), or outside corners of the eyes that point upward (upslanting palpebral fissures). Affected individuals may have severe nearsightedness (high myopia) or abnormalities in the light-sensitive tissue at the back of the eye (the retina) or the nerves that carry information from the eyes to the brain (optic nerves).Additional facial differences associated with Bohring-Opitz syndrome can include a flat nasal bridge, nostrils that open to the front rather than downward (anteverted nares), a high arch or opening in the roof of the mouth (high arched or cleft palate), a split in the upper lip (cleft lip), a small lower jaw (micrognathia), low-set ears that are rotated backward, a red birthmark (nevus simplex) on the face (usually the forehead), a low frontal hairline often with eyebrows that grow together in the middle (synophrys), and excessive body and facial hair (hirsutism) that increases with age.Some individuals with Bohring-Opitz syndrome have poor growth before birth (intrauterine growth retardation). During infancy, they grow and gain weight slowly and often have severe feeding difficulties with recurrent vomiting.People with this condition often have characteristic body positioning, known as Bohring-Opitz syndrome posture. This posture consists of slouching shoulders, bent elbows and wrists, hands positioned with the wrists or all of the fingers angled outward toward the fifth finger (ulnar deviation), with the legs usually extended straight. Affected individuals usually stop exhibiting the Bohring-Opitz syndrome posture as they get older. Other abnormalities include joint deformities (called contractures) that are apparent at birth in the knees, hips, or other joints and abnormal muscle tone. Affected individuals can have recurrent infections and heart, kidney, or genital abnormalities. In rare cases, a childhood form of kidney cancer known as Wilms tumor can develop.Some individuals with Bohring-Opitz syndrome do not survive past early childhood, while others live into adolescence or early adulthood. The most common causes of death are heart problems, abnormalities of the throat and airways that cause pauses in breathing (obstructive apnea), and lung infections. ad Autosomal dominant ASXL1 https://medlineplus.gov/genetics/gene/asxl1 Bohring syndrome BOPS BOS C-like syndrome Oberklaid-Danks syndrome Opitz trigonocephaly-like syndrome GTR C0796232 MeSH D003398 MeSH D008607 OMIM 605039 SNOMED CT 720565000 2018-07 2020-08-18 Boomerang dysplasia https://medlineplus.gov/genetics/condition/boomerang-dysplasia descriptionBoomerang dysplasia is a disorder that affects the development of bones throughout the body. Affected individuals are born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. Bones in the spine, rib cage, pelvis, and limbs may be underdeveloped or in some cases absent. As a result of the limb bone abnormalities, individuals with this condition have very short arms and legs. Pronounced bowing of the upper leg bones (femurs) gives them a "boomerang" shape.Some individuals with boomerang dysplasia have a sac-like protrusion of the brain (encephalocele). They may also have an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. Affected individuals typically have a distinctive nose that is broad with very small nostrils and an underdeveloped partition between the nostrils (septum).Individuals with boomerang dysplasia typically have an underdeveloped rib cage that affects the development and functioning of the lungs. As a result, affected individuals are usually stillborn or die shortly after birth from respiratory failure. ad Autosomal dominant FLNB https://medlineplus.gov/genetics/gene/flnb Piepkorn dysplasia GTR C0432201 MeSH D010009 OMIM 112310 SNOMED CT 254054000 2011-09 2020-08-18 Bosma arhinia microphthalmia syndrome https://medlineplus.gov/genetics/condition/bosma-arhinia-microphthalmia-syndrome descriptionBosma arhinia microphthalmia syndrome (BAMS) is a rare condition characterized by abnormalities of the nose and eyes and problems with puberty.The key feature of BAMS is arhinia, which is the absence of an external nose. While most people with BAMS are born without a nose, some affected individuals have a severely underdeveloped (hypoplastic) nose. Affected individuals may also be missing the brain structure involved in the sense of smell (olfactory bulb). Because of these abnormalities, people with BAMS have an impaired ability to smell and, consequently, to taste.In most people with BAMS, the eyeballs are abnormally small (microphthalmia) or absent (anophthalmia), which causes severe vision impairment or blindness. Additional eye abnormalities common in BAMS include a gap or hole in one of several structures of the eye (coloboma) and clouding of the lenses of the eyes (cataracts).Additional head and face abnormalities that can occur in people with BAMS include a high arch or opening in the roof of the mouth (high-arched or cleft palate), absence of the sinuses behind the nose (paranasal sinuses), blockage of the nasal passages (choanal atresia), narrowing of the tear ducts (nasolacrimal duct stenosis), or a small upper jaw (hypoplastic maxilla). Many of these abnormalities contribute to difficulty breathing, particularly in affected babies. Some affected individuals have abnormal external ears.Individuals with BAMS also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Without treatment, these hormone problems often result in delayed puberty. Affected males may also have underdeveloped reproductive tissues and undescended testes (cryptorchidism). ad Autosomal dominant SMCHD1 https://medlineplus.gov/genetics/gene/smchd1 Arhinia choanal atresia microphthalmia Arhinia, choanal atresia, and microphthalmia Arhinia, choanal atresia, microphthalmia, and hypogonadotropic hypogonadism BAM syndrome BAMS Bosma syndrome Gifford-Bosma syndrome Hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome Ruprecht Majewski syndrome GTR C1863878 MeSH D000015 OMIM 603457 SNOMED CT 720511000 2017-07 2023-03-21 Boucher-Neuhäuser syndrome https://medlineplus.gov/genetics/condition/boucher-neuhauser-syndrome descriptionBoucher-Neuhäuser syndrome is a rare disorder that affects movement, vision, and sexual development. It is part of a continuous spectrum of neurological conditions, known as PNPLA6-related disorders, that share a genetic cause and have a combination of overlapping features. Boucher-Neuhäuser syndrome is characterized by three specific features: ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy.Ataxia describes difficulty with coordination and balance. In Boucher-Neuhäuser syndrome, it arises from a loss of cells (atrophy) in the part of the brain involved in coordinating movements (the cerebellum). Affected individuals have an unsteady walking style (gait) and frequent falls.Another key feature of Boucher-Neuhäuser syndrome is hypogonadotropic hypogonadism, which is a condition affecting the production of hormones that direct sexual development. Affected individuals have a delay in development of the typical signs of puberty, such as the growth of facial hair and deepening of the voice in males, and the start of monthly periods (menstruation) and breast development in females. Other hormone abnormalities lead to short stature in some affected individuals.The third characteristic feature of Boucher-Neuhäuser syndrome is eye abnormalities, most commonly chorioretinal dystrophy. Chorioretinal dystrophy refers to problems with the light-sensitive tissue that lines the back of the eye (the retina) and a nearby tissue layer called the choroid. These eye abnormalities lead to impaired vision. People with Boucher-Neuhäuser syndrome can also have abnormal eye movements, including involuntary side-to-side movements of the eyes (nystagmus).The key features of Boucher-Neuhäuser syndrome can begin anytime from infancy to adulthood, although at least one feature usually occurs by adolescence. Ataxia is often the initial symptom of the disorder, but vision problems or delayed puberty can be the earliest finding. Vision and movement problems worsen slowly throughout life and can result in blindness or the need for a wheelchair for mobility in the most severely affected individuals.People with Boucher-Neuhäuser syndrome can have additional medical problems, including muscle stiffness (spasticity); impaired speech (dysarthria); and difficulty processing, learning, or remembering information (cognitive impairment). ar Autosomal recessive PNPLA6 https://medlineplus.gov/genetics/gene/pnpla6 Ataxia-hypogonadism-choroidal dystrophy syndrome BNHS BNS Cerebellar ataxia with hypogonadism and choroidal dystrophy syndrome Chorioretinal dystrophy, spinocerebellar ataxia, and hypogonadotropic hypogonadism Spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy GTR C1859093 MeSH D052439 OMIM 215470 SNOMED CT 715984007 2016-10 2020-08-18 Bowen-Conradi syndrome https://medlineplus.gov/genetics/condition/bowen-conradi-syndrome descriptionBowen-Conradi syndrome is a disorder that affects many parts of the body and is usually fatal in infancy. Affected individuals have a low birth weight, experience feeding problems, and grow very slowly. Their head is unusually small overall (microcephaly), but is longer than expected compared with its width (dolichocephaly). Characteristic facial features include a prominent, high-bridged nose and an unusually small jaw (micrognathia) and chin. Affected individuals typically have pinky fingers that are curved toward or away from the ring finger (fifth finger clinodactyly) or permanently flexed (camptodactyly), feet with soles that are rounded outward (rocker-bottom feet), and restricted joint movement.Other features that occur in some affected individuals include seizures; structural abnormalities of the kidneys, heart, brain, or other organs; and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Affected males may have the opening of the urethra on the underside of the penis (hypospadias) or undescended testes (cryptorchidism).Babies with Bowen-Conradi syndrome do not achieve developmental milestones such as smiling or sitting, and they usually do not survive more than 6 months. ar Autosomal recessive EMG1 https://medlineplus.gov/genetics/gene/emg1 Bowen Hutterite syndrome Bowen syndrome, Hutterite type Bowen-Conradi Hutterite syndrome BWCNS Hutterite syndrome GTR C1859405 MeSH D000015 OMIM 211180 SNOMED CT 711153001 2015-02 2020-08-18 Bradyopsia https://medlineplus.gov/genetics/condition/bradyopsia descriptionBradyopsia is a rare condition that affects vision. The term "bradyopsia" is from the Greek words for slow vision. In affected individuals, the eyes adapt more slowly than usual to changing light conditions. For example, people with this condition are blinded for several seconds when going from a dark environment into a bright one, such as when walking out of a darkened movie theater into daylight. Their eyes also have trouble adapting from bright light to dark conditions, such as when driving into a dark tunnel on a sunny day.Some people with bradyopsia also have difficulty seeing some moving objects, particularly small objects moving against a bright background. As a result, they often have trouble watching or participating in sports with a ball, such as soccer or tennis. People with bradyopsia can have reduced sharpness (acuity) of vision, although acuity may depend on the conditions under which vision is tested. Visual acuity may appear to be severely affected if it is tested under bright lights, but it can be near normal if tested in a dim environment. The ability to see colors and distinguish between them is normal.The vision problems associated with bradyopsia become apparent in early childhood. They are usually stable, which means they do not worsen over time. ar Autosomal recessive RGS9 https://medlineplus.gov/genetics/gene/rgs9 RGS9BP https://medlineplus.gov/genetics/gene/rgs9bp PERRS Prolonged electroretinal response suppression GTR C1842073 MeSH D015785 OMIM 608415 SNOMED CT 711163009 2014-11 2020-08-18 Brain-lung-thyroid syndrome https://medlineplus.gov/genetics/condition/brain-lung-thyroid-syndrome descriptionBrain-lung-thyroid syndrome is a group of conditions that affect the brain, lungs, and thyroid gland (a butterfly-shaped gland in the lower neck). Brain-lung-thyroid syndrome historically included problems with all three organs, although the designation now encompasses a combination of brain, lung, and thyroid problems. About 50 percent of affected individuals have problems with all three organs, about 30 percent have brain and thyroid problems, and about 10 percent have brain and lung problems. The brain alone is affected in 10 to 20 percent of people with the condition. Such cases are sometimes called isolated benign hereditary chorea.Nearly everyone with brain-lung-thyroid syndrome has brain-related movement abnormalities. Benign hereditary chorea is the most common feature of the syndrome. This feature is associated with involuntary jerking movements (chorea) of the face, torso, and limbs; writhing movements (athetosis) of the limbs; and other movement problems. Individuals with brain-lung-thyroid syndrome can have other abnormalities, such as difficulty coordinating movements (ataxia), muscle twitches (myoclonus), and involuntary muscle contractions that result in twisting and repetitive movements (dystonia). The movement problems typically begin around age 1, although they can begin in early infancy or later in life, and are often preceded by weak muscle tone (hypotonia). They can delay the development of walking. The movement problems usually remain stable and can improve over time. Some affected individuals also have learning difficulties or intellectual disability.Thyroid problems are the next most common feature of brain-lung-thyroid syndrome. The thyroid gland makes hormones that help regulate a wide variety of critical body functions, including growth, brain development, and the rate of chemical reactions in the body (metabolism). Many affected individuals have reduced thyroid function from birth (congenital hypothyroidism), resulting in lower-than-normal levels of thyroid hormones. Others have a milder condition called compensated or subclinical hypothyroidism, in which thyroid hormone levels are within the normal range, even though the thyroid is not functioning properly. While most people with brain-lung-thyroid syndrome have a normal-sized thyroid, the gland is reduced in size (hypoplastic) or absent (aplastic) in some affected individuals. Although a shortage of thyroid hormones can cause intellectual disability and other neurological problems, it is unclear whether such issues in individuals with brain-lung-thyroid syndrome are due to hypothyroidism or to the brain abnormalities related to the condition.Lung problems are common in brain-lung-thyroid syndrome. Some affected newborns have respiratory distress syndrome, which causes extreme difficulty breathing and can be life-threatening. Other affected individuals develop widespread lung damage (interstitial lung disease) or scarring in the lungs (pulmonary fibrosis), both of which can also lead to breathing problems. Recurrent lung infections, which can be life-threatening, also occur in people with brain-lung-thyroid syndrome. People with brain-lung-thyroid syndrome have a higher risk of developing lung cancer than do people in the general population. ad Autosomal dominant NKX2-1 https://medlineplus.gov/genetics/gene/nkx2-1 BLT syndrome Brain-thyroid-lung syndrome CAHTP Choreoathetosis, hypothyroidism, and neonatal respiratory distress Chreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction GTR C0393584 GTR C1970269 MeSH D002819 MeSH D003409 MeSH D012127 OMIM 610978 SNOMED CT 719098007 2017-01 2023-03-21 Branchio-oculo-facial syndrome https://medlineplus.gov/genetics/condition/branchio-oculo-facial-syndrome descriptionBranchio-oculo-facial syndrome is a condition that affects development before birth, particularly of structures in the face and neck. Its characteristic features include skin anomalies on the neck, malformations of the eyes and ears, and distinctive facial features."Branchio-" refers to the branchial arches, which are structures in the developing embryo that give rise to tissues in the face and neck. In people with branchio-oculo-facial syndrome, the first and second branchial arches do not develop properly, leading to abnormal patches of skin, typically on the neck or near the ears. These patches can be unusually thin, hairy, or red and densely packed with blood vessels (hemangiomatous). In a small number of individuals, tissue from a gland called the thymus is abnormally located on the skin of the neck (dermal thymus). Problems with branchial arch development underlie many of the other features of branchio-oculo-facial syndrome."Oculo-" refers to the eyes. Many people with branchio-oculo-facial syndrome have malformations of the eyes that can lead to vision impairment. These abnormalities include unusually small eyeballs (microphthalmia), no eyeballs (anophthalmia), a gap or split in structures that make up the eyes (coloboma), or blockage of the tear ducts (nasolacrimal duct stenosis).Problems with development of the face lead to distinctive facial features in people with branchio-oculo-facial syndrome. Many affected individuals have a split in the upper lip (cleft lip) or a pointed upper lip that resembles a poorly repaired cleft lip (often called a pseudocleft lip) with or without an opening in the roof of the mouth (cleft palate). Other facial characteristics include widely spaced eyes (hypertelorism), an increased distance between the inner corners of the eyes (telecanthus), outside corners of the eyes that point upward (upslanting palpebral fissures), a broad nose with a flattened tip, and weakness of the muscles in the lower face. The ears are also commonly affected, resulting in malformed or prominent ears. Abnormalities of the inner ear or of the tiny bones in the ears (ossicles) can cause hearing loss in people with this condition.Branchio-oculo-facial syndrome can affect other structures and tissues as well. Some affected individuals have kidney abnormalities, such as malformed kidneys or multiple kidney cysts. Nail and teeth abnormalities also occur, and some people with this condition have prematurely graying hair. ad Autosomal dominant TFAP2A https://medlineplus.gov/genetics/gene/tfap2a BOFS Branchial clefts with characteristic facies, growth retardation, imperforate nasolacrimal duct, and premature aging Hemangiomatous branchial clefts-lip pseudocleft syndrome Lip pseudocleft-hemagiomatous branchial cyst syndrome GTR C0376524 MeSH D019465 OMIM 113620 SNOMED CT 449821007 2012-09 2020-08-18 Branchiootorenal/branchiootic syndrome https://medlineplus.gov/genetics/condition/branchiootorenal-branchiootic-syndrome descriptionBranchiootorenal (BOR) syndrome is a condition that disrupts the development of tissues in the neck and causes malformations of the ears and kidneys. The signs and symptoms of this condition vary widely, even among members of the same family. Branchiootic (BO) syndrome includes many of the same features as BOR syndrome, but affected individuals do not have kidney abnormalities. The two conditions are otherwise so similar that researchers often consider them together (BOR/BO syndrome or branchiootorenal spectrum disorders)."Branchio-" refers to the second branchial arch, which is a structure in the developing embryo that gives rise to tissues in the front and side of the neck. In people with BOR/BO syndrome, abnormal development of the second branchial arch can result in the formation of masses in the neck called branchial cleft cysts. Some affected people have abnormal holes or pits called fistulae in the side of the neck just above the collarbone. Fistulae can form tunnels into the neck, exiting in the mouth near the tonsil. Branchial cleft cysts and fistulae can cause health problems if they become infected, so they are often removed surgically."Oto-" and "-otic" refer to the ear; most people with BOR/BO syndrome have hearing loss and other ear abnormalities. The hearing loss can be sensorineural, meaning it is caused by abnormalities in the inner ear; conductive, meaning it results from changes in the small bones in the middle ear; or mixed, meaning it is caused by a combination of inner ear and middle ear abnormalities. Some affected people have tiny holes in the skin or extra bits of tissue just in front of the ear. These are called preauricular pits and preauricular tags, respectively."Renal" refers to the kidneys; BOR syndrome (but not BO syndrome) causes abnormalities of kidney structure and function. These abnormalities range from mild to severe and can affect one or both kidneys. In some cases, end-stage renal disease (ESRD) develops later in life. This serious condition occurs when the kidneys become unable to filter fluids and waste products from the body effectively. ad Autosomal dominant SIX1 https://medlineplus.gov/genetics/gene/six1 EYA1 https://medlineplus.gov/genetics/gene/eya1 SIX5 https://medlineplus.gov/genetics/gene/six5 BO syndrome BOR BOR syndrome BOS Branchio-oto-renal syndrome Branchio-otorenal dysplasia Branchio-otorenal syndrome Branchiootic syndrome Branchiootorenal dysplasia Branchiootorenal spectrum disorders Branchiootorenal syndrome Melnick-Fraser syndrome GTR C1842124 GTR C1865143 GTR C1970479 GTR C4551702 MeSH D019280 OMIM 113650 OMIM 120502 OMIM 602588 OMIM 608389 OMIM 610896 SNOMED CT 290006 2016-03 2020-08-18 Breast cancer https://medlineplus.gov/genetics/condition/breast-cancer descriptionBreast cancer is a disease in which certain cells in the breast become abnormal and multiply uncontrollably to form a tumor. Although breast cancer is much more common in women, this form of cancer can also develop in men. In both women and men, the most common form of breast cancer begins in cells lining the milk ducts (ductal cancer). In women, cancer can also develop in the glands that produce milk (lobular cancer). Most men have little or no lobular tissue, so lobular cancer in men is very rare. In its early stages, breast cancer usually does not cause pain and may exhibit no noticeable symptoms. As the cancer progresses, signs and symptoms can include a lump or thickening in or near the breast; a change in the size or shape of the breast; nipple discharge, tenderness, or retraction (turning inward); and skin irritation, dimpling, redness, or scaliness. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a person definitely has breast cancer.In some cases, cancerous cells can invade surrounding breast tissue. In these cases, the condition is known as invasive breast cancer. Sometimes, tumors spread to other parts of the body. If breast cancer spreads, cancerous cells most often appear in the bones, liver, lungs, or brain. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.A small percentage of all breast cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary breast cancers tend to develop earlier in life than noninherited (sporadic) cases, and new (primary) tumors are more likely to develop in both breasts. n Not inherited ad Autosomal dominant u Pattern unknown FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 BRCA1 https://medlineplus.gov/genetics/gene/brca1 RAD51 https://medlineplus.gov/genetics/gene/rad51 BRCA2 https://medlineplus.gov/genetics/gene/brca2 TP53 https://medlineplus.gov/genetics/gene/tp53 PTEN https://medlineplus.gov/genetics/gene/pten ATM https://medlineplus.gov/genetics/gene/atm STK11 https://medlineplus.gov/genetics/gene/stk11 NBN https://medlineplus.gov/genetics/gene/nbn CDH1 https://medlineplus.gov/genetics/gene/cdh1 H19 https://medlineplus.gov/genetics/gene/h19 TERT https://medlineplus.gov/genetics/gene/tert CYP19A1 https://medlineplus.gov/genetics/gene/cyp19a1 MAP3K1 https://medlineplus.gov/genetics/gene/map3k1 BARD1 https://www.ncbi.nlm.nih.gov/gene/580 CASP8 https://www.ncbi.nlm.nih.gov/gene/841 CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 LSP1 https://www.ncbi.nlm.nih.gov/gene/4046 MRE11 https://www.ncbi.nlm.nih.gov/gene/4361 RAD51C https://www.ncbi.nlm.nih.gov/gene/5889 XRCC2 https://www.ncbi.nlm.nih.gov/gene/7516 XRCC3 https://www.ncbi.nlm.nih.gov/gene/7517 CHEK2 https://www.ncbi.nlm.nih.gov/gene/11200 TOX3 https://www.ncbi.nlm.nih.gov/gene/27324 PALB2 https://www.ncbi.nlm.nih.gov/gene/79728 BRIP1 https://www.ncbi.nlm.nih.gov/gene/83990 Breast cancer, familial Breast carcinoma Cancer of breast Malignant neoplasm of breast Malignant tumor of breast Mammary cancer GTR C0006142 GTR C1861906 GTR C3469522 ICD-10-CM C50.01 ICD-10-CM C50.011 ICD-10-CM C50.012 ICD-10-CM C50.019 ICD-10-CM C50.02 ICD-10-CM C50.021 ICD-10-CM C50.022 ICD-10-CM C50.029 ICD-10-CM C50.11 ICD-10-CM C50.111 ICD-10-CM C50.112 ICD-10-CM C50.119 ICD-10-CM C50.21 ICD-10-CM C50.211 ICD-10-CM C50.212 ICD-10-CM C50.219 ICD-10-CM C50.22 ICD-10-CM C50.221 ICD-10-CM C50.222 ICD-10-CM C50.229 ICD-10-CM C50.31 ICD-10-CM C50.311 ICD-10-CM C50.312 ICD-10-CM C50.319 ICD-10-CM C50.32 ICD-10-CM C50.321 ICD-10-CM C50.322 ICD-10-CM C50.329 ICD-10-CM C50.41 ICD-10-CM C50.411 ICD-10-CM C50.412 ICD-10-CM C50.419 ICD-10-CM C50.42 ICD-10-CM C50.421 ICD-10-CM C50.422 ICD-10-CM C50.429 ICD-10-CM C50.51 ICD-10-CM C50.511 ICD-10-CM C50.512 ICD-10-CM C50.519 ICD-10-CM C50.52 ICD-10-CM C50.521 ICD-10-CM C50.522 ICD-10-CM C50.529 ICD-10-CM C50.61 ICD-10-CM C50.611 ICD-10-CM C50.612 ICD-10-CM C50.619 ICD-10-CM C50.62 ICD-10-CM C50.621 ICD-10-CM C50.622 ICD-10-CM C50.629 ICD-10-CM C50.81 ICD-10-CM C50.811 ICD-10-CM C50.812 ICD-10-CM C50.819 ICD-10-CM C50.82 ICD-10-CM C50.821 ICD-10-CM C50.822 ICD-10-CM C50.829 ICD-10-CM C50.91 ICD-10-CM C50.911 ICD-10-CM C50.912 ICD-10-CM C50.919 ICD-10-CM C50.92 ICD-10-CM C50.921 ICD-10-CM C50.922 ICD-10-CM C50.929 ICD-10-CM D05.0 ICD-10-CM D05.00 ICD-10-CM D05.01 ICD-10-CM D05.02 ICD-10-CM D05.1 ICD-10-CM D05.10 ICD-10-CM D05.11 ICD-10-CM D05.12 ICD-10-CM D05.9 ICD-10-CM D05.90 ICD-10-CM D05.91 ICD-10-CM D05.92 ICD-10-CM Z15.01 ICD-10-CM Z80.3 MeSH D001943 OMIM 114480 OMIM 604370 OMIM 612555 SNOMED CT 126926005 SNOMED CT 254837009 SNOMED CT 254838004 SNOMED CT 254843006 SNOMED CT 865954003 2015-05 2025-04-03 Brody myopathy https://medlineplus.gov/genetics/condition/brody-myopathy descriptionBrody myopathy is a condition that affects the skeletal muscles, which are the muscles used for movement. Affected individuals experience muscle cramping and stiffening after exercise or other strenuous activity, especially in cold temperatures. These symptoms typically begin in childhood. They are usually painless, but in some cases can cause mild discomfort. The muscles usually relax after a few minutes of rest. Most commonly affected are the muscles of the arms, legs, and face (particularly the eyelids).In some people with Brody myopathy, exercise leads to the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. ad Autosomal dominant ar Autosomal recessive ATP2A1 https://medlineplus.gov/genetics/gene/atp2a1 Brody disease GTR C1832918 MeSH D009135 OMIM 601003 SNOMED CT 703530005 2012-01 2020-08-18 Brugada syndrome https://medlineplus.gov/genetics/condition/brugada-syndrome descriptionBrugada syndrome is a condition that causes a disruption of the heart's normal rhythm. Specifically, this disorder can lead to irregular heartbeats in the heart's lower chambers (ventricles), which is an abnormality called ventricular arrhythmia. If untreated, the irregular heartbeats can cause fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep.Brugada syndrome usually becomes apparent in adulthood, although it can develop any time throughout life. Signs and symptoms related to arrhythmias, including sudden death, can occur from early infancy to late adulthood. Sudden death typically occurs around age 40. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than 1 year. SIDS is characterized by sudden and unexplained death, usually during sleep.Sudden unexplained nocturnal death syndrome (SUNDS) is a condition characterized by unexpected cardiac arrest in young adults, usually at night during sleep. This condition was originally described in Southeast Asian populations, where it is a major cause of death. Researchers have determined that SUNDS and Brugada syndrome are the same disorder. ad Autosomal dominant SCN5A https://medlineplus.gov/genetics/gene/scn5a CACNA1C https://medlineplus.gov/genetics/gene/cacna1c HCN4 https://medlineplus.gov/genetics/gene/hcn4 TRPM4 https://medlineplus.gov/genetics/gene/trpm4 CACNA2D1 https://www.ncbi.nlm.nih.gov/gene/781 CACNB2 https://www.ncbi.nlm.nih.gov/gene/783 KCND3 https://www.ncbi.nlm.nih.gov/gene/3752 KCNJ8 https://www.ncbi.nlm.nih.gov/gene/3764 SCN1B https://www.ncbi.nlm.nih.gov/gene/6324 SCN2B https://www.ncbi.nlm.nih.gov/gene/6327 SLMAP https://www.ncbi.nlm.nih.gov/gene/7871 KCNE3 https://www.ncbi.nlm.nih.gov/gene/10008 GPD1L https://www.ncbi.nlm.nih.gov/gene/23171 KCNE5 https://www.ncbi.nlm.nih.gov/gene/23630 RANGRF https://www.ncbi.nlm.nih.gov/gene/29098 SCN3B https://www.ncbi.nlm.nih.gov/gene/55800 Bangungut Idiopathic ventricular fibrillation, Brugada type Pokkuri death syndrome Sudden unexpected nocturnal death syndrome Sudden unexplained death syndrome SUDS SUNDS GTR C1142166 GTR C4551804 MeSH D053840 OMIM 601144 SNOMED CT 418818005 2015-03 2020-08-18 Bunion https://medlineplus.gov/genetics/condition/bunion descriptionA bunion, known technically as hallux valgus, is a bony bump on the side of the foot at the base of the big toe. Bunions develop slowly as pressure on the joint at the base of the big toe causes the toe to move out of place, leaning inward toward the second toe. Because this joint carries a lot of weight during activities like standing and walking, bunions can cause foot pain, stiffness, redness, and swelling. Calluses may form where the big toe and second toe rub together or on the ball of the foot. Unless they are treated, bunions get worse over time, and it may become difficult to wear regular shoes or walk without pain. Bunions can occur in one or both feet.In most cases, bunions develop in adulthood. Rarely, children may be born with bunions (known as congenital hallux valgus) or develop them later in childhood (juvenile or adolescent hallux valgus). u Pattern unknown Bunion of great toe Hallux abductovalgus Hallux valgus HAV HV ICD-10-CM M21.61 ICD-10-CM M21.611 ICD-10-CM M21.612 ICD-10-CM M21.619 MeSH D000071378 SNOMED CT 122480009 2018-08 2020-08-18 Burn-McKeown syndrome https://medlineplus.gov/genetics/condition/burn-mckeown-syndrome descriptionBurn-McKeown syndrome is a disorder that is present from birth (congenital) and involves abnormalities of the nasal passages, characteristic facial features, hearing loss, heart abnormalities, and short stature.In people with Burn-McKeown syndrome, both nasal passages are usually narrowed (bilateral choanal stenosis) or completely blocked (bilateral choanal atresia), which can cause life-threatening breathing problems in infancy without surgical repair. Typical facial features include narrow openings of the eyelids (short palpebral fissures); a gap (coloboma) in the lower eyelids; widely spaced eyes (hypertelorism); a prominent bridge of the nose; a short space between the nose and the upper lip (philtrum); a small opening of the mouth (microstomia); and large, protruding ears.Some people with Burn-McKeown syndrome have congenital hearing loss in both ears which varies in severity among affected individuals. The hearing loss is described as mixed, which means that it is caused by both changes in the inner ear (sensorineural hearing loss) and changes in the middle ear (conductive hearing loss).Other features that can occur in Burn-McKeown syndrome include mild short stature and congenital heart defects such as patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly; in severe cases, it can lead to heart failure. Intelligence is unaffected in Burn-McKeown syndrome. ar Autosomal recessive TXNL4A https://medlineplus.gov/genetics/gene/txnl4a Bilateral choanal atresia, cardiac defects, deafness, and dysmorphic appearance BMKS Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome Oculo-oto-facial dysplasia Oculootofacial dysplasia OOFD GTR C1837822 MeSH D000015 OMIM 608572 SNOMED CT 720640005 2016-08 2023-02-06 Buschke-Ollendorff syndrome https://medlineplus.gov/genetics/condition/buschke-ollendorff-syndrome descriptionBuschke-Ollendorff syndrome is a hereditary disorder that primarily affects the skin and bones. Specifically, the condition is characterized by skin growths called connective tissue nevi and bone abnormalities, most commonly a pattern of increased bone density called osteopoikilosis. Buschke-Ollendorff syndrome is classified as a disorder of connective tissues, which provide support, strength, and flexibility to organs and tissues throughout the body.Connective tissue nevi are small, noncancerous lumps on the skin. They tend to appear in childhood and are widespread in people with Buschke-Ollendorff syndrome. In some cases, the nevi are subtle and hard to feel. The most common form of these nevi are elastomas, which are made up of a type of stretchy connective tissue called elastic fibers. Less commonly, affected individuals have nevi called collagenomas, which are made up of another type of connective tissue called collagen.Osteopoikilosis, which is from the Greek words for "spotted bones," refers to small, round areas of increased bone density that appear as bright spots on x-rays. Osteopoikilosis usually occurs near the ends of the long bones of the arms and legs, and in the bones of the hands, feet, and pelvis. The areas of increased bone density appear during childhood. They do not cause pain or other health problems.Other bone abnormalities can also occur with Buschke-Ollendorff syndrome, although they are less common. For example, a small percentage of affected individuals have melorheostosis, which is characterized by excess bone growth on the surface of existing bones in a pattern resembling dripping candle wax. Melorheostosis usually affects the bones in one arm or leg, although it can also affect bones in other areas of the body. This abnormality can cause long-lasting (chronic) pain, permanent joint deformities (contractures), and a limited range of motion of the affected body part. ad Autosomal dominant LEMD3 https://medlineplus.gov/genetics/gene/lemd3 BOS Dermatofibrosis disseminata lenticularis Dermatofibrosis lenticularis disseminata Dermatofibrosis lenticularis disseminata with osteopoikilosis Dermatofibrosis, disseminated, with osteopoikilosis Dermatoosteopoikilosis Osteopathia condensans disseminata GTR C0265514 MeSH D010023 OMIM 166700 SNOMED CT 60399005 SNOMED CT 9147009 2018-05 2024-10-02 C3 glomerulopathy https://medlineplus.gov/genetics/condition/c3-glomerulopathy descriptionC3 glomerulopathy is a group of related conditions that cause the kidneys to malfunction. The major features of C3 glomerulopathy include high levels of protein in the urine (proteinuria), blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in many areas of the body. Affected individuals may have particularly low levels of a protein called complement component 3 (or C3) in the blood.The kidney problems associated with C3 glomerulopathy tend to worsen over time. About half of affected individuals develop end-stage renal disease (ESRD) within 10 years after their diagnosis. ESRD is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.Researchers have identified two major forms of C3 glomerulopathy: dense deposit disease and C3 glomerulonephritis. Although the two disorders cause similar kidney problems, the features of dense deposit disease tend to appear earlier than those of C3 glomerulonephritis, usually in adolescence. However, the signs and symptoms of either disease may not begin until adulthood.One of the two forms of C3 glomerulopathy, dense deposit disease, can also be associated with other conditions unrelated to kidney function. For example, people with dense deposit disease may have acquired partial lipodystrophy, a condition characterized by a lack of fatty (adipose) tissue under the skin in the upper part of the body. Additionally, some people with dense deposit disease develop a buildup of yellowish deposits called drusen in the light-sensitive tissue at the back of the eye (the retina). These deposits usually appear in childhood or adolescence and can cause vision problems later in life. ar Autosomal recessive CFH https://medlineplus.gov/genetics/gene/cfh CFI https://medlineplus.gov/genetics/gene/cfi C3 https://medlineplus.gov/genetics/gene/c3 CFHR5 https://medlineplus.gov/genetics/gene/cfhr5 C8A https://medlineplus.gov/genetics/gene/c8a CFB https://www.ncbi.nlm.nih.gov/gene/629 C3AR1 https://www.ncbi.nlm.nih.gov/gene/719 CR1 https://www.ncbi.nlm.nih.gov/gene/1378 CFD https://www.ncbi.nlm.nih.gov/gene/1675 CFHR1 https://www.ncbi.nlm.nih.gov/gene/3078 CFHR2 https://www.ncbi.nlm.nih.gov/gene/3080 CD46 https://www.ncbi.nlm.nih.gov/gene/4179 ADAM19 https://www.ncbi.nlm.nih.gov/gene/8728 CFHR3 https://www.ncbi.nlm.nih.gov/gene/10878 C3 glomerulonephritis C3G DDD DDD/MPGNII Dense deposit disease Membranoproliferative glomerulonephritis type II GTR C0268743 GTR C0398777 GTR C3553720 GTR C4055342 GTR CN381177 ICD-10-CM N00.6 ICD-10-CM N01.6 ICD-10-CM N02.6 ICD-10-CM N03.6 ICD-10-CM N04.6 ICD-10-CM N05.6 ICD-10-CM N06.6 ICD-10-CM N07.6 MeSH D015432 OMIM 609814 OMIM 614809 SNOMED CT 197599000 SNOMED CT 59479006 2015-12 2020-08-18 CASK-related intellectual disability https://medlineplus.gov/genetics/condition/cask-related-intellectual-disability descriptionCASK-related intellectual disability is a disorder of brain development that has two main forms: microcephaly with pontine and cerebellar hypoplasia (MICPCH), and X-linked intellectual disability (XL-ID) with or without nystagmus. Within each of these forms, males typically have more severe signs and symptoms than do females; the more severe MICPCH mostly affects females, likely because only a small number of males survive to birth.People with MICPCH often have an unusually small head at birth, and the head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Individuals with this condition have underdevelopment (hypoplasia) of areas of the brain called the cerebellum and the pons. The cerebellum is the part of the brain that coordinates movement. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals from the cerebellum to the rest of the brain.Individuals with MICPCH have intellectual disability that is usually severe. They may have sleep disturbances and exhibit self-biting, hand flapping, or other abnormal repetitive behaviors. Seizures are also common in this form of the disorder.People with MICPCH do not usually develop language skills, and most do not learn to walk. They have hearing loss caused by nerve problems in the inner ear (sensorineural hearing loss), and most also have abnormalities affecting the eyes. These abnormalities include underdevelopment of the nerves that carry information from the eyes to the brain (optic nerve hypoplasia), breakdown of the light-sensing tissue at the back of the eyes (retinopathy), and eyes that do not look in the same direction (strabismus). Characteristic facial features may include arched eyebrows; a short, broad nose; a lengthened area between the nose and mouth (philtrum); a protruding upper jaw (maxilla); a short chin; and large ears.Individuals with MICPCH may have weak muscle tone (hypotonia) in the torso along with increased muscle tone (hypertonia) and stiffness (spasticity) in the limbs. Movement problems such as involuntary tensing of various muscles (dystonia) may also occur in this form of the disorder.XL-ID with or without nystagmus (rapid, involuntary eye movements) is a milder form of CASK-related intellectual disability. The intellectual disability in this form of the disorder can range from mild to severe; some affected females have normal intelligence. About half of affected individuals have nystagmus. Seizures and rhythmic shaking (tremors) may also occur in this form. xd X-linked dominant CASK https://medlineplus.gov/genetics/gene/cask CASK-related disorders X-linked intellectual deficit, Najm type GTR C2677903 MeSH D008607 OMIM 300422 OMIM 300749 SNOMED CT 703389002 2014-03 2024-09-17 CATSPER1-related nonsyndromic male infertility https://medlineplus.gov/genetics/condition/catsper1-related-nonsyndromic-male-infertility descriptionCATSPER1-related nonsyndromic male infertility is a condition that affects the function of sperm, leading to difficulty conceiving children (a condition called infertility). People with this condition produce sperm that have decreased movement (motility). Affected individuals may also produce fewer sperm cells or sperm cells that are abnormally shaped. These sperm abnormalities prevent people with this condition from conceiving without assisted reproductive technologies. ar Autosomal recessive CATSPER1 https://medlineplus.gov/genetics/gene/catsper1 CATSPER-related nonsyndromic male infertility CATSPER1-related male infertility GTR C2751811 MeSH D007248 OMIM 612997 SNOMED CT 236792002 2024-04 2025-03-06 CAV3-related distal myopathy https://medlineplus.gov/genetics/condition/cav3-related-distal-myopathy descriptionCAV3-related distal myopathy is one form of distal myopathy, a group of disorders characterized by weakness and loss of function affecting the muscles farthest from the center of the body (distal muscles), such as those of the hands and feet. People with CAV3-related distal myopathy experience wasting (atrophy) and weakness of the small muscles in the hands and feet that generally become noticeable in adulthood. A bump or other sudden impact on the muscles, especially those in the forearms, may cause them to exhibit repetitive tensing (percussion-induced rapid contraction). The rapid contractions can continue for up to 30 seconds and may be painful. Overgrowth (hypertrophy) of the calf muscles can also occur in CAV3-related distal myopathy. The muscles closer to the center of the body (proximal muscles) such as the thighs and upper arms are normal in this condition. ad Autosomal dominant CAV3 https://medlineplus.gov/genetics/gene/cav3 Distal myopathy, Tateyama type MPDT GTR C3280443 MeSH D049310 OMIM 614321 SNOMED CT 711265009 2014-05 2020-08-18 CDKL5 deficiency disorder https://medlineplus.gov/genetics/condition/cdkl5-deficiency-disorder descriptionCDKL5 deficiency disorder is characterized by seizures that begin in infancy, followed by significant delays in many aspects of development.Seizures in CDKL5 deficiency disorder usually begin within the first 3 months of life, and can appear as early as the first week after birth. The types of seizures change with age, and may follow a predictable pattern. The most common types are generalized tonic-clonic seizures, which involve a loss of consciousness, muscle rigidity, and convulsions; tonic seizures, which are characterized by abnormal muscle contractions; and epileptic spasms, which involve short episodes of muscle jerks. Seizures occur daily in most people with CDKL5 deficiency disorder, although they can have periods when they are seizure-free. Seizures in CDKL5 deficiency disorder usually do not get better with treatment.Development is impaired in children with CDKL5 deficiency disorder. Most have severe intellectual disability and little or no speech. The development of gross motor skills, such as sitting, standing, and walking, is delayed or not achieved. About one-third of affected individuals are able to walk independently. Fine motor skills, such as picking up small objects with the fingers, are also impaired; about half of affected individuals have purposeful use of their hands. Most people with this condition have vision problems (cortical visual impairment).Other common features of CDKL5 deficiency disorder include repetitive hand movements (stereotypies), such as clapping, hand licking, and hand sucking; teeth grinding (bruxism); disrupted sleep; feeding difficulties; and gastrointestinal problems including constipation and backflow of acidic stomach contents into the esophagus (gastroesophageal reflux). Some affected individuals have episodes of irregular breathing. Distinctive facial features in some people with CDKL5 deficiency disorder include a high and broad forehead, large and deep-set eyes, a well-defined space between the nose and upper lip (philtrum), full lips, widely spaced teeth, and a high roof of the mouth (palate). Other physical differences can also occur, such as an unusually small head size (microcephaly), side-to-side curvature of the spine (scoliosis), and tapered fingers.CDKL5 deficiency disorder was previously classified as an atypical form of Rett syndrome. These conditions have common features, including seizures, intellectual disability, and other problems with development. However, the signs and symptoms associated with CDKL5 deficiency disorder and its genetic cause are distinct from those of Rett syndrome, and CDKL5 deficiency disorder is now considered a separate condition. xd X-linked dominant CDKL5 https://medlineplus.gov/genetics/gene/cdkl5 CDKL5 deficiency CDKL5 disorder CDKL5 encephalopathy CDKL5-related epilepsy CDKL5-related epileptic encephalopathy Cyclin-dependent kinase-like 5 deficiency disorder Early infantile epileptic encephalopathy 2 GTR C4750718 MeSH D013036 OMIM 300672 SNOMED CT 718393002 2017-11 2024-07-19 CHARGE syndrome https://medlineplus.gov/genetics/condition/charge-syndrome descriptionCHARGE syndrome is a disorder that affects many areas of the body. CHARGE is an abbreviation for several of the features common in the disorder: coloboma, heart defects, atresia choanae (also known as choanal atresia), growth retardation, genital abnormalities, and ear abnormalities. The pattern of malformations varies among individuals with this disorder, and the multiple health problems can be life-threatening in infancy. Affected individuals usually have several major characteristics or a combination of major and minor characteristics.The major characteristics of CHARGE syndrome are common in this disorder and occur less frequently in other disorders. Most individuals with CHARGE syndrome have a gap or hole in one of the structures of the eye (coloboma), which forms during early development. A coloboma may be present in one or both eyes and may impair a person's vision, depending on its size and location. Some affected individuals also have abnormally small or underdeveloped eyes (microphthalmia). In many people with CHARGE syndrome, one or both nasal passages are narrowed (choanal stenosis) or completely blocked (choanal atresia), which can cause difficulty breathing. Affected individuals frequently have cranial nerve abnormalities. The cranial nerves emerge directly from the brain and extend to various areas of the head and neck, controlling muscle movement and transmitting sensory information. Abnormal function of certain cranial nerves can cause swallowing problems, facial paralysis, a sense of smell that is diminished (hyposmia) or completely absent (anosmia), and mild to profound hearing loss. People with CHARGE syndrome also typically have middle and inner ear abnormalities, which can contribute to hearing problems, and unusually shaped external ears.While the minor characteristics of CHARGE syndrome are common in this disorder, they are also frequently present in people without the disorder. The minor characteristics include heart defects; slow growth starting in late infancy; delayed development of motor skills, such as sitting unsupported and walking; and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Affected individuals frequently have hypogonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, males with CHARGE syndrome are often born with an unusually small penis (micropenis) and undescended testes (cryptorchidism). Abnormalities of external genitalia are seen less often in affected females. Puberty can be incomplete or delayed in affected males and females. Another minor feature of CHARGE syndrome is tracheoesophageal fistula, which is an abnormal connection (fistula) between the esophagus and the trachea. Most people with CHARGE syndrome also have distinctive facial features, including a square-shaped face and differences in appearance between the right and left sides of the face (facial asymmetry). Affected individuals have a wide range of cognitive function, from normal intelligence to major learning disabilities with absent speech and poor communication.Less common features of CHARGE syndrome include kidney abnormalities; immune system problems; abnormal curvature of the spine (scoliosis or kyphosis); and limb abnormalities, such as extra fingers or toes (polydactyly), missing fingers or toes (oligodactyly), an inward and upward turning foot (club foot), and abnormalities of the long bones of the arms and legs. ad Autosomal dominant CHD7 https://medlineplus.gov/genetics/gene/chd7 CHARGE association Hall-Hittner syndrome GTR C0265354 MeSH D058747 OMIM 214800 SNOMED CT 47535005 2017-02 2020-08-18 CHD2 myoclonic encephalopathy https://medlineplus.gov/genetics/condition/chd2-myoclonic-encephalopathy descriptionCHD2 myoclonic encephalopathy is a condition characterized by recurrent seizures (epilepsy), abnormal brain function (encephalopathy), and intellectual disability. Epilepsy begins in childhood, typically between ages 6 months and 4 years. Each individual may experience a variety of seizure types. The most common are myoclonic seizures, which involve involuntary muscle twitches. Other seizure types include sudden episodes of weak muscle tone (atonic seizures); partial or complete loss of consciousness (absence seizures); seizures brought on by high body temperature (febrile seizure); or tonic-clonic seizures, which involve loss of consciousness, muscle rigidity, and convulsions. Some people with CHD2 myoclonic encephalopathy have photosensitive epilepsy, in which seizures are triggered by flashing lights. Some people with CHD2 myoclonic encephalopathy experience a type of seizure called atonic-myoclonic-absence seizure, which begins with a drop of the head, followed by loss of consciousness, then rigid movements of the arms. Epilepsy can worsen, causing prolonged episodes of seizure activity that last several minutes, known as status epilepticus. The seizures associated with CHD2 myoclonic encephalopathy are called refractory because they usually do not respond to therapy with anti-epileptic medications.Other signs and symptoms of CHD2 myoclonic encephalopathy include intellectual disability that ranges from mild to severe and delayed development of speech. Rarely, individuals can have a loss of acquired skills (developmental regression) following the onset of epilepsy. Some people with CHD2 myoclonic encephalopathy have autism spectrum disorders, which are conditions characterized by impaired communication and social interaction. In some instances, areas with a loss of brain tissue (atrophy) have been found with medical imaging. ad Autosomal dominant CHD2 https://medlineplus.gov/genetics/gene/chd2 CHD2 encephalopathy CHD2-related neurodevelopmental disorders GTR C3809278 MeSH D004831 OMIM 615369 SNOMED CT 192845009 2016-11 2020-08-18 CHILD syndrome https://medlineplus.gov/genetics/condition/child-syndrome descriptionCHILD syndrome is a condition that affects the development of several parts of the body. The name of the condition is an acronym of the major features: congenital hemidysplasia with ichthyosiform erythroderma and limb defects. The signs and symptoms of this disorder may vary from person to person, but they are typically limited to only one side of the body ("hemi-" means "half," and "dysplasia" refers to abnormal growth). The right side of the body is affected more often than the left side.People with CHILD syndrome often have a skin condition characterized by large patches of skin that are red and inflamed (erythroderma) and covered with yellow, flaky scales (ichthyosis). This condition is most likely to occur in skin folds and creases and usually does not affect the face. The skin abnormalities are typically present at birth or appear within the first few weeks of life and may improve with time. CHILD syndrome may also disrupt the formation of the arms and legs during early development. Some children with this disorder have shortened bones in the fingers or toes, while others have shortened or missing limbs. The limb abnormalities typically occur on the same side of the body as the skin abnormalities. Some children have a curvature of the spine (scoliosis) or joint deformities that restrict movement (contractures). In some cases, CHILD syndrome affects the development of the brain, heart, lungs, and kidneys. xd X-linked dominant NSDHL https://medlineplus.gov/genetics/gene/nsdhl CHILD nevus Congenital hemidysplasia with ichthyosiform erythroderma and limb defects Congenital hemidysplasia with ichthyosiform nevus and limbs defects Ichthyosiform erythroderma, unilateral, with ipsilateral malformations, especially absence deformity of limbs GTR C0265267 MeSH D016113 OMIM 308050 SNOMED CT 17608003 2024-07 2025-03-10 CHMP2B-related frontotemporal dementia https://medlineplus.gov/genetics/condition/chmp2b-related-frontotemporal-dementia descriptionCHMP2B-related frontotemporal dementia is a progressive brain disorder that affects personality, behavior, and language. The symptoms of this disorder usually become noticeable in a person's fifties or sixties, and affected people survive about 3 to 21 years after the appearance of symptoms.Changes in personality and behavior are the most common early signs of CHMP2B-related frontotemporal dementia. These changes include inappropriate emotional responses, restlessness, loss of initiative, and neglect of personal hygiene. Affected individuals may overeat sweet foods or place non-food items into their mouths (hyperorality). Additionally, it may become difficult for affected individuals to interact with others in a socially appropriate manner. They increasingly require help with personal care and other activities of daily living.Many people with CHMP2B-related frontotemporal dementia develop progressive problems with speech and language (aphasia). They may have trouble speaking, although they can often understand others' speech and written text. Affected individuals may also have difficulty using numbers (dyscalculia). In the later stages of the disease, many completely lose the ability to communicate.Several years after signs and symptoms first appear, some people with CHMP2B-related frontotemporal dementia develop problems with movement. These movement abnormalities include rigidity, tremors, uncontrolled muscle tensing (dystonia), and involuntary muscle spasms (myoclonus). As the disease progresses, most affected individuals become unable to walk. ad Autosomal dominant CHMP2B https://medlineplus.gov/genetics/gene/chmp2b Chromosome 3-linked frontotemporal dementia DTM1 FTD-3 FTD-CHMP2B FTD3 GTR C1833296 MeSH D057180 OMIM 600795 SNOMED CT 702393003 2010-08 2023-11-13 CHOPS syndrome https://medlineplus.gov/genetics/condition/chops-syndrome descriptionCHOPS syndrome is a disorder involving multiple abnormalities that are present from birth (congenital). The name "CHOPS" is an abbreviation for a list of features of the disorder including cognitive impairment, coarse facial features, heart defects, obesity, lung (pulmonary) involvement, short stature, and skeletal abnormalities.Children with CHOPS syndrome have intellectual disability and delayed development of skills such as sitting and walking. Characteristic facial features include a round face; thick hair; thick eyebrows that grow together in the middle (synophrys); wide-set, bulging eyes with long eyelashes; a short nose; and down-turned corners of the mouth.Most affected individuals are born with a heart defect called patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly; in severe cases, it can lead to heart failure. Multiple heart abnormalities have sometimes been found in children with CHOPS syndrome. In addition to PDA, affected individuals may have ventricular septal defect, which is a defect in the muscular wall (septum) that separates the right and left sides of the heart's lower chamber.People with CHOPS syndrome have abnormalities of the throat and airways that cause momentary cessation of breathing while asleep (obstructive sleep apnea). These abnormalities can also cause affected individuals to breathe food or fluids into the lungs accidentally, which can lead to a potentially life-threatening bacterial lung infection (aspiration pneumonia) and chronic lung disease. Affected individuals are shorter than more than 97 percent of their peers and are overweight for their height. They also have skeletal differences including unusually short fingers and toes (brachydactyly) and abnormally-shaped spinal bones (vertebrae).Other features that can occur in CHOPS syndrome include a small head size (microcephaly); hearing loss; clouding of the lens of the eye (cataract); a single, horseshoe-shaped kidney; and, in affected males, undescended testes (cryptorchidism). ad Autosomal dominant AFF4 https://medlineplus.gov/genetics/gene/aff4 Cognitive impairment, coarse facies, heart defects, obesity, pulmonary involvement, short stature, and skeletal dysplasia GTR C4085597 MeSH D000015 OMIM 616368 2015-10 2020-08-18 CHST3-related skeletal dysplasia https://medlineplus.gov/genetics/condition/chst3-related-skeletal-dysplasia descriptionCHST3-related skeletal dysplasia is a genetic condition characterized by bone and joint abnormalities that worsen over time. Affected individuals have short stature throughout life, with an adult height under 4 and a half feet. Joint dislocations, most often affecting the knees, hips, and elbows, are present at birth (congenital). Other bone and joint abnormalities can include an inward- and upward-turning foot (clubfoot), a limited range of motion in large joints, and abnormal curvature of the spine. The features of CHST3-related skeletal dysplasia are usually limited to the bones and joints; however, minor heart defects have been reported in a few affected individuals.Researchers have not settled on a preferred name for this condition. It is sometimes known as autosomal recessive Larsen syndrome based on its similarity to another skeletal disorder called Larsen syndrome. Other names that have been used to describe the condition include spondyloepiphyseal dysplasia, Omani type; humero-spinal dysostosis; and chondrodysplasia with multiple dislocations. Recently, researchers have proposed the umbrella term CHST3-related skeletal dysplasia to refer to bone and joint abnormalities resulting from mutations in the CHST3 gene. ar Autosomal recessive CHST3 https://medlineplus.gov/genetics/gene/chst3 Autosomal recessive Larsen syndrome CDMD Chondrodysplasia with multiple dislocations Humero-spinal dysostosis SED with luxations, CHST3 type SED, Omani type Spondyloepiphyseal dysplasia with congenital joint dislocations Spondyloepiphyseal dysplasia, Omani type GTR C3278404 MeSH D010009 OMIM 143095 SNOMED CT 702400006 2012-10 2023-11-10 CLCN2-related leukoencephalopathy https://medlineplus.gov/genetics/condition/clcn2-related-leukoencephalopathy descriptionCLCN2-related leukoencephalopathy is a disorder that affects the brain. People with this condition have neurological problems that become apparent anytime from childhood to adulthood; the problems generally do not worsen much over time. Most affected individuals have difficulty with coordination and balance (ataxia) but can walk without support, and many have frequent headaches. Individuals diagnosed in childhood usually also have learning disabilities, while those whose symptoms begin in adulthood typically also have vision problems. These vision problems are due to breakdown of the light-sensing tissue at the back of the eyes (retinopathy) or degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. Some affected individuals have mild muscle stiffness (spasticity). Affected males are unable to father children (infertile).Rarely, affected individuals have dizziness (vertigo), ringing in the ears (tinnitus), hearing loss, episodes of abnormal movements (paroxysmal kinesigenic dyskinesia), or psychiatric disorders. However, it is unclear whether these are features of CLCN2-related leukoencephalopathy or coincidental findings.The neurological problems in CLCN2-related leukoencephalopathy are caused by abnormalities in the brain. People with this condition have leukoencephalopathy, an abnormality of the brain's white matter that can be detected with medical imaging. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In affected individuals, the myelin becomes fluid-filled (edematous), impairing nerve impulse transmission. ar Autosomal recessive CLCN2 https://medlineplus.gov/genetics/gene/clcn2 CC2L Leukoencephalopathy with ataxia Leukoencephalopathy with mild cerebellar ataxia and white matter edema Leukoencephalopathy with white matter edema LKPAT MeSH D056784 OMIM 615651 2017-12 2020-08-18 CLN1 disease https://medlineplus.gov/genetics/condition/cln1-disease descriptionCLN1 disease is an inherited disorder that primarily affects the nervous system. Individuals with this condition have normal development in infancy, but typically by 18 months they become increasingly irritable and begin to lose previously acquired skills (developmental regression). In affected children, nerve cells in the brain die over time, leading to an overall loss of brain tissue (brain atrophy) and an unusually small head (microcephaly). Children with CLN1 disease have decreased muscle tone (hypotonia), intellectual and motor disability, and rarely are able to speak or walk. Some affected children develop repetitive hand movements. By age 2, individuals with this condition often have muscle twitches (myoclonus), recurrent seizures (epilepsy), and vision loss. Some affected children develop frequent respiratory infections. As the condition worsens, children have severe feeding difficulties that often require a feeding tube. Children with CLN1 disease usually do not survive past childhood.Some people with CLN1 disease do not develop symptoms until later in childhood or in adulthood. As with younger affected children, older individuals develop a decline in intellectual function, myoclonus, epilepsy, and vision loss. In these individuals, life expectancy depends on when signs and symptoms of CLN1 disease develop and their severity; affected individuals may survive only into adolescence or through adulthood. Adults with CLN1 disease may also have movement disorders, including impaired muscle coordination (ataxia) or a pattern of movement abnormalities known as parkinsonism.CLN1 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive PPT1 https://medlineplus.gov/genetics/gene/ppt1 CLN1 Infantile Batten disease Infantile neuronal ceroid lipofuscinosis Neuronal ceroid lipofuscinosis 1 Neuronal ceroid lipofuscinosis, infantile Santavuori-Haltia disease GTR C0268281 GTR C1850451 ICD-10-CM E75.4 MeSH D009472 OMIM 256730 SNOMED CT 58258004 2016-10 2025-04-03 CLN10 disease https://medlineplus.gov/genetics/condition/cln10-disease descriptionCLN10 disease is a severe disorder that primarily affects the nervous system. Individuals with this condition typically show signs and symptoms soon after birth. These signs and symptoms can include muscle rigidity, respiratory failure, and prolonged episodes of seizure activity that last several minutes (status epilepticus). It is likely that some affected individuals also have seizures before birth while in the womb. Infants with CLN10 disease have unusually small heads (microcephaly) with brains that may be less than half the normal size. There is a loss of brain cells in areas that coordinate movement (the cerebellum) and control thinking and emotions (the cerebral cortex). Nerve cells in the brain also lack a fatty substance called myelin, which protects them and promotes efficient transmission of nerve impulses. Infants with CLN10 disease often die hours to weeks after birth.In some individuals with CLN10 disease, the condition does not appear until later in life, between late infancy and adulthood. These individuals have a gradual loss of brain cells and often develop problems with balance and coordination (ataxia), loss of speech, a progressive loss in intellectual functioning (cognitive decline), and vision loss. Individuals with later-onset CLN10 disease have a shortened lifespan, depending on when their signs and symptoms first started.CLN10 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs). All of these disorders affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive CTSD https://medlineplus.gov/genetics/gene/ctsd Cathepsin D deficiency Cathepsin D deficient neuronal ceroid lipofuscinosis CLN10 Congenital neuronal ceroid lipofuscinosis Neuronal ceroid lipofuscinosis 10 Neuronal ceroid lipofuscinosis due to cathepsin D deficiency ICD-10-CM E75.4 MeSH D009472 OMIM 610127 SNOMED CT 720830009 SNOMED CT 720831008 2016-10 2020-08-18 CLN11 disease https://medlineplus.gov/genetics/condition/cln11-disease descriptionCLN11 disease is a disorder that primarily affects the nervous system. Individuals with this condition typically show signs and symptoms in adolescence or early adulthood. This condition is characterized by recurrent seizures (epilepsy), vision loss, problems with balance and coordination (cerebellar ataxia), and a decline in intellectual function.Seizures in CLN11 disease often involve a loss of consciousness, muscle stiffness (rigidity), and generalized convulsions (tonic-clonic seizures).Vision loss is gradual over time and is due to a condition called retinitis pigmentosa, which is caused by the breakdown of the light-sensitive layer at the back of the eye (retina). People with CLN11 disease can also develop clouding of the lenses of the eyes (cataracts) and rapid, involuntary eye movements (nystagmus).Affected individuals can also develop muscle twitches (myoclonus), walking problems and falling (gait disturbance), and impaired speech (dysarthria). Over time, people with CLN11 disease develop short-term memory loss and loss of executive function, which is the ability to plan and implement problem-solving strategies and actions. They may also become irritable and impulsive. Some affected individuals experience visual hallucinations involving people or animals.CLN11 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs). All of these disorders affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive GRN https://medlineplus.gov/genetics/gene/grn Ceroid lipofuscinosis, neuronal, 11 GRN-related neuronal ceroid-lipofuscinosis GTR C3539123 ICD-10-CM E75.4 MeSH D009472 OMIM 614706 SNOMED CT 62009002 2020-04 2023-03-21 CLN2 disease https://medlineplus.gov/genetics/condition/cln2-disease descriptionCLN2 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin between ages 2 and 4. The initial features usually include recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision loss. CLN2 disease affects motor skills, such as sitting and walking, and speech development. This condition also causes the loss of previously acquired skills (developmental regression), intellectual disability that gradually gets worse, and behavioral problems. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens.Some children with CLN2 disease do not develop symptoms until later in childhood, typically after age 4. These individuals tend to have milder features overall compared to those diagnosed earlier, but with more severe ataxia. They have a shortened life expectancy, although they tend to survive into adulthood.CLN2 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive TPP1 https://medlineplus.gov/genetics/gene/tpp1 Jansky-Bielschowsky disease Late-infantile Batten disease Late-infantile neuronal ceroid lipofuscinosis LINCL Neuronal ceroid lipofuscinosis, late-infantile GTR C0022340 GTR C0027877 GTR C1876161 ICD-10-CM E75.4 MeSH D009472 OMIM 204500 SNOMED CT 14637005 2016-11 2020-08-18 CLN3 disease https://medlineplus.gov/genetics/condition/cln3-disease descriptionCLN3 disease is an inherited disorder that primarily affects the nervous system. After 4 to 6 years of normal development, children with this condition develop vision impairment, intellectual disability, movement problems, speech difficulties, and seizures, which worsen over time.In children with CLN3 disease, problems with vision often begin between the ages of 4 and 8 years. Vision impairment is caused by a breakdown of the light-sensitive tissue at the back of the eye (retinal degeneration), which worsens with age. People with CLN3 disease are often blind by late childhood or adolescence. Also around age 4 to 8, children with CLN3 disease start to fall behind in school. They have difficulty learning new information and lose previously acquired skills (developmental regression), usually beginning with loss of the ability to speak in complete sentences.Seizures and movement abnormalities often develop in adolescence in people with CLN3 disease. These abnormalities include muscle rigidity or stiffness, clumsiness, slow or diminished movements (hypokinesia), and a stooped posture. Over time, affected individuals lose the ability to walk or sit independently and require wheelchair assistance. Rarely, people with CLN3 disease develop a distorted view of reality (psychosis) or false perceptions (hallucinations). Some affected individuals have an abnormal heart rhythm (arrhythmia) later in life. Most people with CLN3 disease live into early adulthood.CLN3 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive CLN3 https://medlineplus.gov/genetics/gene/cln3 Batten-Mayou disease Batten-Spielmeyer-Vogt disease CLN3-related neuronal ceroid-lipofuscinosis Juvenile Batten disease Juvenile cerebroretinal degeneration Juvenile neuronal ceroid lipofuscinosis Spielmeyer-Vogt disease GTR C0751383 ICD-10-CM E75.4 MeSH D009472 OMIM 204200 SNOMED CT 61663001 2020-02 2021-02-16 CLN4 disease https://medlineplus.gov/genetics/condition/cln4-disease descriptionCLN4 disease is a condition that primarily affects the nervous system, causing problems with movement and intellectual function that worsen over time. The signs and symptoms of CLN4 disease typically appear around age 30, but they can develop anytime between adolescence and late adulthood.People with CLN4 disease often develop seizures and uncontrollable muscle jerks (myoclonic epilepsy), a decline in intellectual function (dementia), problems with coordination and balance (ataxia), tremors or other involuntary movements (motor tics), and speech difficulties (dysarthria). The signs and symptoms of CLN4 disease worsen over time, and affected individuals usually survive about 15 years after the disorder begins.CLN4 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. (The adult forms of NCLs, which includes CLN4 disease, are sometimes known as Kufs disease.) All the NCLs affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ad Autosomal dominant DNAJC5 https://medlineplus.gov/genetics/gene/dnajc5 Adult neuronal ceroid lipofuscinosis Ceroid lipofuscinosis, neuronal, 4B, autosomal dominant CLN4B Parry disease GTR C1834207 ICD-10-CM E75.4 MeSH D009472 OMIM 162350 SNOMED CT 62009002 2017-01 2020-08-18 CLN5 disease https://medlineplus.gov/genetics/condition/cln5-disease descriptionCLN5 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition can begin anytime between childhood and early adulthood, but they typically appear around age 5. Children with CLN5 disease often have normal development until they experience the first signs of the condition, which are usually problems with movement that might seem like clumsiness, and a loss of previously acquired motor skills (developmental regression). Other features of the condition include recurrent seizures that involve uncontrollable muscle jerks (myoclonic epilepsy), difficulty coordinating movements (ataxia), vision loss, speech problems, and a decline in intellectual function. The life expectancy of people with CLN5 disease varies; affected individuals usually survive into adolescence or mid-adulthood.CLN5 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive CLN5 https://medlineplus.gov/genetics/gene/cln5 Finnish variant late infantile neuronal ceroid lipofuscinosis Finnish vLINCL Jansky-Bielschowsky disease Late-infantile neuronal ceroid lipofuscinosis Neuronal ceroid lipofuscinosis 5 Neuronal ceroid lipofuscinosis, late-infantile VLINCL GTR C1850442 ICD-10-CM E75.4 MeSH D009472 OMIM 256731 SNOMED CT 14637005 2016-11 2021-02-03 CLN6 disease https://medlineplus.gov/genetics/condition/cln6-disease descriptionCLN6 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin between early and late childhood, but sometimes they can appear in adulthood.Most children with CLN6 disease initially experience the loss of previously acquired skills (developmental regression). Affected individuals can also develop recurrent seizures (epilepsy), difficulty coordinating movements (ataxia), muscle twitches (myoclonus), impaired speech (dysarthria), and vision loss. The movement problems worsen over time until affected children cannot walk, stand, or sit without assistance. Intellectual function also declines over time. Most children with CLN6 disease do not survive into adulthood.Some people with CLN6 disease do not show signs or symptoms of the condition until adulthood, typically after age 30. These individuals can have epilepsy, ataxia, dysarthria, and a progressive loss of intellectual function. CLN6 disease usually does not cause vision loss in affected adults. Adults with this condition do not often survive more than 10 years after diagnosis.CLN6 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive CLN6 https://medlineplus.gov/genetics/gene/cln6 Ceroid lipofuscinosis neuronal 6 CLN6-related neuronal ceroid lipofuscinosis Neuronal ceroid lipofuscinosis 6 GTR C5551375 GTR C5561927 ICD-10-CM E75.4 MeSH D009472 OMIM 601780 SNOMED CT 14637005 2017-01 2023-08-18 CLN7 disease https://medlineplus.gov/genetics/condition/cln7-disease descriptionCLN7 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin between ages 2 and 7. The initial features are usually vision loss and problems with movement that might seem like clumsiness. Additional signs and symptoms of CLN7 disease include muscle twitches (myoclonus), difficulty coordinating movements (ataxia), recurrent seizures (epilepsy), and speech impairment. Mental functioning and motor skills (such as sitting and walking) decline with age. Individuals with CLN7 disease typically do not survive past their teens.CLN7 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive MFSD8 https://medlineplus.gov/genetics/gene/mfsd8 CLN7 CLN7 disease, late infantile MFSD8-related neuronal ceroid lipofuscinosis GTR C1838571 ICD-10-CM E75.4 MeSH D009472 OMIM 610951 SNOMED CT 14637005 2016-12 2021-06-01 CLN8 disease https://medlineplus.gov/genetics/condition/cln8-disease descriptionCLN8 disease is an inherited disorder that varies in severity and primarily affects the nervous system. The condition is generally separated into less-severe and more-severe forms, based on the types of signs and symptoms that develop and life expectancy.The less-severe form of CLN8 disease, sometimes referred to as Northern epilepsy, is characterized by recurrent seizures (epilepsy) and a decline in intellectual function that begins between ages 5 and 10. The seizures in this form may be resistant to treatment and are often the generalized tonic-clonic type, which involve muscle rigidity, convulsions, and loss of consciousness. Some people with this form of CLN8 disease also experience partial seizures, which do not cause a loss of consciousness. The seizures occur approximately one to two times per month until adolescence; by early adulthood the frequency decreases to about four to six times per year. By middle age, seizures become even less frequent. In addition to seizures, affected individuals experience a gradual decline in intellectual function and develop problems with coordination and balance. Vision problems may occur in early to mid-adulthood. Individuals with the less-severe form of CLN8 disease often live into late adulthood.The more-severe form of CLN8 disease typically begins between ages 2 and 7.The seizures in this form involve uncontrollable muscle jerks (myoclonic epilepsy). Individuals with the more-severe form have a more pronounced decline in intellectual function and usually lose the ability to speak. Vision loss is also common. People with this form of CLN8 disease have increasing difficulty walking and coordinating movements (ataxia), eventually becoming immobile. Individuals with the more-severe form of CLN8 disease usually survive only into late childhood or adolescence.CLN8 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ar Autosomal recessive CLN8 https://medlineplus.gov/genetics/gene/cln8 Neuronal ceroid lipofuscinosis 8 GTR C1838570 GTR C1864923 ICD-10-CM E75.4 MeSH D009472 MeSH D020191 OMIM 600143 OMIM 610003 SNOMED CT 703526007 2016-12 2020-08-18 CLPB deficiency https://medlineplus.gov/genetics/condition/clpb-deficiency descriptionCLPB deficiency is a rare disorder characterized by neurological problems and a shortage of infection-fighting white blood cells (neutropenia). Signs and symptoms of the condition develop by early childhood, and their severity varies widely among affected individuals.In the most severely affected individuals, features of CLPB deficiency are apparent in infancy and sometimes at birth. Affected babies have serious neurological problems, which can include an exaggerated startle reaction (hyperekplexia) to unexpected stimuli such as loud noises, reduced movement, muscle tone that is either decreased (hypotonia) or increased (hypertonia), swallowing problems, difficulty breathing, and recurrent seizures (epilepsy). These babies may also have movement abnormalities, such as difficulty coordinating movements (ataxia), involuntary tensing of the muscles (dystonia), or uncontrolled movements of the body (dyskinesia). In addition, these babies have recurrent, life-threatening infections due to severe neutropenia. Affected individuals are at risk of developing a blood cell disorder called myelodysplastic syndrome or a form of blood cancer called leukemia. Because of their severe health problems, affected infants usually live only a few weeks or months.Moderately affected individuals have neurological problems similar to those described above, although they are less severe. They include hypotonia, muscle stiffness (spasticity), and movement abnormalities. Other features of moderate CLPB deficiency include epilepsy and mild to severe intellectual disability. Neutropenia in these individuals can lead to recurrent infections, although they are not life-threatening.Mildly affected individuals have no neurological problems, and although they have neutropenia, it does not increase the risk of infections. Some people with mild CLPB deficiency develop deposits of calcium in the kidneys (nephrocalcinosis) or kidney (renal) cysts.Many people with mild, moderate, or severe CLPB deficiency have clouding of the lenses of the eyes (cataracts) from birth (congenital) or beginning in infancy.CLPB deficiency is associated with increased levels of a substance called 3-methylglutaconic acid in the urine (3-methylglutaconic aciduria). This abnormality, which provides a clue to the diagnosis, does not appear to cause any health problems. ar Autosomal recessive CLPB https://medlineplus.gov/genetics/gene/clpb 3-methylglutaconic aciduria type 7 3-methylglutaconic aciduria type VII 3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia 3-methylglutaconic aciduria-cataract-neurologic involvement-neutropenia syndrome MEGCANN MGA7 MGCA7 GTR C5676893 MeSH D001927 OMIM 616271 2017-02 2023-08-22 COG5-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/cog5-congenital-disorder-of-glycosylation descriptionCOG5-congenital disorder of glycosylation (COG5-CDG, formerly known as congenital disorder of glycosylation type IIi) is an inherited condition that causes neurological problems and other abnormalities. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.Individuals with COG5-CDG typically develop signs and symptoms of the condition during infancy. These individuals often have weak muscle tone (hypotonia) and delayed development. Other neurological features include moderate to severe intellectual disability, poor coordination, and difficulty walking. Some affected individuals never learn to speak. Other features of COG5-CDG include short stature, an unusually small head size (microcephaly), and distinctive facial features, which can include ears that are set low and rotated backward, a short neck with a low hairline in the back, and a prominent nose. Less commonly, affected individuals can have hearing loss caused by changes in the inner ear (sensorineural hearing loss), vision impairment, damage to the nerves that control bladder function (a condition called neurogenic bladder), liver disease, and joint deformities (contractures). ar Autosomal recessive COG5 https://medlineplus.gov/genetics/gene/cog5 Carbohydrate deficient glycoprotein syndrome type IIi CDG IIi CDG2I CDGIIi COG5-CDG Congenital disorder of glycosylation type IIi GTR C3150876 MeSH D018981 OMIM 613612 SNOMED CT 721100009 2014-08 2021-11-26 COL4A1-related brain small-vessel disease https://medlineplus.gov/genetics/condition/col4a1-related-brain-small-vessel-disease descriptionCOL4A1-related brain small-vessel disease is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. COL4A1-related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. Stroke is often the first symptom of this condition, typically occurring in mid-adulthood. In affected individuals, stroke is usually caused by bleeding in the brain (hemorrhagic stroke) rather than a lack of blood flow in the brain (ischemic stroke), although either type can occur. Individuals with this condition are at increased risk of having more than one stroke in their lifetime. People with COL4A1-related brain small vessel disease also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI). Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras.Some people with COL4A1-related brain small-vessel disease have an eye abnormality called Axenfeld-Rieger anomaly. Axenfeld-Rieger anomaly involves underdevelopment and eventual tearing of the colored part of the eye (iris) and a pupil that is not in the center of the eye. Other eye problems experienced by people with COL4A1-related brain small-vessel disease include clouding of the lens of the eye (cataract) and the presence of arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eye (arterial retinal tortuosity). Axenfeld-Rieger anomaly and cataract can cause impaired vision. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss.The severity of the condition varies greatly among affected individuals. Some individuals with COL4A1-related brain small-vessel disease do not have any signs or symptoms of the condition. ad Autosomal dominant COL4A1 https://medlineplus.gov/genetics/gene/col4a1 Brain small-vessel disease with hemorrhage MeSH D002543 OMIM 175780 SNOMED CT 443929000 2011-09 2020-08-18 CUL3-related neurodevelopmental disorder https://medlineplus.gov/genetics/condition/cul3-related-neurodevelopmental-disorder descriptionCUL3-related neurodevelopmental disorder is a condition that affects neurological and physical development. Children with CUL3-related neurodevelopmental disorder may have intellectual disability or specific learning disorders. They may also experience delayed development of speech and motor skills, such as sitting and walking. Some individuals with this condition may have autism spectrum disorder, a developmental condition that affects communication and social skills. Movement abnormalities can also occur in people with CUL3-related neurodevelopmental disorder. Affected individuals may have weak muscle tone (hypotonia) in childhood. In adulthood, they may develop involuntary muscle tensing (dystonia), rhythmic shaking (tremor), or other uncontrolled movements (spasms). People with CUL3-related neurodevelopmental disorder can have distinctive facial features, including a long, triangular-shaped face; a large forehead; a large, rounded nose; small ears; deep-set eyes; or a pointed chin. Some affected individuals have a larger than normal head (macrocephaly). Many people with CUL3-related neurodevelopmental disorder have hand and foot abnormalities. Hand abnormalities can include small pinky (fifth) fingers that curve inward (clinodactyly), narrow thumbs, underdevelopment of the muscle at the base of the thumb (thenar hypoplasia), or a single crease across the palm of the hand. Foot abnormalities can include high arches of the feet (pes cavus); bunions; fusion of the skin between some toes (cutaneous syndactyly); or joint deformities (contractures) in the ankles, feet, or toes. A few individuals with CUL3-related neurodevelopmental disorder have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some affected infants have a backflow of stomach acids into the esophagus (gastroesophageal reflux disease or GERD), which tends to go away after childhood. Rarely, recurrent seizures (epilepsy), congenital heart abnormalities, or genitourinary abnormalities occur in people with CUL3-related neurodevelopmental disorder.  ad Autosomal dominant+New variant CUL3 https://medlineplus.gov/genetics/gene/cul3 NEDAUS Neurodevelopmental disorder with or without autism or seizures GTR C5543225 ICD-10-CM MeSH OMIM 619239 SNOMED CT 2023-09 2023-10-10 Caffey disease https://medlineplus.gov/genetics/condition/caffey-disease descriptionCaffey disease, also called infantile cortical hyperostosis, is a bone disorder that most often occurs in babies. Excessive new bone formation (hyperostosis) is characteristic of Caffey disease. The bone abnormalities mainly affect the jawbone, shoulder blades (scapulae), collarbones (clavicles), and the shafts (diaphyses) of long bones in the arms and legs. Affected bones may double or triple in width, which can be seen by x-ray imaging. In some cases two bones that are next to each other, such as two ribs or the pairs of long bones in the forearms (radius and ulna) or lower legs (tibia and fibula) become fused together. Babies with Caffey disease also have swelling of joints and of soft tissues such as muscles, with pain and redness in the affected areas. Affected infants can also be feverish and irritable.The signs and symptoms of Caffey disease are usually apparent by the time an infant is 5 months old. In rare cases, skeletal abnormalities can be detected by ultrasound imaging during the last few weeks of development before birth. Lethal prenatal cortical hyperostosis, a more severe disorder that appears earlier in development and is often fatal before or shortly after birth, is sometimes called lethal prenatal Caffey disease; however, it is generally considered to be a separate disorder.For unknown reasons, the swelling and pain associated with Caffey disease typically go away within a few months. Through a normal process called bone remodeling, which replaces old bone tissue with new bone, the excess bone is usually reabsorbed by the body and undetectable on x-ray images by the age of 2. However, if two adjacent bones have fused, they may remain that way, possibly resulting in complications. For example, fused rib bones can lead to curvature of the spine (scoliosis) or limit expansion of the chest, resulting in breathing problems.Most people with Caffey disease have no further problems related to the disorder after early childhood. Occasionally, another episode of hyperostosis occurs years later. In addition, some adults who had Caffey disease in infancy have other abnormalities of the bones and connective tissues, which provide strength and flexibility to structures throughout the body. Affected adults may have loose joints (joint laxity), stretchy (hyperextensible) skin, or be prone to protrusion of organs through gaps in muscles (hernias). ad Autosomal dominant COL1A1 https://medlineplus.gov/genetics/gene/col1a1 Caffey-Silverman syndrome De Toni-Caffey disease Infantile cortical hyperostosis GTR C0020497 MeSH D006958 OMIM 114000 SNOMED CT 24752008 2013-04 2020-08-18 Campomelic dysplasia https://medlineplus.gov/genetics/condition/campomelic-dysplasia descriptionCampomelic dysplasia is a severe disorder that affects development of the skeleton, reproductive system, and other parts of the body. This condition is often life-threatening in the newborn period.The term "campomelic" comes from the Greek words for "bent limb." Affected individuals are typically born with bowing of the long bones in the legs, and occasionally, bowing in the arms. Bowing can cause characteristic skin dimples to form over the curved bone, especially on the lower legs. People with campomelic dysplasia usually have short legs, dislocated hips, underdeveloped shoulder blades, 11 pairs of ribs instead of 12, bone abnormalities in the neck, and inward- and upward-turning feet (clubfeet). These skeletal abnormalities begin developing before birth and can often be seen on ultrasound. When affected individuals have features of this disorder but do not have bowed limbs, they are said to have acampomelic campomelic dysplasia.Approximately 75 percent of affected individuals with a typical male chromosome pattern (46,XY) have normal female genitalia or genitalia that do not look clearly male or clearly female. Internal reproductive organs may not correspond with the external genitalia; the internal organs can be male (testes), female (ovaries), or a combination of the two. For example, an individual with female external genitalia may have testes or a combination of testes and ovaries.Affected individuals have distinctive facial features, including a small chin, prominent eyes, and a flat face. They also have a large head compared to their body size. A particular group of physical features, called Pierre Robin sequence, is common in people with campomelic dysplasia. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). People with campomelic dysplasia are often born with weakened cartilage that forms the upper respiratory tract. This abnormality, called laryngotracheomalacia, partially blocks the airway and causes difficulty breathing. Laryngotracheomalacia contributes to the poor survival of infants with campomelic dysplasia.Only a few people with campomelic dysplasia survive past infancy. As these individuals age, they may develop an abnormal curvature of the spine (scoliosis) and other spine abnormalities that compress the spinal cord. People with campomelic dysplasia may also have short stature and hearing loss. ad Autosomal dominant SOX9 https://medlineplus.gov/genetics/gene/sox9 Campomelic dwarfism Campomelic syndrome Camptomelic dysplasia GTR C1861922 ICD-10-CM MeSH D055036 OMIM 114290 SNOMED CT 74928006 2009-05 2023-10-27 Camurati-Engelmann disease https://medlineplus.gov/genetics/condition/camurati-engelmann-disease descriptionCamurati-Engelmann disease is a skeletal condition that is characterized by abnormally thick bones (hyperostosis) in the arms, legs, and skull.The thick limb bones can lead to bone pain and muscle weakness in the arms and legs and cause individuals with Camurati-Engelmann disease to tire quickly. Bone pain ranges from mild to severe and can increase with stress, activity, or cold weather. Leg weakness can make it difficult to stand up from a seated position and some affected individuals develop a waddling or unsteady walk. Additional limb abnormalities include joint deformities (contractures), knock knees, and flat feet (pes planus). Swelling and redness (erythema) of the limbs and an abnormal curvature of the spine can also occur.Individuals with Camurati-Engelmann disease may have an unusually thick skull, which can lead to an abnormally large head (macrocephaly) and lower jaw (mandible), a prominent forehead (frontal bossing), and bulging eyes with shallow eye sockets (ocular proptosis). These changes to the head and face become more prominent with age and are most noticeable in affected adults. In about a quarter of individuals with Camurati-Engelmann disease, the thickened skull increases pressure on the brain or compresses the spinal cord, which can cause a variety of neurological problems, including headaches, hearing loss, vision problems, dizziness (vertigo), ringing in the ears (tinnitus), and facial paralysis.The degree of hyperostosis varies among individuals with Camurati-Engelmann disease as does the age at which they experience their first symptoms.Other, rare features of Camurati-Engelmann disease include abnormally long limbs in proportion to height, a decrease in muscle mass and body fat, delayed teething (dentition), frequent cavities, delayed puberty, a shortage of red blood cells (anemia), an enlarged liver and spleen (hepatosplenomegaly), thinning of the skin, and excessively sweaty (hyperhidrotic) hands and feet. ad Autosomal dominant TGFB1 https://medlineplus.gov/genetics/gene/tgfb1 Camurati-Engelmann syndrome CED Diaphyseal dysplasia Diaphyseal hyperostosis Diaphyseal osteosclerosis Engelmann disease PDD Progressive diaphyseal dysplasia GTR C0011989 ICD-10-CM Q78.3 MeSH D003966 OMIM 131300 OMIM 606631 SNOMED CT 34643004 2017-11 2024-09-17 Canavan disease https://medlineplus.gov/genetics/condition/canavan-disease descriptionCanavan disease is a rare inherited disorder that damages the ability of nerve cells (neurons) in the brain to send and receive messages. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies disrupt the growth or maintenance of the myelin sheath, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses.Neonatal/infantile Canavan disease is the most common and most severe form of the condition. Affected infants appear normal for the first few months of life, but by age 3 to 5 months, problems with development become noticeable. These infants usually do not develop motor skills such as turning over, controlling head movement, and sitting without support. Other common features of this condition include weak muscle tone (hypotonia), an unusually large head size (macrocephaly), and irritability. Feeding and swallowing difficulties, seizures, and sleep disturbances may also develop.The mild/juvenile form of Canavan disease is less common. Affected individuals have mildly delayed development of speech and motor skills starting in childhood. These delays may be so mild and nonspecific that they are never recognized as being caused by Canavan disease.The life expectancy for people with Canavan disease varies. Most people with the neonatal/infantile form live only into childhood, although some survive into adolescence or beyond. People with the mild/juvenile form do not appear to have a shortened lifespan. ar Autosomal recessive ASPA https://medlineplus.gov/genetics/gene/aspa ACY2 deficiency Aminoacylase 2 deficiency Aspa deficiency Aspartoacylase deficiency Canavan's disease GTR C0206307 GTR C0751663 GTR C4017127 ICD-10-CM E75.29 MeSH D017825 OMIM 271900 SNOMED CT 80544005 2015-04 2025-04-03 Cantú syndrome https://medlineplus.gov/genetics/condition/cantu-syndrome descriptionCantú syndrome is a rare condition characterized by excess hair growth (hypertrichosis), a distinctive facial appearance, heart defects, and several other abnormalities. The features of the disorder vary among affected individuals.People with Cantú syndrome have thick scalp hair that extends onto the forehead and grows down onto the cheeks in front of the ears. They also have increased body hair, especially on the back, arms, and legs. Most affected individuals have a large head (macrocephaly) and distinctive facial features that are described as "coarse." These include a broad nasal bridge, skin folds covering the inner corner of the eyes (epicanthal folds), and a wide mouth with full lips. As affected individuals get older, the face lengthens, the chin becomes more prominent, and the eyes become deep-set.Many infants with Cantú syndrome are born with a heart defect such as an enlarged heart (cardiomegaly) or patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. Other heart problems have also been found in people with Cantú syndrome, including an abnormal buildup of fluid around the heart (pericardial effusion) and high blood pressure in the blood vessels that carry blood from the heart to the lungs (pulmonary hypertension).Additional features of this condition include distinctive skeletal abnormalities, a large body size (macrosomia) at birth, a reduced amount of fat under the skin (subcutaneous fat) beginning in childhood, deep horizontal creases in the palms of the hands and soles of the feet, and an increased susceptibility to respiratory infections. Other signs and symptoms that have been reported include abnormal swelling in the body's tissues (lymphedema), side-to-side curvature of the spine (scoliosis), and reduced bone density (osteopenia). Some affected children have weak muscle tone (hypotonia) that delays the development of motor skills such as sitting, standing, and walking. Most have mildly delayed speech, and some affected children have mild intellectual disability or learning problems. ad Autosomal dominant ABCC9 https://medlineplus.gov/genetics/gene/abcc9 Cantu syndrome Hypertrichosis-osteochondrodysplasia-cardiomegaly syndrome Hypertrichotic osteochondrodysplasia GTR C0795905 MeSH D010009 OMIM 239850 SNOMED CT 239087008 2013-01 2020-08-18 Cap myopathy https://medlineplus.gov/genetics/condition/cap-myopathy descriptionCap myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with cap myopathy have muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body, but they are most severely affected in the muscles of the face, neck, and limbs. The muscle weakness, which begins at birth or during childhood, can worsen over time.Affected individuals may have feeding and swallowing difficulties in infancy. They typically have delayed development of motor skills such as sitting, crawling, standing, and walking. They may fall frequently, tire easily, and have difficulty running, climbing stairs, or jumping. In some cases, the muscles used for breathing are affected, and life-threatening breathing difficulties can occur.People with cap myopathy may have a high arch in the roof of the mouth (high-arched palate), severely drooping eyelids (ptosis), and a long face. Some affected individuals develop an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis).The name cap myopathy comes from characteristic abnormal cap-like structures that can be seen in muscle cells when muscle tissue is viewed under a microscope. The severity of cap myopathy is related to the percentage of muscle cells that have these caps. Individuals in whom 70 to 75 percent of muscle cells have caps typically have severe breathing problems and may not survive childhood, while those in whom 10 to 30 percent of muscle cells have caps have milder symptoms and can live into adulthood. n Not inherited ad Autosomal dominant ACTA1 https://medlineplus.gov/genetics/gene/acta1 TPM3 https://medlineplus.gov/genetics/gene/tpm3 TPM2 https://medlineplus.gov/genetics/gene/tpm2 Cap disease Congenital myopathy with caps MeSH D020914 OMIM 609284 OMIM 609285 SNOMED CT 703532002 2012-04 2020-08-18 Capillary malformation-arteriovenous malformation syndrome https://medlineplus.gov/genetics/condition/capillary-malformation-arteriovenous-malformation-syndrome descriptionCapillary malformation-arteriovenous malformation syndrome (CM-AVM) is a disorder of the vascular system, which is the body's complex network of blood vessels. The vascular system consists of arteries, which carry oxygen-rich blood from the heart to the body's various organs and tissues; veins, which carry blood back to the heart; and capillaries, which are tiny blood vessels that connect arteries and veins.CM-AVM is characterized by capillary malformations (CMs), which are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations look like multiple small, round, pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, arms, and legs. These spots may be visible from birth or may develop during childhood. By themselves, capillary malformations usually do not cause any health problems.In some people with CM-AVM, capillary malformations are the only sign of the disorder. However, other affected individuals also have more serious vascular abnormalities known as arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs). AVMs and AVFs are abnormal connections between arteries, veins, and capillaries that affect blood circulation. Depending on where they occur in the body, these abnormalities can be associated with complications including abnormal bleeding, migraine headaches, seizures, and heart failure. In some cases the complications can be life-threatening. In people with CM-AVM, complications of AVMs and AVFs tend to appear in infancy or early childhood; however, some of these vascular abnormalities never cause any symptoms.Some vascular abnormalities seen in CM-AVM are similar to those that occur in a condition called Parkes Weber syndrome. In addition to vascular abnormalities, Parkes Weber syndrome usually involves overgrowth of one limb. CM-AVM and some cases of Parkes Weber syndrome have the same genetic cause. ad Autosomal dominant RASA1 https://medlineplus.gov/genetics/gene/rasa1 Capillary malformation-arteriovenous malformation CM-AVM GTR C4747394 MeSH D054079 OMIM 608354 SNOMED CT 703533007 2011-08 2023-03-21 Carbamoyl phosphate synthetase I deficiency https://medlineplus.gov/genetics/condition/carbamoyl-phosphate-synthetase-i-deficiency descriptionCarbamoyl phosphate synthetase I deficiency is an inherited disorder that causes ammonia to accumulate in the blood (hyperammonemia). Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The brain is especially sensitive to the effects of excess ammonia.In the first few days of life, infants with carbamoyl phosphate synthetase I deficiency typically exhibit the effects of hyperammonemia, which may include unusual sleepiness, poorly regulated breathing rate or body temperature, unwillingness to feed, vomiting after feeding, unusual body movements, seizures, or coma. Affected individuals who survive the newborn period may experience recurrence of these symptoms if diet is not carefully managed or if they experience infections or other stressors. They may also have delayed development and intellectual disability.In some people with carbamoyl phosphate synthetase I deficiency, signs and symptoms may be less severe and appear later in life. ar Autosomal recessive CPS1 https://medlineplus.gov/genetics/gene/cps1 Carbamoyl-phosphate synthase I deficiency disease Carbamyl-phosphate synthetase I deficiency disease Congenital hyperammonemia, type I GTR C4082171 ICD-10-CM E72.29 MeSH D020165 OMIM 237300 SNOMED CT 62522004 2006-08 2020-08-18 Carbonic anhydrase VA deficiency https://medlineplus.gov/genetics/condition/carbonic-anhydrase-va-deficiency descriptionCarbonic anhydrase VA deficiency is an inherited disorder characterized by episodes during which the balance of certain substances in the body is disrupted (known as metabolic crisis) and brain function is abnormal (known as acute encephalopathy). These potentially life-threatening episodes can cause poor feeding, vomiting, weight loss, tiredness (lethargy), rapid breathing (tachypnea), seizures, or coma.During an episode, people with carbonic anhydrase VA deficiency have excess ammonia in the blood (hyperammonemia), problems with acid-base balance in the blood (metabolic acidosis and respiratory alkalosis), low glucose in the blood (hypoglycemia), and reduced production of a substance called bicarbonate in the liver. These imbalances lead to the signs and symptoms that occur during the episodes.People with carbonic anhydrase VA deficiency typically first experience episodes of the disorder by age 2. These episodes may be triggered by going without food (fasting) for longer than usual between meals or when energy demands are increased, such as during illness. Between episodes, children with carbonic anhydrase VA deficiency are generally healthy, and more than half have no further episodes after the first one. Some affected children have mildly delayed development or learning disabilities, while others develop normally for their age.The risk of metabolic crisis and acute encephalopathy is thought to decrease after childhood. Because of the small number of people with carbonic anhydrase VA deficiency who have come to medical attention, the effects of this disorder in adults are not well understood. ar Autosomal recessive CA5A https://medlineplus.gov/genetics/gene/ca5a CA-VA deficiency CA5AD Hyperammonemia due to carbonic anhydrase VA deficiency Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency Mitochondrial carbonic anhydrase va deficiency GTR C4706871 MeSH D020739 MeSH D022124 OMIM 615751 2016-09 2021-11-26 Cardiofaciocutaneous syndrome https://medlineplus.gov/genetics/condition/cardiofaciocutaneous-syndrome descriptionCardiofaciocutaneous syndrome is a disorder that affects many parts of the body, particularly the heart (cardio-), facial features (facio-), and the skin and hair (cutaneous). People with this condition also have delayed development and intellectual disability, usually ranging from moderate to severe.Heart defects occur in most people with cardiofaciocutaneous syndrome. The heart problems most commonly associated with this condition include malformations of one of the heart valves that impairs blood flow from the heart to the lungs (pulmonic stenosis), a hole between the two upper chambers of the heart (atrial septal defect), and a form of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy).Cardiofaciocutaneous syndrome is also characterized by distinctive facial features. These include a high forehead that narrows at the temples, a short nose, widely spaced eyes (ocular hypertelorism), outside corners of the eyes that point downward (down-slanting palpebral fissures), droopy eyelids (ptosis), a small chin, and low-set ears. Overall, the face is broad and long, and the facial features are sometimes described as "coarse."Skin abnormalities occur in almost everyone with cardiofaciocutaneous syndrome. Many affected people have dry, rough skin; dark-colored moles (nevi); wrinkled palms and soles; and a skin condition called keratosis pilaris, which causes small bumps to form on the arms, legs, and face. People with cardiofaciocutaneous syndrome also tend to have thin, dry, curly hair and sparse or absent eyelashes and eyebrows.Infants with cardiofaciocutaneous syndrome typically have weak muscle tone (hypotonia), feeding difficulties, and a failure to grow and gain weight at the normal rate (failure to thrive). Additional features of this disorder in children and adults can include an unusually large head (macrocephaly), short stature, problems with vision, and seizures.The signs and symptoms of cardiofaciocutaneous syndrome overlap significantly with those of two other genetic conditions, Costello syndrome and Noonan syndrome. The three conditions are distinguished by their genetic cause and specific patterns of signs and symptoms; however, it can be difficult to tell these conditions apart, particularly in infancy. Unlike Costello syndrome, which significantly increases a person's cancer risk, cancer does not appear to be a major feature of cardiofaciocutaneous syndrome. ad Autosomal dominant KRAS https://medlineplus.gov/genetics/gene/kras BRAF https://medlineplus.gov/genetics/gene/braf MAP2K1 https://medlineplus.gov/genetics/gene/map2k1 MAP2K2 https://medlineplus.gov/genetics/gene/map2k2 Cardio-facio-cutaneous syndrome CFC syndrome GTR C1275081 MeSH D004476 MeSH D006330 OMIM 115150 SNOMED CT 403770008 2012-05 2023-03-21 Carney complex https://medlineplus.gov/genetics/condition/carney-complex descriptionCarney complex is a disorder that is characterized by changes in skin coloring (pigmentation) and an increased risk of tumors. Many of the signs and symptoms of Carney complex become apparent during adolescence or early adulthood.Almost all people with Carney complex have areas of unusual skin pigmentation. Brown or black skin spots called lentigines may appear anywhere on the body, but they tend to occur around the lips, eyes, or genitalia. In addition, some affected individuals have at least one blue-black mole called a blue nevus.People with Carney complex have an increased risk of developing noncancerous (benign) tumors called myxomas in the heart (cardiac myxoma), skin, breast, and other parts of the body. Cardiac myxomas may be found in one or more chambers of the heart. These tumors can block the flow of blood through the heart, which can cause serious complications, including sudden death. Skin myxomas appear as small bumps on the surface of the skin or as lumps underneath the skin. In people with Carney complex, myxomas tend to recur after they are removed.Individuals with Carney complex may also develop tumors in hormone-producing (endocrine) glands, such as the adrenal glands located on top of each kidney. Approximately 25 percent of people with Carney complex develop a specific type of adrenal tumor called primary pigmented nodular adrenocortical disease (PPNAD). PPNAD causes the adrenal glands to produce too much of the hormone cortisol. High levels of cortisol can lead to the development of Cushing syndrome, which is characterized by weight gain in the face and upper body, slow growth in children, bone loss, fragile skin, fatigue, and other health problems.Tumors of other endocrine tissues, such as the thyroid, testes, and ovaries, are also seen in people with Carney complex. Many affected individuals have tumors on the thyroid gland called adenomas. Occasionally, people with thyroid adenomas develop thyroid cancer.In people with Carney complex, adenomas may also form in the pituitary gland, which is located at the base of the brain. A pituitary adenoma usually causes the production of too much growth hormone. Excess growth hormone can lead to a condition called acromegaly, which is characterized by large hands and feet, arthritis, and distinctive facial features that are often described as "coarse."Approximately 10 percent of people with Carney complex develop a rare tumor called psammomatous melanotic schwannoma (PMS). This tumor occurs in specialized cells called Schwann cells that wrap around and insulate nerve cells. These tumors are usually benign, but they can become cancerous (malignant).Although most tumors that develop in people with Carney complex are benign, some affected individuals develop cancer over time. Complications associated with cardiac myxomas, PMS, or cancer can shorten the life expectancy for some affected individuals. ad Autosomal dominant+New variant PRKAR1A https://medlineplus.gov/genetics/gene/prkar1a Carney complex type 1 Carney complex type 2 Carney Syndrome LAMB (Lentigines, atrial myxoma, mucocutaneous myoma, blue nevi) NAME (Nevi, atrial myxoma, skin myxoma, ephelides) GTR C0406810 GTR C1854540 GTR C2607929 MeSH D056733 OMIM 160980 OMIM 605244 SNOMED CT 733491005 2025-03 2025-03-10 Carnitine palmitoyltransferase I deficiency https://medlineplus.gov/genetics/condition/carnitine-palmitoyltransferase-i-deficiency descriptionCarnitine palmitoyltransferase I (CPT I) deficiency is a condition that prevents the body from using certain fats for energy. The signs and symptoms of CPT I deficiency are often brought on by episodes of increased energy demands in the body such as illness or periods of fasting. During these times, affected individuals usually develop low levels of glucose in the blood and a low level of ketones, which are normally produced when fats are broken down to be used for energy. Together, these signs are called hypoketotic hypoglycemia. This may cause individuals to experience confusion, seizures, or a lack of energy (lethargy).People with CPT I deficiency can also develop an enlarged liver (hepatomegaly) that is not able to remove toxins from the blood efficiently. These toxins build up and can affect brain function (hepatic encephalopathy). As long as no brain damage occurs during these episodes of hepatic encephalopathy, individuals with CPT I deficiency often have normal development.Health can decline quickly in people with CPT I deficiency. Affected individuals are encouraged to avoid prolonged fasting to prevent serious health problems. Individuals with CPT I deficiency are at risk for nervous system damage, liver failure, coma, and sudden death. These problems can begin any time between infancy to adulthood, though some individuals experience no health problems at all.CPT I deficiency is often detected shortly after birth by newborn screening, which identifies abnormal levels of certain compounds in the blood. People with CPT I deficiency have high levels of a compound called carnitine. Cells use carnitine, a natural substance that is acquired mostly through the diet, to process fats and produce energy. ar Autosomal recessive CPT1A https://medlineplus.gov/genetics/gene/cpt1a Carnitine palmitoyltransferase IA deficiency CPT 1A deficiency CPT deficiency, hepatic, type I CPT I deficiency Hepatic CPT deficiency Hepatic CPT1 L-CPT1 deficiency Liver form of carnitine palmitoyltransferase deficiency Nonketotic hypoglycemia GTR C1829703 MeSH D008052 OMIM 255120 SNOMED CT 238001003 2025-03 2025-03-17 Carnitine palmitoyltransferase II deficiency https://medlineplus.gov/genetics/condition/carnitine-palmitoyltransferase-ii-deficiency descriptionCarnitine palmitoyltransferase II (CPT II) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods of fasting. There are three main types of CPT II deficiency that vary in severity and the age at which symptoms first appear: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form.The lethal neonatal form of CPT II deficiency becomes apparent soon after birth. Infants with this form of the disorder develop respiratory failure, liver failure, a weakened heart muscle (cardiomyopathy), and an irregular heartbeat (arrhythmia). In many cases, the brain and kidneys are also structurally abnormal. Affected individuals have low levels of glucose in the blood and low levels of ketones, which are produced during the breakdown of fats and used for energy. Together, these signs are called hypoketotic hypoglycemia. If affected individuals fast for long periods of time, they can experience seizures or coma. Because of these serious health complications, infants with the lethal neonatal form of CPT II deficiency usually live for only a few days to a few months.The severe infantile hepatocardiomuscular form of CPT II deficiency affects the liver, heart, and muscles. Signs and symptoms usually appear within the first year of life. This form involves recurring episodes of hypoketotic hypoglycemia, seizures, liver dysfunction, cardiomyopathy, arrhythmia, and muscle weakness (myopathy) in the arms and legs. Signs and symptoms of this form of CPT II deficiency can be triggered by fasting or by illnesses such as viral infections. Individuals with the severe infantile hepatocardiomuscular form of CPT II deficiency are at risk for liver failure, nervous system damage, coma, and sudden death.The myopathic form is the least severe type of CPT II deficiency. This form is characterized by recurrent episodes of muscle pain (myalgia) and occasional weakness that is associated with the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin. This excess myoglobin may cause urine to be red or brown (myoglobinuria). Episodes of myalgia and rhabdomyolysis may be triggered by exercise, stress, exposure to extreme temperatures, infections, or fasting. The first episode of myalgia usually occurs during childhood or adolescence. The severity and frequency of episodes varies among affected individuals. Most people with the myopathic form of CPT II deficiency have no signs or symptoms of the disorder between episodes.People with CPT II deficiency are often encouraged to avoid triggers such as long periods of fasting and intensive exercise to limit the occurrence of serious health problems.CPT II deficiency is often detected shortly after birth by newborn screening, which identifies abnormal levels of certain compounds in the blood. In individuals with CPT II deficiency, the blood levels of certain fats are elevated. ar Autosomal recessive CPT2 https://medlineplus.gov/genetics/gene/cpt2 Carnitine palmitoyltransferase 2 deficiency CPT II deficiency CPT2 deficiency GTR C0342790 GTR C1833508 GTR C1833511 GTR C1833518 ICD-10-CM E71.314 MeSH D008052 OMIM 255110 OMIM 600649 OMIM 608836 SNOMED CT 238002005 2025-03 2025-03-17 Carnitine-acylcarnitine translocase deficiency https://medlineplus.gov/genetics/condition/carnitine-acylcarnitine-translocase-deficiency descriptionCarnitine-acylcarnitine translocase (CACT) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Signs and symptoms of this disorder usually begin soon after birth and may include breathing problems, seizures, and an irregular heartbeat (arrhythmia). Affected individuals typically have low blood glucose (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. People with CACT deficiency also usually have excess ammonia in the blood (hyperammonemia), an enlarged liver (hepatomegaly), and a weakened heart muscle (cardiomyopathy).Many infants with CACT deficiency do not survive the newborn period. Some affected individuals have a less severe form of the condition and do not develop signs and symptoms until early childhood. These individuals are at risk for liver failure, nervous system damage, coma, and sudden death. ar Autosomal recessive SLC25A20 https://medlineplus.gov/genetics/gene/slc25a20 CACT deficiency Carnitine acylcarnitine translocase deficiency Carnitine-acylcarnitine carrier deficiency GTR C0342791 MeSH D008052 OMIM 212138 SNOMED CT 238003000 2010-11 2023-07-26 Carpal tunnel syndrome https://medlineplus.gov/genetics/condition/carpal-tunnel-syndrome descriptionCarpal tunnel syndrome is a disorder caused by disturbances in nerve function (neuropathy), leading to pain and numbness or tingling (paresthesia) primarily in the wrist and hand. While carpal tunnel syndrome can occur at any age, it most often affects people between the ages of 40 and 60. In more than half of cases, both hands are affected; however, the severity may vary between hands. When only one hand is affected, it is most often the hand used for writing (the dominant hand).In carpal tunnel syndrome, the pain or paresthesia is usually felt in the wrist, the palm, and the first four fingers of the hand. These signs and symptoms often develop during sleep and are noticeable upon waking. Affected individuals typically shake their hand to get rid of the pain and numbness, a characteristic move known as the flick sign. As the condition advances, the signs and symptoms begin to occur during the day as well. Affected individuals may have difficulty performing manual tasks such as turning doorknobs, fastening buttons, or opening jars. The symptoms of carpal tunnel syndrome may be triggered by certain activities that flex or extend the wrist, such as driving, typing, or holding a telephone.Over time, people with carpal tunnel syndrome can have muscle and nerve wasting (atrophy) in the affected hand and a reduced ability to detect sensations, which can be mistaken for an improvement of symptoms. u Pattern unknown COL1A1 https://medlineplus.gov/genetics/gene/col1a1 COL5A1 https://medlineplus.gov/genetics/gene/col5a1 COL11A1 https://medlineplus.gov/genetics/gene/col11a1 TTR https://medlineplus.gov/genetics/gene/ttr BGN https://www.ncbi.nlm.nih.gov/gene/633 GSTM1 https://www.ncbi.nlm.nih.gov/gene/2944 IL6R https://www.ncbi.nlm.nih.gov/gene/3570 SH3TC2 https://www.ncbi.nlm.nih.gov/gene/79628 Amyotrophy, thenar, of carpal origin Carpal canal Carpal tunnel Compression neuropathy, carpal tunnel CTS Distal median nerve compression Distal median nerve entrapment Entrapment neuropathy, carpal tunnel Median neuropathy, carpal tunnel GTR C0007286 ICD-10-CM G56.00 MeSH D002349 OMIM 115430 OMIM 613353 SNOMED CT 57406009 2018-11 2020-08-18 Carpenter syndrome https://medlineplus.gov/genetics/condition/carpenter-syndrome descriptionCarpenter syndrome is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems.Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). In severely affected individuals, the abnormal fusion of the skull bones results in a deformity called a cloverleaf skull. Craniosynostosis can cause differences between the two sides of the head and face (craniofacial asymmetry). Early fusion of the skull bones can affect the development of the brain and lead to increased pressure within the skull (intracranial pressure). Premature fusion of the skull bones can cause several characteristic facial features in people with Carpenter syndrome. Distinctive facial features may include a flat nasal bridge, outside corners of the eyes that point downward (down-slanting palpebral fissures), low-set and abnormally shaped ears, underdeveloped upper and lower jaws, and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary (baby) teeth. Vision problems also frequently occur.Abnormalities of the fingers and toes include fusion of the skin between two or more fingers or toes (cutaneous syndactyly), unusually short fingers or toes (brachydactyly), or extra fingers or toes (polydactyly). In Carpenter syndrome, cutaneous syndactyly is most common between the third (middle) and fourth (ring) fingers, and polydactyly frequently occurs next to the big or second toe or the fifth (pinky) finger.People with Carpenter syndrome often have intellectual disability, which can range from mild to profound. However, some individuals with this condition have normal intelligence. The cause of intellectual disability is unknown, as the severity of craniosynostosis does not appear to be related to the severity of intellectual disability.Other features of Carpenter syndrome include obesity that begins in childhood, a soft out-pouching around the belly-button (umbilical hernia), hearing loss, and heart defects. Additional skeletal abnormalities such as deformed hips, a rounded upper back that also curves to the side (kyphoscoliosis), and knees that are angled inward (genu valgum) frequently occur. Nearly all affected males have genital abnormalities, most frequently undescended testes (cryptorchidism).A few people with Carpenter syndrome have organs or tissues within their chest and abdomen that are in mirror-image reversed positions. This abnormal placement may affect several internal organs (situs inversus); just the heart (dextrocardia), placing the heart on the right side of the body instead of on the left; or only the major (great) arteries of the heart, altering blood flow.The signs and symptoms of this disorder vary considerably, even within the same family. The life expectancy for individuals with Carpenter syndrome is shortened but extremely variable.The signs and symptoms of Carpenter syndrome are similar to another genetic condition called Greig cephalopolysyndactyly syndrome. The overlapping features, which include craniosynostosis, polydactyly, and heart abnormalities, can cause these two conditions to be misdiagnosed; genetic testing is often required for an accurate diagnosis. ar Autosomal recessive RAB23 https://medlineplus.gov/genetics/gene/rab23 MEGF8 https://medlineplus.gov/genetics/gene/megf8 ACPS II Acrocephalopolysyndactyly 2 Acrocephalopolysyndactyly type II Acrocephalosyndactyly, type II Type II acrocephalosyndactyly GTR C1275078 GTR C3554247 MeSH D000168 OMIM 201000 OMIM 614976 SNOMED CT 403767009 2013-05 2020-08-18 Cartilage-hair hypoplasia https://medlineplus.gov/genetics/condition/cartilage-hair-hypoplasia descriptionCartilage-hair hypoplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair (hypotrichosis); and abnormal immune system function (immune deficiency) that can lead to recurrent infections.People with cartilage-hair hypoplasia have unusually short limbs and short stature from birth. They typically have malformations in the cartilage near the ends of the long bones in the arms and legs (metaphyseal chondrodysplasia), which then affects development of the bone itself. Most people with cartilage-hair hypoplasia are unusually flexible in some joints, but they may have difficulty extending their elbows fully.Affected individuals have hair that is lighter in color than that of other family members because the core of each hair, which contains some of the pigment that contributes the hair's color, is missing. The missing core also makes each strand of hair thinner, causing the hair to have a sparse appearance overall. Unusually light-colored skin (hypopigmentation), malformed nails, and dental abnormalities may also be seen in this disorder.The extent of the immune deficiency in cartilage-hair hypoplasia varies from mild to severe. Affected individuals with the most severe immune problems are considered to have severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi and are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. Most people with cartilage-hair hypoplasia, even those who have milder immune deficiency, experience infections of the respiratory system, ears, and sinuses. In particular, the chicken pox virus (varicella) often causes dangerous infections in people with this disorder. Autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs, occur in some people with cartilage-hair hypoplasia. Affected individuals are also at an increased risk of developing cancer, particularly certain skin cancers (basal cell carcinomas), cancer of blood-forming cells (leukemia), and cancer of immune system cells (lymphoma).Some people with cartilage-hair hypoplasia experience gastrointestinal problems. These problems may include an inability to properly absorb nutrients or intolerance of a protein called gluten found in wheat and other grains (celiac disease). Affected individuals may have Hirschsprung disease, an intestinal disorder that causes severe constipation, intestinal blockage, and enlargement of the colon. Narrowing of the anus (anal stenosis) or blockage of the esophagus (esophageal atresia) may also occur. ar Autosomal recessive RMRP https://medlineplus.gov/genetics/gene/rmrp Cartilage-hair syndrome CHH McKusick's metaphyseal chondrodysplasia syndrome Metaphyseal chondrodysplasia, McKusick type Metaphyseal chondrodysplasia, recessive type GTR C0220748 MeSH D004392 OMIM 250250 SNOMED CT 7720002 2008-11 2021-11-24 Catecholaminergic polymorphic ventricular tachycardia https://medlineplus.gov/genetics/condition/catecholaminergic-polymorphic-ventricular-tachycardia descriptionCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition characterized by an abnormal heart rhythm (arrhythmia). As the heart rate increases in response to physical activity or emotional stress, it can trigger an abnormally fast heartbeat called ventricular tachycardia. Episodes of ventricular tachycardia can cause light-headedness, dizziness, and fainting (syncope). In people with CPVT, these episodes typically begin in childhood.If CPVT is not recognized and treated, an episode of ventricular tachycardia may cause the heart to stop beating (cardiac arrest), leading to sudden death. Researchers suspect that CPVT may be a significant cause of sudden death in children and young adults without recognized heart abnormalities. ad Autosomal dominant ar Autosomal recessive RYR2 https://medlineplus.gov/genetics/gene/ryr2 CASQ2 https://medlineplus.gov/genetics/gene/casq2 CALM1 https://www.ncbi.nlm.nih.gov/gene/801 CALM2 https://www.ncbi.nlm.nih.gov/gene/805 CALM3 https://www.ncbi.nlm.nih.gov/gene/808 TECRL https://www.ncbi.nlm.nih.gov/gene/253017 Bidirectional tachycardia induced by catecholamines Catecholamine-induced polymorphic ventricular tachycardia CPVT Familial polymorphic ventricular tachycardia FPVT GTR C1631597 GTR C2677794 ICD-10-CM I47.2 MeSH D017180 OMIM 604772 OMIM 611938 SNOMED CT 419671004 2020-07 2020-08-18 Caudal regression syndrome https://medlineplus.gov/genetics/condition/caudal-regression-syndrome descriptionCaudal regression syndrome is a disorder that impacts the development of the lower (caudal) part of the spine. The condition can affect many parts of the lower body, including the lower back and limbs, the genitourinary tract, and the gastrointestinal tract.In people with this disorder, the bones of the lower spine (vertebrae) are misshapen or missing. The end of the spinal cord, the bundle of nerves and cells protected by the vertebrae, may also be malformed or missing. Sometimes, the spinal cord is abnormally connected (tethered) to nearby tissues. People with caudal regression syndrome can also have an abnormal curvature of the spine (lordosis or kyphosis). The spinal abnormalities may affect the size and shape of the chest, which very rarely leads to breathing problems.Individuals with caudal regression syndrome may have small hip bones. The buttocks tend to be flat and dimpled. The bones of the legs are typically underdeveloped, and the joints in the lower limbs may be unusually stiff and difficult to move. In some affected individuals, the legs are bent with the knees pointing out to the side and the feet tucked underneath the hips (sometimes called a frog leg-like position). These individuals may have webbed skin behind their knees. In other affected individuals, the knees may not bend, and the legs remain in a straight position. Their feet may be inward- and upward-turning (clubfeet) or outward- and upward-turning (calcaneovalgus). Some people with caudal regression syndrome have reduced or excessive sensation in their lower limbs. Sensitivity differs from person to person and from one area of the limb to another.Mobility in people with caudal regression syndrome is varied. Some individuals with the condition walk independently, and others require mobility aids, such as braces, crutches, walkers, or wheelchairs.Abnormalities in the genitourinary tract in people with caudal regression syndrome are diverse. Urinary tract problems can result from abnormalities in the lowest part of the spinal cord, which contains the nerves that control bladder function. Damage to these nerves can cause a condition called neurogenic bladder, which makes it difficult to control the flow of urine. In addition, the kidneys may be malformed in people with caudal regression syndrome; defects include a missing kidney (unilateral renal agenesis), kidneys that are fused together (horseshoe kidney), or duplication of the tubes that carry urine from each kidney to the bladder (ureteral duplication). These kidney abnormalities and neurogenic bladder can lead to frequent urinary tract infections and the backflow (reflux) of urine into the kidneys, which damage the kidneys and can cause progressive kidney failure.Genital abnormalities in people with caudal regression syndrome can include the urethra opening on the underside of the penis (hypospadias) or undescended testes (cryptorchidism). Some affected people may have an abnormal connection between the rectum and vagina (rectovaginal fistula). In severe cases, people with this condition may have underdeveloped genitalia (genital agenesis).People with caudal regression syndrome may have abnormal twisting (malrotation) of the large intestine, an obstruction of the anal opening (imperforate anus), soft out-pouchings in the lower abdomen (inguinal hernias), or other malformations of the gastrointestinal tract. Affected individuals are often constipated and may have difficulty with bowel control.The upper part of the body can also be affected. Some people with caudal regression syndrome have a heart condition or hearing problems.  u Pattern unknown Caudal dysgenesis syndrome Caudal dysplasia sequence Caudal regression sequence CRS Lumbo-sacral agenesis SA/CRS Sacral agenesis Sacral defect with anterior meningocele GTR C0300948 GTR C1838568 ICD-10-CM MeSH D013118 OMIM 600145 SNOMED CT 205425003 SNOMED CT 253189008 SNOMED CT 723973002 SNOMED CT 8301004 2023-09 2025-01-31 Celiac disease https://medlineplus.gov/genetics/condition/celiac-disease descriptionCeliac disease is a condition in which the immune system is abnormally sensitive to gluten, a protein found in wheat, rye, and barley. Celiac disease is an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Without a strict, lifelong gluten-free diet, inflammation resulting from immune system overactivity may cause a wide variety of signs and symptoms involving many parts of the body.Celiac disease can develop at any age after an individual starts eating foods containing gluten. The classic symptoms of the condition result from inflammation affecting the gastrointestinal tract. This inflammation damages the villi, which are small, finger-like projections that line the small intestine and provide a greatly increased surface area to absorb nutrients. In celiac disease, the villi become shortened and eventually flatten out. Intestinal damage causes diarrhea and poor absorption of nutrients, which may lead to weight loss. Abdominal pain, swelling (distention), and food intolerances are common in celiac disease. Inflammation associated with celiac disease may lead to an increased risk of developing certain gastrointestinal cancers such as cancers of the small intestine or esophagus.Inflammation and poor nutrient absorption may lead to problems affecting many other organs and systems of the body in affected individuals. These health problems may include iron deficiency that results in a low number of red blood cells (anemia), vitamin deficiencies, low bone mineral density (osteoporosis), itchy skin rashes (dermatitis herpetiformis), defects in the enamel of the teeth, chronic fatigue, joint pain, poor growth, delayed puberty, infertility, or repeated miscarriages. Neurological problems have also been associated with celiac disease; these include migraine headaches, depression, attention-deficit/hyperactivity disorder (ADHD), and recurrent seizures (epilepsy). Many people with celiac disease have one or more of these varied health problems but do not have gastrointestinal symptoms. This form of the condition is called nonclassic celiac disease. Researchers now believe that nonclassic celiac disease is actually more common than the classic form.Celiac disease often goes undiagnosed because many of its signs and symptoms are nonspecific, which means they may occur in many disorders. Most people who have one or more of these nonspecific health problems do not have celiac disease. On average, a diagnosis of celiac disease is not made until 6 to 10 years after symptoms begin.Some people have silent celiac disease, in which they have no symptoms of the disorder. However, people with silent celiac disease do have immune proteins in their blood (antibodies) that are common in celiac disease. They also have inflammatory damage to their small intestine that can be detected with a biopsy.In a small number of cases, celiac disease does not improve with a gluten-free diet and progresses to a condition called refractory sprue. Refractory sprue is characterized by chronic inflammation of the gastrointestinal tract, poor absorption of nutrients, and an increased risk of developing a type of cancer of the immune cells called T-cell lymphoma. u Pattern unknown HLA-DQB1 https://medlineplus.gov/genetics/gene/hla-dqb1 HLA-DQA1 https://medlineplus.gov/genetics/gene/hla-dqa1 Celiac sprue Gluten enteropathy Sprue GTR C0007570 ICD-10-CM K90.0 MeSH D002446 OMIM 212750 SNOMED CT 396331005 2011-10 2025-12-22 Central core disease https://medlineplus.gov/genetics/condition/central-core-disease descriptionCentral core disease is a disorder that affects muscles used for movement (skeletal muscles). This condition causes muscle weakness that ranges from barely noticeable to very severe. The severity of muscle weakness may differ even among affected members of the same family.Most people with central core disease experience persistent, mild muscle weakness that does not worsen with time. This weakness affects the muscles near the center of the body (proximal muscles), particularly muscles in the shoulders, upper legs, and hips. Muscle weakness in affected infants can delay the development of motor skills such as sitting, standing, and walking; most people with this condition are able to walk independently. Affected individuals may experience muscle pain (myalgia) or extreme fatigue in response to physical activity (exercise intolerance). Central core disease is also associated with eyes that do not look in the same direction (strabismus), a rounded upper back that also curves to the side (kyphoscoliosis), foot deformities, hip dislocation, and joint deformities called contractures that restrict the movement of certain joints. In severe cases, affected infants experience weakness in the muscles of the face, profound low muscle tone (hypotonia), and serious or life-threatening breathing problems.Many people with central core disease also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate (tachycardia) and body temperature (hyperthermia), abnormally fast breathing (tachypnea), muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.Central core disease gets its name from disorganized areas called central cores, which are typically found in the center of skeletal muscle cells, but can be at the edges or span the length of the cell, in many affected individuals. These abnormal regions can only been seen when muscle tissue is viewed under a microscope. These central cores are often present in cells with few or no mitochondria, which produce energy within cells. Although the presence of central cores can help doctors diagnose central core disease, it is unclear how they are related to muscle weakness and the other features of this condition. ar Autosomal recessive ad Autosomal dominant RYR1 https://medlineplus.gov/genetics/gene/ryr1 CCD CCO Central core myopathy Myopathy, central core Shy's disease Shy-Magee syndrome MeSH D020512 OMIM 117000 SNOMED CT 43152001 2007-10 2023-03-27 Central precocious puberty https://medlineplus.gov/genetics/condition/central-precocious-puberty descriptionCentral precocious puberty is a condition that causes early sexual development in girls and boys. While puberty normally starts between ages 8 and 13 in girls and between ages 9 and 14 in boys, girls with central precocious puberty begin exhibiting signs before age 8, and boys with this disorder begin before age 9. Signs of puberty include development of pubic and underarm hair, a rapid increase in height (commonly referred to as a "growth spurt"), acne, and underarm odor. Girls also develop breasts and begin their menstrual periods. Boys have growth of the penis and testes and deepening of the voice. Because of the early growth spurt, children with central precocious puberty may be taller than their peers; however, they may stop growing abnormally early. Without proper treatment, some affected individuals are shorter in adulthood compared with other members of their family. Developing ahead of their peers can be emotionally difficult for affected individuals and may lead to psychological and behavioral problems. ad Autosomal dominant MKRN3 https://medlineplus.gov/genetics/gene/mkrn3 KISS1 https://www.ncbi.nlm.nih.gov/gene/3814 KISS1R https://www.ncbi.nlm.nih.gov/gene/84634 CPP Gonadotropin-dependent precocious puberty GTR C3805879 GTR C3809199 ICD-10-CM E30.1 MeSH D011629 OMIM 176400 OMIM 615346 SNOMED CT 237816004 2016-10 2024-09-17 Centronuclear myopathy https://medlineplus.gov/genetics/condition/centronuclear-myopathy descriptionCentronuclear myopathy is a condition characterized by muscle weakness (myopathy) and wasting (atrophy) in the skeletal muscles, which are the muscles used for movement. The severity of centronuclear myopathy varies among affected individuals, even among members of the same family.People with centronuclear myopathy begin experiencing muscle weakness at any time from birth to early adulthood. The muscle weakness slowly worsens over time and can lead to delayed development of motor skills, such as crawling or walking; muscle pain during exercise; and difficulty walking. Some affected individuals may need wheelchair assistance as the muscles atrophy and weakness becomes more severe. In rare instances, the muscle weakness improves over time.Some people with centronuclear myopathy experience mild to severe breathing problems related to the weakness of muscles needed for breathing. People with centronuclear myopathy may have droopy eyelids (ptosis) and weakness in other facial muscles, including the muscles that control eye movement. People with this condition may also have foot abnormalities, a high arch in the roof of the mouth (high-arched palate), and abnormal side-to-side curvature of the spine (scoliosis). Rarely, individuals with centronuclear myopathy have a weakened heart muscle (cardiomyopathy), disturbances in nerve function (neuropathy), or intellectual disability.A key feature of centronuclear myopathy is the displacement of the nucleus in muscle cells, which can be viewed under a microscope. Normally the nucleus is found at the edges of the rod-shaped muscle cells, but in people with centronuclear myopathy the nucleus is located in the center of these cells. How the change in location of the nucleus affects muscle cell function is unknown. ad Autosomal dominant ar Autosomal recessive DNM2 https://medlineplus.gov/genetics/gene/dnm2 RYR1 https://medlineplus.gov/genetics/gene/ryr1 TTN https://medlineplus.gov/genetics/gene/ttn BIN1 https://medlineplus.gov/genetics/gene/bin1 SPEG https://www.ncbi.nlm.nih.gov/gene/10290 CCDC78 https://www.ncbi.nlm.nih.gov/gene/124093 CNM Myopathy, centronuclear GTR C0175709 GTR C4014814 GTR C4707232 ICD-10-CM G71.2 MeSH D020914 OMIM 160150 OMIM 255200 OMIM 614807 OMIM 615959 SNOMED CT 240081004 SNOMED CT 716696006 2015-11 2023-08-18 Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy https://medlineplus.gov/genetics/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy descriptionCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, usually called CADASIL, is an inherited condition that causes stroke and other impairments. This condition affects blood flow in small blood vessels, particularly cerebral vessels within the brain. The muscle cells surrounding these blood vessels (vascular smooth muscle cells) are abnormal and gradually die. In the brain, the resulting blood vessel damage (arteriopathy) can cause migraines, often with visual sensations or auras, or recurrent seizures (epilepsy).Damaged blood vessels reduce blood flow and can cause areas of tissue death (infarcts) throughout the body. An infarct in the brain can lead to a stroke. In individuals with CADASIL, a stroke can occur at any time from childhood to late adulthood, but typically happens during mid-adulthood. People with CADASIL often have more than one stroke in their lifetime. Recurrent strokes can damage the brain over time. Strokes that occur in the subcortical region of the brain, which is involved in reasoning and memory, can cause progressive loss of intellectual function (dementia) and changes in mood and personality.Many people with CADASIL also develop leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).The age at which the signs and symptoms of CADASIL first begin varies greatly among affected individuals, as does the severity of these features.CADASIL is not associated with the common risk factors for stroke and heart attack, such as high blood pressure and high cholesterol, although some affected individuals might also have these health problems. ad Autosomal dominant NOTCH3 https://medlineplus.gov/genetics/gene/notch3 CADASIL Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy Familial vascular leukoencephalopathy Hereditary dementia, multi-infarct type GTR C4551768 MeSH D046589 OMIM 125310 SNOMED CT 390936003 2008-05 2020-08-18 Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy https://medlineplus.gov/genetics/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy descriptionCerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CARASIL, is an inherited condition that causes stroke and other impairments.Abnormalities affecting the brain and other parts of the nervous system become apparent in an affected person's twenties or thirties. Often, muscle stiffness (spasticity) in the legs and problems with walking are the first signs of the disorder. About half of affected individuals have a stroke or similar episode before age 40. As the disease progresses, most people with CARASIL also develop mood and personality changes, a decline in thinking ability (dementia), memory loss, and worsening problems with movement.Other characteristic features of CARASIL include premature hair loss (alopecia) and attacks of low back pain. The hair loss often begins during adolescence and is limited to the scalp. Back pain, which develops in early to mid-adulthood, results from the breakdown (degeneration) of the discs that separate the bones of the spine (vertebrae) from one another.The signs and symptoms of CARASIL worsen slowly with time. Over the course of several years, affected individuals become less able to control their emotions and communicate with others. They increasingly require help with personal care and other activities of daily living; after a few years, they become unable to care for themselves. Most affected individuals die within a decade after signs and symptoms first appear, although few people with the disease have survived for 20 to 30 years. ar Autosomal recessive HTRA1 https://medlineplus.gov/genetics/gene/htra1 CARASIL Familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension Maeda syndrome Nemoto disease GTR C1838577 MeSH D002539 OMIM 600142 SNOMED CT 703219008 2011-04 2020-08-18 Cerebral cavernous malformation https://medlineplus.gov/genetics/condition/cerebral-cavernous-malformation descriptionCerebral cavernous malformations are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls, and they lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, the blood vessels are prone to leakage, which can cause the health problems related to this condition. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the brain and spinal cord (which are described as cerebral).Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related health problems. Other people with this condition may experience serious signs and symptoms such as headaches, seizures, paralysis, hearing or vision loss, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time.There are two forms of the condition: familial and sporadic. The familial form is passed from parent to child, and affected individuals typically have multiple cerebral cavernous malformations. The sporadic form occurs in people with no family history of the disorder. These individuals typically have only one malformation. ad Autosomal dominant KRIT1 https://medlineplus.gov/genetics/gene/krit1 CCM2 https://medlineplus.gov/genetics/gene/ccm2 PDCD10 https://medlineplus.gov/genetics/gene/pdcd10 Cavernoma Cavernous angioma CCM Central nervous system cavernous hemangioma Cerebral cavernous hemangioma Familial cavernous hemangioma Familial cavernous malformation Familial cerebral cavernous angioma Familial cerebral cavernous malformation Intracerebral cavernous hemangioma GTR C1366911 GTR C1864040 GTR C1864041 GTR C2919945 MeSH D020786 OMIM 116860 SNOMED CT 444869007 2012-11 2024-09-17 Cerebral folate transport deficiency https://medlineplus.gov/genetics/condition/cerebral-folate-transport-deficiency descriptionCerebral folate transport deficiency is a disorder that develops from a shortage (deficiency) of the B-vitamin folate (also called vitamin B9) in the brain. Affected children have normal development during infancy, but around age 2 they begin to lose previously acquired mental and movement abilities (psychomotor regression). They develop intellectual disability, speech difficulties, and recurrent seizures (epilepsy). Movement problems such as tremors and difficulty coordinating movements (ataxia) can be severe, and some affected individuals need wheelchair assistance. Affected individuals have leukodystrophy, which is a loss of a type of brain tissue known as white matter. White matter consists of nerve fibers covered by a fatty substance called myelin that promotes the rapid transmission of nerve impulses. Leukodystrophy contributes to the neurological problems that occur in cerebral folate transport deficiency. Without treatment, these neurological problems worsen over time. ar Autosomal recessive FOLR1 https://medlineplus.gov/genetics/gene/folr1 Cerebral folate deficiency FOLR1 deficiency Neurodegeneration due to cerebral folate transport deficiency GTR C2751584 MeSH D019150 OMIM 613068 SNOMED CT 711403001 2014-09 2020-08-18 Cerebro-facio-thoracic dysplasia https://medlineplus.gov/genetics/condition/cerebro-facio-thoracic-dysplasia descriptionCerebro-facio-thoracic dysplasia is a rare condition characterized by abnormal development (dysplasia) of the brain (cerebro) and structures in the face (facio) and torso (thoracic). The problems with development lead to the key features of cerebro-facio-thoracic dysplasia, which include severe intellectual disability, distinctive facial features, and abnormalities of the ribs and spinal bones (vertebrae).In addition to intellectual disability, individuals with cerebro-facio-thoracic dysplasia have delayed development of speech and movement (motor) skills, and in some, these skills never develop. Nearly one-quarter of affected individuals never learn to speak and almost half are unable to walk. Weak muscle tone (hypotonia) and difficulty feeding occur in some affected infants. People with cerebro-facio-thoracic dysplasia can have neurodevelopmental problems, such as anxiety, autism spectrum disorder, or self-injuring behavior; however, many people with the condition are described as friendly and good-natured.Distinctive facial features common in cerebro-facio-thoracic dysplasia include a wide, short skull (brachycephaly); highly arched eyebrows or eyebrows that grow together in the middle (synophrys); widely spaced eyes (hypertelorism); a wide nasal bridge; low-set ears; an upper lip with pronounced curves (Cupid's bow upper lip); and small teeth (microdontia). Some affected individuals have overgrowth of the gums (gingival hyperplasia), an opening in the roof of the mouth (cleft palate), or a split in the upper lip (cleft lip).Problems with bone development in the torso (thorax) commonly leads to bone abnormalities such as two or more ribs that are joined together (fused) or ribs that are abnormally shaped with two prongs at one end (bifid ribs). Many people with cerebro-facio-thoracic dysplasia have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae; some vertebrae may also be fused. Additionally, the shoulder blades can be affected in people with this condition.A wide variety of other features can occur in cerebro-facio-thoracic dysplasia, such as abnormalities involving the eyes, skin, or hair. Heart defects, digestive problems, or genitourinary problems (such as abnormal kidneys or reproductive organs) can also occur. Affected individuals may also have bone or joint abnormalities in other parts of the body. ar Autosomal recessive TMCO1 https://medlineplus.gov/genetics/gene/tmco1 Cerebrofaciothoracic dysplasia CFSMR CFTD Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome Pascual-Castroviejo syndrome TMCO1 defect syndrome GTR C1859252 MeSH D008607 MeSH D019465 OMIM 213980 SNOMED CT 720635002 2019-03 2023-07-12 Cerebrotendinous xanthomatosis https://medlineplus.gov/genetics/condition/cerebrotendinous-xanthomatosis descriptionCerebrotendinous xanthomatosis is a disorder characterized by abnormal storage of fats (lipids) in many areas of the body. People with this disorder cannot break down certain lipids effectively, specifically different forms of cholesterol, so these fats accumulate in the body in the form of fatty yellow nodules called xanthomas. These xanthomas are most commonly found in the brain and in connective tissue called tendons that attach muscle to bone, which is reflected in the condition name (cerebro- meaning brain and -tendinous referring to tendons).People with cerebrotendinous xanthomatosis often develop neurological problems in early adulthood that are thought to be caused by an abnormal accumulation of fats and an increasing number of xanthomas in the brain. These neurological problems include recurrent seizures (epilepsy), movement disorders, impaired speech (dysarthria), loss of sensation in the arms and legs (peripheral neuropathy), decline in intellectual function (dementia), hallucinations, and depression. Xanthomas can accumulate in the fatty substance that insulates and protects nerves (myelin), causing the destruction of myelin and disrupting nerve signaling in the brain. Degeneration (atrophy) of brain tissue caused by excess lipid deposits also contributes to the neurological problems.Xanthomas in the tendons begin to form in early adulthood. The most common areas for xanthomas to develop are tendons in the hands, elbows, knees, neck, and in the Achilles tendon, which connects the heel of the foot to the calf muscles in the leg. Tendon xanthomas may cause discomfort and interfere with tendon flexibility. While many affected people develop tendon xanthomas, these nodules may not be easily visible underneath the skin.Other features of cerebrotendinous xanthomatosis include clouding of the lenses of the eyes (cataracts) and chronic diarrhea in childhood; a reduced ability to produce and release a digestive fluid called bile (cholestasis), which can lead to a yellowing of the skin or whites of the eyes (jaundice); and progressively brittle bones that are prone to fracture (osteoporosis). People with cerebrotendinous xanthomatosis are also at an increased risk of developing cardiovascular disease or respiratory failure because of lipid accumulation in the heart or lungs, respectively. If untreated, the signs and symptoms related to cerebrotendinous xanthomatosis worsen over time; however, this condition varies greatly among those who are affected. ar Autosomal recessive CYP27A1 https://medlineplus.gov/genetics/gene/cyp27a1 Cerebral cholesterinosis Cerebrotendinous cholesterinosis Cholestanol storage disease Cholestanolosis CTX Van Bogaert-Scherer-Epstein disease GTR C0238052 ICD-10-CM E75.5 MeSH D019294 OMIM 213700 SNOMED CT 63246000 2008-03 2020-08-18 Chanarin-Dorfman syndrome https://medlineplus.gov/genetics/condition/chanarin-dorfman-syndrome descriptionChanarin-Dorfman syndrome is a condition in which fats (lipids) build up in the body. Affected individuals have trouble breaking down certain fats called triglycerides; these fats then accumulate in organs and tissues, including the skin, liver, muscles, intestine, and bone marrow. People with Chanarin-Dorfman syndrome have dry, scaly skin (ichthyosis), which is usually present at birth. They may also have lower eyelids that turn out so that the inner surface is exposed (ectropion). Additional features of Chanarin-Dorfman syndrome may include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts), hearing loss, short stature, progressive muscle weakness (myopathy), and intellectual disabilities. Some people with Chanarin-Dorfman syndrome develop liver failure. The signs and symptoms of Chanarin-Dorfman syndrome can vary greatly among individuals, which can delay the diagnosis of the condition. ar Autosomal recessive ABHD5 https://medlineplus.gov/genetics/gene/abhd5 CDS Chanarin-Dorfman disease DCS Dorfman-Chanarin disease Dorfman-Chanarin syndrome Ichthyosiform Erythroderma with Leukocyte Vacuolation Ichthyotic neutral lipid storage disease Neutral lipid storage disease with ichthyosis NLSDI Triglyceride storage disease with ichthyosis Triglyceride storage disease with impaired long-chain fatty acid oxidation GTR C0268238 ICD-10-CM MeSH D008052 OMIM 275630 SNOMED CT 19604005 2024-05 2024-05-07 Channelopathy-associated congenital insensitivity to pain https://medlineplus.gov/genetics/condition/channelopathy-associated-congenital-insensitivity-to-pain descriptionChannelopathy-associated congenital insensitivity to pain is a condition that inhibits the ability to perceive physical pain. From birth, affected individuals never feel pain in any part of their body when injured. People with this condition can feel the difference between sharp and dull and hot and cold, but they cannot sense, for example, that a hot beverage is burning their tongue. Pain is a vital signal that helps people avoid danger and injuries. People who cannot feel pain experience more  injuries and may have shorter life expectancies.The first signs of channelopathy-associated congenital insensitivity to pain often occur when an infant shows no response to stimuli such as an injury or medical procedures like vaccines. Young children with this condition may have wounds from biting or burning themselves.A lack of pain awareness often leads individuals to develop wounds, bruises, broken bones, and other health issues that may go undetected. Long lasting joint injuries (often occurring alongside broken bones) can lead to joint deformities and often the loss of normal use of that body part. Eye injuries that go unnoticed can lead to vision loss. Many people with channelopathy-associated congenital insensitivity to pain also have a complete loss of the sense of smell (anosmia).Channelopathy-associated congenital insensitivity to pain is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. ar Autosomal recessive SCN9A https://medlineplus.gov/genetics/gene/scn9a Asymbolia for pain Channelopathy-associated insensitivity to pain CIP CIP-SCN9A Congenital analgesia Congenital indifference to pain Congenital pain indifference Indifference to pain, congenital, autosomal recessive Pain insensitivity, congenital GTR C1855739 ICD-10-CM MeSH D000699 OMIM 243000 SNOMED CT 403605007 2023-05 2023-05-18 Char syndrome https://medlineplus.gov/genetics/condition/char-syndrome descriptionChar syndrome is a condition that affects the development of the face, heart, and limbs. It is characterized by a combination of three major features: a distinctive facial appearance, a heart defect called patent ductus arteriosus, and hand abnormalities.Most people with Char syndrome have a characteristic facial appearance that includes flattened cheek bones and a flat nasal bridge (the area of the nose between the eyes). The tip of the nose is also flat and broad. The eyes are wide-set with droopy eyelids (ptosis) and outside corners that point downward (down-slanting palpebral fissures). Additional facial differences include a shortened distance between the nose and upper lip (a short philtrum), a triangular-shaped mouth, and thick, prominent lips.Patent ductus arteriosus is a common heart defect in newborns, and it occurs in most babies with Char syndrome. Before birth, the ductus arteriosus forms a connection between two major arteries (the aorta and the pulmonary artery). This connection normally closes shortly after birth, but it remains open in babies with patent ductus arteriosus. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly. In severe cases, it can lead to heart failure. People with patent ductus arteriosus also have an increased risk of infection.Hand abnormalities are another feature of Char syndrome. In most people with this condition, the middle section of the fifth (pinky) finger is shortened or absent. Other abnormalities of the hands and feet have been reported but are less common. ad Autosomal dominant TFAP2B https://medlineplus.gov/genetics/gene/tfap2b Patent ductus arteriosus with facial dysmorphism and abnormal fifth digits GTR C1868570 MeSH D000015 MeSH D004374 OMIM 169100 SNOMED CT 703534001 2022-08 2022-08-08 Charcot-Marie-Tooth disease https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease descriptionCharcot-Marie-Tooth disease encompasses a group of disorders called hereditary sensory and motor neuropathies that damage the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves that worsens over time can result in alteration or loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity and age of onset even among members of the same family. Some people never realize they have the disorder because their symptoms are so mild, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in very rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy.Typically, the earliest symptoms of Charcot-Marie-Tooth disease result from muscle atrophy in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (steppage gait) and increase the risk of ankle injuries and tripping. As the disease worsens, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair.Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with Charcot-Marie-Tooth disease typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In rare cases, affected individuals have loss of vision or gradual hearing loss that sometimes leads to deafness.There are several types of Charcot-Marie-Tooth disease, which are differentiated by their effects on nerve cells and patterns of inheritance. Type 1 (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to transmit nerve impulses. These abnormalities slow the transmission of nerve impulses and can affect the health of the nerve fiber. Type 2 (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body to muscles or to sense organs. These abnormalities reduce the strength of the nerve impulse. People with CMT2 may develop amyotrophic lateral sclerosis (ALS), a condition characterized by progressive muscle weakness, a loss of muscle mass, and an inability to control movement.In forms of Charcot-Marie-Tooth disease classified as intermediate type, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both myelin and axons. Type 4 (CMT4) is distinguished from the other types by its pattern of inheritance; it can affect either the axons or the myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in genes on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) indicate different genetic causes.Sometimes other, historical names are used to refer to particular forms of  Charcot-Marie-Tooth disease. For example, Roussy-Levy syndrome is a form of CMT11 with the additional feature of rhythmic shaking (tremors).  Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called type 3 (CMT3). Depending on the specific gene that is altered, this severe, early-onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome. ad Autosomal dominant xd X-linked dominant ar Autosomal recessive PMP22 https://medlineplus.gov/genetics/gene/pmp22 MPZ https://medlineplus.gov/genetics/gene/mpz KIF1B https://medlineplus.gov/genetics/gene/kif1b GJB1 https://medlineplus.gov/genetics/gene/gjb1 GARS1 https://medlineplus.gov/genetics/gene/gars1 ATP7A https://medlineplus.gov/genetics/gene/atp7a LMNA https://medlineplus.gov/genetics/gene/lmna SETX https://medlineplus.gov/genetics/gene/setx HSPB1 https://medlineplus.gov/genetics/gene/hspb1 MFN2 https://medlineplus.gov/genetics/gene/mfn2 DNM2 https://medlineplus.gov/genetics/gene/dnm2 BSCL2 https://medlineplus.gov/genetics/gene/bscl2 MT-ATP6 https://medlineplus.gov/genetics/gene/mt-atp6 DCTN1 https://medlineplus.gov/genetics/gene/dctn1 SLC12A6 https://medlineplus.gov/genetics/gene/slc12a6 VCP https://medlineplus.gov/genetics/gene/vcp SPG11 https://medlineplus.gov/genetics/gene/spg11 HSPB8 https://medlineplus.gov/genetics/gene/hspb8 PRPS1 https://medlineplus.gov/genetics/gene/prps1 IGHMBP2 https://medlineplus.gov/genetics/gene/ighmbp2 SPTLC1 https://medlineplus.gov/genetics/gene/sptlc1 NAGLU https://medlineplus.gov/genetics/gene/naglu SURF1 https://medlineplus.gov/genetics/gene/surf1 TRPV4 https://medlineplus.gov/genetics/gene/trpv4 DYNC1H1 https://medlineplus.gov/genetics/gene/dync1h1 DNMT1 https://medlineplus.gov/genetics/gene/dnmt1 MPV17 https://medlineplus.gov/genetics/gene/mpv17 HINT1 https://medlineplus.gov/genetics/gene/hint1 ATP1A1 https://medlineplus.gov/genetics/gene/atp1a1 AARS1 https://www.ncbi.nlm.nih.gov/gene/16 COX6A1 https://www.ncbi.nlm.nih.gov/gene/1337 DRP2 https://www.ncbi.nlm.nih.gov/gene/1821 EGR2 https://www.ncbi.nlm.nih.gov/gene/1959 HARS1 https://www.ncbi.nlm.nih.gov/gene/3035 HK1 https://www.ncbi.nlm.nih.gov/gene/3098 DNAJB2 https://www.ncbi.nlm.nih.gov/gene/3300 KARS1 https://www.ncbi.nlm.nih.gov/gene/3735 KIF5A https://www.ncbi.nlm.nih.gov/gene/3798 MARS1 https://www.ncbi.nlm.nih.gov/gene/4141 MME https://www.ncbi.nlm.nih.gov/gene/4311 NEFH https://www.ncbi.nlm.nih.gov/gene/4744 NEFL https://www.ncbi.nlm.nih.gov/gene/4747 PDK3 https://www.ncbi.nlm.nih.gov/gene/5165 SBF1 https://www.ncbi.nlm.nih.gov/gene/6305 WARS1 https://www.ncbi.nlm.nih.gov/gene/7453 RAB7A https://www.ncbi.nlm.nih.gov/gene/7879 CNTNAP1 https://www.ncbi.nlm.nih.gov/gene/8506 YARS1 https://www.ncbi.nlm.nih.gov/gene/8565 SGPL1 https://www.ncbi.nlm.nih.gov/gene/8879 MCM3AP https://www.ncbi.nlm.nih.gov/gene/8888 MTMR2 https://www.ncbi.nlm.nih.gov/gene/8898 HSPB3 https://www.ncbi.nlm.nih.gov/gene/8988 AIFM1 https://www.ncbi.nlm.nih.gov/gene/9131 LITAF https://www.ncbi.nlm.nih.gov/gene/9516 BAG3 https://www.ncbi.nlm.nih.gov/gene/9531 ARHGEF10 https://www.ncbi.nlm.nih.gov/gene/9639 FIG4 https://www.ncbi.nlm.nih.gov/gene/9896 SCO2 https://www.ncbi.nlm.nih.gov/gene/9997 SIGMAR1 https://www.ncbi.nlm.nih.gov/gene/10280 NDRG1 https://www.ncbi.nlm.nih.gov/gene/10397 DCTN2 https://www.ncbi.nlm.nih.gov/gene/10540 MORC2 https://www.ncbi.nlm.nih.gov/gene/22880 TRIM2 https://www.ncbi.nlm.nih.gov/gene/23321 ABHD12 https://www.ncbi.nlm.nih.gov/gene/26090 PTRH2 https://www.ncbi.nlm.nih.gov/gene/51651 GDAP1 https://www.ncbi.nlm.nih.gov/gene/54332 DHTKD1 https://www.ncbi.nlm.nih.gov/gene/55526 JPH1 https://www.ncbi.nlm.nih.gov/gene/56704 PLEKHG5 https://www.ncbi.nlm.nih.gov/gene/57449 PRX https://www.ncbi.nlm.nih.gov/gene/57716 GNB4 https://www.ncbi.nlm.nih.gov/gene/59345 INF2 https://www.ncbi.nlm.nih.gov/gene/64423 COA7 https://www.ncbi.nlm.nih.gov/gene/65260 SH3TC2 https://www.ncbi.nlm.nih.gov/gene/79628 SBF2 https://www.ncbi.nlm.nih.gov/gene/81846 MED25 https://www.ncbi.nlm.nih.gov/gene/81857 LRSAM1 https://www.ncbi.nlm.nih.gov/gene/90678 SLC25A46 https://www.ncbi.nlm.nih.gov/gene/91137 FGD4 https://www.ncbi.nlm.nih.gov/gene/121512 17 https://medlineplus.gov/genetics/chromosome/17 Charcot-Marie-Tooth hereditary neuropathy Charcot-Marie-Tooth syndrome CMT Hereditary motor and sensory neuropathy HMSN Peroneal muscular atrophy PMA GTR C0007959 ICD-10-CM G60.0 MeSH D002607 OMIM 118200 OMIM 118210 OMIM 118220 OMIM 118230 OMIM 118300 OMIM 145900 OMIM 148360 OMIM 180800 OMIM 214370 OMIM 214400 OMIM 256855 OMIM 302800 OMIM 310490 OMIM 311070 OMIM 600361 OMIM 600882 OMIM 601098 OMIM 601152 OMIM 601382 OMIM 601455 OMIM 601472 OMIM 601596 OMIM 604563 OMIM 605253 OMIM 605285 OMIM 605588 OMIM 605589 OMIM 606071 OMIM 606482 OMIM 606595 OMIM 607677 OMIM 607678 OMIM 607684 OMIM 607706 OMIM 607734 OMIM 607736 OMIM 607791 OMIM 607831 OMIM 608323 OMIM 608340 OMIM 608673 OMIM 609260 OMIM 609311 OMIM 611228 OMIM 613287 OMIM 614228 OMIM 614436 OMIM 614455 OMIM 616505 SNOMED CT 398100001 SNOMED CT 45853006 2018-10 2023-03-27 Chediak-Higashi syndrome https://medlineplus.gov/genetics/condition/chediak-higashi-syndrome descriptionChediak-Higashi syndrome is a condition that affects many parts of the body, particularly the immune system. This disease damages immune system cells, leaving them less able to fight off invaders such as viruses and bacteria. As a result, most people with Chediak-Higashi syndrome have repeated and persistent infections starting in infancy or early childhood. These infections tend to be very serious or life-threatening.Chediak-Higashi syndrome is also characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and light-colored hair, often with a metallic sheen. Oculocutaneous albinism also causes vision problems such as reduced sharpness; rapid, involuntary eye movements (nystagmus); and increased sensitivity to light (photophobia).Many people with Chediak-Higashi syndrome have problems with blood clotting (coagulation) that lead to easy bruising and abnormal bleeding. In adulthood, Chediak-Higashi syndrome can also affect the nervous system, causing weakness, clumsiness, difficulty with walking, and seizures.If the disease is not successfully treated, most children with Chediak-Higashi syndrome reach a stage of the disorder known as the accelerated phase. This severe phase of the disease is thought to be triggered by a viral infection. In the accelerated phase, white blood cells (which normally help fight infection) divide uncontrollably and invade many of the body's organs. The accelerated phase is associated with fever, episodes of abnormal bleeding, overwhelming infections, and organ failure. These medical problems are usually life-threatening in childhood.A small percentage of people with Chediak-Higashi syndrome have a milder form of the condition that appears later in life. People with the adult form of the disorder have less noticeable changes in pigmentation and are less likely to have recurrent, severe infections. They do, however, have a significant risk of progressive neurological problems such as tremors, difficulty with movement and balance (ataxia), reduced sensation and weakness in the arms and legs (peripheral neuropathy), and a decline in intellectual functioning. ar Autosomal recessive LYST https://medlineplus.gov/genetics/gene/lyst Chediak-Steinbrinck-Higashi syndrome CHS Oculocutaneous albinism with leukocyte defect GTR C0007965 ICD-10-CM E70.330 MeSH D002609 OMIM 214500 SNOMED CT 111396008 2008-02 2023-03-21 Cherubism https://medlineplus.gov/genetics/condition/cherubism descriptionCherubism is a disorder characterized by abnormal bone tissue in the jaw. Beginning in early childhood, both the lower jaw (the mandible) and the upper jaw (the maxilla) become enlarged as bone is replaced with painless, cyst-like growths. These growths give the cheeks a swollen, rounded appearance and often interfere with normal tooth development. In some people the condition is so mild that it may not be noticeable, while other cases are severe enough to cause problems with vision, breathing, speech, and swallowing. Enlargement of the jaw usually continues throughout childhood and stabilizes during puberty. The abnormal growths are gradually replaced with normal bone in early adulthood. As a result, many affected adults have a normal facial appearance.Most people with cherubism have few, if any, signs and symptoms affecting other parts of the body. Rarely, however, this condition occurs as part of another genetic disorder. For example, abnormal jaw growth, like that in cherubism, can occur in Ramon syndrome, which also involves short stature, intellectual disability, and overgrowth of the gums (gingival fibrosis). Additionally, cherubism-like growths have been reported in rare cases of Noonan syndrome (a developmental disorder characterized by unusual facial characteristics, short stature, and heart defects), fragile X syndrome (a condition primarily affecting males that causes learning disabilities and cognitive impairment), and neurofibromatosis type 1 (a condition primarily characterized by multiple skin tumors). ad Autosomal dominant SH3BP2 https://medlineplus.gov/genetics/gene/sh3bp2 Familial benign giant-cell tumor of the jaw Familial fibrous dysplasia of jaw Familial multilocular cystic disease of the jaws GTR C0008029 MeSH D002636 OMIM 118400 SNOMED CT 76098004 2020-03 2021-06-01 Childhood absence epilepsy https://medlineplus.gov/genetics/condition/childhood-absence-epilepsy descriptionChildhood absence epilepsy is a condition characterized by recurrent seizures (epilepsy). This condition begins in childhood, usually between ages 3 and 8. Affected children have absence seizures (also known as petit mal seizures), which are brief episodes of impaired consciousness that look like staring spells. During seizures, children are not aware of and do not respond to people or activities around them. The seizures usually last several seconds and they occur often, up to 200 times each day.Some affected individuals have febrile seizures before they develop childhood absence epilepsy. Febrile seizures are involuntary muscle contractions (convulsions) brought on by a high body temperature (fever).In most people with childhood absence epilepsy, the absence seizures disappear in adolescence. However, some affected individuals continue to have absence seizures into adulthood, or they may develop generalized tonic-clonic seizures, which cause muscle rigidity, convulsions, and loss of consciousness, or myoclonic seizures, which are characterized by rapid, uncontrolled muscle jerks. ad Autosomal dominant GABRA1 https://medlineplus.gov/genetics/gene/gabra1 GABRB3 https://www.ncbi.nlm.nih.gov/gene/2562 GABRG2 https://www.ncbi.nlm.nih.gov/gene/2566 JRK https://www.ncbi.nlm.nih.gov/gene/8629 CACNA1H https://www.ncbi.nlm.nih.gov/gene/8912 Absence epilepsy, childhood Petit mal epilepsy Pykno-epilepsy Pyknolepsy GTR C1838604 GTR C1843244 GTR C1970160 GTR C2677087 GTR C2749872 GTR No longer reported MeSH D004832 OMIM 600131 OMIM 607681 OMIM 611942 OMIM 612269 SNOMED CT 50866000 2018-08 2020-08-18 Childhood myocerebrohepatopathy spectrum https://medlineplus.gov/genetics/condition/childhood-myocerebrohepatopathy-spectrum descriptionChildhood myocerebrohepatopathy spectrum, commonly called MCHS, is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. MCHS typically becomes apparent in children from a few months to 3 years old. People with this condition usually have problems with their muscles (myo-), brain (cerebro-), and liver (hepato-).Common signs and symptoms of MCHS include muscle weakness (myopathy), developmental delay or a deterioration of intellectual function, and liver disease. Another possible sign of this condition is a toxic buildup of lactic acid in the body (lactic acidosis). Often, affected children are unable to gain weight and grow at the expected rate (failure to thrive).Additional signs and symptoms of MCHS can include a form of kidney disease called renal tubular acidosis, inflammation of the pancreas (pancreatitis), recurrent episodes of nausea and vomiting (cyclic vomiting), or hearing loss. ar Autosomal recessive POLG https://medlineplus.gov/genetics/gene/polg MCHS GTR C0205710 MeSH D028361 SNOMED CT 702366001 2011-06 2020-08-18 Cholangiocarcinoma https://medlineplus.gov/genetics/condition/cholangiocarcinoma descriptionCholangiocarcinoma is a group of cancers that begin in the bile ducts. Bile ducts are branched tubes that connect the liver and gallbladder to the small intestine. They carry bile, which is a fluid that helps the body digest fats that are in food. Bile is made in the liver and stored in the gallbladder before being released in the small intestine after a person eats.Cholangiocarcinoma is classified by its location in relation to the liver. Intrahepatic cholangiocarcinoma begins in the small bile ducts within the liver. This is the least common form of the disease, accounting for less than 10 percent of all cases. Perihilar cholangiocarcinoma (also known as a Klatskin tumor) begins in an area called the hilum, where the right and left major bile ducts join and leave the liver. It is the most common form of the disease, accounting for more than half of all cases. The remaining cases are classified as distal cholangiocarcinomas, which begin in bile ducts outside the liver. The perihilar and distal forms of the disease, which both occur outside the liver, are sometimes grouped together and called extrahepatic cholangiocarcinoma.The three types of cholangiocarcinoma do not usually cause any symptoms in their early stages, and this cancer is usually not diagnosed until it has already spread beyond the bile ducts to other tissues. Symptoms often result when bile ducts become blocked by the tumor. The most common symptom is jaundice, in which the skin and whites of the eyes turn yellow. Other symptoms can include extreme tiredness (fatigue), itching, dark-colored urine, loss of appetite, unintentional weight loss, abdominal pain, and light-colored and greasy stools. These symptoms are described as "nonspecific" because they can be features of many different diseases.Most people who develop cholangiocarcinoma are older than 65. Because this cancer is often not discovered until it has already spread, it can be challenging to treat effectively. Affected individuals can survive for several months to several years after diagnosis, depending on the location of the cancer and how advanced it is. u Pattern unknown n Not inherited RB1 https://medlineplus.gov/genetics/gene/rb1 FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 BRCA1 https://medlineplus.gov/genetics/gene/brca1 BRCA2 https://medlineplus.gov/genetics/gene/brca2 TP53 https://medlineplus.gov/genetics/gene/tp53 PTEN https://medlineplus.gov/genetics/gene/pten TSC1 https://medlineplus.gov/genetics/gene/tsc1 NF1 https://medlineplus.gov/genetics/gene/nf1 SMAD4 https://medlineplus.gov/genetics/gene/smad4 KRAS https://medlineplus.gov/genetics/gene/kras BRAF https://medlineplus.gov/genetics/gene/braf GNAS https://medlineplus.gov/genetics/gene/gnas TERT https://medlineplus.gov/genetics/gene/tert NRAS https://medlineplus.gov/genetics/gene/nras ARID1A https://medlineplus.gov/genetics/gene/arid1a IDH2 https://medlineplus.gov/genetics/gene/idh2 LAMA2 https://medlineplus.gov/genetics/gene/lama2 IDH1 https://medlineplus.gov/genetics/gene/idh1 PIK3CA https://medlineplus.gov/genetics/gene/pik3ca EGFR https://medlineplus.gov/genetics/gene/egfr BAP1 https://medlineplus.gov/genetics/gene/bap1 ARAF https://www.ncbi.nlm.nih.gov/gene/369 CDK6 https://www.ncbi.nlm.nih.gov/gene/1021 ERBB3 https://www.ncbi.nlm.nih.gov/gene/2065 MET https://www.ncbi.nlm.nih.gov/gene/4233 PEG3 https://www.ncbi.nlm.nih.gov/gene/5178 PTPN3 https://www.ncbi.nlm.nih.gov/gene/5774 ROBO2 https://www.ncbi.nlm.nih.gov/gene/6092 NDC80 https://www.ncbi.nlm.nih.gov/gene/10403 RNF43 https://www.ncbi.nlm.nih.gov/gene/54894 PBRM1 https://www.ncbi.nlm.nih.gov/gene/55193 RADIL https://www.ncbi.nlm.nih.gov/gene/55698 PCDHA13 https://www.ncbi.nlm.nih.gov/gene/56136 KMT2C https://www.ncbi.nlm.nih.gov/gene/58508 CC Cholangiocarcinoma of biliary tract Cholangiocellular carcinoma Distal cholangiocarcinoma Extrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma Perihilar cholangiocarcinoma GTR C3810156 ICD-10-CM C22.1 MeSH D018281 OMIM 615619 SNOMED CT 312104005 SNOMED CT 70179006 2016-08 2020-08-18 Chordoma https://medlineplus.gov/genetics/condition/chordoma descriptionA chordoma is a rare type of cancerous tumor that can occur anywhere along the spine, from the base of the skull to the tailbone. Chordomas grow slowly, gradually extending into the bone and soft tissue around them. They often recur after treatment, and in about 40 percent of cases the cancer spreads (metastasizes) to other areas of the body, such as the lungs.Approximately half of all chordomas occur at the base of the spine (sacrum), about one third occur in the base of the skull (occiput), and the rest occur in the cervical (neck), thoracic (upper back), or lumbar (lower back) vertebrae of the spine. As the chordoma grows, it puts pressure on the adjacent areas of the brain or spinal cord, leading to the signs and symptoms of the disorder. A chordoma anywhere along the spine may cause pain, weakness, or numbness in the back, arms, or legs. A chordoma at the base of the skull (occipital chordoma) may lead to double vision (diplopia) and headaches. A chordoma that occurs in the tailbone (coccygeal chordoma) may result in a lump large enough to be felt through the skin and may cause problems with bladder or bowel function.Chordomas typically occur in adults between ages 40 and 70. About 5 percent of chordomas are diagnosed in children. For reasons that are unclear, males are affected about twice as often as females. ad Autosomal dominant n Not inherited TBXT https://medlineplus.gov/genetics/gene/tbxt CHDM Chordocarcinoma Chordoepithelioma Notochordal sarcoma Notochordoma GTR C0008487 ICD-10-CM C41.2 MeSH D002817 OMIM 215400 SNOMED CT 50007008 2012-01 2020-08-18 Chorea-acanthocytosis https://medlineplus.gov/genetics/condition/chorea-acanthocytosis descriptionChorea-acanthocytosis is primarily a neurological disorder that affects movement in many parts of the body. Chorea refers to the involuntary jerking movements made by people with this disorder. People with this condition also have abnormal star-shaped red blood cells (acanthocytosis). This condition is one of a group of conditions called neuroacanthocytoses that involve neurological problems and abnormal red blood cells.In addition to chorea, another common feature of chorea-acanthocytosis is involuntary tensing of various muscles (dystonia), such as those in the limbs, face, mouth, tongue, and throat. These muscle twitches can cause vocal tics (such as grunting), involuntary belching, and limb spasms. Eating can also be impaired as tongue and throat twitches can interfere with chewing and swallowing food. People with chorea-acanthocytosis may uncontrollably bite their tongue, lips, and inside of the mouth. Nearly half of all people with chorea-acanthocytosis have seizures.Individuals with chorea-acanthocytosis may develop difficulty processing, learning, and remembering information (cognitive impairment). They may have reduced sensation and weakness in their arms and legs (peripheral neuropathy) and muscle weakness (myopathy). Impaired muscle and nerve functioning commonly cause speech difficulties in individuals with this condition, and can lead to an inability to speak.Behavioral changes are a common feature of chorea-acanthocytosis and may be the first sign of this condition. These behavioral changes may include changes in personality, obsessive-compulsive disorder (OCD), lack of self-restraint, and the inability to take care of oneself.The signs and symptoms of chorea-acanthocytosis usually begin in early to mid-adulthood. The movement problems of this condition worsen with age. Loss of cells (atrophy) in certain brain regions is the major cause of the neurological problems seen in people with chorea-acanthocytosis. ar Autosomal recessive VPS13A https://medlineplus.gov/genetics/gene/vps13a CHAC Choreoacanthocytosis Neuroacanthocytosis GTR C0393576 MeSH D054546 OMIM 200150 SNOMED CT 26848004 SNOMED CT 66881004 2008-05 2020-08-18 Choroideremia https://medlineplus.gov/genetics/condition/choroideremia descriptionChoroideremia is a condition characterized by progressive vision loss that mainly affects males. The first symptom of this condition is usually an impairment of night vision (night blindness), which can occur in early childhood. A progressive narrowing of the field of vision (tunnel vision) follows, as well as a decrease in the ability to see details (visual acuity). These vision problems are due to an ongoing loss of cells (atrophy) in the specialized light-sensitive tissue that lines the back of the eye (retina) and a nearby network of blood vessels (the choroid). The vision impairment in choroideremia worsens over time, but the progression varies among affected individuals. However, all individuals with this condition will develop blindness, most commonly in late adulthood. xr X-linked recessive CHM https://medlineplus.gov/genetics/gene/chm Choroidal sclerosis Progressive tapetochoroidal dystrophy TCD GTR C0008525 ICD-10-CM H31.21 MeSH D015794 OMIM 303100 SNOMED CT 15989831000119105 SNOMED CT 75241009 2008-07 2020-08-18 Christianson syndrome https://medlineplus.gov/genetics/condition/christianson-syndrome descriptionChristianson syndrome is a disorder that primarily affects the nervous system. This condition becomes apparent in infancy. Its characteristic features include delayed development, intellectual disability, an inability to speak, problems with balance and coordination (ataxia), and difficulty standing or walking. Individuals who do learn to walk lose the ability in childhood. Most affected children also have recurrent seizures (epilepsy), beginning between ages 1 and 2.Other features seen in many people with Christianson syndrome include a small head size (microcephaly); a long, narrow face with prominent nose, jaw, and ears; an open mouth and uncontrolled drooling; and abnormal eye movements. Affected children often have a happy demeanor with frequent smiling and spontaneous laughter. xr X-linked recessive SLC9A6 https://medlineplus.gov/genetics/gene/slc9a6 Angelman-like syndrome, X-linked Intellectual deficit, X-linked, South African type GTR C2678194 MeSH D038901 OMIM 300243 SNOMED CT 702354007 2012-04 2020-08-18 Chronic atrial and intestinal dysrhythmia https://medlineplus.gov/genetics/condition/chronic-atrial-and-intestinal-dysrhythmia descriptionChronic atrial and intestinal dysrhythmia (CAID) is a disorder affecting the heart and the digestive system. CAID disrupts the normal rhythm of the heartbeat; affected individuals have a heart rhythm abnormality called sick sinus syndrome. The disorder also impairs the rhythmic muscle contractions that propel food through the intestines (peristalsis), causing a digestive condition called intestinal pseudo-obstruction. The heart and digestive issues develop at the same time, usually by age 20.Sick sinus syndrome (also known as sinus node dysfunction) is an abnormality of the sinoatrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally, which usually causes the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia) or rapidly switches from being too fast to being too slow (tachycardia-bradycardia syndrome). Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue).In intestinal pseudo-obstruction, impairment of peristalsis leads to a buildup of partially digested food in the intestines, abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those caused by an intestinal blockage (obstruction) such as a tumor, but in intestinal pseudo-obstruction no such blockage is found. ar Autosomal recessive SGO1 https://medlineplus.gov/genetics/gene/sgo1 CAID Cohesinopathy affecting heart and gut rhythm MeSH D001145 MeSH D007418 OMIM 616201 SNOMED CT 720507006 2015-05 2023-03-21 Chronic granulomatous disease https://medlineplus.gov/genetics/condition/chronic-granulomatous-disease descriptionChronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body from foreign invaders such as bacteria and fungi. Individuals with chronic granulomatous disease may have recurrent bacterial and fungal infections. People with this condition may also have areas of inflammation (granulomas) in various tissues that can result in damage to those tissues. The features of chronic granulomatous disease usually first appear in childhood, although some individuals do not show symptoms until later in life.People with chronic granulomatous disease typically have at least one serious bacterial or fungal infection every 3 to 4 years. The lungs are the most frequent area of infection; pneumonia is a common feature of this condition. Individuals with chronic granulomatous disease may develop a type of fungal pneumonia, called mulch pneumonitis, which causes fever and shortness of breath after exposure to decaying organic materials such as mulch, hay, or dead leaves. Exposure to these organic materials and the numerous fungi involved in their decomposition causes people with chronic granulomatous disease to develop fungal infections in their lungs. Other common areas of infection in people with chronic granulomatous disease include the skin, liver, and lymph nodes.Inflammation can occur in many different areas of the body in people with chronic granulomatous disease. Most commonly, granulomas occur in the gastrointestinal tract and the genitourinary tract. In many cases the intestinal wall is inflamed, causing a form of inflammatory bowel disease that varies in severity but can lead to stomach pain, diarrhea, bloody stool, nausea, and vomiting. Other common areas of inflammation in people with chronic granulomatous disease include the stomach, colon, and rectum, as well as the mouth, throat, and skin. Additionally, granulomas within the gastrointestinal tract can lead to tissue breakdown and pus production (abscesses). Inflammation in the stomach can prevent food from passing through to the intestines (gastric outlet obstruction), leading to an inability to digest food. These digestive problems cause vomiting after eating and weight loss. In the genitourinary tract, inflammation can occur in the kidneys and bladder. Inflammation of the lymph nodes (lymphadenitis) and bone marrow (osteomyelitis), which both produce immune cells, can lead to further impairment of the immune system.Rarely, people with chronic granulomatous disease develop autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs.Repeated episodes of infection and inflammation reduce the life expectancy of individuals with chronic granulomatous disease; however, with treatment, most affected individuals live into mid- to late adulthood. ar Autosomal recessive xr X-linked recessive NCF1 https://medlineplus.gov/genetics/gene/ncf1 CYBA https://medlineplus.gov/genetics/gene/cyba CYBB https://medlineplus.gov/genetics/gene/cybb NCF2 https://medlineplus.gov/genetics/gene/ncf2 NCF4 https://medlineplus.gov/genetics/gene/ncf4 Autosomal recessive chronic granulomatous disease CGD Granulomatous disease, chronic X-linked chronic granulomatous disease GTR C1844376 GTR C1856245 GTR C1856251 GTR C1856255 GTR C3151409 ICD-10-CM D71 MeSH D006105 OMIM 233690 OMIM 233700 OMIM 233710 OMIM 306400 OMIM 613960 SNOMED CT 387759001 2012-08 2020-08-18 Chronic myeloid leukemia https://medlineplus.gov/genetics/condition/chronic-myeloid-leukemia descriptionChronic myeloid leukemia is a slow-growing cancer of the blood-forming tissue (bone marrow). Normal bone marrow produces red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting. In chronic myeloid leukemia, the bone marrow produces too many white blood cells. Initially, these cells function relatively normally. However, as the condition progresses, immature white blood cells called myeloblasts (or blasts) accumulate in the blood and bone marrow. The overgrowth of myeloblasts impairs development of other blood cells, leading to a shortage of red blood cells (anemia) and platelets.Chronic myeloid leukemia usually begins after age 60. Common features include excessive tiredness (fatigue), fever, and weight loss. Many affected individuals develop an enlarged spleen (splenomegaly), which can cause a feeling of fullness in the abdomen and a loss of appetite. About half of people with chronic myeloid leukemia do not initially have any signs and symptoms and are diagnosed when a blood test is performed for another reason.The condition consists of three phases: the chronic phase, the accelerated phase, and the blast phase (or blast crisis). In the chronic phase, the number of mature white blood cells is elevated, and myeloblasts account for less than 10 percent of blood cells. Signs and symptoms of the condition during this phase are typically mild or absent and worsen slowly. The chronic phase can last from months to years. In the accelerated phase, the number of myeloblasts is slightly higher, making up 10 to 29 percent of blood cells. The signs and symptoms continue to worsen. The accelerated phase usually lasts 4 to 6 months, although it is skipped in some affected individuals. In blast crisis, 30 percent or more of blood or bone marrow cells are myeloblasts. Signs and symptoms are most severe in this phase, including a massively enlarged spleen, bone pain, and weight loss. Serious infections and uncontrolled bleeding can be life-threatening. n Not inherited ABL1 https://medlineplus.gov/genetics/gene/abl1 BCR https://medlineplus.gov/genetics/gene/bcr 9 https://medlineplus.gov/genetics/chromosome/9 22 https://medlineplus.gov/genetics/chromosome/22 CGL Chronic granulocytic leukemia Chronic myelocytic leukemia Chronic myelogenous leukemia CML GTR CN0023473 ICD-10-CM C92.1 ICD-10-CM C92.10 ICD-10-CM C92.11 ICD-10-CM C92.12 MeSH D015464 OMIM 608232 SNOMED CT 92818009 2016-09 2020-09-08 Chylomicron retention disease https://medlineplus.gov/genetics/condition/chylomicron-retention-disease descriptionChylomicron retention disease is an inherited disorder that impairs the normal absorption of fats, cholesterol, and certain vitamins from food. The features of chylomicron retention disease primarily affect the gastrointestinal system and nervous system.Chylomicron retention disease begins in infancy or early childhood. Affected children have slow growth and weight gain, frequent (chronic) diarrhea, and foul-smelling stools (steatorrhea). They also have reduced blood cholesterol levels (hypocholesterolemia). Some individuals with chylomicron retention disease develop an abnormal buildup of fats in the liver called hepatic stenosis and can have an enlarged liver.Other features of chylomicron retention disease develop later in childhood and often impair the function of the nervous system. Affected people may develop decreased reflexes (hyporeflexia) and a decreased ability to sense vibrations. Rarely, affected individuals have heart abnormalities or muscle wasting (amyotrophy). ar Autosomal recessive SAR1B https://medlineplus.gov/genetics/gene/sar1b Anderson disease Anderson syndrome CMRD Hypobetalipoproteinemia with accumulation of apolipoprotein B-like protein in intestinal cells Lipid transport defect of intestine GTR C0795956 ICD-10-CM E78.3 MeSH D006995 OMIM 246700 SNOMED CT 702364003 2008-10 2022-05-17 Citrullinemia https://medlineplus.gov/genetics/condition/citrullinemia descriptionCitrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Two types of citrullinemia have been described; they have different signs and symptoms and are caused by mutations in different genes.Type I citrullinemia (also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up, they experience a progressive lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. Some affected individuals develop serious liver problems. The health problems associated with type I citrullinemia are life-threatening in many cases. Less commonly, a milder form of type I citrullinemia can develop later in childhood or adulthood. This later-onset form is associated with intense headaches, blind spots (scotomas), problems with balance and muscle coordination (ataxia), and lethargy. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder.Type II citrullinemia chiefly affects the nervous system, causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. Affected individuals often have specific food preferences, preferring protein-rich and fatty foods and avoiding carbohydrate-rich foods. The signs and symptoms of this disorder typically appear during adulthood (adult-onset) and can be triggered by certain medications, infections, surgery, and alcohol intake. These signs and symptoms can be life-threatening in people with adult-onset type II citrullinemia.Adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This liver condition is also known as neonatal-onset type II citrullinemia. NICCD blocks the flow of bile (a digestive fluid produced by the liver) and prevents the body from processing certain nutrients properly. In many cases, the signs and symptoms of NICCD go away within a year. In rare cases, affected individuals develop other signs and symptoms in early childhood after seeming to recover from NICCD, including delayed growth, extreme tiredness (fatigue), specific food preferences (mentioned above), and abnormal amounts of fats (lipids) in the blood (dyslipidemia). This condition is known as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD). Years or even decades later, some people with NICCD or FTTDCD develop the features of adult-onset type II citrullinemia. ar Autosomal recessive ASS1 https://medlineplus.gov/genetics/gene/ass1 SLC25A13 https://medlineplus.gov/genetics/gene/slc25a13 CIT Citrullinuria GTR C1853942 GTR C1863844 GTR C4721769 ICD-10-CM E72.23 MeSH D020159 OMIM 215700 OMIM 603471 OMIM 605814 SNOMED CT 398680004 2017-05 2020-08-18 Cleidocranial dysplasia https://medlineplus.gov/genetics/condition/cleidocranial-dysplasia descriptionCleidocranial dysplasia is a condition that primarily affects development of the bones and teeth. Signs and symptoms of cleidocranial dysplasia can vary widely in severity, even within the same family.Individuals with cleidocranial dysplasia usually have underdeveloped or absent collarbones, also called clavicles ("cleido-" in the condition name refers to these bones). As a result, their shoulders are narrow and sloping, can be brought unusually close together in front of the body, and in some cases can be made to meet in the middle of the body. Delayed maturation of the skull (cranium) is also characteristic of this condition, including delayed closing of the growth lines where the bones of the skull meet (sutures) and larger than normal spaces (fontanelles) between the skull bones that are noticeable as "soft spots" on the heads of infants. The fontanelles normally close in early childhood, but they may remain open throughout life in people with this disorder. Some individuals with cleidocranial dysplasia have extra pieces of bone called Wormian bones within the sutures.Affected individuals are often shorter than other members of their family at the same age. Many also have short, tapered fingers and broad thumbs; flat feet; knock knees; short shoulder blades (scapulae); and an abnormal curvature of the spine (scoliosis). Typical facial features include a wide, short skull (brachycephaly); a prominent forehead; wide-set eyes (hypertelorism); a flat nose; and a small upper jaw.Individuals with cleidocranial dysplasia often have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture, at a relatively early age. Women with cleidocranial dysplasia have an increased risk of requiring a cesarean section when delivering a baby, due to a narrow pelvis preventing passage of the infant's head.Dental abnormalities are very common in cleidocranial dysplasia and can include delayed loss of the primary (baby) teeth; delayed appearance of the secondary (adult) teeth; unusually shaped, peg-like teeth; misalignment of the teeth and jaws (malocclusion); and extra teeth, sometimes accompanied by cysts in the gums.In addition to skeletal and dental abnormalities, people with cleidocranial dysplasia may have hearing loss and are prone to sinus and ear infections. Some young children with this condition are mildly delayed in the development of motor skills such as crawling and walking, but intelligence is unaffected. ad Autosomal dominant RUNX2 https://medlineplus.gov/genetics/gene/runx2 Cleidocranial dysostosis Dento-osseous dysplasia Marie-Sainton syndrome GTR C0008928 MeSH D002973 OMIM 119600 SNOMED CT 65976001 2017-08 2020-08-18 Clopidogrel resistance https://medlineplus.gov/genetics/condition/clopidogrel-resistance descriptionClopidogrel resistance is a condition in which the drug clopidogrel is less effective than normal in people who are treated with it. Clopidogrel (also known as Plavix) is an antiplatelet drug, which means that it prevents blood cells called platelets from sticking together (aggregating) and forming blood clots. This drug is typically given to prevent blood clot formation in individuals with a history of stroke; heart attack; a blood clot in the deep veins of the arms or legs (deep vein thrombosis); or plaque buildup (atherosclerosis) in the blood vessels leading from the heart, which are opened by placement of a small thin tube (stent).People with clopidogrel resistance who receive clopidogrel are at risk of serious, sometimes fatal, complications. These individuals may have another heart attack or stroke caused by abnormal blood clot formation; those with stents can develop blood clots (thromboses) within the stents, impeding blood flow.People with clopidogrel resistance can be divided into two categories: intermediate metabolizers and poor metabolizers. Intermediate metabolizers are able to process some clopidogrel, so they receive partial benefit from the treatment but are not protected from developing a harmful blood clot. Poor metabolizers process little or no clopidogrel, so they receive very limited benefit from the treatment and are at risk of forming a harmful blood clot.Clopidogrel resistance does not appear to cause any health problems other than those associated with clopidogrel drug treatment. ac Autosomal codominant CYP2C19 https://medlineplus.gov/genetics/gene/cyp2c19 CYP2C19-related poor drug metabolism Poor metabolism of clopidogrel Resistance to clopidogrel GTR C2674941 MeSH D004305 OMIM 609535 SNOMED CT 419253001 2015-12 2023-11-24 Clouston syndrome https://medlineplus.gov/genetics/condition/clouston-syndrome descriptionClouston syndrome is a form of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of some or all of the ectodermal structures, which include the skin, hair, nails, teeth, and sweat glands. Specifically, Clouston syndrome is characterized by abnormalities of the hair, nails, and skin, with the teeth and sweat glands being unaffected.In infants with Clouston syndrome, scalp hair is sparse, patchy, and lighter in color than the hair of other family members; it is also fragile and easily broken. By puberty, the hair problems may worsen until all the hair on the scalp is lost (total alopecia). The eyelashes, eyebrows, underarm (axillary) hair, and pubic hair are also sparse or absent.Abnormal growth of fingernails and toenails (nail dystrophy) is also characteristic of Clouston syndrome. The nails may appear white in the first years of life. They grow slowly and gradually become thick and misshapen. In some people with Clouston syndrome, nail dystrophy is the most noticeable feature of the disorder.Many people with Clouston syndrome have thick skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis); areas of the skin, especially over the joints, that are darker in color than the surrounding skin (hyperpigmentation); and widened and rounded tips of the fingers (clubbing). ad Autosomal dominant GJB6 https://medlineplus.gov/genetics/gene/gjb6 Clouston hidrotic ectodermal dysplasia Clouston's syndrome ECTD2 Ectodermal dysplasia 2, Clouston type HED2 Hidrotic ectodermal dysplasia 2 GTR C0162361 MeSH D004476 OMIM 129500 SNOMED CT 54209007 2014-03 2020-08-18 Coats plus syndrome https://medlineplus.gov/genetics/condition/coats-plus-syndrome descriptionCoats plus syndrome is an inherited condition characterized by an eye disorder called Coats disease plus abnormalities of the brain, bones, gastrointestinal system, and other parts of the body.Coats disease affects the retina, which is the tissue at the back of the eye that detects light and color. The disorder causes blood vessels in the retina to be abnormally enlarged (dilated) and twisted. The abnormal vessels leak fluid, which can eventually cause the layers of the retina to separate (retinal detachment). These eye abnormalities often result in vision loss.People with Coats plus syndrome also have brain abnormalities including abnormal deposits of calcium (calcification), the development of fluid-filled pockets called cysts, and loss of a type of brain tissue known as white matter (leukodystrophy). These brain abnormalities worsen over time, causing slow growth, movement disorders, seizures, and a decline in intellectual function.Other features of Coats plus syndrome include low bone density (osteopenia), which causes bones to be fragile and break easily, and a shortage of red blood cells (anemia), which can lead to unusually pale skin (pallor) and extreme tiredness (fatigue). Affected individuals can also have serious or life-threatening complications including abnormal bleeding in the gastrointestinal tract, high blood pressure in the vein that supplies blood to the liver (portal hypertension), and liver failure. Less common features of Coats plus syndrome can include sparse, prematurely gray hair; malformations of the fingernails and toenails; and abnormalities of skin coloring (pigmentation), such as light brown patches called café-au-lait spots.Coats plus syndrome and a disorder called leukoencephalopathy with calcifications and cysts (LCC; also called Labrune syndrome) have sometimes been grouped together under the umbrella term cerebroretinal microangiopathy with calcifications and cysts (CRMCC) because they feature very similar brain abnormalities. However, researchers recently found that Coats plus syndrome and LCC have different genetic causes, and they are now generally described as separate disorders instead of variants of a single condition. ar Autosomal recessive CTC1 https://medlineplus.gov/genetics/gene/ctc1 Cerebroretinal microangiopathy with calcifications and cysts CRMCC GTR C4552029 MeSH D012164 OMIM 612199 SNOMED CT 711482008 2014-04 2023-03-21 Cockayne syndrome https://medlineplus.gov/genetics/condition/cockayne-syndrome descriptionCockayne syndrome is a rare disorder characterized by an abnormally small head size (microcephaly), a failure to gain weight and grow at the expected rate (failure to thrive) leading to very short stature, and delayed development. The signs and symptoms of this condition are usually apparent from infancy, and they worsen over time. Most affected individuals have an increased sensitivity to sunlight (photosensitivity), and in some cases even a small amount of sun exposure can cause a sunburn or blistering of the skin. Other signs and symptoms often include hearing loss, vision loss, severe tooth decay, bone abnormalities, hands and feet that are cold all the time, and changes in the brain that can be seen on brain scans.People with Cockayne syndrome have a serious reaction to an antibiotic medication called metronidazole. If affected individuals take this medication, it can cause life-threatening liver failure.Cockayne syndrome is sometimes divided into types I, II, and III based on the severity and age of onset of symptoms. However, the differences between the types are not always clear-cut, and some researchers believe the signs and symptoms reflect a spectrum instead of distinct types. Cockayne syndrome type II is also known as cerebro-oculo-facio-skeletal (COFS) syndrome, and while some researchers consider it to be a separate but similar condition, others classify it as part of the Cockayne syndrome disease spectrum. ar Autosomal recessive ERCC6 https://medlineplus.gov/genetics/gene/ercc6 ERCC8 https://medlineplus.gov/genetics/gene/ercc8 CS Dwarfism-retinal atrophy-deafness syndrome GTR C0009207 MeSH D003057 OMIM 133540 OMIM 214150 OMIM 216400 SNOMED CT 21086008 2016-05 2023-08-22 Coffin-Lowry syndrome https://medlineplus.gov/genetics/condition/coffin-lowry-syndrome descriptionCoffin-Lowry syndrome is a condition that affects many parts of the body. The signs and symptoms are usually more severe in males than in females, although the features of this disorder range from very mild to severe in affected women.Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability and delayed development. Affected women may be cognitively normal, or they may have intellectual disability ranging from mild to profound. Beginning in childhood or adolescence, some people with this condition experience brief episodes of collapse when excited or startled by a loud noise. These attacks are called stimulus-induced drop episodes (SIDEs).Most affected males and some affected females have distinctive facial features including a prominent forehead, widely spaced and downward-slanting eyes, a short nose with a wide tip, and a wide mouth with full lips. These features become more pronounced with age. Soft hands with short, tapered fingers are also characteristic of Coffin-Lowry syndrome. Additional features of this condition include short stature, an unusually small head (microcephaly), progressive abnormal curvature of the spine (kyphoscoliosis), and other skeletal abnormalities. xd X-linked dominant RPS6KA3 https://medlineplus.gov/genetics/gene/rps6ka3 CLS Mental retardation with osteocartilaginous abnormalities GTR C0265252 MeSH D038921 OMIM 303600 SNOMED CT 15182000 2008-01 2020-08-18 Coffin-Siris syndrome https://medlineplus.gov/genetics/condition/coffin-siris-syndrome descriptionCoffin-Siris syndrome is a condition that affects several body systems. Although there are many variable signs and symptoms, hallmarks of this condition include developmental disability, abnormalities of the fifth (pinky) fingers or toes, and characteristic facial features.Most affected individuals have mild to severe intellectual disability or delayed development of speech and motor skills such as sitting and walking. Another feature of Coffin-Siris syndrome is underdevelopment (hypoplasia) of the tips of the fingers or toes, or hypoplasia or absence of the nails. These abnormalities are most common on the fifth fingers or toes. In addition, most people with Coffin-Siris syndrome have facial features described as coarse. These features typically include a wide nose with a flat nasal bridge, a wide mouth with thick lips, and thick eyebrows and eyelashes. Affected individuals can have excess hair on other parts of the face and body (hirsutism), but scalp hair is often sparse. People with Coffin-Siris syndrome can have a range of facial features, and not all affected individuals have the typical features. In addition, people with this condition may have an abnormally small head (microcephaly).Additionally, some infants and children with Coffin-Siris syndrome have frequent respiratory infections, difficulty feeding, and an inability to gain weight at the expected rate (failure to thrive). Other signs and symptoms that may occur in people with this condition include short stature, low muscle tone (hypotonia), and abnormally loose (lax) joints. Abnormalities of the eyes, brain, heart, and kidneys may also be present. ad Autosomal dominant ARID1A https://medlineplus.gov/genetics/gene/arid1a ARID1B https://medlineplus.gov/genetics/gene/arid1b SMARCA4 https://medlineplus.gov/genetics/gene/smarca4 SMARCB1 https://medlineplus.gov/genetics/gene/smarcb1 SMARCE1 https://medlineplus.gov/genetics/gene/smarce1 SOX11 https://medlineplus.gov/genetics/gene/sox11 DPF2 https://www.ncbi.nlm.nih.gov/gene/5977 SMARCC2 https://www.ncbi.nlm.nih.gov/gene/6601 SOX4 https://www.ncbi.nlm.nih.gov/gene/6659 ARID2 https://www.ncbi.nlm.nih.gov/gene/196528 CSS Dwarfism-onychodysplasia Fifth digit syndrome Mental retardation with hypoplastic fifth fingernails and toenails Short stature-onychodysplasia GTR C0265338 MeSH D008607 OMIM 135900 SNOMED CT 10007009 2013-05 2021-08-30 Cohen syndrome https://medlineplus.gov/genetics/condition/cohen-syndrome descriptionCohen syndrome is an inherited disorder that affects many parts of the body and is characterized by developmental delay, intellectual disability, small head size (microcephaly), and weak muscle tone (hypotonia). Other features common in this condition include worsening nearsightedness (myopia), breakdown (degeneration) of the light-sensitive tissue at the back of the eye (retinal dystrophy), an unusually large range of joint movement (hypermobility), and distinctive facial features. These facial features typically include thick hair and eyebrows, long eyelashes, unusually-shaped eyes (down-slanting and wave-shaped), a bulbous nasal tip, a smooth or shortened area between the nose and the upper lip (philtrum), and prominent upper central teeth. The combination of the last two facial features results in an open mouth.The features of Cohen syndrome vary widely among affected individuals. Additional signs and symptoms in some individuals with this disorder include low levels of white blood cells (neutropenia), overly friendly behavior, and obesity that develops in late childhood or adolescence. When obesity is present, it typically occurs around the torso, with the arms and legs remaining slender (called truncal obesity). Individuals with Cohen syndrome may also have narrow hands and feet, and slender fingers. ar Autosomal recessive VPS13B https://medlineplus.gov/genetics/gene/vps13b Hypotonia, obesity, and prominent incisors Norio syndrome Obesity-hypotonia syndrome Pepper syndrome Prominent incisors-obesity-hypotonia syndrome GTR C0265223 MeSH D000015 MeSH D002658 OMIM 216550 SNOMED CT 56604005 2017-06 2021-11-26 Cold-induced sweating syndrome https://medlineplus.gov/genetics/condition/cold-induced-sweating-syndrome descriptionCold-induced sweating syndrome is characterized by problems with regulating body temperature and other abnormalities affecting many parts of the body. In infancy, the features of this condition are often known as Crisponi syndrome. Researchers originally thought that cold-induced sweating syndrome and Crisponi syndrome were separate disorders, but it is now widely believed that they represent the same condition at different times during life.Infants with Crisponi syndrome have unusual facial features, including a flat nasal bridge, upturned nostrils, a long space between the nose and upper lip (philtrum), a high arched roof of the mouth (palate), a small chin (micrognathia), and low-set ears. The muscles in the lower part of the face are weak, leading to severe feeding difficulties, excessive drooling, and breathing problems. Other physical abnormalities associated with Crisponi syndrome include a scaly skin rash, an inability to fully extend the elbows, overlapping fingers and tightly fisted hands, and malformations of the feet and toes. Affected infants startle easily and often tense their facial muscles into a grimace-like expression. By six months of age, infants with Crisponi syndrome develop unexplained high fevers that increase the risk of seizures and sudden death.Many of the health problems associated with Crisponi syndrome improve with time, and affected individuals who survive the newborn period go on to develop other features of cold-induced sweating syndrome in early childhood. Within the first decade of life, affected individuals begin having episodes of profuse sweating (hyperhidrosis) and shivering involving the face, torso, and arms. The excessive sweating is usually triggered by exposure to temperatures below about 65 or 70 degrees Fahrenheit, but it can also be triggered by nervousness or eating sugary foods. Paradoxically, affected individuals tend not to sweat in warmer conditions, instead becoming flushed and overheated in hot environments.Adolescents with cold-induced sweating syndrome typically develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Although infants may develop life-threatening fevers, affected individuals who survive infancy have a normal life expectancy. ar Autosomal recessive CLCF1 https://medlineplus.gov/genetics/gene/clcf1 CRLF1 https://medlineplus.gov/genetics/gene/crlf1 CISS CNTF receptor-related disorders Crisponi syndrome Sohar-Crisponi syndrome GTR C1832409 GTR C1848947 GTR C1853198 GTR C4310742 MeSH D000015 MeSH D005334 OMIM 272430 OMIM 610313 OMIM 617055 SNOMED CT 702363009 2012-08 2023-11-07 Cole disease https://medlineplus.gov/genetics/condition/cole-disease descriptionCole disease is a disorder that affects the skin. People with this disorder have areas of unusually light-colored skin (hypopigmentation), typically on the arms and legs, and spots of thickened skin on the palms of the hands and the soles of the feet (punctate palmoplantar keratoderma). These skin features are present at birth or develop in the first year of life.In some cases, individuals with Cole disease develop abnormal accumulations of the mineral calcium (calcifications) in the tendons, which can cause pain during movement. Calcifications may also occur in the skin or breast tissue. ad Autosomal dominant ENPP1 https://medlineplus.gov/genetics/gene/enpp1 Guttate hypopigmentation and punctate palmoplantar keratoderma with or without ectopic calcification GTR C3809781 ICD-10-CM L85.2 MeSH D007645 OMIM 615522 SNOMED CT 711154007 2015-01 2023-07-19 Collagen VI-related dystrophy https://medlineplus.gov/genetics/condition/collagen-vi-related-myopathy descriptionCollagen VI-related dystrophy is a group of disorders that affect skeletal muscles (which are the muscles used for movement) and connective tissue (which provides strength and flexibility to the skin, joints, and other structures throughout the body). Most affected individuals have muscle weakness and joint deformities called contractures that restrict movement of the affected joints and worsen over time. Researchers have described several forms of collagen VI-related dystrophy, which range in severity: Bethlem muscular dystrophy is the mildest, an intermediate form is moderate in severity, and Ullrich congenital muscular dystrophy is the most severe.People with Bethlem muscular dystrophy usually have low muscle tone (hypotonia) in infancy. Muscle weakness can begin at any age but often appears in childhood to early adulthood. The muscle weakness is slowly progressive, with about two-thirds of affected individuals over age 50 needing walking assistance, particularly when outdoors. Affected individuals usually develop contractures by adulthood, typically in their fingers, elbows, shoulders, and ankles. Older individuals may develop weakness in respiratory muscles, which can cause breathing problems. Some people with this mild form of collagen VI-related dystrophy have skin abnormalities, including small bumps called follicular hyperkeratosis on the arms and legs; soft, velvety skin on the palms of the hands and soles of the feet; and abnormal wound healing that creates shallow scars.The intermediate form of collagen VI-related dystrophy is characterized by muscle weakness that begins in infancy. Affected children are able to walk, although walking becomes increasingly difficult starting in early adulthood. They develop contractures in their fingers, elbows, shoulders, and ankles in childhood. In some affected people, the respiratory muscles are weakened, requiring people to use a machine to help them breathe (mechanical ventilation), particularly during sleep.People with Ullrich congenital muscular dystrophy have severe muscle weakness beginning soon after birth. Some affected individuals are never able to walk and others can walk only with support. Those who can walk often lose the ability, usually in early adolescence. Individuals with Ullrich congenital muscular dystrophy develop contractures in their shoulders, elbows, hips, and knees, which further impair movement. Many individuals with this form of the condition have loose joints (joint laxity) in the fingers, wrists, toes, ankles, and other joints. Affected individuals need continuous mechanical ventilation to help them breathe while sleeping, and some may need it in the daytime. As in Bethlem muscular dystrophy, some people with Ullrich congenital muscular dystrophy have follicular hyperkeratosis; soft, velvety skin on the palms and soles; and abnormal wound healing.Individuals with collagen VI-related dystrophy often have signs and symptoms of multiple forms of this condition, so it can be difficult to assign a specific diagnosis. The overlap in disease features, in addition to their common cause, is why these once separate conditions are now considered part of the same disease spectrum. ad Autosomal dominant ar Autosomal recessive COL6A1 https://medlineplus.gov/genetics/gene/col6a1 COL6A2 https://medlineplus.gov/genetics/gene/col6a2 COL6A3 https://medlineplus.gov/genetics/gene/col6a3 Col6-RDs Collagen type VI-related disorders Collagen VI-related dystrophies Collagen VI-related myopathies Collagen VI-related myopathy ColVI myopathies GTR C0410179 GTR C1834674 GTR CN117976 GTR CN230143 ICD-10-CM MeSH D009136 OMIM 158810 OMIM 254090 SNOMED CT 193222002 SNOMED CT 240062007 2015-10 2022-07-19 Coloboma https://medlineplus.gov/genetics/condition/coloboma descriptionColoboma is an eye abnormality that occurs before birth. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in one of several parts of the eye, including the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or the optic nerves, which carry information from the eyes to the brain.Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision. Colobomas affecting the iris, which result in a "keyhole" appearance of the pupil, generally do not lead to vision loss. Colobomas involving the retina result in vision loss in specific parts of the visual field. Large retinal colobomas or those affecting the optic nerve can cause low vision, which means vision loss that cannot be completely corrected with glasses or contact lenses.Some people with coloboma also have a condition called microphthalmia. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.People with coloboma may also have other eye abnormalities, including clouding of the lens of the eye (cataract), increased pressure inside the eye (glaucoma) that can damage the optic nerve, vision problems such as nearsightedness (myopia), involuntary back-and-forth eye movements (nystagmus), or separation of the retina from the back of the eye (retinal detachment).Some individuals have coloboma as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When coloboma occurs by itself, it is described as nonsyndromic or isolated.Colobomas involving the eyeball should be distinguished from gaps that occur in the eyelids. While these eyelid gaps are also called colobomas, they arise from abnormalities in different structures during early development. xr X-linked recessive xd X-linked dominant ar Autosomal recessive n Not inherited ad Autosomal dominant ACTG1 https://medlineplus.gov/genetics/gene/actg1 TCOF1 https://medlineplus.gov/genetics/gene/tcof1 SALL4 https://medlineplus.gov/genetics/gene/sall4 SALL1 https://medlineplus.gov/genetics/gene/sall1 ZEB2 https://medlineplus.gov/genetics/gene/zeb2 CHD7 https://medlineplus.gov/genetics/gene/chd7 BCOR https://medlineplus.gov/genetics/gene/bcor PAX2 https://medlineplus.gov/genetics/gene/pax2 PTCH1 https://medlineplus.gov/genetics/gene/ptch1 FOXL2 https://medlineplus.gov/genetics/gene/foxl2 SOX2 https://medlineplus.gov/genetics/gene/sox2 GJA1 https://medlineplus.gov/genetics/gene/gja1 PAX6 https://medlineplus.gov/genetics/gene/pax6 PORCN https://medlineplus.gov/genetics/gene/porcn LRP2 https://medlineplus.gov/genetics/gene/lrp2 HCCS https://medlineplus.gov/genetics/gene/hccs OTX2 https://medlineplus.gov/genetics/gene/otx2 SHH https://medlineplus.gov/genetics/gene/shh SIX3 https://medlineplus.gov/genetics/gene/six3 ZIC2 https://medlineplus.gov/genetics/gene/zic2 KMT2D https://medlineplus.gov/genetics/gene/kmt2d FREM1 https://medlineplus.gov/genetics/gene/frem1 GDF6 https://medlineplus.gov/genetics/gene/gdf6 GDF3 https://medlineplus.gov/genetics/gene/gdf3 DPYD https://medlineplus.gov/genetics/gene/dpyd PQBP1 https://medlineplus.gov/genetics/gene/pqbp1 POLR1C https://medlineplus.gov/genetics/gene/polr1c POLR1D https://medlineplus.gov/genetics/gene/polr1d TFAP2A https://medlineplus.gov/genetics/gene/tfap2a KAT6B https://medlineplus.gov/genetics/gene/kat6b ACTB https://medlineplus.gov/genetics/gene/actb SMOC1 https://medlineplus.gov/genetics/gene/smoc1 FRAS1 https://medlineplus.gov/genetics/gene/fras1 FREM2 https://medlineplus.gov/genetics/gene/frem2 GRIP1 https://medlineplus.gov/genetics/gene/grip1 RAB3GAP1 https://medlineplus.gov/genetics/gene/rab3gap1 RAB3GAP2 https://medlineplus.gov/genetics/gene/rab3gap2 TBC1D20 https://medlineplus.gov/genetics/gene/tbc1d20 ALDH1A3 https://www.ncbi.nlm.nih.gov/gene/220 BMP4 https://www.ncbi.nlm.nih.gov/gene/652 BMP7 https://www.ncbi.nlm.nih.gov/gene/655 CRYAA https://www.ncbi.nlm.nih.gov/gene/1409 CRYBA4 https://www.ncbi.nlm.nih.gov/gene/1413 CRYBB2 https://www.ncbi.nlm.nih.gov/gene/1415 ERCC1 https://www.ncbi.nlm.nih.gov/gene/2067 ERCC5 https://www.ncbi.nlm.nih.gov/gene/2073 HMGB3 https://www.ncbi.nlm.nih.gov/gene/3149 HMX1 https://www.ncbi.nlm.nih.gov/gene/3166 IGBP1 https://www.ncbi.nlm.nih.gov/gene/3476 MAF https://www.ncbi.nlm.nih.gov/gene/4094 SIX6 https://www.ncbi.nlm.nih.gov/gene/4990 PDE6D https://www.ncbi.nlm.nih.gov/gene/5147 RARB https://www.ncbi.nlm.nih.gov/gene/5915 RBP4 https://www.ncbi.nlm.nih.gov/gene/5950 SALL2 https://www.ncbi.nlm.nih.gov/gene/6297 FZD5 https://www.ncbi.nlm.nih.gov/gene/7855 NAA10 https://www.ncbi.nlm.nih.gov/gene/8260 FADD https://www.ncbi.nlm.nih.gov/gene/8772 PIGL https://www.ncbi.nlm.nih.gov/gene/9487 SEMA3E https://www.ncbi.nlm.nih.gov/gene/9723 DHX38 https://www.ncbi.nlm.nih.gov/gene/9785 ABCB6 https://www.ncbi.nlm.nih.gov/gene/10058 YAP1 https://www.ncbi.nlm.nih.gov/gene/10413 MAB21L2 https://www.ncbi.nlm.nih.gov/gene/10586 VAX1 https://www.ncbi.nlm.nih.gov/gene/11023 RPGRIP1L https://www.ncbi.nlm.nih.gov/gene/23322 FNBP4 https://www.ncbi.nlm.nih.gov/gene/23360 TMEM98 https://www.ncbi.nlm.nih.gov/gene/26022 RAX https://www.ncbi.nlm.nih.gov/gene/30062 CLDN19 https://www.ncbi.nlm.nih.gov/gene/30063 TBX22 https://www.ncbi.nlm.nih.gov/gene/50945 CRIM1 https://www.ncbi.nlm.nih.gov/gene/51232 TMX3 https://www.ncbi.nlm.nih.gov/gene/54495 TENM3 https://www.ncbi.nlm.nih.gov/gene/55714 CC2D2A https://www.ncbi.nlm.nih.gov/gene/57545 FAM111A https://www.ncbi.nlm.nih.gov/gene/63901 STRA6 https://www.ncbi.nlm.nih.gov/gene/64220 SRD5A3 https://www.ncbi.nlm.nih.gov/gene/79644 MFRP https://www.ncbi.nlm.nih.gov/gene/83552 TMEM67 https://www.ncbi.nlm.nih.gov/gene/91147 C12orf57 https://www.ncbi.nlm.nih.gov/gene/113246 SCLT1 https://www.ncbi.nlm.nih.gov/gene/132320 ATOH7 https://www.ncbi.nlm.nih.gov/gene/220202 TBC1D32 https://www.ncbi.nlm.nih.gov/gene/221322 VSX2 https://www.ncbi.nlm.nih.gov/gene/338917 PRSS56 https://www.ncbi.nlm.nih.gov/gene/646960 Congenital ocular coloboma Microphthalmia, isolated, with coloboma Ocular coloboma Uveoretinal coloboma GTR C0009363 GTR C4011974 ICD-10-CM H47.31 ICD-10-CM H47.311 ICD-10-CM H47.312 ICD-10-CM H47.313 ICD-10-CM H47.319 ICD-10-CM Q12.2 ICD-10-CM Q13.0 MeSH D003103 OMIM 120200 OMIM 216820 SNOMED CT 93390002 2011-11 2024-10-02 Color vision deficiency https://medlineplus.gov/genetics/condition/color-vision-deficiency descriptionColor vision deficiency (sometimes called color blindness) represents a group of conditions that affect the perception of color. Red-green color vision defects are the most common form of color vision deficiency. Affected individuals have trouble distinguishing between some shades of red, yellow, and green. Blue-yellow color vision defects (also called tritan defects), which are rarer, cause problems with differentiating shades of blue and green and cause difficulty distinguishing dark blue from black. These two forms of color vision deficiency disrupt color perception but do not affect the sharpness of vision (visual acuity).A less common and more severe form of color vision deficiency called blue cone monochromacy causes very poor visual acuity and severely reduced color vision. Affected individuals have additional vision problems, which can include increased sensitivity to light (photophobia), involuntary back-and-forth eye movements (nystagmus), and nearsightedness (myopia). Blue cone monochromacy is sometimes considered to be a form of achromatopsia, a disorder characterized by a partial or total lack of color vision with other vision problems. xr X-linked recessive ad Autosomal dominant OPN1LW https://medlineplus.gov/genetics/gene/opn1lw OPN1MW https://medlineplus.gov/genetics/gene/opn1mw OPN1SW https://medlineplus.gov/genetics/gene/opn1sw Color blindness Color vision defects Defective color vision Vision defect, color GTR C0155017 GTR C0339537 ICD-10-CM H53.5 ICD-10-CM H53.50 ICD-10-CM H53.51 ICD-10-CM H53.52 ICD-10-CM H53.53 ICD-10-CM H53.54 ICD-10-CM H53.55 ICD-10-CM H53.59 MeSH D003117 OMIM 190900 OMIM 303700 OMIM 303800 OMIM 303900 SNOMED CT 193683001 SNOMED CT 24704003 SNOMED CT 367469000 SNOMED CT 51445007 SNOMED CT 51886007 SNOMED CT 77479002 2015-01 2020-08-18 Combined malonic and methylmalonic aciduria https://medlineplus.gov/genetics/condition/combined-malonic-and-methylmalonic-aciduria descriptionCombined malonic and methylmalonic aciduria (CMAMMA) is a condition characterized by high levels of certain chemicals, known as malonic acid and methylmalonic acid, in the body. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated.The signs and symptoms of CMAMMA can begin in childhood. In some children, the buildup of acids causes the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs. Other signs and symptoms may include involuntary muscle tensing (dystonia), weak muscle tone (hypotonia), developmental delay, an inability to grow and gain weight at the expected rate (failure to thrive), low blood glucose (hypoglycemia), and coma. Some affected children have an unusually small head size (microcephaly).Other people with CMAMMA do not develop signs and symptoms until adulthood. These individuals usually have neurological problems, such as seizures, loss of memory, a decline in thinking ability, or psychiatric diseases. ar Autosomal recessive ACSF3 https://medlineplus.gov/genetics/gene/acsf3 CMAMMA GTR C3280314 MeSH D008661 OMIM 614265 SNOMED CT 702365002 2013-01 2023-07-26 Combined oxidative phosphorylation deficiency 1 https://medlineplus.gov/genetics/condition/combined-oxidative-phosphorylation-deficiency-1 descriptionCombined oxidative phosphorylation deficiency 1 is a severe condition that primarily impairs neurological and liver function.Most people with combined oxidative phosphorylation deficiency 1 have severe brain dysfunction (encephalopathy) that worsens over time; they also have difficulty growing and gaining weight at the expected rate (failure to thrive). In some cases, affected individuals have abnormal muscle tone (increased or decreased), developmental delay, seizures, loss of sensation in the limbs (peripheral neuropathy), and an unusually small head (microcephaly). Liver disease is common in people with combined oxidative phosphorylation deficiency 1, with individuals quickly developing liver failure. Individuals with this condition also usually have a potentially life-threatening buildup of a chemical called lactic acid in the body (lactic acidosis).The neurological features of combined oxidative phosphorylation deficiency 1 are largely due to brain abnormalities that include thinning of the tissue that connects the two halves of the brain (corpus callosum hypoplasia) and loss of brain tissue called white matter (leukodystrophy), particularly in an area of the brain called the basal ganglia, which normally helps control movement.Individuals with combined oxidative phosphorylation deficiency 1 usually do not survive past early childhood, although some people live longer. ar Autosomal recessive GFM1 https://medlineplus.gov/genetics/gene/gfm1 COXPD1 Early fatal progressive hepatoencephalopathy Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 GTR C1836797 MeSH D028361 OMIM 609060 2017-09 2020-08-18 Combined pituitary hormone deficiency https://medlineplus.gov/genetics/condition/combined-pituitary-hormone-deficiency descriptionCombined pituitary hormone deficiency is a condition that causes a partial or complete loss (deficiency) of two or more hormones that are normally produced by the pituitary gland. The pituitary gland, which is located at the base of the brain, produces hormones that are needed for growth, development, and other critical body functions. A lack of pituitary hormones can affect growth and development.The signs and symptoms of combined pituitary hormone deficiency depend on the specific hormones involved. The hormones that are produced by the pituitary gland include growth hormone (GH), which is needed for normal growth; follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which play a role in sexual development and the ability to have biological children (fertility); thyroid-stimulating hormone (TSH), which triggers the release of hormones that control how the body uses energy; prolactin, which stimulates the production of breast milk; and adrenocorticotropic hormone (ACTH), which influences how the body responds to stress and helps maintain normal levels of glucose in the blood and blood pressure levels.Though the features of combined pituitary hormone deficiency can vary, affected individuals often do not grow at the expected rate, and short stature usually becomes apparent in early childhood. Infants with combined pituitary hormone deficiency may have persistent yellowing of the skin and the whites of the eyes (jaundice), low levels of glucose in the blood (hypoglycemia), and genital abnormalities. Features of combined pituitary hormone deficiency include fatigue, changes in weight, delayed or absent puberty, and problems with fertility. Additional signs and symptoms may include abnormal development of the head and face (craniofacial abnormalities), brain abnormalities, recurrent seizures (epilepsy), and developmental delays. Some affected individuals have eye disorders. These include optic nerve hypoplasia, which is a disorder that affects the nerves that carry visual information from the eyes to the brain.The signs and symptoms of combined pituitary hormone deficiency can resemble those seen in other disorders, which may delay a diagnosis. Because the signs and symptoms of combined pituitary hormone deficiency can vary widely and often overlap with other conditions, some researchers have suggested that combined pituitary hormone deficiency is part of a spectrum of related disorders rather than a single disorder.Combined pituitary hormone deficiency can be congenital or acquired. Acquired combined pituitary hormone deficiency is caused by factors that occur later in life, such as infections or tumors. When combined pituitary hormone deficiency is not acquired, the condition is called congenital. ar Autosomal recessive x X-linked ad Autosomal dominant+New variant FGFR1 https://medlineplus.gov/genetics/gene/fgfr1 PROKR2 https://medlineplus.gov/genetics/gene/prokr2 CHD7 https://medlineplus.gov/genetics/gene/chd7 SOX2 https://medlineplus.gov/genetics/gene/sox2 PAX6 https://medlineplus.gov/genetics/gene/pax6 HESX1 https://medlineplus.gov/genetics/gene/hesx1 OTX2 https://medlineplus.gov/genetics/gene/otx2 PROP1 https://medlineplus.gov/genetics/gene/prop1 FGF8 https://medlineplus.gov/genetics/gene/fgf8 BMP4 https://www.ncbi.nlm.nih.gov/gene/652 GLI2 https://www.ncbi.nlm.nih.gov/gene/2736 GLI3 https://www.ncbi.nlm.nih.gov/gene/2737 FOXA2 https://www.ncbi.nlm.nih.gov/gene/3170 IGSF1 https://www.ncbi.nlm.nih.gov/gene/3547 POU1F1 https://www.ncbi.nlm.nih.gov/gene/5449 ROBO1 https://www.ncbi.nlm.nih.gov/gene/6091 SOX3 https://www.ncbi.nlm.nih.gov/gene/6658 TGIF1 https://www.ncbi.nlm.nih.gov/gene/7050 LHX3 https://www.ncbi.nlm.nih.gov/gene/8022 ARNT2 https://www.ncbi.nlm.nih.gov/gene/9915 PNPLA6 https://www.ncbi.nlm.nih.gov/gene/10908 RAX https://www.ncbi.nlm.nih.gov/gene/30062 RNPC3 https://www.ncbi.nlm.nih.gov/gene/55599 ZSWIM6 https://www.ncbi.nlm.nih.gov/gene/57688 TCF7L1 https://www.ncbi.nlm.nih.gov/gene/83439 LHX4 https://www.ncbi.nlm.nih.gov/gene/89884 TBC1D32 https://www.ncbi.nlm.nih.gov/gene/221322 CPHD Panhypopituitarism GTR C4273747 ICD-10-CM E23.0 MeSH D007018 OMIM 182230 OMIM 221750 OMIM 262600 OMIM 262700 OMIM 613038 OMIM 613986 OMIM 618160 OMIM 620303 SNOMED CT 190470005 SNOMED CT 237682009 SNOMED CT 237683004 SNOMED CT 32390006 SNOMED CT 367460001 SNOMED CT 71003000 SNOMED CT 91187007 2025-05 2025-05-07 Common variable immune deficiency https://medlineplus.gov/genetics/condition/common-variable-immune-deficiency descriptionCommon variable immune deficiency (CVID) is a disorder that impairs the immune system. People with CVID are highly susceptible to infection from foreign invaders such as bacteria, or more rarely, viruses and often develop recurrent infections, particularly in the lungs, sinuses, and ears. Pneumonia is common in people with CVID. Over time, recurrent infections can lead to chronic lung disease. Affected individuals may also experience infection or inflammation of the gastrointestinal tract, which can cause diarrhea and weight loss. Abnormal accumulation of immune cells causes enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly) in some people with CVID. Immune cells can accumulate in other organs, forming small lumps called granulomas.Approximately 25 percent of people with CVID have an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's tissues and organs. The blood cells are most frequently affected by autoimmune attacks in CVID; the most commonly occurring autoimmune disorders are immune thrombocytopenia, which is an abnormal bleeding disorder caused by a decrease in cells involved in blood clotting called platelets, and autoimmune hemolytic anemia, which results in premature destruction of red blood cells. Other autoimmune disorders such as rheumatoid arthritis can occur. Individuals with CVID also have a greater than normal risk of developing certain types of cancer, including a cancer of immune system cells called non-Hodgkin lymphoma and less frequently, stomach (gastric) cancer.People with CVID may start experiencing signs and symptoms of the disorder anytime between childhood and adulthood; most people with CVID are diagnosed in their twenties or thirties. The life expectancy of individuals with CVID varies depending on the severity and frequency of illnesses they experience. Most people with CVID live into adulthood.There are many different types of CVID that are distinguished by genetic cause. People with the same type of CVID may have varying signs and symptoms. ar Autosomal recessive ad Autosomal dominant u Pattern unknown TNFRSF13B https://medlineplus.gov/genetics/gene/tnfrsf13b CD19 https://www.ncbi.nlm.nih.gov/gene/930 MS4A1 https://www.ncbi.nlm.nih.gov/gene/931 CD81 https://www.ncbi.nlm.nih.gov/gene/975 LRBA https://www.ncbi.nlm.nih.gov/gene/987 CR2 https://www.ncbi.nlm.nih.gov/gene/1380 NFKB1 https://www.ncbi.nlm.nih.gov/gene/4790 NFKB2 https://www.ncbi.nlm.nih.gov/gene/4791 PRKCD https://www.ncbi.nlm.nih.gov/gene/5580 IKZF1 https://www.ncbi.nlm.nih.gov/gene/10320 ICOS https://www.ncbi.nlm.nih.gov/gene/29851 IL21 https://www.ncbi.nlm.nih.gov/gene/59067 TNFRSF13C https://www.ncbi.nlm.nih.gov/gene/115650 Common variable hypogammaglobulinemia Common variable immunodeficiency CVID Immunodeficiency, common variable GTR C0009447 ICD-10-CM D83 ICD-10-CM D83.0 ICD-10-CM D83.8 ICD-10-CM D83.9 MeSH D017074 OMIM 240500 OMIM 607594 OMIM 613493 OMIM 613494 OMIM 613495 OMIM 613496 OMIM 614699 OMIM 614700 OMIM 615559 OMIM 615577 OMIM 615767 OMIM 616576 OMIM 616873 SNOMED CT 191011000 SNOMED CT 23238000 2014-07 2023-08-22 Complement component 2 deficiency https://medlineplus.gov/genetics/condition/complement-component-2-deficiency descriptionComplement component 2 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses. People with complement component 2 deficiency have a significantly increased risk of recurrent bacterial infections, specifically of the lungs (pneumonia), the membrane covering the brain and spinal cord (meningitis), and the blood (sepsis), which may be life-threatening. These infections most commonly occur in infancy and childhood and become less frequent in adolescence and adulthood.Complement component 2 deficiency is also associated with an increased risk of developing autoimmune disorders such as systemic lupus erythematosus (SLE) or vasculitis. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. Between 10 and 20 percent of individuals with complement component 2 deficiency develop SLE. Females with complement component 2 deficiency are more likely to have SLE than affected males, but this is also true of SLE in the general population.The severity of complement component 2 deficiency varies widely. While some affected individuals experience recurrent infections and other immune system difficulties, others do not have any health problems related to the disorder. ar Autosomal recessive C2 https://medlineplus.gov/genetics/gene/c2 C2 deficiency C2D Complement 2 deficiency GTR C0398756 MeSH D007153 OMIM 217000 SNOMED CT 234599007 2014-06 2020-08-18 Complement component 8 deficiency https://medlineplus.gov/genetics/condition/complement-component-8-deficiency descriptionComplement component 8 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria. People with complement component 8 deficiency have a significantly increased risk of recurrent bacterial infections, particularly by a bacterium called Neisseria meningitidis. Infection by this bacterium causes inflammation of the membranes surrounding the brain and spinal cord (meningitis). Although meningitis can be life-threatening, individuals with complement component 8 deficiency are less likely to die from the infection than people in the general population who contract it.The severity of complement component 8 deficiency varies widely. While some people with this condition experience one or more infections, others do not have any health problems related to the disorder.There are two types of complement component 8 deficiency, types I and II, classified by their genetic cause. The two types have the same signs and symptoms. ar Autosomal recessive C8A https://medlineplus.gov/genetics/gene/c8a C8B https://medlineplus.gov/genetics/gene/c8b C8 deficiency GTR C3151080 GTR C3151081 ICD-10-CM D84.1 MeSH D007153 OMIM 613789 OMIM 613790 SNOMED CT 234614005 SNOMED CT 234616007 2015-12 2020-08-18 Complement factor I deficiency https://medlineplus.gov/genetics/condition/complement-factor-i-deficiency descriptionComplement factor I deficiency is a disorder that affects the immune system. People with this condition are prone to recurrent infections, including infections of the upper respiratory tract, ears, skin, and urinary tract. They may also contract more serious infections such as pneumonia, meningitis, and sepsis, which may be life-threatening.Some people with complement factor I deficiency have a kidney disorder called glomerulonephritis with isolated C3 deposits. Complement factor I deficiency can also be associated with autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus (SLE). Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. ar Autosomal recessive CFI https://medlineplus.gov/genetics/gene/cfi C3 inactivator deficiency Complement component 3 inactivator deficiency Hereditary factor I deficiency disease GTR C0019250 MeSH D007153 OMIM 610984 SNOMED CT 234621005 2010-09 2020-08-18 Complete LCAT deficiency https://medlineplus.gov/genetics/condition/complete-lcat-deficiency descriptionComplete LCAT deficiency is a disorder that primarily affects the eyes and kidneys.In complete LCAT deficiency, the clear front surface of the eyes (the corneas) gradually becomes cloudy. The cloudiness, which generally first appears in early childhood, consists of small grayish dots of cholesterol (opacities) distributed across the corneas. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals; it aids in many functions of the body but can become harmful in excessive amounts. As complete LCAT deficiency progresses, the corneal cloudiness worsens and can lead to severely impaired vision.People with complete LCAT deficiency often have kidney disease that begins in adolescence or early adulthood. The kidney problems get worse over time and may eventually lead to kidney failure. Individuals with this disorder also usually have a condition known as hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Anemia can cause pale skin, weakness, fatigue, and more serious complications.Other features of complete LCAT deficiency that occur in some affected individuals include enlargement of the liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy) or an accumulation of fatty deposits on the artery walls (atherosclerosis). ar Autosomal recessive LCAT https://medlineplus.gov/genetics/gene/lcat Familial LCAT deficiency Familial lecithin-cholesterol acyltransferase deficiency FLD LCAT deficiency Lecithin acyltransferase deficiency Lecithin:cholesterol acyltransferase deficiency Norum disease Norum's disease GTR C0023195 MeSH D007863 OMIM 245900 SNOMED CT 238091006 2013-08 2020-08-18 Complete plasminogen activator inhibitor 1 deficiency https://medlineplus.gov/genetics/condition/complete-plasminogen-activator-inhibitor-1-deficiency descriptionComplete plasminogen activator inhibitor 1 deficiency (complete PAI-1 deficiency) is a disorder that causes abnormal bleeding. In people with this disorder, bleeding associated with injury can be excessive and last longer than usual.Individuals with complete PAI-1 deficiency may experience prolonged nosebleeds, excessive bleeding after medical or dental procedures, easy bruising, and significant bleeding into the joints or soft tissues after even a minor injury. Internal bleeding after an injury, especially bleeding around the brain (intracranial hemorrhage), can be life-threatening. Affected females may have excessive bleeding associated with menstruation (menorrhagia) and abnormal bleeding in pregnancy and childbirth.In addition to bleeding problems, some people with complete PAI-1 deficiency develop scar tissue in the heart (cardiac fibrosis), which can lead to heart failure. ar Autosomal recessive SERPINE1 https://medlineplus.gov/genetics/gene/serpine1 Complete PAI-1 deficiency Congenital plasminogen activator inhibitor type 1 deficiency Homozygous PAI-1 deficiency Hyperfibrinolysis due to PAI1 deficiency PAI-1 deficiency PAI-1D PAI1 deficiency Plasminogen activator inhibitor type 1 deficiency Plasminogen inhibitor-1 deficiency Quantitative PAI-1 deficiency GTR C2750067 MeSH D025861 OMIM 613329 SNOMED CT 717407006 2017-10 2020-08-18 Cone-rod dystrophy https://medlineplus.gov/genetics/condition/cone-rod-dystrophy descriptionCone-rod dystrophy is a group of related eye disorders that causes vision loss, which becomes more severe over time. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with cone-rod dystrophy, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.The first signs and symptoms of cone-rod dystrophy, which often occur in childhood, are usually decreased sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). These features are typically followed by impaired color vision (dyschromatopsia), blind spots (scotomas) in the center of the visual field, and partial side (peripheral) vision loss. Over time, affected individuals develop night blindness and a worsening of their peripheral vision, which can limit independent mobility. Decreasing visual acuity makes reading increasingly difficult and most affected individuals are legally blind by mid-adulthood. As the condition progresses, individuals may develop involuntary eye movements (nystagmus).There are more than 30 types of cone-rod dystrophy, which are distinguished by their genetic cause and their pattern of inheritance: autosomal recessive, autosomal dominant, and X-linked. Additionally, cone-rod dystrophy can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body. ad Autosomal dominant xr X-linked recessive ar Autosomal recessive PRPH2 https://medlineplus.gov/genetics/gene/prph2 CNGA3 https://medlineplus.gov/genetics/gene/cnga3 CNGB3 https://medlineplus.gov/genetics/gene/cngb3 CACNA1F https://medlineplus.gov/genetics/gene/cacna1f CRB1 https://medlineplus.gov/genetics/gene/crb1 GUCY2D https://medlineplus.gov/genetics/gene/gucy2d RPGR https://medlineplus.gov/genetics/gene/rpgr ABCA4 https://medlineplus.gov/genetics/gene/abca4 PDE6C https://medlineplus.gov/genetics/gene/pde6c CRX https://medlineplus.gov/genetics/gene/crx CFAP410 https://www.ncbi.nlm.nih.gov/gene/755 GUCA1A https://www.ncbi.nlm.nih.gov/gene/2978 TULP1 https://www.ncbi.nlm.nih.gov/gene/7287 ADAM9 https://www.ncbi.nlm.nih.gov/gene/8754 PROM1 https://www.ncbi.nlm.nih.gov/gene/8842 UNC119 https://www.ncbi.nlm.nih.gov/gene/9094 RAB28 https://www.ncbi.nlm.nih.gov/gene/9364 SEMA4A https://www.ncbi.nlm.nih.gov/gene/10510 RIMS1 https://www.ncbi.nlm.nih.gov/gene/22999 TTLL5 https://www.ncbi.nlm.nih.gov/gene/23093 AIPL1 https://www.ncbi.nlm.nih.gov/gene/23746 CNNM4 https://www.ncbi.nlm.nih.gov/gene/26504 RPGRIP1 https://www.ncbi.nlm.nih.gov/gene/57096 PITPNM3 https://www.ncbi.nlm.nih.gov/gene/83394 RAX2 https://www.ncbi.nlm.nih.gov/gene/84839 CDHR1 https://www.ncbi.nlm.nih.gov/gene/92211 CACNA2D4 https://www.ncbi.nlm.nih.gov/gene/93589 DRAM2 https://www.ncbi.nlm.nih.gov/gene/128338 CFAP418 https://www.ncbi.nlm.nih.gov/gene/157657 KCNV2 https://www.ncbi.nlm.nih.gov/gene/169522 POC1B https://www.ncbi.nlm.nih.gov/gene/282809 EYS https://www.ncbi.nlm.nih.gov/gene/346007 CERKL https://www.ncbi.nlm.nih.gov/gene/375298 Cone-rod degeneration Cone-rod retinal dystrophy CORD CRD Retinal cone-rod dystrophy Tapetoretinal degeneration GTR C1423873 GTR C1832976 GTR C1833564 GTR C1835865 GTR C1844776 GTR C1845407 GTR C1846529 GTR C1858806 GTR C1863634 GTR C1866293 GTR C2675210 GTR C2750720 GTR C3150912 GTR C3281045 GTR C3489532 GTR C3554610 GTR C3809299 GTR C4014501 GTR C4014856 GTR C4085590 ICD-10-CM H35.52 MeSH D000071700 OMIM 120970 OMIM 300085 OMIM 300476 OMIM 304020 OMIM 600624 OMIM 600977 OMIM 601777 OMIM 602093 OMIM 603649 OMIM 604116 OMIM 605549 OMIM 608194 OMIM 610283 OMIM 610381 OMIM 612657 OMIM 612775 OMIM 615163 OMIM 615374 OMIM 615860 OMIM 615973 OMIM 616502 SNOMED CT 80328002 2016-02 2020-08-18 Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency https://medlineplus.gov/genetics/condition/congenital-adrenal-hyperplasia-due-to-11-beta-hydroxylase-deficiency descriptionCongenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency is one of a group of disorders (collectively called congenital adrenal hyperplasia) that affect the adrenal glands. The adrenal glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with CAH due to 11-beta-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones.There are two types of CAH due to 11-beta-hydroxylase deficiency, the classic form and the non-classic form. The classic form is the more severe of the two types.Females with the classic form of CAH due to 11-beta-hydroxylase deficiency have external genitalia that do not look clearly male or female (atypical genitalia). However, the internal reproductive organs develop normally. Males and females with the classic form of this condition have early development of their secondary sexual characteristics such as growth of facial and pubic hair, deepening of the voice, appearance of acne, and onset of a growth spurt. The early growth spurt can prevent growth later in adolescence and lead to short stature in adulthood. In addition, approximately two-thirds of individuals with the classic form of CAH due to 11-beta-hydroxylase deficiency have high blood pressure (hypertension). Hypertension typically develops within the first year of life.Females with the non-classic form of CAH due to 11-beta-hydroxylase deficiency have normal female genitalia. As affected females get older, they may develop excessive body hair growth (hirsutism) and irregular menstruation. Males with the non-classic form of this condition do not typically have any signs or symptoms except for short stature. Hypertension is not a feature of the non-classic form of CAH due to 11-beta-hydroxylase deficiency. ar Autosomal recessive CYP11B1 https://medlineplus.gov/genetics/gene/cyp11b1 11 beta hydroxylase deficiency 11b hydroxylase deficiency Adrenal hyperplasia, hypertensive form Deficiency of steroid 11-beta-monooxygenase P450C11B1 deficiency Steroid 11 beta hydroxylase deficiency GTR C0268292 ICD-10-CM E25.0 MeSH D000312 OMIM 202010 SNOMED CT 124214007 SNOMED CT 237751000 2011-03 2023-07-26 Congenital afibrinogenemia https://medlineplus.gov/genetics/condition/congenital-afibrinogenemia descriptionCongenital afibrinogenemia is a bleeding disorder caused by impairment of the blood clotting process. Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, bleeding is uncontrolled in people with congenital afibrinogenemia. Newborns with this condition often experience prolonged bleeding from the umbilical cord stump after birth. Nosebleeds (epistaxis) and bleeding from the gums or tongue are common and can occur after minor trauma or in the absence of injury (spontaneous bleeding). Some affected individuals experience bleeding into the spaces between joints (hemarthrosis) or the muscles (hematoma). Rarely, bleeding in the brain or other internal organs occurs, which can be fatal. Women with congenital afibrinogenemia can have abnormally heavy menstrual bleeding (menorrhagia). Without proper treatment, women with this disorder may have difficulty carrying a pregnancy to term, resulting in repeated miscarriages. ar Autosomal recessive FGA https://medlineplus.gov/genetics/gene/fga FGB https://medlineplus.gov/genetics/gene/fgb FGG https://medlineplus.gov/genetics/gene/fgg Afibrinogenemia Familial afibrinogenemia GTR C0019250 MeSH D000347 OMIM 202400 SNOMED CT 154818001 2012-02 2020-08-18 Congenital anomalies of kidney and urinary tract https://medlineplus.gov/genetics/condition/congenital-anomalies-of-kidney-and-urinary-tract descriptionCongenital anomalies of kidney and urinary tract (CAKUT) is a group of abnormalities affecting the kidneys or other structures of the urinary tract. The additional parts of the urinary tract that may be affected include the bladder, the tubes that carry urine from each kidney to the bladder (the ureters), and the tube that carries urine from the bladder out of the body (the urethra). CAKUT results from abnormal development of the urinary system and is present from birth (congenital), although the abnormality may not become apparent until later in life.Individuals with CAKUT have one or more kidney or urinary tract abnormalities. For paired structures, like the kidneys and ureters, one or both may be affected. Many different developmental abnormalities are classified as CAKUT, including underdevelopment or absence of a kidney (renal hypodysplasia or agenesis), a kidney formed of fluid-filled sacs called cysts (multicystic dysplastic kidney), buildup of urine in the kidneys (hydronephrosis), an extra ureter leading to the kidney (duplex kidney or duplicated collecting system), a blockage in a ureter where it joins the kidney (ureteropelvic junction obstruction), an abnormally wide ureter (megaureter), backflow of urine from the bladder into the ureter (vesicoureteral reflux), and an abnormal membrane in the urethra that blocks the flow of urine out of the bladder (posterior urethral valve).CAKUT varies in severity. The abnormalities can result in recurrent urinary tract infections or a buildup of urine in the urinary tract, which may damage the kidneys or other structures. Severe CAKUT can result in life-threatening kidney failure and end-stage renal disease.CAKUT is often one of several features of a condition that affects multiple body systems (syndromic CAKUT). For example, renal coloboma syndrome, 17q12 deletion syndrome, renal cysts and diabetes (RCAD) syndrome, Fraser syndrome, Townes-Brocks syndrome, and branchio-oto-renal syndrome can cause kidney or urinary tract abnormalities in addition to other problems. However, urinary system abnormalities sometimes occur without other signs and symptoms, which is known as nonsyndromic or isolated CAKUT. u Pattern unknown ar Autosomal recessive n Not inherited ad Autosomal dominant SALL1 https://medlineplus.gov/genetics/gene/sall1 SIX1 https://medlineplus.gov/genetics/gene/six1 EYA1 https://medlineplus.gov/genetics/gene/eya1 SIX5 https://medlineplus.gov/genetics/gene/six5 PAX2 https://medlineplus.gov/genetics/gene/pax2 WNT4 https://medlineplus.gov/genetics/gene/wnt4 FREM1 https://medlineplus.gov/genetics/gene/frem1 FRAS1 https://medlineplus.gov/genetics/gene/fras1 FREM2 https://medlineplus.gov/genetics/gene/frem2 GRIP1 https://medlineplus.gov/genetics/gene/grip1 HNF1B https://medlineplus.gov/genetics/gene/hnf1b BMP4 https://www.ncbi.nlm.nih.gov/gene/652 TBX18 https://www.ncbi.nlm.nih.gov/gene/9096 SIX2 https://www.ncbi.nlm.nih.gov/gene/10736 DSTYK https://www.ncbi.nlm.nih.gov/gene/25778 SOX17 https://www.ncbi.nlm.nih.gov/gene/64321 GREB1L https://www.ncbi.nlm.nih.gov/gene/80000 CAKUT GTR C1968949 MeSH D014564 MeSH D014570 OMIM 143400 OMIM 610805 SNOMED CT 118642009 SNOMED CT 44513007 2018-10 2023-03-21 Congenital bilateral absence of the vas deferens https://medlineplus.gov/genetics/condition/congenital-bilateral-absence-of-the-vas-deferens descriptionCongenital bilateral absence of the vas deferens occurs in males when the tubes that carry sperm out of the testes (the vas deferens) fail to develop properly. Although the testes usually develop and function normally, sperm cannot be transported through the vas deferens to become part of semen. As a result, men with this condition are unable to father children (infertile) unless they use assisted reproductive technologies. This condition has not been reported to affect sex drive or sexual performance.This condition can occur alone or as a sign of cystic fibrosis, an inherited disease of the mucus glands. Cystic fibrosis causes progressive damage to the respiratory system and chronic digestive system problems. Many men with congenital bilateral absence of the vas deferens do not have the other characteristic features of cystic fibrosis; however, some men with this condition may experience mild respiratory or digestive problems. ar Autosomal recessive CFTR https://medlineplus.gov/genetics/gene/cftr Absence of vas deferens Absent vasa CAVD CBAVD Congenital absence of vas deferens Congenital aplasia of vas deferens Congenital bilateral absence of vas deferens GTR C0403814 ICD-10-CM Q55.3 MeSH D052801 OMIM 277180 SNOMED CT 275416002 SNOMED CT 5286009 2008-01 2023-03-21 Congenital bile acid synthesis defect type 1 https://medlineplus.gov/genetics/condition/congenital-bile-acid-synthesis-defect-type-1 descriptionCongenital bile acid synthesis defect type 1 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Bile is used during digestion to absorb fats and fat-soluble vitamins, such as vitamins A, D, E, and K. People with congenital bile acid synthesis defect type 1 cannot produce (synthesize) bile acids, which are a component of bile that stimulate bile flow and help it absorb fats and fat-soluble vitamins. As a result, an abnormal form of bile is produced.The signs and symptoms of congenital bile acid synthesis defect type 1 often develop during the first weeks of life, but they can begin anytime from infancy into adulthood. Affected infants often have a failure to gain weight and grow at the expected rate (failure to thrive) and yellowing of the skin and eyes (jaundice) due to impaired bile flow and a buildup of partially formed bile. Excess fat in the feces (steatorrhea) is an additional feature of congenital bile acid synthesis defect type 1. As the condition progresses, affected individuals can develop liver abnormalities including an enlarged liver (hepatomegaly), inflammation, or chronic liver disease (cirrhosis). The spleen may also become enlarged (splenomegaly). The inability to absorb certain fat-soluble vitamins (vitamin D in particular) can result in softening and weakening of the bones (rickets) in some individuals.If left untreated, congenital bile acid synthesis defect type 1 often leads to cirrhosis and death in childhood. ar Autosomal recessive HSD3B7 https://medlineplus.gov/genetics/gene/hsd3b7 3beta-HSDH deficiency 3beta-hydroxy-delta-5-C27-steroid dehydrogenase deficiency 3beta-hydroxy-delta-5-C27-steroid oxidoreductase deficiency CBAS1 GTR C1843116 MeSH D002779 OMIM 607765 SNOMED CT 238033007 2015-04 2020-08-18 Congenital bile acid synthesis defect type 2 https://medlineplus.gov/genetics/condition/congenital-bile-acid-synthesis-defect-type-2 descriptionCongenital bile acid synthesis defect type 2 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Bile is used during digestion to absorb fats and fat-soluble vitamins, such as vitamins A, D, E, and K. People with congenital bile acid synthesis defect type 2 cannot produce (synthesize) bile acids, which are a component of bile that stimulate bile flow and help it absorb fats and fat-soluble vitamins. As a result, an abnormal form of bile is produced.The signs and symptoms of congenital bile acid synthesis defect type 2 often develop in infancy. Affected infants usually have a failure to gain weight and grow at the expected rate (failure to thrive) and yellowing of the skin and eyes (jaundice) due to impaired bile flow and a buildup of partially formed bile. Excess fat in the feces (steatorrhea) is another feature of congenital bile acid synthesis defect type 2. As the condition progresses, affected individuals can develop liver abnormalities including inflammation or chronic liver disease (cirrhosis). Some individuals with congenital bile acid synthesis defect type 2 cannot absorb certain fat-soluble vitamins, which can result in softening and weakening of the bones (rickets) or problems with blood clotting that lead to prolonged bleeding.If left untreated, congenital bile acid synthesis defect type 2 typically leads to cirrhosis and death in childhood. ar Autosomal recessive AKR1D1 https://medlineplus.gov/genetics/gene/akr1d1 CBAS2 Cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency GTR C1856127 MeSH D002779 OMIM 235555 SNOMED CT 238035000 2015-04 2020-08-18 Congenital cataracts, facial dysmorphism, and neuropathy https://medlineplus.gov/genetics/condition/congenital-cataracts-facial-dysmorphism-and-neuropathy descriptionCongenital cataracts, facial dysmorphism, and neuropathy (CCFDN) is a rare disorder that affects several parts of the body. It is characterized by a clouding of the lens of the eyes at birth (congenital cataracts) and other eye abnormalities, such as small or poorly developed eyes (microphthalmia) and abnormal eye movements (nystagmus). Affected individuals, particularly males, often have distinctive facial features that become more apparent as they reach adulthood. These features include a prominent midface, a large nose, protruding teeth, and a small lower jaw.CCFDN causes progressive damage to the peripheral nerves, which connect the brain and spinal cord to muscles and sensory cells. This nerve damage is known as peripheral neuropathy. Weakness in the legs, followed by the arms, begins in the first few years of life, and as a result children with CCFDN have delayed development of motor skills such as standing and walking. In adolescence, affected individuals develop sensory abnormalities such as numbness and tingling, mainly in the legs. By adulthood they typically have significant difficulties with mobility. Muscle weakness can also lead to skeletal abnormalities such as hand and foot deformities and abnormal curvature of the spine.People with CCFDN may have problems with balance and coordination (ataxia), tremors, and difficulty with movements that involve judging distance or scale (dysmetria). Some have mild intellectual disability. Individuals with CCFDN have short stature, are typically underweight, and have reduced bone density.A complication called rhabdomyolysis occurs in some people with CCFDN, typically following a viral infection or, in rare cases, during or after surgery. Rhabdomyolysis is a breakdown of muscle tissue that results in severe muscle weakness. The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). The presence of myoglobin causes the urine to be red or brown. The muscles may take up to a year to recover, and the episodes may worsen the muscle weakness caused by the neuropathy. ar Autosomal recessive CTDP1 https://medlineplus.gov/genetics/gene/ctdp1 CCFDN GTR C1858726 MeSH D015417 OMIM 604168 SNOMED CT 702433001 2010-04 2020-08-18 Congenital central hypoventilation syndrome https://medlineplus.gov/genetics/condition/congenital-central-hypoventilation-syndrome descriptionCongenital central hypoventilation syndrome (CCHS) is a disorder that affects normal breathing. People with this disorder take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Ordinarily, the part of the nervous system that controls involuntary body processes (autonomic nervous system) would react to such an imbalance by stimulating the individual to breathe more deeply or wake up. This nervous system reaction is impaired in people with CCHS. They must be supported with a machine to help them breathe (mechanical ventilation) or a device that stimulates a normal breathing pattern (diaphragm pacemaker). Some affected individuals need this support 24 hours a day, while others need it only at night.Symptoms of CCHS usually become apparent shortly after birth when affected infants hypoventilate upon falling asleep. In these infants, a lack of oxygen in the blood often causes a bluish appearance of the skin or lips (cyanosis). In some milder cases, CCHS may not become apparent until later in life.In addition to the breathing problem, people with CCHS may have difficulty regulating their heart rate and blood pressure, for example, in response to exercise or changes in body position. They also have decreased perception of pain, low body temperature, and occasional episodes of heavy sweating.People with CCHS may have additional problems affecting the nervous system. About 20 percent of people with CCHS have abnormalities in the nerves that control the digestive tract (Hirschsprung disease), resulting in severe constipation, intestinal blockage, and enlargement of the colon. (Some researchers refer to the combination of CCHS and Hirschsprung disease as Haddad syndrome.) Some affected individuals develop learning difficulties or other neurological problems. People with CCHS are also at increased risk of developing certain tumors of the nervous system called neuroblastomas, ganglioneuromas, and ganglioneuroblastomas.Additionally, individuals with CCHS usually have eye abnormalities, including a decreased response of the pupils to light. People with CCHS, especially children, may have a characteristic appearance with a short, wide, somewhat flattened face often described as "box-shaped."In CCHS, life expectancy and the extent of any intellectual disabilities depend on the severity of the disorder, timing of the diagnosis, and the success of treatment. ad Autosomal dominant PHOX2B https://medlineplus.gov/genetics/gene/phox2b CCHS Congenital central hypoventilation Congenital failure of autonomic control Haddad syndrome Ondine syndrome Ondine-Hirschsprung disease GTR C1275808 ICD-10-CM G47.35 MeSH D020182 OMIM 209880 SNOMED CT 399040002 2008-09 2023-03-21 Congenital contractural arachnodactyly https://medlineplus.gov/genetics/condition/congenital-contractural-arachnodactyly descriptionCongenital contractural arachnodactyly is a disorder that affects many parts of the body. People with this condition typically are tall with long limbs (dolichostenomelia) and long, slender fingers and toes (arachnodactyly). They often have permanently bent joints (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Additional features of congenital contractural arachnodactyly include underdeveloped muscles, a rounded upper back that also curves to the side (kyphoscoliosis), permanently bent fingers and toes (camptodactyly), ears that look "crumpled," and a protruding chest (pectus carinatum). Rarely, people with congenital contractural arachnodactyly have heart defects such as an enlargement of the blood vessel that distributes blood from the heart to the rest of the body (aortic root dilatation) or a leak in one of the valves that control blood flow through the heart (mitral valve prolapse). The life expectancy of individuals with congenital contractural arachnodactyly varies depending on the severity of symptoms but is typically not shortened.A rare, severe form of congenital contractural arachnodactyly involves both heart and digestive system abnormalities in addition to the skeletal features described above; individuals with this severe form of the condition usually do not live past infancy. ad Autosomal dominant FBN2 https://medlineplus.gov/genetics/gene/fbn2 Arthrogyroposis, distal, type 9 Beals syndrome Beals-Hecht syndrome CCA Contractural arachnodactyly, congenital DA9 Distal arthrogyropsis type 9 GTR C0220668 MeSH D001176 OMIM 121050 SNOMED CT 205821003 2008-02 2020-08-18 Congenital deafness with labyrinthine aplasia, microtia, and microdontia https://medlineplus.gov/genetics/condition/congenital-deafness-with-labyrinthine-aplasia-microtia-and-microdontia descriptionCongenital deafness with labyrinthine aplasia, microtia, and microdontia (also called LAMM syndrome) is a condition that affects development of the ears and teeth. In people with this condition, the structures that form the inner ear are usually completely absent (labyrinthine aplasia). Rarely, affected individuals have some underdeveloped inner ear structures in one or both ears. The abnormalities of the inner ear cause a form of hearing loss called sensorineural deafness that is present from birth (congenital). Because the inner ear is important for balance as well as hearing, development of motor skills, such as sitting and crawling, may be delayed in affected infants. In addition, people with LAMM syndrome often have abnormally small outer ears (microtia) with narrow ear canals. They can also have unusually small, widely spaced teeth (microdontia). ar Autosomal recessive FGF3 https://medlineplus.gov/genetics/gene/fgf3 Congenital deafness with inner ear agenesis, microtia, and microdontia Deafness with LAMM LAMM syndrome GTR C1853144 MeSH D006311 OMIM 610706 SNOMED CT 702360007 2012-11 2020-08-18 Congenital diaphragmatic hernia https://medlineplus.gov/genetics/condition/congenital-diaphragmatic-hernia descriptionCongenital diaphragmatic hernia is a defect in the diaphragm. The diaphragm, which is composed of muscle and other fibrous tissue, separates the organs in the abdomen from those in the chest. Abnormal development of the diaphragm before birth leads to defects ranging from a thinned area in the diaphragm to its complete absence. An absent or partially formed diaphragm results in an abnormal opening (hernia) that allows the stomach and intestines to move into the chest cavity and crowd the heart and lungs. This crowding can lead to underdevelopment of the lungs (pulmonary hypoplasia), potentially resulting in life-threatening breathing difficulties that are apparent from birth.In 5 to 10 percent of affected individuals, signs and symptoms of congenital diaphragmatic hernia appear later in life and may include breathing problems or abdominal pain from protrusion of the intestine into the chest cavity. In about 1 percent of cases, congenital diaphragmatic hernia has no symptoms; it may be detected incidentally when medical imaging is done for other reasons.Congenital diaphragmatic hernias are often classified by their position. A Bochdalek hernia is a defect in the side or back of the diaphragm. Between 80 and 90 percent of congenital diaphragmatic hernias are of this type. A Morgnani hernia is a defect involving the front part of the diaphragm. This type of congenital diaphragmatic hernia, which accounts for approximately 2 percent of cases, is less likely to cause severe symptoms at birth. Other types of congenital diaphragmatic hernia, such as those affecting the central region of the diaphragm, or those in which the diaphragm muscle is absent with only a thin membrane in its place, are rare. u Pattern unknown GATA4 https://www.ncbi.nlm.nih.gov/gene/2626 ZFPM2 https://www.ncbi.nlm.nih.gov/gene/23414 Congenital diaphragmatic defect GTR C1857284 GTR C1857781 ICD-10-CM Q79.0 MeSH D006548 OMIM 142340 OMIM 222400 OMIM 610187 SNOMED CT 17190001 2011-01 2024-05-22 Congenital dyserythropoietic anemia https://medlineplus.gov/genetics/condition/congenital-dyserythropoietic-anemia descriptionCongenital dyserythropoietic anemia (CDA) is a rare group of inherited blood disorders that affects the development of red blood cells. In people with CDA, immature red blood cells do not develop into normal, mature cells. As a result, affected individuals have a significant reduction in the number of functional red blood cells (anemia). The term "dyserythropoietic" refers to the abnormal red blood cell shape that occurs in people with this condition. People with CDA typically have mild to moderate anemia. In some cases, affected individuals have severe anemia that may require frequent blood transfusions to replenish the supply of red blood cells.The signs and symptoms of CDA can include tiredness (fatigue), weakness, yellowing of the skin and eyes (jaundice), and an enlarged liver and spleen (hepatosplenomegaly). CDA also causes the body to absorb too much iron (iron overload), which can damage tissues and organs.There are multiple types of CDA. Each type has a different genetic cause and distinct but overlapping patterns of signs and symptoms.CDA type I is characterized by moderate to severe anemia that typically begins in childhood or adolescence, although the condition can be detected before birth in some cases. In addition to the signs and symptoms common to all types of CDA, individuals with CDA type I can have skeletal issues, including short stature or abnormalities of the fingers or toes.The anemia associated with CDA type II can range from mild to severe, and it usually develops in adolescence or early adulthood. Individuals with CDA type II may develop hard deposits in the gallbladder called gallstones in addition to the usual signs and symptoms of CDA.CDA type III can result in anemia that ranges from mild to severe, depending on the genetic cause, and typically begins in infancy or childhood. Some people with CDA type III do not receive a diagnosis until later in life because they have very mild symptoms. In some cases, individuals with CDA type III develop a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma). Some people with CDA type III have eye abnormalities that can cause vision impairment.CDA type IV is characterized by moderate to severe anemia that typically develops early in life, although the condition can be detected before birth in some cases. Affected individuals can have extensive swelling caused by fluid accumulation before birth (hydrops fetalis). In addition to the signs and symptoms that are common to all types of CDA, individuals with CDA type IV often have short stature. ar Autosomal recessive ad Autosomal dominant+1 affected parent CDAN1 https://medlineplus.gov/genetics/gene/cdan1 SEC23B https://medlineplus.gov/genetics/gene/sec23b KIF23 https://medlineplus.gov/genetics/gene/kif23 CDIN1 https://medlineplus.gov/genetics/gene/cdin1 RACGAP1 https://medlineplus.gov/genetics/gene/racgap1 KLF1 https://medlineplus.gov/genetics/gene/klf1 Anemia, dyserythropoietic, congenital CDA congenital dyserythropoietic anaemia GTR C0002876 ICD-10-CM D64.4 MeSH D000742 OMIM 105600 OMIM 224100 OMIM 224120 OMIM 613673 OMIM 615631 OMIM 619789 SNOMED CT 26409005 SNOMED CT 52951008 SNOMED CT 59548005 SNOMED CT 68870007 2025-03 2025-03-04 Congenital fiber-type disproportion https://medlineplus.gov/genetics/condition/congenital-fiber-type-disproportion descriptionCongenital fiber-type disproportion is a condition that primarily affects skeletal muscles, which are muscles used for movement. People with this condition typically experience muscle weakness (myopathy), particularly in the muscles of the shoulders, upper arms, hips, and thighs. Weakness can also affect the muscles of the face and muscles that control eye movement (ophthalmoplegia), sometimes causing droopy eyelids (ptosis). Individuals with congenital fiber-type disproportion generally have a long face, a high arch in the roof of the mouth (high-arched palate), and crowded teeth.Individuals with congenital fiber-type disproportion may have joint deformities (contractures) and an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Approximately 30 percent of people with this disorder experience mild to severe breathing problems related to weakness of muscles needed for breathing. Some people who experience these breathing problems require use of a machine to help regulate their breathing at night (noninvasive mechanical ventilation), and occasionally during the day as well. About 30 percent of affected individuals have difficulty swallowing due to muscle weakness in the throat. Rarely, people with this condition have a weakened and enlarged heart muscle (dilated cardiomyopathy).The severity of congenital fiber-type disproportion varies widely. It is estimated that up to 25 percent of affected individuals experience severe muscle weakness at birth and die in infancy or childhood. Others have only mild muscle weakness that becomes apparent in adulthood. Most often, the signs and symptoms of this condition appear by age 1. The first signs of this condition are usually decreased muscle tone (hypotonia) and muscle weakness. In most cases, muscle weakness does not worsen over time, and in some instances it may improve. Although motor skills such as standing and walking may be delayed, many affected children eventually learn to walk. These individuals often have less stamina than their peers, but they remain active. Rarely, people with this condition have a progressive decline in muscle strength over time. These individuals may lose the ability to walk and require wheelchair assistance. ar Autosomal recessive ad Autosomal dominant x X-linked RYR1 https://medlineplus.gov/genetics/gene/ryr1 SELENON https://medlineplus.gov/genetics/gene/selenon MYH7 https://medlineplus.gov/genetics/gene/myh7 ACTA1 https://medlineplus.gov/genetics/gene/acta1 TPM3 https://medlineplus.gov/genetics/gene/tpm3 TPM2 https://medlineplus.gov/genetics/gene/tpm2 CFTD CFTDM Congenital myopathy with fiber type disproportion GTR C0546264 MeSH D020914 OMIM 255310 SNOMED CT 240084007 2010-07 2020-08-18 Congenital fibrosis of the extraocular muscles https://medlineplus.gov/genetics/condition/congenital-fibrosis-of-the-extraocular-muscles descriptionCongenital fibrosis of the extraocular muscles (CFEOM) is a disorder of the nervous system that affects use of the muscles that surround the eyes (extraocular muscles). These muscles control eye movement and the direction of the eyes (for example, looking straight ahead). CFEOM impairs control of these muscles. As a result, affected individuals are unable to move their eyes normally. Most people with this condition have difficulty looking upward, and their side-to-side eye movement may also be limited. The eyes may look in different directions (strabismus). Instead of moving their eyes, affected individuals may need to turn their head to track moving objects. Additionally, most people with CFEOM have droopy eyelids (ptosis), which further limits their vision.Researchers have identified several forms of CFEOM, designated CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome (sometimes called CFEOM4). The specific problems with eye movement vary among the types, and some types are associated with additional signs and symptoms. People with CFEOM1 and CFEOM2 have only the eye problems described above. In CFEOM1, the eyes typically point downward, whereas in CFEOM2, the eyes usually turn outward.CFEOM3 can include additional neurological problems, such as intellectual disability; difficulty with social skills; a smaller-than-normal head size (microcephaly); muscle weakness in the face; nonfunctioning vocal cords; and a set of symptoms called Kallmann syndrome, which features delayed or absent puberty and an impaired sense of smell. Some affected individuals develop pain, weakness, or a decreased ability to feel sensations in the limbs (peripheral neuropathy), which can begin in childhood or adulthood.Brain abnormalities can also occur in people with CFEOM3. Some have abnormal development of the white matter, which is brain tissue containing nerve cell fibers (axons) that transmit nerve impulses. A particular form of CFEOM3, known as CFEOM3 with polymicrogyria, is characterized by abnormal development of the brain, in which the folds and ridges on the surface of the brain are smaller and more numerous than usual.Tukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities in addition to problems with eye movement. ar Autosomal recessive ad Autosomal dominant KIF21A https://medlineplus.gov/genetics/gene/kif21a PHOX2A https://medlineplus.gov/genetics/gene/phox2a TUBB3 https://medlineplus.gov/genetics/gene/tubb3 TUBB2B https://medlineplus.gov/genetics/gene/tubb2b CFEOM Congenital external ophthalmoplegia Congenital fibrosis of extraocular muscles Congenital fibrosis syndrome General fibrosis syndrome GTR C1302995 MeSH D015785 OMIM 135700 OMIM 600638 OMIM 602078 OMIM 609428 SNOMED CT 204217005 SNOMED CT 400946004 2019-10 2023-08-18 Congenital generalized lipodystrophy https://medlineplus.gov/genetics/condition/congenital-generalized-lipodystrophy descriptionCongenital generalized lipodystrophy (also called Berardinelli-Seip congenital lipodystrophy) is a rare condition characterized by an almost total lack of fatty (adipose) tissue in the body and a very muscular appearance. Adipose tissue is found in many parts of the body, including beneath the skin and surrounding the internal organs. It stores fat for energy and also provides cushioning. Congenital generalized lipodystrophy is part of a group of related disorders known as lipodystrophies, which are all characterized by a loss of adipose tissue. A shortage of adipose tissue leads to the storage of fat elsewhere in the body, such as in the liver and muscles, which causes serious health problems.The signs and symptoms of congenital generalized lipodystrophy are usually apparent from birth or early childhood. One of the most common features is insulin resistance, a condition in which the body's tissues are unable to recognize insulin, a hormone that normally helps to regulate levels of blood glucose, also called blood sugar. Insulin resistance may develop into a more serious disease called diabetes mellitus. Most affected individuals also have high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia), which can lead to the development of small yellow deposits of fat under the skin called eruptive xanthomas and inflammation of the pancreas (pancreatitis). Additionally, congenital generalized lipodystrophy causes an abnormal buildup of fats in the liver (hepatic steatosis), which can result in an enlarged liver (hepatomegaly) and liver failure. Some affected individuals develop a form of heart disease called hypertrophic cardiomyopathy, which can lead to heart failure and an abnormal heart rhythm (arrhythmia) that can cause sudden death.People with congenital generalized lipodystrophy have a distinctive physical appearance. They appear very muscular because they have an almost complete absence of adipose tissue and an overgrowth of muscle tissue. A lack of adipose tissue under the skin also makes the veins appear prominent. Affected individuals tend to have prominent bones above the eyes (orbital ridges), large hands and feet, and a prominent belly button (umbilicus). Affected females may have an enlarged clitoris (clitoromegaly), an increased amount of body hair (hirsutism), irregular menstrual periods, and multiple cysts on the ovaries, which may be related to hormonal changes. Many people with this disorder develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.Researchers have described four types of congenital generalized lipodystrophy, which are distinguished by their genetic cause. The types also have some differences in their typical signs and symptoms. For example, in addition to the features described above, some people with congenital generalized lipodystrophy type 1 develop cysts in the long bones of the arms and legs after puberty. Type 2 can be associated with intellectual disability, which is usually mild to moderate. Type 3 appears to cause poor growth and short stature, along with other health problems. Type 4 is associated with muscle weakness, delayed development, joint abnormalities, a narrowing of the lower part of the stomach (pyloric stenosis), and severe arrhythmia that can lead to sudden death. ar Autosomal recessive BSCL2 https://medlineplus.gov/genetics/gene/bscl2 AGPAT2 https://medlineplus.gov/genetics/gene/agpat2 CAV1 https://medlineplus.gov/genetics/gene/cav1 CAVIN1 https://medlineplus.gov/genetics/gene/cavin1 Berardinelli-Seip congenital lipodystrophy Berardinelli-Seip syndrome Brunzell syndrome (with bone cysts) BSCL Generalized lipodystrophy Lipodystrophy, congenital generalized Seip syndrome Total lipodystrophy GTR C0221032 GTR C1720862 GTR C1720863 GTR C2675861 GTR C2750069 MeSH D052497 OMIM 269700 OMIM 608594 OMIM 612526 OMIM 613327 SNOMED CT 284449005 2015-12 2023-07-26 Congenital hepatic fibrosis https://medlineplus.gov/genetics/condition/congenital-hepatic-fibrosis descriptionCongenital hepatic fibrosis is a disease of the liver that is present from birth. The liver has many important functions, including producing various substances needed by the body and breaking down other substances into smaller parts to be used or removed from the body.Congenital hepatic fibrosis is characterized by abnormal formation of the bile ducts and the blood vessels of the hepatic portal system. Bile ducts carry bile (a fluid that helps to digest fats) from the liver to the gallbladder and small intestine. The hepatic portal system is a branching network of veins (portal veins) that carry blood from the gastrointestinal tract to the liver for processing.A buildup of scar tissue (fibrosis) in the portal tracts also occurs in this disorder. Portal tracts are structures in the liver that bundle the vessels through which blood, lymph, and bile flow. Lymph is a fluid that helps exchange immune cells, proteins, and other substances between the blood and tissues. Fibrosis in the portal tracts can restrict the normal movement of fluids in these vessels.Narrowing of the portal veins due to malformation and portal tract fibrosis results in high blood pressure in the hepatic portal system (portal hypertension). Portal hypertension impairs the flow of blood from the gastrointestinal tract, causing an increase in pressure in the veins of the esophagus, stomach, and intestines. These veins may stretch and their walls may become thin, leading to a risk of abnormal bleeding.People with congenital hepatic fibrosis have an enlarged liver and spleen (hepatosplenomegaly). The liver is also abnormally shaped. Affected individuals also have an increased risk of infection of the bile ducts (cholangitis), hard deposits in the gallbladder or bile ducts (gallstones), and cancer of the liver or gallbladder.Congenital hepatic fibrosis may occur alone, in which case it is called isolated congenital hepatic fibrosis. More frequently, it occurs as a feature of genetic syndromes that also affect the kidneys, such as polycystic kidney disease (PKD). ad Autosomal dominant xr X-linked recessive ar Autosomal recessive CHF Congenital fibrose liver GTR C0009714 MeSH D008107 OMIM 263200 SNOMED CT 79607001 2012-01 2023-04-06 Congenital hyperinsulinism https://medlineplus.gov/genetics/condition/congenital-hyperinsulinism descriptionCongenital hyperinsulinism is a condition that causes individuals to have abnormally high levels of insulin. Insulin is a hormone that helps control levels of blood glucose, also called blood sugar. People with this condition have frequent episodes of low blood glucose (hypoglycemia). In infants and young children, these episodes are characterized by a lack of energy (lethargy), irritability, or difficulty feeding. Repeated episodes of low blood glucose increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma.The severity of congenital hyperinsulinism varies widely among affected individuals, even among members of the same family. About 60 percent of infants with this condition experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. Unlike typical episodes of hypoglycemia, which occur most often after periods without food (fasting) or after exercising, episodes of hypoglycemia in people with congenital hyperinsulinism can also occur after eating. ad Autosomal dominant ar Autosomal recessive HADH https://medlineplus.gov/genetics/gene/hadh ABCC8 https://medlineplus.gov/genetics/gene/abcc8 KCNJ11 https://medlineplus.gov/genetics/gene/kcnj11 HNF1A https://medlineplus.gov/genetics/gene/hnf1a GCK https://medlineplus.gov/genetics/gene/gck HNF4A https://medlineplus.gov/genetics/gene/hnf4a GLUD1 https://www.ncbi.nlm.nih.gov/gene/2746 SLC16A1 https://www.ncbi.nlm.nih.gov/gene/6566 UCP2 https://www.ncbi.nlm.nih.gov/gene/7351 Hyperinsulinemia hypoglycemia of infancy Infancy hyperinsulinemia hypoglycemia Neonatal hyperinsulinism Persistent hyperinsulinemia hypoglycemia of infancy Persistent hyperinsulinemic hypoglycemia PHHI hypoglycemia GTR C1847555 GTR C1864902 GTR C1864948 GTR C1864952 GTR C1865290 GTR C2931832 GTR C2931833 GTR C3888018 ICD-10-CM E16.1 MeSH D044903 OMIM 256450 OMIM 601820 OMIM 602485 OMIM 606762 OMIM 609968 OMIM 609975 OMIM 610021 SNOMED CT 360339005 2014-01 2023-07-19 Congenital hypothyroidism https://medlineplus.gov/genetics/condition/congenital-hypothyroidism descriptionCongenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital). The thyroid gland is a butterfly-shaped tissue in the lower neck. It makes iodine-containing hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). People with congenital hypothyroidism have lower-than-normal levels of these important hormones.Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80 to 85 percent of cases, the thyroid gland is absent, severely reduced in size (hypoplastic), or abnormally located. These cases are classified as thyroid dysgenesis. In the remainder of cases, a normal-sized or enlarged thyroid gland (goiter) is present, but production of thyroid hormones is decreased or absent. Most of these cases occur when one of several steps in the hormone synthesis process is impaired; these cases are classified as thyroid dyshormonogenesis. Less commonly, reduction or absence of thyroid hormone production is caused by impaired stimulation of the production process (which is normally done by a structure at the base of the brain called the pituitary gland), even though the process itself is unimpaired. These cases are classified as central (or pituitary) hypothyroidism.Signs and symptoms of congenital hypothyroidism result from the shortage of thyroid hormones. Affected babies may show no features of the condition, although some babies with congenital hypothyroidism are less active and sleep more than normal. They may have difficulty feeding and experience constipation. If untreated, congenital hypothyroidism can lead to intellectual disability and slow growth. In the United States and many other countries, all hospitals test newborns for congenital hypothyroidism. If treatment begins in the first two weeks after birth, infants usually develop normally.Congenital hypothyroidism can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic. Some common forms of syndromic hypothyroidism include Pendred syndrome, Bamforth-Lazarus syndrome, and brain-lung-thyroid syndrome. ad Autosomal dominant ar Autosomal recessive SLC26A4 https://medlineplus.gov/genetics/gene/slc26a4 PAX8 https://medlineplus.gov/genetics/gene/pax8 TSHB https://medlineplus.gov/genetics/gene/tshb TSHR https://medlineplus.gov/genetics/gene/tshr TG https://medlineplus.gov/genetics/gene/tg SLC5A5 https://medlineplus.gov/genetics/gene/slc5a5 TPO https://medlineplus.gov/genetics/gene/tpo DUOX2 https://medlineplus.gov/genetics/gene/duox2 NKX2-5 https://www.ncbi.nlm.nih.gov/gene/1482 THRA https://www.ncbi.nlm.nih.gov/gene/7067 TRHR https://www.ncbi.nlm.nih.gov/gene/7201 IYD https://www.ncbi.nlm.nih.gov/gene/389434 DUOXA2 https://www.ncbi.nlm.nih.gov/gene/405753 CH CHT Congenital myxedema Cretinism GTR C0010308 GTR C0342196 GTR C1291299 GTR C1846632 GTR C1848805 GTR C1869118 GTR C3493776 ICD-10-CM E03.0 ICD-10-CM E03.1 ICD-10-CM E03.8 ICD-10-CM E03.9 MeSH D003409 OMIM 218700 OMIM 274400 OMIM 274500 OMIM 274900 OMIM 275200 OMIM 607200 SNOMED CT 190268003 SNOMED CT 237515009 SNOMED CT 278503003 SNOMED CT 367524008 SNOMED CT 64491003 SNOMED CT 75065003 2015-09 2023-01-23 Congenital insensitivity to pain with anhidrosis https://medlineplus.gov/genetics/condition/congenital-insensitivity-to-pain-with-anhidrosis descriptionCongenital insensitivity to pain with anhidrosis (CIPA) has two characteristic features: the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). This condition is also known as hereditary sensory and autonomic neuropathy type IV. The signs and symptoms of CIPA appear early, usually at birth or during infancy, but with careful medical attention, affected individuals can live into adulthood.An inability to feel pain and temperature often leads to repeated severe injuries. Unintentional self-injury is common in people with CIPA, typically by biting the tongue, lips, or fingers, which may lead to spontaneous amputation of the affected area. In addition, people with CIPA heal slowly from skin and bone injuries. Repeated trauma can lead to chronic bone infections (osteomyelitis) or a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.Normally, sweating helps cool the body temperature. However, in people with CIPA, anhidrosis often causes recurrent, extremely high fevers (hyperpyrexia) and seizures brought on by high temperature (febrile seizures).In addition to the characteristic features, there are other signs and symptoms of CIPA. Many affected individuals have thick, leathery skin (lichenification) on the palms of their hands or misshapen fingernails or toenails. They can also have patches on their scalp where hair does not grow (hypotrichosis). About half of people with CIPA show signs of hyperactivity or emotional instability, and many affected individuals have intellectual disability. Some people with CIPA have weak muscle tone (hypotonia) when they are young, but muscle strength and tone become more normal as they get older. ar Autosomal recessive NTRK1 https://medlineplus.gov/genetics/gene/ntrk1 CIPA Hereditary insensitivity to pain with anhidrosis Hereditary sensory and autonomic neuropathy type IV Hereditary sensory and autonomic neuropathy, type 4 HSAN type IV HSAN4 GTR C0020074 MeSH D009477 OMIM 256800 SNOMED CT 62985007 2011-05 2020-08-18 Congenital leptin deficiency https://medlineplus.gov/genetics/condition/congenital-leptin-deficiency descriptionCongenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. Without treatment, the extreme hunger continues and leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret.People with congenital leptin deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Without treatment, affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile). ar Autosomal recessive LEP https://medlineplus.gov/genetics/gene/lep LEPD Leptin deficiency Obesity due to congenital leptin deficiency Obesity, morbid, due to leptin deficiency Obesity, morbid, nonsyndromic 1 Obesity, severe, due to leptin deficiency GTR C3554224 MeSH D009767 OMIM 614962 SNOMED CT 700150001 2013-12 2020-08-18 Congenital mirror movement disorder https://medlineplus.gov/genetics/condition/congenital-mirror-movement-disorder descriptionCongenital mirror movement disorder is a condition in which intentional movements of one side of the body are mirrored by involuntary movements of the other side. For example, when an affected individual makes a fist with the right hand, the left hand makes a similar movement. The mirror movements in people with this disorder primarily affect the arms, and the hands and fingers are always involved. This pattern of movements is present from infancy or early childhood and usually persists throughout a person's life.People with congenital mirror movement disorder can have some difficulty with certain daily activities, particularly with those that require different movements in each hand, such as typing on a keyboard. They may experience discomfort or pain in their arms during prolonged use of the hands.The extent of the mirror movements in people with congenital mirror movement disorder can vary, even within the same family. In most cases, the involuntary movements are noticeable but less pronounced than the corresponding voluntary movements. The extent of the movements typically stay the same throughout the lifetime of an affected individual.In general, mirror movements are the only feature associated with this condition. In some cases, however, people with congenital mirror movement disorder can have partial or complete absence (agenesis) of the tissue that connects the left and right halves of the brain (corpus callosum).Mirror movements can also occur in people who do not have congenital mirror movement disorder. Mild mirror movements are common during the normal development of young children, and they typically disappear before age 7. They can also develop later in life in people with neurodegenerative disorders such as Parkinson's disease. Mirror movements may also be present in people with certain conditions that have a wider range of signs and symptoms (syndromes). ar Autosomal recessive ad Autosomal dominant+1 affected parent RAD51 https://medlineplus.gov/genetics/gene/rad51 DCC https://medlineplus.gov/genetics/gene/dcc NTN1 https://medlineplus.gov/genetics/gene/ntn1 CMM Congenital mirror movements Familial congenital controlateral synkinesia Familial congenital mirror movements Hereditary congenital controlateral synkinesia Hereditary congenital mirror movements Isolated congenital controlateral synkinesia Isolated congenital mirror movements Mirror movements 1 GTR C1834870 MeSH D009069 OMIM 157600 OMIM 614508 OMIM 618264 SNOMED CT 229247004 2025-05 2025-05-19 Congenital myasthenic syndromes https://medlineplus.gov/genetics/condition/congenital-myasthenic-syndrome descriptionCongenital myasthenic syndromes are a group of conditions that are characterized by weak muscles that tire easily (myasthenia). In people with these conditions, myasthenia typically begins shortly after birth or during early childhood. The most commonly affected muscles are the muscles in the head and neck (bulbar muscles) that control chewing and swallowing, speech, and facial expressions; the muscles that move the eyes and eyelids; and the muscles in the arms and legs. However, any of the muscles used for movement (skeletal muscles) can be affected.In individuals with congenital myasthenic syndromes, episodes of severe weakness or breathing problems may be triggered by fevers, infection, or tiring physical activity. The severity of the myasthenia varies greatly, from minor muscle weakness to severe weakness that may require wheelchair assistance.Babies with congenital myasthenic syndromes may have feeding difficulties. Some affected babies may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis). In severe instances, a lack of movement before birth can lead to joint deformities (contractures) that cause joint stiffness (arthrogryposis) and impair movement.Children with congenital myasthenic syndromes may have speech problems (dysarthria) or swallowing difficulties (dysphagia). The development of motor skills, such as crawling or walking, may be delayed in these children. ar Autosomal recessive ad Autosomal dominant SCN4A https://medlineplus.gov/genetics/gene/scn4a PLEC https://medlineplus.gov/genetics/gene/plec DES https://medlineplus.gov/genetics/gene/des CHRNG https://medlineplus.gov/genetics/gene/chrng CHAT https://medlineplus.gov/genetics/gene/chat CHRNE https://medlineplus.gov/genetics/gene/chrne RAPSN https://medlineplus.gov/genetics/gene/rapsn COLQ https://medlineplus.gov/genetics/gene/colq DOK7 https://medlineplus.gov/genetics/gene/dok7 SLC25A1 https://medlineplus.gov/genetics/gene/slc25a1 CHD8 https://medlineplus.gov/genetics/gene/chd8 PURA https://medlineplus.gov/genetics/gene/pura AGRN https://www.ncbi.nlm.nih.gov/gene/180 CHRNA1 https://www.ncbi.nlm.nih.gov/gene/1134 CHRNB1 https://www.ncbi.nlm.nih.gov/gene/1140 CHRND https://www.ncbi.nlm.nih.gov/gene/1144 COL13A1 https://www.ncbi.nlm.nih.gov/gene/1305 DPAGT1 https://www.ncbi.nlm.nih.gov/gene/1798 GFPT1 https://www.ncbi.nlm.nih.gov/gene/2673 LAMA5 https://www.ncbi.nlm.nih.gov/gene/3911 LAMB2 https://www.ncbi.nlm.nih.gov/gene/3913 LRP4 https://www.ncbi.nlm.nih.gov/gene/4038 MUSK https://www.ncbi.nlm.nih.gov/gene/4593 MYO9A https://www.ncbi.nlm.nih.gov/gene/4649 SLC18A3 https://www.ncbi.nlm.nih.gov/gene/6572 SNAP25 https://www.ncbi.nlm.nih.gov/gene/6616 VAMP1 https://www.ncbi.nlm.nih.gov/gene/6843 PREPL https://www.ncbi.nlm.nih.gov/gene/9581 RPH3A https://www.ncbi.nlm.nih.gov/gene/22895 UNC13A https://www.ncbi.nlm.nih.gov/gene/23025 MACF1 https://www.ncbi.nlm.nih.gov/gene/23499 TOR1AIP1 https://www.ncbi.nlm.nih.gov/gene/26092 GMPPB https://www.ncbi.nlm.nih.gov/gene/29925 SLC5A7 https://www.ncbi.nlm.nih.gov/gene/60482 TEFM https://www.ncbi.nlm.nih.gov/gene/79736 ALG2 https://www.ncbi.nlm.nih.gov/gene/85365 SYT2 https://www.ncbi.nlm.nih.gov/gene/127833 ALG14 https://www.ncbi.nlm.nih.gov/gene/199857 CMS Congenital myasthenia Congenital myasthenic syndrome GTR C0751882 ICD-10-CM G70.2 MeSH D020294 OMIM 254210 OMIM 254300 OMIM 601462 OMIM 603034 OMIM 605809 OMIM 608930 OMIM 608931 OMIM 610542 OMIM 614198 OMIM 614750 OMIM 615120 OMIM 616040 OMIM 616224 OMIM 616227 OMIM 616228 OMIM 616304 OMIM 616313 OMIM 616314 OMIM 616321 OMIM 616322 OMIM 616323 OMIM 616324 OMIM 616325 OMIM 616326 OMIM 616720 OMIM 617143 OMIM 617239 OMIM 618197 OMIM 618198 OMIM 618323 OMIM 619461 SNOMED CT 230670003 SNOMED CT 230672006 2026-02 2026-02-13 Congenital nephrotic syndrome https://medlineplus.gov/genetics/condition/congenital-nephrotic-syndrome descriptionCongenital nephrotic syndrome is a kidney condition that begins in infancy and typically leads to irreversible kidney failure (end-stage renal disease) by early childhood. Children with congenital nephrotic syndrome begin to have symptoms of the condition between birth and 3 months.The features of congenital nephrotic syndrome are caused by failure of the kidneys to filter waste products from the blood and remove them in urine. Signs and symptoms of this condition are excessive protein in the urine (proteinuria), increased cholesterol in the blood (hypercholesterolemia), an abnormal buildup of fluid in the abdominal cavity (ascites), and swelling (edema). Affected individuals may also have blood in the urine (hematuria), which can lead to a reduced number of red blood cells (anemia) in the body, abnormal blood clotting, or reduced amounts of certain white blood cells. Low white blood cell counts can lead to a weakened immune system and frequent infections in people with congenital nephrotic syndrome.Children with congenital nephrotic syndrome typically develop end-stage renal disease between ages 2 and 8, although with treatment, some may not have kidney failure until adolescence or early adulthood. ar Autosomal recessive WT1 https://medlineplus.gov/genetics/gene/wt1 NPHS1 https://medlineplus.gov/genetics/gene/nphs1 NPHS2 https://medlineplus.gov/genetics/gene/nphs2 LAMB2 https://www.ncbi.nlm.nih.gov/gene/3913 PLCE1 https://www.ncbi.nlm.nih.gov/gene/51196 Familial nephrotic syndrome GTR C0403399 GTR C1868672 ICD-10-CM N04 MeSH D009404 OMIM 256300 OMIM 600995 SNOMED CT 48796009 2016-07 2020-08-18 Congenital plasminogen deficiency https://medlineplus.gov/genetics/condition/congenital-plasminogen-deficiency descriptionCongenital plasminogen deficiency is a disorder that results in inflamed growths on the mucous membranes, which are the moist tissues that line body openings such as the eyelids and the inside of the mouth. Development of the growths are usually triggered by infections or injury, but they may also occur spontaneously in the absence of known triggers. The growths may recur after being removed.Congenital plasminogen deficiency most often affects the conjunctiva, which are the mucous membranes that protect the white part of the eye (the sclera) and line the eyelids. A characteristic feature of this disorder is ligneous conjunctivitis, in which a buildup of a protein called fibrin causes inflammation of the conjunctiva (conjunctivitis) and leads to thick, woody (ligneous), inflamed growths that are yellow, white, or red. Ligneous conjunctivitis most often occurs on the inside of the eyelids. However, in about one-third of cases, ligneous conjunctivitis over the sclera grows onto the cornea, which is the clear covering that protects the colored part of the eye (the iris) and pupil. Such growths can tear the cornea or cause scarring. These corneal problems as well as obstruction by growths inside the eyelid can lead to vision loss.People with congenital plasminogen deficiency may also develop ligneous growths on other mucous membranes, including the inside of the mouth and the gums; the lining of the nasal cavity; and in females, the vagina. Growths on the mucous membranes that line the gastrointestinal tract may result in ulcers. The growths may also develop in the windpipe, which can cause life-threatening airway obstruction, especially in children. In a small number of cases, affected individuals are born with impaired drainage of the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF), resulting in a buildup of this fluid in the skull (occlusive hydrocephalus). It is unclear how this feature is related to the other signs and symptoms of congenital plasminogen deficiency. ar Autosomal recessive PLG https://medlineplus.gov/genetics/gene/plg Hypoplasminogenemia Plasminogen deficiency, type I GTR C1968804 ICD-10-CM H10.51 ICD-10-CM H10.511 ICD-10-CM H10.512 ICD-10-CM H10.513 ICD-10-CM H10.519 MeSH D020147 OMIM 217090 SNOMED CT 403435005 SNOMED CT 95841006 2012-08 2021-11-26 Congenital stromal corneal dystrophy https://medlineplus.gov/genetics/condition/congenital-stromal-corneal-dystrophy descriptionCongenital stromal corneal dystrophy is an inherited eye disorder that primarily affects the clear layer that covers the front surface of the eye (cornea). Affected individuals have multiple corneal opacities, which are damaged areas that cause the cornea to appear cloudy or opaque rather than transparent. These corneal opacities form in the thickest layer of the cornea (stroma) and are typically present in both eyes (bilateral) from birth or soon thereafter. The corneas of affected individuals may also be thicker than normal and have an irregular surface. These corneal changes lead to a loss of visual acuity, which can impair a person’s ability to see clearly. Without treatment, visual acuity can worsen over time.Congenital stromal corneal dystrophy is often associated with additional eye abnormalities, including eyes that do not look in the same direction (strabismus) and "lazy eye" (amblyopia). Less commonly, affected individuals may have involuntary eye movements (nystagmus) or increased sensitivity to light (photophobia). ad Autosomal dominant+New variant DCN https://medlineplus.gov/genetics/gene/dcn Congenital hereditary stromal dystrophy of the cornea Congenital stromal dystrophy of the cornea CSCD Decorin-associated congenital stromal corneal dystrophy Dystrophia corneae parenchymatosa congenita Witschel dystrophy GTR C1864738 MeSH D003317 OMIM 610048 SNOMED CT 702359002 2025-03 2025-03-03 Congenital sucrase-isomaltase deficiency https://medlineplus.gov/genetics/condition/congenital-sucrase-isomaltase-deficiency descriptionCongenital sucrase-isomaltase deficiency is a rare genetic disorder that affects an individual's ability to digest certain sugars. People with this condition cannot break down the sugars sucrose and maltose. Sucrose (a sugar found in fruits, and also known as table sugar) and maltose (the sugar found in grains) are called disaccharides because they are made of two simple sugars. Disaccharides are broken down into simple sugars during digestion. Sucrose is broken down into glucose and another simple sugar called fructose, and maltose is broken down into two glucose molecules. People with congenital sucrase-isomaltase deficiency cannot break down the sugars sucrose and maltose, and other compounds made from these sugar molecules (carbohydrates).Congenital sucrase-isomaltase deficiency usually becomes apparent after an infant is weaned and starts to consume fruits, juices, grains, and other starchy food. After ingestion of sucrose or maltose, an affected individual will typically experience stomach cramps, bloating, excess gas production, and diarrhea. These digestive problems can lead to failure to gain weight and grow at the expected rate (failure to thrive) and malnutrition. ar Autosomal recessive SI https://medlineplus.gov/genetics/gene/si Congenital sucrose intolerance Congenital sucrose-isomaltose malabsorption CSID Disaccharide intolerance I SI deficiency Sucrase-isomaltase deficiency GTR C1283620 ICD-10-CM E74.31 MeSH D002239 OMIM 222900 SNOMED CT 78373000 2023-02 2023-02-14 Constitutional mismatch repair deficiency syndrome https://medlineplus.gov/genetics/condition/constitutional-mismatch-repair-deficiency-syndrome descriptionConstitutional mismatch repair deficiency (CMMRD) syndrome is a rare disorder that greatly increases the risk of developing different types of cancer throughout a person's lifetime. Affected individuals often develop their first cancer in childhood. The cancers that most commonly occur in people with CMMRD are cancers of the colon and rectum (collectively referred to as colorectal cancer), blood (leukemia or lymphoma), and brain.Approximately 50 percent of people with CMMRD will develop cancer by age 10, and 90 percent will develop cancer by age 18. Brain cancers, leukemias, and lymphomas tend to occur at a younger age than colorectal cancer in affected individuals. Nearly all people with CMMRD will develop a second cancer if they survive the first cancer. People with CMMRD often develop multiple abnormal growths (polyps) on the lining of the colon. If these polyps are not removed, they may become cancerous over time. Brain cancers in people with CMMRD are often high-grade gliomas or glioblastomas, which are tumors that are made up of cells called glial cells. The most common blood cancers in people with CMMRD are non-Hodgkin lymphomas, such as lymphoblastic lymphoma. These cancers primarily affect white blood cells known as T cells. Other cancers that can occur in people who have CMMRD include cancers of the small intestine, urinary tract, or lining of the uterus. Cancers of the connective tissue and bone (sarcomas) may also develop. Some affected individuals have patches of skin that are unusually light in color (hypopigmented). Many people with CMMRD develop features similar to those seen in people with a condition called neurofibromatosis type 1. These features include changes in skin coloring (pigmentation), which are characterized by multiple flat patches on the skin that are darker than the surrounding area (café-au-lait spots). Because of these shared features, CMMRD is sometimes initially misdiagnosed as neurofibromatosis type 1. Many people with CMMRD also develop a noncancerous (benign) feature called developmental venous anomaly, which is a rearrangement of the small veins in the brain. This feature can only be seen with medical imaging.Due to the young age at which people with CMMRD develop cancer, the lifespan of affected individuals is typically shortened, with many people surviving only into adolescence or early adulthood. ar Autosomal recessive ad Autosomal dominant MLH1 https://medlineplus.gov/genetics/gene/mlh1 MSH2 https://medlineplus.gov/genetics/gene/msh2 MSH6 https://medlineplus.gov/genetics/gene/msh6 PMS2 https://medlineplus.gov/genetics/gene/pms2 CMMRD GTR C5399763 MeSH D015179 OMIM 276300 OMIM 619096 OMIM 619097 OMIM 619101 2025-05 2025-05-08 Core binding factor acute myeloid leukemia https://medlineplus.gov/genetics/condition/core-binding-factor-acute-myeloid-leukemia descriptionCore binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection, red blood cells (erythrocytes) that carry oxygen, and platelets (thrombocytes) that are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets.People with CBF-AML have a shortage of all types of mature blood cells: a shortage of white blood cells (leukopenia) leads to increased susceptibility to infections, a low number of red blood cells (anemia) causes fatigue and weakness, and a reduction in the amount of platelets (thrombocytopenia) can result in easy bruising and abnormal bleeding. Other symptoms of CBF-AML may include fever and weight loss.While acute myeloid leukemia is generally a disease of older adults, CBF-AML often begins in young adulthood and can occur in childhood. Compared to other forms of acute myeloid leukemia, CBF-AML has a relatively good prognosis: about 90 percent of individuals with CBF-AML recover from their disease following treatment, compared with 25 to 40 percent of those with other forms of acute myeloid leukemia. However, the disease recurs in approximately half of them after successful treatment of the initial occurrence. n Not inherited KRAS https://medlineplus.gov/genetics/gene/kras NRAS https://medlineplus.gov/genetics/gene/nras KIT https://medlineplus.gov/genetics/gene/kit RUNX1 https://medlineplus.gov/genetics/gene/runx1 RUNX1T1 https://medlineplus.gov/genetics/gene/runx1t1 MYH11 https://medlineplus.gov/genetics/gene/myh11 CBFB https://medlineplus.gov/genetics/gene/cbfb FLT3 https://medlineplus.gov/genetics/gene/flt3 8 https://medlineplus.gov/genetics/chromosome/8 16 https://medlineplus.gov/genetics/chromosome/16 21 https://medlineplus.gov/genetics/chromosome/21 CBF acute myeloid leukemia CBF-AML Core-binding factor AML GTR C0023467 MeSH D015470 OMIM 601626 SNOMED CT 702446006 SNOMED CT 838355002 2013-11 2020-09-08 Cornelia de Lange syndrome https://medlineplus.gov/genetics/condition/cornelia-de-lange-syndrome descriptionCornelia de Lange syndrome is a developmental disorder that affects many parts of the body. The features of this disorder vary widely among affected individuals and range from relatively mild to severe.Cornelia de Lange syndrome is characterized by slow growth before and after birth leading to short stature; intellectual disability that is usually moderate to severe; and abnormalities of bones in the arms, hands, and fingers. Most people with Cornelia de Lange syndrome also have distinctive facial features, including arched eyebrows that often meet in the middle (synophrys), long eyelashes, low-set ears, small and widely spaced teeth, and a small and upturned nose. Many affected individuals also have features similar to autism spectrum disorder, a developmental condition that affects communication and social interaction.Additional signs and symptoms of Cornelia de Lange syndrome can include excessive body hair (hypertrichosis), an unusually small head (microcephaly), hearing loss, and problems with the digestive tract. Some people with this condition are born with an opening in the roof of the mouth called a cleft palate.  Seizures, heart defects, and eye problems have also been reported in people with this condition. xr X-linked recessive ad Autosomal dominant NIPBL https://medlineplus.gov/genetics/gene/nipbl SMC1A https://medlineplus.gov/genetics/gene/smc1a SMC3 https://medlineplus.gov/genetics/gene/smc3 ANKRD11 https://medlineplus.gov/genetics/gene/ankrd11 HDAC8 https://medlineplus.gov/genetics/gene/hdac8 RAD21 https://medlineplus.gov/genetics/gene/rad21 BRD4 https://www.ncbi.nlm.nih.gov/gene/23476 BDLS Brachmann-de Lange syndrome CdLS De Lange syndrome Typus degenerativus amstelodamensis GTR C0270972 GTR C1853099 GTR C3550903 GTR C3553517 GTR C4551851 MeSH D003635 OMIM 122470 OMIM 300590 OMIM 300882 OMIM 610759 OMIM 614701 SNOMED CT 40354009 2022-04 2023-08-22 Corticosteroid-binding globulin deficiency https://medlineplus.gov/genetics/condition/corticosteroid-binding-globulin-deficiency descriptionCorticosteroid-binding globulin deficiency is a condition with subtle signs and symptoms, the most frequent being extreme tiredness (fatigue), especially after physical exertion. Many people with this condition have unusually low blood pressure (hypotension). Some affected individuals have a fatty liver or experience chronic pain, particularly in their muscles. These features vary among affected individuals, even those within the same family.Many people with corticosteroid-binding globulin deficiency have only one or two of these features; others have no signs and symptoms of the disorder and are only diagnosed after a relative is found to be affected.Some people with corticosteroid-binding globulin deficiency also have a condition called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The features of ME/CFS are prolonged fatigue that interferes with daily activities, as well as general symptoms, such as sore throat or headaches. ar Autosomal recessive SERPINA6 https://medlineplus.gov/genetics/gene/serpina6 CBG deficiency Transcortin deficiency GTR C1852529 MeSH D030342 OMIM 611489 SNOMED CT 237768001 2014-03 2023-07-26 Corticosterone methyloxidase deficiency https://medlineplus.gov/genetics/condition/corticosterone-methyloxidase-deficiency descriptionCorticosterone methyloxidase deficiency, also known as aldosterone synthase deficiency, is a disorder characterized by excessive amounts of sodium released in the urine (salt wasting), along with insufficient release of potassium in the urine, usually beginning in the first few weeks of life. This imbalance leads to low levels of sodium and high levels of potassium in the blood (hyponatremia and hyperkalemia, respectively). Individuals with corticosterone methyloxidase deficiency can also have high levels of acid in the blood (metabolic acidosis).The hyponatremia, hyperkalemia, and metabolic acidosis associated with corticosterone methyloxidase deficiency can cause nausea, vomiting, dehydration, low blood pressure, extreme tiredness (fatigue), and muscle weakness. Affected infants often experience failure to thrive, which means they do not gain weight and grow at the expected rate. Severe cases of corticosterone methyloxidase deficiency can result in seizures and coma and can be life-threatening. However, affected individuals who survive infancy generally have a normal life expectancy, and the signs and symptoms of the disorder typically become milder or disappear by adulthood. ar Autosomal recessive CYP11B2 https://medlineplus.gov/genetics/gene/cyp11b2 18-hydroxylase deficiency 18-oxidase deficiency Aldosterone deficiency Aldosterone deficiency due to deficiency of steroid 18-hydroxylase Aldosterone deficiency due to deficiency of steroid 18-oxidase Aldosterone synthase deficiency CMO deficiency Congenital hypoaldosteronism Corticosterone 18-monooxygenase deficiency Corticosterone methyl oxidase deficiency Familial hyperreninemic hypoaldosteronism Steroid 18-hydroxylase deficiency Steroid 18-oxidase deficiency Visser-Cost syndrome GTR C0268293 GTR C3463917 MeSH D006994 OMIM 203400 OMIM 610600 SNOMED CT 47757001 2013-11 2024-10-02 Costeff syndrome https://medlineplus.gov/genetics/condition/costeff-syndrome descriptionCosteff syndrome is an inherited condition characterized by vision loss, delayed development, and movement problems. Vision loss is primarily caused by degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. This optic nerve atrophy often begins in infancy or early childhood and results in vision impairment that worsens over time. Some affected individuals have rapid and involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).Development of motor skills, such as walking, is often delayed in people with Costeff syndrome. Affected individuals may also have speech difficulties (dysarthria). While some people with Costeff syndrome have mild to moderate intellectual disability, many have normal intelligence.Movement problems in people with Costeff syndrome develop in late childhood and include muscle stiffness (spasticity), impaired muscle coordination (ataxia), and involuntary jerking movements (choreiform movements). As a result of these movement difficulties, individuals with Costeff syndrome may require wheelchair assistance.Costeff syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine (3-methylglutaconic aciduria). The amount of this substance does not appear to influence the signs and symptoms of the condition. Costeff syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of 3-methylglutaconic aciduria. People with Costeff syndrome also have high levels of another acid called 3-methylglutaric acid in their urine. ar Autosomal recessive OPA3 https://medlineplus.gov/genetics/gene/opa3 3-methylglutaconic aciduria type 3 3-methylglutaconic aciduria type III Autosomal recessive OPA3 Autosomal recessive optic atrophy 3 Costeff optic atrophy syndrome Infantile optic atrophy with chorea and spastic paraplegia Iraqi Jewish optic atrophy plus MGA, type III MGA3 OPA3 defect Optic atrophy plus syndrome GTR C0574084 ICD-10-CM E71.111 MeSH D008661 OMIM 258501 SNOMED CT 297232009 2019-02 2020-08-18 Costello syndrome https://medlineplus.gov/genetics/condition/costello-syndrome descriptionCostello syndrome is a rare disorder that affects many parts of the body. This condition is characterized by delayed development, loose folds of skin (which are especially noticeable on the hands and feet), unusually flexible joints, heart problems, short stature, and distinctive facial features.Children with Costello syndrome are often delayed in reaching developmental milestones, such as speaking, sitting, and walking. Affected individuals may also have intellectual disabilities that can vary in severity.Distinctive facial features in people with Costello syndrome typically include a prominent forehead, full cheeks, and full lips. Infants with Costello syndrome may be larger than average at birth, but most have difficulty eating and grow more slowly than other children. Affected individuals may have gastrointestinal problems that include constipation or a backflow of stomach acids into the esophagus (gastroesophageal reflux or GERD). People with this condition have short stature compared to their family and peers and may have reduced growth hormone levels. Heart problems are common, including an abnormal heartbeat (arrhythmia), structural heart defects, and a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Neurological problems in people with Costello syndrome include seizures, weak muscle tone (hypotonia), and a structural abnormality of the brain called a Chiari I malformation. Costello syndrome can cause vision problems, such as nearsightedness (myopia), farsightedness (hyperopia), or eyes that do not point in the same direction (strabismus). Hearing loss may also occur.Other signs and symptoms of Costello syndrome can include tight Achilles tendons (which connect the calf muscles to the heel), recurrent respiratory infections, dry and thickened skin, skeletal abnormalities, and dental problems.Beginning in early childhood, people with Costello syndrome have a higher risk of developing certain cancerous and noncancerous tumors compared to the general population. The most common noncancerous tumors associated with this condition are papillomas, which are small, wart-like growths that usually develop around the nose and mouth or near the anus. The most common cancerous tumor associated with Costello syndrome is a childhood cancer called rhabdomyosarcoma, which begins in muscle tissue. Neuroblastoma, a tumor that arises in developing nerve cells, has also been reported in children and adolescents with this syndrome. In addition, some teenagers with Costello syndrome have developed transitional cell carcinoma, a form of bladder cancer that is usually seen in older adults. The signs and symptoms of Costello syndrome overlap significantly with those of two other genetic conditions, cardiofaciocutaneous syndrome (CFC syndrome) and Noonan syndrome. In affected infants, it can be difficult to tell the three conditions apart based on their physical features. However, the conditions can be distinguished by their genetic causes and by the specific patterns of signs and symptoms that develop later in childhood. ad Autosomal dominant+New variant HRAS https://medlineplus.gov/genetics/gene/hras Faciocutaneoskeletal syndrome FCS syndrome GTR C0587248 MeSH D056685 OMIM 218040 SNOMED CT 309776008 2023-09 2023-09-06 Cowden syndrome https://medlineplus.gov/genetics/condition/cowden-syndrome descriptionCowden syndrome is a genetic disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers.Almost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person's late twenties.Cowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus (the endometrium). Other cancers that have been identified in people with Cowden syndrome include kidney cancer, colorectal cancer, and an agressive form of skin cancer called melanoma. Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. People with Cowden syndrome are also more likely to develop more than one cancer during their lifetimes compared to the general population. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. Additional signs and symptoms can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. A small percentage of affected individuals have delayed development, intellectual disability, or autism spectrum disorder, which can affect communication and social interaction.Some people do not meet the strict criteria for a clinical diagnosis of Cowden syndrome, but they have some of the characteristic features of the condition, particularly the cancers. These individuals are often described as having Cowden-like syndrome. Both Cowden syndrome and Cowden-like syndrome are caused by mutations in the same genes.The features of Cowden syndrome overlap with those of another disorder called Bannayan-Riley-Ruvalcaba syndrome. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors.  Some people with Cowden syndrome have relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other affected individuals have the characteristic features of both conditions. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome (named for the genetic cause of the conditions) instead of two distinct conditions. ad Autosomal dominant PTEN https://medlineplus.gov/genetics/gene/pten SEC23B https://medlineplus.gov/genetics/gene/sec23b SDHD https://medlineplus.gov/genetics/gene/sdhd SDHC https://medlineplus.gov/genetics/gene/sdhc SDHB https://medlineplus.gov/genetics/gene/sdhb AKT1 https://medlineplus.gov/genetics/gene/akt1 KLLN https://medlineplus.gov/genetics/gene/klln PIK3CA https://medlineplus.gov/genetics/gene/pik3ca WWP1 https://medlineplus.gov/genetics/gene/wwp1 CD Cowden disease Cowden's disease Cowden's syndrome CS MHAM Multiple hamartoma syndrome GTR C0018553 GTR C3554517 GTR C3554518 GTR C3554519 GTR C4225179 GTR CN072330 ICD-10-CM Q85.8 MeSH D006223 OMIM 158350 OMIM 615107 OMIM 615108 OMIM 615109 OMIM 616858 SNOMED CT 58037000 2012-09 2023-03-27 Cranioectodermal dysplasia https://medlineplus.gov/genetics/condition/cranioectodermal-dysplasia descriptionCranioectodermal dysplasia is a disorder that affects many parts of the body. The most common features involve bone abnormalities and abnormal development of certain tissues known as ectodermal tissues, which include the skin, hair, nails, and teeth. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.Distinctive abnormalities of the skull and face are common in people with cranioectodermal dysplasia. Most affected individuals have a prominent forehead (frontal bossing) and an elongated head (dolichocephaly) due to abnormal fusion of certain skull bones (sagittal craniosynostosis). A variety of facial abnormalities can occur in people with this condition; these include low-set ears that may also be rotated backward, an increased distance between the inner corners of the eyes (telecanthus), and outside corners of the eyes that point upward or downward (upslanting or downslanting palpebral fissures) among others.Development of bones in the rest of the skeleton is also affected in this condition. Abnormalities in the long bones of the arms and legs (metaphyseal dysplasia) lead to short limbs and short stature. In addition, affected individuals often have short fingers (brachydactyly). Some people with this condition have short rib bones and a narrow rib cage, which can cause breathing problems, especially in affected newborns.Abnormal development of ectodermal tissues in people with cranioectodermal dysplasia can lead to sparse hair, small or missing teeth, short fingernails and toenails, and loose skin.Cranioectodermal dysplasia can affect additional organs and tissues in the body. A kidney disorder known as nephronophthisis occurs in many people with this condition, and it can lead to a life-threatening failure of kidney function known as end-stage renal disease. Abnormalities of the liver, heart, or eyes also occur in people with cranioectodermal dysplasia. ar Autosomal recessive IFT122 https://medlineplus.gov/genetics/gene/ift122 IFT43 https://medlineplus.gov/genetics/gene/ift43 WDR19 https://medlineplus.gov/genetics/gene/wdr19 WDR35 https://medlineplus.gov/genetics/gene/wdr35 CED Sensenbrenner syndrome GTR C0432235 GTR C3150874 GTR C3279807 GTR C3280616 MeSH D000015 MeSH D004476 OMIM 218330 OMIM 613610 OMIM 614099 OMIM 614378 SNOMED CT 254093009 2013-11 2020-08-18 Craniofacial microsomia https://medlineplus.gov/genetics/condition/craniofacial-microsomia descriptionCraniofacial microsomia is a term used to describe a spectrum of abnormalities that primarily affect the development of the skull (cranium) and face before birth. Microsomia means abnormal smallness of body structures. Most people with craniofacial microsomia have differences in the size and shape of facial structures between the right and left sides of the face (facial asymmetry). In about two-thirds of cases, both sides of the face have abnormalities, which usually differ from one side to the other. Other individuals with craniofacial microsomia are affected on only one side of the face. The facial characteristics in craniofacial microsomia typically include underdevelopment of one side of the upper or lower jaw (maxillary or mandibular hypoplasia), which can cause dental problems and difficulties with feeding and speech. In cases of severe mandibular hypoplasia, breathing may also be affected.People with craniofacial microsomia usually have ear abnormalities affecting one or both ears, typically to different degrees. They may have growths of skin (skin tags) in front of the ear (preauricular tags), an underdeveloped or absent external ear (microtia or anotia), or a closed or absent ear canal; these abnormalities may lead to hearing loss. Eye problems are less common in craniofacial microsomia, but some affected individuals have an unusually small eyeball (microphthalmia) or other eye abnormalities that result in vision loss.Abnormalities in other parts of the body, such as malformed bones of the spine (vertebrae), abnormally shaped kidneys, and heart defects, may also occur in people with craniofacial microsomia.Many other terms have been used for craniofacial microsomia. These other names generally refer to forms of craniofacial microsomia with specific combinations of signs and symptoms, although sometimes they are used interchangeably. Hemifacial microsomia often refers to craniofacial microsomia with maxillary or mandibular hypoplasia. People with hemifacial microsomia and noncancerous (benign) growths in the eye called epibulbar dermoids may be said to have Goldenhar syndrome or oculoauricular dysplasia. ad Autosomal dominant ar Autosomal recessive Asymmetric hypoplasia of facial structures Auriculobranchiogenic dysplasia CFM Facioauriculovertebral dysplasia FAV First and second branchial arch syndrome First and second pharyngeal arch syndromes Goldenhar syndrome Goldenhar-Gorlin syndrome Hemifacial microsomia HFM Lateral facial dysplasia OAV complex OAVS Oculoauriculovertebral spectrum Oral-mandibular-auricular syndrome Otomandibular dysostosis Unilateral intrauterine facial necrosis Unilateral mandibulofacial dysostosis GTR C3495417 MeSH D006053 MeSH D019465 OMIM 164210 SNOMED CT 109393007 SNOMED CT 205418005 SNOMED CT 254025006 SNOMED CT 254026007 SNOMED CT 367462009 SNOMED CT 703973009 2012-03 2024-10-02 Craniofacial-deafness-hand syndrome https://medlineplus.gov/genetics/condition/craniofacial-deafness-hand-syndrome descriptionCraniofacial-deafness-hand syndrome is characterized by distinctive facial features, profound hearing loss, and hand abnormalities.The distinctive facial features of people with craniofacial-deafness-hand syndrome result from a variety of developmental abnormalities involving the skull (cranium) and face. Affected individuals often have underdeveloped or absent nasal bones resulting in a small nose, thin nostrils, and a flattened mid-face with a flat nasal bridge. Individuals with this condition typically also have widely spaced eyes (ocular hypertelorism), narrowed openings of the eyes (narrowed palpebral fissures), a small upper jaw (hypoplastic maxilla), and a small mouth with pursed lips.People with this condition also have profound hearing loss that is caused by abnormalities in the inner ear (sensorineural deafness). Hearing loss in these individuals is present from birth.In affected individuals, a common abnormality of the muscles in the hand is a malformation in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). People with craniofacial-deafness-hand syndrome may also have permanently bent third, fourth, and fifth fingers (camptodactyly), which can limit finger movement and lead to joint deformities called contractures. Contractures in the wrist can further impair hand movements. ad Autosomal dominant PAX3 https://medlineplus.gov/genetics/gene/pax3 CDHS GTR C1852510 MeSH D006319 MeSH D019465 OMIM 122880 SNOMED CT 702362004 2012-08 2020-08-18 Craniofrontonasal syndrome https://medlineplus.gov/genetics/condition/craniofrontonasal-syndrome descriptionCraniofrontonasal syndrome is a rare condition characterized by the premature closure of certain bones of the skull (craniosynostosis) during development, which affects the shape of the head and face. The condition is named for the areas of the body that are typically affected: the skull (cranio-), face (fronto-), and nose (nasal).In people with craniofrontonasal syndrome, the skull bones along the coronal suture, which is the growth line that goes over the head from ear to ear, closes early. These changes can result in an abnormally shaped head and distinctive facial features. The size and shape of facial structures may differ between the right and left sides of the face (facial asymmetry) in individuals with craniofrontonasal syndrome. Affected individuals may also have wide-set eyes (ocular hypertelorism), eyes that do not point in the same direction (strabismus), involuntary eye movements (nystagmus), a slit (cleft) in the tip of the nose, a wide nasal bridge, an upper lip that points outward (called a tented lip), or a cleft in the upper lip with or without a cleft in roof of the mouth (palate). Some affected individuals have brain abnormalities, such as absent or underdeveloped tissue connecting the left and right halves of the brain (agenesis or dysgenesis of the corpus callosum). However, intelligence is usually unaffected in people with this condition. Females with craniofrontonasal syndrome typically have more severe signs and symptoms than affected males, who often have hypertelorism and rarely, cleft lip.Other common features of craniofrontonasal syndrome include extra folds of skin on the neck (webbed neck), ridged nails, unusual curving of the fingers or toes (clinodactyly), extra fingers (polydactyly) or fingers that are fused together (syndactyly), low-set breasts, a sunken chest (pectus excavatum), a spine that curves to the side (scoliosis), or narrow and sloped shoulders with reduced range of motion. People with this condition may also have eyebrows that grow together in the middle (synophrys), a widow's peak hairline with a low hairline in the back, or wiry hair. x X-linked EFNB1 https://medlineplus.gov/genetics/gene/efnb1 CFND CFNS Craniofrontonasal dysplasia Craniofrontonasal dystosis GTR C0220767 MeSH D019465 OMIM 304110 SNOMED CT 715421009 2020-01 2020-08-18 Craniometaphyseal dysplasia https://medlineplus.gov/genetics/condition/craniometaphyseal-dysplasia descriptionCraniometaphyseal dysplasia is a rare condition characterized by thickening (overgrowth) of bones in the skull (cranium) and abnormalities in a region at the end of long bones known as the metaphysis. The abnormal bone growth continues throughout life. Except in the most severe cases, the lifespan of people with craniometaphyseal dysplasia is normal.Bone overgrowth in the head causes many of the signs and symptoms of craniometaphyseal dysplasia. Affected individuals typically have distinctive facial features such as a wide nasal bridge, a prominent forehead, wide-set eyes (hypertelorism), and a prominent jaw. Excess bone formation in the jaw can delay teething (dentition) or result in absent (non-erupting) teeth. Infants with craniometaphyseal dysplasia may have breathing or feeding problems caused by narrow nasal passages. In severe cases, abnormal bone growth can pinch (compress) the nerves that extend from the brain to various areas of the head and neck (cranial nerves). Compression of the cranial nerves can lead to paralyzed facial muscles (facial nerve palsy), blindness, or deafness.The x-rays of individuals with craniometaphyseal dysplasia show unusually shaped long bones, particularly long bones in the legs. The ends of these bones are wider and appear less dense than usual in people with this condition.There are two types of craniometaphyseal dysplasia, which are distinguished by their pattern of inheritance and genetic cause. They are known as the autosomal dominant and autosomal recessive types. ar Autosomal recessive ad Autosomal dominant ANKH https://medlineplus.gov/genetics/gene/ankh GJA1 https://medlineplus.gov/genetics/gene/gja1 Autosomal dominant craniometaphyseal dysplasia Autosomal recessive craniometaphyseal dysplasia CMD CMDD CMDJ CMDR Craniometaphyseal dysplasia, Jackson type GTR C1852502 GTR C2931244 MeSH D009139 OMIM 123000 SNOMED CT 254134004 SNOMED CT 254135003 SNOMED CT 36601008 2018-06 2020-08-18 Cri-du-chat syndrome https://medlineplus.gov/genetics/condition/cri-du-chat-syndrome descriptionCri-du-chat (cat's cry) syndrome, also known as 5p- (5p minus) syndrome, is a chromosomal condition that results when a piece of chromosome 5 is missing. Infants with this condition often have a high-pitched cry that sounds like that of a cat. The disorder is characterized by intellectual disability and delayed development, small head size (microcephaly), low birth weight, and weak muscle tone (hypotonia) in infancy. Affected individuals also have distinctive facial features, including widely set eyes (hypertelorism), low-set ears, a small jaw, and a rounded face. Some children with cri-du-chat syndrome are born with a heart defect. n Not inherited CTNND2 https://medlineplus.gov/genetics/gene/ctnnd2 5 https://medlineplus.gov/genetics/chromosome/5 5p deletion syndrome 5p- syndrome Cat cry syndrome Chromosome 5p- syndrome Monosomy 5p GTR C0010314 ICD-10-CM Q93.4 MeSH D003410 OMIM 123450 SNOMED CT 70173007 2010-02 2022-10-25 Crigler-Najjar syndrome https://medlineplus.gov/genetics/condition/crigler-najjar-syndrome descriptionCrigler-Najjar syndrome is a severe condition characterized by high levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (called unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Crigler-Najjar syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia).Bilirubin has an orange-yellow tint, and hyperbilirubinemia causes yellowing of the skin and whites of the eyes (jaundice). In Crigler-Najjar syndrome, jaundice is apparent at birth or in infancy. Severe unconjugated hyperbilirubinemia can lead to a condition called kernicterus, which is a form of brain damage caused by the accumulation of unconjugated bilirubin in the brain and nerve tissues. Babies with kernicterus are often extremely tired (lethargic) and may have weak muscle tone (hypotonia). These babies may experience episodes of increased muscle tone (hypertonia) and arching of their backs. Kernicterus can lead to other neurological problems, including involuntary writhing movements of the body (choreoathetosis), hearing problems, or intellectual disability.Crigler-Najjar syndrome is divided into two types. Type 1 (CN1) is very severe, and affected individuals can die in childhood due to kernicterus, although with proper treatment, they may survive longer. Type 2 (CN2) is less severe. People with CN2 are less likely to develop kernicterus, and most affected individuals survive into adulthood. ar Autosomal recessive UGT1A1 https://medlineplus.gov/genetics/gene/ugt1a1 Crigler Najjar syndrome Familial nonhemolytic unconjugated hyperbilirubinemia Hereditary unconjugated hyperbilirubinemia GTR C0010324 GTR C2931132 ICD-10-CM E80.5 MeSH D003414 OMIM 218800 OMIM 606785 SNOMED CT 28259009 SNOMED CT 68067009 SNOMED CT 8933000 2012-02 2020-08-18 Critical congenital heart disease https://medlineplus.gov/genetics/condition/critical-congenital-heart-disease descriptionCritical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus. u Pattern unknown JAG1 https://medlineplus.gov/genetics/gene/jag1 GJA1 https://medlineplus.gov/genetics/gene/gja1 NOTCH1 https://medlineplus.gov/genetics/gene/notch1 MED13L https://medlineplus.gov/genetics/gene/med13l NKX2-5 https://www.ncbi.nlm.nih.gov/gene/1482 GATA4 https://www.ncbi.nlm.nih.gov/gene/2626 GATA6 https://www.ncbi.nlm.nih.gov/gene/2627 GDF1 https://www.ncbi.nlm.nih.gov/gene/2657 SMAD6 https://www.ncbi.nlm.nih.gov/gene/4091 FOXH1 https://www.ncbi.nlm.nih.gov/gene/8928 HAND1 https://www.ncbi.nlm.nih.gov/gene/9421 ZFPM2 https://www.ncbi.nlm.nih.gov/gene/23414 CFC1 https://www.ncbi.nlm.nih.gov/gene/55997 NKX2-6 https://www.ncbi.nlm.nih.gov/gene/137814 CCHD Critical congenital heart defects GTR C0013481 GTR C0039685 GTR C0040761 GTR C0152021 GTR C0152101 GTR C1415817 GTR C3151221 GTR C3280795 ICD-10-CM Q20.1 ICD-10-CM Q21.3 ICD-10-CM Q22.0 ICD-10-CM Q22.4 ICD-10-CM Q22.5 ICD-10-CM Q23.4 ICD-10-CM Q25.1 MeSH D006330 OMIM 106700 OMIM 120000 OMIM 178370 OMIM 187500 OMIM 217095 OMIM 224700 OMIM 241550 OMIM 265150 OMIM 605067 OMIM 605376 OMIM 608808 OMIM 613854 OMIM 614435 SNOMED CT 17394001 SNOMED CT 204296002 SNOMED CT 204354004 SNOMED CT 204357006 SNOMED CT 218728005 SNOMED CT 253443005 SNOMED CT 253590009 SNOMED CT 253591008 SNOMED CT 26146002 SNOMED CT 39905002 SNOMED CT 399228007 SNOMED CT 443379009 SNOMED CT 447832002 SNOMED CT 447914003 SNOMED CT 448599000 SNOMED CT 448794008 SNOMED CT 45503006 SNOMED CT 61959006 SNOMED CT 62067003 SNOMED CT 63042009 SNOMED CT 719955006 SNOMED CT 7305005 SNOMED CT 7484005 SNOMED CT 86299006 2013-05 2024-05-24 Crohn's disease https://medlineplus.gov/genetics/condition/crohns-disease descriptionCrohn's disease is a complex, long-lasting (chronic) disorder that primarily affects the digestive system. This condition involves an abnormal immune response that causes excess inflammation. It most often affects the intestinal walls, particularly in the lower part of the small intestine (the ileum) and portions of the large intestine (the colon). However, inflammation can occur in any part of the digestive system, from the mouth to the anus. The inflamed tissues become thick and swollen, and the inner surfaces of the digestive system may develop open sores (ulcers).Crohn's disease most commonly appears in a person's late teens or twenties, although the disease can begin at any age. Signs and symptoms tend to flare up multiple times throughout life. The most common features of this condition are persistent diarrhea, abdominal pain and cramping, loss of appetite, weight loss, and fever. Some people with Crohn's disease have blood in the stool from inflamed tissues in the intestine; over time, chronic bleeding can lead to a low number of red blood cells (anemia). In some cases, Crohn's disease can also cause inflammation affecting the joints, eyes, or skin.Intestinal blockage is a common complication of Crohn's disease. Blockages are caused by swelling or a buildup of scar tissue in the intestinal walls. Some affected individuals also develop fistulae, which are abnormal connections between the intestine and other tissues. Fistulae occur when ulcers break through the intestinal wall and passages form between loops of the intestine or between the intestine and nearby structures (such as the bladder, vagina, or skin).Crohn's disease is one common form of inflammatory bowel disease (IBD). Another type of IBD, ulcerative colitis, also causes chronic inflammation of the intestinal lining. Unlike Crohn's disease, which can affect any part of the digestive system, ulcerative colitis typically causes inflammation only in the colon. u Pattern unknown LRRK2 https://medlineplus.gov/genetics/gene/lrrk2 SLC22A5 https://medlineplus.gov/genetics/gene/slc22a5 NOD2 https://medlineplus.gov/genetics/gene/nod2 ATG16L1 https://medlineplus.gov/genetics/gene/atg16l1 IL23R https://medlineplus.gov/genetics/gene/il23r IRGM https://medlineplus.gov/genetics/gene/irgm STAT3 https://medlineplus.gov/genetics/gene/stat3 JAK2 https://medlineplus.gov/genetics/gene/jak2 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 IL10 https://www.ncbi.nlm.nih.gov/gene/3586 IL12B https://www.ncbi.nlm.nih.gov/gene/3593 MUC2 https://www.ncbi.nlm.nih.gov/gene/4583 SLC22A4 https://www.ncbi.nlm.nih.gov/gene/6583 TYK2 https://www.ncbi.nlm.nih.gov/gene/7297 Colitis, granulomatous Crohn disease Crohn's enteritis Enteritis, granulomatous Enteritis, regional GTR CN260071 ICD-10-CM K50 ICD-10-CM K50.0 ICD-10-CM K50.00 ICD-10-CM K50.01 ICD-10-CM K50.011 ICD-10-CM K50.012 ICD-10-CM K50.013 ICD-10-CM K50.014 ICD-10-CM K50.018 ICD-10-CM K50.019 ICD-10-CM K50.1 ICD-10-CM K50.10 ICD-10-CM K50.11 ICD-10-CM K50.111 ICD-10-CM K50.112 ICD-10-CM K50.113 ICD-10-CM K50.114 ICD-10-CM K50.118 ICD-10-CM K50.119 ICD-10-CM K50.8 ICD-10-CM K50.80 ICD-10-CM K50.81 ICD-10-CM K50.811 ICD-10-CM K50.812 ICD-10-CM K50.813 ICD-10-CM K50.814 ICD-10-CM K50.818 ICD-10-CM K50.819 ICD-10-CM K50.9 ICD-10-CM K50.90 ICD-10-CM K50.91 ICD-10-CM K50.911 ICD-10-CM K50.912 ICD-10-CM K50.913 ICD-10-CM K50.914 ICD-10-CM K50.918 ICD-10-CM K50.919 MeSH D003424 OMIM 191390 OMIM 266600 OMIM 601458 OMIM 604519 OMIM 605225 OMIM 606348 OMIM 606668 OMIM 606674 OMIM 606675 OMIM 608448 OMIM 611081 OMIM 612241 OMIM 612244 OMIM 612245 OMIM 612255 OMIM 612259 OMIM 612261 OMIM 612262 OMIM 612278 OMIM 612288 OMIM 612354 OMIM 612380 OMIM 612381 OMIM 612566 OMIM 612567 OMIM 612796 OMIM 613148 SNOMED CT 34000006 SNOMED CT 38106008 SNOMED CT 50440006 SNOMED CT 52457000 2017-12 2024-10-02 Crouzon syndrome https://medlineplus.gov/genetics/condition/crouzon-syndrome descriptionCrouzon syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.Many features of Crouzon syndrome result from the premature fusion of the skull bones. Abnormal growth of these bones leads to wide-set, bulging eyes and vision problems caused by shallow eye sockets; eyes that do not point in the same direction (strabismus); a beaked nose; and an underdeveloped upper jaw. In addition, people with Crouzon syndrome may have dental problems and hearing loss, which is sometimes accompanied by narrow ear canals. A few individuals with Crouzon syndrome have an opening in the lip and the roof of the mouth (cleft lip and palate). The severity of these signs and symptoms varies among affected people. Individuals with Crouzon syndrome usually have normal intelligence. ad Autosomal dominant FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 CFD1 Craniofacial dysarthrosis Craniofacial dysostosis Craniofacial dysostosis syndrome Craniofacial dysostosis type 1 Crouzon craniofacial dysostosis Crouzon disease Crouzon's disease GTR C0010273 ICD-10-CM Q75.1 MeSH D003394 OMIM 123500 SNOMED CT 28861008 2008-02 2023-08-22 Crouzon syndrome with acanthosis nigricans https://medlineplus.gov/genetics/condition/crouzon-syndrome-with-acanthosis-nigricans descriptionCrouzon syndrome with acanthosis nigricans is a disorder characterized by the premature joining of certain bones of the skull (craniosynostosis) during development and a skin condition called acanthosis nigricans.The signs and symptoms of Crouzon syndrome with acanthosis nigricans overlap with those of a similar condition called Crouzon syndrome. Both conditions involve premature fusion of the skull bones, which affects the shape of the head and face. Other common features of both conditions include wide-set, bulging eyes due to shallow eye sockets; eyes that do not point in the same direction (strabismus); a small, beaked nose; and a flat or sunken appearance of the middle of the face (midface hypoplasia). Less common features that can occur in either disorder include an opening in the roof of the mouth (cleft palate), dental problems, or hearing loss. People with Crouzon syndrome or Crouzon syndrome with acanthosis nigricans usually have normal intelligence.Crouzon syndrome with acanthosis nigricans is distinguished from Crouzon syndrome by several features, including skin abnormalities. Acanthosis nigricans is a skin condition characterized by thick, dark, velvety skin in body folds and creases, including the neck and underarms. People with Crouzon syndrome with acanthosis nigricans may also have other skin abnormalities; for example, scars in the thick, dark areas of skin are flat and pale. These scars are usually from surgical procedures that are commonly needed in affected individuals. Additionally, in some people with the condition, one or both nasal passages are narrowed (choanal stenosis) or completely blocked (choanal atresia), which can cause difficulty breathing. A buildup of fluid in the brain (hydrocephalus) can also occur. Nasal passage abnormalities and hydrocephalus are rare in Crouzon syndrome. Less common features of Crouzon syndrome with acanthosis nigricans include subtle changes in the bones of the spine (vertebrae), abnormalities of the finger bones, and noncancerous growths in the jaw called cementomas. ad Autosomal dominant FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 CAN Crouzonodermoskeletal syndrome GTR C2677099 ICD-10-CM Q75.1 MeSH D000052 MeSH D003394 MeSH D003398 OMIM 612247 SNOMED CT 702361006 2017-03 2020-08-18 Cryptogenic cirrhosis https://medlineplus.gov/genetics/condition/cryptogenic-cirrhosis descriptionCryptogenic cirrhosis is a condition that impairs liver function. People with this condition develop irreversible liver disease caused by scarring of the liver (cirrhosis), typically in mid- to late adulthood.The liver is a part of the digestive system that helps break down food, store energy, and remove waste products, including toxins. Minor damage to the liver can be repaired by the body. However, severe or long-term damage can lead to the replacement of normal liver tissue with scar tissue.In the early stages of cryptogenic cirrhosis, people often have no symptoms because the liver has enough normal tissue to function. Signs and symptoms become apparent as more of the liver is replaced by scar tissue. Affected individuals can experience fatigue, weakness, loss of appetite, weight loss, nausea, swelling (edema), enlarged blood vessels, and yellowing of the skin and whites of the eyes (jaundice).People with cryptogenic cirrhosis may develop high blood pressure in the vein that supplies blood to the liver (portal hypertension). Cryptogenic cirrhosis can lead to type 2 diabetes, although the mechanism is unclear. Some people with cryptogenic cirrhosis develop cancer of the liver (hepatocellular cancer). ad Autosomal dominant n Not inherited u Pattern unknown KRT8 https://www.ncbi.nlm.nih.gov/gene/3856 KRT18 https://www.ncbi.nlm.nih.gov/gene/3875 Cirrhosis, cryptogenic GTR C0267809 ICD-10-CM K74.69 MeSH D008103 OMIM 215600 SNOMED CT 89580002 2016-03 2023-03-21 Cushing disease https://medlineplus.gov/genetics/condition/cushing-disease descriptionCushing disease is caused by elevated levels of a hormone called cortisol, which leads to a wide variety of signs and symptoms. This condition usually occurs in adults between the ages of 20 and 50; however, children may also be affected. The first sign of this condition is usually weight gain around the trunk and in the face. Affected individuals may get stretch marks (striae) on their thighs and abdomen and bruise easily. Individuals with Cushing disease can develop a hump on their upper back caused by abnormal deposits of fat. People with this condition can have muscle weakness, severe tiredness, and progressively thin and brittle bones that are prone to fracture (osteoporosis). They also have a weakened immune system and are at an increased risk of infections. Cushing disease can cause mood disorders such as anxiety, irritability, and depression. This condition can also affect a person's concentration and memory. People with Cushing disease have an increased chance of developing high blood pressure (hypertension) and diabetes. Women with Cushing disease may experience irregular menstruation and have excessive hair growth (hirsutism) on their face, abdomen, and legs. Men with Cushing disease may have erectile dysfunction. Children with Cushing disease typically experience slow growth. u Pattern unknown Hypercortisolism Pituitary ACTH hypersecretion Pituitary Cushing syndrome Pituitary-dependant Cushing syndrome Pituitary-dependant hypercortisolism Pituitary-dependant hypercortisolism disorder GTR C0221406 ICD-10-CM E24.0 MeSH D047748 OMIM 219090 SNOMED CT 190502001 SNOMED CT 237734007 SNOMED CT 88803002 2026-03 2023-07-25 Cutis laxa https://medlineplus.gov/genetics/condition/cutis-laxa descriptionCutis laxa is a disorder of connective tissue, which is the tissue that provides structure and strength to the muscles, joints, organs, and skin. Most cases are inherited, but some are acquired, which means they do not appear to be caused by genetic variations. While signs and symptoms of inherited cutis laxa are often noticeable in infancy or childhood, acquired cutis laxa typically appears later in life. This summary primarily describes inherited forms of cutis laxa.  The term "cutis laxa" is Latin for loose or lax skin, and this condition is characterized by skin that is sagging and not stretchy (inelastic). The skin often hangs in loose folds, causing the face and other parts of the body to have a droopy or wrinkled appearance. Extremely wrinkled skin may be particularly noticeable on the neck and in the armpits and groin.Cutis laxa can also affect connective tissue in other parts of the body, including the heart, blood vessels, intestines, and lungs. The disorder can cause heart problems and abnormal narrowing, bulging, or tearing of critical blood vessels. Affected individuals may have soft out-pouchings in the lower abdomen (inguinal hernia) or around the belly button (umbilical hernia). Sacs called diverticula can also develop in the walls of certain organs, such as the bladder and intestines. During childhood, some people with cutis laxa develop a life-long lung disease called emphysema, which can make it difficult to breathe. Depending on which organs and tissues are affected, the signs and symptoms of cutis laxa can range from mild to life-threatening.Researchers have described several different forms of cutis laxa. The forms are often distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. In general, the autosomal recessive forms of cutis laxa tend to be more severe than the autosomal dominant forms, although some people with autosomal dominant cutis laxa are severely affected. In addition to the features described above, people with autosomal recessive cutis laxa can have delayed development, intellectual disability, seizures, problems with movement, or eye or bone abnormalities.The X-linked form of cutis laxa is often called occipital horn syndrome. This form of the disorder is considered a mild type of Menkes syndrome, which is a condition that affects copper levels in the body. In addition to sagging and inelastic skin, occipital horn syndrome is characterized by wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose joints.Other rare conditions, including arterial tortuosity syndrome, geroderma osteodysplastica, and RIN2 syndrome, are sometimes classified as cutis laxa-related conditions, because affected individuals can have loose, sagging skin. These conditions each have a particular pattern of signs and symptoms affecting different tissues and body systems. ar Autosomal recessive xr X-linked recessive ad Autosomal dominant ATP7A https://medlineplus.gov/genetics/gene/atp7a ELN https://medlineplus.gov/genetics/gene/eln EFEMP2 https://medlineplus.gov/genetics/gene/efemp2 FBLN5 https://medlineplus.gov/genetics/gene/fbln5 ATP6V0A2 https://medlineplus.gov/genetics/gene/atp6v0a2 ALDH18A1 https://medlineplus.gov/genetics/gene/aldh18a1 PYCR1 https://medlineplus.gov/genetics/gene/pycr1 LTBP4 https://medlineplus.gov/genetics/gene/ltbp4 ATP6V1A https://www.ncbi.nlm.nih.gov/gene/523 ATP6V1E1 https://www.ncbi.nlm.nih.gov/gene/529 ATP6AP1 https://www.ncbi.nlm.nih.gov/gene/537 ATP6AP2 https://www.ncbi.nlm.nih.gov/gene/10159 Dermatolysis Dermatomegaly GTR C0268350 GTR C0268353 GTR C0268355 GTR C3665335 MeSH D003483 OMIM 123700 OMIM 219100 OMIM 219150 OMIM 219200 OMIM 304150 OMIM 612940 OMIM 613177 OMIM 614100 OMIM 614434 OMIM 614437 OMIM 614438 OMIM 616603 SNOMED CT 58588007 SNOMED CT 59399004 SNOMED CT 59451000 SNOMED CT 73856006 2022-03 2021-08-05 Cyclic neutropenia https://medlineplus.gov/genetics/condition/cyclic-neutropenia descriptionCyclic neutropenia is a disorder that causes frequent infections and other health problems in affected individuals. People with this condition have recurrent episodes of neutropenia during which there is a shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. The episodes of neutropenia are apparent at birth or soon afterward. For most affected individuals, neutropenia recurs every 21 days and lasts about 3 to 5 days.Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses, so people with cyclic neutropenia typically develop recurrent infections of the sinuses, respiratory tract, and skin. Additionally, people with this condition often develop open sores (ulcers) in the mouth and colon, inflammation of the throat (pharyngitis) and gums (gingivitis), recurrent fever, or abdominal pain. People with cyclic neutropenia have these health problems only during episodes of neutropenia. At times when their neutrophil levels are normal, they are not at an increased risk of infection and inflammation. ad Autosomal dominant ELANE https://medlineplus.gov/genetics/gene/elane Cyclic hematopoesis Cyclic leucopenia Periodic neutropenia GTR C0221023 ICD-10-CM D70.4 MeSH D009503 OMIM 162800 SNOMED CT 191347008 2012-01 2020-08-18 Cyclic vomiting syndrome https://medlineplus.gov/genetics/condition/cyclic-vomiting-syndrome descriptionCyclic vomiting syndrome is a disorder that causes recurrent episodes of nausea, vomiting, and tiredness (lethargy). This condition is diagnosed most often in young children, but it can affect people of any age.The episodes of nausea, vomiting, and lethargy last anywhere from an hour to 10 days. An affected person may vomit several times per hour, potentially leading to a dangerous loss of fluids (dehydration). Additional symptoms can include unusually pale skin (pallor), abdominal pain, diarrhea, headache, fever, and an increased sensitivity to light (photophobia) or to sound (phonophobia). In most affected people, the signs and symptoms of each attack are quite similar. These attacks can be debilitating, making it difficult for an affected person to go to work or school.Episodes of nausea, vomiting, and lethargy can occur regularly or apparently at random, or can be triggered by a variety of factors. The most common triggers are emotional excitement and infections. Other triggers can include periods without eating (fasting), temperature extremes, lack of sleep, overexertion, allergies, ingesting certain foods or alcohol, and menstruation.If the condition is not treated, episodes usually occur four to 12 times per year. Between attacks, vomiting is absent, and nausea is either absent or much reduced. However, many affected people experience other symptoms during and between episodes, including pain, lethargy, digestive disorders such as gastroesophageal reflux and irritable bowel syndrome, and fainting spells (syncope). People with cyclic vomiting syndrome are also more likely than people without the disorder to experience depression, anxiety, and panic disorder. It is unclear whether these health conditions are directly related to nausea and vomiting.Cyclic vomiting syndrome is often considered to be a variant of migraines, which are severe headaches often associated with pain, nausea, vomiting, and extreme sensitivity to light and sound. Cyclic vomiting syndrome is likely the same as or closely related to a condition called abdominal migraine, which is characterized by attacks of stomach pain and cramping. Attacks of nausea, vomiting, or abdominal pain in childhood may be replaced by migraine headaches as an affected person gets older. Many people with cyclic vomiting syndrome or abdominal migraine have a family history of migraines.Most people with cyclic vomiting syndrome have normal intelligence, although some affected people have developmental delay or intellectual disability. Autism spectrum disorder, which affects communication and social interaction, have also been associated with cyclic vomiting syndrome. Additionally, muscle weakness (myopathy) and seizures are possible. People with any of these additional features are said to have cyclic vomiting syndrome plus. m mitochondrial u Pattern unknown mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Abdominal migraine CVS Cyclical vomiting Cyclical vomiting syndrome Periodic vomiting ICD-10-CM G43.A ICD-10-CM G43.A0 ICD-10-CM G43.A1 MeSH D014839 OMIM 500007 SNOMED CT 18773000 2014-03 2024-09-17 Cystic fibrosis https://medlineplus.gov/genetics/condition/cystic-fibrosis descriptionCystic fibrosis is an inherited disease characterized by the buildup of thick, sticky mucus that can damage many of the body's organs. The disorder's most common signs and symptoms include progressive damage to the respiratory system and chronic digestive system problems. The features of the disorder and their severity varies among affected individuals.Mucus is a slippery substance that lubricates and protects the linings of the airways, digestive system, reproductive system, and other organs and tissues. In people with cystic fibrosis, the body produces mucus that is abnormally thick and sticky. This abnormal mucus can clog the airways, leading to severe problems with breathing and bacterial infections in the lungs. These infections cause chronic coughing, wheezing, and inflammation. Over time, mucus buildup and infections result in permanent lung damage, including the formation of scar tissue (fibrosis) and cysts in the lungs.Most people with cystic fibrosis also have digestive problems. Some affected babies have meconium ileus, a blockage of the intestine that occurs shortly after birth. Other digestive problems result from a buildup of thick, sticky mucus in the pancreas. The pancreas is an organ that produces insulin (a hormone that helps control blood glucose levels). It also makes enzymes that help digest food. In people with cystic fibrosis, mucus often damages the pancreas, impairing its ability to produce insulin and digestive enzymes. Problems with digestion can lead to diarrhea, malnutrition, poor growth, and weight loss. In adolescence or adulthood, a shortage of insulin can cause a form of diabetes known as cystic fibrosis-related diabetes mellitus (CFRDM).Cystic fibrosis used to be considered a fatal disease of childhood. With improved treatments and better ways to manage the disease, many people with cystic fibrosis now live well into adulthood. Adults with cystic fibrosis experience health problems affecting the respiratory, digestive, and reproductive systems. Most men with cystic fibrosis have congenital bilateral absence of the vas deferens (CBAVD), a condition in which the tubes that carry sperm (the vas deferens) are blocked by mucus and do not develop properly. Men with CBAVD are unable to father children (infertile) unless they undergo fertility treatment. Women with cystic fibrosis may experience complications in pregnancy. ar Autosomal recessive CFTR https://medlineplus.gov/genetics/gene/cftr CF Cystic fibrosis of pancreas Fibrocystic disease of pancreas Mucoviscidosis GTR C0010674 ICD-10-CM E84 ICD-10-CM E84.0 ICD-10-CM E84.1 ICD-10-CM E84.11 ICD-10-CM E84.19 ICD-10-CM E84.8 ICD-10-CM E84.9 ICD-10-CM Z14.1 MeSH D003550 OMIM 219700 SNOMED CT 190905008 SNOMED CT 235978006 SNOMED CT 86555001 2008-01 2025-04-03 Cystinosis https://medlineplus.gov/genetics/condition/cystinosis descriptionCystinosis is a condition characterized by accumulation of the amino acid cystine (a building block of proteins) within cells. Excess cystine damages cells and often forms crystals that can build up and cause problems in many organs and tissues. The kidneys and eyes are especially vulnerable to damage; the muscles, thyroid, pancreas, and testes may also be affected.There are three distinct types of cystinosis. In order of decreasing severity, they are nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis.Nephropathic cystinosis begins in infancy, causing poor growth and a particular type of kidney damage (renal Fanconi syndrome) in which certain molecules that should be reabsorbed into the bloodstream are instead eliminated in the urine. The kidney problems lead to the loss of important minerals, salts, fluids, and many other nutrients. The loss of nutrients impairs growth and may result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. The nutrient imbalances in the body lead to increased urination, thirst, dehydration, and abnormally acidic blood (acidosis). By about the age of 2, cystine crystals may be present in the clear covering of the eye (cornea). The buildup of these crystals in the eye causes pain and an increased sensitivity to light (photophobia). Untreated children will experience complete kidney failure by about the age of 10. Other signs and symptoms that may occur in untreated people, especially after adolescence, include muscle deterioration, blindness, inability to swallow, diabetes, thyroid and nervous system problems, and an inability to father children (infertility) in affected men.The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age. Intermediate cystinosis typically becomes apparent in affected individuals in adolescence. Malfunctioning kidneys and corneal crystals are the main initial features of this disorder. If intermediate cystinosis is left untreated, complete kidney failure will occur, but usually not until the late teens to mid-twenties.People with non-nephropathic or ocular cystinosis typically experience photophobia due to cystine crystals in the cornea, but usually do not develop kidney malfunction or most of the other signs and symptoms of cystinosis. Due to the absence of severe symptoms, the age at which this form of cystinosis is diagnosed varies widely. ar Autosomal recessive CTNS https://medlineplus.gov/genetics/gene/ctns Cystine storage disease GTR C4316899 ICD-10-CM E72.04 MeSH D003554 OMIM 219750 OMIM 219800 OMIM 219900 SNOMED CT 190681003 SNOMED CT 22830006 SNOMED CT 236466005 2008-02 2020-08-18 Cystinuria https://medlineplus.gov/genetics/condition/cystinuria descriptionCystinuria is a condition characterized by the buildup of the amino acid cystine, a building block of most proteins, in the kidneys and bladder. As the kidneys filter blood to create urine, cystine is normally absorbed back into the bloodstream. People with cystinuria cannot properly reabsorb cystine into their bloodstream, so the amino acid accumulates in their urine.As urine becomes more concentrated in the kidneys, the excess cystine forms crystals. Larger crystals become stones that may lodge in the kidneys or in the bladder. Sometimes cystine crystals combine with calcium molecules in the kidneys to form large stones. These crystals and stones can create blockages in the urinary tract and reduce the ability of the kidneys to eliminate waste through urine. The stones also provide sites where bacteria may cause infections. ar Autosomal recessive SLC7A9 https://medlineplus.gov/genetics/gene/slc7a9 SLC3A1 https://medlineplus.gov/genetics/gene/slc3a1 CSNU GTR C0010691 ICD-10-CM E72.01 MeSH D003555 OMIM 220100 SNOMED CT 85020001 2009-01 2020-08-18 Cytochrome P450 oxidoreductase deficiency https://medlineplus.gov/genetics/condition/cytochrome-p450-oxidoreductase-deficiency descriptionCytochrome P450 oxidoreductase deficiency is a disorder of hormone production. This condition specifically affects steroid hormones, which are needed for normal development and reproduction. The hormonal changes associated with cytochrome P450 oxidoreductase deficiency can affect the development of the reproductive system, skeleton, and other parts of the body. These signs and symptoms are usually present at birth or become apparent in early childhood.The signs and symptoms of cytochrome P450 oxidoreductase deficiency vary from mild to severe. Signs and symptoms of mild cases can include a failure to begin menstruation by age 16 (primary amenorrhea), an inability to have biological children (infertility) in both men and women, and a condition called polycystic ovarian syndrome (PCOS). PCOS is characterized by a hormonal imbalance in women that can lead to irregular menstruation, acne, excess body hair (hirsutism), and weight gain.People with moderate cases of cytochrome P450 oxidoreductase deficiency may have external genitalia that do not look clearly male or female, and they may have infertility. People with moderate cytochrome P450 oxidoreductase deficiency usually do not have skeletal abnormalities.The severe form of cytochrome P450 oxidoreductase deficiency is sometimes called Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis. Hormonal changes in affected males and females lead to the development of genital differences, as well as infertility. Severe cases are also characterized by skeletal abnormalities, particularly involving bones of the head and face. These include premature fusion of the skull bones (craniosynostosis), a flattened mid-face, a prominent forehead, and low-set ears. Other skeletal abnormalities can include joint deformities (contractures) that limit movement; unusually long, slender fingers (arachnodactyly); bowing of the thigh bones; and radiohumeral synostosis, which is a bone abnormality that locks the elbows in a bent position. A blockage of the nasal passages (choanal atresia), intellectual disability, and delayed development are also associated with the severe form of the disorder.Some women who are pregnant with fetuses affected by cytochrome P450 oxidoreductase deficiency experience mild symptoms of the disorder even though they themselves do not have the disorder. They may develop excessive body hair growth (hirsutism), acne, and a deep voice. These changes go away soon after delivery. ar Autosomal recessive POR https://medlineplus.gov/genetics/gene/por Antley-Bixler syndrome Antley-Bixler syndrome with disordered steroidogenesis Antley-Bixler syndrome-like phenotype with disordered steroidogenesis Combined partial deficiency of 17-hydroxylase and 21-hydroxylase Congenital adrenal hyperplasia due to apparent combined p450c17 and p450c21 deficiency POR deficiency PORD GTR C1860042 ICD-10-CM MeSH D054882 OMIM 201750 SNOMED CT 62964007 2014-02 2023-10-26 Cytochrome c oxidase deficiency https://medlineplus.gov/genetics/condition/cytochrome-c-oxidase-deficiency descriptionCytochrome c oxidase deficiency is a genetic condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Signs and symptoms of cytochrome c oxidase deficiency usually begin before age 2 but can appear later in mildly affected individuals.The severity of cytochrome c oxidase deficiency varies widely among affected individuals, even among those in the same family. People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other related health problems. More severely affected people have problems in multiple body systems, often including severe brain dysfunction (encephalomyopathy). Approximately one-quarter of individuals with cytochrome c oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver (hepatomegaly), which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening.Many people with cytochrome c oxidase deficiency have a specific group of features known as Leigh syndrome. The signs and symptoms of Leigh syndrome include loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome c oxidase deficiency is one of the many causes of Leigh syndrome.Many individuals with cytochrome c oxidase deficiency do not survive past childhood, although some individuals with mild signs and symptoms live into adolescence or adulthood. m mitochondrial ar Autosomal recessive SURF1 https://medlineplus.gov/genetics/gene/surf1 COX6B1 https://www.ncbi.nlm.nih.gov/gene/1340 COX8A https://www.ncbi.nlm.nih.gov/gene/1351 COX10 https://www.ncbi.nlm.nih.gov/gene/1352 COX15 https://www.ncbi.nlm.nih.gov/gene/1355 MT-CO1 https://www.ncbi.nlm.nih.gov/gene/4512 MT-CO2 https://www.ncbi.nlm.nih.gov/gene/4513 MT-CO3 https://www.ncbi.nlm.nih.gov/gene/4514 SCO1 https://www.ncbi.nlm.nih.gov/gene/6341 COX5A https://www.ncbi.nlm.nih.gov/gene/9377 SCO2 https://www.ncbi.nlm.nih.gov/gene/9997 LRPPRC https://www.ncbi.nlm.nih.gov/gene/10128 FASTKD2 https://www.ncbi.nlm.nih.gov/gene/22868 COA3 https://www.ncbi.nlm.nih.gov/gene/28958 TACO1 https://www.ncbi.nlm.nih.gov/gene/51204 COA7 https://www.ncbi.nlm.nih.gov/gene/65260 COA8 https://www.ncbi.nlm.nih.gov/gene/84334 COX14 https://www.ncbi.nlm.nih.gov/gene/84987 COX20 https://www.ncbi.nlm.nih.gov/gene/116228 COA6 https://www.ncbi.nlm.nih.gov/gene/388753 COA5 https://www.ncbi.nlm.nih.gov/gene/493753 PET100 https://www.ncbi.nlm.nih.gov/gene/100131801 PET117 https://www.ncbi.nlm.nih.gov/gene/100303755 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Complex IV deficiency COX deficiency Cytochrome-c oxidase deficiency Mitochondrial complex IV deficiency GTR C3554534 GTR C4225154 GTR C4225304 GTR C5399977 MeSH D030401 OMIM 220110 OMIM 604377 OMIM 615119 OMIM 616500 OMIM 616501 SNOMED CT 67434000 2012-10 2023-08-17 Cytogenetically normal acute myeloid leukemia https://medlineplus.gov/genetics/condition/cytogenetically-normal-acute-myeloid-leukemia descriptionCytogenetically normal acute myeloid leukemia (CN-AML) is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection, red blood cells (erythrocytes) that carry oxygen, and platelets (thrombocytes) that are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets.People with CN-AML have a shortage of all types of mature blood cells: a shortage of white blood cells (leukopenia) leads to increased susceptibility to infections, a low number of red blood cells (anemia) causes fatigue and weakness, and a reduction in the amount of platelets (thrombocytopenia) can result in easy bruising and abnormal bleeding. Other symptoms of CN-AML may include fever and weight loss.The age at which CN-AML begins ranges from childhood to late adulthood. CN-AML is said to be an intermediate-risk cancer because the prognosis varies: some affected individuals respond well to normal treatment while others may require stronger treatments. The age at which the condition begins and the prognosis are affected by the specific genetic factors involved in the condition. ad Autosomal dominant n Not inherited WT1 https://medlineplus.gov/genetics/gene/wt1 NRAS https://medlineplus.gov/genetics/gene/nras CEBPA https://medlineplus.gov/genetics/gene/cebpa IDH2 https://medlineplus.gov/genetics/gene/idh2 RUNX1 https://medlineplus.gov/genetics/gene/runx1 FLT3 https://medlineplus.gov/genetics/gene/flt3 NPM1 https://medlineplus.gov/genetics/gene/npm1 IDH1 https://medlineplus.gov/genetics/gene/idh1 DNMT3A https://medlineplus.gov/genetics/gene/dnmt3a KMT2A https://www.ncbi.nlm.nih.gov/gene/4297 Acute myelogenous leukemia with normal karyotype CN-AML NK-AML Normal karyotype acute myeloid leukemia GTR C0023467 MeSH D015470 OMIM 601626 SNOMED CT 703387000 2013-12 2023-03-27 D-bifunctional protein deficiency https://medlineplus.gov/genetics/condition/d-bifunctional-protein-deficiency descriptionD-bifunctional protein deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with D-bifunctional protein deficiency have weak muscle tone (hypotonia) and seizures. Most babies with this condition never acquire any developmental skills. Some may reach very early developmental milestones such as the ability to follow movement with their eyes or control their head movement, but they experience a gradual loss of these skills (developmental regression) within a few months. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with D-bifunctional protein deficiency do not survive past the age of 2. A small number of individuals with this disorder are somewhat less severely affected. They may acquire additional basic skills, such as voluntary hand movements or unsupported sitting, before experiencing developmental regression, and they may survive longer into childhood than more severely affected individuals.Individuals with D-bifunctional protein deficiency may have unusual facial features, including a high forehead, widely spaced eyes (hypertelorism), a lengthened area between the nose and mouth (philtrum), and a high arch of the hard palate at the roof of the mouth. Affected infants may also have an unusually large space between the bones of the skull (fontanelle). An enlarged liver (hepatomegaly) occurs in about half of affected individuals. Because these features are similar to those of another disorder called Zellweger syndrome (part of a group of disorders called the Zellweger spectrum), D-bifunctional protein deficiency is sometimes called pseudo-Zellweger syndrome. ar Autosomal recessive HSD17B4 https://medlineplus.gov/genetics/gene/hsd17b4 17-beta-hydroxysteroid dehydrogenase IV deficiency Bifunctional peroxisomal enzyme deficiency DBP deficiency PBFE deficiency Peroxisomal bifunctional enzyme deficiency Pseudo-Zellweger syndrome Zellweger-like syndrome GTR C0342870 ICD-10-CM E71.541 MeSH D018901 OMIM 261515 SNOMED CT 238068007 2014-04 2025-04-04 DICER1 syndrome https://medlineplus.gov/genetics/condition/dicer1-syndrome descriptionDICER1 syndrome is an inherited disorder that increases the risk of a variety of cancerous and noncancerous (benign) tumors, most commonly certain types of tumors that occur in the lungs, kidneys, ovaries, and thyroid (a butterfly-shaped gland in the lower neck). Affected individuals can develop one or more types of tumors, and members of the same family can have different types. However, the risk of tumor formation in individuals with DICER1 syndrome is only moderately increased compared with tumor risk in the general population; most individuals with genetic changes associated with this condition never develop tumors.People with DICER1 syndrome who develop tumors most commonly develop pleuropulmonary blastoma, which is characterized by tumors that grow in lung tissue or in the outer covering of the lungs (the pleura). These tumors occur in infants and young children and are rare in adults. Pleuropulmonary blastoma is classified as one of three types on the basis of tumor characteristics: in type I, the growths are composed of air-filled pockets called cysts; in type II, the growths contain both cysts and solid tumors (or nodules); and in type III, the growth is a solid tumor that can fill a large portion of the chest. Pleuropulmonary blastoma is considered cancerous, and types II and III can spread (metastasize), often to the brain, liver, or bones. Individuals with pleuropulmonary blastoma may also develop an abnormal accumulation of air in the chest cavity that can lead to the collapse of a lung (pneumothorax).Cystic nephroma, which involves multiple benign fluid-filled cysts in the kidneys, can also occur; in people with DICER1 syndrome, the cysts develop early in childhood.DICER1 syndrome is also associated with tumors in the ovaries known as Sertoli-Leydig cell tumors, which typically develop in affected women in their teens or twenties. Some Sertoli-Leydig cell tumors release the male sex hormone testosterone; in these cases, affected women may develop facial hair, a deep voice, and other male characteristics. Some affected women have irregular menstrual cycles. Sertoli-Leydig cell tumors usually do not metastasize.People with DICER1 syndrome are also at risk of multinodular goiter, which is enlargement of the thyroid gland caused by the growth of multiple fluid-filled or solid tumors (both referred to as nodules). The nodules are generally slow-growing and benign. Despite the growths, the thyroid's function is often normal. Rarely, individuals with DICER1 syndrome develop thyroid cancer (thyroid carcinoma). ad Autosomal dominant DICER1 https://medlineplus.gov/genetics/gene/dicer1 DICER1-related pleuropulmonary blastoma cancer predisposition syndrome Pleuropulmonary blastoma familial tumor and dysplasia syndrome Pleuropulmonary blastoma family tumor susceptibility syndrome GTR C1266144 MeSH D009386 OMIM 138800 OMIM 601200 SNOMED CT 702411003 2013-05 2020-08-18 DLG4-related synaptopathy https://medlineplus.gov/genetics/condition/dlg4-related-synaptopathy descriptionDLG4-related synaptopathy is a condition that affects neurological development. This condition is characterized by delayed development and mild to moderate intellectual disabilities that typically becomes evident before age 2. Over time, many individuals with DLG4-related synaptopathy lose skills that they have learned, such as speech or motor skills. About 20 percent of people with this condition cannot speak. Affected individuals often have neurodevelopmental disorders, such as autism spectrum disorder or attention-deficit/hyperactivity disorder. About half of individuals with this condition have recurrent seizures (epilepsy) that typically begin in childhood. Brain changes can also occur. These include brain tissue loss (atrophy) and abnormalities of the tissue connecting the left and right halves of the brain (corpus callosum) or the  hippocampus, which is a region of the brain that is involved in learning and memory.Individuals with DLG4-related synaptopathy can also have weak muscle tone (hyptonia), loose joints (joint laxity), or a spine that curves to the side (scoliosis). Movement problems, including impaired muscle coordination (ataxia), involuntary muscle coordination (dystonia), or rhythmic shaking (tremor) are common in people with this condition. Other problems can include migraine, sleep problems, or anxiety. Some people with DLG4-related synaptopathy have a distinctive body type that includes a long face, slim body, and long fingers.Less commonly, DLG4-related synaptopathy can affect a person's vision. Affected individuals can have eyes that do not point in the same direction (strabismus), farsightedness (hyperopia), or involuntary movements of the eyes (nystagmus). Some affected individuals have blindness because the area of the brain responsible for processing vision is impaired. DLG4-related synaptopathy can also cause gastrointestinal difficulties that make it difficult to eat. These can include a backflow of stomach acids into the esophagus (gastroesophageal reflux disease or GERD). ad Autosomal dominant+New variant DLG4 https://medlineplus.gov/genetics/gene/dlg4 Intellectual developmental disorder 62 intellectual developmental disorder, autosomal dominant 62 SHINE syndrome sleep disturbances, hypotonia, intellectual disability, neurologic disorder, and epilepsy syndrome GTR C5394083 ICD-10-CM MeSH OMIM 618793 SNOMED CT 2023-11 2023-11-03 DNMT3A overgrowth syndrome https://medlineplus.gov/genetics/condition/dnmt3a-overgrowth-syndrome descriptionDNMT3A overgrowth syndrome is a disorder characterized by faster than normal growth before and after birth, subtle differences in facial features, and intellectual disability.Individuals with DNMT3A overgrowth syndrome are often longer than normal at birth and are taller than their peers throughout life. Many affected individuals become overweight in late childhood or adolescence. They may also have an abnormally large head size (macrocephaly).The characteristic facial appearance of individuals with DNMT3A overgrowth syndrome includes a round face; thick, horizontal eyebrows; and narrowed openings of the eyes (narrowed palpebral fissures). Additionally, the upper front teeth are often larger than normal.Intellectual disability in DNMT3A overgrowth syndrome ranges from mild to severe. Individuals may have features of autism spectrum disorder, which are characterized by impaired communication and socialization skills.Individuals with DNMT3A overgrowth syndrome may have other signs and symptoms, including a rounded upper back that also curves to the side (kyphoscoliosis), heart defects, flat feet (pes planus), weak muscle tone (hypotonia), or joints that are loose and very flexible (hypermobile joints). Psychological disorders such as depression, anxiety, or obsessive-compulsive disorder can also occur in this disorder. ad Autosomal dominant DNMT3A https://medlineplus.gov/genetics/gene/dnmt3a Tatton-Brown-Rahman syndrome TBRS GTR C4014545 MeSH D005877 OMIM 615879 2017-09 2022-08-03 DOCK8 immunodeficiency syndrome https://medlineplus.gov/genetics/condition/dock8-immunodeficiency-syndrome descriptionDOCK8 immunodeficiency syndrome is a disorder of the immune system. The condition is characterized by recurrent infections that are severe and can be life-threatening. The infections can be caused by bacteria, viruses, or fungi. Skin infections cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling. People with DOCK8 immunodeficiency syndrome also tend to have frequent bouts of pneumonia and other respiratory tract infections. Other immune system-related problems in people with DOCK8 immunodeficiency syndrome include an inflammatory skin disorder called eczema, food or environmental allergies, and asthma.DOCK8 immunodeficiency syndrome is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood; the levels can be more than 10 times higher than normal for no known reason. IgE normally triggers an immune response against foreign invaders in the body, particularly parasitic worms, and plays a role in allergies. It is unclear why people with DOCK8 immunodeficiency syndrome have such high levels of this protein. People with DOCK8 immunodeficiency syndrome also have highly elevated numbers of certain white blood cells called eosinophils (hypereosinophilia). Eosinophils aid in the immune response and are involved in allergic reactions.Some people with DOCK8 immunodeficiency syndrome have neurological problems, such as paralysis that affects the face or one side of the body (hemiplegia). Blockage of blood flow in the brain or abnormal bleeding in the brain, both of which can lead to stroke, can also occur in DOCK8 immunodeficiency syndrome.People with DOCK8 immunodeficiency syndrome have a greater-than-average risk of developing cancer, particularly cancers of the blood or skin.DOCK8 immunodeficiency syndrome is also commonly called autosomal recessive hyper-IgE syndrome. However, researchers have identified several conditions that feature elevated levels of IgE and that follow an autosomal recessive pattern of inheritance. Each of these conditions has its own set of additional signs and symptoms and a different genetic cause. Some doctors consider these conditions forms of hyper-IgE syndrome, while others consider them independent disorders. ar Autosomal recessive DOCK8 https://medlineplus.gov/genetics/gene/dock8 AR-HIES Autosomal recessive HIES Autosomal recessive hyper-IgE syndrome CID due to DOCK8 deficiency Combined immunodeficiency due to DOCK8 deficiency DOCK8 deficiency Hyper IgE recurrent infection syndrome, autosomal recessive Hyper immunoglobulin E syndrome, autosomal recessive Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive Hyperimmunoglobulin E syndrome type 2 Non-skeletal hyper-IgE syndrome GTR C4722305 ICD-10-CM D82.4 MeSH D007153 OMIM 243700 2019-08 2020-08-18 DOLK-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/dolk-congenital-disorder-of-glycosylation descriptionDOLK-congenital disorder of glycosylation (DOLK-CDG, formerly known as congenital disorder of glycosylation type Im) is an inherited condition that often affects the heart but can also involve other body systems. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.Individuals with DOLK-CDG typically develop signs and symptoms of the condition during infancy or early childhood. Nearly all individuals with DOLK-CDG develop a weakened and enlarged heart (dilated cardiomyopathy). Other frequent signs and symptoms include recurrent seizures; developmental delay; poor muscle tone (hypotonia); and dry, scaly skin (ichthyosis). Less commonly, affected individuals can have distinctive facial features, kidney disease, hormonal abnormalities, or eye problems.Individuals with DOLK-CDG typically do not survive into adulthood, often because of complications related to dilated cardiomyopathy, and some do not survive past infancy. ar Autosomal recessive DOLK https://medlineplus.gov/genetics/gene/dolk CDG1M Congenital disorder of glycosylation, type Im DK1 deficiency Dolichol kinase deficiency DOLK-CDG GTR C1835849 MeSH D018981 OMIM 610768 SNOMED CT 718712005 2016-03 2021-11-26 DOORS syndrome https://medlineplus.gov/genetics/condition/doors-syndrome descriptionDOORS syndrome is a disorder involving multiple abnormalities that are present from birth (congenital). "DOORS" is an abbreviation for the major features of the disorder including deafness; short or absent nails (onychodystrophy); short fingers and toes (osteodystrophy); developmental delay and intellectual disability (previously called mental retardation); and seizures. Some people with DOORS syndrome do not have all of these features.Most people with DOORS syndrome have profound hearing loss caused by changes in the inner ears (sensorineural deafness). Developmental delay and intellectual disability are also often severe in this disorder.The nail abnormalities affect both the hands and the feet in DOORS syndrome. Impaired growth of the bones at the tips of the fingers and toes (hypoplastic terminal phalanges) account for the short fingers and toes characteristic of this disorder. Some affected individuals also have an extra bone and joint in their thumbs, causing the thumbs to look more like the other fingers (triphalangeal thumbs).The seizures that occur in people with DOORS syndrome usually start in infancy. The most common seizures in people with this condition are generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Affected individuals may also have other types of seizures, including partial seizures, which affect only one area of the brain and do not cause a loss of consciousness; absence seizures, which cause loss of consciousness for a short period that appears as a staring spell; or myoclonic seizures, which cause rapid, uncontrolled muscle jerks. In some affected individuals the seizures increase in frequency and become more severe and difficult to control, and a potentially life-threatening prolonged seizure (status epilepticus) can occur.Other features that can occur in people with DOORS syndrome include an unusually small head size (microcephaly) and facial differences, most commonly a wide, bulbous nose. A narrow or high arched roof of the mouth (palate), broadening of the ridges in the upper and lower jaw that contain the sockets of the teeth (alveolar ridges), or shortening of the membrane between the floor of the mouth and the tongue (frenulum) have also been observed in some affected individuals. People with DOORS syndrome may also have dental abnormalities, structural abnormalities of the heart or urinary tract, and abnormally low levels of thyroid hormones (hypothyroidism). Most affected individuals also have higher-than-normal levels of a substance called 2-oxoglutaric acid in their urine; these levels can fluctuate between normal and elevated. ar Autosomal recessive TBC1D24 https://medlineplus.gov/genetics/gene/tbc1d24 Autosomal recessive deafness-onychodystrophy syndrome Deafness, onychodystrophy, osteodystrophy, and mental retardation syndrome Deafness-oncychodystrophy-osteodystrophy-intellectual disability syndrome Deafness-onychoosteodystrophy-intellectual disability syndrome Digitorenocerebral syndrome DOOR syndrome DRC syndrome Eronen syndrome MeSH D000015 OMIM 220500 SNOMED CT 719800009 2015-12 2020-08-18 Dandy-Walker malformation https://medlineplus.gov/genetics/condition/dandy-walker-malformation descriptionDandy-Walker malformation affects brain development, primarily development of the cerebellum, which is the part of the brain that coordinates movement. In individuals with this condition, various parts of the cerebellum develop abnormally, resulting in malformations that can be observed with medical imaging. The central part of the cerebellum (the vermis) is absent or very small and may be abnormally positioned. The right and left sides of the cerebellum may be small as well. In affected individuals, a fluid-filled cavity between the brainstem and the cerebellum (the fourth ventricle) and the part of the skull that contains the cerebellum and the brainstem (the posterior fossa) are abnormally large. These abnormalities often result in problems with movement, coordination, intellect, mood, and other neurological functions.In the majority of individuals with Dandy-Walker malformation, signs and symptoms caused by abnormal brain development are present at birth or develop within the first year of life. Some children have a buildup of fluid in the brain (hydrocephalus) that may cause increased head size (macrocephaly). Up to half of affected individuals have intellectual disability that ranges from mild to severe, and those with normal intelligence may have learning disabilities. Children with Dandy-Walker malformation often have delayed development, particularly a delay in motor skills such as crawling, walking, and coordinating movements. People with Dandy-Walker malformation may experience muscle stiffness and partial paralysis of the lower limbs (spastic paraplegia), and they may also have seizures. While rare, hearing and vision problems can be features of this condition.Less commonly, other brain abnormalities have been reported in people with Dandy-Walker malformation. These abnormalities include an underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum), a sac-like protrusion of the brain through an opening at the back of the skull (occipital encephalocele), or a failure of some nerve cells (neurons) to migrate to their proper location in the brain during development. These additional brain malformations are associated with more severe signs and symptoms.Dandy-Walker malformation typically affects only the brain, but problems in other systems can include heart defects, malformations of the urogenital tract, extra fingers or toes (polydactyly) or fused fingers or toes (syndactyly), or abnormal facial features.In 10 to 20 percent of people with Dandy-Walker malformation, signs and symptoms of the condition do not appear until late childhood or into adulthood. These individuals typically have a different range of features than those affected in infancy, including headaches, an unsteady walking gait, paralysis of facial muscles (facial palsy), increased muscle tone, muscle spasms, and mental and behavioral changes. Rarely, people with Dandy-Walker malformation have no health problems related to the condition.Problems related to hydrocephalus or complications of its treatment are the most common cause of death in people with Dandy-Walker malformation. u Pattern unknown FOXC1 https://medlineplus.gov/genetics/gene/foxc1 ZIC1 https://www.ncbi.nlm.nih.gov/gene/7545 ZIC4 https://www.ncbi.nlm.nih.gov/gene/84107 Dandy-Walker complex Dandy-Walker cyst Dandy-Walker deformity Dandy-Walker syndrome DWM DWS Hydrocephalus, internal, Dandy-Walker type Hydrocephalus, noncommunicating, Dandy-Walker type Luschka-Magendie foramina atresia GTR C0010964 ICD-10-CM Q03.1 MeSH D003616 OMIM 220200 SNOMED CT 14447001 SNOMED CT 840471002 2012-07 2020-08-18 Danon disease https://medlineplus.gov/genetics/condition/danon-disease descriptionDanon disease is a condition characterized by weakening of the heart muscle (cardiomyopathy); weakening of the muscles used for movement, called skeletal muscles (myopathy); and intellectual disabilities. People with Danon disease may develop the condition at different ages. Signs and symptoms of this condition appear about 15 years earlier in males than in females. Males first experience health problems in childhood or adolescence; without treatment, these individuals typically live into early adulthood. Females start experiencing health problems in early adulthood and typically survive into mid-adulthood without treatment.Cardiomyopathy is the most common symptom of Danon disease, and it occurs in all males and in most females. Beginning in childhood, most affected males develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that may make it harder for the heart to pump blood. Others with Danon disease may have dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. About half of females with Danon disease have hypertrophic cardiomyopathy, and the other half have dilated cardiomyopathy. Rarely, individuals with hypertrophic cardiomyopathy later develop dilated cardiomyopathy. Either type of cardiomyopathy can lead to heart failure and premature death.Individuals with Danon disease can have other heart-related signs and symptoms, including a sensation of fluttering or pounding in the chest (palpitations), an abnormal heartbeat (arrhythmia), or chest pain. Many affected individuals have abnormalities of the electrical signals that control the heartbeat (conduction abnormalities). Affected individuals often have a specific conduction abnormality known as cardiac preexcitation. The type of cardiac preexcitation most often seen in people with Danon disease is called the Wolff-Parkinson-White syndrome pattern.Skeletal myopathy occurs in most males with Danon disease and in some affected females. The weakness typically occurs in the muscles of the shoulders, neck, and upper thighs. Many males with Danon disease have elevated levels of an enzyme called creatine kinase in their blood, which often indicates muscle disease.Most males with Danon disease have mild intellectual disabilities, but this is much less common in affected females.There can be other signs and symptoms of the condition in addition to the three characteristic features. Several affected individuals have had gastrointestinal disease, breathing problems, or visual abnormalities. x X-linked LAMP2 https://medlineplus.gov/genetics/gene/lamp2 Glycogen storage disease type 2B Glycogen storage disease type IIb Lysosomal glycogen storage disease with normal acid maltase Lysosomal glycogen storage disease without acid maltase deficiency Lysosome-associated membrane protein 2 (LAMP2) deficiency X-linked pseudoglycogenosis II X-linked vacuolar cardiomyopathy and myopathy GTR C0878677 MeSH D052120 OMIM 300257 SNOMED CT 419097006 2024-04 2025-06-12 Darier disease https://medlineplus.gov/genetics/condition/darier-disease descriptionDarier disease is a skin condition characterized by wart-like blemishes on the body. The blemishes are usually yellowish in color, are hard to the touch, can appear greasy, and can emit a strong odor. The most common sites for blemishes are the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ears. The mucous membranes can also be affected, with blemishes occurring on the roof of the mouth (palate), tongue, gums, and inside the cheeks and throat. Other features of Darier disease include nail abnormalities, such as red and white streaks in the nails with an irregular texture, and small pits in the palms of the hands and soles of the feet.The wart-like blemishes characteristic of Darier disease usually appear in late childhood to early adulthood. The severity of the disease varies over time; affected people experience flare-ups and with periods when they have fewer blemishes. The appearance of the blemishes is influenced by environmental factors. Most people with Darier disease will develop more blemishes during the summer when they are exposed to heat and humidity. The number of blemishes can also increase when an affected person is exposed to ultraviolet light; experiences minor injury or friction, such as rubbing or scratching; or takes certain medications.On occasion, people with Darier disease may have neurological disorders such as mild intellectual disabilities, epilepsy, and depression. Learning and behavior difficulties have also been reported in people with Darier disease. Researchers do not know if these conditions, which are common in the general population, are associated with the genetic changes that cause Darier disease, or if they are coincidental. Some researchers believe that behavioral problems might be linked to the social stigma experienced by people with numerous skin blemishes.A form of Darier disease known as the linear or segmental form is characterized by blemishes on localized areas of the skin. The blemishes are not as widespread as they are in typical Darier disease. Some people with the linear form of this condition have the nail abnormalities that are seen in people with classic Darier disease, but these abnormalities occur only on one side of the body. ad Autosomal dominant+Inherited or new variant ATP2A2 https://medlineplus.gov/genetics/gene/atp2a2 Darier's disease Darier-White disease Keratosis follicularis GTR C0022595 MeSH D007644 OMIM 124200 SNOMED CT 239110000 SNOMED CT 400018004 SNOMED CT 403783009 SNOMED CT 403784003 SNOMED CT 403785002 SNOMED CT 403786001 SNOMED CT 403787005 SNOMED CT 48611009 2024-01 2024-01-12 Deafness and myopia syndrome https://medlineplus.gov/genetics/condition/deafness-and-myopia-syndrome descriptionDeafness and myopia syndrome is a disorder that causes problems with both hearing and vision. People with this disorder have moderate to profound hearing loss in both ears that may worsen over time. The hearing loss may be described as sensorineural, meaning that it is related to changes in the inner ear, or it may be caused by auditory neuropathy, which is a problem with the transmission of sound (auditory) signals from the inner ear to the brain. The hearing loss is either present at birth (congenital) or begins in infancy, before the child learns to speak (prelingual).Affected individuals also have severe nearsightedness (high myopia). These individuals are able to see nearby objects clearly, but objects that are farther away appear blurry. The myopia is usually diagnosed by early childhood. ar Autosomal recessive SLITRK6 https://medlineplus.gov/genetics/gene/slitrk6 Deafness and myopia Deafness, cochlear, plus DFNMYP High myopia and sensorineural deafness High myopia-sensorineural deafness syndrome Myopia and deafness GTR C3806275 MeSH D006319 MeSH D009216 OMIM 221200 SNOMED CT 720506002 2015-10 2023-03-21 Deafness-dystonia-optic neuronopathy syndrome https://medlineplus.gov/genetics/condition/deafness-dystonia-optic-neuronopathy-syndrome descriptionDeafness-dystonia-optic neuronopathy (DDON) syndrome, also known as Mohr-Tranebjærg syndrome, is characterized by hearing loss that begins early in life, problems with movement, impaired vision, and behavior problems. This condition occurs almost exclusively in males.The first symptom of DDON syndrome is hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), which begins in early childhood. The hearing impairment worsens over time, and most affected individuals have profound hearing loss by age 10.People with DDON syndrome typically begin to develop problems with movement during their teens, although the onset of these symptoms varies among affected individuals. Some people experience involuntary tensing of the muscles (dystonia), while others have difficulty coordinating movements (ataxia). The problems with movement usually worsen over time.Individuals with DDON syndrome have normal vision during childhood, but they may develop vision problems due to breakdown of the nerves that carry information from the eyes to the brain (optic atrophy). Affected individuals can develop an increased sensitivity to light (photophobia) or other vision problems beginning in adolescence. Their sharpness of vision (visual acuity) slowly worsens, often leading to legal blindness in mid-adulthood.People with this condition may also have behavior problems, including changes in personality and aggressive or paranoid behaviors. They also usually develop a gradual decline in thinking and reasoning abilities (dementia) in their forties. The lifespan of individuals with DDON syndrome depends on the severity of the disorder. People with severe cases have survived into their teenage years, while those with milder cases have lived into their sixties. xr X-linked recessive TIMM8A https://medlineplus.gov/genetics/gene/timm8a Deafness syndrome, progressive, with blindness, dystonia, fractures, and mental deficiency Deafness-dystonia-optic atrophy syndrome Jensen syndrome Mohr-Tranebjærg syndrome Opticoacoustic nerve atrophy with dementia GTR C0796074 MeSH D040181 OMIM 304700 SNOMED CT 702423009 2008-09 2020-08-18 Deafness-infertility syndrome https://medlineplus.gov/genetics/condition/deafness-infertility-syndrome descriptionDeafness-infertility syndrome is a condition characterized by hearing loss and difficulty conceiving children (a condition called infertility). Affected individuals have moderate to severe sensorineural hearing loss, which is caused by abnormalities in the inner ear. The hearing loss is typically diagnosed in early childhood and does not worsen over time. Individuals with this condition produce sperm that have decreased movement (motility). As a result, they cannot conceive without assisted reproductive technologies. ar Autosomal recessive STRC https://medlineplus.gov/genetics/gene/strc CATSPER2 https://medlineplus.gov/genetics/gene/catsper2 15 https://medlineplus.gov/genetics/chromosome/15 Chromosome 15q15.3 deletion syndrome DIS Sensorineural deafness and infertility Sensorineural deafness and male infertility GTR C1970187 ICD-10-CM MeSH D007248 OMIM 611102 SNOMED CT 700489002 2024-04 2025-03-06 Dementia with Lewy bodies https://medlineplus.gov/genetics/condition/dementia-with-lewy-bodies descriptionDementia with Lewy bodies is a nervous system disorder characterized by a decline in intellectual function (dementia), a group of movement problems known as parkinsonism, visual hallucinations, sudden changes (fluctuations) in behavior and intellectual ability, and acting out dreams while asleep (REM sleep behavior disorder). This condition typically affects older adults, most often developing between ages 50 and 85. The life expectancy of individuals with dementia with Lewy bodies varies; people typically survive about 5 to 7 years after they are diagnosed.REM sleep behavior disorder may be the first sign of dementia with Lewy bodies. It can occur years before other symptoms appear. Individuals with REM sleep behavior disorder act out their dreams, talking and moving in their sleep when they should be still. This behavior becomes less pronounced as dementia with Lewy bodies worsens and additional features develop.Dementia is often the second major feature to develop in dementia with Lewy bodies. Initially, this intellectual decline may be mild or seem to come and go. In this condition, dementia often leads to impaired ability to perform visual-spatial tasks such as assembling puzzles. Affected individuals may also have poor problem-solving skills (executive functioning), speech difficulties, and reduced inhibitions. Problems with memory typically do not occur until later.Most people with dementia with Lewy bodies experience visual hallucinations, which often involve people or animals. Fluctuations in behavior and thought processes (cognition) include sudden changes in attention, unintelligible speech, and brief episodes of altered consciousness that may appear as staring spells.Parkinsonism is usually the last major feature to develop in people with dementia with Lewy bodies, although it can appear earlier in some individuals. The movement problems typically include tremors, rigidity, unusually slow movement (bradykinesia), and impaired balance and coordination (postural instability). Affected individuals may require walking aids or wheelchair assistance over time.Individuals with dementia with Lewy bodies may also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), fainting episodes (syncope), reduced sense of smell, increased saliva production and drooling, difficulty controlling the flow of urine (incontinence), or constipation. ad Autosomal dominant GBA1 https://medlineplus.gov/genetics/gene/gba1 APOE https://medlineplus.gov/genetics/gene/apoe SNCA https://medlineplus.gov/genetics/gene/snca SNCB https://medlineplus.gov/genetics/gene/sncb Dementia of the Lewy body type Dementia, Lewy body Diffuse Lewy body disease DLB LBD Lewy body dementia Lewy body disease GTR C0752347 ICD-10-CM G31.83 MeSH D020961 OMIM 127750 SNOMED CT 80098002 2018-10 2024-07-18 Dent disease https://medlineplus.gov/genetics/condition/dent-disease descriptionDent disease is a chronic kidney disorder that occurs almost exclusively in males. The kidney problems seen in affected individuals are a result of damage to structures called proximal tubules. These structures help reabsorb water, protein, and other nutrients into the bloodstream or release them into the urine.The signs and symptoms of Dent disease tend to appear in childhood and worsen over time. However, the features and the severity of Dent disease vary greatly among affected individuals.The most frequent sign of Dent disease is the loss of small proteins in the urine (also called low-molecular-weight or LMW proteinuria). Too much calcium in the urine (hypercalciuria) is another common sign of Dent disease. LMW proteinuria and hypercalciuria may be the only signs of Dent disease in affected children.Additional signs and symptoms of Dent disease can include calcium deposits in the kidneys (nephrocalcinosis) and kidney stones (nephrolithiasis). Kidney stones can cause abdominal pain and blood in the urine (hematuria). Thirty to 80 percent of people with Dent disease develop kidney failure in early to mid-adulthood. Kidney failure can be life-threatening and occurs when the kidneys are no longer able to effectively filter fluids and waste products from the body.In some people with Dent disease, low levels of vitamin D and other factors can cause bones to soften and weaken. This can result in a condition called rickets or a similar condition called osteomalacia. These conditions can cause bone pain and make bones more likely to break. Rickets can also be associated with bowed legs, difficulty walking, and short stature.Researchers have described two forms of Dent disease that are caused by changes in different genes: Dent disease 1 and Dent disease 2. Both forms are characterized by the features described above, but Dent disease 2 can also be associated with mild intellectual disabilities and developmental delays. People with Dent disease 2 may also have a clouding of the lens of the eye (cataract) that does not typically cause severe visual impairment. Studies have also suggested that people with Dent disease 2 may be more likely to develop a painful skin condition called hidradenitis suppurativa. ad Autosomal dominant+New variant x X-linked OCRL https://medlineplus.gov/genetics/gene/ocrl CLCN5 https://medlineplus.gov/genetics/gene/clcn5 Dent syndrome Dent's disease Dents disease Low-molecular-weight proteinuria with hypercalciuria and nephrocalcinosis Renal Fanconi syndrome with nephrocalcinosis and renal stones X-linked recessive hypercalciuric hypophosphatemic rickets X-linked recessive nephrolithiasis GTR C1845167 GTR C1848336 MeSH D057973 OMIM 300009 OMIM 300555 SNOMED CT 444645005 2026-04 2026-04-10 Dentatorubral-pallidoluysian atrophy https://medlineplus.gov/genetics/condition/dentatorubral-pallidoluysian-atrophy descriptionDentatorubral-pallidoluysian atrophy (DRPLA) is a progressive brain disorder that causes involuntary movements, mental and emotional problems, and a decline in thinking ability. The average age of onset for DRPLA is around 30 years, but this condition can appear any time between infancy and mid-adulthood.The signs and symptoms of DRPLA differ somewhat between affected children and adults. When DRPLA appears before age 20, it most often involves episodes of involuntary muscle jerking or twitching (myoclonus), seizures, behavioral changes, intellectual disabilities, and problems with balance and coordination (ataxia). When DRPLA begins after age 20, the most frequent signs and symptoms are ataxia, uncontrollable movements of the limbs (choreoathetosis), psychiatric symptoms such as delusions, and deterioration of intellectual function (dementia). ad Autosomal dominant ATN1 https://medlineplus.gov/genetics/gene/atn1 DRPLA Haw River syndrome Myoclonic epilepsy with choreoathetosis Naito-Oyanagi disease NOD GTR C0751781 MeSH D020191 OMIM 125370 SNOMED CT 68116008 2023-12 2023-12-05 Dentinogenesis imperfecta https://medlineplus.gov/genetics/condition/dentinogenesis-imperfecta descriptionDentinogenesis imperfecta is a disorder of tooth development. This condition causes the teeth to be discolored (most often a blue-gray or yellow-brown color) and translucent. Teeth are also weaker than normal, making them prone to rapid wear, breakage, and loss. These problems can affect both primary (baby) teeth and permanent teeth.Researchers have described three types of dentinogenesis imperfecta with similar dental abnormalities. Type I occurs in people who have osteogenesis imperfecta, a genetic condition in which bones are brittle and easily broken. Dentinogenesis imperfecta type II and type III usually occur in people without other inherited disorders. A few older individuals with type II have had progressive high-frequency hearing loss in addition to dental abnormalities, but it is not known whether this hearing loss is related to dentinogenesis imperfecta.Some researchers believe that dentinogenesis imperfecta type II and type III, along with a condition called dentin dysplasia type II, are actually forms of a single disorder. The signs and symptoms of dentin dysplasia type II are very similar to those of dentinogenesis imperfecta. However, dentin dysplasia type II affects the primary teeth much more than the permanent teeth. ad Autosomal dominant DSPP https://medlineplus.gov/genetics/gene/dspp DGI Hereditary opalescent dentin GTR C0399378 GTR C2973527 ICD-10-CM Q78.0 MeSH D003811 OMIM 125420 OMIM 125490 OMIM 125500 SNOMED CT 196286005 SNOMED CT 234969005 SNOMED CT 234970006 2009-10 2023-03-21 Denys-Drash syndrome https://medlineplus.gov/genetics/condition/denys-drash-syndrome descriptionDenys-Drash syndrome is a condition that affects the kidneys and genitalia.Denys-Drash syndrome is characterized by kidney disease that begins within the first few months of life. Affected individuals have a condition called diffuse glomerulosclerosis, in which scar tissue forms throughout glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Denys-Drash syndrome, this condition often leads to kidney failure in childhood. People with Denys-Drash syndrome have an estimated 90 percent chance of developing a rare form of kidney cancer known as Wilms tumor. Affected individuals may develop multiple tumors in one or both kidneys.Although males with Denys-Drash syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female or the genitalia appear female-typical. The testes of affected males are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. As a result, males with Denys-Drash are typically unable to have biological children (infertile).Affected females usually have normal genitalia and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome. ad Autosomal dominant WT1 https://medlineplus.gov/genetics/gene/wt1 DDS Drash syndrome Nephropathy, Wilms tumor, and genital anomalies Wilms tumor and pseudohermaphroditism GTR C0950121 ICD-10-CM MeSH D030321 OMIM 194080 SNOMED CT 236385009 2013-03 2023-10-27 Deoxyguanosine kinase deficiency https://medlineplus.gov/genetics/condition/deoxyguanosine-kinase-deficiency descriptionDeoxyguanosine kinase deficiency is an inherited disorder that can disrupt the normal function of the liver, brain, and muscles. Researchers have described different forms of this disorder. Approximately 75 percent of affected individuals have the hepatocerebral form, which causes serious problems in the liver (hepato-) and brain (cerebral). Approximately 20 percent of people with deoxyguanosine kinase deficiency have the isolated hepatic form, which causes liver disease without serious neurological problems. The myopathic form is the least common form; it affects approximately 5 percent of people with deoxyguanosine kinase deficiency. The myopathic form causes problems with the skeletal muscles, which are the muscles used for movement. The signs and symptoms of deoxyguanosine kinase deficiency can vary, even among members of the same family. Infants with the hepatocerebral form of deoxyguanosine kinase deficiency typically have low blood glucose levels (hypoglycemia) and a buildup of lactic acid in the body (lactic acidosis) soon after birth. Within the first few weeks of life, these infants typically begin to show signs of liver disease and brain dysfunction. Neurological signs and symptoms may include weak muscle tone (hypotonia), abnormal involuntary eye movements (nystagmus), developmental delays, and, rarely, seizures. Early signs of liver disease may include an enlarged liver (hepatomegaly) and yellowing of the skin and the whites of the eyes (jaundice). Liver disease usually progresses to liver failure. Signs and symptoms of the isolated hepatic form of deoxyguanosine kinase deficiency may appear soon after birth or during childhood. Like those with the hepatocerebral form, people with the hepatic form often have liver disease that worsens over time and may progress to liver failure. Some affected individuals have additional signs and symptoms that indicate the involvement of other body systems, such as the kidneys and the heart. Signs and symptoms of the myopathic form often appear in adulthood, although they sometimes appear earlier in life. In addition to problems with the skeletal muscles, people with the myopathic form of deoxyguanosine kinase deficiency can have heart problems, brain abnormalities, or weakness of the eye muscles. People with the myopathic form typically do not have liver disease. Without intervention, most individuals with deoxyguanosine kinase deficiency have a shortened life expectancy. Those with liver disease typically do not survive past early childhood, while those with the myopathic form may survive into middle or late adulthood.  ar Autosomal recessive DGUOK https://medlineplus.gov/genetics/gene/dguok DGUOK deficiency DGUOK-related mitochondrial DNA depletion syndrome, hepatocerebral form Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK deficiency MTDPS3 GTR CN074093 MeSH D028361 OMIM 251880 SNOMED CT 237995002 2024-08 2025-12-16 Depression https://medlineplus.gov/genetics/condition/depression descriptionDepression (also known as major depression or major depressive disorder) is a psychiatric disorder that affects mood, behavior, and overall health. It causes prolonged feelings of sadness, emptiness, or hopelessness, and a loss of interest in activities that were once enjoyed. People with depression may also have changes in appetite (leading to overeating or not eating enough), changes in sleeping patterns (sleeping too much or not being able to sleep), loss of energy, and difficulty concentrating. Although depression is considered primarily a mental health disorder, it can also have physical features including headaches, other unexplained aches and pains, unusually slow or fast movements, and digestive problems. To be diagnosed with depression, an individual must have signs and symptoms nearly every day for at least 2 weeks. However, the features of this condition vary widely.Depression most commonly begins in late adolescence or early adulthood, although it can appear at any age. If untreated, episodes of depression can last for weeks, months, or years, and can go away and come back (recur). Affected individuals may have difficulty functioning in their daily lives, including at school or work. People with depression have a higher risk of substance abuse problems and dying by suicide than the general population.Several health conditions are closely related to depression or have depression as a characteristic feature. These include dysthymia (which has long-lasting signs and symptoms that are similar to, but not as severe as, those of depression), perinatal or postpartum depression (which occurs around or following the birth of a child), seasonal affective disorder (which is triggered by the changing of the seasons), bipolar disorder (which can include both "highs," or manic episodes, and depressive episodes), and generalized anxiety disorder. In people with schizoaffective disorder, depression or another mood disorder occurs together with features of schizophrenia (a brain disorder that affects a person's thinking, sense of self, and perceptions). u Pattern unknown Clinical depression Depressive disorder Major depression Major depressive disorder MDD Unipolar depression GTR C1269683 ICD-10-CM F32 ICD-10-CM F32.0 ICD-10-CM F32.1 ICD-10-CM F32.2 ICD-10-CM F32.3 ICD-10-CM F32.4 ICD-10-CM F32.5 ICD-10-CM F32.81 ICD-10-CM F32.89 ICD-10-CM F32.9 ICD-10-CM F33 ICD-10-CM F33.0 ICD-10-CM F33.1 ICD-10-CM F33.3 ICD-10-CM F33.4 ICD-10-CM F33.40 ICD-10-CM F33.42 ICD-10-CM F33.8 ICD-10-CM F33.9 MeSH D003863 OMIM 608516 OMIM 608520 OMIM 608691 SNOMED CT 35489007 SNOMED CT 871840004 2018-04 2023-08-18 Dermatofibrosarcoma protuberans https://medlineplus.gov/genetics/condition/dermatofibrosarcoma-protuberans descriptionDermatofibrosarcoma protuberans is a rare type of cancer that causes a tumor in the deep layers of skin. This condition is a type of soft tissue sarcoma, which are cancers that affect skin, fat, muscle, and similar tissues.In dermatofibrosarcoma protuberans, the tumor most often starts as a small, firm patch of skin, usually 1 to 5 centimeters in diameter, that is usually purplish, reddish, or flesh-colored. The tumor typically grows slowly and can become a raised nodule. Occasionally, the tumor begins as a flat or depressed patch of skin (plaque). Tumors are most commonly found on the torso and can also be found on the arms, legs, head, or neck. Affected individuals usually first show signs of this condition in their thirties, but the age at which a tumor appears varies widely.In dermatofibrosarcoma protuberans, the tumor has a tendency to return after being removed. However, it does not often spread to other parts of the body (metastasize).There are several variants of dermatofibrosarcoma protuberans in which different cell types are involved in the tumor. Bednar tumors, often called pigmented dermatofibrosarcoma protuberans, contain dark-colored (pigmented) cells called melanin-containing dendritic cells. Myxoid dermatofibrosarcoma protuberans tumors contain an abnormal type of connective tissue known as myxoid stroma. Giant cell fibroblastoma, which is sometimes referred to as juvenile dermatofibrosarcoma protuberans because it typically affects children and adolescents, is characterized by giant cells in the tumor.Rarely, the tumors involved in the different types of dermatofibrosarcoma protuberans can have regions that look similar to fibrosarcoma, a more aggressive type of soft tissue sarcoma. In these cases, the condition is called fibrosarcomatous dermatofibrosarcoma protuberans or FS-DFSP. FS-DFSP tumors are more likely to metastasize than tumors in the other types of dermatofibrosarcoma protuberans. n Not inherited COL1A1 https://medlineplus.gov/genetics/gene/col1a1 PDGFB https://medlineplus.gov/genetics/gene/pdgfb 17 https://medlineplus.gov/genetics/chromosome/17 22 https://medlineplus.gov/genetics/chromosome/22 Darier-Ferrand tumor Darier-Hoffmann tumor Dermatofibrosarcoma DFSP GTR C3693482 MeSH D018223 OMIM 607907 SNOMED CT 276799004 2011-09 2020-09-08 Desmoid tumor https://medlineplus.gov/genetics/condition/desmoid-tumor descriptionA desmoid tumor is an abnormal growth that arises from connective tissue, which is the tissue that provides strength and flexibility to structures such as bones, ligaments, and muscles. Affected individuals typically develop a single tumor, although some have multiple tumors. Desmoid tumors most often develop when people are in their 30s or 40s, although they can occur anytime between adolescence and late adulthood.Tumors that form in the abdomen or abdominal wall are called abdominal desmoid tumors, those that arise from the tissue that connects the abdominal organs are called intra-abdominal desmoid tumors, and tumors found in other regions of the body are called extra-abdominal desmoid tumors. Extra-abdominal tumors occur most often in the shoulders, upper arms, and upper legs.Desmoid tumors are fibrous, much like scar tissue. They are generally noncancerous (benign) because they do not spread to other parts of the body (metastasize); however, they can aggressively invade the surrounding tissue and can be very difficult to remove surgically. Desmoid tumors can recur, even after they are removed. In about 20 percent of cases, the tumors shrink or disappear with minimal or no treatment (spontaneously regress).Desmoid tumors may not cause any signs or symptoms. When they do cause symptoms, the most common one is pain. The pain is often due to the tumor pressing against nearby organs, tissues, or blood vessels. Other signs and symptoms are often caused by growth of the tumor into the surrounding tissue, and they can vary based on the size and location of the tumor. Intra-abdominal desmoid tumors can block the bowel, causing constipation. Extra-abdominal desmoid tumors can restrict the movement of affected joints, making it difficult to move the arms or legs.Desmoid tumors can also occur in combination with other conditions. Desmoid tumors are found in 10 to 30 percent of people with an inherited form of colon cancer called familial adenomatous polyposis (FAP). These individuals typically develop intra-abdominal desmoid tumors in addition to abnormal growths (called polyps) and cancerous tumors in the colon. Desmoid tumors that are not part of FAP are described as sporadic. ad Autosomal dominant+1 affected parent n Not inherited APC https://medlineplus.gov/genetics/gene/apc CTNNB1 https://medlineplus.gov/genetics/gene/ctnnb1 Aggressive fibromatosis Desmoid fibromatosis Desmoid-type fibromatosis Familial infiltrative fibromatosis Hereditary desmoid disease Musculoaponeurotic fibromatosis GTR C1851124 MeSH D018222 OMIM 135290 SNOMED CT 399994005 SNOMED CT 47284001 SNOMED CT 725049005 2025-08 2025-08-26 Desmosterolosis https://medlineplus.gov/genetics/condition/desmosterolosis descriptionDesmosterolosis is a condition that is characterized by neurological problems, such as brain abnormalities and developmental delay, and can also include other signs and symptoms.Children with desmosterolosis have delayed speech and motor skills (such as sitting and walking). Later in childhood, some affected individuals are able to walk with support; verbal communication is often limited to a few words or phrases. Common brain abnormalities in desmosterolosis include malformation of the tissue that connects the left and right halves of the brain (the corpus callosum) and loss of white matter, which consists of nerve fibers covered by a fatty substance called myelin.People with desmosterolosis commonly have muscle stiffness (spasticity) and stiff, rigid joints (arthrogryposis) affecting their hands and feet. Other features seen in some affected individuals include short stature, abnormal head size (either larger or smaller than normal), a small lower jaw (micrognathia), an opening in the roof of the mouth (cleft palate), involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus), heart defects, and seizures. ar Autosomal recessive DHCR24 https://medlineplus.gov/genetics/gene/dhcr24 Deficiency of 3beta-hydroxysterol delta24-reductase GTR C1865596 MeSH D008052 OMIM 602398 SNOMED CT 709490002 2014-08 2020-08-18 Developmental and epileptic encephalopathy 1 https://medlineplus.gov/genetics/condition/developmental-and-epileptic-encephalopathy-1 descriptionDevelopmental and epileptic encephalopathy 1 (DEE1) is a seizure disorder characterized by a type of seizure known as infantile spasms. The spasms usually appear before the age of 1. Several types of spasms have been described, but the most commonly reported type involves bending at the waist and neck and extending the arms and legs (sometimes called a jackknife spasm). Each spasm lasts only seconds, but they occur in clusters several minutes long. Although individuals do not usually have spasms while they are sleeping, the spasms commonly occur just after awakening. Infantile spasms usually stop by age 5, but many children then develop other types of seizures that recur throughout their lives.Most babies with DEE1 have characteristic results on an electroencephalogram (EEG), a test used to measure the electrical activity of the brain. The EEG of these individuals typically shows an irregular pattern known as hypsarrhythmia, and this finding can help differentiate infantile spasms from other types of seizures.Early in life, babies with DEE1 stop developing normally and begin to lose skills they have acquired (developmental regression), such as sitting, rolling over, and babbling. Most affected individuals also have intellectual disability throughout their lives. xr X-linked recessive ARX https://medlineplus.gov/genetics/gene/arx Early infantile epileptic encephalopathy-1 EIEE1 Epileptic encephalopathy, early infantile, 1 Infantile epileptic-dyskinetic encephalopathy ISSX ISSX1 X-linked infantile spasm syndrome X-linked infantile spasm syndrome 1 X-linked Ohtahara syndrome X-linked West syndrome GTR C0037769 GTR C3463992 MeSH D038901 OMIM 308350 SNOMED CT 28055006 2017-11 2020-11-13 Diamond-Blackfan anemia https://medlineplus.gov/genetics/condition/diamond-blackfan-anemia descriptionDiamond-Blackfan anemia is a disorder that primarily affects the bone marrow. People with this condition often also have physical abnormalities affecting various parts of the body.The major function of bone marrow is to produce new blood cells. In Diamond-Blackfan anemia, the bone marrow malfunctions and fails to make enough red blood cells, which carry oxygen to the body's tissues. The resulting shortage of red blood cells (anemia) usually becomes apparent during the first year of life. Symptoms of anemia include fatigue, weakness, and an abnormally pale appearance (pallor).People with Diamond-Blackfan anemia have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS), which is a disorder in which immature blood cells fail to develop normally. Individuals with Diamond-Blackfan anemia also have an increased risk of developing a bone marrow cancer known as acute myeloid leukemia (AML), a type of bone cancer called osteosarcoma, and other cancers.Approximately half of individuals with Diamond-Blackfan anemia have physical abnormalities. They may have an unusually small head size (microcephaly) and a low frontal hairline, along with distinctive facial features such as wide-set eyes (hypertelorism); droopy eyelids (ptosis); a broad, flat bridge of the nose; small, low-set ears; and a small lower jaw (micrognathia). Affected individuals may also have an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). They may have a short, webbed neck; shoulder blades that are smaller and higher than usual; and abnormalities of their hands, most commonly malformed or absent thumbs. About one-third of affected individuals have slow growth leading to short stature.Other features of Diamond-Blackfan anemia may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), or eyes that do not look in the same direction (strabismus). Affected individuals may also have kidney abnormalities; structural defects of the heart; and, in males, the opening of the urethra on the underside of the penis (hypospadias).The severity of Diamond-Blackfan anemia may vary, even within the same family. Increasingly, individuals with "non-classical" Diamond-Blackfan anemia have been identified. This form of the disorder typically has less severe symptoms. For example, some affected individuals have mild anemia beginning later in childhood or in adulthood, while others have some of the physical features but no bone marrow problems. ad Autosomal dominant RPL35A https://medlineplus.gov/genetics/gene/rpl35a RPS17 https://medlineplus.gov/genetics/gene/rps17 RPS24 https://medlineplus.gov/genetics/gene/rps24 RPS19 https://medlineplus.gov/genetics/gene/rps19 RPL5 https://medlineplus.gov/genetics/gene/rpl5 RPL11 https://medlineplus.gov/genetics/gene/rpl11 GATA1 https://medlineplus.gov/genetics/gene/gata1 RPS10 https://medlineplus.gov/genetics/gene/rps10 RPS26 https://medlineplus.gov/genetics/gene/rps26 RPL15 https://www.ncbi.nlm.nih.gov/gene/6138 RPL26 https://www.ncbi.nlm.nih.gov/gene/6154 RPL27 https://www.ncbi.nlm.nih.gov/gene/6155 RPL31 https://www.ncbi.nlm.nih.gov/gene/6160 RPS7 https://www.ncbi.nlm.nih.gov/gene/6201 RPS15 https://www.ncbi.nlm.nih.gov/gene/6209 RPS27 https://www.ncbi.nlm.nih.gov/gene/6232 RPS27A https://www.ncbi.nlm.nih.gov/gene/6233 RPS28 https://www.ncbi.nlm.nih.gov/gene/6234 RPS29 https://www.ncbi.nlm.nih.gov/gene/6235 RPL36 https://www.ncbi.nlm.nih.gov/gene/25873 TSR2 https://www.ncbi.nlm.nih.gov/gene/90121 Aase syndrome Aase-Smith syndrome II BDA BDS Blackfan Diamond anemia Blackfan-Diamond disease Blackfan-Diamond syndrome Chronic congenital agenerative anemia Congenital erythroid hypoplastic anemia Congenital hypoplastic anemia of Blackfan and Diamond Congenital pure red cell anemia Congenital pure red cell aplasia DBA Erythrogenesis imperfecta Hypoplastic congenital anemia Inherited erythroblastopenia Pure hereditary red cell aplasia GTR C1260899 ICD-10-CM D61.01 MeSH D029503 OMIM 105650 OMIM 300946 OMIM 606129 OMIM 606164 OMIM 610629 OMIM 612527 OMIM 612528 OMIM 612561 OMIM 612562 OMIM 612563 OMIM 613308 OMIM 613309 OMIM 614900 OMIM 615550 OMIM 615909 OMIM 617408 OMIM 617409 SNOMED CT 191240007 SNOMED CT 71988008 SNOMED CT 88854002 2018-08 2020-08-18 Diastrophic dysplasia https://medlineplus.gov/genetics/condition/diastrophic-dysplasia descriptionDiastrophic dysplasia is a disorder of cartilage and bone development. Affected individuals have short stature with very short arms and legs. Most also have early-onset joint pain (osteoarthritis) and joint deformities called contractures, which restrict movement. These joint problems often make it difficult to walk and tend to worsen with age. Additional features of diastrophic dysplasia include an inward- and upward-turning foot (clubfoot), progressive abnormal curvature of the spine, and unusually positioned thumbs (hitchhiker thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth (a cleft palate). Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears.The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis type 2; however, diastrophic dysplasia tends to be less severe. Although some affected infants have breathing problems, most people with diastrophic dysplasia live into adulthood. ar Autosomal recessive SLC26A2 https://medlineplus.gov/genetics/gene/slc26a2 Diastrophic dwarfism DTD GTR C0220726 ICD-10-CM Q77.5 MeSH D010009 OMIM 222600 SNOMED CT 58561002 2020-05 2020-08-18 Dihydrolipoamide dehydrogenase deficiency https://medlineplus.gov/genetics/condition/dihydrolipoamide-dehydrogenase-deficiency descriptionDihydrolipoamide dehydrogenase deficiency is a severe condition that can affect several body systems. Signs and symptoms of this condition usually appear shortly after birth, and they can vary widely among affected individuals.A common feature of dihydrolipoamide dehydrogenase deficiency is a potentially life-threatening buildup of lactic acid in tissues (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. Neurological problems are also common in this condition; the first symptoms in affected infants are often decreased muscle tone (hypotonia) and extreme tiredness (lethargy). As the problems worsen, affected infants can have difficulty feeding, decreased alertness, and seizures. Liver problems can also occur in dihydrolipoamide dehydrogenase deficiency, ranging from an enlarged liver (hepatomegaly) to life-threatening liver failure. In some affected people, liver disease, which can begin anytime from infancy to adulthood, is the primary symptom. The liver problems are usually associated with recurrent vomiting and abdominal pain. Rarely, people with dihydrolipoamide dehydrogenase deficiency experience weakness of the muscles used for movement (skeletal muscles), particularly during exercise; droopy eyelids; or a weakened heart muscle (cardiomyopathy). Other features of this condition include excess ammonia in the blood (hyperammonemia), a buildup of molecules called ketones in the body (ketoacidosis), or low blood glucose levels (hypoglycemia).Typically, the signs and symptoms of dihydrolipoamide dehydrogenase deficiency occur in episodes that may be triggered by fever, injury, or other stresses on the body. Affected individuals are usually symptom-free between episodes. Many infants with this condition do not survive the first few years of life because of the severity of these episodes. Affected individuals who survive past early childhood often have delayed growth and neurological problems, including intellectual disability, muscle stiffness (spasticity), difficulty coordinating movements (ataxia), and seizures. ar Autosomal recessive DLD https://medlineplus.gov/genetics/gene/dld Dihydrolipoyl dehydrogenase deficiency DLD deficiency E3 deficiency Lactic acidosis due to LAD deficiency Lactic acidosis due to lipoamide dehydrogenase deficiency Lipoamide dehydrogenase deficiency Maple syrup urine disease, type III GTR C5574660 MeSH D028361 OMIM 246900 SNOMED CT 29914000 2014-09 2023-07-26 Dihydropyrimidinase deficiency https://medlineplus.gov/genetics/condition/dihydropyrimidinase-deficiency descriptionDihydropyrimidinase deficiency is a disorder that can cause neurological and gastrointestinal problems in some affected individuals. Other people with dihydropyrimidinase deficiency have no signs or symptoms related to the disorder, and in these individuals the condition can be diagnosed only by laboratory testing.The neurological abnormalities that occur most often in people with dihydropyrimidinase deficiency are intellectual disability, seizures, and weak muscle tone (hypotonia). An abnormally small head size (microcephaly) and autistic behaviors that affect communication and social interaction also occur in some individuals with this condition.Gastrointestinal problems that occur in dihydropyrimidinase deficiency include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and recurrent episodes of vomiting (cyclic vomiting). Affected individuals can also have deterioration (atrophy) of the small, finger-like projections (villi) that line the small intestine and provide a large surface area with which to absorb nutrients. This condition, called villous atrophy, can lead to difficulty absorbing nutrients from foods (malabsorption), resulting in a failure to grow and gain weight at the expected rate (failure to thrive).People with dihydropyrimidinase deficiency, including those who otherwise exhibit no symptoms, may be vulnerable to severe, potentially life-threatening toxic reactions to certain drugs called fluoropyrimidines that are used to treat cancer. Common examples of these drugs are 5-fluorouracil and capecitabine. These drugs may not be broken down efficiently and can build up to toxic levels in the body (fluoropyrimidine toxicity), leading to drug reactions including gastrointestinal problems, blood abnormalities, and other signs and symptoms. ar Autosomal recessive DPYS https://medlineplus.gov/genetics/gene/dpys Dihydropyrimidinuria Dihydrouracil amidohydrolase deficiency DPH deficiency DPYS deficiency GTR C0342803 MeSH D011686 OMIM 222748 SNOMED CT 238014002 2014-09 2020-08-18 Dihydropyrimidine dehydrogenase deficiency https://medlineplus.gov/genetics/condition/dihydropyrimidine-dehydrogenase-deficiency descriptionDihydropyrimidine dehydrogenase deficiency is a disorder characterized by a wide range of severity, with neurological problems in some individuals and no signs or symptoms in others.In people with severe dihydropyrimidine dehydrogenase deficiency, the disorder becomes apparent in infancy. These affected individuals have neurological problems such as recurrent seizures (epilepsy), intellectual disability, a small head size (microcephaly), increased muscle tone (hypertonia), delayed development of motor skills such as walking, and autistic behaviors that affect communication and social interaction. Other affected individuals are asymptomatic, which means they do not have any signs or symptoms of the condition. Individuals with asymptomatic dihydropyrimidine dehydrogenase deficiency may be identified only by laboratory testing.People with dihydropyrimidine dehydrogenase deficiency, including those who otherwise exhibit no symptoms, are vulnerable to severe, potentially life-threatening toxic reactions to certain drugs called fluoropyrimidines that are used to treat cancer. Common examples of these drugs are 5-fluorouracil and capecitabine. These drugs are not broken down efficiently by people with dihydropyrimidine dehydrogenase deficiency and build up to toxic levels in the body (fluoropyrimidine toxicity). Severe inflammation and ulceration of the lining of the gastrointestinal tract (mucositis) may occur, which can lead to signs and symptoms including mouth sores, abdominal pain, bleeding, nausea, vomiting, and diarrhea. Fluoropyrimidine toxicity may also lead to low numbers of white blood cells (neutropenia), which increases the risk of infections. It can also be associated with low numbers of platelets in the blood (thrombocytopenia), which impairs blood clotting and may lead to abnormal bleeding (hemorrhage). Redness, swelling, numbness, and peeling of the skin on the palms and soles (hand-foot syndrome); shortness of breath; and hair loss may also occur. ar Autosomal recessive ad Autosomal dominant DPYD https://medlineplus.gov/genetics/gene/dpyd Dihydropyrimidinuria DPD deficiency Familial pyrimidemia Hereditary thymine-uraciluria MeSH D054067 OMIM 274270 SNOMED CT 77365006 2011-11 2020-08-18 Dilated cardiomyopathy with ataxia syndrome https://medlineplus.gov/genetics/condition/dilated-cardiomyopathy-with-ataxia-syndrome descriptionDilated cardiomyopathy with ataxia (DCMA) syndrome is an inherited condition characterized by heart problems, movement difficulties, and other features affecting multiple body systems.Beginning in infancy to early childhood, most people with DCMA syndrome develop dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Some affected individuals also have long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats. The irregular heartbeats (arrhythmia) can lead to fainting (syncope) or cardiac arrest and sudden death. Rarely, heart problems improve over time; however, in most cases of DCMA syndrome, affected individuals do not survive past childhood due to heart failure. A small percentage of people with DCMA syndrome have no heart problems at all.By age 2, children with DCMA syndrome have problems with coordination and balance (ataxia). These movement problems can result in delay of motor skills such as standing and walking, but most older children with DCMA syndrome can walk without support.In addition to heart problems and movement difficulties, most individuals with DCMA syndrome grow slowly before and after birth, which leads to short stature. Additionally, many affected individuals have mild intellectual disability. Many males with DCMA syndrome have genital abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). Other common features of DCMA syndrome include unusually small red blood cells (microcytic anemia), which can cause pale skin; an abnormal buildup of fats in the liver (hepatic steatosis), which can damage the liver; and the degeneration of nerve cells that carry visual information from the eyes to the brain (optic nerve atrophy), which can lead to vision loss.DCMA syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine. The amount of acid does not appear to influence the signs and symptoms of the condition. DCMA syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with DCMA syndrome also have high urine levels of another acid called 3-methylglutaric acid. ar Autosomal recessive DNAJC19 https://medlineplus.gov/genetics/gene/dnajc19 3-methylglutaconic aciduria type V DCMA DCMA syndrome DNAJC19 defect MGA type V MGA5 MGCA5 GTR C1857776 ICD-10-CM E71.111 MeSH D008661 OMIM 610198 SNOMED CT 711412004 2014-07 2020-08-18 Distal 18q deletion syndrome https://medlineplus.gov/genetics/condition/distal-18q-deletion-syndrome descriptionDistal 18q deletion syndrome is a chromosomal condition that occurs when a piece of the long (q) arm of chromosome 18 is missing. The term "distal" means that the missing piece occurs near one end of the chromosome. Distal 18q deletion syndrome can lead to a wide variety of signs and symptoms among affected individuals.Some common features of distal 18q deletion syndrome include short stature (often due to growth hormone deficiency), weak muscle tone (hypotonia), hearing loss due to ear canals that are narrow (aural stenosis) or absent (aural atresia), and foot abnormalities such as an inward or upward-turning foot (clubfoot) or feet with soles that are rounded outward (rocker-bottom feet). Eye movement disorders and other vision problems, an opening in the roof of the mouth (cleft palate), an underactive thyroid gland (hypothyroidism), heart abnormalities that are present from birth (congenital heart defects), kidney problems, genital abnormalities, and skin problems may also occur in this disorder. Some affected individuals have mild facial differences such as deep-set eyes, a flat or sunken appearance of the middle of the face (midface hypoplasia), a wide mouth, and prominent ears. These features are often not noticeable except in a detailed medical evaluation.Distal 18q deletion syndrome can also affect the nervous system. A common neurological feature of this disorder is impaired myelin production (dysmyelination). Myelin is a fatty substance that insulates nerve cells and promotes the rapid transmission of nerve impulses. The formation of a protective myelin sheath around nerve cells (myelination) normally begins before birth and continues into adulthood. In people with distal 18q deletion syndrome, myelination is often delayed and proceeds more slowly than normal; affected individuals may never have normal adult myelin levels. Most people with distal 18q deletion syndrome have neurological problems, although it is unclear to what extent these problems are related to the dysmyelination. These problems include delayed development, learning disabilities, and intellectual disability that can range from mild to severe. Seizures; hyperactivity; mood disorders such as anxiety, irritability, and depression; and features of autism spectrum disorder that affect communication and social interaction may also occur. Some affected individuals have an unusually small head size (microcephaly). n Not inherited ad Autosomal dominant TCF4 https://medlineplus.gov/genetics/gene/tcf4 TSHZ1 https://www.ncbi.nlm.nih.gov/gene/10194 18 https://medlineplus.gov/genetics/chromosome/18 18q deletion syndrome 18q- syndrome Chromosome 18 long arm deletion syndrome Chromosome 18q deletion syndrome Chromosome 18q monosomy Chromosome 18q- syndrome Del(18q) syndrome Monosomy 18q GTR C0432443 MeSH D025063 OMIM 601808 2017-02 2024-10-02 Distal arthrogryposis type 1 https://medlineplus.gov/genetics/condition/distal-arthrogryposis-type-1 descriptionDistal arthrogryposis type 1 is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The term "arthrogryposis" comes from the Greek words for joint (arthro-) and crooked or hooked (gryposis). The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). Clubfoot, which is an inward- and upward-turning foot, is also commonly seen with distal arthrogryposis type 1. The specific hand and foot abnormalities vary among affected individuals. However, this condition typically does not cause any signs and symptoms affecting other parts of the body. ad Autosomal dominant MYBPC1 https://medlineplus.gov/genetics/gene/mybpc1 TPM2 https://medlineplus.gov/genetics/gene/tpm2 AMCD1 Arthrogryposis, distal, type 1 DA1 GTR C0220662 MeSH D001176 OMIM 108120 SNOMED CT 715314008 2011-01 2020-08-18 Distal hereditary motor neuropathy, type II https://medlineplus.gov/genetics/condition/distal-hereditary-motor-neuropathy-type-ii descriptionDistal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells (neurons) in the brain and spinal cord. This condition specifically affects motor neurons, which are specialized cells that control muscle movement. Damage to motor neurons results in muscle weakness that worsens over time. Distal hereditary motor neuropathy, type II weakness primarily affects movement in the legs.The signs and symptoms of distal hereditary motor neuropathy, type II often begin in adolescence to mid-adulthood. The initial symptoms of the disorder are cramps or weakness in the muscles of the big toe and, later, the entire foot. During the next 5 to 10 years, affected individuals experience a gradual loss of muscle tissue (atrophy) in the lower legs, which can lead to problems with walking (gait disturbance) and high arches (pes cavus). Over time, the lower legs may become paralyzed. The thigh muscles may also undergo muscle atrophy, although this generally occurs later and is less severe than the muscle atrophy in the lower legs.Some individuals with distal hereditary motor neuropathy, type II can also experience weaken the muscles in the hands and forearms. This weakening is less severe than the weakening in the lower limbs and does not usually lead to paralysis. In rare cases, affected individuals experience hearing loss.People with distal hereditary motor neuropathy, type II can have exaggerated reflexes (hyperreflexia) or other minor disturbances in the nerves used to detect sensations (sensory neuropathy). Sensory neuropathy is uncommon in people with distal hereditary motor neuropathy, type II and is typically a feature of a disorder calledCharcot-Marie-Tooth disease. These two disorders have overlapping features and can also share a genetic ad Autosomal dominant HSPB1 https://medlineplus.gov/genetics/gene/hspb1 HSPB8 https://medlineplus.gov/genetics/gene/hspb8 HSPB3 https://www.ncbi.nlm.nih.gov/gene/8988 FBXO38 https://www.ncbi.nlm.nih.gov/gene/81545 Distal hereditary motor neuronopathy, type II HMN II HMN2 HMND2 GTR C1834692 GTR C2608087 GTR C3150619 GTR C3888271 MeSH D009134 OMIM 158590 OMIM 608634 OMIM 613376 OMIM 615575 SNOMED CT 230247001 2025-03 2025-03-04 Distal hereditary motor neuropathy, type V https://medlineplus.gov/genetics/condition/distal-hereditary-motor-neuropathy-type-v descriptionDistal hereditary motor neuropathy, type V is a disorder that affects nerve cells (neurons) in the spinal cord. This condition specifically affects motor neurons, which are specialized cells that control muscle movement. Damage to motor neurons results in muscle weakness that worsens over time. In people with distal hereditary motor neuropathy, type V, this weakness primarily affects movement in the muscles that are furthest from the center of the body (distal muscles), such as the muscles in the hands and feet.Signs and symptoms of distal hereditary motor neuropathy, type V usually begin during adolescence, but they can appear any time between infancy and the mid-30s. The first symptom of this condition is often cramps in the hands that are brought on by exposure to cold temperatures.The characteristic features of distal hereditary motor neuropathy, type V are weakness and wasting (atrophy) of muscles of the hand, specifically on the side of the index finger near the thumb and in the palm of the hand at the base of the thumb.About half of individuals with distal hereditary motor neuropathy, type V develop muscle weakness in the feet and lower legs. This can lead to problems with walking (gait disturbance), difficulty lifting the front part of the foot (foot drop), and a high foot arch (pes cavus).People with distal hereditary motor neuropathy, type V can have exaggerated reflexes (hyperreflexia) or other disturbances in the nerves that are used to detect sensations (sensory neuropathy). Although sensory neuropathy is uncommon in people with distal hereditary motor neuropathy, type V, it is typical of a disorder called Charcot-Marie-Tooth disease. These two disorders have overlapping features and can also share a genetic cause. People with distal hereditary motor neuropathy, type V typically have a normal life expectancy. ad Autosomal dominant GARS1 https://medlineplus.gov/genetics/gene/gars1 BSCL2 https://medlineplus.gov/genetics/gene/bscl2 REEP1 https://medlineplus.gov/genetics/gene/reep1 DHMN5 DHMNV Distal hereditary motor neuronopathy type 5 Distal hereditary motor neuronopathy, type V Distal spinal muscular atrophy, type V DSMAV HMN V Spinal muscular atrophy, distal type V Spinal muscular atrophy, distal, with upper limb predominance GTR C1833308 GTR C3553656 GTR C5436838 GTR CN031873 MeSH D009134 OMIM 600794 OMIM 614751 OMIM 619112 SNOMED CT 230247001 2025-03 2025-03-10 Distal myopathy 2 https://medlineplus.gov/genetics/condition/distal-myopathy-2 descriptionDistal myopathy 2 is a condition characterized by weakness of specific muscles that begins in adulthood. It is a form of muscular dystrophy that specifically involves muscles in the throat, lower legs, and forearms. Muscles farther from the center of the body, like the muscles of the lower legs and forearms, are known as distal muscles.Muscle weakness in the ankles is usually the first symptom of distal myopathy 2. The weakness can also affect muscles in the hands, wrists, and shoulders. At first, the muscle weakness may be on only one side of the body, but both sides are eventually involved. This muscle weakness can slowly worsen and make actions like walking and lifting the fingers difficult.Another characteristic feature of distal myopathy 2 is weakness of the vocal cords and throat. This weakness initially causes the voice to sound weak or breathy (hypophonic). Eventually, the voice becomes gurgling, hoarse, and nasal. The weakness can also cause difficulty swallowing (dysphagia). ad Autosomal dominant MATR3 https://medlineplus.gov/genetics/gene/matr3 Distal myopathy with vocal cord and pharyngeal signs Distal myopathy with vocal cord weakness Matrin 3 distal myopathy MPD2 Myopathia distalis type 2 VCPDM Vocal cord and pharyngeal weakness with distal myopathy GTR C3807521 MeSH D049310 OMIM 606070 SNOMED CT 702383005 2011-11 2020-08-18 Donnai-Barrow syndrome https://medlineplus.gov/genetics/condition/donnai-barrow-syndrome descriptionDonnai-Barrow syndrome is an inherited disorder that affects many parts of the body. This disorder is characterized by unusual facial features, including prominent, wide-set eyes with outer corners that point downward; a short bulbous nose with a flat nasal bridge; ears that are rotated backward; and a widow's peak hairline.Individuals with Donnai-Barrow syndrome have severe hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). In addition, they often experience vision problems, including extreme nearsightedness (high myopia), detachment or deterioration of the light-sensitive tissue in the back of the eye (the retina), and progressive vision loss. Some have a gap or split in the colored part of the eye (iris coloboma).In almost all people with Donnai-Barrow syndrome, the tissue connecting the left and right halves of the brain (corpus callosum) is underdeveloped or absent. Affected individuals may also have other structural abnormalities of the brain. They generally have mild to moderate intellectual disability and developmental delay.People with Donnai-Barrow syndrome may also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a congenital diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the developing heart and lungs. An opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel may also occur in affected individuals. Occasionally people with Donnai-Barrow syndrome have abnormalities of the intestine, heart, or other organs. ar Autosomal recessive LRP2 https://medlineplus.gov/genetics/gene/lrp2 DBS DBS/FOAR syndrome Diaphragmatic hernia-exomphalos-corpus callosum agenesis Diaphragmatic hernia-exomphalos-hypertelorism syndrome Faciooculoacousticorenal syndrome FOAR syndrome GTR C1857277 MeSH D015499 OMIM 222448 SNOMED CT 702418009 2009-05 2020-08-18 Donohue syndrome https://medlineplus.gov/genetics/condition/donohue-syndrome descriptionDonohue syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. Severe insulin resistance leads to problems with regulating blood glucose levels and affects the development and function of organs and tissues throughout the body.Severe insulin resistance underlies the varied signs and symptoms of Donohue syndrome. Individuals with Donohue syndrome are unusually small starting before birth, and affected infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features that become apparent soon after birth include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; excessive body hair growth (hirsutism); multiple cysts on the ovaries in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Donohue syndrome include bulging eyes, thick lips, upturned nostrils, and low-set ears. Affected individuals develop recurrent, life-threatening infections beginning in infancy.Donohue syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Rabson-Mendenhall syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Donohue syndrome represents the most severe end of the spectrum; most children with this condition do not survive beyond age 2. ar Autosomal recessive INSR https://medlineplus.gov/genetics/gene/insr Donohue's syndrome Leprechaunism Leprechaunism syndrome GTR C0265344 MeSH D056731 OMIM 246200 SNOMED CT 111307005 2014-12 2023-07-19 Dopa-responsive dystonia https://medlineplus.gov/genetics/condition/dopa-responsive-dystonia descriptionDopa-responsive dystonia is a disorder that involves involuntary muscle contractions, tremors, and other uncontrolled movements (dystonia). The features of this condition range from mild to severe. This form of dystonia is called dopa-responsive dystonia because the signs and symptoms typically improve with sustained use of a medication known as L-Dopa.Signs and symptoms of dopa-responsive dystonia usually appear during childhood, most commonly around age 6. The first signs of the condition are typically the development of inward- and upward-turning feet (clubfeet) and dystonia in the lower limbs. The dystonia spreads to the upper limbs over time; beginning in adolescence, the whole body is typically involved. Affected individuals may have unusual limb positioning and a lack of coordination when walking or running. Some people with this condition have sleep problems or episodes of depression more frequently than would normally be expected.Over time, affected individuals often develop a group of movement abnormalities called parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability).The movement difficulties associated with dopa-responsive dystonia usually worsen with age but stabilize around age 30. A characteristic feature of dopa-responsive dystonia is worsening of movement problems later in the day and an improvement of symptoms in the morning, after sleep (diurnal fluctuation).Rarely, the movement problems associated with dopa-responsive dystonia do not appear until adulthood. In these adult-onset cases, parkinsonism usually develops before dystonia, and movement problems are slow to worsen and do not show diurnal fluctuations. ar Autosomal recessive ad Autosomal dominant GCH1 https://medlineplus.gov/genetics/gene/gch1 TH https://medlineplus.gov/genetics/gene/th SPR https://medlineplus.gov/genetics/gene/spr DRD Dystonia 5, dopa-responsive type Hereditary progressive dystonia with marked diurnal fluctuation GTR C0268468 GTR C1851920 GTR C2673535 MeSH D004421 OMIM 128230 OMIM 605407 OMIM 612716 SNOMED CT 230332007 SNOMED CT 45116002 SNOMED CT 715768000 SNOMED CT 715827001 2012-05 2023-11-07 Dopamine beta-hydroxylase deficiency https://medlineplus.gov/genetics/condition/dopamine-beta-hydroxylase-deficiency descriptionDopamine beta-hydroxylase deficiency is a condition that affects the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. The signs and symptoms of dopamine beta-hydroxylase deficiency are caused by a lack of norepinephrine, one of the main chemical messengers (neurotransmitters) of the autonomic nervous system.Although the signs and symptoms of dopamine beta-hydroxylase deficiency can appear during infancy, people often do not receive a diagnosis until their symptoms worsen during adolescence. Early signs and symptoms may include droopy eyelids (ptosis) and low blood pressure (hypotension). Infants with dopamine beta-hydroxylase deficiency may also experience vomiting, dehydration, decreased body temperature, and low blood glucose (hypoglycemia), which may lead to frequent hospitalizations.By adolescence or early adulthood, people with dopamine beta-hydroxylase deficiency often have a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. Affected individuals typically experience extreme fatigue during exercise (exercise intolerance) due to their problems maintaining a normal blood pressure.Other features of dopamine beta-hydroxylase deficiency include nasal congestion, an inability to stand for a prolonged period of time, and retrograde ejaculation, which is a discharge of semen backwards into the bladder.Symptoms of dopamine beta-hydroxylase deficiency may improve with treatment. If the condition is not treated, symptoms often worsen during adolescence. ar Autosomal recessive DBH https://medlineplus.gov/genetics/gene/dbh DBH deficiency Dopamine β-hydroxylase deficiency GTR C4746777 MeSH D001342 OMIM 223360 SNOMED CT 237923004 2024-07 2024-07-31 Dopamine transporter deficiency syndrome https://medlineplus.gov/genetics/condition/dopamine-transporter-deficiency-syndrome descriptionDopamine transporter deficiency syndrome is a rare movement disorder. The condition is also known as infantile parkinsonism-dystonia because the problems with movement (dystonia and parkinsonism, described below) usually start in infancy and worsen over time. However, the features of the condition sometimes do not appear until childhood or later.People with dopamine transporter deficiency syndrome develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia is widespread (generalized), affecting many different muscles. The continuous muscle cramping and spasms cause difficulty with basic activities, including speaking, eating, drinking, picking up objects, and walking.As the condition worsens, affected individuals develop parkinsonism, which is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, and an inability to hold the body upright and balanced (postural instability). Other signs and symptoms that can develop include abnormal eye movements; reduced facial expression (hypomimia); disturbed sleep; frequent episodes of pneumonia; and problems with the digestive system, including a backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and constipation.People with dopamine transporter deficiency syndrome may have a shortened lifespan, although the long-term effects of this condition are not fully understood. Children with this condition have died from pneumonia and breathing problems. When the first signs and symptoms appear later in life, affected individuals may survive into adulthood. ar Autosomal recessive SLC6A3 https://medlineplus.gov/genetics/gene/slc6a3 DTDS Infantile parkinsonism-dystonia Parkinsonism-dystonia, infantile PKDYS GTR C5700336 MeSH D010300 MeSH D020821 OMIM 613135 SNOMED CT 722763000 2015-10 2023-08-22 Dowling-Degos disease https://medlineplus.gov/genetics/condition/dowling-degos-disease descriptionDowling-Degos disease is a skin condition characterized by a lacy or net-like (reticulate) pattern of abnormally dark skin coloring (hyperpigmentation), particularly in the body's folds and creases. These skin changes typically first appear in the armpits and groin area and can later spread to other skin folds such as the crook of the elbow, back of the knee, and under the breasts. Less commonly, pigmentation changes can also occur on the neck, wrists, back of the hands, face, scalp, scrotum, and vulva. These areas of hyperpigmentation typically cause no health problems.Individuals with Dowling-Degos disease may also have dark spots (lesions) on the face and back that resemble blackheads, red bumps around the mouth that resemble acne, or pitted scars on the face similar to acne scars but with no history of acne. Fluid-filled sacs within the hair follicle (pilar cysts) may develop, most commonly on the scalp. Rarely, affected individuals have patches of skin that are unusually light in color (hypopigmented).In rare cases, individuals with Dowling-Degos disease experience itching (pruritus) or burning sensations on the skin. These feelings can be triggered by UV light, sweating, or friction on the skin.The pigmentation changes characteristic of Dowling-Degos disease typically begin in late childhood or in adolescence, although in some individuals, features of the condition do not appear until adulthood. New areas of hyperpigmentation tend to develop over time, and the other skin lesions tend to increase in number as well. While the skin changes associated with Dowling-Degos disease may cause distress or anxiety, they typically cause no other health problems.A condition called Galli-Galli disease has signs and symptoms similar to those of Dowling-Degos disease. In addition to pigmentation changes, individuals with Galli-Galli disease also have a breakdown of cells in the outer layer of skin (acantholysis). Acantholysis can cause skin irritation and itchiness and lead to reddened or missing patches of skin (erosions). These conditions used to be considered two separate disorders, but Galli-Galli disease and Dowling-Degos disease are now regarded as the same condition. ad Autosomal dominant KRT5 https://medlineplus.gov/genetics/gene/krt5 PSENEN https://medlineplus.gov/genetics/gene/psenen POGLUT1 https://medlineplus.gov/genetics/gene/poglut1 POFUT1 https://medlineplus.gov/genetics/gene/pofut1 Dark dot disease DDD Dowling-Degos-Kitamura disease Reticular pigment anomaly of flexures Reticular pigmented anomaly of flexures GTR C3809147 GTR C3810313 GTR C4552092 MeSH D012873 OMIM 179850 OMIM 615327 OMIM 615674 OMIM 615696 SNOMED CT 239054009 2017-08 2020-08-18 Down syndrome https://medlineplus.gov/genetics/condition/down-syndrome descriptionDown syndrome is a chromosomal condition that is associated with intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy. All affected individuals experience cognitive delays, but the intellectual disability is usually mild to moderate.People with Down syndrome often have a characteristic facial appearance that includes a flattened appearance to the face, outside corners of the eyes that point upward (upslanting palpebral fissures), small ears, a short neck, and a tongue that tends to stick out of the mouth. Affected individuals may have a variety of birth defects. Many people with Down syndrome have small hands and feet and a single crease across the palms of the hands. About half of all affected children are born with a heart defect. Digestive abnormalities, such as a blockage of the intestine, are less common.Individuals with Down syndrome have an increased risk of developing several medical conditions. These include gastroesophageal reflux, which is a backflow of acidic stomach contents into the esophagus, and celiac disease, which is an intolerance of a wheat protein called gluten. About 15 percent of people with Down syndrome have an underactive thyroid gland (hypothyroidism). The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones. Individuals with Down syndrome also have an increased risk of hearing and vision problems. Additionally, a small percentage of children with Down syndrome develop cancer of blood-forming cells (leukemia).Delayed development and behavioral problems are often reported in children with Down syndrome. Affected individuals can have growth problems and their speech and language develop later and more slowly than in children without Down syndrome. Additionally, speech may be difficult to understand in individuals with Down syndrome. Behavioral issues can include attention problems, obsessive/compulsive behavior, and stubbornness or tantrums. A small percentage of people with Down syndrome are also diagnosed with developmental conditions called autism spectrum disorders, which affect communication and social interaction.People with Down syndrome often experience a gradual decline in thinking ability (cognition) as they age, usually starting around age 50. Down syndrome is also associated with an increased risk of developing Alzheimer's disease, a brain disorder that results in a gradual loss of memory, judgment, and ability to function. Approximately half of adults with Down syndrome develop Alzheimer's disease. Although Alzheimer's disease is usually a disorder that occurs in older adults, people with Down syndrome commonly develop this condition earlier, in their fifties or sixties. n Not inherited 21 https://medlineplus.gov/genetics/chromosome/21 47,XX,+21 47,XY,+21 Down's syndrome Trisomy 21 Trisomy G GTR C0013080 ICD-10-CM Q90 ICD-10-CM Q90.0 ICD-10-CM Q90.1 ICD-10-CM Q90.2 ICD-10-CM Q90.9 MeSH D004314 OMIM 190685 SNOMED CT 205615000 SNOMED CT 205616004 SNOMED CT 254264002 SNOMED CT 371045000 SNOMED CT 41040004 2012-06 2024-10-02 Duane-radial ray syndrome https://medlineplus.gov/genetics/condition/duane-radial-ray-syndrome descriptionDuane-radial ray syndrome is a disorder that affects the eyes and causes abnormalities of bones in the arms and hands. This condition is characterized by a particular problem with eye movement called Duane anomaly (also known as Duane syndrome). This abnormality results from the improper development of certain nerves that control eye movement. Duane anomaly limits outward eye movement (toward the ear), and in some cases may limit inward eye movement (toward the nose). Also, as the eye moves inward, the eye opening becomes narrower and the eyeball may pull back (retract) into its socket.Bone abnormalities in the hands include malformed or absent thumbs, an extra thumb, or a long thumb that looks like a finger. Partial or complete absence of bones in the forearm is also common. Together, these hand and arm abnormalities are known as radial ray malformations.People with the combination of Duane anomaly and radial ray malformations may have a variety of other signs and symptoms. These features include unusually shaped ears, hearing loss, heart and kidney defects, a distinctive facial appearance, an inward- and upward-turning foot (clubfoot), and fused spinal bones (vertebrae).The varied signs and symptoms of Duane-radial ray syndrome often overlap with features of other disorders. For example, acro-renal-ocular syndrome is characterized by Duane anomaly and other eye abnormalities, radial ray malformations, and kidney defects. Both conditions are caused by mutations in the same gene. Based on these similarities, researchers suspect that Duane-radial ray syndrome and acro-renal-ocular syndrome are part of an overlapping set of syndromes with many possible signs and symptoms. The features of Duane-radial ray syndrome are also similar to those of a condition called Holt-Oram syndrome; however, these two disorders are caused by mutations in different genes. ad Autosomal dominant SALL4 https://medlineplus.gov/genetics/gene/sall4 DRRS Okihiro syndrome GTR C1623209 ICD-10-CM H50.81 ICD-10-CM H50.811 ICD-10-CM H50.812 MeSH D004370 OMIM 607323 SNOMED CT 699867001 2009-12 2020-08-18 Dubin-Johnson syndrome https://medlineplus.gov/genetics/condition/dubin-johnson-syndrome descriptionDubin-Johnson syndrome is a condition characterized by jaundice, which is a yellowing of the skin and whites of the eyes. In most affected people jaundice appears during adolescence or early adulthood. Jaundice is typically the only feature of Dubin-Johnson syndrome, but some people can experience weakness, mild abdominal pain, nausea, or vomiting. In most people with Dubin-Johnson syndrome, certain deposits build up in the liver but do not seem to impair liver function. The deposits make the liver appear black when viewed with medical imaging.Rarely, jaundice develops soon after birth in individuals with Dubin-Johnson syndrome. Affected infants typically also have enlarged livers (hepatomegaly) and a severely reduced ability to produce and release a digestive fluid called bile (cholestasis). As these children get older, their liver problems go away and they usually do not have any related health problems later in life. ar Autosomal recessive ABCC2 https://medlineplus.gov/genetics/gene/abcc2 Black liver-jaundice syndrome Chronic idiopathic jaundice Chronic idiopathic jaundice with pigmented liver DJS Dubin-Sprinz syndrome Hyperbilirubinemia II Hyperbilirubinemia, Dubin-Johnson type Jaundice, chronic idiopathic GTR C0022350 ICD-10-CM E80.6 MeSH D007566 OMIM 237500 SNOMED CT 44553005 2009-03 2023-11-07 Duchenne and Becker muscular dystrophy https://medlineplus.gov/genetics/condition/duchenne-and-becker-muscular-dystrophy descriptionMuscular dystrophies are a group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy). The Duchenne and Becker types of muscular dystrophy are two related conditions that primarily affect skeletal muscles, which are used for movement, and heart (cardiac) muscle. These forms of muscular dystrophy occur almost exclusively in males.Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused by different mutations in the same gene. The two conditions differ in their severity, age of onset, and rate of progression. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by adolescence. The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate.Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called cardiomyopathy. This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. These heart problems worsen rapidly and become life-threatening in most cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond.A related condition called X-linked dilated cardiomyopathy is a form of heart disease caused by mutations in the same gene as Duchenne and Becker muscular dystrophy, and it is sometimes classified as subclinical Becker muscular dystrophy. People with X-linked dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing. xr X-linked recessive DMD https://medlineplus.gov/genetics/gene/dmd DBMD Duchenne/Becker muscular dystrophy Muscular dystrophy, Duchenne and Becker types Muscular dystrophy, pseudohypertrophic GTR C0013264 GTR C0917713 MeSH D020388 OMIM 300376 OMIM 310200 SNOMED CT 387732009 SNOMED CT 76670001 2012-02 2023-03-21 Dupuytren contracture https://medlineplus.gov/genetics/condition/dupuytren-contracture descriptionDupuytren contracture is characterized by a deformity of the hand in which the joints of one or more fingers cannot be fully straightened (extended); their mobility is limited to a range of bent (flexed) positions. The condition is a disorder of connective tissue, which supports the body's muscles, joints, organs, and skin and provides strength and flexibility to structures throughout the body. In particular, Dupuytren contracture results from shortening and thickening of connective tissues in the hand, including fat and bands of fibrous tissue called fascia; the skin is also involved.In men, Dupuytren contracture most often occurs after age 50. In women, it tends to appear later and be less severe. However, Dupuytren contracture can occur at any time of life, including childhood. The disorder can make it more difficult or impossible for affected individuals to perform manual tasks such as preparing food, writing, or playing musical instruments.Dupuytren contracture often first occurs in only one hand, affecting the right hand twice as often as the left. About 80 percent of affected individuals eventually develop features of the condition in both hands.Dupuytren contracture typically first appears as one or more small hard nodules that can be seen and felt under the skin of the palm. In some affected individuals the nodules remain the only sign of the disorder, and occasionally even go away without treatment, but in most cases the condition gradually gets worse. Over months or years, tight bands of tissue called cords develop. These cords gradually draw the affected fingers downward so that they curl toward the palm. As the condition worsens, it becomes difficult or impossible to extend the affected fingers. The fourth (ring) finger is most often involved, followed by the fifth (little), third (middle), and second (index) fingers. Occasionally the thumb is involved. The condition is also known as Dupuytren disease, and "Dupuytren contracture" most accurately refers to later stages when finger mobility is affected; however, the term is also commonly used as a general name for the condition.About one-quarter of people with Dupuytren contracture experience uncomfortable inflammation or sensations of tenderness, burning, or itching in the affected hand. They may also feel pressure or tension, especially when attempting to straighten affected joints.People with Dupuytren contracture are at increased risk of developing other disorders in which similar connective tissue abnormalities affect other parts of the body. These include Garrod pads, which are nodules that develop on the knuckles; Ledderhose disease, also called plantar fibromatosis, which affects the feet; scar tissue in the shoulder that causes pain and stiffness (adhesive capsulitis or frozen shoulder); and, in males, Peyronie disease, which causes abnormal curvature of the penis. u Pattern unknown n Not inherited WNT4 https://medlineplus.gov/genetics/gene/wnt4 SFRP4 https://medlineplus.gov/genetics/gene/sfrp4 WNT2 https://www.ncbi.nlm.nih.gov/gene/7472 WNT7B https://www.ncbi.nlm.nih.gov/gene/7477 SULF1 https://www.ncbi.nlm.nih.gov/gene/23213 EPDR1 https://www.ncbi.nlm.nih.gov/gene/54749 C8orf34 https://www.ncbi.nlm.nih.gov/gene/116328 RSPO2 https://www.ncbi.nlm.nih.gov/gene/340419 Contraction of palmar fascia Dupuytren disease Dupuytren's contracture Familial palmar fibromatosis Palmar fascial fibromatosis Palmar fibromas ICD-10-CM M72.0 MeSH D004387 OMIM 126900 SNOMED CT 274142002 2016-09 2024-09-17 Dysequilibrium syndrome https://medlineplus.gov/genetics/condition/dysequilibrium-syndrome descriptionDysequilibrium syndrome (DES) is a group of disorders that are characterized by abnormal brain development, which causes intellectual disabilities and problems with balance and coordination (ataxia). The specific signs and symptoms and the severity of the condition can vary among affected individuals.In people with DES, the part of the brain that coordinates movement (cerebellum) may be unusually small and underdeveloped (cerebellar hypoplasia). This can lead to ataxia that is present from birth and typically does not worsen over time. Additional brain abnormalities may include further loss of tissue (atrophy) in the cerebellum; fewer folds and grooves (gyri) on the surface of the brain; and a small brainstem, which is the area of the brain that connects the brain to the spinal cord.Children with DES may have low muscle tone (hypotonia) and delayed development of motor skills such as walking. Some affected individuals learn to walk later in childhood, while others are never able to walk independently. Additional features of DES may include intellectual disabilities that can vary from mild to profound; rapid, involuntary eye movements (nystagmus); and eyes that do not look in the same direction (strabismus). People with DES may also have difficulty speaking (dysarthria) or be unable to speak. Flat feet (pes planus), seizures, and short stature have been reported in some people with DES. ar Autosomal recessive VLDLR https://medlineplus.gov/genetics/gene/vldlr CA8 https://www.ncbi.nlm.nih.gov/gene/767 ATP8A2 https://www.ncbi.nlm.nih.gov/gene/51761 WDR81 https://www.ncbi.nlm.nih.gov/gene/124997 CAMRQ CAMRQ syndrome Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome Cerebellar ataxia-intellectual disability-dysequilibrium syndrome DES Non-progressive cerebellar ataxia-intellectual disability syndrome GTR C0394006 MeSH D002524 OMIM 224050 OMIM 610185 OMIM 613227 OMIM 615268 SNOMED CT 230782004 2026-03 2026-03-02 Dyserythropoietic anemia and thrombocytopenia https://medlineplus.gov/genetics/condition/dyserythropoietic-anemia-and-thrombocytopenia descriptionDyserythropoietic anemia and thrombocytopenia is a condition that affects blood cells and primarily occurs in males. A main feature of this condition is a type of anemia called dyserythropoietic anemia, which is characterized by a shortage of red blood cells. The term "dyserythropoietic" refers to the abnormal red blood cell formation that occurs in this condition. In affected individuals, immature red blood cells are unusually shaped and cannot develop into functional mature cells, leading to a shortage of healthy red blood cells. People with dyserythropoietic anemia and thrombocytopenia can have another blood disorder characterized by a reduced level of circulating platelets (thrombocytopenia). Platelets are cells that normally assist with blood clotting. Thrombocytopenia can cause easy bruising and abnormal bleeding. While people with dyserythropoietic anemia and thrombocytopenia can have signs and symptoms of both blood disorders, some are primarily affected by anemia, while others are more affected by thrombocytopenia.The most severe cases of dyserythropoietic anemia and thrombocytopenia are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. For many others, the signs and symptoms of dyserythropoietic anemia and thrombocytopenia begin in infancy. People with this condition experience prolonged bleeding or bruising after minor trauma or even in the absence of injury (spontaneous bleeding). Anemia can cause pale skin, weakness, and fatigue. Severe anemia may create a need for frequent blood transfusions to replenish the supply of red blood cells; however, repeated blood transfusions over many years can cause health problems such as excess iron in the blood. People with dyserythropoietic anemia and thrombocytopenia may also have a shortage of white blood cells (neutropenia), which can make them prone to recurrent infections. Additionally, they may have an enlarged spleen (splenomegaly). The severity of these abnormalities varies among affected individuals.Some people with dyserythropoietic anemia and thrombocytopenia have additional blood disorders such as beta thalassemia or congenital erythropoietic porphyria. Beta thalassemia is a condition that reduces the production of hemoglobin, which is the iron-containing protein in red blood cells that carries oxygen. A decrease in hemoglobin can lead to a shortage of oxygen in cells and tissues throughout the body. Congenital erythropoietic porphyria is another disorder that impairs hemoglobin production. People with congenital erythropoietic porphyria are also very sensitive to sunlight, and areas of skin exposed to the sun can become fragile and blistered. xr X-linked recessive GATA1 https://medlineplus.gov/genetics/gene/gata1 Dyserythropoietic anemia with thrombocytopenia GATA-1-related thrombocytopenia with dyserythropoiesis GATA1-related cytopenia GATA1-related X-linked cytopenia X-linked macrothrombocytopenia GTR C3550789 MeSH D013921 OMIM 300367 SNOMED CT 713388002 2010-07 2023-03-21 Dyskeratosis congenita https://medlineplus.gov/genetics/condition/dyskeratosis-congenita descriptionDyskeratosis congenita is a disorder that can affect many parts of the body. There are three features that are characteristic of this disorder: fingernails and toenails that grow poorly or are abnormally shaped (nail dystrophy); changes in skin coloring (pigmentation), especially on the neck and chest, in a pattern often described as "lacy"; and white patches inside the mouth (oral leukoplakia).People with dyskeratosis congenita have an increased risk of developing several life-threatening conditions. They are especially vulnerable to disorders that impair bone marrow function. These disorders disrupt the ability of the bone marrow to produce new blood cells. Affected individuals may develop aplastic anemia, also known as bone marrow failure, which occurs when the bone marrow does not produce enough new blood cells. They are also at higher than average risk for myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally; this condition may progress to a form of blood cancer called leukemia. People with dyskeratosis congenita are also at increased risk of developing leukemia even if they never develop myelodysplastic syndrome. In addition, they have a higher than average risk of developing other cancers, especially cancers of the head, neck, anus, or genitals.People with dyskeratosis congenita may also develop pulmonary fibrosis, a condition that causes scar tissue (fibrosis) to build up in the lungs, decreasing the transport of oxygen into the bloodstream. Additional signs and symptoms that occur in some people with dyskeratosis congenita include eye abnormalities such as narrow tear ducts that may become blocked, preventing drainage of tears and leading to eyelid irritation; dental problems; hair loss or prematurely grey hair; low bone mineral density (osteoporosis); degeneration (avascular necrosis) of the hip and shoulder joints; or liver disease. Some affected males may have narrowing (stenosis) of the urethra, which is the tube that carries urine out of the body from the bladder. Urethral stenosis may lead to difficult or painful urination and urinary tract infections.The severity of dyskeratosis congenita varies widely among affected individuals. The least severely affected individuals have only a few mild physical features of the disorder and normal bone marrow function. More severely affected individuals have many of the characteristic physical features and experience bone marrow failure, cancer, or pulmonary fibrosis by early adulthood.While most people with dyskeratosis congenita have normal intelligence and development of motor skills such as standing and walking, developmental delay may occur in some severely affected individuals. In one severe form of the disorder called Hoyeraal Hreidaarsson syndrome, affected individuals have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. Another severe variant called Revesz syndrome involves abnormalities in the light-sensitive tissue at the back of the eye (retina) in addition to the other symptoms of dyskeratosis congenita. ar Autosomal recessive xr X-linked recessive ad Autosomal dominant TERC https://medlineplus.gov/genetics/gene/terc TERT https://medlineplus.gov/genetics/gene/tert DKC1 https://medlineplus.gov/genetics/gene/dkc1 TINF2 https://medlineplus.gov/genetics/gene/tinf2 CTC1 https://medlineplus.gov/genetics/gene/ctc1 RTEL1 https://www.ncbi.nlm.nih.gov/gene/51750 WRAP53 https://www.ncbi.nlm.nih.gov/gene/55135 NOP10 https://www.ncbi.nlm.nih.gov/gene/55505 NHP2 https://www.ncbi.nlm.nih.gov/gene/55651 Zinsser-Cole-Engman syndrome GTR C0265965 MeSH D019871 OMIM 127550 OMIM 224230 OMIM 268130 OMIM 305000 OMIM 613987 OMIM 613988 OMIM 613989 OMIM 613990 OMIM 615190 SNOMED CT 74911008 2014-02 2020-08-18 Dystonia 16 https://medlineplus.gov/genetics/condition/dystonia-16 descriptionDystonia 16 is one of many forms of dystonia, which is a group of conditions characterized by involuntary movements, twisting (torsion) and tensing of various muscles, and unusual positioning of affected body parts. Dystonia 16 can appear at any age from infancy through adulthood, although it most often begins in childhood.The signs and symptoms of dystonia 16 vary among people with the condition. In many affected individuals, the disorder first affects muscles in one or both arms or legs. Tensing (contraction) of the muscles often sets the affected limb in an abnormal position, which may be painful and can lead to difficulty performing tasks, such as walking. In others, muscles in the neck are affected first, causing the head to be pulled backward and positioned with the chin in the air (retrocollis).In dystonia 16, muscles of the jaw, lips, and tongue are also commonly affected (oromandibular dystonia), causing difficulty opening and closing the mouth and problems with swallowing and speech. Speech can also be affected by involuntary tensing of the muscles that control the vocal cords (laryngeal dystonia), resulting in a quiet, breathy voice or an inability to speak clearly. Dystonia 16 gradually gets worse, eventually involving muscles in most parts of the body.Some people with dystonia 16 develop a pattern of movement abnormalities known as parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). In dystonia 16, parkinsonism is relatively mild if it develops at all.The signs and symptoms of dystonia 16 usually do not get better when treated with drugs that are typically used for movement disorders. ad Autosomal dominant ar Autosomal recessive PRKRA https://medlineplus.gov/genetics/gene/prkra DYT-PRKRA DYT16 Young-onset dystonia-(parkinsonism) GTR C2677567 MeSH D020821 OMIM 612067 SNOMED CT 722435003 2019-06 2020-08-18 Dystonia 6 https://medlineplus.gov/genetics/condition/dystonia-6 descriptionDystonia 6 is one of many forms of dystonia, which is a group of conditions characterized by involuntary movements, twisting (torsion) and tensing of various muscles, and unusual positioning of affected body parts. Dystonia 6 can appear at any age from childhood through adulthood; the average age of onset is 18.The signs and symptoms of dystonia 6 vary among affected individuals. The disorder usually first impacts muscles of the head and neck, causing problems with speaking (dysarthria) and eating (dysphagia). Eyelid twitching (blepharospasm) may also occur. Involvement of one or more limbs is common, and in some cases occurs before the head and neck problems. Dystonia 6 gradually gets worse, and it may eventually involve most of the body. ad Autosomal dominant THAP1 https://medlineplus.gov/genetics/gene/thap1 DYT6 DYT6 dystonia Idiopathic torsion dystonia of mixed type Primary dystonia, DYT6 type THAP1 dystonia Torsion dystonia 6 GTR C1414216 ICD-10-CM G24.1 MeSH D020821 OMIM 602629 SNOMED CT 702448007 2013-11 2020-08-18 Dystrophic epidermolysis bullosa https://medlineplus.gov/genetics/condition/dystrophic-epidermolysis-bullosa descriptionDystrophic epidermolysis bullosa is one of the major forms of a group of conditions called epidermolysis bullosa. Epidermolysis bullosa cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. The signs and symptoms of dystrophic epidermolysis bullosa vary widely among affected individuals. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, scarring, and other serious medical problems.Researchers classify dystrophic epidermolysis bullosa into major types based on the inheritance pattern and features of the condition. Although the types differ in severity, their features overlap significantly and they are caused by mutations in the same gene.Recessive dystrophic epidermolysis bullosa severe generalized (RDEB-sev gen) is the classic form of the condition and is the most severe. Affected infants are typically born with widespread blistering and areas of missing skin, often caused by trauma that occurs during birth. Most often, blisters are present over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract. As the blisters heal, they result in severe scarring. Scarring in the mouth and esophagus can make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. Additional complications of ongoing scarring can include fusion of the skin between the fingers and toes, loss of fingernails and toenails, joint deformities (contractures) that restrict movement, and eye inflammation leading to vision loss. Additionally, people with RDEB-sev gen have a very high risk of developing a form of skin cancer called squamous cell carcinoma in young adulthood. In these individuals, the cancer tends to be unusually aggressive and is often life-threatening.Other types of recessive dystrophic epidermolysis bullosa fall along a spectrum referred to as RDEB-generalized and localized (RDEB-gen and -loc). These forms of the condition are somewhat less severe than RDEB-sev gen and are distinguished by the affected regions of the body. Blistering is often limited to the hands, feet, knees, and elbows in mild cases, but may be widespread in more severe cases. Rare forms affect specific regions of the body, such as the shins or the abdomen. Affected people often have malformed fingernails and toenails. The RDEB-gen and -loc types involve scarring in the areas where blisters occur, but these forms of the condition do not cause the severe scarring characteristic of RDEB-sev gen.Another major type of this condition is known as dominant dystrophic epidermolysis bullosa (DDEB). The signs and symptoms of this condition tend to be milder than those of the recessive forms, with blistering often limited to the hands, feet, knees, and elbows. The blisters heal with scarring, but it is less severe than in recessive forms of this condition. Most affected people have malformed fingernails and toenails, and the nails may be lost over time. In the mildest cases, abnormal nails are the only sign of the condition. ad Autosomal dominant ar Autosomal recessive COL7A1 https://medlineplus.gov/genetics/gene/col7a1 DEB Epidermolysis bullosa dystrophica Epidermolysis bullosa, dystrophic GTR C0079294 GTR C0079474 GTR C0432322 ICD-10-CM Q81.2 MeSH D016108 OMIM 131750 OMIM 226600 SNOMED CT 111389006 SNOMED CT 254185007 SNOMED CT 254186008 SNOMED CT 254188009 SNOMED CT 48528004 SNOMED CT 75875004 2020-02 2020-08-18 Early-onset glaucoma https://medlineplus.gov/genetics/condition/early-onset-glaucoma descriptionGlaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term "early-onset glaucoma" may be used when the disorder appears before the age of 40.In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.Structural abnormalities that impede fluid drainage in the eye increase ocular pressure. These abnormalities may be present at birth and usually become apparent during the first year of life. Such structural abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 3 without other associated abnormalities, it is called primary congenital glaucoma.Other individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma. ar Autosomal recessive ad Autosomal dominant MYOC https://medlineplus.gov/genetics/gene/myoc CYP1B1 https://medlineplus.gov/genetics/gene/cyp1b1 Hereditary glaucoma GTR C1842028 GTR C2981140 ICD-10-CM Q15.0 MeSH D005901 OMIM 137750 OMIM 231300 SNOMED CT 415176004 SNOMED CT 71111008 2022-04 2022-04-04 Early-onset isolated dystonia https://medlineplus.gov/genetics/condition/early-onset-isolated-dystonia descriptionEarly-onset isolated dystonia is one of many forms of dystonia, which is a group of conditions characterized by involuntary tensing of the muscles (muscle contractions), twisting of specific body parts such as an arm or a leg, rhythmic shaking (tremors), and other uncontrolled movements. An isolated dystonia is one that occurs without other abnormal movements or other neurological symptoms, such as seizures, a loss of intellectual function, or developmental or intellectual delay. Early-onset isolated dystonia does not affect a person's intelligence. The signs and symptoms of early-onset isolated dystonia tend to occur in mid-childhood or adolescence. Abnormal muscle spasms in an arm or a leg are usually the first sign. These unusual movements initially occur while a person is doing a specific action, such as writing or  walking. In some affected people, dystonia later spreads to other parts of the body and the movements may become persistent and present when at rest and not doing an activity. The abnormal movements persist throughout life, but they do not usually cause pain.The signs and symptoms of early-onset isolated dystonia vary from person to person, even among affected members of the same family.  The mildest cases affect only a single part of the body, causing isolated problems such as abnormal posture and spasms of the hand while attempting to write (writer's cramp). Severe cases involve abnormal movements affecting many parts of the body. ad Autosomal dominant TOR1A https://medlineplus.gov/genetics/gene/tor1a Dystonia musculorum deformans 1 DYT1 Early-onset generalized torsion dystonia Early-onset primary dystonia Oppenheim dystonia Oppenheim's dystonia Primary torsion dystonia GTR C1851945 ICD-10-CM G24.1 MeSH D020821 OMIM 128100 SNOMED CT 22451001 2022-04 2022-04-22 Early-onset myopathy with fatal cardiomyopathy https://medlineplus.gov/genetics/condition/early-onset-myopathy-with-fatal-cardiomyopathy descriptionEarly-onset myopathy with fatal cardiomyopathy (EOMFC) is an inherited muscle disease that affects the skeletal muscles, which are used for movement, and the heart (cardiac) muscle. This condition is characterized by skeletal muscle weakness that becomes apparent in early infancy. Affected individuals have delayed development of motor skills, such as sitting, standing, and walking. Beginning later in childhood, people with EOMFC may also develop joint deformities called contractures that restrict the movement of the neck and back. Scoliosis, which is an abnormal side-to-side curvature of the spine, also develops in late childhood.A form of heart disease called dilated cardiomyopathy is another feature of EOMFC. Dilated cardiomyopathy enlarges and weakens the cardiac muscle, preventing the heart from pumping blood efficiently. Signs and symptoms of this condition can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. The heart abnormalities associated with EOMFC usually become apparent in childhood, after the skeletal muscle abnormalities. The heart disease worsens quickly, and it often causes heart failure and sudden death in adolescence or early adulthood. ar Autosomal recessive TTN https://medlineplus.gov/genetics/gene/ttn EOMFC Salih CMD Salih congenital muscular dystrophy Salih myopathy Titinopathy & early-onset myopathy with fatal cardiomyopathy GTR C2673677 MeSH D009135 OMIM 611705 SNOMED CT 702343002 2012-02 2023-01-13 Ehlers-Danlos syndrome https://medlineplus.gov/genetics/condition/ehlers-danlos-syndrome descriptionEhlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications.The various forms of Ehlers-Danlos syndrome have been classified in several different ways. Originally, 11 forms of Ehlers-Danlos syndrome were named using Roman numerals to indicate the types (type I, type II, and so on). In 1997, researchers proposed a simpler classification (the Villefranche nomenclature) that reduced the number of types to six and gave them descriptive names based on their major features. In 2017, the classification was updated to include rare forms of Ehlers-Danlos syndrome that were identified more recently. The 2017 classification describes 13 types of Ehlers-Danlos syndrome.An unusually large range of joint movement (hypermobility) occurs in most forms of Ehlers-Danlos syndrome, and it is a hallmark feature of the hypermobile type. Infants and children with hypermobility often have weak muscle tone (hypotonia), which can delay the development of motor skills such as sitting, standing, and walking. The loose joints are unstable and prone to dislocation and chronic pain. In the arthrochalasia type of Ehlers-Danlos syndrome, infants have hypermobility and dislocations of both hips at birth.Many people with the Ehlers-Danlos syndromes have soft, velvety skin that is highly stretchy (elastic) and fragile. Affected individuals tend to bruise easily, and some types of the condition also cause abnormal scarring. People with the classical form of Ehlers-Danlos syndrome experience wounds that split open with little bleeding and leave scars that widen over time to create characteristic "cigarette paper" scars. The dermatosparaxis type of the disorder is characterized by loose skin that sags and wrinkles, and extra (redundant) folds of skin may be present.Bleeding problems are common in the vascular type of Ehlers-Danlos syndrome and are caused by unpredictable tearing (rupture) of blood vessels and organs. These complications can lead to easy bruising, internal bleeding, a hole in the wall of the intestine (intestinal perforation), or stroke. During pregnancy, women with vascular Ehlers-Danlos syndrome may experience rupture of the uterus. Additional forms of Ehlers-Danlos syndrome that involve rupture of the blood vessels include the kyphoscoliotic, classical, and classical-like types.Other types of Ehlers-Danlos syndrome have additional signs and symptoms. The cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart. People with the kyphoscoliotic type experience severe curvature of the spine that worsens over time and can interfere with breathing by restricting lung expansion. A type of Ehlers-Danlos syndrome called brittle cornea syndrome is characterized by thinness of the clear covering of the eye (the cornea) and other eye abnormalities. The spondylodysplastic type features short stature and skeletal abnormalities such as abnormally curved (bowed) limbs. Abnormalities of muscles, including hypotonia and permanently bent joints (contractures), are among the characteristic signs of the musculocontractural and myopathic forms of Ehlers-Danlos syndrome. The periodontal type causes abnormalities of the teeth and gums. ad Autosomal dominant ar Autosomal recessive COL1A1 https://medlineplus.gov/genetics/gene/col1a1 COL1A2 https://medlineplus.gov/genetics/gene/col1a2 COL3A1 https://medlineplus.gov/genetics/gene/col3a1 COL5A1 https://medlineplus.gov/genetics/gene/col5a1 COL5A2 https://medlineplus.gov/genetics/gene/col5a2 PLOD1 https://medlineplus.gov/genetics/gene/plod1 ADAMTS2 https://medlineplus.gov/genetics/gene/adamts2 TNXB https://medlineplus.gov/genetics/gene/tnxb FKBP14 https://medlineplus.gov/genetics/gene/fkbp14 AEBP1 https://www.ncbi.nlm.nih.gov/gene/165 C1R https://www.ncbi.nlm.nih.gov/gene/715 C1S https://www.ncbi.nlm.nih.gov/gene/716 COL12A1 https://www.ncbi.nlm.nih.gov/gene/1303 PRDM5 https://www.ncbi.nlm.nih.gov/gene/11107 B4GALT7 https://www.ncbi.nlm.nih.gov/gene/11285 DSE https://www.ncbi.nlm.nih.gov/gene/29940 ZNF469 https://www.ncbi.nlm.nih.gov/gene/84627 SLC39A13 https://www.ncbi.nlm.nih.gov/gene/91252 CHST14 https://www.ncbi.nlm.nih.gov/gene/113189 B3GALT6 https://www.ncbi.nlm.nih.gov/gene/126792 EDS Ehlers Danlos disease GTR C0013720 GTR C0268342 GTR C1851801 GTR C1866294 GTR C2700425 GTR C3281160 GTR C3508773 GTR C3809845 GTR C4303789 GTR C4310681 GTR C4551499 ICD-10-CM Q79.6 MeSH D004535 OMIM 130000 OMIM 130010 OMIM 130020 OMIM 130050 OMIM 130060 OMIM 130070 OMIM 130080 OMIM 130090 OMIM 225310 OMIM 225320 OMIM 225400 OMIM 225410 OMIM 229200 OMIM 314400 OMIM 601776 OMIM 606408 OMIM 608763 OMIM 614557 OMIM 615349 OMIM 615539 OMIM 617174 OMIM 618000 SNOMED CT 17025000 SNOMED CT 20766005 SNOMED CT 25606004 SNOMED CT 30652003 SNOMED CT 398114001 SNOMED CT 55711009 SNOMED CT 83470009 2017-11 2024-09-17 Ellis-van Creveld syndrome https://medlineplus.gov/genetics/condition/ellis-van-creveld-syndrome descriptionEllis-van Creveld syndrome is an inherited disorder of bone growth that results in very short stature (dwarfism). People with this condition have particularly short forearms and lower legs and a narrow chest with short ribs. Ellis-van Creveld syndrome is also characterized by the presence of extra fingers and toes (polydactyly), malformed fingernails and toenails, and dental abnormalities. More than half of affected individuals are born with a heart defect, which can cause serious or life-threatening health problems.The features of Ellis-van Creveld syndrome overlap with those of another, milder condition called Weyers acrofacial dysostosis. Like Ellis-van Creveld syndrome, Weyers acrofacial dysostosis involves tooth and nail abnormalities, although affected individuals have less pronounced short stature and typically do not have heart defects. The two conditions are caused by mutations in the same genes. ar Autosomal recessive EVC https://medlineplus.gov/genetics/gene/evc EVC2 https://medlineplus.gov/genetics/gene/evc2 Chondroectodermal dysplasia Ellis-van Creveld dysplasia GTR C0013903 ICD-10-CM Q77.6 MeSH D004613 OMIM 225500 SNOMED CT 62501005 2012-12 2023-03-27 Emanuel syndrome https://medlineplus.gov/genetics/condition/emanuel-syndrome descriptionEmanuel syndrome is a chromosomal disorder that disrupts normal development and affects many parts of the body. Infants with Emanuel syndrome have weak muscle tone (hypotonia) and fail to gain weight and grow at the expected rate (failure to thrive). Their development is significantly delayed, and most affected individuals have severe to profound intellectual disability.Other features of Emanuel syndrome include an unusually small head (microcephaly), distinctive facial features, and a small lower jaw (micrognathia). Ear abnormalities are common, including small holes in the skin just in front of the ears (preauricular pits or sinuses). About half of all affected infants are born with an opening in the roof of the mouth (cleft palate) or a high arched palate. Males with Emanuel syndrome often have genital abnormalities. Additional signs of this condition can include heart defects and absent or unusually small (hypoplastic) kidneys; these problems can be life-threatening in infancy or childhood. ad Autosomal dominant 11 https://medlineplus.gov/genetics/chromosome/11 22 https://medlineplus.gov/genetics/chromosome/22 Der(22) syndrome due to 3:1 meiotic disjunction events Supernumerary der(22) syndrome Supernumerary der(22)t(11;22) syndrome Supernumerary derivative 22 chromosome syndrome MeSH D025063 OMIM 609029 SNOMED CT 702417004 2008-10 2020-09-08 Emery-Dreifuss muscular dystrophy https://medlineplus.gov/genetics/condition/emery-dreifuss-muscular-dystrophy descriptionEmery-Dreifuss muscular dystrophy is a condition that primarily affects muscles used for movement (skeletal muscles) and the heart (cardiac muscle). Among the earliest features of this disorder are joint deformities called contractures. Contractures restrict the movement of certain joints, most often the elbows, ankles, and neck, and usually become noticeable in early childhood. Most affected individuals also experience muscle weakness and wasting that worsen slowly over time, beginning in muscles of the upper arms and lower legs and later also affecting muscles in the shoulders and hips.Almost all people with Emery-Dreifuss muscular dystrophy develop heart problems by adulthood. In many cases, these heart problems are abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects) and abnormal heart rhythms (arrhythmias). If untreated, these abnormalities can lead to a sensation of fluttering or pounding in the chest (palpitations), an unusually slow heartbeat (bradycardia), fainting (syncope), heart failure, and an increased risk of sudden death.Researchers have identified several types of Emery-Dreifuss muscular dystrophy that are distinguished by their pattern of inheritance: X-linked, autosomal dominant, and autosomal recessive. The types usually have similar signs and symptoms, although a small percentage of people with the autosomal dominant form experience heart problems without any weakness or wasting of skeletal muscles. ad Autosomal dominant ar Autosomal recessive xr X-linked recessive LMNA https://medlineplus.gov/genetics/gene/lmna EMD https://medlineplus.gov/genetics/gene/emd SYNE1 https://medlineplus.gov/genetics/gene/syne1 FHL1 https://medlineplus.gov/genetics/gene/fhl1 SYNE2 https://www.ncbi.nlm.nih.gov/gene/23224 TMEM43 https://www.ncbi.nlm.nih.gov/gene/79188 Benign scapuloperoneal muscular dystrophy with early contractures EDMD Emery-Dreifuss syndrome Muscular dystrophy, Emery-Dreifuss type GTR C0410189 MeSH D020389 OMIM 181350 OMIM 310300 OMIM 612998 OMIM 612999 OMIM 614302 OMIM 616516 SNOMED CT 111508004 2017-05 2020-08-18 Encephalocraniocutaneous lipomatosis https://medlineplus.gov/genetics/condition/encephalocraniocutaneous-lipomatosis descriptionEncephalocraniocutaneous lipomatosis (ECCL) is a rare condition that primarily affects the brain, eyes, and skin of the head and face. Most of this condition's signs and symptoms are present from birth, and they vary widely among affected individuals.A hallmark feature of ECCL is a noncancerous tumor under the scalp covered by a smooth, hairless patch of skin. This type of tumor, called a nevus psiloliparus, is made up of fatty tissue. Some people with ECCL also have noncancerous tumors under the skin elsewhere on the head or face. Many have small flaps of skin called skin tags on the eyelids and around the eyes. Hair loss (alopecia), thin or missing patches of skin on the scalp (dermal hypoplasia or aplasia), and changes in skin coloring (pigmentation) are also possible.The most common eye abnormality in ECCL is a noncancerous growth called a choristoma. These growths can be present in one or both eyes and may affect vision.About two-thirds of people with ECCL have noncancerous fatty tumors inside the brain or around the spinal cord. These tumors are called intracranial lipomas and intraspinal lipomas, respectively. Affected individuals also have an increased risk of developing a type of brain cancer called a glioma. The brain and spinal cord abnormalities associated with ECCL can cause seizures, abnormal tensing of the muscles, and intellectual disability ranging from mild to profound. However, about one-third of affected individuals have normal intelligence.Other kinds of growths may also occur in people with ECCL, including noncancerous jaw tumors. n Not inherited FGFR1 https://medlineplus.gov/genetics/gene/fgfr1 ECCL Fishman syndrome (formerly) Haberland syndrome (formerly) GTR C0406612 MeSH D005128 MeSH D008068 MeSH D020752 OMIM 613001 SNOMED CT 238905009 2016-11 2020-08-18 Enlarged parietal foramina https://medlineplus.gov/genetics/condition/enlarged-parietal-foramina descriptionEnlarged parietal foramina is an inherited condition of impaired skull development. It is characterized by enlarged openings (foramina) in the parietal bones, which are the two bones that form the top and sides of the skull. This condition is due to incomplete bone formation (ossification) within the parietal bones. The openings are symmetrical and circular in shape, ranging in size from a few millimeters to several centimeters wide. Parietal foramina are a normal feature of fetal development, but typically they close before the baby is born, usually by the fifth month of pregnancy. However, in people with this condition, the parietal foramina remain open throughout life.The enlarged parietal foramina are soft to the touch due to the lack of bone at those areas of the skull. People with enlarged parietal foramina usually do not have any related health problems; however, scalp defects, seizures, and structural brain abnormalities have been noted in a small percentage of affected people. Pressure applied to the openings can lead to severe headaches, and individuals with this condition have an increased risk of brain damage or skull fractures if any trauma is experienced in the area of the openings.There are two forms of enlarged parietal foramina, called type 1 and type 2, which differ in their genetic cause. ad Autosomal dominant MSX2 https://medlineplus.gov/genetics/gene/msx2 ALX4 https://medlineplus.gov/genetics/gene/alx4 Catlin marks Cranium bifidum Cranium bifidum occultum Fenestrae parietals symmetricae Foramina parietalia permagna FPP Giant parietal foramina Hereditary cranium bifidum Parietal foramina PFM Symmetric parietal foramina GTR C1865044 GTR C1868598 GTR C1868599 MeSH D004413 OMIM 168500 OMIM 609597 SNOMED CT 718099006 2016-03 2020-08-18 Eosinophil peroxidase deficiency https://medlineplus.gov/genetics/condition/eosinophil-peroxidase-deficiency descriptionEosinophil peroxidase deficiency is a condition that affects certain white blood cells called eosinophils but causes no health problems in affected individuals. Eosinophils aid in the body's immune response. During a normal immune response, these cells are turned on (activated), and they travel to the area of injury or inflammation. The cells then release proteins and other compounds that have a toxic effect on severely damaged cells or invading organisms. One of these proteins is called eosinophil peroxidase. In eosinophil peroxidase deficiency, eosinophils have little or no eosinophil peroxidase. A lack of this protein does not seem to affect the eosinophils' ability to carry out an immune response.Because eosinophil peroxidase deficiency does not cause any health problems, this condition is often diagnosed when blood tests are done for other reasons or when a family member has been diagnosed with the condition. ar Autosomal recessive EPX https://medlineplus.gov/genetics/gene/epx EPXD Peroxidase and phospholipid deficiency in eosinophils Presentey anomaly GTR C1850000 MeSH D007960 OMIM 261500 SNOMED CT 711160007 2014-12 2020-08-18 Epidermal nevus https://medlineplus.gov/genetics/condition/epidermal-nevus descriptionAn epidermal nevus (plural: nevi) is an abnormal, noncancerous (benign) patch of skin caused by an overgrowth of cells in the outermost layer of skin (epidermis). Epidermal nevi are typically seen at birth or develop in early childhood. Affected individuals have one or more nevi that vary in size.There are several types of epidermal nevus that are defined in part by the type of epidermal cell involved. The epidermis is composed primarily of a specific cell type called a keratinocyte. One group of epidermal nevi, called keratinocytic or nonorganoid epidermal nevi, includes nevi that involve only keratinocytes. Keratinocytic epidermal nevi are typically found on the torso or limbs. They can be flat, tan or brown patches of skin or raised, velvety patches. As affected individuals age, the nevi can become thicker and darker and develop a wart-like (verrucous) appearance. Often, keratinocytic epidermal nevi follow a pattern on the skin known as the lines of Blaschko. The lines of Blaschko, which are normally invisible on skin, are thought to follow the paths along which cells migrate as the skin develops before birth. Keratinocytic epidermal nevi are also known as linear epidermal nevi or verrucous epidermal nevi, based on characteristics of their appearance.Other types of epidermal nevi involve additional types of epidermal cells, such as the cells that make up the hair follicles, the sweat glands, or the sebaceous glands (glands in the skin that produce a substance that protects the skin and hair). These nevi comprise a group called organoid epidermal nevi. A common type of organoid epidermal nevus is called nevus sebaceous. Nevi in this group are waxy, yellow-orange patches of skin, usually on the scalp or face. The patch is typically hairless, leaving a distinct region of baldness (alopecia). Similar to keratinocytic epidermal nevi, nevi sebaceous can become thicker and more verrucous over time. In about one-quarter of people with a nevus sebaceous, a tumor forms in the same region as the nevus. The tumor is usually benign, although rarely cancerous (malignant) tumors develop.Some affected individuals have only an epidermal nevus and no other abnormalities. However, sometimes people with an epidermal nevus also have problems in other body systems, such as the brain, eyes, or bones. In these cases, the affected individual has a condition called an epidermal nevus syndrome. There are several different epidermal nevus syndromes characterized by the type of epidermal nevus involved. n Not inherited FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 HRAS https://medlineplus.gov/genetics/gene/hras FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 KRAS https://medlineplus.gov/genetics/gene/kras NRAS https://medlineplus.gov/genetics/gene/nras PIK3CA https://medlineplus.gov/genetics/gene/pik3ca Epidermal naevus GTR C0334082 MeSH D009506 OMIM 162900 SNOMED CT 239107007 2016-08 2020-08-18 Epidermolysis bullosa simplex https://medlineplus.gov/genetics/condition/epidermolysis-bullosa-simplex descriptionEpidermolysis bullosa simplex is one of a group of genetic conditions called epidermolysis bullosa that cause the skin to be very fragile and to blister easily. Blisters and areas of skin loss (erosions) occur in response to minor injury or friction, such as rubbing or scratching. Epidermolysis bullosa simplex is one of the major forms of epidermolysis bullosa. The signs and symptoms of this condition vary widely among affected individuals. Blistering primarily affects the hands and feet in mild cases, and the blisters usually heal without leaving scars. Severe cases of this condition involve widespread blistering that can lead to infections, dehydration, and other medical problems. Severe cases may be life-threatening in infancy.Researchers have identified four major types of epidermolysis bullosa simplex.Although the types differ in severity, their features overlap significantly, and they are caused by mutations in the same genes. Most researchers now consider the major forms of this condition to be part of a single disorder with a range of signs and symptoms.The mildest form of epidermolysis bullosa simplex, known as the localized type (formerly called the Weber-Cockayne type), is characterized by skin blistering that begins anytime between childhood and adulthood and is usually limited to the hands and feet. Later in life, skin on the palms of the hands and soles of the feet may thicken and harden (hyperkeratosis).The Dowling-Meara type is the most severe form of epidermolysis bullosa simplex. Extensive, severe blistering can occur anywhere on the body, including the inside of the mouth, and blisters may appear in clusters. Blistering is present from birth and tends to improve with age. Affected individuals also experience abnormal nail growth and hyperkeratosis of the palms and soles.Another form of epidermolysis bullosa simplex, known as the other generalized type (formerly called the Koebner type), is associated with widespread blisters that appear at birth or in early infancy. The blistering tends to be less severe than in the Dowling-Meara type.Epidermolysis bullosa simplex with mottled pigmentation is characterized by patches of darker skin on the trunk, arms, and legs that fade in adulthood. This form of the disorder also involves skin blistering from early infancy, hyperkeratosis of the palms and soles, and abnormal nail growth.In addition to the four major types described above, researchers have identified another skin condition related to epidermolysis bullosa simplex, which they call the Ogna type. It is caused by mutations in a gene that is not associated with the other types of epidermolysis bullosa simplex. It is unclear whether the Ogna type is a subtype of epidermolysis bullosa simplex or represents a separate form of epidermolysis bullosa.Several other variants of epidermolysis bullosa simplex have been proposed, but they appear to be very rare. ad Autosomal dominant ar Autosomal recessive KRT5 https://medlineplus.gov/genetics/gene/krt5 KRT14 https://medlineplus.gov/genetics/gene/krt14 PLEC https://medlineplus.gov/genetics/gene/plec EBS GTR C0079298 GTR C0432317 ICD-10-CM Q81.0 MeSH D016110 OMIM 131760 OMIM 131800 OMIM 131900 OMIM 131950 OMIM 131960 OMIM 601001 OMIM 609352 SNOMED CT 254180002 SNOMED CT 398071000 SNOMED CT 67144006 SNOMED CT 90496008 2013-05 2023-08-22 Epidermolysis bullosa with pyloric atresia https://medlineplus.gov/genetics/condition/epidermolysis-bullosa-with-pyloric-atresia descriptionEpidermolysis bullosa with pyloric atresia (EB-PA) is a condition that affects the skin and digestive tract. This condition is one of several forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be fragile and to blister easily. Affected infants are often born with widespread blistering and areas of missing skin. Blisters continue to appear in response to minor injury or friction, such as rubbing or scratching. Most often, blisters occur over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract.People with EB-PA are also born with pyloric atresia, which is a blockage (obstruction) of the lower part of the stomach (the pylorus). This obstruction prevents food from emptying out of the stomach into the intestine. Signs of pyloric atresia include vomiting, a swollen (distended) abdomen, and an absence of stool. Pyloric atresia is life-threatening and must be repaired with surgery soon after birth.Other complications of EB-PA can include fusion of the skin between the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that restrict movement, and hair loss (alopecia). Some affected individuals are also born with malformations of the urinary tract, including the kidneys and bladder.Because the signs and symptoms of EB-PA are so severe, many infants with this condition do not survive beyond the first year of life. In those who survive, the condition may improve with time; some affected individuals have little or no blistering later in life. However, many affected individuals who live past infancy experience severe health problems, including blistering and the formation of red, bumpy patches called granulation tissue. Granulation tissue most often forms on the skin around the mouth, nose, fingers, and toes. It can also build up in the airway, leading to difficulty breathing. ar Autosomal recessive PLEC https://medlineplus.gov/genetics/gene/plec ITGA6 https://medlineplus.gov/genetics/gene/itga6 ITGB4 https://medlineplus.gov/genetics/gene/itgb4 Carmi syndrome EB-PA Junctional epidermolysis bullosa with pyloric atresia PA-JEB GTR C2677349 GTR C5676875 GTR C5676957 ICD-10-CM Q81.0 MeSH D004820 OMIM 226730 OMIM 612138 SNOMED CT 53748002 2009-09 2023-08-18 Epidermolytic hyperkeratosis https://medlineplus.gov/genetics/condition/epidermolytic-hyperkeratosis descriptionEpidermolytic hyperkeratosis is a skin disorder that is present at birth. Affected babies may have very red skin (erythroderma) and severe blisters. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis).As affected individuals get older, blistering is less frequent, erythroderma becomes less evident, and the skin becomes thick (hyperkeratotic), especially over joints, on areas of skin that come into contact with each other, or on the scalp or neck. This thickened skin is usually darker than normal. Bacteria can grow in the thick skin, often causing a distinct odor.Epidermolytic hyperkeratosis can be categorized into two types. People with PS-type epidermolytic hyperkeratosis have thick skin on the palms of their hands and soles of their feet (palmoplantar or palm/sole hyperkeratosis) in addition to other areas of the body. People with the other type, NPS-type, do not have extensive palmoplantar hyperkeratosis but do have hyperkeratosis on other areas of the body.Epidermolytic hyperkeratosis is part of a group of conditions called ichthyoses, which refers to the scaly skin seen in individuals with related disorders. However, in epidermolytic hyperkeratosis, the skin is thick but not scaly as in some of the other conditions in the group. ad Autosomal dominant ar Autosomal recessive KRT1 https://medlineplus.gov/genetics/gene/krt1 KRT10 https://medlineplus.gov/genetics/gene/krt10 BCIE BIE Bullous congenital ichthyosiform erythroderma Bullous erythroderma ichthyosiforme Bullous erythroderma ichthyosiformis congenita of Brocq Bullous ichthyosiform erythroderma EHK Epidermolytic ichthyosis Hyperkeratosis, epidermolytic GTR C0079153 ICD-10-CM Q80.3 MeSH D017488 OMIM 113800 SNOMED CT 254167000 2011-11 2020-08-18 Epilepsy of infancy with migrating focal seizures https://medlineplus.gov/genetics/condition/epilepsy-of-infancy-with-migrating-focal-seizures descriptionEpilepsy of infancy with migrating focal seizures (EIMFS) is a form of recurrent seizures (epilepsy) that begins early in life. Seizures typically start before the age of 6 months. Babies with this condition can reach early developmental milestones, such as the ability to follow movement with their eyes or control their head movement. However, as seizure activity develops, children with EIMFS typically stop developing new skills and may experience a gradual loss of existing skills (developmental regression).Focal motor seizures are the most common type of seizure seen in children with EIMFS. Focal motor seizures start in one area of the brain and affect muscle (motor) activity on one side of the body. Affected individuals may have more than one focal seizure at a time, and seizure activity can spread (migrate) from one brain region to another during an episode.Although the seizures that are associated with EIMFS may be relatively infrequent at first, the seizure frequency increases rapidly. Affected individuals often experience several seizures per day; in some cases, the seizures may seem almost continuous. Children with EIMFS may also have individual seizures that last for several minutes (status epilepticus). After a year or more of persistent seizures, the episodes may become less frequent.In children with EIMFS, seizures can affect the growth of the brain, leading to a small head size (microcephaly). The problems with brain development can also cause significant developmental delays and intellectual disabilities. Many affected individuals do not learn to walk or talk. Additional signs and symptoms of EIMFS may include weak muscle tone (hypotonia), abnormal tensing of the muscles (spasticity), and abnormal involuntary muscle movements.EIMFS is one of a group of severe epilepsies called developmental and epileptic encephalopathies (DEEs). These disorders are characterized by significant developmental delays and seizures that begin early in life and may be difficult to treat.Though some people with EIMFS have had milder signs and symptoms, many affected individuals do not survive past early childhood because of the serious health problems that are associated with this condition. x X-linked ar Autosomal recessive ad Autosomal dominant CDKL5 https://medlineplus.gov/genetics/gene/cdkl5 SMC1A https://medlineplus.gov/genetics/gene/smc1a PIGA https://medlineplus.gov/genetics/gene/piga SCN1A https://medlineplus.gov/genetics/gene/scn1a ATP1A3 https://medlineplus.gov/genetics/gene/atp1a3 KCNQ2 https://medlineplus.gov/genetics/gene/kcnq2 GABRA1 https://medlineplus.gov/genetics/gene/gabra1 KCNT1 https://medlineplus.gov/genetics/gene/kcnt1 TBC1D24 https://medlineplus.gov/genetics/gene/tbc1d24 CHD2 https://medlineplus.gov/genetics/gene/chd2 SCN8A https://medlineplus.gov/genetics/gene/scn8a SCN2A https://medlineplus.gov/genetics/gene/scn2a GABRB1 https://www.ncbi.nlm.nih.gov/gene/2560 GABRB3 https://www.ncbi.nlm.nih.gov/gene/2562 ITPA https://www.ncbi.nlm.nih.gov/gene/3704 KARS1 https://www.ncbi.nlm.nih.gov/gene/3735 QARS1 https://www.ncbi.nlm.nih.gov/gene/5859 AIMP1 https://www.ncbi.nlm.nih.gov/gene/9255 ALG3 https://www.ncbi.nlm.nih.gov/gene/10195 PLCB1 https://www.ncbi.nlm.nih.gov/gene/23236 WWOX https://www.ncbi.nlm.nih.gov/gene/51741 SLC12A5 https://www.ncbi.nlm.nih.gov/gene/57468 SLC25A22 https://www.ncbi.nlm.nih.gov/gene/79751 BRAT1 https://www.ncbi.nlm.nih.gov/gene/221927 HCN1 https://www.ncbi.nlm.nih.gov/gene/348980 DEE 14 Developmental and epileptic encephalopathy 14 Early infantile epileptic encephalopathy 14 EIEE14 EIMFS Epilepsy with migrating focal seizure in infancy Malignant migrating partial epilepsy of infancy Malignant migrating partial seizures of infancy MFSI Migrating focal seizures of infancy Migrating partial epilepsy of infancy Migrating partial seizures of infancy MMPEI MMPSI MPEI MPSI GTR C3554195 MeSH D013036 OMIM 614959 SNOMED CT 432001000124109 2025-07 2025-07-02 Epilepsy-aphasia spectrum https://medlineplus.gov/genetics/condition/epilepsy-aphasia-spectrum descriptionThe epilepsy-aphasia spectrum is a group of conditions that have overlapping signs and symptoms. A key feature of these conditions is impairment of language skills (aphasia). The language problems can affect speaking, reading, and writing. Another feature of epilepsy-aphasia spectrum disorders is certain patterns of abnormal electrical activity in the brain, which are detected by a test called an electroencephalogram (EEG). Many people with conditions in this spectrum develop recurrent seizures (epilepsy), and some have mild to severe intellectual disability. The conditions in the epilepsy-aphasia spectrum, which all begin in childhood, include Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike-and-wave during sleep syndrome (ECSWS), autosomal dominant rolandic epilepsy with speech dyspraxia (ADRESD), intermediate epilepsy-aphasia disorder (IEAD), atypical childhood epilepsy with centrotemporal spikes (ACECTS), and childhood epilepsy with centrotemporal spikes (CECTS).LKS and ECSWS are at the severe end of the spectrum. Both usually feature a characteristic abnormal pattern of electrical activity in the brain called continuous spike and waves during slow-wave sleep (CSWS). This pattern occurs while the affected child is sleeping, specifically during deep (slow-wave) sleep.Most children with LKS develop normally in early childhood, although some speak later than their peers. However, affected children lose language skills beginning around age 5. This loss typically begins with verbal agnosia, which is the inability to understand speech. As LKS develops, the ability to express speech is also impaired. Approximately 70 percent of children with LKS have seizures, typically of a type described as focal (or partial) because the seizure activity occurs in specific regions of the brain rather than affecting the entire brain.About half of children with ECSWS develop normally in early childhood, while others have delayed development of speech and motor skills. Although children with ECSWS typically lose a range of previously acquired skills, including those involved in language, movement, learning, or behavior, not everyone with ECSWS has aphasia. Seizures occur in approximately 80 percent of children with ECSWS and can include a variety of types, such as atypical absence seizures, which involve short periods of staring blankly; hemiclonic seizures, which cause rhythmic jerking of one side of the body; or generalized tonic-clonic seizures, which cause stiffening and rhythmic jerking of the entire body.CECTS is at the mild end of the epilepsy-aphasia spectrum. Affected children have rolandic seizures; these seizures are triggered by abnormal activity in an area of the brain called the rolandic region, which is part of the cerebrum. The seizures, which usually occur during sleep, cause twitching, numbness, or tingling of the face or tongue, often causing drooling and impairing speech. In most people with CECTS, the seizures disappear by the end of adolescence. Most affected individuals develop normally, although some have difficulty coordinating the movements of the mouth and tongue needed for clear speech (dyspraxia) or impairment of language skills.The other conditions in the epilepsy-aphasia spectrum are less common and fall in the middle of the spectrum. Children with IEAD usually have delayed development or regression of language skills. Some have seizures and most have abnormal electrical activity in their brains during sleep, although it is not prominent enough to be classified as CSWS. ACECTS features seizures and developmental regression that can affect movement, language, and attention. Children with ACECTS have abnormal electrical activity in the brain that is sometimes classified as CSWS. ADRESD is characterized by focal seizures, speech difficulties due to dyspraxia, and learning disability. ad Autosomal dominant GRIN2A https://medlineplus.gov/genetics/gene/grin2a Acquired aphasia with epilepsy DEE/EE-SWAS Developmental and/or epileptic encephalopathy with spike-wave activation in Sleep Epilepsy with continuous spike-wave in sleep Epilepsy with electrographic status epilepticus in sleep FESD Focal epilepsies with speech and language disorders Focal epilepsy with speech disorder and with or without mental retardation ICD-10-CM MeSH D004827 MeSH D007805 MeSH D013064 MeSH D018887 MeSH D019305 OMIM 245570 SNOMED CT 230384001 SNOMED CT 230438007 SNOMED CT 230439004 SNOMED CT 44145005 2016-11 2022-09-14 Episodic ataxia https://medlineplus.gov/genetics/condition/episodic-ataxia descriptionEpisodic ataxia is a group of related conditions that affect the nervous system and cause problems with movement and coordination. People with episodic ataxia have episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraines, blurred or double vision, slurred speech, and ringing in the ears (tinnitus). Seizures, muscle weakness, and paralysis that affect one side of the body (hemiplegia) may also occur during these episodes. Additionally, a muscle abnormality called myokymia or an eye abnormality called nystagmus can occur during or between episodes. Myokymia causes muscle cramping; stiffness; or continuous, fine muscle twitching that appears as rippling under the skin. Nystagmus refers to rapid, involuntary eye movements.Episodes of ataxia and other symptoms can begin anytime from early childhood to adulthood. They can be triggered by environmental factors such as stress, caffeine, alcohol, certain medications, physical activity, and illness. The duration of episodes may vary from seconds to days, and the frequency ranges from several episodes per day to one or two every few months. Between episodes, affected individuals may have no signs or symptoms. However, some continue to experience ataxia, which may worsen over time.Some children with episodic ataxia have delayed development of speech or motor skills, such as standing and walking. They may also have learning difficulties.Researchers have identified at least 11 types of episodic ataxia, distinguished by their pattern of signs and symptoms, age of onset, length of episodes, and genetic cause. ad Autosomal dominant CACNA1A https://medlineplus.gov/genetics/gene/cacna1a KCNA1 https://medlineplus.gov/genetics/gene/kcna1 SLC1A3 https://medlineplus.gov/genetics/gene/slc1a3 SCN2A https://medlineplus.gov/genetics/gene/scn2a FGF14 https://www.ncbi.nlm.nih.gov/gene/2259 EA GTR C1719788 GTR C1720416 GTR C2677843 ICD-10-CM MeSH D001259 OMIM 108500 OMIM 160120 OMIM 600111 OMIM 601949 OMIM 606552 OMIM 606554 OMIM 611907 SNOMED CT 420932006 SNOMED CT 421182009 SNOMED CT 421455009 2023-05 2025-08-18 Erdheim-Chester disease https://medlineplus.gov/genetics/condition/erdheim-chester-disease descriptionErdheim-Chester disease is a rare type of slow-growing blood cancer called a histiocytic neoplasm, which results in overproduction of cells called histiocytes. Histiocytes normally function to destroy foreign substances and protect the body from infection. In Erdheim-Chester disease, the excess production of histiocytes (histiocytosis) leads to inflammation that can damage organs and tissues throughout the body, causing them to become thickened, dense, and scarred (fibrotic); this tissue damage may lead to organ failure.People with Erdheim-Chester disease often have bone pain, especially in the lower legs and upper arms, due to an abnormal increase in bone density (osteosclerosis). Damage to the pituitary gland (a structure at the base of the brain that produces several hormones, including a hormone that controls the amount of water released in the urine) may result in hormonal problems such as a condition called diabetes insipidus that leads to excessive urination. Abnormally high pressure of the cerebrospinal fluid within the skull (intracranial hypertension) caused by accumulation of histiocytes in the brain may result in headaches, seizures, cognitive impairment, or problems with movement or sensation. People with this condition can also have shortness of breath, heart or kidney disease, protruding eyes (exophthalmos), skin growths, or inability to conceive a child (infertility). Affected individuals may also experience fever, night sweats, fatigue, weakness, and weight loss.The signs and symptoms of Erdheim-Chester disease usually appear between the ages of 40 and 60, although the disorder can occur at any age. The severity of the condition varies widely; some affected individuals have few or no associated health problems, while others have severe complications that can be life-threatening. n Not inherited BRAF https://medlineplus.gov/genetics/gene/braf Lipid granulomatosis Polyostotic sclerosing histiocytosis MeSH D031249 SNOMED CT 703711007 2015-05 2023-03-21 Erythrokeratodermia variabilis et progressiva https://medlineplus.gov/genetics/condition/erythrokeratodermia-variabilis-et-progressiva descriptionErythrokeratodermia variabilis et progressiva (EKVP) is a skin disorder that is present at birth or becomes apparent in infancy. Although its signs and symptoms vary, the condition is characterized by two major features. The first is hyperkeratosis, which is rough, thickened skin. These patches are usually reddish-brown and can either affect many parts of the body or occur in only a small area. They tend to be fixed, meaning they rarely spread or go away. However, the patches can vary in size and shape, and in some affected people they get larger over time. The areas of hyperkeratosis are generally symmetric, which means they occur in the same places on the right and left sides of the body.The second major feature of EKVP is patches of reddened skin called erythematous areas. Unlike the hyperkeratosis that occurs in this disorder, the erythematous areas are usually transient, which means they come and go. They vary in size, shape, and location, and can occur anywhere on the body. The redness is more common in childhood and can be triggered by sudden changes in temperature, emotional stress, or trauma or irritation to the area. It usually fades within hours to days. ad Autosomal dominant ar Autosomal recessive GJB3 https://medlineplus.gov/genetics/gene/gjb3 GJA1 https://medlineplus.gov/genetics/gene/gja1 KRT83 https://medlineplus.gov/genetics/gene/krt83 GJB4 https://medlineplus.gov/genetics/gene/gjb4 EKV EKV-P EKVP Erythrokeratodermia variabilis Erythrokeratodermia variabilis of Mendes da Costa Erythrokeratodermia, progressive symmetric Progressive symmetrical erythrokeratoderma of Gottron GTR C4551486 MeSH D056266 OMIM 133200 OMIM 617524 OMIM 617525 OMIM 617526 OMIM 617756 SNOMED CT 70041004 2018-10 2024-10-02 Erythromelalgia https://medlineplus.gov/genetics/condition/erythromelalgia descriptionErythromelalgia is a condition characterized by episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet. These episodes are usually triggered by increased body temperature, which may be caused by exercise or entering a warm room. Ingesting alcohol or spicy foods may also trigger an episode. Wearing warm socks, tight shoes, or gloves can cause a pain episode so debilitating that it can impede everyday activities such as wearing shoes and walking. Pain episodes can prevent an affected person from going to school or work regularly.The signs and symptoms of erythromelalgia typically begin in childhood, although mildly affected individuals may have their first pain episode later in life. As individuals with erythromelalgia get older and the disease progresses, the hands and feet may be constantly red, and the affected areas can extend from the hands to the arms, shoulders, and face, and from the feet to the entire legs.Erythromelalgia is often considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. ad Autosomal dominant SCN9A https://medlineplus.gov/genetics/gene/scn9a Erythermalgia Familial erythromelalgia Primary erythromelalgia GTR C0014805 ICD-10-CM I73.81 MeSH D004916 OMIM 133020 SNOMED CT 37151006 SNOMED CT 403390002 2012-11 2020-08-18 Esophageal atresia/tracheoesophageal fistula https://medlineplus.gov/genetics/condition/esophageal-atresia-tracheoesophageal-fistula descriptionEsophageal atresia/tracheoesophageal fistula (EA/TEF) is a condition resulting from abnormal development before birth of the tube that carries food from the mouth to the stomach (the esophagus). During early development, the esophagus and windpipe (trachea) begin as a single tube that normally divides into the two adjacent passages between four and eight weeks after conception. If this separation does not occur properly, EA/TEF is the result.In esophageal atresia (EA), the upper esophagus does not connect (atresia) to the lower esophagus and stomach. Almost 90 percent of babies born with esophageal atresia also have a tracheoesophageal fistula (TEF), in which the esophagus and the trachea are abnormally connected, allowing fluids from the esophagus to get into the airways and interfere with breathing. A small number of infants have only one of these abnormalities.There are several types of EA/TEF, classified by the location of the malformation and the structures that are affected. In more than 80 percent of cases, the lower section of the malformed esophagus is connected to the trachea (EA with a distal TEF). Other possible configurations include having the upper section of the malformed esophagus connected to the trachea (EA with a proximal TEF), connections to the trachea from both the upper and lower sections of the malformed esophagus (EA with proximal and distal TEF), an esophagus that is malformed but does not connect to the trachea (isolated EA), and a connection to the trachea from an otherwise normal esophagus (H-type TEF with no EA).While EA/TEF arises during fetal development, it generally becomes apparent shortly after birth. Saliva, liquids fed to the infant, or digestive fluids may enter the windpipe through the tracheoesophageal fistula, leading to coughing, respiratory distress, and a bluish appearance of the skin or lips (cyanosis). Esophageal atresia blocks liquids fed to the infant from entering the stomach, so they are spit back up, sometimes along with fluids from the respiratory tract. EA/TEF is a life-threatening condition; affected babies generally require surgery to correct the malformation in order to allow feeding and prevent lung damage from repeated exposure to esophageal fluids.EA/TEF occurs alone (isolated EA/TEF) in about 40 percent of affected individuals. In other cases it occurs with other birth defects or as part of a genetic syndrome (non-isolated or syndromic EA/TEF). n Not inherited EA/TEF ICD-10-CM Q39.0 ICD-10-CM Q39.1 MeSH D004933 OMIM 189960 SNOMED CT 26179002 2012-08 2024-04-17 Essential pentosuria https://medlineplus.gov/genetics/condition/essential-pentosuria descriptionEssential pentosuria is a condition characterized by high levels of a sugar called L-xylulose in urine. The condition is so named because L-xylulose is a type of sugar called a pentose. Despite the excess sugar, affected individuals have no associated health problems. ar Autosomal recessive DCXR https://medlineplus.gov/genetics/gene/dcxr Essential benign pentosuria L-xylulose reductase deficiency L-xylulosuria Pentosuria Xylitol dehydrogenase deficiency GTR C0268162 MeSH D002239 OMIM 260800 SNOMED CT 190764000 2015-01 2020-08-18 Essential thrombocythemia https://medlineplus.gov/genetics/condition/essential-thrombocythemia descriptionEssential thrombocythemia is a condition characterized by an increased number of platelets (thrombocythemia). Platelets (thrombocytes) are blood cells involved in blood clotting. While some people with this condition have no symptoms, others develop problems associated with the excess platelets.Abnormal blood clotting (thrombosis) is common in people with essential thrombocythemia and causes many signs and symptoms of this condition. Clots that block blood flow to the brain can cause strokes or temporary stroke-like episodes known as transient ischemic attacks. Thrombosis in the legs can cause leg pain, swelling, or both. In addition, clots can travel to the lungs (pulmonary embolism), blocking blood flow in the lungs and causing chest pain and difficulty breathing (dyspnea).Another problem in essential thrombocythemia is abnormal bleeding, which occurs more often in people with a very high number of platelets. Affected people may have nosebleeds, bleeding gums, or bleeding in the gastrointestinal tract. It is thought that bleeding occurs because a specific protein in the blood that helps with clotting is reduced, although why the protein is reduced is unclear.Other signs and symptoms of essential thrombocythemia include an enlarged spleen (splenomegaly); weakness; headaches; or a sensation in the skin of burning, tingling, or prickling. Some people with essential thrombocythemia have episodes of severe pain, redness, and swelling (erythromelalgia), which commonly occur in the hands and feet. ad Autosomal dominant JAK2 https://medlineplus.gov/genetics/gene/jak2 TET2 https://medlineplus.gov/genetics/gene/tet2 MPL https://medlineplus.gov/genetics/gene/mpl THPO https://medlineplus.gov/genetics/gene/thpo CALR https://medlineplus.gov/genetics/gene/calr Essential thrombocytosis Primary thrombocythemia Primary thrombocytosis GTR C3277671 ICD-10-CM D47.3 MeSH D013920 OMIM 187950 SNOMED CT 109994006 SNOMED CT 128844009 2014-09 2020-08-18 Essential tremor https://medlineplus.gov/genetics/condition/essential-tremor descriptionEssential tremor is a movement disorder that causes involuntary, rhythmic shaking (tremor), especially in the hands. It is distinguished from tremor that results from other disorders or known causes, such as Parkinson's disease or head trauma. Essential tremor usually occurs alone, without other neurological signs or symptoms. However, some experts think that essential tremor can include additional features, such as mild balance problems.Essential tremor usually occurs with movements and can occur during many different types of activities, such as eating, drinking, or writing. Essential tremor can also occur when the muscles are opposing gravity, such as when the hands are extended. It is usually not evident at rest.In addition to the hands and arms, muscles of the trunk, face, head, and neck may also exhibit tremor in this disorder; the legs and feet are less often involved. Head tremor may appear as a "yes-yes" or "no-no" movement while the affected individual is seated or standing. In some people with essential tremor, the tremor may affect the voice (vocal tremor).Essential tremor does not shorten the lifespan. However, it may interfere with fine motor skills such as using eating utensils, writing, shaving, or applying makeup, and in some cases these and other activities of daily living can be greatly impaired. Symptoms of essential tremor may be aggravated by emotional stress, anxiety, fatigue, hunger, caffeine, cigarette smoking, or temperature extremes.Essential tremor may appear at any age but is most common in older adults. Some studies have suggested that people with essential tremor have a higher than average risk of developing neurological conditions including Parkinson's disease or sensory problems such as hearing loss, especially in individuals whose tremor appears after age 65. u Pattern unknown ad Autosomal dominant Benign essential tremor Familial tremor Hereditary essential tremor GTR C1860861 ICD-10-CM G25.0 MeSH D020329 OMIM 190300 SNOMED CT 609558009 2013-05 2024-09-17 Ethylmalonic encephalopathy https://medlineplus.gov/genetics/condition/ethylmalonic-encephalopathy descriptionEthylmalonic encephalopathy is an inherited disorder that affects several body systems, particularly the nervous system. Neurological signs and symptoms include delayed development and the loss of previously acquired skills (developmental regression), weak muscle tone (hypotonia), seizures, and abnormal movements. The body's network of blood vessels (the vascular system) is also affected. Children with this disorder often develop rashes of tiny red spots (petechiae) caused by bleeding under the skin and blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis). Chronic diarrhea is another common feature of ethylmalonic encephalopathy.The signs and symptoms of ethylmalonic encephalopathy are apparent at birth or begin in the first few months of life. Problems with the nervous system typically worsen over time, and most affected individuals survive only into early childhood. ar Autosomal recessive ETHE1 https://medlineplus.gov/genetics/gene/ethe1 Encephalopathy, petechiae, and ethylmalonic aciduria EPEMA syndrome GTR C1865349 MeSH D001928 OMIM 602473 SNOMED CT 723307008 2017-08 2020-08-18 Ewing sarcoma https://medlineplus.gov/genetics/condition/ewing-sarcoma descriptionEwing sarcoma is a cancerous tumor that occurs in bones or soft tissues, such as cartilage or nerves. There are several types of Ewing sarcoma, including Ewing sarcoma of bone, extraosseous Ewing sarcoma, peripheral primitive neuroectodermal tumor (pPNET), and Askin tumor. These tumors are considered to be related because they have similar genetic causes. These types of Ewing sarcoma can be distinguished from one another by the tissue in which the tumor develops. Approximately 87 percent of Ewing sarcomas are Ewing sarcoma of bone, which is a bone tumor that usually occurs in the thigh bones (femurs), pelvis, ribs, or shoulder blades. Extraosseous (or extraskeletal) Ewing sarcoma describes tumors in the soft tissues around bones, such as cartilage. pPNETs occur in nerve tissue and can be found in many parts of the body. A type of pPNET found in the chest is called Askin tumor.Ewing sarcomas most often occur in children and young adults. Affected individuals usually feel stiffness, pain, swelling, or tenderness of the bone or surrounding tissue. Sometimes, there is a lump near the surface of the skin that feels warm and soft to the touch. Often, children have a fever that does not go away. Ewing sarcoma of bone can cause weakening of the involved bone, and affected individuals may have a broken bone with no obvious cause.It is common for Ewing sarcoma to spread to other parts of the body (metastasize), usually to the lungs, to other bones, or to the bone marrow. n Not inherited EWSR1 https://medlineplus.gov/genetics/gene/ewsr1 FLI1 https://medlineplus.gov/genetics/gene/fli1 FUS https://medlineplus.gov/genetics/gene/fus ERG https://www.ncbi.nlm.nih.gov/gene/2078 ETV1 https://www.ncbi.nlm.nih.gov/gene/2115 ETV4 https://www.ncbi.nlm.nih.gov/gene/2118 FEV https://www.ncbi.nlm.nih.gov/gene/54738 11 https://medlineplus.gov/genetics/chromosome/11 22 https://medlineplus.gov/genetics/chromosome/22 Ewing family of tumors Ewing tumor Ewing's sarcoma Ewing's tumor Tumor of the Ewing family GTR C0553580 MeSH D012512 OMIM 612219 SNOMED CT 128783001 SNOMED CT 307608006 SNOMED CT 447951009 SNOMED CT 76909002 2012-05 2020-09-08 FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome https://medlineplus.gov/genetics/condition/fbxl4-related-encephalomyopathic-mitochondrial-dna-depletion-syndrome descriptionFBXL4-related encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome is a severe condition that begins in infancy and affects multiple body systems. It is primarily associated with brain dysfunction combined with muscle weakness (encephalomyopathy).Infants with FBXL4-related encephalomyopathic mtDNA depletion syndrome have weak muscle tone (hypotonia) and a failure to grow or gain weight at the expected rate (failure to thrive). Children with FBXL4-related encephalomyopathic mtDNA depletion syndrome have delayed development of mental and motor skills and severely impaired speech development. Many affected individuals have seizures, movement abnormalities, and an unusually small head size (microcephaly) with a loss of nerve cells in the brain (cerebral atrophy).All individuals with FBXL4-related encephalomyopathic mtDNA depletion syndrome have a buildup of a chemical called lactic acid in the body (lactic acidosis), and about half of individuals have an accumulation of ammonia in the blood. Buildup of these substances can be life-threatening. Many affected individuals also have heart abnormalities, such as congenital heart defects or heart rhythm abnormalities (arrhythmias). In addition, individuals with this condition can have vision problems, hearing loss, liver abnormalities (hepatopathy), and immune deficiency due to a decrease in white blood cells. Many children with FBXL4-related encephalomyopathic mtDNA depletion syndrome have distinctive facial features that can include thick eyebrows; outside corners of the eyes that point upward (upslanting palpebral fissures); a broad nasal bridge and tip; and a long, smooth space between the upper lip and nose (philtrum).Because the encephalomyopathy and other signs and symptoms are so severe, people with FBXL4-related encephalomyopathic mtDNA depletion syndrome usually live only into early childhood. ar Autosomal recessive FBXL4 https://medlineplus.gov/genetics/gene/fbxl4 FBXL4 deficiency FBXL4-related early onset mitochondrial encephalopathy Mitochondrial DNA depletion syndrome 13, encephalomyopathic type MTDPS13 GTR C3809592 MeSH D017237 OMIM 615471 2017-05 2023-11-13 FG syndrome https://medlineplus.gov/genetics/condition/fg-syndrome descriptionFG syndrome is a genetic condition that affects many parts of the body and occurs almost exclusively in males. "FG" represents the surname initials of the first family diagnosed with the disorder.FG syndrome affects intelligence and behavior. Almost everyone with the condition has intellectual disability, which ranges from mild to severe. Affected individuals tend to be friendly, inquisitive, and hyperactive, with a short attention span. Compared to people with other forms of intellectual disability, their socialization and daily living skills are strong, while verbal communication and language skills tend to be weaker.The physical features of FG syndrome include weak muscle tone (hypotonia), broad thumbs, and wide first (big) toes. Abnormalities of the tissue connecting the left and right halves of the brain (the corpus callosum) are also common. Most affected individuals have constipation, and many have abnormalities of the anus such as an obstruction of the anal opening (imperforate anus). People with FG syndrome also tend to have a distinctive facial appearance including small, underdeveloped ears; a tall, prominent forehead; and outside corners of the eyes that point downward (down-slanting palpebral fissures).Additional features seen in some people with FG syndrome include widely set eyes (hypertelorism), an upswept frontal hairline, and a large head compared to body size (relative macrocephaly). Other health problems have also been reported, including heart defects, seizures, undescended testes (cryptorchidism) in males, and a soft out-pouching in the lower abdomen (an inguinal hernia). xr X-linked recessive FLNA https://medlineplus.gov/genetics/gene/flna MED12 https://medlineplus.gov/genetics/gene/med12 CASK https://medlineplus.gov/genetics/gene/cask UPF3B https://www.ncbi.nlm.nih.gov/gene/65109 FGS FGS1 Keller syndrome Mental retardation, large head, imperforate anus, congenital hypotonia, and partial agenesis of the corpus callosum OKS Opitz-Kaveggia syndrome GTR C0220769 GTR C1845119 GTR C1845546 GTR C1845902 MeSH D000015 MeSH D038901 OMIM 300321 OMIM 300406 OMIM 300422 OMIM 300581 OMIM 305450 SNOMED CT 49984004 2012-12 2020-08-18 FOXG1 syndrome https://medlineplus.gov/genetics/condition/foxg1-syndrome descriptionFOXG1 syndrome is a condition characterized by impaired development and structural brain abnormalities. Affected infants are small at birth, and their heads grow more slowly than normal, leading to an unusually small head size (microcephaly) by early childhood. The condition is associated with a particular pattern of brain malformations that includes a thin or underdeveloped connection between the right and left halves of the brain (a structure called the corpus callosum), reduced folds and grooves (gyri) on the surface of the brain, and a smaller than usual amount of brain tissue known as white matter.FOXG1 syndrome affects most aspects of development, and children with the condition typically have severe intellectual disability. Abnormal or involuntary movements, such as jerking movements of the arms and legs and repeated hand motions, are common, and most affected children do not learn to sit or walk without assistance. Babies and young children with FOXG1 syndrome often have feeding problems, sleep disturbances, seizures, irritability, and excessive crying. Affected individuals may have autism spectrum disorder, which is characterized by limited communication and social interaction, including poor eye contact and a near absence of speech and language skills. FOXG1 syndrome was previously described as a congenital variant of Rett syndrome, which is a similar disorder of brain development. Both disorders are characterized by impaired development, intellectual disability, and problems with communication and language. However, Rett syndrome is diagnosed almost exclusively in females, while FOXG1 syndrome affects both males and females. Rett syndrome also involves a period of apparently normal early development that does not occur in FOXG1 syndrome. Because of these differences, physicians and researchers now usually consider FOXG1 syndrome to be distinct from Rett syndrome. ad Autosomal dominant FOXG1 https://medlineplus.gov/genetics/gene/foxg1 14 https://medlineplus.gov/genetics/chromosome/14 FOXG1-related disorder GTR C3150705 MeSH D020271 OMIM 613454 SNOMED CT 702450004 2013-12 2023-03-28 FOXP2-related speech and language disorder https://medlineplus.gov/genetics/condition/foxp2-related-speech-and-language-disorder descriptionFOXP2-related speech and language disorder affects the development of speech and language beginning in early childhood. Affected individuals have a condition known as childhood apraxia of speech (CAS), which makes it difficult to produce the sequences of sounds and syllables needed to form words. CAS is caused by abnormalities in the parts of the brain that plan and coordinate the movements of the lips, mouth, and tongue. Children with FOXP2-related speech and language disorder say their first words later than other children, typically between 18 months and 7 years of age. Their speech is often difficult to understand, although the clarity of speech usually improves over time.  In addition to having problems with producing speech (expressive language), people with FOXP2-related speech and language disorder may have difficulty understanding speech (receptive language). Some affected individuals also have trouble with other language-related skills, such as reading, spelling, and grammar. Less commonly, individuals with FOXP2-related speech and language disorder have features of autism spectrum disorder, which is a condition characterized by impaired social skills and communication problems. Some affected individuals have difficulty with motor skills such as walking, writing, or buttoning clothes, but these typically improve with treatment. Some affected individuals may have learning difficulties.  ad Autosomal dominant+Inherited or new variant ad Autosomal dominant FOXP2 https://medlineplus.gov/genetics/gene/foxp2 Speech and language disorder with orofacial dyspraxia Speech-language disorder 1 GTR C0750927 MeSH D001072 OMIM 602081 SNOMED CT 229703009 2025-03 2025-01-21 Fabry disease https://medlineplus.gov/genetics/condition/fabry-disease descriptionFabry disease is an inherited disorder that results from the buildup of a type of fat, called globotriaosylceramide, in the body's cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Characteristic features of Fabry disease include episodes of pain, particularly in the hands and feet (acroparesthesias); clusters of small, dark red spots on the skin called angiokeratomas; a decreased ability to sweat (hypohidrosis); cloudiness or streaks in the front part of the eye (corneal opacity or corneal verticillata); problems with the gastrointestinal system; ringing in the ears (tinnitus); and hearing loss. Additional signs and symptoms are possible, which can vary among affected individuals.Fabry disease also involves potentially life-threatening complications such as progressive kidney failure, heart failure, and stroke. Some affected individuals have milder forms of the disorder that appear later in life and typically involve only the heart, kidneys, or blood vessels in the brain. x X-linked GLA https://medlineplus.gov/genetics/gene/gla Alpha-galactosidase A deficiency Anderson-Fabry disease Angiokeratoma corporis diffusum Angiokeratoma diffuse Ceramide trihexosidase deficiency Fabry's disease GLA deficiency Hereditary dystopic lipidosis GTR C0002986 ICD-10-CM E75.21 MeSH D000795 OMIM 301500 SNOMED CT 124464003 SNOMED CT 16652001 SNOMED CT 838319005 2007-03 2022-07-29 Facioscapulohumeral muscular dystrophy https://medlineplus.gov/genetics/condition/facioscapulohumeral-muscular-dystrophy descriptionFacioscapulohumeral muscular dystrophy is a disorder characterized by muscle weakness and wasting (atrophy). This condition gets its name from the muscles that are affected most often: those of the face (facio-), around the shoulder blades (scapulo-), and in the upper arms (humeral). The signs and symptoms of facioscapulohumeral muscular dystrophy usually appear in adolescence. However, the onset and severity of the condition varies widely. Milder cases may not become noticeable until later in life, whereas rare severe cases become apparent in infancy or early childhood.Weakness involving the facial muscles or shoulders is usually the first symptom of this condition. Facial muscle weakness often makes it difficult to drink from a straw, whistle, or turn up the corners of the mouth when smiling. Weakness in muscles around the eyes can prevent the eyes from closing fully while a person is asleep, which can lead to dry eyes and other eye problems. For reasons that are unclear, weakness may be more severe in one side of the face than the other. Weak shoulder muscles tend to make the shoulder blades (scapulae) protrude from the back, a common sign known as scapular winging. Weakness in muscles of the shoulders and upper arms can make it difficult to raise the arms over the head or throw a ball.The muscle weakness associated with facioscapulohumeral muscular dystrophy worsens slowly over decades and may spread to other parts of the body. Weakness in muscles of the lower legs can lead to a condition called foot drop, which affects walking and increases the risk of falls. Muscular weakness in the hips and pelvis can make it difficult to climb stairs or walk long distances. Additionally, affected individuals may have an exaggerated curvature of the lower back (lordosis) due to weak abdominal muscles. About 20 percent of affected individuals eventually require the use of a wheelchair.Additional signs and symptoms of facioscapulohumeral muscular dystrophy can include mild high-tone hearing loss and abnormalities involving the light-sensitive tissue at the back of the eye (the retina). These signs are often not noticeable and may be discovered only during medical testing. Rarely, facioscapulohumeral muscular dystrophy affects the heart (cardiac) muscle or muscles needed for breathing.Researchers have described two types of facioscapulohumeral muscular dystrophy: type 1 (FSHD1) and type 2 (FSHD2). The two types have the same signs and symptoms and are distinguished by their genetic cause. ad Autosomal dominant SMCHD1 https://medlineplus.gov/genetics/gene/smchd1 DUX4 https://medlineplus.gov/genetics/gene/dux4 4 https://medlineplus.gov/genetics/chromosome/4 Facio-scapulo-humeral dystrophy Facioscapulohumeral atrophy Facioscapulohumeral type progressive muscular dystrophy Facioscapuloperoneal muscular dystrophy FSH muscular dystrophy FSHD Muscular dystrophy, facioscapulohumeral GTR C0238288 GTR C1834671 MeSH D020391 OMIM 158900 OMIM 158901 SNOMED CT 399091004 2014-07 2023-08-22 Factor V Leiden thrombophilia https://medlineplus.gov/genetics/condition/factor-v-leiden-thrombophilia descriptionFactor V Leiden thrombophilia is an inherited disorder of blood clotting. Factor V Leiden is the name of a specific gene mutation that results in thrombophilia, which is an increased tendency to form abnormal blood clots that can block blood vessels.People with factor V Leiden thrombophilia have a higher than average risk of developing a type of blood clot called a deep venous thrombosis (DVT). DVTs occur most often in the legs, although they can also occur in other parts of the body, including the brain, eyes, liver, and kidneys. Factor V Leiden thrombophilia also increases the risk that clots will break away from their original site and travel through the bloodstream. These clots can lodge in the lungs, where they are known as pulmonary emboli. Although factor V Leiden thrombophilia increases the risk of blood clots, only about 10 percent of individuals with the factor V Leiden mutation ever develop abnormal clots.The factor V Leiden mutation is associated with a slightly increased risk of pregnancy loss (miscarriage). Women with this mutation are two to three times more likely to have multiple (recurrent) miscarriages or a pregnancy loss during the second or third trimester. Some research suggests that the factor V Leiden mutation may also increase the risk of other complications during pregnancy, including pregnancy-induced high blood pressure (preeclampsia), slow fetal growth, and early separation of the placenta from the uterine wall (placental abruption). However, the association between the factor V Leiden mutation and these complications has not been confirmed. Most women with factor V Leiden thrombophilia have normal pregnancies. u Pattern unknown F5 https://medlineplus.gov/genetics/gene/f5 APC resistance, Leiden type Hereditary resistance to activated protein C GTR C1861171 ICD-10-CM D68.51 MeSH D020016 OMIM 188055 SNOMED CT 421527008 2023-08 2025-04-03 Factor V deficiency https://medlineplus.gov/genetics/condition/factor-v-deficiency descriptionFactor V deficiency is a rare bleeding disorder. The signs and symptoms of this condition can begin at any age, although the most severe cases are apparent in childhood. Factor V deficiency commonly causes nosebleeds; easy bruising; bleeding under the skin; bleeding of the gums; and prolonged or excessive bleeding following surgery, trauma, or childbirth. Women with factor V deficiency can have heavy or prolonged menstrual bleeding (menorrhagia). Bleeding into joint spaces (hemarthrosis) can also occur, although it is rare. Severely affected individuals have an increased risk of bleeding inside the skull (intracranial hemorrhage), in the lungs (pulmonary hemorrhage), or in the gastrointestinal tract, which can be life-threatening. ar Autosomal recessive F5 https://medlineplus.gov/genetics/gene/f5 Labile factor deficiency Owren disease Owren's disease Parahemophilia Proaccelerin deficiency GTR C0015499 MeSH D005166 OMIM 227400 SNOMED CT 4320005 2013-05 2025-04-03 Factor VII deficiency https://medlineplus.gov/genetics/condition/factor-vii-deficiency descriptionFactor VII deficiency is a rare bleeding disorder that varies in severity among affected individuals. The signs and symptoms of this condition can begin at any age, although the most severe cases are apparent in infancy. However, up to one-third of people with factor VII deficiency never have any bleeding problems. Factor VII deficiency commonly causes nosebleeds (epistaxis), bleeding of the gums, easy bruising, and prolonged or excessive bleeding following surgery or physical injury. Bleeding into joint spaces (hemarthrosis) and blood in the urine (hematuria) occasionally occur. Many women with factor VII deficiency have heavy or prolonged menstrual bleeding (menorrhagia). Severely affected individuals have an increased risk of bleeding inside the skull (intracranial hemorrhage) or in the gastrointestinal tract, which can be life-threatening. Although factor VII deficiency is primarily associated with increased bleeding, some people with the condition have excessive blood clotting (thrombosis). ar Autosomal recessive n Not inherited F7 https://medlineplus.gov/genetics/gene/f7 F7 deficiency Hypoproconvertinemia Proconvertin deficiency Prothrombin conversion accelerator deficiency Serum prothrombin conversion accelerator deficiency GTR C0015503 MeSH D005168 OMIM 227500 SNOMED CT 37193007 2016-10 2020-08-18 Factor X deficiency https://medlineplus.gov/genetics/condition/factor-x-deficiency descriptionFactor X deficiency is a rare bleeding disorder that varies in severity among affected individuals. The signs and symptoms of this condition can begin at any age, although the most severe cases are apparent in childhood. Factor X deficiency commonly causes nosebleeds, easy bruising, bleeding under the skin, bleeding of the gums, blood in the urine (hematuria), and prolonged or excessive bleeding following surgery or trauma. Women with factor X deficiency can have heavy or prolonged menstrual bleeding (menorrhagia) or excessive bleeding in childbirth, and may be at increased risk of pregnancy loss (miscarriage). Bleeding into joint spaces (hemarthrosis) occasionally occurs. Severely affected individuals have an increased risk of bleeding inside the skull (intracranial hemorrhage), in the lungs (pulmonary hemorrhage), or in the gastrointestinal tract, which can be life-threatening. n Not inherited ar Autosomal recessive F10 https://medlineplus.gov/genetics/gene/f10 Congenital Stuart factor deficiency F10 deficiency Stuart-Prower factor deficiency GTR C0015519 ICD-10-CM D68.2 MeSH D005171 OMIM 227600 SNOMED CT 76642003 2015-01 2020-08-18 Factor XI deficiency https://medlineplus.gov/genetics/condition/factor-xi-deficiency descriptionFactor XI deficiency is a disorder that can cause abnormal bleeding due to a shortage (deficiency) of the factor XI protein, which is involved in blood clotting. This condition is classified as either partial or severe based on the degree of deficiency of the factor XI protein. However, regardless of the severity of the protein deficiency, most affected individuals have relatively mild bleeding problems, and some people with this disorder have few if any symptoms. The most common feature of factor XI deficiency is prolonged bleeding after trauma or surgery, especially involving the inside of the mouth and nose (oral and nasal cavities) or the urinary tract. If the bleeding is left untreated after surgery, solid swellings consisting of congealed blood (hematomas) can develop in the surgical area.Other signs and symptoms of this disorder can include frequent nosebleeds, easy bruising, bleeding under the skin, and bleeding of the gums. Women with this disorder can have heavy or prolonged menstrual bleeding (menorrhagia) or prolonged bleeding after childbirth. In contrast to some other bleeding disorders, spontaneous bleeding into the urine (hematuria), gastrointestinal tract, or skull cavity are not common in factor XI deficiency, although they can occur in severely affected individuals. Bleeding into the muscles or joints, which can cause long-term disability in other bleeding disorders, generally does not occur in this condition. ad Autosomal dominant ar Autosomal recessive F11 https://medlineplus.gov/genetics/gene/f11 F11 deficiency Factor 11 deficiency Haemophilia C Hemophilia C Plasma thromboplastin antecedent deficiency PTA deficiency Rosenthal factor deficiency Rosenthal syndrome Rosenthal's disease GTR C0015523 ICD-10-CM D68.1 MeSH D005173 OMIM 612416 SNOMED CT 49762007 2017-05 2020-08-18 Factor XIII deficiency https://medlineplus.gov/genetics/condition/factor-xiii-deficiency descriptionFactor XIII deficiency is a rare bleeding disorder. Researchers have identified an inherited form and a less severe form that is acquired during a person's lifetime.Signs and symptoms of inherited factor XIII deficiency begin soon after birth, usually with abnormal bleeding from the umbilical cord stump. If the condition is not treated, affected individuals may have episodes of excessive and prolonged bleeding that can be life-threatening. Abnormal bleeding can occur after surgery or minor trauma. The condition can also cause spontaneous bleeding into the joints or muscles, leading to pain and disability. Women with inherited factor XIII deficiency tend to have heavy or prolonged menstrual bleeding (menorrhagia) and may experience recurrent pregnancy losses (miscarriages). Other signs and symptoms of inherited factor XIII deficiency include nosebleeds, bleeding of the gums, easy bruising, problems with wound healing, bleeding after surgery, and abnormal scar formation. Inherited factor XIII deficiency also increases the risk of spontaneous bleeding inside the skull (intracranial hemorrhage), which is the leading cause of death in people with this condition.Acquired factor XIII deficiency becomes apparent later in life. People with the acquired form are less likely to have severe or life-threatening episodes of abnormal bleeding than those with the inherited form. ar Autosomal recessive F13A1 https://medlineplus.gov/genetics/gene/f13a1 F13B https://medlineplus.gov/genetics/gene/f13b Deficiency of factor XIII Deficiency, Laki-Lorand factor Fibrin stabilizing factor deficiency GTR C2750481 GTR C2750514 MeSH D005177 OMIM 613225 OMIM 613235 SNOMED CT 18604004 2015-08 2020-08-18 Familial HDL deficiency https://medlineplus.gov/genetics/condition/familial-hdl-deficiency descriptionFamilial HDL deficiency is a condition characterized by low levels of high-density lipoprotei% (HDL) in the blood. HDL is a molecule that transports cholesterol and certain fats called phospholipids through the bloodstream from the body's tissues to the liver. Once in the liver, cholesterol and phospholipids are redistributed to other tissues or removed from the body. HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. People with familial HDL deficiency may develop cardiovascular disease at a relatively young age, often before age 50.Severely reduced levels of HDL in the blood is a characteristic feature of a related disorder called Tangier disease. People with Tangier disease have additional signs and symptoms, such as disturbances in nerve function; enlarged, orange-colored tonsils; and clouding of the clear covering of the eye (corneal clouding). However, people with familial HDL deficiency do not have these additional features. ad Autosomal dominant ABCA1 https://medlineplus.gov/genetics/gene/abca1 APOA1 https://medlineplus.gov/genetics/gene/apoa1 Familial hypoalphalipoproteinemia FHA HDL deficiency, type 2 HDLD Low serum HDL cholesterol Primary hypoalphalipoproteinemia MeSH D052456 OMIM 604091 SNOMED CT 15346004 SNOMED CT 190785000 2012-11 2024-09-17 Familial Mediterranean fever https://medlineplus.gov/genetics/condition/familial-mediterranean-fever descriptionFamilial Mediterranean fever is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints.  These episodes are often accompanied by fever and sometimes a rash or headache. Occasionally inflammation may occur in other parts of the body, such as the heart; the membrane surrounding the brain and spinal cord; and in males, the testicles. In about half of affected individuals, attacks are preceded by mild signs and symptoms known as a prodrome. Prodromal symptoms include mildly uncomfortable sensations in the area that will later become inflamed, or more general feelings of discomfort.The first episode of illness in familial Mediterranean fever usually occurs in childhood or the teenage years, but in some cases, the initial attack occurs much later in life. Typically, episodes last 12 to 72 hours and can vary in severity. Episodes generally occur once a month, and in affected women of reproductive age, attacks often correspond with menstruation or ovulation. However, the length of time between episodes can range from days to years. During these periods, affected individuals usually have no signs or symptoms related to the condition. However, without treatment to help prevent attacks and complications, a buildup of protein deposits (amyloidosis) in the body's organs and tissues may occur, especially in the kidneys, which can lead to kidney failure. ad Autosomal dominant ar Autosomal recessive MEFV https://medlineplus.gov/genetics/gene/mefv SAA1 https://medlineplus.gov/genetics/gene/saa1 Benign paroxysmal peritonitis Familial paroxysmal polyserositis FMF MEF Recurrent polyserositis Reimann periodic disease Siegal-Cattan-Mamou disease Wolff periodic disease GTR C0031069 GTR C1851347 ICD-10-CM E85.0 MeSH D010505 OMIM 134610 OMIM 249100 SNOMED CT 12579009 2008-09 2026-03-04 Familial acute myeloid leukemia with mutated CEBPA https://medlineplus.gov/genetics/condition/familial-acute-myeloid-leukemia-with-mutated-cebpa descriptionFamilial acute myeloid leukemia with mutated CEBPA is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection; red blood cells (erythrocytes) that carry oxygen; and platelets (thrombocytes), which are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets.People with familial acute myeloid leukemia with mutated CEBPA have a shortage of white blood cells (leukopenia), leading to increased susceptibility to infections. A low number of red blood cells (anemia) also occurs in this disorder, resulting in fatigue and weakness. Affected individuals also have a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding. Other symptoms of familial acute myeloid leukemia with mutated CEBPA may include fever and weight loss.While acute myeloid leukemia is generally a disease of older adults, familial acute myeloid leukemia with mutated CEBPA often begins earlier in life, and it has been reported to occur as early as age 4. Between 50 and 65 percent of affected individuals survive their disease, compared with 25 to 40 percent of those with other forms of acute myeloid leukemia. However, people with familial acute myeloid leukemia with mutated CEBPA have a higher risk of having a new primary occurrence of this disorder after successful treatment of the initial occurrence. ad Autosomal dominant CEBPA https://medlineplus.gov/genetics/gene/cebpa CEBPA-dependent familial acute myeloid leukemia Familial acute myeloid leukaemia GTR C0023467 MeSH D015470 OMIM 601626 SNOMED CT 397340004 2012-05 2020-08-18 Familial adenomatous polyposis https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis descriptionFamilial adenomatous polyposis (FAP) is an inherited disorder that is characterized by a greatly increased risk of cancer of the large intestine (colon) and rectum (collectively known as colorectal cancer). People with FAP have multiple precancerous (benign) growths (polyps) in the colon, and one or more of these polyps will likely develop into colorectal cancer. There are two forms of FAP: the classic type and the attenuated type.The classic type of FAP is the more severe type. People with classic FAP develop colon polyps as early as childhood. By age 35 years, 95 percent of people with classic FAP will have colon polyps. Once polyps appear in people with classic FAP, the number of polyps increases quickly. People with classic FAP may have hundreds to thousands of colon polyps. Unless the colon is removed, one or more of these polyps will become cancerous (malignant). Individuals with classic FAP typically develop colorectal cancer around 40 years old, and at least 90 percent of affected individuals will develop colorectal cancer by age 50 years if they do not have a procedure that removes their colon beforehand (preventative colectomy).The attenuated type of FAP is the less severe form. People with attenuated FAP tend to have fewer polyps (an average of 30) that develop later in life (early to mid-adulthood) than those with classic FAP. People with attenuated FAP have a 70 percent lifetime risk of colorectal cancer, with cancer typically developing around 55 years old. People with attenuated FAP may or may not be advised to have a preventative colectomy.Less commonly, people with FAP may develop other types of cancer. Affected individuals are at increased risk of developing cancer of the stomach, pancreas, a gland in the lower neck (thyroid gland), liver (specifically, a form known as hepatoblastoma), brain (specifically, a form known as medulloblastoma), or a section of the small intestine (duodenum).People with FAP can also have benign growths in their bones (osteomas), in their skin (cysts), or in the small glands located on top of the kidneys called adrenal glands (adrenal masses). Other benign growths called desmoid tumors develop in 10 to 30 percent of people with FAP. These fibrous tumors usually occur in the abdomen or abdominal wall. Desmoid tumors tend to recur after they are surgically removed.People with FAP may also have dental abnormalities, which can include teeth that do not break through the gums, one or more missing teeth, extra (supernumerary) teeth, and dental cysts. Individuals with FAP often have an eye problem called congenital hypertrophy of the retinal pigment epithelium (CHRPE). CHRPE is characterized by flat lesions on the light-sensitive tissue that lines the back of the eye (retina) that can be seen during an eye exam. CHRPE does not cause any vision problems and occurs in up to 80 percent of people with FAP. ad Autosomal dominant+1 affected parent APC https://medlineplus.gov/genetics/gene/apc Adenomatous familial polyposis Adenomatous familial polyposis syndrome Adenomatous polyposis coli Familial multiple polyposis syndrome FAP GTR C2713442 MeSH D011125 OMIM 175100 SNOMED CT 423471004 SNOMED CT 72900001 2025-08 2025-08-26 Familial atrial fibrillation https://medlineplus.gov/genetics/condition/familial-atrial-fibrillation descriptionFamilial atrial fibrillation is an inherited abnormality of the heart's normal rhythm. Atrial fibrillation is characterized by episodes of uncoordinated electrical activity (fibrillation) in the heart's upper chambers (the atria), which cause a fast and irregular heartbeat. If untreated, this abnormal heart rhythm (arrhythmia) can lead to dizziness, chest pain, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, or fainting (syncope). Atrial fibrillation also increases the risk of stroke and sudden death. Complications of atrial fibrillation can occur at any age, although some people with this heart condition never experience any health problems associated with the disorder. ad Autosomal dominant LMNA https://medlineplus.gov/genetics/gene/lmna KCNQ1 https://medlineplus.gov/genetics/gene/kcnq1 KCNH2 https://medlineplus.gov/genetics/gene/kcnh2 SCN5A https://medlineplus.gov/genetics/gene/scn5a KCNJ2 https://medlineplus.gov/genetics/gene/kcnj2 PRKAG2 https://medlineplus.gov/genetics/gene/prkag2 RYR2 https://medlineplus.gov/genetics/gene/ryr2 ABCC9 https://medlineplus.gov/genetics/gene/abcc9 NKX2-5 https://www.ncbi.nlm.nih.gov/gene/1482 GJA5 https://www.ncbi.nlm.nih.gov/gene/2702 KCNA5 https://www.ncbi.nlm.nih.gov/gene/3741 MYL4 https://www.ncbi.nlm.nih.gov/gene/4635 NPPA https://www.ncbi.nlm.nih.gov/gene/4878 SCN1B https://www.ncbi.nlm.nih.gov/gene/6324 SCN2B https://www.ncbi.nlm.nih.gov/gene/6327 SCN4B https://www.ncbi.nlm.nih.gov/gene/6330 NUP155 https://www.ncbi.nlm.nih.gov/gene/9631 KCNE2 https://www.ncbi.nlm.nih.gov/gene/9992 SCN3B https://www.ncbi.nlm.nih.gov/gene/55800 Atrial fibrillation, familial Auricular fibrillation GTR C1837014 GTR C1843687 GTR C1862394 GTR C2677106 GTR C2677294 GTR C3151431 GTR C3151464 GTR C3279693 GTR C3279695 GTR C3809311 GTR C3809312 GTR C4013560 GTR C4013699 GTR C4014269 GTR C4310636 ICD-10-CM I48 ICD-10-CM I48.3 ICD-10-CM I48.4 ICD-10-CM I48.9 MeSH D001281 OMIM 607554 OMIM 608583 OMIM 608988 OMIM 611493 OMIM 611494 OMIM 612201 OMIM 612240 OMIM 613055 OMIM 613980 OMIM 614022 OMIM 614049 OMIM 614050 OMIM 615377 OMIM 615378 OMIM 615770 OMIM 617280 SNOMED CT 49436004 2017-10 2020-08-18 Familial candidiasis https://medlineplus.gov/genetics/condition/familial-candidiasis descriptionFamilial candidiasis is an inherited tendency to develop infections caused by a type of fungus called Candida. Affected individuals typically have infections of the skin, the nails, and the moist lining of body cavities (mucous membranes). These infections are recurrent and persistent, which means they come back repeatedly and can last a long time. This pattern of infection is called chronic mucocutaneous candidiasis.Candida is commonly present on the skin and on the mucous membranes, and in most people usually causes no health problems. However, certain medications (such as antibiotics and corticosteroids) and other factors can lead to occasional overgrowth of Candida (candidiasis) in the mouth (where it is known as thrush) or in the vagina. These episodes, commonly called yeast infections, usually last only a short time before being cleared by a healthy immune system.Most people with familial candidiasis have chronic or recurrent yeast infections that begin in early childhood. Skin infections lead to a rash with crusty, thickened patches; when these patches occur on the scalp, they can cause loss of hair in the affected area (scarring alopecia). Candidiasis of the nails can result in thick, cracked, and discolored nails and swelling and redness of the surrounding skin. Thrush and gastrointestinal symptoms such as bloating, constipation, or diarrhea are common in affected individuals. Women with familial candidiasis can develop frequent vaginal yeast infections, and infants can have yeast infections on the skin that cause persistent diaper rash.Depending on the genetic change involved in this condition, some affected individuals are at risk for developing systemic candidiasis, a more severe condition in which the infection spreads through the bloodstream to various organs including the brain and the meninges, which are the membranes covering the brain and spinal cord. Systemic candidiasis can be life-threatening.Chronic or recurrent yeast infections can occur in people without familial candidiasis. Some individuals experience recurrent candidiasis as part of a general susceptibility to infections because their immune systems are impaired by a disease such as acquired immune deficiency syndrome (AIDS) or severe combined immunodeficiency (SCID), medications, or other factors. Other individuals have syndromes such as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or autosomal dominant hyper-IgE syndrome (AD-HIES) that include a tendency to develop candidiasis along with other signs and symptoms affecting various organs and systems of the body. ad Autosomal dominant ar Autosomal recessive CARD9 https://medlineplus.gov/genetics/gene/card9 IL17RC https://medlineplus.gov/genetics/gene/il17rc STAT1 https://medlineplus.gov/genetics/gene/stat1 RORC https://www.ncbi.nlm.nih.gov/gene/6097 TRAF3IP2 https://www.ncbi.nlm.nih.gov/gene/10758 IL17RA https://www.ncbi.nlm.nih.gov/gene/23765 CLEC7A https://www.ncbi.nlm.nih.gov/gene/64581 IL17F https://www.ncbi.nlm.nih.gov/gene/112744 Familial chronic mucocutaneous candidiasis GTR C0341024 ICD-10-CM B37 MeSH D002178 OMIM 114580 OMIM 212050 OMIM 607644 OMIM 613108 OMIM 613953 OMIM 613956 OMIM 614162 OMIM 615527 OMIM 616445 OMIM 616622 SNOMED CT 235073000 2016-09 2024-09-17 Familial dysautonomia https://medlineplus.gov/genetics/condition/familial-dysautonomia descriptionFamilial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain. ar Autosomal recessive ELP1 https://medlineplus.gov/genetics/gene/elp1 FD HSAN type III HSAN3 HSN-III Riley-Day syndrome GTR C0013364 ICD-10-CM G90.1 MeSH D004402 OMIM 223900 SNOMED CT 29159009 2007-05 2025-04-03 Familial encephalopathy with neuroserpin inclusion bodies https://medlineplus.gov/genetics/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies descriptionFamilial encephalopathy with neuroserpin inclusion bodies (FENIB) is a disorder that causes progressive dysfunction of the brain (encephalopathy). This condition is characterized by a loss of intellectual functioning (dementia) and seizures.The first signs of intellectual impairment in individuals with FENIB may be problems with attention and concentration. Affected individuals may have trouble regulating their thoughts or speech. As the condition progresses, personality changes develop, and judgment, insight, and memory become impaired. Affected individuals lose the ability to perform the activities of daily living, and most eventually require comprehensive care.People with FENIB have seizures that involve a sudden, involuntary muscle jerking or twitching (myoclonus). Many also experience at least one other form of seizure, typically generalized seizures that involve a loss of consciousness, muscle rigidity, and convulsions. In rare cases, people with FENIB have prolonged episodes of seizure activity that last several minutes (status epilepticus). In most people with FENIB, anti-seizure medications are not effective. Many people with FENIB have other types of involuntary movement (dyskinesia).The signs and symptoms of FENIB can appear at any age, and they vary in severity. In severe cases, dementia can appear in childhood or adolescence and is often the first sign of the condition. Less severe cases are characterized by a progressive decline in intellectual functioning that begins in mid- to late adulthood.People with FENIB have a shortened life expectancy. The earlier the signs and symptoms appear, the greater the impact on life expectancy. Causes of death in people with FENIB include status epilepticus and pneumonia. ad Autosomal dominant+Inherited or new variant SERPINI1 https://medlineplus.gov/genetics/gene/serpini1 Familial dementia with neuroserpin inclusion bodies FENIB Neuroserpin encephalopathy neuroserpinosis Progressive myoclonus epilepsy associated with neuroserpin inclusion bodies Progressive myoclonus epilepsy associated with neuroserpinosis GTR C1858680 MeSH D004831 MeSH D020271 OMIM 604218 SNOMED CT 702421006 2026-02 2026-02-19 Familial erythrocytosis https://medlineplus.gov/genetics/condition/familial-erythrocytosis descriptionFamilial erythrocytosis is an inherited condition characterized by an increased number of red blood cells (erythrocytes). The primary function of these cells is to carry oxygen from the lungs to tissues and organs throughout the body. Signs and symptoms of familial erythrocytosis can include headaches, dizziness, nosebleeds, and shortness of breath. The excess red blood cells also increase the risk of developing abnormal blood clots that can block the flow of blood through arteries and veins. If these clots restrict blood flow to essential organs and tissues (particularly the heart, lungs, or brain), they can cause life-threatening complications such as a heart attack or stroke. However, many people with familial erythrocytosis experience only mild signs and symptoms or never have any problems related to their extra red blood cells. ar Autosomal recessive ad Autosomal dominant VHL https://medlineplus.gov/genetics/gene/vhl EGLN1 https://medlineplus.gov/genetics/gene/egln1 EPAS1 https://medlineplus.gov/genetics/gene/epas1 EPOR https://medlineplus.gov/genetics/gene/epor Benign familial polycythemia Congenital erythrocytosis Familial polycythemia Hereditary erythrocytosis Primary familial polycythemia GTR C1837915 GTR C1853286 GTR C2673187 ICD-10-CM D75.0 MeSH D011086 OMIM 133100 OMIM 263400 OMIM 609820 OMIM 611783 SNOMED CT 17342003 2012-08 2020-08-18 Familial exudative vitreoretinopathy https://medlineplus.gov/genetics/condition/familial-exudative-vitreoretinopathy descriptionFamilial exudative vitreoretinopathy is a hereditary disorder that can cause vision loss that worsens over time. This condition affects the retina, the specialized light-sensitive tissue that lines the back of the eye. In people with this disorder, blood vessels do not fully develop at the outer edges (periphery) of the retina, which reduces the blood supply to this tissue. This prolonged reduction in blood supply (chronic ischemia) causes continued damage to the retina and can lead to worsening of the condition. The signs and symptoms of familial exudative vitreoretinopathy vary widely, even within the same family. In many affected individuals, the retinal abnormalities never cause any vision problems. Other people with this condition develop abnormal vessels that leak. This  causes chronic inflammation which, over time, can lead to fluid under the retina (exudate). A reduction in the retina's blood supply causes the retina to fold, tear, or separate from the back of the eye (retinal detachment). The resulting retinal damage can lead to vision loss and blindness. Other eye abnormalities are also possible, including eyes that do not look in the same direction (strabismus) and a visible whiteness (leukocoria) in the normally black pupil.Some people with familial exudative vitreoretinopathy also have a condition known as osteoporosis-pseudoglioma syndrome, which is characterized by reduced bone density. People with this condition have weakened bones and an increased risk of fractures. ar Autosomal recessive xr X-linked recessive ad Autosomal dominant NDP https://medlineplus.gov/genetics/gene/ndp FZD4 https://medlineplus.gov/genetics/gene/fzd4 LRP5 https://medlineplus.gov/genetics/gene/lrp5 CTNNB1 https://medlineplus.gov/genetics/gene/ctnnb1 KIF11 https://www.ncbi.nlm.nih.gov/gene/3832 TSPAN12 https://www.ncbi.nlm.nih.gov/gene/23554 ZNF408 https://www.ncbi.nlm.nih.gov/gene/79797 FEVR GTR C1844579 GTR C1851402 GTR C1866176 GTR C2750079 GTR C4225316 MeSH D012164 OMIM 133780 OMIM 305390 OMIM 601813 OMIM 605750 OMIM 613310 OMIM 616468 SNOMED CT 232063007 2024-02 2025-03-06 Familial focal epilepsy with variable foci https://medlineplus.gov/genetics/condition/familial-focal-epilepsy-with-variable-foci descriptionFamilial focal epilepsy with variable foci (FFEVF) is an uncommon form of recurrent seizures (epilepsy) that runs in families. Seizures associated with FFEVF can begin at any time from infancy to adulthood. The seizures are described as focal or partial, which means they begin in one region of the brain and do not cause a loss of consciousness. In more than 70 percent of affected individuals, these seizures begin in one of two areas of the brain, either the temporal lobe or the frontal lobe. The region of the brain where the seizures start tends to stay the same over time. In rare instances, seizure activity that starts in one area spreads to affect the entire brain and causes a loss of consciousness, muscle stiffening, and rhythmic jerking. Episodes that begin as partial seizures and spread throughout the brain are known as secondarily generalized seizures.Among family members with FFEVF, individuals may not have the same brain region affected (variable foci), meaning that one person's seizures may not begin in the same part of the brain as their affected relative.Some individuals with FFEVF also have a brain malformation called focal cortical dysplasia. Seizures in these individuals are typically not well-controlled with medication.Most people with FFEVF are intellectually normal, and there are no problems with their brain function between seizures. However, some people with FFEVF have developed psychiatric disorders (such as schizophrenia), behavioral problems, or intellectual disability. It is unclear whether these additional features are directly related to epilepsy in these individuals. ad Autosomal dominant DEPDC5 https://medlineplus.gov/genetics/gene/depdc5 NPRL2 https://medlineplus.gov/genetics/gene/nprl2 NPRL3 https://medlineplus.gov/genetics/gene/nprl3 Familial partial epilepsy with variable foci FFEVF Partial epilepsy with variable foci GTR C4310708 GTR C4310709 GTR C4551983 MeSH D004828 OMIM 604364 OMIM 617116 OMIM 617118 2017-03 2020-08-18 Familial glucocorticoid deficiency https://medlineplus.gov/genetics/condition/familial-glucocorticoid-deficiency descriptionFamilial glucocorticoid deficiency is a condition that occurs when the adrenal glands, which are hormone-producing glands located on top of each kidney, do not produce certain hormones called glucocorticoids. These hormones, which include cortisol and corticosterone, aid in immune system function, play a role in maintaining normal blood sugar (glucose) levels, help trigger nerve cell signaling in the brain, and serve many other purposes in the body.A shortage of adrenal hormones (adrenal insufficiency) causes the signs and symptoms of familial glucocorticoid deficiency. These signs and symptoms often begin in infancy or early childhood. Most affected children first develop low blood glucose (hypoglycemia). These hypoglycemic children can fail to grow and gain weight at the expected rate (failure to thrive). If left untreated, hypoglycemia can lead to seizures, learning difficulties, and other neurological problems. Hypoglycemia that is left untreated for prolonged periods can lead to neurological damage and death. Other features of familial glucocorticoid deficiency can include recurrent infections and skin coloring darker than that of other family members (hyperpigmentation).There are multiple types of familial glucocorticoid deficiency, which are distinguished by their genetic cause. ar Autosomal recessive MC2R https://medlineplus.gov/genetics/gene/mc2r MRAP https://medlineplus.gov/genetics/gene/mrap NNT https://medlineplus.gov/genetics/gene/nnt MCM4 https://www.ncbi.nlm.nih.gov/gene/4173 TXNRD2 https://www.ncbi.nlm.nih.gov/gene/10587 ACTH resistance Adrenal unresponsiveness to ACTH Glucocorticoid deficiency Hereditary unresponsiveness to adrenocorticotropic hormone Isolated glucocorticoid deficiency GTR C1864947 GTR C3553587 GTR C4049650 GTR C4049714 MeSH D000309 OMIM 202200 OMIM 607398 OMIM 609197 OMIM 609981 OMIM 614736 SNOMED CT 71974009 2015-02 2023-07-19 Familial hemiplegic migraine https://medlineplus.gov/genetics/condition/familial-hemiplegic-migraine descriptionFamilial hemiplegic migraine is a form of migraine headache that runs in families. Migraines usually cause intense, throbbing pain in one area of the head, often accompanied by nausea, vomiting, and extreme sensitivity to light and sound. These recurrent headaches typically begin in childhood or adolescence and can be triggered by certain foods, emotional stress, and minor head trauma. Each headache may last from a few hours to a few days.In some types of migraine, including familial hemiplegic migraine, a pattern of neurological symptoms called an aura precedes the headache. The most common symptoms associated with an aura are temporary visual changes such as blind spots (scotomas), flashing lights, zig-zagging lines, and double vision. In people with familial hemiplegic migraine, auras are also characterized by temporary numbness or weakness, often affecting one side of the body (hemiparesis). Additional features of an aura can include difficulty with speech, confusion, and drowsiness. An aura typically develops gradually over a few minutes and lasts about an hour.Unusually severe migraine episodes have been reported in some people with familial hemiplegic migraine. These episodes have included fever, seizures, prolonged weakness, coma, and, rarely, death. Although most people with familial hemiplegic migraine recover completely between episodes, neurological symptoms such as memory loss and problems with attention can last for weeks or months. About 20 percent of people with this condition develop mild but permanent difficulty coordinating movements (ataxia), which may worsen with time, and rapid, involuntary eye movements called nystagmus. ad Autosomal dominant CACNA1A https://medlineplus.gov/genetics/gene/cacna1a ATP1A2 https://medlineplus.gov/genetics/gene/atp1a2 SCN1A https://medlineplus.gov/genetics/gene/scn1a PRRT2 https://medlineplus.gov/genetics/gene/prrt2 Hemiplegic migraine, familial Hemiplegic-ophthalmoplegic migraine GTR C0338484 GTR C1864987 GTR C1865322 ICD-10-CM G43.409 MeSH D020325 OMIM 141500 OMIM 602481 OMIM 609634 SNOMED CT 95656000 2014-01 2023-03-21 Familial hemophagocytic lymphohistiocytosis https://medlineplus.gov/genetics/condition/familial-hemophagocytic-lymphohistiocytosis descriptionFamilial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells (lymphocytes) called T cells, natural killer cells, B cells, and macrophages (histiocytes). Excessive amounts of immune system proteins called cytokines are also produced. This overactivation of the immune system causes fever and damages the liver and spleen, resulting in enlargement of these organs.Familial hemophagocytic lymphohistiocytosis also destroys blood-producing cells in the bone marrow, a process called hemophagocytosis. As a result, affected individuals have low numbers of red blood cells (anemia) and a reduction in the number of platelets, which are involved in clotting. A reduction in platelets may cause easy bruising and abnormal bleeding.The brain may also be affected in familial hemophagocytic lymphohistiocytosis. As a result, affected individuals may experience irritability, delayed closure of the bones of the skull in infants, neck stiffness, abnormal muscle tone, impaired muscle coordination, paralysis, blindness, seizures, and coma. In addition to neurological problems, familial hemophagocytic lymphohistiocytosis can cause abnormalities of the heart, kidneys, and other organs and tissues. Affected individuals also have an increased risk of developing cancers of blood-forming cells (leukemia and lymphoma).Signs and symptoms of familial hemophagocytic lymphohistiocytosis usually become apparent during infancy, although occasionally they appear later in life. They usually occur when the immune system launches an exaggerated response to an infection, but may also occur in the absence of infection. Without treatment, most people with familial hemophagocytic lymphohistiocytosis survive only a few months. ar Autosomal recessive PRF1 https://medlineplus.gov/genetics/gene/prf1 UNC13D https://medlineplus.gov/genetics/gene/unc13d STXBP2 https://www.ncbi.nlm.nih.gov/gene/6813 STX11 https://www.ncbi.nlm.nih.gov/gene/8676 Familial erythrophagocytic lymphohistiocytosis Familial hemophagocytic histiocytosis Familial hemophagocytic lymphocytosis Familial hemophagocytic reticulosis FEL FHL FHLH Hemophagocytic syndrome HPLH Primary hemophagocytic hymphohistiocytosis GTR C0272199 ICD-10-CM D76.1 MeSH D051359 OMIM 267700 OMIM 603552 OMIM 603553 OMIM 608898 OMIM 613101 SNOMED CT 398250003 2011-01 2020-08-18 Familial hyperaldosteronism https://medlineplus.gov/genetics/condition/familial-hyperaldosteronism descriptionFamilial hyperaldosteronism is a group of inherited conditions in which the adrenal glands, which are small glands located on top of each kidney, produce too much of the hormone aldosterone. Aldosterone helps control the amount of salt retained by the kidneys. Excess aldosterone causes the kidneys to retain more salt than normal, which in turn increases the body's fluid levels and blood pressure. People with familial hyperaldosteronism may develop severe high blood pressure (hypertension), often early in life. Without treatment, hypertension increases the risk of strokes, heart attacks, and kidney failure.Familial hyperaldosteronism is categorized into three types, distinguished by their clinical features and genetic causes. In familial hyperaldosteronism type I, hypertension generally appears in childhood to early adulthood and can range from mild to severe. This type can be treated with steroid medications called glucocorticoids, so it is also known as glucocorticoid-remediable aldosteronism (GRA). In familial hyperaldosteronism type II, hypertension usually appears in early to middle adulthood and does not improve with glucocorticoid treatment. In most individuals with familial hyperaldosteronism type III, the adrenal glands are enlarged up to six times their normal size. These affected individuals have severe hypertension that starts in childhood. The hypertension is difficult to treat and often results in damage to organs such as the heart and kidneys. Rarely, individuals with type III have milder symptoms with treatable hypertension and no adrenal gland enlargement.There are other forms of hyperaldosteronism that are not familial. These conditions are caused by various problems in the adrenal glands or kidneys. In some cases, a cause for the increase in aldosterone levels cannot be found. ad Autosomal dominant CYP11B1 https://medlineplus.gov/genetics/gene/cyp11b1 CYP11B2 https://medlineplus.gov/genetics/gene/cyp11b2 KCNJ5 https://medlineplus.gov/genetics/gene/kcnj5 Familial primary aldosteronism FH Hereditary aldosteronism Hyperaldosteronism, familial GTR C3713420 ICD-10-CM E26.02 MeSH D006929 OMIM 103900 OMIM 605635 OMIM 613677 SNOMED CT 703231005 2014-04 2023-08-21 Familial hypercholesterolemia https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia descriptionFamilial hypercholesterolemia is an inherited condition characterized by very high levels of cholesterol in the blood. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). The body needs this substance to build cell membranes, make certain hormones, and produce compounds that aid in fat digestion. In people with familial hypercholesterolemia, the body is unable to get rid of extra cholesterol, and it builds up in the blood. Too much cholesterol increases a person's risk of developing heart disease.People with familial hypercholesterolemia have a high risk of developing a form of heart disease called coronary artery disease at a young age. This condition occurs when excess cholesterol in the bloodstream is deposited on the inner walls of blood vessels, particularly the arteries that supply blood to the heart (coronary arteries). The abnormal buildup of cholesterol forms clumps (plaques) that narrow and harden artery walls. As the plaques get bigger, they can clog the arteries and restrict the flow of blood to the heart. The buildup of plaques in coronary arteries causes a form of chest pain called angina and greatly increases a person's risk of having a heart attack.Familial hypercholesterolemia can also cause health problems related to the buildup of excess cholesterol in tissues other than the heart and blood vessels. If cholesterol accumulates in the tissues that attach muscles to bones (tendons), it causes characteristic growths called tendon xanthomas. These growths most often affect the Achilles tendons, which attach the calf muscles to the heels, and tendons in the hands and fingers. Yellowish cholesterol deposits can develop under the skin of the eyelids and are known as xanthelasmata. Cholesterol can also accumulate at the edges of the clear, front surface of the eye (the cornea), leading to a gray-colored ring called an arcus cornealis. ar Autosomal recessive ad Autosomal dominant LDLR https://medlineplus.gov/genetics/gene/ldlr APOB https://medlineplus.gov/genetics/gene/apob LDLRAP1 https://medlineplus.gov/genetics/gene/ldlrap1 PCSK9 https://medlineplus.gov/genetics/gene/pcsk9 Familial hypercholesterolaemia FH GTR C0020445 GTR C1704417 GTR C1863512 GTR C1863551 ICD-10-CM E78.0 ICD-10-CM E78.01 MeSH D006937 OMIM 143890 OMIM 144010 OMIM 603776 OMIM 603813 SNOMED CT 238076009 SNOMED CT 238081000 SNOMED CT 397915002 SNOMED CT 398036000 2020-01 2022-05-16 Familial hypertrophic cardiomyopathy https://medlineplus.gov/genetics/condition/familial-hypertrophic-cardiomyopathy descriptionHypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle. When multiple members of a family have the condition, it is known as familial hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy also occurs in people with no family history; these cases are considered nonfamilial hypertrophic cardiomyopathy. In familial hypertrophic cardiomyopathy, cardiac thickening usually occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). In some people, thickening of the interventricular septum impedes the flow of oxygen-rich blood from the heart, which may lead to an abnormal heart sound during a heartbeat (heart murmur) and other signs and symptoms of the condition. Other affected individuals do not have physical obstruction of blood flow, but the pumping of blood is less efficient, which can also lead to symptoms of the condition. Familial hypertrophic cardiomyopathy often begins in adolescence or young adulthood, although it can develop at any time throughout life.The symptoms of familial hypertrophic cardiomyopathy are variable, even within the same family. Many affected individuals have no symptoms. Other people with familial hypertrophic cardiomyopathy may experience chest pain; shortness of breath, especially with physical exertion; a sensation of fluttering or pounding in the chest (palpitations); lightheadedness; dizziness; and fainting.While most people with familial hypertrophic cardiomyopathy are symptom-free or have only mild symptoms, this condition can have serious consequences. It can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation.Nonfamilial hypertrophic cardiomyopathy tends to be milder. This form typically begins later in life than familial hypertrophic cardiomyopathy, and affected individuals have a lower risk of serious cardiac events and sudden death than people with the familial form. ad Autosomal dominant PRKAG2 https://medlineplus.gov/genetics/gene/prkag2 MYH7 https://medlineplus.gov/genetics/gene/myh7 TTN https://medlineplus.gov/genetics/gene/ttn TNNI3 https://medlineplus.gov/genetics/gene/tnni3 TNNT2 https://medlineplus.gov/genetics/gene/tnnt2 MYBPC3 https://medlineplus.gov/genetics/gene/mybpc3 ACTC1 https://www.ncbi.nlm.nih.gov/gene/70 ACTN2 https://www.ncbi.nlm.nih.gov/gene/88 MYL2 https://www.ncbi.nlm.nih.gov/gene/4633 MYL3 https://www.ncbi.nlm.nih.gov/gene/4634 PLN https://www.ncbi.nlm.nih.gov/gene/5350 TPM1 https://www.ncbi.nlm.nih.gov/gene/7168 VCL https://www.ncbi.nlm.nih.gov/gene/7414 CSRP3 https://www.ncbi.nlm.nih.gov/gene/8048 TCAP https://www.ncbi.nlm.nih.gov/gene/8557 MYOZ2 https://www.ncbi.nlm.nih.gov/gene/51778 JPH2 https://www.ncbi.nlm.nih.gov/gene/57158 NEXN https://www.ncbi.nlm.nih.gov/gene/91624 CALR3 https://www.ncbi.nlm.nih.gov/gene/125972 Brock's disease Familial asymmetric septal hypertrophy HCM Hereditary ventricular hypertrophy Heritable hypertrophic cardiomyopathy Idiopathic hypertrophic subaortic stenosis Subaortic hypertrophic stenosis GTR C1860752 GTR C1861862 GTR C1861864 GTR C3495498 ICD-10-CM MeSH D024741 OMIM 115195 OMIM 115196 OMIM 115197 OMIM 192600 OMIM 600858 OMIM 607487 OMIM 608751 OMIM 608758 OMIM 612098 OMIM 612124 OMIM 613243 OMIM 613251 OMIM 613255 OMIM 613690 OMIM 613765 OMIM 613838 OMIM 613873 OMIM 613874 OMIM 613876 OMIM 614676 SNOMED CT 360465008 SNOMED CT 83978005 2023-01 2024-09-17 Familial hypobetalipoproteinemia https://medlineplus.gov/genetics/condition/familial-hypobetalipoproteinemia descriptionFamilial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. This condition is characterized by low levels of a fat-like substance called cholesterol in the blood. The severity of signs and symptoms experienced by people with FHBL vary widely. The most mildly affected individuals have few problems with absorbing fats from the diet and no related signs and symptoms. Many individuals with FHBL develop an abnormal buildup of fats in the liver called hepatic steatosis or fatty liver. In more severely affected individuals, fatty liver may progress to chronic liver disease (cirrhosis). Individuals with severe FHBL have greater difficulty absorbing fats as well as fat-soluble vitamins such as vitamin E and vitamin A. This difficulty in fat absorption leads to excess fat in the feces (steatorrhea). In childhood, these digestive problems can result in an inability to grow or gain weight at the expected rate (failure to thrive). ac Autosomal codominant APOB https://medlineplus.gov/genetics/gene/apob PCSK9 https://medlineplus.gov/genetics/gene/pcsk9 ANGPTL3 https://www.ncbi.nlm.nih.gov/gene/27329 FHBL Hypobetalipoproteinemia GTR C1857970 GTR C1862596 ICD-10-CM E78.6 MeSH D006995 OMIM 605019 OMIM 615558 SNOMED CT 190786004 SNOMED CT 238093009 SNOMED CT 238094003 SNOMED CT 60193003 2012-08 2021-05-18 Familial isolated hyperparathyroidism https://medlineplus.gov/genetics/condition/familial-isolated-hyperparathyroidism descriptionFamilial isolated hyperparathyroidism is an inherited condition that is characterized by overactive parathyroid glands (hyperparathyroidism). The four parathyroid glands are located in the neck. They release a hormone called parathyroid hormone that regulates the amount of calcium in the blood. In people with familial isolated hyperparathyroidism, too much parathyroid hormone is produced, and levels of calcium in the blood become elevated (hypercalcemia). Hypercalcemia causes many of the common signs and symptoms of familial isolated hyperparathyroidism, such as kidney stones, nausea, vomiting, high blood pressure (hypertension), thinning of the bones (osteoporosis), weakness, and fatigue.Many people with familial isolated hyperparathyroidism have one or more noncancerous (benign) tumors called adenomas. Typically, only one of the four parathyroid glands is affected, but sometimes more than one gland has an adenoma. Rarely, the tumor can become cancerous; this is called parathyroid carcinoma.In some cases, familial isolated hyperparathyroidism may not be diagnosed until adulthood. Often, the first indication of the condition is elevated calcium levels that are identified during a routine blood test, even though the affected individual may not yet have signs or symptoms of hyperparathyroidism or hypercalcemia. ad Autosomal dominant MEN1 https://medlineplus.gov/genetics/gene/men1 CDC73 https://medlineplus.gov/genetics/gene/cdc73 CASR https://medlineplus.gov/genetics/gene/casr GCM2 https://medlineplus.gov/genetics/gene/gcm2 FIHP GTR C1832615 GTR C1840402 GTR C4479229 ICD-10-CM E21.0 MeSH D049950 OMIM 145000 OMIM 239200 OMIM 617343 SNOMED CT 237653008 2026-01 2026-01-23 Familial isolated pituitary adenoma https://medlineplus.gov/genetics/condition/familial-isolated-pituitary-adenoma descriptionFamilial isolated pituitary adenoma (FIPA) is an inherited condition characterized by development of a noncancerous tumor in the pituitary gland (called a pituitary adenoma). The pituitary gland, which is found at the base of the brain, produces hormones that control many important body functions.Tumors that form in the pituitary gland can release excess levels of one or more hormones, although some tumors do not produce hormones (nonfunctioning pituitary adenomas). Those that do are typically distinguished by the particular hormones they produce. Prolactinomas are the most common tumors in FIPA. These tumors release prolactin, a hormone that stimulates breast milk production in females. Both women and men can develop prolactinomas, although they are more common in women. In women, these tumors may lead to changes in the menstrual cycle or difficulty becoming pregnant. Some affected women may produce breast milk, even though they are not pregnant or nursing. In men, prolactinomas may cause erectile dysfunction or decreased interest in sex. Rarely, affected men produce breast milk. Large prolactinomas can press on nearby tissues such as the nerves that carry information from the eyes to the brain (the optic nerves), causing problems with vision.Another type of tumor called somatotropinoma is also common in FIPA. These tumors release growth hormone (also called somatotropin), which promotes growth of the body. Somatotropinomas in children or adolescents can lead to increased height (gigantism), because the long bones of their arms and legs are still growing. In adults, growth of the long bones has stopped, but the tumors can cause overgrowth of the hands, feet, and face (acromegaly) as well as other tissues.Less common tumor types in FIPA include somatolactotropinomas, nonfunctioning pituitary adenomas, adrenocorticotropic hormone-secreting tumors (which cause a condition known as Cushing disease), thyrotropinomas, and gonadotropinomas. In a family with the condition, affected members can develop the same type of tumor (homogenous FIPA) or different types (heterogenous FIPA).In FIPA, pituitary tumors usually occur at a younger age than sporadic pituitary adenomas, which are not inherited. In general, FIPA tumors are also larger than sporadic pituitary tumors. Often, people with FIPA have macroadenomas, which are tumors larger than 10 millimeters.Familial pituitary adenomas can occur as one of many features in other inherited conditions such as multiple endocrine neoplasia type 1 and Carney complex; however, in FIPA, the pituitary adenomas are described as isolated because only the pituitary gland is affected. ad Autosomal dominant AIP https://medlineplus.gov/genetics/gene/aip FIPA GTR C4538355 MeSH D010911 OMIM 102200 SNOMED CT 702375004 2013-08 2020-08-18 Familial lipoprotein lipase deficiency https://medlineplus.gov/genetics/condition/familial-lipoprotein-lipase-deficiency descriptionFamilial lipoprotein lipase deficiency is an inherited condition that disrupts the normal breakdown of fats in the body, resulting in an increase of certain kinds of fats.People with familial lipoprotein lipase deficiency typically develop signs and symptoms before age 10, with one-quarter showing symptoms by age 1. The first symptom of this condition is usually abdominal pain, which can vary from mild to severe. The abdominal pain is often due to inflammation of the pancreas (pancreatitis). These episodes of pancreatitis begin as sudden (acute) attacks. If left untreated, pancreatitis can develop into a chronic condition that can damage the pancreas and, in rare cases, be life-threatening.Affected individuals may also have an enlarged liver and spleen (hepatosplenomegaly). The higher the levels of fat in the body, the larger the liver and spleen become. As fat levels rise, certain white blood cells called macrophages take in excess fat in an attempt to rid fat from the bloodstream. After taking in fat, the macrophages travel to the liver and spleen, where the fatty cells accumulate.Approximately half of individuals with familial lipoprotein lipase deficiency develop small yellow deposits of fat under the skin called eruptive xanthomas. These fat deposits most commonly appear on the trunk, buttocks, knees, and arms. Eruptive xanthomas are small (about 1 millimeter in diameter), but individual xanthomas can cluster together to form larger patches. They are generally not painful unless exposed to repeated friction or abrasion. Eruptive xanthomas begin to appear when fat intake increases and levels rise; the deposits disappear when fat intake slows and levels decrease.The blood of people with familial lipoprotein lipase deficiency can have a milky appearance due to its high fat content. When fat levels get very high in people with this condition, fats can accumulate in blood vessels in the tissue that lines the back of the eye (the retina). The fat buildup gives this tissue a pale pink appearance when examined (lipemia retinalis). This fat accumulation does not affect vision and will disappear once fats from the diet are reduced and levels in the body decrease.In people with familial lipoprotein lipase deficiency, increased fat levels can also cause neurological features, such as depression, memory loss, and mild intellectual decline (dementia). These problems are remedied when dietary fat levels normalize. ar Autosomal recessive LPL https://medlineplus.gov/genetics/gene/lpl Burger-Grutz syndrome Endogenous hypertriglyceridaemia Familial fat-induced hypertriglyceridemia Familial hyperchylomicronemia Familial LPL deficiency Hyperlipoproteinemia type I Hyperlipoproteinemia type Ia Lipase D deficiency LIPD deficiency Lipoprotein lipase deficiency, familial GTR C0023817 ICD-10-CM E78.3 MeSH D008072 OMIM 238600 SNOMED CT 238086005 SNOMED CT 267435002 SNOMED CT 275598004 SNOMED CT 403827000 2015-02 2020-08-18 Familial male-limited precocious puberty https://medlineplus.gov/genetics/condition/familial-male-limited-precocious-puberty descriptionFamilial male-limited precocious puberty is a condition that causes early sexual maturity in males; females are not affected. Boys with this disorder begin exhibiting the signs of puberty in early childhood, between the ages of 2 and 5. Signs of male puberty include a deepening voice, acne, increased body hair, underarm odor, growth of the penis and testes, and spontaneous erections. Changes in behavior, such as increased aggression and early interest in sex, may also occur. Without treatment, affected boys grow quickly at first, but they stop growing earlier than usual. As a result, they tend to be shorter in adulthood compared with other members of their family. ad Autosomal dominant LHCGR https://medlineplus.gov/genetics/gene/lhcgr Familial gonadotrophin-independent sexual precocity GIPP Gonadotrophin-independent precocious puberty Precocious pseudopuberty Pubertas praecox Testotoxicosis GTR C0342549 ICD-10-CM E29.0 MeSH D011629 OMIM 176410 SNOMED CT 725295005 2012-08 2024-09-18 Familial osteochondritis dissecans https://medlineplus.gov/genetics/condition/familial-osteochondritis-dissecans descriptionFamilial osteochondritis dissecans is a condition that affects the joints and is associated with abnormal cartilage. Cartilage is a tough but flexible tissue that covers the ends of the bones at joints and is also part of the developing skeleton. A characteristic feature of familial osteochondritis dissecans is areas of bone damage (lesions) caused by detachment of cartilage and a piece of the underlying bone from the end of the bone at a joint. People with this condition develop multiple lesions that affect several joints, primarily the knees, elbows, hips, and ankles. The lesions cause stiffness, pain, and swelling in the joint. Often, the affected joint feels like it catches or locks during movement. Other characteristic features of familial osteochondritis dissecans include short stature and development of a joint disorder called osteoarthritis at an early age. Osteoarthritis is characterized by the breakdown of joint cartilage and the underlying bone. It causes pain and stiffness and restricts the movement of joints.A similar condition called sporadic osteochondritis dissecans is associated with a single lesion in one joint, most often the knee. These cases may be caused by injury to or repetitive use of the joint (often sports-related). Some people with sporadic osteochondritis dissecans develop osteoarthritis in the affected joint, especially if the lesion occurs later in life after the bone has stopped growing. Short stature is not associated with this form of the condition. ad Autosomal dominant ACAN https://medlineplus.gov/genetics/gene/acan FOCD OCD OD Osteochondritis dissecans, short stature, and early-onset osteoarthritis GTR C3665488 ICD-10-CM M93.2 ICD-10-CM M93.20 ICD-10-CM M93.21 ICD-10-CM M93.211 ICD-10-CM M93.212 ICD-10-CM M93.219 ICD-10-CM M93.22 ICD-10-CM M93.221 ICD-10-CM M93.222 ICD-10-CM M93.229 ICD-10-CM M93.23 ICD-10-CM M93.231 ICD-10-CM M93.232 ICD-10-CM M93.239 ICD-10-CM M93.24 ICD-10-CM M93.241 ICD-10-CM M93.242 ICD-10-CM M93.249 ICD-10-CM M93.25 ICD-10-CM M93.251 ICD-10-CM M93.252 ICD-10-CM M93.259 ICD-10-CM M93.26 ICD-10-CM M93.261 ICD-10-CM M93.262 ICD-10-CM M93.269 ICD-10-CM M93.27 ICD-10-CM M93.271 ICD-10-CM M93.272 ICD-10-CM M93.279 ICD-10-CM M93.28 ICD-10-CM M93.29 MeSH D010008 OMIM 165800 SNOMED CT 82562007 2012-10 2023-03-21 Familial paroxysmal kinesigenic dyskinesia https://medlineplus.gov/genetics/condition/familial-paroxysmal-kinesigenic-dyskinesia descriptionFamilial paroxysmal kinesigenic dyskinesia is a disorder characterized by episodes of abnormal movement that range from mild to severe. In the condition name, the word paroxysmal indicates that the abnormal movements come and go over time, kinesigenic means that episodes are triggered by movement, and dyskinesia refers to involuntary movement of the body.People with familial paroxysmal kinesigenic dyskinesia experience episodes of irregular jerking or shaking movements that are brought on by sudden motion, such as standing up quickly or being startled. An episode may involve slow, prolonged muscle contractions (dystonia); small, fast, "dance-like" motions (chorea); writhing movements of the limbs (athetosis); or, rarely, flailing movements of the limbs (ballismus). Familial paroxysmal kinesigenic dyskinesia may affect one or both sides of the body. The type of abnormal movement varies among affected individuals, even among members of the same family. In many people with familial paroxysmal kinesigenic dyskinesia, a pattern of symptoms called an aura immediately precedes the episode. The aura is often described as a crawling or tingling sensation in the affected body part. Individuals with this condition do not lose consciousness during an episode and do not experience any symptoms between episodes.Individuals with familial paroxysmal kinesigenic dyskinesia usually first experience episodes during childhood or adolescence.  Episodes typically last less than five minutes, and the frequency of episodes ranges from one per month to 100 per day. In most affected individuals, episodes occur less often with age.In some people with familial paroxysmal kinesigenic dyskinesia the disorder begins in infancy with recurring seizures characteristic of those in a condition called benign familial infantile seizures. These seizures usually develop in the first year of life and stop by age 3. When benign familial infantile seizures are associated with familial paroxysmal kinesigenic dyskinesia, the condition is known as infantile convulsions and choreoathetosis (ICCA). In families with ICCA, some individuals develop only benign familial infantile seizures, some have only familial paroxysmal kinesigenic dyskinesia, and others have ICCA, which has features of both conditions. ad Autosomal dominant SLC2A1 https://medlineplus.gov/genetics/gene/slc2a1 PNKD https://medlineplus.gov/genetics/gene/pnkd KCNA1 https://medlineplus.gov/genetics/gene/kcna1 CHRNA4 https://medlineplus.gov/genetics/gene/chrna4 PRRT2 https://medlineplus.gov/genetics/gene/prrt2 DEPDC5 https://medlineplus.gov/genetics/gene/depdc5 Dystonia 10 Episodic kinesigenic dyskinesia Familial paroxysmal dystonia Paroxysmal kinesigenic choreoathetosis Paroxysmal kinesigenic dyskinesia GTR C4552000 MeSH D020820 OMIM 128200 SNOMED CT 609221008 2022-02 2022-02-11 Familial paroxysmal nonkinesigenic dyskinesia https://medlineplus.gov/genetics/condition/familial-paroxysmal-nonkinesigenic-dyskinesia descriptionFamilial paroxysmal nonkinesigenic dyskinesia is a disorder of the nervous system that causes episodes of involuntary movement. Paroxysmal indicates that the abnormal movements come and go over time. Nonkinesigenic means that episodes are not triggered by sudden movement. Dyskinesia broadly refers to involuntary movement of the body.People with familial paroxysmal nonkinesigenic dyskinesia experience episodes of abnormal movement that are brought on by alcohol, caffeine, stress, fatigue, menses, or excitement or develop without a known cause. Episodes are not induced by exercise or sudden movement and do not occur during sleep. An episode is characterized by irregular, jerking or shaking movements that range from mild to severe. In this disorder, the dyskinesia can include slow, prolonged contraction of muscles (dystonia); small, fast, "dance-like" motions (chorea); writhing movements of the limbs (athetosis); and, rarely, flailing movements of the limbs (ballismus). The dyskinesia also affects muscles in the torso and face. The type of abnormal movement varies among affected individuals, even among affected members of the same family. Individuals with familial paroxysmal nonkinesigenic dyskinesia do not lose consciousness during an episode. Most people do not experience any neurological symptoms between episodes.Individuals with familial paroxysmal nonkinesigenic dyskinesia usually begin to show signs and symptoms of the disorder during childhood or their early teens. Episodes typically last 1 to 4 hours, and the frequency of episodes ranges from several per day to one per year. In some affected individuals, episodes occur less often with age. ad Autosomal dominant PNKD https://medlineplus.gov/genetics/gene/pnkd Familial paroxysmal choreoathetosis Mount-Reback syndrome Nonkinesigenic choreoathetosis Paroxysmal dystonic choreoathetosis Paroxysmal nonkinesigenic dyskinesia PDC PNKD GTR C1869117 GTR C1970149 MeSH D020820 OMIM 118800 OMIM 611147 SNOMED CT 609218006 2017-08 2020-08-18 Familial partial lipodystrophy https://medlineplus.gov/genetics/condition/familial-partial-lipodystrophy descriptionFamilial partial lipodystrophy is a rare condition characterized by an abnormal distribution of fatty (adipose) tissue. Adipose tissue is normally found in many parts of the body, including beneath the skin and surrounding the internal organs. It stores fat as a source of energy and also provides cushioning. In people with familial partial lipodystrophy, adipose tissue is lost from the arms, legs, and hips, giving these parts of the body a very muscular appearance. The fat that cannot be stored in the limbs builds up around the face and neck, and inside the abdomen. Excess fat in these areas gives individuals an appearance described as "cushingoid," because it resembles the physical features associated with a hormonal disorder called Cushing disease. This abnormal fat distribution can begin anytime from childhood to adulthood.Abnormal storage of fat in the body can lead to health problems in adulthood. Many people with familial partial lipodystrophy develop insulin resistance, a condition in which the body's tissues cannot adequately respond to insulin, which is a hormone that normally helps to regulate blood sugar (glucose) levels. Insulin resistance may worsen to become a more serious disease called diabetes mellitus. Some people with familial partial lipodystrophy develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.Most people with familial partial lipodystrophy also have high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia), which can lead to inflammation of the pancreas (pancreatitis). Familial partial lipodystrophy can also cause an abnormal buildup of fats in the liver (hepatic steatosis), which can result in an enlarged liver (hepatomegaly) and abnormal liver function. After puberty, some affected females develop multiple cysts on the ovaries, an increased amount of body hair (hirsutism), and an inability to conceive (infertility), which are likely related to hormonal changes.Researchers have described at least six forms of familial partial lipodystrophy, which are distinguished by their genetic cause. The most common form of familial partial lipodystrophy is type 2, also called Dunnigan disease. In addition to the signs and symptoms described above, some people with this type of the disorder develop muscle weakness (myopathy), abnormalities of the heart muscle (cardiomyopathy), a form of heart disease called coronary artery disease, and problems with the electrical system that coordinates the heartbeat (the conduction system). ad Autosomal dominant ar Autosomal recessive LMNA https://medlineplus.gov/genetics/gene/lmna ADRA2A https://www.ncbi.nlm.nih.gov/gene/150 AKT2 https://www.ncbi.nlm.nih.gov/gene/208 LIPE https://www.ncbi.nlm.nih.gov/gene/3991 PLIN1 https://www.ncbi.nlm.nih.gov/gene/5346 PPARG https://www.ncbi.nlm.nih.gov/gene/5468 CIDEC https://www.ncbi.nlm.nih.gov/gene/63924 Dunnigan-Kobberling syndrome FPL Kobberling-Dunnigan syndrome Lipodystrophy, familial partial GTR C0271694 MeSH D052496 OMIM 151660 OMIM 604367 OMIM 608600 OMIM 613877 OMIM 615238 OMIM 615980 SNOMED CT 49292002 2016-09 2023-08-22 Familial pityriasis rubra pilaris https://medlineplus.gov/genetics/condition/familial-pityriasis-rubra-pilaris descriptionFamilial pityriasis rubra pilaris is a rare genetic condition that affects the skin. The name of the condition reflects its major features: The term "pityriasis" refers to scaling; "rubra" means redness; and "pilaris" suggests the involvement of hair follicles in this disorder. Affected individuals have a salmon-colored skin rash covered in fine scales. This rash occurs in patches all over the body, with distinct areas of unaffected skin between the patches. Affected individuals also develop bumps called follicular keratoses that occur around hair follicles. The skin on the palms of the hands and soles of the feet often becomes thick, hard, and callused, a condition known as palmoplantar keratoderma.Researchers have distinguished six types of pityriasis rubra pilaris based on the features of the disorder and the age at which signs and symptoms appear. The familial form is usually considered part of type V, which is also known as the atypical juvenile type. People with familial pityriasis rubra pilaris typically have skin abnormalities from birth or early childhood, and these skin problems persist throughout life. ad Autosomal dominant CARD14 https://medlineplus.gov/genetics/gene/card14 Familial PRP GTR C0032027 ICD-10-CM L44.0 MeSH D010916 OMIM 173200 SNOMED CT 238622008 2013-03 2020-08-18 Familial porencephaly https://medlineplus.gov/genetics/condition/familial-porencephaly descriptionFamilial porencephaly is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. In familial porencephaly, fluid-filled cysts develop in the brain (porencephaly) during fetal development or soon after birth. These cysts typically occur in only one side of the brain and vary in size. The cysts are thought to be the result of bleeding within the brain (hemorrhagic stroke). People with this condition also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).During infancy, people with familial porencephaly typically have paralysis affecting one side of the body (infantile hemiplegia). Affected individuals may also have recurrent seizures (epilepsy), migraine headaches, speech problems, intellectual disability, and uncontrolled muscle tensing (dystonia). Some people are severely affected, and others may have no symptoms related to the brain cysts. ad Autosomal dominant COL4A1 https://medlineplus.gov/genetics/gene/col4a1 Autosomal dominant porencephaly type 1 Infantile hemiplegia with porencephaly Porencephaly type 1 GTR C1867983 ICD-10-CM Q04.6 MeSH D065708 OMIM 175780 SNOMED CT 38353004 2011-09 2020-08-18 Familial restrictive cardiomyopathy https://medlineplus.gov/genetics/condition/familial-restrictive-cardiomyopathy descriptionFamilial restrictive cardiomyopathy is a genetic form of heart disease. For the heart to beat normally, the heart (cardiac) muscle must contract and relax in a coordinated way. Oxygen-rich blood from the lungs travels first through the upper chambers of the heart (the atria), and then to the lower chambers of the heart (the ventricles).In people with familial restrictive cardiomyopathy, the heart muscle is stiff and cannot fully relax after each contraction. Impaired muscle relaxation causes blood to back up in the atria and lungs, which reduces the amount of blood in the ventricles.Familial restrictive cardiomyopathy can appear anytime from childhood to adulthood. The first signs and symptoms of this condition in children are failure to gain weight and grow at the expected rate (failure to thrive), extreme tiredness (fatigue), and fainting. Children who are severely affected may also have abnormal swelling or puffiness (edema), increased blood pressure, an enlarged liver, an abnormal buildup of fluid in the abdominal cavity (ascites), and lung congestion. Some children with familial restrictive cardiomyopathy do not have any obvious signs or symptoms, but they may die suddenly due to heart failure. Without treatment, the majority of affected children survive only a few years after they are diagnosed.Adults with familial restrictive cardiomyopathy typically first develop shortness of breath, fatigue, and a reduced ability to exercise. Some individuals have an irregular heart beat (arrhythmia) and may also experience a sensation of fluttering or pounding in the chest (palpitations) and dizziness. Abnormal blood clots are commonly seen in adults with this condition. Without treatment, approximately one-third of adults with familial restrictive cardiomyopathy do not survive more than five years after diagnosis. ad Autosomal dominant MYH7 https://medlineplus.gov/genetics/gene/myh7 TNNI3 https://medlineplus.gov/genetics/gene/tnni3 DES https://medlineplus.gov/genetics/gene/des TNNT2 https://medlineplus.gov/genetics/gene/tnnt2 ACTC1 https://www.ncbi.nlm.nih.gov/gene/70 Cardiomyopathy, restrictive RCM GTR C0340429 GTR C1861861 GTR C2676271 ICD-10-CM I42.5 MeSH D002313 OMIM 115210 OMIM 609578 OMIM 612422 SNOMED CT 233878008 2011-01 2025-09-30 Familial thoracic aortic aneurysm and dissection https://medlineplus.gov/genetics/condition/familial-thoracic-aortic-aneurysm-and-dissection descriptionFamilial thoracic aortic aneurysm and dissection (familial TAAD) involves problems with the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Familial TAAD affects the upper part of the aorta, near the heart. This part of the aorta is called the thoracic aorta because it is located in the chest (thorax). Other vessels that carry blood from the heart to the rest of the body (arteries) can also be affected.In familial TAAD, the aorta can become weakened and stretched (aortic dilatation), which can lead to a bulge in the blood vessel wall (an aneurysm). Aortic dilatation may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection), allowing blood to flow abnormally between the layers. These aortic abnormalities are potentially life-threatening because they can decrease blood flow to other parts of the body such as the brain or other vital organs, or cause the aorta to break open (rupture).The occurrence and timing of these aortic abnormalities vary, even within the same affected family. They can begin in childhood or not occur until late in life. Aortic dilatation is generally the first feature of familial TAAD to develop, although in some affected individuals dissection occurs with little or no aortic dilatation.Aortic aneurysms usually have no symptoms. However, depending on the size, growth rate, and location of these abnormalities, they can cause pain in the jaw, neck, chest, or back; swelling in the arms, neck, or head; difficult or painful swallowing; hoarseness; shortness of breath; wheezing; a chronic cough; or coughing up blood. Aortic dissections usually cause severe, sudden chest or back pain, and may also result in unusually pale skin (pallor), a very faint pulse, numbness or tingling (paresthesias) in one or more limbs, or paralysis.Familial TAAD may not be associated with other signs and symptoms. However, some individuals in affected families show mild features of related conditions called Marfan syndrome or Loeys-Dietz syndrome. These features include tall stature, stretch marks on the skin, an unusually large range of joint movement (joint hypermobility), and either a sunken or protruding chest. Occasionally, people with familial TAAD develop aneurysms in the brain or in the section of the aorta located in the abdomen (abdominal aorta). Some people with familial TAAD have heart abnormalities that are present from birth (congenital). Affected individuals may also have a soft out-pouching in the lower abdomen (inguinal hernia), an abnormal curvature of the spine (scoliosis), or a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin (dermal capillaries). However, these conditions are also common in the general population. Depending on the genetic cause of familial TAAD in particular families, they may have an increased risk of developing blockages in smaller arteries, which can lead to heart attack and stroke. ad Autosomal dominant FBN1 https://medlineplus.gov/genetics/gene/fbn1 TGFBR2 https://medlineplus.gov/genetics/gene/tgfbr2 ACTA2 https://medlineplus.gov/genetics/gene/acta2 TGFBR1 https://medlineplus.gov/genetics/gene/tgfbr1 SMAD3 https://medlineplus.gov/genetics/gene/smad3 MYH11 https://medlineplus.gov/genetics/gene/myh11 MYLK https://www.ncbi.nlm.nih.gov/gene/4638 PRKG1 https://www.ncbi.nlm.nih.gov/gene/5592 Annuloaortic ectasia Congenital aneurysm of ascending aorta FAA Familial aortic aneurysm Familial aortic dissection Familial TAAD Familial thoracic aortic aneurysm FTAAD TAA TAAD Thoracic aortic aneurysm GTR C4707243 ICD-10-CM I71.0 ICD-10-CM I71.00 ICD-10-CM I71.01 ICD-10-CM I71.03 ICD-10-CM I71.1 ICD-10-CM I71.2 ICD-10-CM I71.5 ICD-10-CM I71.6 MeSH D017545 OMIM 132900 OMIM 607086 OMIM 607087 OMIM 611788 OMIM 613780 OMIM 615436 SNOMED CT 433068007 2015-01 2023-08-22 Fanconi anemia https://medlineplus.gov/genetics/condition/fanconi-anemia descriptionFanconi anemia is a condition that is characterized by bone marrow failure, physical differences, organ problems, and an increased risk of certain cancers.Approximately 90 percent of people with Fanconi anemia have impaired bone marrow function. Bone marrow primarily produces new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infections; and platelets, which are necessary for normal blood clotting. In people with Fanconi anemia, impaired bone marrow function leads to a decrease in the production of all blood cells (aplastic anemia). Affected individuals experience extreme tiredness (fatigue) due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia). People with Fanconi anemia may also develop myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally.People with Fanconi anemia often have growth problems before or after birth that often result in short stature. Affected individuals can also have irregular skin coloring such as unusually light-colored skin (hypopigmentation) or café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. People with Fanconi anemia can have skeletal problems that often include malformed thumbs or forearms or an unusually small head size (microcephaly).Problems in hormone-producing (endocrine) tissues are common in people with Fanconi anemia, including abnormally low levels of thyroid hormones (hypothyroidism), and high blood glucose levels (hyperglycemia). Individuals with Fanconi anemia can also have eye abnormalities such as small or abnormally shaped eyes or malformed or absent kidneys and other defects of the urinary tract.  Less frequent problems include gastrointestinal abnormalities, heart defects, brain abnormalities, and hearing loss. People with Fanconi anemia may have abnormal genitalia or malformations of the reproductive system, which can result in difficulty having biological children (infertility).Individuals with Fanconi anemia have an increased risk of developing a cancer of blood-forming cells called acute myeloid leukemia (AML). They are also at risk of developing tumors of the liver, gastrointestinal system, genital tract, or head and neck (known as head and neck squamous cell carcinoma). The likelihood of a person with Fanconi anemia developing one of these cancers is between 10 and 30 percent. ar Autosomal recessive x X-linked xr X-linked recessive ad Autosomal dominant BRCA1 https://medlineplus.gov/genetics/gene/brca1 RAD51 https://medlineplus.gov/genetics/gene/rad51 BRCA2 https://medlineplus.gov/genetics/gene/brca2 FANCA https://medlineplus.gov/genetics/gene/fanca FANCC https://medlineplus.gov/genetics/gene/fancc FANCG https://medlineplus.gov/genetics/gene/fancg ERCC4 https://www.ncbi.nlm.nih.gov/gene/2072 FANCD2 https://www.ncbi.nlm.nih.gov/gene/2177 FANCE https://www.ncbi.nlm.nih.gov/gene/2178 FANCB https://www.ncbi.nlm.nih.gov/gene/2187 FANCF https://www.ncbi.nlm.nih.gov/gene/2188 RAD51C https://www.ncbi.nlm.nih.gov/gene/5889 XRCC2 https://www.ncbi.nlm.nih.gov/gene/7516 MAD2L2 https://www.ncbi.nlm.nih.gov/gene/10459 UBE2T https://www.ncbi.nlm.nih.gov/gene/29089 FANCL https://www.ncbi.nlm.nih.gov/gene/55120 RFWD3 https://www.ncbi.nlm.nih.gov/gene/55159 FANCI https://www.ncbi.nlm.nih.gov/gene/55215 FANCM https://www.ncbi.nlm.nih.gov/gene/57697 PALB2 https://www.ncbi.nlm.nih.gov/gene/79728 FAAP100 https://www.ncbi.nlm.nih.gov/gene/80233 BRIP1 https://www.ncbi.nlm.nih.gov/gene/83990 SLX4 https://www.ncbi.nlm.nih.gov/gene/84464 FA Fanconi hypoplastic anemia Fanconi pancytopenia Fanconi panmyelopathy GTR C0015625 ICD-10-CM D61.09 MeSH D005199 OMIM 227650 SNOMED CT 30575002 2025-03 2025-05-19 Farber lipogranulomatosis https://medlineplus.gov/genetics/condition/farber-lipogranulomatosis descriptionFarber lipogranulomatosis is a rare inherited condition involving the breakdown and use of fats in the body (a process known as lipid metabolism). In affected individuals, lipids accumulate abnormally in cells and tissues throughout the body, particularly around the joints. Researchers had previously categorized Farber lipogranulomatosis into subtypes based on characteristic features, but the condition is now thought to be a spectrum of overlapping signs of symptoms.Three classic signs occur in Farber lipogranulomatosis: a hoarse voice or a weak cry, small lumps of fat under the skin and in other tissues (lipogranulomas), and swollen and painful joints. Signs and symptoms typically first develop in infancy.In addition to the classic signs, Farber lipogranulomatosis often affects multiple body systems. Affected individuals can have developmental delay, behavioral problems, or seizures. In severe cases, people experience progressive decline in brain and spinal cord (central nervous system) function, a buildup of fluid in the brain (hydrocephalus), loss (atrophy) of brain tissue, paralysis of the arms and legs (quadriplegia), loss of speech, or involuntary muscle jerks (myoclonus).  People with Farber lipogranulomatosis often have enlarged liver, spleen, and immune system tissues due to massive lipid deposits. Lipid deposits may also occur in the eyes and lungs, leading to vision problems and breathing difficulty. Affected individuals may develop thinning of the bones (osteoporosis) that worsens over time.Because of the severity of the signs and symptoms of the condition, individuals with Farber lipogranulomatosis generally do not survive past childhood. ar Autosomal recessive ASAH1 https://medlineplus.gov/genetics/gene/asah1 AC deficiency Acid ceramidase deficiency Acylsphingosine deacylase deficiency Ceramidase deficiency Farber disease Farber's disease Farber's lipogranulomatosis Farber-Uzman syndrome GTR C0268255 ICD-10-CM E75.29 MeSH D055577 OMIM 228000 SNOMED CT 79935000 2013-12 2022-05-23 Farsightedness https://medlineplus.gov/genetics/condition/farsightedness descriptionFarsightedness, also known as hyperopia, is an eye condition that causes blurry near vision. People who are farsighted have more trouble seeing things that are close up (such as when reading or using a computer) than things that are far away (such as when driving).For normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. Some people who are farsighted have eyeballs that are too short from front to back. Others have a cornea or lens that is abnormally shaped. These changes cause light entering the eye to be focused too far back, behind the retina instead of on its surface. It is this difference that causes nearby objects to appear blurry. In a person with this condition, one eye may be more farsighted than the other.If it is not treated with corrective lenses or surgery, farsightedness can lead to eye strain, excess tearing, squinting, frequent blinking, headaches, difficulty reading, and problems with hand-eye coordination. However, some children with the eye changes characteristic of farsightedness do not notice any blurring of their vision or related signs and symptoms early in life. Other parts of the visual system are able to compensate, at least temporarily, for the changes that would otherwise cause light to be focused in the wrong place.Most infants are born with a mild degree of farsightedness, which goes away on its own as the eyes grow. In some children, farsightedness persists or is more severe. Children with a severe degree of farsightedness, described as high hyperopia, are at an increased risk of developing other eye conditions, particularly "lazy eye" (amblyopia) and eyes that do not look in the same direction (strabismus). These conditions can cause significant visual impairment.In general, older adults also have difficulty seeing things close up; this condition is known as presbyopia. Presbyopia develops as the lens of the eye becomes thicker and less flexible with age and the muscles surrounding the lens weaken. Although it is sometimes described as "farsightedness," presbyopia is caused by a different mechanism than hyperopia and is considered a separate condition. u Pattern unknown MFRP https://www.ncbi.nlm.nih.gov/gene/83552 PRSS56 https://www.ncbi.nlm.nih.gov/gene/646960 Far-sightedness Farsighted Hypermetropia Hyperopia Long-sighted Long-sightedness ICD-10-CM H52.0 ICD-10-CM H52.00 ICD-10-CM H52.01 ICD-10-CM H52.02 ICD-10-CM H52.03 MeSH D006956 OMIM 238950 SNOMED CT 38101003 2018-09 2020-08-18 Fatty acid hydroxylase-associated neurodegeneration https://medlineplus.gov/genetics/condition/fatty-acid-hydroxylase-associated-neurodegeneration descriptionFatty acid hydroxylase-associated neurodegeneration (FAHN) is a progressive disorder of the nervous system (neurodegeneration) characterized by problems with movement and vision that begin during childhood or adolescence.Changes in the way a person walks (gait) and frequent falls are usually the first noticeable signs of FAHN. Affected individuals gradually develop extreme muscle stiffness (spasticity) and exaggerated reflexes. They typically have involuntary muscle cramping (dystonia), problems with coordination and balance (ataxia), or both. The movement problems worsen over time, and some people with this condition eventually require wheelchair assistance.People with FAHN often develop vision problems, which occur due to deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and difficulties with the muscles that control eye movement. Affected individuals may have a loss of sharp vision (reduced visual acuity), decreased field of vision, impaired color perception, eyes that do not look in the same direction (strabismus), rapid involuntary eye movements (nystagmus), or difficulty moving the eyes intentionally (supranuclear gaze palsy).Speech impairment (dysarthria) also occurs in FAHN, and severely affected individuals may lose the ability to speak. People with this disorder may also have difficulty chewing or swallowing (dysphagia). In severe cases, they may develop malnutrition and require a feeding tube. The swallowing difficulties can lead to a bacterial lung infection called aspiration pneumonia, which can be life-threatening. As the disorder progresses, some affected individuals experience seizures and a decline in intellectual function.Magnetic resonance imaging (MRI) of the brain in people with FAHN shows signs of iron accumulation, especially in an area of the brain called the globus pallidus, which is involved in regulating movement. Similar patterns of iron accumulation are seen in certain other neurological disorders such as infantile neuroaxonal dystrophy and pantothenate kinase-associated neurodegeneration. All these conditions belong to a class of disorders called neurodegeneration with brain iron accumulation (NBIA). ar Autosomal recessive FA2H https://medlineplus.gov/genetics/gene/fa2h Dysmyelinating leukodystrophy and spastic paraparesis FAHN Spastic paraplegia 35 GTR C3496228 MeSH D020271 OMIM 612319 SNOMED CT 702419001 2012-10 2020-08-18 Feingold syndrome https://medlineplus.gov/genetics/condition/feingold-syndrome descriptionFeingold syndrome is a disorder that affects many parts of the body. There are two types of Feingold syndrome, distinguished by their genetic cause; both types have similar features that can vary among affected individuals.Individuals with Feingold syndrome type 1 or type 2 have characteristic abnormalities of their fingers and toes. Almost all people with this condition have a specific hand abnormality called brachymesophalangy, which refers to shortening of the second and fifth fingers. Other common abnormalities include fifth fingers that curve inward (clinodactyly), underdeveloped thumbs (thumb hypoplasia), and fusion (syndactyly) of the second and third toes or the fourth and fifth toes.Additional common features of both types of Feingold syndrome include an unusually small head size (microcephaly), a small jaw (micrognathia), a narrow opening of the eyelids (short palpebral fissures), and mild to moderate learning disabilities. Less often, affected individuals have hearing loss, short stature, or kidney or heart abnormalities.People with Feingold syndrome type 1 are frequently born with a blockage in part of their digestive system called gastrointestinal atresia. In most cases, the blockage occurs in the esophagus (esophageal atresia) or in part of the small intestine (duodenal atresia). Individuals with type 2 do not have gastrointestinal atresias. ad Autosomal dominant MYCN https://medlineplus.gov/genetics/gene/mycn MIR17HG https://medlineplus.gov/genetics/gene/mir17hg 13 https://medlineplus.gov/genetics/chromosome/13 Brunner-Winter syndrome Microcephaly-mesobrachyphalangy-tracheoesophageal fistula (MMT) syndrome Microcephaly-oculo-digito-esophageal-duodenal (MODED) syndrome Oculo-digito-esophagoduodental (ODED) syndrome GTR C0796068 GTR C3280489 GTR C4551774 MeSH D030342 OMIM 164280 OMIM 614326 SNOMED CT 702431004 2018-06 2020-09-08 Fibrochondrogenesis https://medlineplus.gov/genetics/condition/fibrochondrogenesis descriptionFibrochondrogenesis is a very severe disorder of bone growth. Affected infants have a very narrow chest, which prevents the lungs from developing normally. Most infants with this condition are stillborn or die shortly after birth from respiratory failure. However, some affected individuals have lived into childhood.Fibrochondrogenesis is characterized by short stature (dwarfism) and other skeletal abnormalities. Affected individuals have shortened long bones in the arms and legs that are unusually wide at the ends (described as dumbbell-shaped). People with this condition also have a narrow chest with short, wide ribs and a round and prominent abdomen. The bones of the spine (vertebrae) are flattened (platyspondyly) and have a characteristic pinched or pear shape that is noticeable on x-rays. Other skeletal abnormalities associated with fibrochondrogenesis include abnormal curvature of the spine and underdeveloped hip (pelvic) bones.People with fibrochondrogenesis also have distinctive facial features. These include prominent eyes, low-set ears, a small mouth with a long upper lip, and a small chin (micrognathia). Affected individuals have a relatively flat-appearing midface, particularly a small nose with a flat nasal bridge and nostrils that open to the front rather than downward (anteverted nares). Vision problems, including severe nearsightedness (high myopia) and clouding of the lens of the eye (cataract), are common in those who survive infancy. Most affected individuals also have sensorineural hearing loss, which is caused by abnormalities of the inner ear. ar Autosomal recessive ad Autosomal dominant COL11A2 https://medlineplus.gov/genetics/gene/col11a2 COL11A1 https://medlineplus.gov/genetics/gene/col11a1 FBCG1 FBCG2 Fibrochondrogenesis-1 Fibrochondrogenesis-2 GTR C3278138 GTR C3281128 MeSH D000015 MeSH D004392 OMIM 228520 OMIM 614524 SNOMED CT 17144009 2016-04 2020-08-18 Fibrodysplasia ossificans progressiva https://medlineplus.gov/genetics/condition/fibrodysplasia-ossificans-progressiva descriptionFibrodysplasia ossificans progressiva is a disorder in which muscle tissue and connective tissue such as tendons and ligaments are gradually replaced by bone (ossified), forming bone outside the skeleton (extra-skeletal or heterotopic bone) that limits movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs.Extra-skeletal bone formation causes progressive loss of mobility as the joints become affected. Inability to fully open the mouth may cause difficulty in speaking and eating. Over time, people with this disorder may experience malnutrition due to their eating problems. They may also have breathing difficulties as a result of extra bone formation around the rib cage that restricts expansion of the lungs.Any trauma to the muscles of an individual with fibrodysplasia ossificans progressiva, such as a fall or invasive medical procedures, may trigger episodes of muscle swelling and inflammation (myositis) followed by more rapid ossification in the injured area. Flare-ups may also be caused by viral illnesses such as influenza.People with fibrodysplasia ossificans progressiva are generally born with malformed big toes. This abnormality of the big toes is a characteristic feature that helps to distinguish this disorder from other bone and muscle problems. Affected individuals may also have short thumbs and other skeletal abnormalities. ad Autosomal dominant ACVR1 https://medlineplus.gov/genetics/gene/acvr1 FOP Myositis ossificans Myositis ossificans progressiva Progressive myositis ossificans Progressive ossifying myositis GTR C0016037 ICD-10-CM M61.1 ICD-10-CM M61.10 ICD-10-CM M61.11 ICD-10-CM M61.111 ICD-10-CM M61.112 ICD-10-CM M61.119 ICD-10-CM M61.12 ICD-10-CM M61.121 ICD-10-CM M61.122 ICD-10-CM M61.129 ICD-10-CM M61.13 ICD-10-CM M61.131 ICD-10-CM M61.132 ICD-10-CM M61.139 ICD-10-CM M61.14 ICD-10-CM M61.141 ICD-10-CM M61.142 ICD-10-CM M61.143 ICD-10-CM M61.144 ICD-10-CM M61.145 ICD-10-CM M61.146 ICD-10-CM M61.15 ICD-10-CM M61.151 ICD-10-CM M61.152 ICD-10-CM M61.159 ICD-10-CM M61.16 ICD-10-CM M61.161 ICD-10-CM M61.162 ICD-10-CM M61.169 ICD-10-CM M61.17 ICD-10-CM M61.171 ICD-10-CM M61.172 ICD-10-CM M61.173 ICD-10-CM M61.174 ICD-10-CM M61.175 ICD-10-CM M61.176 ICD-10-CM M61.177 ICD-10-CM M61.178 ICD-10-CM M61.179 ICD-10-CM M61.18 ICD-10-CM M61.19 MeSH D009221 OMIM 135100 SNOMED CT 82725007 2007-08 2022-07-15 Fibromyalgia https://medlineplus.gov/genetics/condition/fibromyalgia descriptionFibromyalgia is a common condition characterized by long-lasting (chronic) pain affecting many areas of the body. The pain is associated with tenderness that occurs with touch or pressure on the muscles, joints, or skin. Some affected individuals also report numbness, tingling, or a burning sensation (paresthesia) in the arms and legs.Other signs and symptoms of fibromyalgia include excessive tiredness (exhaustion); sleep problems, such as waking up feeling unrefreshed; and problems with memory or thinking clearly. People with fibromyalgia often report additional types of pain, including headaches, back and neck pain, sore throat, pain or clicking in the jaw (temporomandibular joint dysfunction), and stomach pain or digestive disorders such as irritable bowel syndrome. They have an increased likelihood of developing mood or psychiatric disorders including depression, anxiety, and obsessive-compulsive disorder. However, many people with fibromyalgia do not have a mental health condition.The major signs and symptoms of fibromyalgia can occur by themselves or together with another chronic pain condition such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, or systemic lupus erythematosus. u Pattern unknown COMT https://medlineplus.gov/genetics/gene/comt ADRB2 https://www.ncbi.nlm.nih.gov/gene/154 HTR2A https://www.ncbi.nlm.nih.gov/gene/3356 SLC6A4 https://www.ncbi.nlm.nih.gov/gene/6532 TAAR1 https://www.ncbi.nlm.nih.gov/gene/134864 Diffuse myofascial pain syndrome Fibromyalgia syndrome Fibromyalgia-fibromyositis syndrome Fibromyositis Fibrositis FMS Myofascial pain syndrome ICD-10-CM M79.7 MeSH D005356 SNOMED CT 203082005 2018-06 2020-09-18 Fibronectin glomerulopathy https://medlineplus.gov/genetics/condition/fibronectin-glomerulopathy descriptionFibronectin glomerulopathy is a kidney disease that usually develops between early and mid-adulthood but can occur at any age. It eventually leads to irreversible kidney failure (end-stage renal disease).Individuals with fibronectin glomerulopathy usually have blood and excess protein in their urine (hematuria and proteinuria, respectively). They also have high blood pressure (hypertension). Some affected individuals develop renal tubular acidosis, which occurs when the kidneys are unable to remove enough acid from the body and the blood becomes too acidic.The kidneys of people with fibronectin glomerulopathy have large deposits of the protein fibronectin-1 in structures called glomeruli. These structures are clusters of tiny blood vessels in the kidneys that filter waste products from blood. The waste products are then released in urine. The fibronectin-1 deposits impair the glomeruli's filtration ability.Fifteen to 20 years following the appearance of signs and symptoms, individuals with fibronectin glomerulopathy often develop end-stage renal disease. Affected individuals may receive treatment in the form of a kidney transplant; in some cases, fibronectin glomerulopathy comes back (recurs) following transplantation. ad Autosomal dominant FN1 https://medlineplus.gov/genetics/gene/fn1 Familial glomerular nephritis with fibronectin deposits Familial lobular glomerulopathy GFND Glomerulopathy with fibronectin deposits Glomerulopathy with giant fibrillar deposits GTR C1866075 ICD-10-CM N07.5 MeSH D015432 OMIM 137950 OMIM 601894 SNOMED CT 236535001 2015-04 2020-08-18 Fish-eye disease https://medlineplus.gov/genetics/condition/fish-eye-disease descriptionFish-eye disease, also called partial LCAT deficiency, is a disorder that causes the clear front surface of the eyes (the corneas) to gradually become cloudy. The cloudiness, which generally first appears in adolescence or early adulthood, consists of small grayish dots of cholesterol (opacities) distributed across the corneas. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals; it aids in many functions of the body but can become harmful in excessive amounts. As fish-eye disease progresses, the corneal cloudiness worsens and can lead to severely impaired vision. ar Autosomal recessive LCAT https://medlineplus.gov/genetics/gene/lcat Alpha-LCAT deficiency Alpha-lecithin:cholesterol acyltransferase deficiency Dyslipoproteinemic corneal dystrophy FED LCATA deficiency Partial LCAT deficiency GTR C0342895 MeSH D007863 OMIM 136120 SNOMED CT 238092004 2013-08 2020-08-18 Floating-Harbor syndrome https://medlineplus.gov/genetics/condition/floating-harbor-syndrome descriptionFloating-Harbor syndrome is a disorder involving short stature, slowing of the mineralization of the bones (delayed bone age), delayed speech development, and characteristic facial features. The condition is named for the hospitals where it was first described, the Boston Floating Hospital and Harbor General Hospital in Torrance, California.Growth deficiency in people with Floating-Harbor syndrome generally becomes apparent in the first year of life, and affected individuals are usually among the shortest 5 percent of their age group. Bone age is delayed in early childhood; for example, an affected 3-year-old child may have bones more typical of a child of 2. However, bone age is usually normal by age 6 to 12.Delay in speech development (expressive language delay) may be severe in Floating-Harbor syndrome, and language impairment can lead to problems in verbal communication. Most affected individuals also have mild intellectual disability. Their development of motor skills, such as sitting and crawling, is similar to that of other children their age.Typical facial features in people with Floating-Harbor syndrome include a triangular face; a low hairline; deep-set eyes; long eyelashes; a large, distinctive nose with a low-hanging separation (overhanging columella) between large nostrils; a shortened distance between the nose and upper lip (a short philtrum); and thin lips. As affected children grow and mature, the nose becomes more prominent.Additionally some affected individuals have finger abnormalities that include short fingers (brachydactyly), widened and rounded tips of the fingers (clubbing), and curved pinky fingers (fifth finger clinodactyly). Other features of Floating-Harbor syndrome can include an unusually high-pitched voice and, in males, undescended testes (cryptorchidism). ad Autosomal dominant SRCAP https://medlineplus.gov/genetics/gene/srcap FHS FLHS Leisti-Hollander-Rimoin syndrome Pelletier-Leisti syndrome GTR C0729582 MeSH D000015 OMIM 136140 SNOMED CT 312214005 2012-12 2020-08-18 Focal dermal hypoplasia https://medlineplus.gov/genetics/condition/focal-dermal-hypoplasia descriptionFocal dermal hypoplasia is a genetic disorder that primarily affects the skin, skeleton, eyes, and face. About 90 percent of affected individuals are female. Males usually have milder signs and symptoms than females. Although intelligence is typically unaffected, some individuals have intellectual disability.People with focal dermal hypoplasia have skin abnormalities present from birth, such as streaks of very thin skin (dermal hypoplasia), yellowish-pink nodules of fat under the skin, areas where the top layers of skin are absent (cutis aplasia), small clusters of veins on the surface of the skin (telangiectases), and streaks of slightly darker or lighter skin. These skin changes may cause pain, itching, irritation, or lead to skin infections. Wart-like growths called papillomas are usually not present at birth but develop with age. Papillomas typically form around the nostrils, lips, anus, and female genitalia. They may also be present in the throat, specifically in the esophagus or larynx, and can cause problems with swallowing, breathing, or sleeping. Papillomas can usually be surgically removed if necessary. Affected individuals may have small, ridged fingernails and toenails. Hair on the scalp can be sparse and brittle or absent.Many individuals with focal dermal hypoplasia have hand and foot abnormalities, including missing fingers or toes (oligodactyly), webbed or fused fingers or toes (syndactyly), and a deep split in the hands or feet with missing fingers or toes and fusion of the remaining digits (ectrodactyly). X-rays can show streaks of altered bone density, called osteopathia striata, that do not cause any symptoms in people with focal dermal hypoplasia.Eye abnormalities are common in individuals with focal dermal hypoplasia, including small eyes (microphthalmia), absent or severely underdeveloped eyes (anophthalmia), and problems with the tear ducts. Affected individuals may also have incomplete development of the light-sensitive tissue at the back of the eye (retina) or the nerve that relays visual information from the eye to the brain (optic nerve). This abnormal development of the retina and optic nerve can result in a gap or split in these structures, which is called a coloboma. Some of these eye abnormalities do not impair vision, while others can lead to low vision or blindness.People with focal dermal hypoplasia may have distinctive facial features. Affected individuals often have a pointed chin, small ears, notched nostrils, and a slight difference in the size and shape of the right and left sides of the face (facial asymmetry). These facial characteristics are typically very subtle. An opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate) may also be present.About half of individuals with focal dermal hypoplasia have abnormalities of their teeth, especially the hard, white material that forms the protective outer layer of each tooth (enamel). Less commonly, abnormalities of the kidneys and gastrointestinal system are present. The kidneys may be fused together, which predisposes affected individuals to kidney infections but does not typically cause significant health problems. The main gastrointestinal abnormality that occurs in people with focal dermal hypoplasia is an omphalocele, which is an opening in the wall of the abdomen that allows the abdominal organs to protrude through the navel. The signs and symptoms of focal dermal hypoplasia vary widely, although almost all affected individuals have skin abnormalities. xd X-linked dominant PORCN https://medlineplus.gov/genetics/gene/porcn Goltz syndrome Goltz-Gorlin syndrome GTR C0016395 MeSH D005489 OMIM 305600 SNOMED CT 205573006 SNOMED CT 2298005 2009-05 2020-08-18 Fragile X syndrome https://medlineplus.gov/genetics/condition/fragile-x-syndrome descriptionFragile X syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females.Affected individuals usually have delayed development of speech and language by age 2. Most males with fragile X syndrome have mild to moderate intellectual disability, while about one-third of affected females are intellectually disabled. Children with fragile X syndrome may also have anxiety and hyperactive behavior such as fidgeting or impulsive actions. They may have attention deficit disorder (ADD), which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. About one-third of individuals with fragile X syndrome have features of autism spectrum disorder that affect communication and social interaction. Seizures occur in about 15 percent of males and about 5 percent of females with fragile X syndrome.Most males and about half of females with fragile X syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, a prominent jaw and forehead, unusually flexible fingers, flat feet, and in males, enlarged testicles (macroorchidism) after puberty. xd X-linked dominant FMR1 https://medlineplus.gov/genetics/gene/fmr1 Fra(X) syndrome FRAXA syndrome FXS Marker X syndrome Martin-Bell syndrome X-linked mental retardation and macroorchidism GTR C0016667 ICD-10-CM Q99.2 MeSH D005600 OMIM 309550 SNOMED CT 613003 2020-04 2020-08-18 Fragile X-associated primary ovarian insufficiency https://medlineplus.gov/genetics/condition/fragile-x-associated-primary-ovarian-insufficiency descriptionFragile X-associated primary ovarian insufficiency (FXPOI) is a condition that affects women and is characterized by reduced function of the ovaries. The ovaries are the female reproductive organs in which egg cells are produced. As a form of primary ovarian insufficiency, FXPOI can cause irregular menstrual cycles, early menopause, an inability to have children (infertility), and elevated levels of a hormone known as follicle stimulating hormone (FSH). FSH is produced in both males and females and helps regulate the development of reproductive cells (eggs in females and sperm in males). In females, the level of FSH rises and falls, but overall it increases as a woman ages. In younger women, elevated levels may indicate early menopause and fertility problems.The severity of FXPOI is variable. The most severely affected women have overt POI (formerly called premature ovarian failure). These women have irregular or absent menstrual periods and elevated FSH levels before age 40. Overt POI often causes infertility. Other women have occult POI; they have normal menstrual periods but reduced fertility, and they may have elevated levels of FSH (in which case, it is called biochemical POI). The reduction in ovarian function caused by FXPOI results in low levels of the hormone estrogen, which leads to many of the common signs and symptoms of menopause, such as hot flashes, insomnia, and thinning of the bones (osteoporosis). Women with FXPOI undergo menopause an average of 5 years earlier than women without the condition. xd X-linked dominant FMR1 https://medlineplus.gov/genetics/gene/fmr1 FMR1-related primary ovarian insufficiency FXPOI Premature ovarian failure 1 X-linked hypergonadotropic ovarian failure GTR C4552079 MeSH D016649 OMIM 311360 SNOMED CT 237788002 2020-04 2023-03-21 Fragile X-associated tremor/ataxia syndrome https://medlineplus.gov/genetics/condition/fragile-x-associated-tremor-ataxia-syndrome descriptionFragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by problems with movement and thinking ability (cognition). FXTAS is a late-onset disorder, usually occurring after age 50, and its signs and symptoms worsen with age. This condition affects males more frequently and severely than females. Affected individuals have areas of damage in the part of the brain that controls movement (the cerebellum) and in a type of brain tissue known as white matter, which can be seen with magnetic resonance imaging (MRI). This damage leads to the movement problems and other impairments associated with FXTAS.The characteristic features of FXTAS are intention tremor, which is trembling or shaking of a limb when trying to perform a voluntary movement such as reaching for an object, and problems with coordination and balance (ataxia). Typically, intention tremors will develop first, followed a few years later by ataxia, although not everyone with FXTAS has both features. Many affected individuals develop other movement problems, such as a pattern of movement abnormalities known as parkinsonism, which includes tremors when not moving (resting tremor), rigidity, and unusually slow movement (bradykinesia). In addition, affected individuals may have reduced sensation, numbness or tingling, pain, or muscle weakness in the lower limbs (peripheral neuropathy). Some people with FXTAS experience problems with the autonomic nervous system, which controls involuntary body functions, leading to the inability to control the bladder or bowel.People with FXTAS commonly have cognitive disabilities. They may develop short-term memory loss and loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Loss of this function impairs skills such as impulse control, self-monitoring, focusing attention appropriately, and cognitive flexibility. Many people with FXTAS experience anxiety, depression, moodiness, or irritability.Some women develop immune system disorders, such as hypothyroidism or fibromyalgia, before the signs and symptoms of FXTAS appear. xd X-linked dominant FMR1 https://medlineplus.gov/genetics/gene/fmr1 Fragile X tremor/ataxia syndrome FXTAS GTR C1839780 MeSH D002526 OMIM 300623 SNOMED CT 448045004 2020-04 2023-03-21 Fragile XE syndrome https://medlineplus.gov/genetics/condition/fragile-xe-syndrome descriptionFragile XE syndrome is a genetic disorder that impairs thinking ability and cognitive functioning. Most affected individuals have mild intellectual disabilities. In some people with this condition, cognitive function is described as borderline, which means that it is below average but not low enough to be classified as an intellectual disability. Females are rarely diagnosed with fragile XE syndrome, likely because the signs and symptoms are so mild, if present at all.Learning disabilities are the most common sign of impaired cognitive function in people with fragile XE syndrome. The learning disabilities are likely a result of communication and behavioral problems, including delayed speech, poor writing skills, hyperactivity, and a short attention span. Some affected individuals display autistic behaviors, such as hand flapping, repetitive behaviors, and intense interest in a particular subject. Unlike some other forms of intellectual disability, cognitive functioning remains steady and does not decline with age in fragile XE syndrome. x X-linked AFF2 https://medlineplus.gov/genetics/gene/aff2 FRAXE intellectual deficit FRAXE intellectual disability FRAXE syndrome GTR C0751157 MeSH D038901 OMIM 309548 SNOMED CT 254288000 2014-01 2025-03-06 Fraser syndrome https://medlineplus.gov/genetics/condition/fraser-syndrome descriptionFraser syndrome is a rare disorder that affects development starting before birth. Characteristic features of this condition include eyes that are completely covered by skin and usually malformed (cryptophthalmos), fusion of the skin between the fingers and toes (cutaneous syndactyly), and abnormalities of the genitalia and the urinary tract (genitourinary anomalies). Other tissues and organs can also be affected. Depending on the severity of the signs and symptoms, Fraser syndrome can be fatal before or shortly after birth; less severely affected individuals can live into childhood or adulthood.Cryptophthalmos is the most common abnormality in people with Fraser syndrome. Both eyes are usually completely covered by skin, but in some cases, only one eye is covered or one or both eyes are partially covered. In cryptophthalmos, the eyes can also be malformed; for example, the eyeballs may be fused to the skin covering them, or they may be small (microphthalmia) or missing (anophthalmia). Eye abnormalities typically lead to impairment or loss of vision in people with Fraser syndrome. Affected individuals can have other problems related to abnormal eye development, including missing eyebrows or eyelashes or a patch of hair extending from the side hairline to the eyebrow.Cutaneous syndactyly typically occurs in both the hands and the feet in Fraser syndrome. In most people with this feature, the skin between the middle three fingers and toes are fused, but the other digits can also be involved. Other abnormalities of the hands and feet can occur in people with Fraser syndrome.Individuals with Fraser syndrome can have abnormalities of the genitalia, such as an enlarged clitoris in females or undescended testes (cryptorchidism) in males. Some affected individuals have external genitalia that do not appear clearly female or male.The most common urinary tract abnormality in Fraser syndrome is the absence of one or both kidneys (renal agenesis). Affected individuals can have other kidney problems or abnormalities of the bladder and other parts of the urinary tract.A variety of other signs and symptoms can be involved in Fraser syndrome, including heart malformations or abnormalities of the voicebox (larynx) or other parts of the respiratory tract. Some affected individuals have facial abnormalities, including ear or nose abnormalities or an opening in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). ar Autosomal recessive FRAS1 https://medlineplus.gov/genetics/gene/fras1 FREM2 https://medlineplus.gov/genetics/gene/frem2 GRIP1 https://medlineplus.gov/genetics/gene/grip1 Cryptophthalmos syndactyly syndrome Cryptophthalmos syndrome Cryptophthalmos with other malformations Fraser's syndrome Fraser-Francois syndrome Meyer-Schwickerath syndrome Ullrich-Feichtiger syndrome GTR C4551480 ICD-10-CM MeSH D058497 OMIM 219000 SNOMED CT 204102004 2014-06 2023-10-27 Frasier syndrome https://medlineplus.gov/genetics/condition/frasier-syndrome descriptionFrasier syndrome is a condition that affects the kidneys and genitalia.Frasier syndrome is characterized by kidney disease that begins in early childhood. Affected individuals have a condition called focal segmental glomerulosclerosis, in which scar tissue forms in some glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Frasier syndrome, this condition often leads to kidney failure by adolescence.Although males with Frasier syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female or the genitalia appear female-typical. The internal reproductive organs (gonads) are typically undeveloped and referred to as streak gonads. These abnormal gonads are nonfunctional and often become cancerous, so they are usually removed surgically early in life.Affected females usually have normal genitalia and gonads and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome. ad Autosomal dominant WT1 https://medlineplus.gov/genetics/gene/wt1 FS GTR C0950122 ICD-10-CM MeSH D052159 OMIM 136680 SNOMED CT 445431000 2013-03 2023-10-27 Free sialic acid storage disorder https://medlineplus.gov/genetics/condition/free-sialic-acid-storage-disorder descriptionFree sialic acid storage disorder (FSASD) is an inherited condition that primarily affects the brain and spinal cord (central nervous system). The signs and symptoms of FSASD can vary from person to person, and the condition is often divided into three forms based on the severity of these features. The severe form of FSASD is called infantile free sialic acid storage disease or ISSD. The signs and symptoms of this form typically appear in infancy. In some cases, a condition called hydrops fetalis, in which excess fluid accumulates in the body, occurs before or soon after birth. Babies with the severe form of FSASD typically have severe developmental delays, weak muscle tone (hypotonia), and an inability to gain weight and grow at the expected rate (failure to thrive). Additional signs and symptoms may include unusual facial features that are often described as "coarse," bone malformations, an enlarged liver and spleen (hepatosplenomegaly), an enlarged heart (cardiomegaly), and seizures. Respiratory infections are common and can be life-threatening; children with the severe form of FSASD typically only survive into early childhood.Children with the least severe form of FSASD, also called Salla disease, may not have the signs and symptoms of the condition at birth. The age at which people develop the signs and symptoms of Salla disease can vary, but hypotonia usually appears during the first year of life. People with Salla disease typically have intellectual disabilities and developmental delays, which can make it difficult for them to learn to walk and talk. Additional signs and symptoms include problems with movement and balance (ataxia); abnormal tensing of the muscles (spasticity); and involuntary slow, writhing movements of the limbs (athetosis). Signs and symptoms typically worsen over time. Although life expectancy may be shortened, individuals with Salla disease often survive into adulthood.People with the intermediate form of FSASD, also called intermediate severe Salla disease, have signs and symptoms that are typically more severe than the signs and symptoms seen in people with Salla disease and less severe than those seen in people with ISSD. ar Autosomal recessive SLC17A5 https://medlineplus.gov/genetics/gene/slc17a5 FSASD Sialic acid storage disease GTR C1096902 GTR C1096903 MeSH D029461 OMIM 269920 OMIM 604369 SNOMED CT 238051008 SNOMED CT 34566007 SNOMED CT 87074006 2024-09 2025-04-03 Freeman-Sheldon syndrome https://medlineplus.gov/genetics/condition/freeman-sheldon-syndrome descriptionFreeman-Sheldon syndrome (also known as Freeman-Burian syndrome) is a condition that primarily affects muscles in the face and skull (craniofacial muscles) and can often affect joints in the hands and feet. The condition is characterized by abnormalities known as contractures, which result from permanent tightening of muscles, skin, tendons, and surrounding tissues, and restrict movement of the affected body part. In Freeman-Sheldon syndrome, contractures in the face lead to a distinctive facial appearance including a small mouth (microstomia) with pursed lips, giving the appearance of whistling. For this reason, Freeman-Sheldon syndrome is sometimes called "whistling face syndrome." Other facial features common in this condition include a chin dimple shaped like an "H" or "V" and unusually deep folds in the skin between the nose and the corners of the mouth (nasolabial folds).People with Freeman-Sheldon syndrome may also have a variety of other facial features, such as a prominent forehead and brow ridges, a sunken appearance of the middle of the face (midface hypoplasia), a short nose, a long area between the nose and mouth (philtrum), and full cheeks. Affected individuals may have a number of abnormalities that affect the eyes. These features can include widely spaced eyes (hypertelorism), deep-set eyes, outside corners of the eyes that point downward (down-slanting palpebral fissures), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and eyes that do not look in the same direction (strabismus).Other features that can occur in Freeman-Sheldon syndrome include an unusually small tongue (microglossia) and jaw (micrognathia) and a high arch in the roof of the mouth (high-arched palate). People with Freeman-Sheldon syndrome may have difficulty swallowing (dysphagia), a failure to gain weight and grow at the expected rate (failure to thrive), and breathing complications that may be life-threatening. Speech problems or hearing impairment can also occur in people with this disorder.In people with Freeman-Sheldon syndrome, contractures in the hands and feet can lead to permanently bent fingers and toes (camptodactyly), a hand deformity in which all of the fingers are angled outward toward the fifth finger (ulnar deviation, also called "windmill vane hand"), and inward- and downward-turning feet (clubfoot). Less commonly, contractures affect the hips, knees, shoulders, or elbows.People with Freeman-Sheldon syndrome may also have abnormalities of the spine, ribs, or chest. Many affected individuals have abnormal side-to-side or front-to-back curvature of the spine (scoliosis or kyphosis) or an abnormally curved lower back (lordosis). In many affected individuals, the muscles between the ribs do not function properly, which can impair breathing or coughing. The ribs or breastbone (sternum) may be abnormally shaped in people with this condition.Intelligence is unaffected in most people with Freeman-Sheldon syndrome, but development of normal milestones may be delayed due to physical abnormalities. ad Autosomal dominant ar Autosomal recessive MYH3 https://medlineplus.gov/genetics/gene/myh3 Craniocarpotarsal dysplasia Craniocarpotarsal dystrophy DA2A Distal arthrogryposis, type 2A FBS Freeman-Burian syndrome FSS Whistling face syndrome Whistling face-windmill vane hand syndrome GTR C0265224 MeSH D003394 OMIM 193700 SNOMED CT 52616002 2010-09 2021-10-28 Friedreich ataxia https://medlineplus.gov/genetics/condition/friedreich-ataxia descriptionFriedreich ataxia is a genetic condition that affects the nervous system and causes movement problems. People with this condition develop impaired muscle coordination (ataxia) that worsens over time. Other features of this condition include the gradual loss of strength and sensation in the arms and legs; muscle stiffness (spasticity); and impaired speech, hearing, and vision. Individuals with Friedreich ataxia often have a form of heart disease called hypertrophic cardiomyopathy, which enlarges and weakens the heart muscle and can be life-threatening. Some affected individuals develop diabetes or an abnormal curvature of the spine (scoliosis).Most people with Friedreich ataxia begin to experience the signs and symptoms of the disorder between ages 5 and 15. Poor coordination and balance are often the first noticeable features. Without treatment, affected individuals typically require the use of a wheelchair about 10 years after signs and symptoms appear.About 25 percent of people with Friedreich ataxia have an atypical form in which signs and symptoms begin after age 25. Affected individuals who develop Friedreich ataxia between ages 26 and 39 are considered to have late-onset Friedreich ataxia (LOFA). When the signs and symptoms begin after age 40 the condition is called very late-onset Friedreich ataxia (VLOFA). LOFA and VLOFA usually progress more slowly than typical Friedreich ataxia. ar Autosomal recessive FXN https://medlineplus.gov/genetics/gene/fxn FA FRDA Friedreich spinocerebellar ataxia Friedrich's ataxia GTR C1856689 MeSH D005621 OMIM 229300 SNOMED CT 10394003 2010-05 2024-12-02 Frontometaphyseal dysplasia https://medlineplus.gov/genetics/condition/frontometaphyseal-dysplasia descriptionFrontometaphyseal dysplasia is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, Melnick-Needles syndrome, and terminal osseous dysplasia. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and bony abnormalities involving various areas of the skeleton.Frontometaphyseal dysplasia is distinguished from the other otopalatodigital spectrum disorders by the presence of joint deformities called contractures that restrict the movement of certain joints. People with frontometaphyseal dysplasia may also have bowed limbs, an abnormal curvature of the spine (scoliosis), and abnormalities of the fingers and hands.Characteristic facial features may include prominent brow ridges; wide-set and downward-slanting eyes; a very small lower jaw and chin (micrognathia); and small, missing, or misaligned teeth. Some affected individuals have hearing loss.In addition to skeletal abnormalities, individuals with frontometaphyseal dysplasia may have obstruction of the ducts between the kidneys and bladder (ureters), heart defects, or constrictions in the passages leading from the windpipe to the lungs (the bronchi) that can cause problems with breathing.There are three types of frontometaphyseal dysplasia, known as type 1, type 2, and type 3. The three types differ in their genetic cause and the way they are inherited. xd X-linked dominant FLNA https://medlineplus.gov/genetics/gene/flna MAP3K7 https://www.ncbi.nlm.nih.gov/gene/6885 TAB2 https://www.ncbi.nlm.nih.gov/gene/23118 FMD GTR C4281559 GTR C4310697 MeSH D010009 OMIM 305620 OMIM 617137 SNOMED CT 62803002 2022-06 2023-02-21 Frontonasal dysplasia https://medlineplus.gov/genetics/condition/frontonasal-dysplasia descriptionFrontonasal dysplasia is a condition that results from abnormal development of the head and face before birth. People with frontonasal dysplasia have at least two of the following features: widely spaced eyes (ocular hypertelorism); a broad nose; a slit (cleft) in one or both sides of the nose; no nasal tip; a central cleft involving the nose, upper lip, or roof of the mouth (palate); incomplete formation of the front of the skull with skin covering the head where bone should be (anterior cranium bifidum occultum); or a widow's peak hairline.Other features of frontonasal dysplasia can include additional facial malformations, absence or malformation of the tissue that connects the left and right halves of the brain (the corpus callosum), and intellectual disability.There are at least three types of frontonasal dysplasia that are distinguished by their genetic causes and their signs and symptoms. In addition to the features previously described, each type of frontonasal dysplasia is associated with other distinctive features. Individuals with frontonasal dysplasia type 1 typically have abnormalities of the nose, a long area between the nose and upper lip (philtrum), and droopy upper eyelids (ptosis). Individuals with frontonasal dysplasia type 2 can have hair loss (alopecia) and an enlarged opening in the two bones that make up much of the top and sides of the skull (enlarged parietal foramina). Males with this form of the condition often have genital abnormalities. Features of frontonasal dysplasia type 3 include eyes that are missing (anophthalmia) or very small (microphthalmia) and low-set ears that are rotated backward. Frontonasal dysplasia type 3 is typically associated with the most severe facial abnormalities, but the severity of the condition varies widely, even among individuals with the same type.Life expectancy of affected individuals depends on the severity of the malformations and whether or not surgical intervention can improve associated health problems, such as breathing and feeding problems caused by the facial clefts. ad Autosomal dominant ar Autosomal recessive ALX4 https://medlineplus.gov/genetics/gene/alx4 ALX1 https://medlineplus.gov/genetics/gene/alx1 ALX3 https://medlineplus.gov/genetics/gene/alx3 FND FNM Frontonasal dysplasia sequence Frontonasal malformation Frontorhiny Median facial cleft syndrome GTR C1876203 GTR C3150703 GTR C3150706 MeSH D019465 OMIM 136760 OMIM 613451 OMIM 613456 SNOMED CT 254005007 SNOMED CT 86610004 2014-04 2020-08-18 Frontotemporal dementia with parkinsonism-17 https://medlineplus.gov/genetics/condition/frontotemporal-dementia-with-parkinsonism-17 descriptionFrontotemporal dementia with parkinsonism-17 (FTDP-17) is a brain disorder. It is part of a group of conditions, called frontotemporal dementia or frontotemporal degeneration, that are characterized by a loss of nerve cells (neurons) in areas of the brain called the frontal and temporal lobes. Over time, a loss of these cells can affect personality, behavior, language, and movement.The signs and symptoms of FTDP-17 usually become noticeable in a person's forties or fifties. Most affected people survive 5 to 10 years after the appearance of symptoms, although a few have survived for two decades or more.Changes in personality and behavior are often early signs of FTDP-17. These changes include a loss of inhibition, inappropriate emotional responses, restlessness, neglect of personal hygiene, and a general loss of interest in activities and events. The disease also leads to deterioration of cognitive functions (dementia), including problems with judgment, planning, and concentration. Some people with FTDP-17 develop psychiatric symptoms, including obsessive-compulsive behaviors, strongly held false beliefs (delusions), and false perceptions (hallucinations). It may become difficult for affected individuals to interact with others in a socially appropriate manner. They increasingly require help with personal care and other activities of daily living.Many people with FTDP-17 develop problems with speech and language. They may have trouble finding words, confuse one word with another (semantic paraphasias), and repeat words spoken by others (echolalia). Difficulties with speech and language worsen over time, and most affected individuals eventually lose the ability to communicate.FTDP-17 is also characterized by problems with movement that worsen over time. Many affected individuals develop features of parkinsonism, including tremors, rigidity, and unusually slow movement (bradykinesia). As the disease progresses, most affected individuals become unable to walk. Some people with FTDP-17 also have restricted up-and-down eye movement (vertical gaze palsy) and rapid abnormal movements of both eyes (saccades). ad Autosomal dominant MAPT https://medlineplus.gov/genetics/gene/mapt DDPAC Disinhibition-dementia-parkinsonism-amytrophy complex Familial Pick's disease FTDP-17 Wilhelmsen-Lynch disease GTR C0338451 MeSH D057180 OMIM 600274 SNOMED CT 702429008 2011-03 2023-11-13 Fryns syndrome https://medlineplus.gov/genetics/condition/fryns-syndrome descriptionFryns syndrome is a condition that affects the development of many parts of the body. Most people with Fryns syndrome have a defect in the muscle that separates the abdomen from the chest cavity (the diaphragm). The most common defect is a congenital diaphragmatic hernia, which is a hole in the diaphragm that develops before birth. This hole allows the stomach and intestines to move into the chest and crowd the heart and lungs. As a result, the lungs often do not develop properly (pulmonary hypoplasia), which can cause life-threatening breathing difficulties in affected infants.People with Fryns syndrome typically have abnormalities of the fingers and toes and distinctive facial features. The tips of the fingers and toes tend to be underdeveloped, so they can look short and stubby and have small nails or no nails at all. Affected individuals may have widely spaced eyes (hypertelorism), a broad and flat nasal bridge, a thick nasal tip, a long space between the nose and upper lip (a long philtrum), a large mouth (macrostomia), and a small lower jaw (micrognathia). Many also have low-set and abnormally shaped ears.Additional features of Fryns syndrome include small eyes (microphthalmia), clouding of the clear outer covering of the eye (the cornea), and an opening in the roof of the mouth (cleft palate) with or without a split in the lip (cleft lip). Fryns syndrome can also affect the development of the brain, heart, digestive system, kidneys, and genitalia.Because there are significant health problems associated with congenital diaphragmatic hernias, most children with Fryns syndrome do not survive past infancy. Affected individuals who do survive into childhood often have severe developmental delays and intellectual disabilities.The features of this condition often overlap with those of other disorders. As a result, Fryns syndrome can be difficult to diagnose. ar Autosomal recessive PIGN https://medlineplus.gov/genetics/gene/pign Diaphragmatic hernia, abnormal face, and distal limb anomalies Diaphragmatic hernia-facial dysmorphism-distal limb anomalies syndrome GTR C0220730 MeSH D000015 MeSH D006548 OMIM 229850 SNOMED CT 702432006 2025-03 2026-02-12 Fuchs endothelial dystrophy https://medlineplus.gov/genetics/condition/fuchs-endothelial-dystrophy descriptionFuchs endothelial dystrophy is a condition that causes vision problems. The first symptom of this condition is typically blurred vision in the morning that usually clears during the day. Over time, affected individuals lose the ability to see details (visual acuity). People with Fuchs endothelial dystrophy also become sensitive to bright lights.Fuchs endothelial dystrophy specifically affects the front surface of the eye called the cornea. Deposits called guttae, which are detectable during an eye exam, form in the middle of the cornea and eventually spread throughout the cornea. These guttae contribute to the ongoing cell death within the cornea, leading to worsening vision problems. Tiny blisters may develop on the cornea, which can burst and cause eye pain.The signs and symptoms of Fuchs endothelial dystrophy usually begin in a person's forties or fifties. A very rare early-onset variant of this condition starts to affect vision in a person's twenties. u Pattern unknown ad Autosomal dominant TCF4 https://medlineplus.gov/genetics/gene/tcf4 COL8A2 https://medlineplus.gov/genetics/gene/col8a2 ATP1B1 https://www.ncbi.nlm.nih.gov/gene/481 LAMC1 https://www.ncbi.nlm.nih.gov/gene/3915 ZEB1 https://www.ncbi.nlm.nih.gov/gene/6935 SLC4A11 https://www.ncbi.nlm.nih.gov/gene/83959 AGBL1 https://www.ncbi.nlm.nih.gov/gene/123624 KANK4 https://www.ncbi.nlm.nih.gov/gene/163782 Fuchs atrophy Fuchs corneal dystrophy Fuchs dystrophy Fuchs endothelial corneal dystrophy Fuchs' endothelial dystrophy GTR C1850959 GTR C2750448 GTR C2750450 GTR C2750451 GTR C3809798 ICD-10-CM H18.51 MeSH D005642 OMIM 136800 OMIM 610158 OMIM 613267 OMIM 613268 OMIM 613269 OMIM 613270 OMIM 613271 OMIM 615523 SNOMED CT 193839007 2011-06 2020-08-18 Fucosidosis https://medlineplus.gov/genetics/condition/fucosidosis descriptionFucosidosis is a condition that affects many areas of the body, especially the brain. The symptoms of fucosidosis can vary from person to person. Affected individuals have intellectual disabilities that worsen with age. Over time, people with this condition tend to lose skills they had previously learned, such as sitting, standing, walking, or talking. Additional signs and symptoms of fucosidosis can include slow growth, abnormal bone development (dysostosis multiplex), and rigid or stiff muscles (spasticity). People with fucosidosis may also have clusters of enlarged blood vessels that form small, dark red spots on the skin (angiokeratomas) and distinctive facial features that are often described as "coarse." Additional features of fucosidosis can include frequent respiratory infections, an enlarged liver and spleen (hepatosplenomegaly), and seizures.In the past, fucosidosis has been divided into two types based on the symptoms and age of onset. Type 1 was used to describe the more severe form of the disorder, with symptoms typically appearing in infancy. Type 2 was used to describe cases with milder symptoms and a slower progression. Currently, many researchers consider the condition to be a spectrum with a wide range in severity.  ar Autosomal recessive FUCA1 https://medlineplus.gov/genetics/gene/fuca1 Alpha-L-fucosidase deficiency Fucosidase deficiency GTR C0016788 ICD-10-CM E77.1 MeSH D005645 OMIM 230000 SNOMED CT 399045007 SNOMED CT 61172008 SNOMED CT 64716005 2024-03 2024-03-14 Fukuyama congenital muscular dystrophy https://medlineplus.gov/genetics/condition/fukuyama-congenital-muscular-dystrophy descriptionFukuyama congenital muscular dystrophy is an inherited condition that predominantly affects the muscles, brain, and eyes. Congenital muscular dystrophies are a group of genetic conditions that cause muscle weakness and muscle wasting (atrophy) beginning early in life. The signs and symptoms of Fukuyama congenital muscular dystrophy can vary from mild to severe.Fukuyama congenital muscular dystrophy affects the skeletal muscles, which are the muscles the body uses for movement. The signs and symptoms of the disorder typically begin in early infancy and include a weak cry, difficulty feeding, and weak muscle tone (hypotonia). Weakness of the facial muscles often leads to a distinctive facial appearance including droopy eyelids (ptosis) and an open mouth. In childhood, muscle weakness and joint deformities (contractures) restrict movement and interfere with the development of motor skills such as sitting, standing, and walking. Children with mild Fukuyama congenital muscular dystrophy may be able to stand or walk on their own, while those with severe signs and symptoms may not be able to sit without support. Fukuyama congenital muscular dystrophy also impairs brain development. People with this condition often have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain has a bumpy, irregular appearance (like that of cobblestones). These irregularities in the structure of the brain lead to delays in the development of motor skills and speech and moderate to severe intellectual disabilities. Social skills are less severely impaired. More than half of all affected children experience seizures.In some people with Fukuyama congenital muscular dystrophy, vision is impaired. They may also have increased pressure in the eye (glaucoma) or abnormalities in the specialized light-sensitive tissue that lines the back of the eye (retina). Individuals with Fukuyama congenital muscular dystrophy often develop heart problems in adolescence. These heart problems worsen over time. Severely affected individuals may also develop swallowing difficulties that can lead to a bacterial lung infection called aspiration pneumonia. The serious medical problems associated with Fukuyama congenital muscular dystrophy can shorten the life expectancy of someone with this condition. ar Autosomal recessive FKTN https://medlineplus.gov/genetics/gene/fktn Congenital muscular dystrophy, Fukuyama type FCMD FKTN-related congenital muscular dystrophy MDDGA4 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 GTR C0410174 MeSH D009136 OMIM 253800 SNOMED CT 111502003 2024-08 2024-08-12 Fumarase deficiency https://medlineplus.gov/genetics/condition/fumarase-deficiency descriptionFumarase deficiency is a condition that primarily affects the nervous system, especially the brain. Affected infants may have an abnormally small head size (microcephaly), abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may also experience seizures. Some people with this disorder have unusual facial features, including a prominent forehead (frontal bossing), low-set ears, a small jaw (micrognathia), widely spaced eyes (ocular hypertelorism), and a depressed nasal bridge. An enlarged liver and spleen (hepatosplenomegaly) may also be associated with this disorder, as well as an excess of red blood cells (polycythemia) or deficiency of white blood cells (leukopenia) in infancy. Affected individuals usually survive only a few months, but a few have lived into early adulthood. ar Autosomal recessive FH https://medlineplus.gov/genetics/gene/fh Fumarate hydratase deficiency Fumaric aciduria GTR C0342770 MeSH D008661 OMIM 606812 SNOMED CT 124616002 SNOMED CT 237983002 2008-04 2020-08-18 Fundus albipunctatus https://medlineplus.gov/genetics/condition/fundus-albipunctatus descriptionFundus albipunctatus is an eye disorder characterized by an impaired ability to see in low light (night blindness) and the presence of whitish-yellow flecks in the retina, which is the specialized light-sensitive tissue in the inner lining of the back of the eye (the fundus). The flecks are detected during an eye examination.Individuals with fundus albipunctatus experience night blindness from an early age. In particular, they have delayed dark adaptation, which means they have trouble adapting from bright light to dark conditions, such as when driving into a dark tunnel on a sunny day. It often takes hours for adaptation to occur. Their vision in bright light is usually normal.The flecks are especially abundant near the outer edge (the periphery) of the retina. Their density varies among affected individuals; some people have numerous flecks that overlap, while others have fewer. For unknown reasons, the flecks get smaller or fade with age in some affected individuals, although night vision does not improve.While fundus albipunctatus typically does not worsen (progress) over time, some individuals with the condition develop other eye conditions, such as breakdown of the central region of the retina known as the macula (macular degeneration) with loss of specialized light receptor cells called cones, which can affect vision in bright light. ar Autosomal recessive RPE65 https://medlineplus.gov/genetics/gene/rpe65 RDH5 https://medlineplus.gov/genetics/gene/rdh5 RLBP1 https://www.ncbi.nlm.nih.gov/gene/6017 Albipunctate retinal dystrophy Lauber's disease Pigmentary retinal dystrophy GTR C0311338 ICD-10-CM H35.52 MeSH D009755 MeSH D015785 OMIM 136880 SNOMED CT 68222009 2017-02 2021-11-24 GABA-transaminase deficiency https://medlineplus.gov/genetics/condition/gaba-transaminase-deficiency descriptionGABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Babies with this disorder have recurrent seizures (epilepsy), uncontrolled limb movements (choreoathetosis), exaggerated reflexes (hyperreflexia), weak muscle tone (hypotonia), and excessive sleepiness (hypersomnolence). Affected babies may grow faster in length than usual (accelerated linear growth), even though they have feeding problems and may not gain weight as quickly as expected (failure to thrive).Children with GABA-transaminase deficiency have profoundly impaired development. Most do not achieve normal developmental milestones of infancy such as following others' movement with their eyes or sitting unassisted. Individuals with this disorder usually do not survive past the first 2 years of life, but some live longer into childhood. ar Autosomal recessive ABAT https://medlineplus.gov/genetics/gene/abat 4 alpha aminobutyrate transaminase deficiency ABAT deficiency GABA transaminase deficiency GABA transferase deficiency GABA-T deficiency Gamma aminobutyrate transaminase deficiency Gamma aminobutyric acid transaminase deficiency Gamma-aminobutyrate transaminase deficiency Gamma-aminobutyric acid transaminase deficiency GTR C0342708 MeSH D020739 OMIM 613163 SNOMED CT 237941007 2018-04 2020-08-18 GLUT1 deficiency syndrome https://medlineplus.gov/genetics/condition/glut1-deficiency-syndrome descriptionGLUT1 deficiency syndrome is a disorder affecting the nervous system that can have a variety of neurological signs and symptoms. Approximately 90 percent of affected individuals have a form of the disorder often referred to as common GLUT1 deficiency syndrome. These individuals generally have frequent seizures (epilepsy) beginning in the first months of life. In newborns, the first sign of the disorder may be involuntary eye movements that are rapid and irregular. Babies with common GLUT1 deficiency syndrome have a normal head size at birth, but growth of the brain and skull is often slow, which can result in an abnormally small head size (microcephaly). People with this form of GLUT1 deficiency syndrome may have developmental delay or intellectual disability. Most affected individuals also have other neurological problems, such as stiffness caused by abnormal tensing of the muscles (spasticity), difficulty in coordinating movements (ataxia), and speech difficulties (dysarthria). Some experience episodes of confusion, lack of energy (lethargy), headaches, or muscle twitches (myoclonus), particularly during periods without food (fasting).About 10 percent of individuals with GLUT1 deficiency syndrome have a form of the disorder often known as non-epileptic GLUT1 deficiency syndrome, which is usually less severe than the common form. People with the non-epileptic form do not have seizures, but they may still have developmental delay and intellectual disability. Most have movement problems such as ataxia or involuntary tensing of various muscles (dystonia); the movement problems may be more pronounced than in the common form.Several conditions that were originally given other names have since been recognized to be variants of GLUT1 deficiency syndrome. These include paroxysmal choreoathetosis with spasticity (dystonia 9); paroxysmal exercise-induced dyskinesia and epilepsy (dystonia 18); and certain types of epilepsy. In rare cases, people with variants of GLUT1 deficiency syndrome produce abnormal red blood cells and have uncommon forms of a blood condition known as anemia, which is characterized by a shortage of red blood cells. ad Autosomal dominant ar Autosomal recessive SLC2A1 https://medlineplus.gov/genetics/gene/slc2a1 De Vivo disease Encephalopathy due to GLUT1 deficiency G1D Glucose transport defect, blood-brain barrier Glucose transporter protein syndrome Glucose transporter type 1 deficiency syndrome Glut1 deficiency GLUT1 DS GTPS GTR C1847501 MeSH D020739 OMIM 606777 SNOMED CT 445252005 2014-03 2022-10-28 GM1 gangliosidosis https://medlineplus.gov/genetics/condition/gm1-gangliosidosis descriptionGM1 gangliosidosis is an inherited disorder that destroys nerve cells (neurons) in the brain and spinal cord. This condition can be classified as one of three major types based on the age at which signs and symptoms first appear. However, the signs and symptoms of these three types can overlap, leading some researchers to believe that GM1 gangliosidosis occurs on a spectrum instead of as three distinct types.The signs and symptoms of the most severe form of GM1 gangliosidosis, called type I or the infantile form, usually develop by the age of 6 months. Infants with this form of the disorder typically appear normal until their development slows and the muscles used for movement weaken. Affected infants eventually lose the skills they had previously acquired (developmentally regress) and may develop an exaggerated startle reaction to loud noises. Over time, children with GM1 gangliosidosis type I develop an enlarged liver and spleen (hepatosplenomegaly) and skeletal abnormalities. Affected children often  have seizures and profound intellectual disability. People with GM1 gangliosidosis type I can lose their vision due to clouding of the clear outer covering of the eye (the cornea) and the breakdown of the light-sensing tissue at the back of the eye (the retina). Affected individuals also develop a red area in the eye known as a cherry-red spot. In some cases, affected individuals have distinctive facial features that are described as "coarse," enlarged gums (gingival hypertrophy), and an enlarged and weakened heart muscle (cardiomyopathy). Individuals with type I usually do not survive past early childhood.GM1 gangliosidosis type II occurs in one of two forms: the late infantile or the juvenile forms. Children with type II develop normally early in life, but they begin to show signs and symptoms of the condition around the age of 18 months (late infantile form) or 5 years (juvenile form). Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, coarse facial features, or enlarged organs. Type II usually progresses more slowly than type I, but it still  shortens life expectancy. People with the late infantile form typically survive into mid-childhood, while those with the juvenile form may live into early adulthood.GM1 gangliosidosis type III is the adult or chronic form of the condition, and this is the mildest form. The age at which symptoms first appear varies in people with GM1 gangliosidosis type III, although most affected individuals develop signs and symptoms in their teens. The characteristic features of this type include involuntary tensing of various muscles (dystonia) and abnormalities of the spinal bones (vertebrae). Life expectancy varies among people with GM1 gangliosidosis type III. ar Autosomal recessive GLB1 https://medlineplus.gov/genetics/gene/glb1 Beta-galactosidase-1 (GLB1) deficiency GTR C0085131 GTR C0268271 GTR C0268272 GTR C0268273 ICD-10-CM E75.19 MeSH D016537 OMIM 230500 OMIM 230600 OMIM 230650 SNOMED CT 124465002 SNOMED CT 18756002 SNOMED CT 238025006 SNOMED CT 238026007 SNOMED CT 238027003 2023-04 2023-04-26 GM2 activator deficiency https://medlineplus.gov/genetics/condition/gm2-activator-deficiency descriptionGM2 activator deficiency (sometimes called GM2 gangliosidosis, AB variant) is a rare inherited disorder that causes progressive brain injury.   Most individuals with GM2 activator deficiency have the acute infantile form of the disease.  Signs and symptoms of acute infantile GM2 activator deficiency typically appear between the ages of 4 and 12 months, when development slows and the muscles used for movement weaken. Infants with acute infantile GM2 activator deficiency stop achieving normal developmental milestones and eventually lose previously acquired skills such as turning over, sitting, and crawling. These infants also develop an exaggerated startle reaction to loud noises. Over time, infants with acute infantile GM2 activator deficiency typically experience seizures, vision loss, and intellectual disabilites. They eventually become unable to respond to their environment. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of the infantile form of this disorder. Infants with acute infantile GM2 activator deficiency may survive into early childhood.Some people with GM2 activator deficiency may develop milder and more variable signs and symptoms later in life. Due to the rarity of this condition, the full spectrum of the late-onset presentation has not been clearly defined. ar Autosomal recessive GM2A https://medlineplus.gov/genetics/gene/gm2a GM2 gangliosidosis, AB variant Hexosaminidase activator deficiency Tay-Sachs disease, AB variant GTR C0268275 ICD-10-CM MeSH D049290 OMIM 272750 SNOMED CT 71253000 2024-03 2024-04-02 GM3 synthase deficiency https://medlineplus.gov/genetics/condition/gm3-synthase-deficiency descriptionGM3 synthase deficiency is characterized by recurrent seizures (epilepsy) and problems with brain development. Within the first few weeks after birth, affected infants become irritable and develop feeding difficulties and vomiting that prevent them from growing and gaining weight at the usual rate. Seizures begin within the first year of life and worsen over time. Multiple types of seizures are possible, including generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Some affected children also experience prolonged episodes of seizure activity called nonconvulsive status epilepticus. The seizures associated with GM3 synthase deficiency tend to be resistant (refractory) to treatment with antiseizure medications.GM3 synthase deficiency profoundly disrupts brain development. Most affected children have severe intellectual disability and do not develop skills such as reaching for objects, speaking, sitting without support, or walking. Some have involuntary twisting or jerking movements of the arms that are described as choreoathetoid. Although affected infants can likely see and hear at birth, vision and hearing become impaired as the disease worsens. It is unknown how long people with GM3 synthase deficiency usually survive.Some affected individuals have changes in skin coloring (pigmentation), including dark freckle-like spots on the arms and legs and light patches on the arms, legs, and face. These changes appear in childhood and may become more or less apparent over time. The skin changes do not cause any symptoms, but they can help doctors diagnose GM3 synthase deficiency in children who also have seizures and delayed development. ar Autosomal recessive ST3GAL5 https://medlineplus.gov/genetics/gene/st3gal5 Amish infantile epilepsy syndrome Epilepsy syndrome, infantile-onset symptomatic Ganglioside GM3 synthase deficiency Infantile-onset symptomatic epilepsy syndrome GTR C1836824 MeSH D004827 OMIM 609056 SNOMED CT 722762005 2014-07 2020-08-18 GNE myopathy https://medlineplus.gov/genetics/condition/gne-myopathy descriptionGNE myopathy is a condition that primarily affects skeletal muscles, which are muscles that the body uses for movement. This disorder causes muscle weakness that appears in late adolescence or early adulthood and worsens over time.Difficulty lifting the front part of the foot (foot drop) is often the first sign of GNE myopathy. For individuals with GNE myopathy, foot drop is caused by weakness of a muscle in the lower leg called the tibialis anterior. This muscle helps raise the foot up. Weakness in the tibialis anterior alters the way a person walks and makes it difficult to run and climb stairs. As the disorder progresses, weakness also develops in the muscles of the upper legs, hips, shoulders, and hands. Unlike most forms of myopathy, GNE myopathy usually does not affect the quadriceps, which are a group of large muscles at the front of the thigh. This condition also does not affect the muscles of the eye or heart, and it does not cause neurological problems. Weakness in leg muscles makes walking increasingly difficult, and most people with GNE myopathy require wheelchair assistance within 20 years after the signs and symptoms of the disorder appear.People with the characteristic features of GNE myopathy have been described in several different populations. When the condition was first reported in Japanese families, researchers called it distal myopathy with rimmed vacuoles (DMRV) or Nonaka myopathy. When a similar disorder was discovered in Iranian Jewish families, researchers called it rimmed vacuole myopathy or hereditary inclusion body myopathy (HIBM). It has since become clear that these conditions are variations of a single disorder caused by changes in the same gene. ar Autosomal recessive GNE https://medlineplus.gov/genetics/gene/gne Distal myopathy with or without rimmed vacuoles Distal myopathy with rimmed vacuoles Distal myopathy, Nonaka type DMRV Hereditary inclusion body myopathy type 2 HIBM2 IBM2 Inclusion body myopathy type 2 Inclusion body myopathy, hereditary, autosomal recessive Inclusion body myopathy, quadriceps-sparing Nonaka distal myopathy Nonaka myopathy QSM Quadriceps-sparing myopathy GTR C1853926 ICD-10-CM MeSH D018979 OMIM 605820 SNOMED CT 702382000 2024-03 2024-04-02 GRACILE syndrome https://medlineplus.gov/genetics/condition/gracile-syndrome descriptionGRACILE syndrome is a severe disorder that begins before birth. GRACILE stands for the condition's characteristic features: growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death.In GRACILE syndrome, growth before birth is slow (intrauterine growth retardation). Affected newborns are smaller than average and have an inability to grow and gain weight at the expected rate (failure to thrive). A characteristic of GRACILE syndrome is excess iron in the liver, which likely begins before birth. Iron levels may begin to improve after birth, although they typically remain elevated. Within the first day of life, infants with GRACILE syndrome have a buildup of a chemical called lactic acid in the body (lactic acidosis). They also have kidney problems that lead to an excess of molecules called amino acids in the urine (aminoaciduria). Babies with GRACILE syndrome have cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to irreversible liver disease (cirrhosis) in the first few months of life.Because of the severe health problems caused by GRACILE syndrome, infants with this condition do not survive for more than a few months, and about half die within a few days of birth. ar Autosomal recessive BCS1L https://medlineplus.gov/genetics/gene/bcs1l Fellman syndrome Finnish lactic acidosis with hepatic hemosiderosis Finnish lethal neonatal metabolic syndrome Growth retardation, amino aciduria, cholestasis, iron overload, lactic acidosis, and early death GTR C1864002 MeSH D008661 OMIM 603358 SNOMED CT 703388005 2014-03 2025-04-03 GRIN2B-related neurodevelopmental disorder https://medlineplus.gov/genetics/condition/grin2b-related-neurodevelopmental-disorder descriptionGRIN2B-related neurodevelopmental disorder is a condition that affects the nervous system. Neurodevelopmental disorders result from impaired growth and development of the central nervous system, which includes the brain and spinal cord, and the nerves connecting them. These disorders often affect learning ability, memory, and behavior and can be associated with other neurological problems.Individuals with GRIN2B-related neurodevelopmental disorder have mild to profound intellectual disability and delayed development of speech and motor skills, such as sitting and walking. Some affected individuals never develop speech or the ability to walk on their own. Many people with this condition have weak muscle tone (hypotonia), which can contribute to the problems developing motor skills and lead to difficulty eating. Some affected individuals have abnormal muscle stiffness (spasticity), which can also cause problems with movement.Recurrent seizures (epilepsy) occur in about half of people with GRIN2B-related neurodevelopmental disorder. About one-quarter of affected individuals have features of autism spectrum disorder, which is characterized by impaired communication and social interaction. Affected individuals may also be hyperactive, impulsive, or easily distractible, and some are described as being overly friendly. Sleeping difficulties can also occur in this condition.Less common features of GRIN2B-related neurodevelopmental disorder include structural brain abnormalities, an unusually small head size (microcephaly), impaired vision, and involuntary muscle movements. ad Autosomal dominant GRIN2B https://medlineplus.gov/genetics/gene/grin2b EIEE27 Epileptic encephalopathy, early infantile, 27 GRIN2B encephalopathy GRIN2B related syndrome GTR C3151411 GTR C4015316 MeSH D001927 MeSH D008607 OMIM 613970 OMIM 616139 2018-09 2023-08-02 GRN-related frontotemporal lobar degeneration https://medlineplus.gov/genetics/condition/grn-related-frontotemporal-lobar-degeneration descriptionGRN-related frontotemporal lobar degeneration is a progressive brain disorder that can affect behavior, language, and movement. The symptoms of this disorder usually become noticeable in a person's fifties or sixties, and affected people typically survive 7 to 13 years after the appearance of symptoms. However, symptoms can begin as early as a person's thirties or as late as a person's eighties. The features of this condition vary significantly, even among affected members of the same family.Behavioral changes are the most common early signs of GRN-related frontotemporal lobar degeneration. These include marked changes in personality, judgment, and insight. It may become difficult for affected individuals to interact with others in a socially appropriate manner. Affected people may also become easily distracted and unable to complete tasks. They increasingly require help with personal care and other activities of daily living.Many people with GRN-related frontotemporal lobar degeneration develop progressive problems with speech and language (aphasia). Affected individuals may have trouble speaking, remembering words and names (dysnomia), and understanding speech. Over time, they may completely lose the ability to communicate (mutism). People with this condition also experience a decline in intellectual function (dementia).Some people with GRN-related frontotemporal lobar degeneration also develop movement disorders, such as parkinsonism and corticobasal syndrome. The signs and symptoms of these disorders include tremors, muscle stiffness (rigidity), unusually slow movement (bradykinesia), walking problems (gait disturbance), involuntary muscle spasms (myoclonus), uncontrolled muscle tensing (dystonia), and an inability to carry out purposeful movements (apraxia). ad Autosomal dominant GRN https://medlineplus.gov/genetics/gene/grn Frontotemporal lobar degeneration FTD-GRN FTD-PGRN FTDP-17 GRN FTDU-17 FTLD FTLD with TDP-43 pathology FTLD-TDP GRN-related frontotemporal dementia HDDD1 HDDD2 Hereditary dysphasic disinhibition dementia GTR C1843792 MeSH D057180 OMIM 607485 SNOMED CT 702426001 2020-04 2023-11-13 Galactosemia https://medlineplus.gov/genetics/condition/galactosemia descriptionGalactosemia is a disorder that affects how the body processes a simple sugar called galactose. A small amount of galactose is present in many foods. It is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas. The signs and symptoms of galactosemia result from an inability to use galactose to produce energy.Researchers have identified several types of galactosemia. These conditions are each caused by mutations in a particular gene and affect different enzymes involved in breaking down galactose.Classic galactosemia, also known as type I, is the most common and most severe form of the condition. If infants with classic galactosemia are not treated promptly with a low-galactose diet, life-threatening complications appear within a few days after birth. Affected infants typically develop feeding difficulties, a lack of energy (lethargy), a failure to gain weight and grow as expected (failure to thrive), yellowing of the skin and whites of the eyes (jaundice), liver damage, and abnormal bleeding. Other serious complications of this condition can include overwhelming bacterial infections (sepsis) and shock. Affected children are also at increased risk of delayed development, clouding of the lens of the eye (cataract), speech difficulties, and intellectual disability. Females with classic galactosemia may develop reproductive problems caused by an early loss of function of the ovaries (premature ovarian insufficiency).Galactosemia type II (also called galactokinase deficiency) and type III (also called galactose epimerase deficiency) cause different patterns of signs and symptoms. Galactosemia type II causes fewer medical problems than the classic type. Affected infants develop cataracts but otherwise experience few long-term complications. The signs and symptoms of galactosemia type III vary from mild to severe and can include cataracts, delayed growth and development, intellectual disability, liver disease, and kidney problems. ar Autosomal recessive GALT https://medlineplus.gov/genetics/gene/galt GALE https://medlineplus.gov/genetics/gene/gale GALK1 https://medlineplus.gov/genetics/gene/galk1 Classic galactosemia Epimerase deficiency galactosemia Galactokinase deficiency disease Galactose epimerase deficiency Galactose-1-phosphate uridyl-transferase deficiency disease GALE deficiency GALK deficiency GALT deficiency UDP-galactose-4-epimerase deficiency disease UTP hexose-1-phosphate uridylyltransferase deficiency GTR C0016952 GTR C0268151 GTR C0268155 GTR C0751161 ICD-10-CM E74.21 MeSH D005693 OMIM 230200 OMIM 230350 OMIM 230400 SNOMED CT 124302001 SNOMED CT 124354006 SNOMED CT 190745006 SNOMED CT 8849004 2008-01 2020-08-18 Galactosialidosis https://medlineplus.gov/genetics/condition/galactosialidosis descriptionGalactosialidosis is a condition that affects many areas of the body. The three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features.The early infantile form of galactosialidosis is associated with extensive swelling caused by fluid accumulation before birth (hydrops fetalis), a soft out-pouching in the lower abdomen (an inguinal hernia), and an enlarged liver and spleen (hepatosplenomegaly). Additional features of this form include abnormal bone development (dysostosis multiplex) and distinctive facial features that are often described as "coarse." Some infants have an enlarged heart (cardiomegaly), an eye abnormality called a cherry-red spot, and kidney disease that can progress to kidney failure. Infants with this form usually are diagnosed between birth and 3 months of age; they typically live to around 6 months of age.The late infantile form of galactosialidosis shares some features with the early infantile form, although the signs and symptoms are somewhat less severe and begin later in infancy. This form is characterized by short stature, dysostosis multiplex, heart valve problems, hepatosplenomegaly, and "coarse" facial features. Other symptoms seen in some individuals with this type include intellectual disabilities, hearing loss, and a cherry-red spot. Children with this condition typically develop symptoms around 2 years old. The life expectancy of individuals with this type varies depending on the severity of symptoms.The juvenile/adult form of galactosialidosis has signs and symptoms that are somewhat different from those of the other two types. This form is distinguished by difficulty coordinating movements (ataxia), muscle twitches (myoclonus), seizures, and intellectual disabilities that worsen over time. People with this form typically also have dark red spots on the skin (angiokeratomas), abnormalities in the bones of the spine, "coarse" facial features, a cherry-red spot, vision loss, and hearing loss. The age at which symptoms begin to develop varies widely among affected individuals, but the average age is 16. This form is typically associated with a nearly normal life expectancy. ar Autosomal recessive CTSA https://medlineplus.gov/genetics/gene/ctsa Deficiency of cathepsin A Goldberg syndrome Lysosomal protective protein deficiency Neuraminidase deficiency with beta-galactosidase deficiency PPCA deficiency GTR C0268233 MeSH D020140 OMIM 256540 SNOMED CT 35691006 2024-01 2024-01-26 Gastrointestinal stromal tumor https://medlineplus.gov/genetics/condition/gastrointestinal-stromal-tumor descriptionA gastrointestinal stromal tumor (GIST) is a type of tumor that occurs in the gastrointestinal tract, most commonly in the stomach or small intestine. This type of tumor is thought to grow from specialized cells found in the gastrointestinal tract called interstitial cells of Cajal (ICCs) or precursors to these cells. Affected individuals can develop one or more tumors. GISTs are usually found in adults between ages 40 and 70; rarely, children and young adults develop this type of tumor. Small tumors may cause no signs or symptoms. However, some people with GISTs may experience pain or swelling in the belly area (abdomen), nausea, vomiting, loss of appetite, or weight loss. Sometimes, tumors cause bleeding into the gastrointestinal tract, which may lead to low red blood cell counts (anemia) and, consequently, weakness and tiredness. Bleeding into the intestines may cause black and tarry stools, and bleeding into the throat or stomach may cause vomiting of blood.Affected individuals with no family history of GIST typically have only one tumor (called a sporadic GIST). People with a family history of GISTs (called familial GISTs) often have multiple tumors and additional signs or symptoms, including noncancerous overgrowth (hyperplasia) of other cells in the gastrointestinal tract and patches of dark skin on various areas of the body. Some affected individuals have a skin condition called urticaria pigmentosa (also known as maculopapular cutaneous mastocytosis), which is characterized by raised patches of brownish skin that sting or itch when touched.A rare form of GIST, called succinate dehydrogenase (SDH)-deficient GIST, tends to occur in childhood or young adulthood and affects females more commonly than males. In this form, tumors are almost always in the stomach. Individuals with an SDH-deficient GIST have a high risk of developing other types of tumors, particularly noncancerous tumors in the nervous system called paragangliomas and noncancerous lung tumors called pulmonary chondromas. When GISTs occur in combination with paragangliomas, the condition is known as Carney-Stratakis syndrome; the combination of GISTs, paragangliomas, and pulmonary chondromas is known as Carney triad; and the combination of GISTs and pulmonary chondroma is known as incomplete Carney triad. ad Autosomal dominant ar Autosomal recessive BRAF https://medlineplus.gov/genetics/gene/braf SDHD https://medlineplus.gov/genetics/gene/sdhd SDHC https://medlineplus.gov/genetics/gene/sdhc SDHB https://medlineplus.gov/genetics/gene/sdhb SDHA https://medlineplus.gov/genetics/gene/sdha KIT https://medlineplus.gov/genetics/gene/kit PDGFRA https://medlineplus.gov/genetics/gene/pdgfra Gastrointestinal stromal neoplasm Gastrointestinal stromal sarcoma GIST GTR C0238198 ICD-10-CM C49.A ICD-10-CM C49.A0 ICD-10-CM C49.A1 ICD-10-CM C49.A2 ICD-10-CM C49.A3 ICD-10-CM C49.A4 ICD-10-CM C49.A5 ICD-10-CM C49.A9 MeSH D046152 OMIM 606764 SNOMED CT 420120006 2014-09 2021-07-14 Gaucher disease https://medlineplus.gov/genetics/condition/gaucher-disease descriptionGaucher disease is an inherited disorder that affects many of the body's organs and tissues. The signs and symptoms of this condition vary widely among affected individuals. Researchers have described several types of Gaucher disease based on their characteristic features.Type 1 Gaucher disease is the most common form of this condition. Type 1 is also called non-neuronopathic Gaucher disease because the brain and spinal cord (the central nervous system) are usually not affected. The features of this condition range from mild to severe and may appear anytime from childhood to adulthood. Major signs and symptoms include enlargement of the liver and spleen (hepatosplenomegaly), a low number of red blood cells (anemia), easy bruising caused by a decrease in blood platelets (thrombocytopenia), bone abnormalities such as bone pain and fractures, and joint conditions such as arthritis.Types 2 and 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by problems that affect the central nervous system. In addition to the signs and symptoms described above, these conditions can cause abnormal eye movements, seizures, and brain damage. Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy. Type 3 Gaucher disease also affects the nervous system, but it tends to worsen more slowly than type 2.The most severe type of Gaucher disease is a very rare form of type 2 called the perinatal lethal form. This condition causes severe or life-threatening complications starting before birth or in infancy. Features of the perinatal lethal form can include extensive swelling caused by fluid accumulation before birth (hydrops fetalis); dry, scaly skin (ichthyosis) or other skin abnormalities; hepatosplenomegaly; distinctive facial features; and serious neurological problems. As its name indicates, most infants with the perinatal lethal form of Gaucher disease survive for only a few days after birth.Another form of Gaucher disease is known as the cardiovascular type (or type 3c) because it primarily affects the heart, causing the heart valves to harden (calcify). People with the cardiovascular form of Gaucher disease may also have eye abnormalities, bone disease, and mild enlargement of the spleen (splenomegaly). ar Autosomal recessive GBA1 https://medlineplus.gov/genetics/gene/gba1 Cerebroside lipidosis syndrome Gaucher splenomegaly Gaucher syndrome Gaucher's disease Gauchers disease GD Glucocerebrosidase deficiency Glucocerebrosidosis Glucosyl cerebroside lipidosis Glucosylceramidase deficiency Glucosylceramide beta-glucosidase deficiency Glucosylceramide lipidosis Kerasin histiocytosis Kerasin lipoidosis Kerasin thesaurismosis Lipoid histiocytosis (kerasin type) GTR C0017205 GTR C0268250 GTR C0268251 GTR C1856476 GTR C1961835 ICD-10-CM E75.22 MeSH D005776 OMIM 230800 OMIM 230900 OMIM 231000 OMIM 231005 SNOMED CT 12246008 SNOMED CT 190794006 SNOMED CT 192791009 SNOMED CT 5963005 SNOMED CT 62201009 SNOMED CT 870313002 2008-01 2025-04-03 Geleophysic dysplasia https://medlineplus.gov/genetics/condition/geleophysic-dysplasia descriptionGeleophysic dysplasia is an inherited condition that is characterized by short stature, thickened skin, joint abnormalities, distinctive facial features, and heart (cardiac) problems. The features and the severity of geleophysic dysplasia can vary among affected individuals.People with geleophysic dysplasia have short stature with especially small hands and feet. A thickening of the skin combined with joint deformities (contractures) can limit movement in the joints, especially in the fingers and wrists. Contractures in the legs and hips may cause people with geleophysic dysplasia to walk on their toes. The joint abnormalities seen in affected individuals typically worsen over time.Geleophysic dysplasia gets its name from the Greek words for happy ("gelios") and nature ("physis") and is derived from the good-natured facial appearance seen in many affected individuals. The distinctive facial features that are associated with this condition include a round face with full cheeks, a small nose with upturned nostrils, a broad nasal bridge, a thin upper lip, upturned corners of the mouth, and a flattened area between the upper lip and the nose (philtrum).People with geleophysic dysplasia often have cardiac problems. Abnormalities of the valves that control the flow of blood through the heart (cardiac valves) are especially common. In affected individuals, the cardiac valves may thicken, which can block blood flow and increase pressure in the heart. These cardiac valve problems can worsen over time. In some cases, people with geleophysic dysplasia have a narrowing of the artery from the heart to the lungs (pulmonary stenosis) or a hole between the two upper chambers of the heart (atrial septal defect).Approximately one third of individuals with geleophysic dysplasia have an abnormality of the windpipe (trachea) or voice box (larynx) that can cause serious breathing problems. These airway problems can also worsen over time. Some affected individuals have recurrent respiratory infections. About one third of people with geleophysic dysplasia do not survive past early childhood due to serious cardiac or respiratory problems.Other features of geleophysic dysplasia can include an enlarged liver (hepatomegaly) and recurrent ear infections, which can lead to hearing loss in some affected individuals. ar Autosomal recessive ad Autosomal dominant+New variant FBN1 https://medlineplus.gov/genetics/gene/fbn1 ADAMTSL2 https://medlineplus.gov/genetics/gene/adamtsl2 LTBP3 https://www.ncbi.nlm.nih.gov/gene/4054 Geleophysic dwarfism GTR C3278147 GTR C3280054 GTR C3489726 GTR C4540511 MeSH D009139 MeSH D017880 OMIM 231050 OMIM 614185 OMIM 617809 SNOMED CT 28557005 2026-02 2026-02-26 Generalized arterial calcification of infancy https://medlineplus.gov/genetics/condition/generalized-arterial-calcification-of-infancy descriptionGeneralized arterial calcification of infancy (GACI) is a disorder affecting the circulatory system that becomes apparent before birth or within the first few months of life. It is characterized by abnormal accumulation of the mineral calcium (calcification) in the walls of the blood vessels that carry blood from the heart to the rest of the body (the arteries). This calcification often occurs along with thickening of the lining of the arterial walls (the intima). These changes lead to narrowing (stenosis) and stiffness of the arteries, which forces the heart to work harder to pump blood. As a result, heart failure may develop in affected individuals, with signs and symptoms including difficulty breathing, accumulation of fluid (edema) in the extremities, a bluish appearance of the skin or lips (cyanosis), severe high blood pressure (hypertension), and an enlarged heart (cardiomegaly).People with GACI may also have calcification in other organs and tissues, particularly around the joints. In addition, they may have hearing loss or softening and weakening of the bones (rickets).Some individuals with GACI also develop features similar to those of another disorder called pseudoxanthoma elasticum (PXE). PXE is characterized by the accumulation of calcium and other minerals (mineralization) in elastic fibers, which are a component of connective tissue. Connective tissue provides strength and flexibility to structures throughout the body. Features characteristic of PXE that also occur in GACI include yellowish bumps called papules on the underarms and other areas of skin that touch when a joint bends (flexor areas); and abnormalities called angioid streaks affecting tissue at the back of the eye, which can be detected during an eye examination.As a result of the cardiovascular problems associated with GACI, individuals with this condition often do not survive past infancy, with death typically caused by a heart attack or stroke. However, affected individuals who survive their first six months, known as the critical period, can live into adolescence or early adulthood. ar Autosomal recessive ABCC6 https://medlineplus.gov/genetics/gene/abcc6 ENPP1 https://medlineplus.gov/genetics/gene/enpp1 Arteriopathia calcificans infantum Diffuse arterial calcifying elastopathy of infancy GACI Idiopathic infantile arterial calcification Idiopathic obliterative arteriopathy IIAC Infantile calcifying arteriopathy Medial coronary sclerosis of infancy Occlusive infantile arteriopathy GTR C3276161 MeSH D061205 OMIM 208000 OMIM 614473 SNOMED CT 68926002 2015-01 2020-08-18 Generalized pustular psoriasis https://medlineplus.gov/genetics/condition/generalized-pustular-psoriasis descriptionGeneralized pustular psoriasis (GPP) is a severe form of a skin disorder called psoriasis. GPP and other forms of psoriasis are caused by abnormal inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, when inflammation is abnormal and uncontrolled, it can damage the body's tissues and organs. Individuals with GPP have repeated episodes in which large areas of skin become red and inflamed and develop small pus-filled blisters (pustules). The skin problems can be accompanied by fever, extreme tiredness (fatigue), muscle weakness, an increased number of white blood cells, and other signs of inflammation throughout the body (systemic inflammation). The inflammation problems subside and reappear often. Episodes can be triggered by infection, exposure to or withdrawal from certain medications, menstruation, or pregnancy, although the trigger is often unknown. GPP can be life-threatening if not treated.While many affected individuals have features only of GPP (called GPP alone), some develop features of another skin condition called psoriasis vulgaris (PV), either before or after GPP appears. PV, the most common form of psoriasis, is characterized by red, scaly patches of skin (plaques) on parts of the body. ar Autosomal recessive ad Autosomal dominant CARD14 https://medlineplus.gov/genetics/gene/card14 IL36RN https://medlineplus.gov/genetics/gene/il36rn AP1S3 https://www.ncbi.nlm.nih.gov/gene/130340 Acute generalised pustular psoriasis Deficiency of the interleukin-36 receptor antagonist DITRA Generalized pustular psoriasis of von Zumbusch GPP Von Zumbusch psoriasis GTR C0343055 GTR C4015235 ICD-10-CM L40.1 MeSH D011565 OMIM 602723 OMIM 614204 OMIM 616106 SNOMED CT 238612002 2017-05 2026-03-04 Genetic epilepsy with febrile seizures plus https://medlineplus.gov/genetics/condition/genetic-epilepsy-with-febrile-seizures-plus descriptionGenetic epilepsy with febrile seizures plus (GEFS+) is a spectrum of seizure disorders of varying severity. GEFS+ is usually diagnosed in families whose members have a combination of febrile seizures, which are triggered by a high fever, and recurrent seizures (epilepsy) of other types, including seizures that are not related to fevers (afebrile seizures). The additional seizure types usually involve both sides of the brain (generalized seizures); however, seizures that involve only one side of the brain (partial seizures) occur in some affected individuals. The most common types of seizure in people with GEFS+ include myoclonic seizures, which cause involuntary muscle twitches; atonic seizures, which involve sudden episodes of weak muscle tone; and absence seizures, which cause loss of consciousness for short periods that appear as staring spells.The most common and mildest feature of the GEFS+ spectrum is simple febrile seizures, which begin in infancy and usually stop by age 5. When the febrile seizures continue after age 5 or other types of seizure develop, the condition is called febrile seizures plus (FS+). Seizures in FS+ usually end in early adolescence.A condition called Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI) is often considered part of the GEFS+ spectrum and is the most severe disorder in this group. Affected infants typically have prolonged seizures lasting several minutes (status epilepticus), which are triggered by fever. Other seizure types, including afebrile seizures, begin in early childhood. These types can include myoclonic or absence seizures. In Dravet syndrome, these seizures are difficult to control with medication, and they can worsen over time. A decline in brain function is also common in Dravet syndrome. Affected individuals usually develop normally in the first year of life, but then development stalls, and some affected children lose already-acquired skills (developmental regression). Many people with Dravet syndrome have difficulty coordinating movements (ataxia) and intellectual disability.Some people with GEFS+ have seizure disorders of intermediate severity that may not fit into the classical diagnosis of simple febrile seizures, FS+, or Dravet syndrome.Family members with GEFS+ may have different combinations of febrile seizures and epilepsy. For example, one affected family member may have only febrile seizures, while another also has myoclonic epilepsy. While GEFS+ is usually diagnosed in families, it can occur in individuals with no history of the condition in their family. ad Autosomal dominant SCN1A https://medlineplus.gov/genetics/gene/scn1a SCN9A https://medlineplus.gov/genetics/gene/scn9a SCN2A https://medlineplus.gov/genetics/gene/scn2a GABRD https://www.ncbi.nlm.nih.gov/gene/2563 GABRG2 https://www.ncbi.nlm.nih.gov/gene/2566 SCN1B https://www.ncbi.nlm.nih.gov/gene/6324 STX1B https://www.ncbi.nlm.nih.gov/gene/112755 GEFS+ Generalized epilepsy with febrile seizures plus GTR C1858672 GTR C1858673 GTR C1858674 GTR C3502809 GTR C4015395 GTR CN120574 MeSH D003294 MeSH D004827 OMIM 604233 OMIM 604403 OMIM 607681 OMIM 613060 OMIM 613863 OMIM 616172 SNOMED CT 699688008 2017-07 2025-08-18 Genitopatellar syndrome https://medlineplus.gov/genetics/condition/genitopatellar-syndrome descriptionGenitopatellar syndrome is a rare condition characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability, and abnormalities affecting other parts of the body.The genital abnormalities in affected males typically include undescended testes (cryptorchidism) and underdevelopment of the scrotum. Affected females can have an enlarged clitoris (clitoromegaly) and small labia.Missing or underdeveloped patellae is the most common skeletal abnormality associated with genitopatellar syndrome. Affected individuals may have additional skeletal problems, including joint deformities (contractures) involving the hips and knees or an inward- and upward-turning foot called a clubfoot. Bone abnormalities of the spine, ribs, collarbone (clavicle), and pelvis have also been reported.Genitopatellar syndrome is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an usually small head (microcephaly) and structural brain abnormalities, including underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum).People with genitopatellar syndrome may have distinctive facial features such as prominent cheeks and eyes, a nose with a rounded tip or a broad bridge, an unusually small chin (micrognathia) or a chin that protrudes (prognathism), and a narrowing of the head at the temples. Many affected infants have weak muscle tone (hypotonia) that leads to breathing and feeding difficulties. The condition can also be associated with abnormalities of the heart, kidneys, and teeth. ad Autosomal dominant KAT6B https://medlineplus.gov/genetics/gene/kat6b Absent patellae, scrotal hypoplasia, renal anomalies, facial dysmorphism, and mental retardation GPS GTR C1853566 MeSH D000015 MeSH D008607 MeSH D014564 OMIM 606170 SNOMED CT 702367005 2013-02 2020-08-18 Gestational diabetes https://medlineplus.gov/genetics/condition/gestational-diabetes descriptionGestational diabetes is a disorder characterized by abnormally high levels of blood glucose (also called blood sugar) during pregnancy. Affected women do not have diabetes before they are pregnant, and most of these women go back to being nondiabetic soon after the baby is born. The disease has a 30 to 70 percent chance of recurring in subsequent pregnancies. Additionally, about half of women with gestational diabetes develop another form of diabetes, known as type 2 diabetes, within a few years after their pregnancy.Gestational diabetes is often discovered during the second trimester of pregnancy. Most affected women have no symptoms, and the disease is discovered through routine screening at their obstetrician's office. If untreated, gestational diabetes increases the risk of pregnancy-associated high blood pressure (called preeclampsia) and early (premature) delivery of the baby.Babies of mothers with gestational diabetes tend to be large (macrosomia), which can cause complications during birth. Infants whose mothers have gestational diabetes are also more likely to develop dangerously low blood glucose levels soon after birth. Later in life, these individuals have an increased risk of developing obesity, heart disease, and type 2 diabetes. u Pattern unknown KCNQ1 https://medlineplus.gov/genetics/gene/kcnq1 KCNJ11 https://medlineplus.gov/genetics/gene/kcnj11 GCK https://medlineplus.gov/genetics/gene/gck IRS1 https://www.ncbi.nlm.nih.gov/gene/3667 MTNR1B https://www.ncbi.nlm.nih.gov/gene/4544 TCF7L2 https://www.ncbi.nlm.nih.gov/gene/6934 IGF2BP2 https://www.ncbi.nlm.nih.gov/gene/10644 CDKAL1 https://www.ncbi.nlm.nih.gov/gene/54901 Diabetes mellitus arising in pregnancy Diabetes mellitus, gestational Diabetes mellitus, pregnancy related Diabetes, pregnancy-induced GDM Gestational diabetes mellitus GTR C0085207 ICD-10-CM O24.4 ICD-10-CM O24.41 ICD-10-CM O24.410 ICD-10-CM O24.414 ICD-10-CM O24.415 ICD-10-CM O24.419 ICD-10-CM O24.42 ICD-10-CM O24.420 ICD-10-CM O24.424 ICD-10-CM O24.425 ICD-10-CM O24.429 ICD-10-CM O24.43 ICD-10-CM O24.430 ICD-10-CM O24.434 ICD-10-CM O24.435 ICD-10-CM O24.439 ICD-10-CM Z86.32 MeSH D016640 OMIM 606176 OMIM 610374 OMIM 610582 SNOMED CT 11687002 SNOMED CT 472699005 2018-01 2023-07-19 Ghosal hematodiaphyseal dysplasia https://medlineplus.gov/genetics/condition/ghosal-hematodiaphyseal-dysplasia descriptionGhosal hematodiaphyseal dysplasia is a rare inherited condition characterized by abnormally thick bones and a shortage of red blood cells (anemia). Signs and symptoms of the condition become apparent in early childhood.In affected individuals, the long bones in the arms and legs are unusually dense and wide. The bone changes specifically affect the shafts of the long bones, called diaphyses, and areas near the ends of the bones called metaphyses. The bone abnormalities can lead to bowing of the legs and difficulty walking.Ghosal hematodiaphyseal dysplasia also causes scarring (fibrosis) of the bone marrow, which is the spongy tissue inside long bones where blood cells are formed. The abnormal bone marrow cannot produce enough red blood cells, which leads to anemia. Signs and symptoms of anemia that have been reported in people with Ghosal hematodiaphyseal dysplasia include extremely pale skin (pallor) and excessive tiredness (fatigue). ar Autosomal recessive TBXAS1 https://medlineplus.gov/genetics/gene/tbxas1 Diaphyseal dysplasia associated with anemia GHDD Ghosal hemato-diaphyseal dysplasia Ghosal syndrome Ghosal-type hemato-diaphyseal dysplasia GTR C1856465 MeSH D010009 OMIM 231095 SNOMED CT 389214003 2014-03 2020-08-18 Giant axonal neuropathy https://medlineplus.gov/genetics/condition/giant-axonal-neuropathy descriptionGiant axonal neuropathy is an inherited condition characterized by abnormally large and dysfunctional axons called giant axons. Axons are specialized extensions of nerve cells (neurons) that transmit nerve impulses. Symptoms of the disorder first become apparent in the peripheral nervous system, in which long axons connect the brain and spinal cord (central nervous system) to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. However, axons in the central nervous system are affected as well.The signs and symptoms of giant axonal neuropathy generally begin in early childhood and get worse over time. Most affected individuals first have problems with walking. Later they may lose sensation, strength, and reflexes in their limbs; experience difficulty coordinating movements (ataxia); and require wheelchair assistance. Many affected individuals have an abnormal curvature of the spine (scoliosis). Visual and hearing problems may also occur. Many individuals with this condition have extremely kinky hair as compared to others in their family.Giant axonal neuropathy can also impact the autonomic nervous system, which controls involuntary body processes. Affected individuals may experience problems with constipation, heat intolerance, and the release of urine (neurogenic bladder), and a reduction in or loss of the ability to sweat.As the disorder worsens, paralysis, seizures, difficulty breathing or swallowing, and a gradual decline in mental function (dementia) can also occur. Most people with giant axonal neuropathy do not survive past their twenties.Some affected individuals have a milder form of giant axonal neuropathy that begins later in life. Movement problems in these individuals are less severe, and the signs and symptoms usually worsen at a slower rate than in the classic form of the condition. Individuals with the milder form often have straight hair, and they may survive into adulthood. ar Autosomal recessive GAN https://medlineplus.gov/genetics/gene/gan GAN Giant axonal disease GTR C1850386 MeSH D056768 OMIM 256850 SNOMED CT 128207002 2016-08 2021-08-17 Giant congenital melanocytic nevus https://medlineplus.gov/genetics/condition/giant-congenital-melanocytic-nevus descriptionGiant congenital melanocytic nevus is a skin condition characterized by an abnormally dark, noncancerous skin patch (nevus) that is composed of pigment-producing cells called melanocytes. It is present from birth (congenital) or is noticeable soon after birth. The nevus may be small in infants, but it will usually grow at the same rate the body grows and will eventually be at least 40 cm (15.75 inches) across. The nevus can appear anywhere on the body, but it is more often found on the trunk or limbs. The color ranges from tan to black and can become darker or lighter over time. The surface of a nevus can be flat, rough, raised, thickened, or bumpy; the surface can vary in different regions of the nevus, and it can change over time. The skin of the nevus is often dry and prone to irritation and itching (dermatitis). Excessive hair growth (hypertrichosis) can occur within the nevus. There is often less fat tissue under the skin of the nevus; the skin may appear thinner there than over other areas of the body.People with giant congenital melanocytic nevus may have more than one nevus (plural: nevi). The other nevi are often smaller than the giant nevus. Affected individuals may have one or two additional nevi or multiple small nevi that are scattered over the skin; these are known as satellite or disseminated nevi.Affected individuals may feel anxiety or emotional stress due to the impact the nevus may have on their appearance and their health. Children with giant congenital melanocytic nevus can develop emotional or behavior problems.Some people with giant congenital melanocytic nevus develop a condition called neurocutaneous melanosis, which is the presence of pigment-producing skin cells (melanocytes) in the tissue that covers the brain and spinal cord. These melanocytes may be spread out or grouped together in clusters. Their growth can cause increased pressure in the brain, leading to headache, vomiting, irritability, seizures, and movement problems. Tumors in the brain may also develop.Individuals with giant congenital melanocytic nevus have an increased risk of developing an aggressive form of skin cancer called melanoma, which arises from melanocytes. Estimates vary, but it is generally thought that people with giant congenital melanocytic nevus have a 5 to 10 percent lifetime risk of developing melanoma. Melanoma commonly begins in the nevus, but it can develop when melanocytes that invade other tissues, such as those in the brain and spinal cord, become cancerous. When melanoma occurs in people with giant congenital melanocytic nevus, the survival rate is low.Other types of tumors can also develop in individuals with giant congenital melanocytic nevus, including soft tissue tumors (sarcomas), fatty tumors (lipomas), and tumors of the nerve cells (schwannomas). n Not inherited BRAF https://medlineplus.gov/genetics/gene/braf NRAS https://medlineplus.gov/genetics/gene/nras Congenital giant pigmented nevus of skin Congenital melanocytic nevus syndrome Giant congenital melanocytic nevi Giant congenital pigmented nevus Giant pigmented hairy nevus GMN GPHN GTR C1842036 ICD-10-CM D22 MeSH D009508 OMIM 137550 SNOMED CT 254815002 2014-12 2023-03-21 Gilbert syndrome https://medlineplus.gov/genetics/condition/gilbert-syndrome descriptionGilbert syndrome is a relatively mild condition characterized by periods of elevated levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin, which has an orange-yellow tint, is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Gilbert syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia). In affected individuals, bilirubin levels fluctuate and very rarely increase to levels that cause jaundice, which is yellowing of the skin and whites of the eyes.Gilbert syndrome is usually recognized in adolescence. If people with this condition have episodes of hyperbilirubinemia, these episodes are generally mild and typically occur when the body is under stress, for instance because of dehydration, prolonged periods without food (fasting), illness, vigorous exercise, or menstruation. Some people with Gilbert syndrome also experience abdominal discomfort or tiredness. However, approximately 30 percent of people with Gilbert syndrome have no signs or symptoms of the condition and are discovered only when routine blood tests reveal elevated unconjugated bilirubin levels. ad Autosomal dominant ar Autosomal recessive UGT1A1 https://medlineplus.gov/genetics/gene/ugt1a1 Constitutional liver dysfunction Familial nonhemolytic jaundice Gilbert disease Gilbert's disease Gilbert's syndrome Gilbert-Lereboullet syndrome Hyperbilirubinemia 1 Meulengracht syndrome Unconjugated benign bilirubinemia GTR C0017551 ICD-10-CM E80.4 MeSH D005878 OMIM 143500 SNOMED CT 27503000 2012-02 2024-09-18 Gillespie syndrome https://medlineplus.gov/genetics/condition/gillespie-syndrome descriptionGillespie syndrome is a disorder that involves eye abnormalities, weak muscle tone from birth (congenital hypotonia), problems with balance and coordinating movements (ataxia), and mild to moderate intellectual disability.Gillespie syndrome is characterized by underdevelopment (hypoplasia) of the colored part of the eye (the iris). In most affected individuals, part of the iris is missing (partial aniridia) in both eyes. In addition, the irises have a characteristic uneven pattern known as "scalloping" at the inner (pupillary) edge. The pupils are enlarged (dilated) and are fixed, which means they do not get smaller (constrict) in response to light. These abnormalities are thought to result from problems in the development or maintenance of the tiny muscles that allow the pupil to contract (sphincter pupillae). The eye abnormalities can cause blurry vision (reduced visual acuity) and increased sensitivity to light (photophobia). Rapid, involuntary eye movements (nystagmus) can also occur in Gillespie syndrome.The balance and movement problems in Gillespie syndrome result from hypoplasia of the cerebellum, which is the part of the brain that coordinates movement. This abnormality can cause hypotonia and delayed development of motor skills such as walking. In addition, difficulty controlling the muscles of the mouth can lead to delayed speech development. The difficulties with coordination generally become noticeable in early childhood when the individual is learning these skills. People with Gillespie syndrome usually continue to have an unsteady pattern of walking (gait) and speech problems throughout life.Other features of Gillespie syndrome can include abnormalities in the bones of the spine (vertebrae) and malformations of the heart. ar Autosomal recessive ad Autosomal dominant ITPR1 https://medlineplus.gov/genetics/gene/itpr1 Aniridia, cerebellar ataxia, and mental retardation Aniridia-cerebellar ataxia-intellectual disability Aniridia-cerebellar ataxia-mental deficiency Partial aniridia-cerebellar ataxia-oligophrenia GTR C0431401 MeSH D015783 OMIM 206700 SNOMED CT 253176002 2019-01 2023-03-21 Gitelman syndrome https://medlineplus.gov/genetics/condition/gitelman-syndrome descriptionGitelman syndrome is a kidney disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.The signs and symptoms of Gitelman syndrome usually appear in late childhood or adolescence. Common features of this condition include painful muscle spasms (tetany), muscle weakness or cramping, dizziness, and salt craving. Also common is a tingling or prickly sensation in the skin (paresthesias), most often affecting the face. Some individuals with Gitelman syndrome experience excessive tiredness (fatigue), low blood pressure, and a painful joint condition called chondrocalcinosis. Studies suggest that Gitelman syndrome may also increase the risk of a potentially dangerous abnormal heart rhythm called ventricular arrhythmia.The signs and symptoms of Gitelman syndrome vary widely, even among affected members of the same family. Most people with this condition have relatively mild symptoms, although affected individuals with severe muscle cramping, paralysis, and slow growth have been reported. ar Autosomal recessive CLCNKB https://medlineplus.gov/genetics/gene/clcnkb SLC12A3 https://medlineplus.gov/genetics/gene/slc12a3 Familial hypokalemia-hypomagnesemia Gitelman's syndrome GS Hypokalemia-hypomagnesemia, primary renotubular, with hypocalciuria Tubular hypomagnesemia-hypokalemia with hypocalcuria GTR C0268450 MeSH D053579 OMIM 263800 SNOMED CT 707756004 2011-02 2020-08-18 Glanzmann thrombasthenia https://medlineplus.gov/genetics/condition/glanzmann-thrombasthenia descriptionGlanzmann thrombasthenia is a bleeding disorder that is characterized by prolonged or spontaneous bleeding starting from birth. People with Glanzmann thrombasthenia tend to bruise easily, have frequent nosebleeds (epistaxis), and may bleed from the gums. They may also develop red or purple spots on the skin caused by bleeding underneath the skin (petechiae) or swelling caused by bleeding within tissues (hematoma). Glanzmann thrombasthenia can also cause prolonged bleeding following injury, trauma, or surgery (including dental work). Women with this condition can have prolonged and sometimes abnormally heavy menstrual bleeding. Affected women also have an increased risk of excessive blood loss during pregnancy and childbirth.About a quarter of individuals with Glanzmann thrombasthenia have bleeding in the gastrointestinal tract, which often occurs later in life. Rarely, affected individuals have bleeding inside the skull (intracranial hemorrhage) or joints (hemarthrosis).The severity and frequency of the bleeding episodes in Glanzmann thrombasthenia can vary greatly among affected individuals, even in the same family. Spontaneous bleeding tends to become less frequent with age. ar Autosomal recessive ITGA2B https://medlineplus.gov/genetics/gene/itga2b ITGB3 https://medlineplus.gov/genetics/gene/itgb3 Deficiency of glycoprotein complex IIb-IIIa Deficiency of platelet fibrinogen receptor Glanzmann disease Glanzmann-Naegeli disorder Glycoprotein IIb/IIIa defect Hereditary hemorrhagic thrombasthenia Hereditary thrombasthenia Platelet fibrinogen receptor deficiency GTR C0040015 ICD-10-CM D69.1 MeSH D013915 OMIM 273800 SNOMED CT 32942005 2015-09 2020-08-18 Globozoospermia https://medlineplus.gov/genetics/condition/globozoospermia descriptionGlobozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility).Normal sperm cells have an oval-shaped head with a cap-like covering called the acrosome. The acrosome contains enzymes that break down the outer membrane of an egg cell, allowing the sperm to fertilize the egg. The sperm cells of males with globozoospermia, however, have a round head and no acrosome. The abnormal sperm are unable to fertilize an egg cell, leading to infertility. ar Autosomal recessive DPY19L2 https://medlineplus.gov/genetics/gene/dpy19l2 Acrosome malformation of spermatozoa Round-headed spermatozoa Spermatogenic failure 9 GTR C0403825 MeSH D000072660 OMIM 613958 SNOMED CT 236818008 2015-04 2020-08-18 Glucose phosphate isomerase deficiency https://medlineplus.gov/genetics/condition/glucose-phosphate-isomerase-deficiency descriptionGlucose phosphate isomerase (GPI) deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness (fatigue), shortness of breath (dyspnea), and a rapid heart rate (tachycardia). An enlarged spleen (splenomegaly), an excess of iron in the blood, and small pebble-like deposits in the gallbladder or bile ducts (gallstones) may also occur in this disorder.Hemolytic anemia in GPI deficiency can range from mild to severe. In the most severe cases, affected individuals do not survive to birth. Individuals with milder disease can survive into adulthood. People with any level of severity of the disorder can have episodes of more severe hemolysis, called hemolytic crises, which can be triggered by bacterial or viral infections.A small percentage of individuals with GPI deficiency also have neurological problems, including intellectual disability and difficulty with coordinating movements (ataxia). ar Autosomal recessive GPI https://medlineplus.gov/genetics/gene/gpi Glucose-6-phosphate isomerase deficiency Glucosephosphate isomerase deficiency GPI deficiency Nonspherocytic hemolytic anemia due to glucose phosphate isomerase deficiency GTR C0272064 MeSH D000745 OMIM 613470 SNOMED CT 124669001 SNOMED CT 234404008 SNOMED CT 52413004 2013-12 2020-08-18 Glucose-6-phosphate dehydrogenase deficiency https://medlineplus.gov/genetics/condition/glucose-6-phosphate-dehydrogenase-deficiency descriptionGlucose-6-phosphate dehydrogenase deficiency is a genetic disorder that affects red blood cells, which carry oxygen from the lungs to tissues throughout the body. In affected individuals, a defect in an enzyme called glucose-6-phosphate dehydrogenase causes red blood cells to break down prematurely. This destruction of red blood cells is called hemolysis.The most common medical problem associated with glucose-6-phosphate dehydrogenase deficiency is hemolytic anemia, which occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the skin and whites of the eyes (jaundice), dark urine, fatigue, shortness of breath, and a rapid heart rate. In people with glucose-6-phosphate dehydrogenase deficiency, hemolytic anemia is most often triggered by bacterial or viral infections or by certain drugs (such as some antibiotics and medications used to treat malaria). Hemolytic anemia can also occur after eating fava beans or inhaling pollen from fava plants (a reaction called favism).Glucose-6-phosphate dehydrogenase deficiency is also a significant cause of mild to severe jaundice in newborns. Many people with this disorder, however, never experience any signs or symptoms and are unaware that they have the condition. x X-linked G6PD https://medlineplus.gov/genetics/gene/g6pd Deficiency of glucose-6-phosphate dehydrogenase G6PD deficiency G6PDD Glucose 6 phosphate dehydrogenase deficiency GTR C2720289 ICD-10-CM D55.0 MeSH D005955 OMIM 305900 SNOMED CT 124134002 SNOMED CT 62403005 2023-04 2025-04-03 Glucose-galactose malabsorption https://medlineplus.gov/genetics/condition/glucose-galactose-malabsorption descriptionGlucose-galactose malabsorption is a condition in which the body cannot take in (absorb) the sugars glucose and galactose, which primarily results in severe diarrhea. Beginning in infancy, severe diarrhea results in weight loss and dehydration that can be life-threatening. Small amounts of the simple sugar glucose in the urine (mild glucosuria) may occur in this disorder. Rarely, affected infants develop kidney stones due to deposits of calcium in the kidneys (nephrocalcinosis).The signs and symptoms of glucose-galactose malabsorption appear early in life when affected infants are fed breast milk or regular infant formulas. These foods contain glucose, galactose, and another sugar called lactose that gets broken down into these two sugars. When these sugar-containing foods are ingested by affected individuals, it leads to diarrhea and other health problems. If foods that contain glucose, galactose, and lactose are removed from the diet, the diarrhea stops. ar Autosomal recessive SLC5A1 https://medlineplus.gov/genetics/gene/slc5a1 Carbohydrate intolerance Complex carbohydrate intolerance Congenital glucose-galactose intolerance Congenital glucose-galactose malabsorption GGM Monosaccharide malabsorption GTR C0268186 MeSH D008286 OMIM 606824 SNOMED CT 190749000 SNOMED CT 27943000 2020-04 2020-08-18 Glutamate formiminotransferase deficiency https://medlineplus.gov/genetics/condition/glutamate-formiminotransferase-deficiency descriptionGlutamate formiminotransferase deficiency is a rare inherited disorder that can affect development.In the past, researchers recognized a mild form and a severe form of glutamate formiminotransferase deficiency. Researchers have since found people who received a diagnosis of glutamate formiminotransferase deficiency as infants who do not appear to have any related health problems. Researchers are actively working to learn more about this condition. The signs and symptoms associated with glutamate formiminotransferase deficiency have ranged from mild developmental delays with high urine levels of a molecule called formiminoglutamate (FIGLU) to more severe intellectual disabilities and megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia) and the remaining red blood cells are larger than normal (megaloblastic). ar Autosomal recessive FTCD https://medlineplus.gov/genetics/gene/ftcd Arakawa syndrome 1 FIGLU-uria Formiminoglutamic acidemia Formiminoglutamic aciduria Formiminotransferase cyclodeaminase deficiency Formiminotransferase deficiency FTCD deficiency GTR C0268609 MeSH D008661 OMIM 229100 SNOMED CT 59761008 2025-06 2025-06-06 Glutaric acidemia type I https://medlineplus.gov/genetics/condition/glutaric-acidemia-type-i descriptionGlutaric acidemia type I (also called glutaric aciduria type I) is an inherited disorder in which the body is unable to process certain proteins properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.People with glutaric acidemia type I have inadequate levels of an enzyme that helps break down the amino acids lysine, hydroxylysine, and tryptophan, which are building blocks of protein. Excessive levels of these amino acids and their intermediate breakdown products can accumulate and cause damage to the brain, particularly the basal ganglia, which are regions that help control movement. Intellectual disability may also occur.The severity of glutaric acidemia type I varies widely; some individuals are only mildly affected, while others have severe problems. In most cases, signs and symptoms first occur in infancy or early childhood, but in a small number of affected individuals, the disorder first becomes apparent in adolescence or adulthood.Some babies with glutaric acidemia type I are born with unusually large heads (macrocephaly). Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity, or decreased muscle tone. Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. Strict dietary control may help limit progression of the neurological damage. Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery. ar Autosomal recessive GCDH https://medlineplus.gov/genetics/gene/gcdh GA I Glutaric acidemia I Glutaric acidemia type 1 Glutaric aciduria I Glutaryl-CoA dehydrogenase deficiency GTR C0268595 MeSH D000592 OMIM 231670 SNOMED CT 76175005 2007-03 2020-08-18 Glutaric acidemia type II https://medlineplus.gov/genetics/condition/glutaric-acidemia-type-ii descriptionGlutaric acidemia type II is an inherited disorder that interferes with the body's ability to break down proteins and fats to produce energy. Incompletely processed proteins and fats can build up in the body and cause the blood and tissues to become too acidic (metabolic acidosis).Glutaric acidemia type II usually appears in infancy or early childhood as a sudden episode called a metabolic crisis, in which acidosis and low blood glucose (hypoglycemia) cause weakness, behavior changes such as poor feeding and decreased activity, and vomiting. These metabolic crises, which can be life-threatening, may be triggered by common childhood illnesses or other stresses.In the most severe cases of glutaric acidemia type II, affected individuals may also be born with physical abnormalities. These may include brain malformations, an enlarged liver (hepatomegaly), a weakened and enlarged heart (dilated cardiomyopathy), fluid-filled cysts and other malformations of the kidneys, unusual facial features, and genital abnormalities. Glutaric acidemia type II may also cause a characteristic odor resembling that of sweaty feet.Some affected individuals have less severe symptoms that begin later in childhood or in adulthood. In the mildest forms of glutaric acidemia type II, muscle weakness developing in adulthood may be the first sign of the disorder. ar Autosomal recessive ETFA https://medlineplus.gov/genetics/gene/etfa ETFB https://medlineplus.gov/genetics/gene/etfb ETFDH https://medlineplus.gov/genetics/gene/etfdh Electron transfer flavoprotein deficiency EMA ETFA deficiency ETFB deficiency ETFDH deficiency Ethylmalonic-adipicaciduria GA II Glutaric acidemia, type 2 Glutaric aciduria, type 2 MAD MADD Multiple acyl-CoA dehydrogenase deficiency Multiple FAD dehydrogenase deficiency GTR C0268596 ICD-10-CM E71.313 MeSH D054069 OMIM 231680 SNOMED CT 22886006 2008-07 2023-07-26 Glutathione synthetase deficiency https://medlineplus.gov/genetics/condition/glutathione-synthetase-deficiency descriptionGlutathione synthetase deficiency is a disorder that prevents the production of an important molecule called glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components.Glutathione synthetase deficiency can be classified into three types: mild, moderate, and severe. Mild glutathione synthetase deficiency usually results in the destruction of red blood cells (hemolytic anemia). In addition, affected individuals may release large amounts of a compound called 5-oxoproline in their urine (5-oxoprolinuria). This compound builds up when glutathione is not processed correctly in cells.Individuals with moderate glutathione synthetase deficiency may experience symptoms beginning shortly after birth including hemolytic anemia, 5-oxoprolinuria, and elevated acidity in the blood and tissues (metabolic acidosis).In addition to the features present in moderate glutathione synthetase deficiency, individuals affected by the severe form of this disorder may experience neurological symptoms. These problems may include seizures; a generalized slowing down of physical reactions, movements, and speech (psychomotor retardation); intellectual disability; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections. ar Autosomal recessive GSS https://medlineplus.gov/genetics/gene/gss 5-oxoprolinemia 5-oxoprolinuria Deficiency of glutathione synthase Deficiency of glutathione synthetase Pyroglutamic acidemia Pyroglutamic aciduria GTR C0398746 GTR C1856399 MeSH D008661 OMIM 231900 OMIM 266130 SNOMED CT 124706000 SNOMED CT 234589002 SNOMED CT 39112005 2015-03 2020-08-18 Glycogen storage disease type 0 https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-0 descriptionGlycogen storage disease type 0 (also known as GSD 0) is a condition caused by the body's inability to form a complex sugar called glycogen, which is a major source of stored energy in the body. GSD 0 has two types: in muscle GSD 0, glycogen formation in the muscles is impaired, and in liver GSD 0, glycogen formation in the liver is impaired.The signs and symptoms of muscle GSD 0 typically begin in early childhood. Affected individuals often experience muscle pain and weakness or episodes of fainting (syncope) following moderate physical activity, such as walking up stairs. The loss of consciousness that occurs with fainting typically lasts up to several hours. Some individuals with muscle GSD 0 have a disruption of the heart's normal rhythm (arrhythmia) known as long QT syndrome. In all affected individuals, muscle GSD 0 impairs the heart's ability to effectively pump blood and increases the risk of cardiac arrest and sudden death, particularly after physical activity. Sudden death from cardiac arrest can occur in childhood or adolescence in people with muscle GSD 0.Individuals with liver GSD 0 usually show signs and symptoms of the disorder in infancy. People with this disorder develop low blood sugar (glucose), known as hypoglycemia, after going long periods of time without food (fasting). Signs of hypoglycemia become apparent when affected infants begin sleeping through the night and stop late-night feedings; these infants exhibit extreme tiredness (lethargy), pale skin (pallor), and nausea. During episodes of fasting, ketone levels in the blood may increase (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars (such as glycogen) are unavailable. These short-term signs and symptoms of liver GSD 0 often improve when food is eaten and glucose levels in the body return to normal. The features of liver GSD 0 vary; they can be mild and go unnoticed for years, or they can include developmental delay and growth failure. ar Autosomal recessive GYS1 https://medlineplus.gov/genetics/gene/gys1 GYS2 https://medlineplus.gov/genetics/gene/gys2 Glycogen storage disease 0 Glycogen synthase deficiency Glycogen synthetase deficiency GSD 0 GSD type 0 Hypoglycemia with deficiency of glycogen synthetase GTR C1855861 GTR C1969054 ICD-10-CM E74.09 MeSH D006008 OMIM 240600 OMIM 611556 SNOMED CT 237964009 2014-01 2023-07-19 Glycogen storage disease type I https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-i descriptionGlycogen storage disease type I (also known as GSDI or von Gierke disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially the liver, kidneys, and small intestines, impairs their ability to function normally.Signs and symptoms of this condition typically appear around the age of 3 or 4 months, when babies start to sleep through the night and do not eat as frequently as newborns. Affected infants may have low blood sugar (hypoglycemia), which can lead to seizures. They can also have a buildup of lactic acid in the body (lactic acidosis), high blood levels of a waste product called uric acid (hyperuricemia), and excess amounts of fats in the blood (hyperlipidemia). As they get older, children with GSDI have thin arms and legs and short stature. An enlarged liver may give the appearance of a protruding abdomen. The kidneys may also be enlarged. Affected individuals may also have diarrhea and deposits of cholesterol in the skin (xanthomas).People with GSDI may experience delayed puberty. Beginning in young to mid-adulthood, affected individuals may have thinning of the bones (osteoporosis), a form of arthritis resulting from uric acid crystals in the joints (gout), kidney disease, and high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Females with this condition may also have abnormal development of the ovaries (polycystic ovaries). In affected teens and adults, tumors called adenomas may form in the liver. Adenomas are usually noncancerous (benign), but occasionally these tumors can become cancerous (malignant).Researchers have described two types of GSDI, which differ in their signs and symptoms and genetic cause. These types are known as glycogen storage disease type Ia (GSDIa) and glycogen storage disease type Ib (GSDIb). Two other forms of GSDI have been described, and they were originally named types Ic and Id. However, these types are now known to be variations of GSDIb; for this reason, GSDIb is sometimes called GSD type I non-a.Many people with GSDIb have a shortage of white blood cells (neutropenia), which can make them prone to recurrent bacterial infections. Neutropenia is usually apparent by age 1. Many affected individuals also have inflammation of the intestinal walls (inflammatory bowel disease). People with GSDIb may have oral problems including cavities, inflammation of the gums (gingivitis), chronic gum (periodontal) disease, abnormal tooth development, and open sores (ulcers) in the mouth. The neutropenia and oral problems are specific to people with GSDIb and are typically not seen in people with GSDIa. ar Autosomal recessive G6PC1 https://medlineplus.gov/genetics/gene/g6pc1 SLC37A4 https://medlineplus.gov/genetics/gene/slc37a4 Glucose-6-phosphate deficiency Glucose-6-phosphate transport defect GSD I GSD type I Hepatorenal form of glycogen storage disease Hepatorenal glycogenosis Von Gierke disease Von Gierke's disease GTR C0017920 GTR C0268146 GTR C2919796 ICD-10-CM E74.01 MeSH D005953 OMIM 232200 OMIM 232220 SNOMED CT 124437004 SNOMED CT 30102006 SNOMED CT 444707001 SNOMED CT 7265005 2010-09 2025-04-03 Glycogen storage disease type III https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-iii descriptionGlycogen storage disease type III (also known as GSDIII or Cori disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles.GSDIII is divided into types IIIa, IIIb, IIIc, and IIId, which are distinguished by their pattern of signs and symptoms. GSD types IIIa and IIIc mainly affect the liver and muscles, and GSD types IIIb and IIId typically affect only the liver. It is very difficult to distinguish between the types of GSDIII that affect the same tissues. GSD types IIIa and IIIb are the most common forms of this condition.Beginning in infancy, individuals with any type of GSDIII may have low blood glucose (hypoglycemia), excess amounts of fats in the blood (hyperlipidemia), and elevated blood levels of liver enzymes. As they get older, children with this condition typically develop an enlarged liver (hepatomegaly). Liver size usually returns to normal during adolescence, but some affected individuals develop chronic liver disease (cirrhosis) and liver failure later in life. People with GSDIII often have slow growth because of their liver problems, which can lead to short stature. In a small percentage of people with GSDIII, noncancerous (benign) tumors called adenomas may form in the liver.Individuals with GSDIIIa may develop muscle weakness (myopathy) later in life. These muscle problems can affect both heart (cardiac) muscle and the muscles that are used for movement (skeletal muscles). Muscle involvement varies greatly among affected individuals. The first signs and symptoms are typically poor muscle tone (hypotonia) and mild myopathy in early childhood. The myopathy may become severe by early to mid-adulthood. Some people with GSDIIIa have a weakened heart muscle (cardiomyopathy), but affected individuals usually do not experience heart failure. Other people affected with GSDIIIa have no cardiac muscle problems. ar Autosomal recessive AGL https://medlineplus.gov/genetics/gene/agl AGL deficiency Cori disease Cori's disease Debrancher deficiency Forbes disease Glycogen debrancher deficiency GSD III GSD3 Limit dextrinosis GTR C0017922 ICD-10-CM E74.03 MeSH D006010 OMIM 232400 SNOMED CT 66937008 2010-09 2023-07-26 Glycogen storage disease type IV https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-iv descriptionGlycogen storage disease type IV (GSD IV) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles. There are five types of GSD IV, which are distinguished by their severity, signs, and symptoms.The fatal perinatal neuromuscular type is the most severe form of GSD IV, with signs developing before birth. Excess fluid may build up around the fetus (polyhydramnios) and in the fetus' body. Affected fetuses have a condition called fetal akinesia deformation sequence, which causes a decrease in fetal movement and can lead to joint stiffness (arthrogryposis) after birth. Infants with the fatal perinatal neuromuscular type of GSD IV have very low muscle tone (severe hypotonia) and muscle wasting (atrophy). These infants usually do not survive past the newborn period due to weakened heart and breathing muscles.The congenital muscular type of GSD IV is usually not evident before birth but develops in early infancy. Affected infants have severe hypotonia, which affects the muscles needed for breathing. These babies often have dilated cardiomyopathy, which enlarges and weakens the heart (cardiac) muscle, preventing the heart from pumping blood efficiently. Infants with the congenital muscular type of GSD IV typically survive only a few months.The progressive hepatic type is the most common form of GSD IV. Within the first months of life, affected infants have difficulty gaining weight and growing at the expected rate (failure to thrive) and develop an enlarged liver (hepatomegaly). Children with this type develop a form of liver disease called cirrhosis that often is irreversible. High blood pressure in the vein that supplies blood to the liver (portal hypertension) and an abnormal buildup of fluid in the abdominal cavity (ascites) can also occur. By age 1 or 2, affected children develop hypotonia. Children with the progressive hepatic type of GSD IV often die of liver failure in early childhood.The non-progressive hepatic type of GSD IV has many of the same features as the progressive hepatic type, but the liver disease is not as severe. In the non-progressive hepatic type, hepatomegaly and liver disease are usually evident in early childhood, but affected individuals typically do not develop cirrhosis. People with this type of the disorder can also have hypotonia and muscle weakness (myopathy). Most individuals with this type survive into adulthood, although life expectancy varies depending on the severity of the signs and symptoms.The childhood neuromuscular type of GSD IV develops in late childhood and is characterized by myopathy and dilated cardiomyopathy. The severity of this type of GSD IV varies greatly; some people have only mild muscle weakness while others have severe cardiomyopathy and die in early adulthood. ar Autosomal recessive GBE1 https://medlineplus.gov/genetics/gene/gbe1 Amylopectinosis Andersen disease Andersen glycogenosis Andersen's disease Brancher deficiency Branching enzyme deficiency Glycogen branching enzyme deficiency Glycogen storage disease IV Glycogen storage disease type 4 Glycogenosis 4 Glycogenosis, type IV GSD IV GSD type IV GSD4 Type IV glycogenosis GTR C0017923 ICD-10-CM E74.09 MeSH D006011 OMIM 232500 SNOMED CT 11179002 SNOMED CT 124267007 2013-02 2023-03-21 Glycogen storage disease type IX https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-ix descriptionGlycogen storage disease type IX (also known as GSD IX) is a condition caused by the inability to break down a complex sugar called glycogen. The different forms of the condition can affect glycogen breakdown in liver cells or muscle cells or sometimes both. A lack of glycogen breakdown interferes with the normal function of the affected tissue.When GSD IX affects the liver, the signs and symptoms typically begin in early childhood. The initial features are usually an enlarged liver (hepatomegaly) and slow growth. Affected children are often shorter than normal. During prolonged periods without food (fasting), affected individuals may have low blood sugar (hypoglycemia) or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars are unavailable. Affected children may have delayed development of motor skills, such as sitting, standing, or walking, and some have mild muscle weakness. Puberty is delayed in some adolescents with GSD IX. In the form of the condition that affects the liver, the signs and symptoms usually improve with age. Typically, individuals catch up developmentally, and adults reach normal height. However, some affected individuals have a buildup of scar tissue (fibrosis) in the liver, which can rarely progress to irreversible liver disease (cirrhosis).GSD IX can affect muscle tissue, although this form of the condition is very rare and not well understood. The features of this form of the condition can appear anytime from childhood to adulthood. Affected individuals may experience fatigue, muscle pain, and cramps, especially during exercise (exercise intolerance). Most affected individuals have muscle weakness that worsens over time. GSD IX can cause myoglobinuria, which occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin that is excreted in the urine. Myoglobinuria can cause the urine to be red or brown.In a small number of people with GSD IX, the liver and muscles are both affected. These individuals develop a combination of the features described above, although the muscle problems are usually mild. xr X-linked recessive ar Autosomal recessive PHKA1 https://medlineplus.gov/genetics/gene/phka1 PHKA2 https://medlineplus.gov/genetics/gene/phka2 PHKB https://medlineplus.gov/genetics/gene/phkb PHKG2 https://medlineplus.gov/genetics/gene/phkg2 GSD IX GSDIX PhK deficiency Phosphorylase b kinase deficiency Phosphorylase kinase deficiency GTR C0543514 GTR C1845151 GTR C2751643 GTR C3694531 MeSH D006008 OMIM 261750 OMIM 300559 OMIM 306000 OMIM 613027 SNOMED CT 235908005 SNOMED CT 860860004 2012-09 2020-08-18 Glycogen storage disease type V https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-v descriptionGlycogen storage disease type V (also known as GSDV or McArdle disease) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells. A lack of glycogen breakdown interferes with the function of muscle cells.People with GSDV typically experience fatigue, muscle pain, and cramps during the first few minutes of exercise (exercise intolerance). Exercise such as weight lifting or jogging usually triggers these symptoms in affected individuals. The discomfort is generally alleviated with rest. If individuals rest after brief exercise and wait for their pain to go away, they can usually resume exercising with little or no discomfort (a characteristic phenomenon known as "second wind").Prolonged or intense exercise can cause muscle damage in people with GSDV. About half of people with GSDV experience breakdown of muscle tissue (rhabdomyolysis). In severe episodes, the destruction of muscle tissue releases a protein called myoglobin, which is filtered through the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, and it is estimated that half of those individuals with GSDV who have myoglobinuria will develop life-threatening kidney failure.The signs and symptoms of GSDV can vary significantly in affected individuals. The features of this condition typically begin in a person's teens or twenties, but they can appear anytime from infancy to adulthood. In most people with GSDV, the muscle weakness worsens over time; however, in about one-third of affected individuals, the muscle weakness is stable. Some people with GSDV experience mild symptoms such as poor stamina; others do not experience any symptoms. ar Autosomal recessive PYGM https://medlineplus.gov/genetics/gene/pygm Glycogen storage disease type 5 Glycogenosis 5 GSD type V GSD V McArdle disease McArdle syndrome McArdle type glycogen storage disease McArdle's disease Muscle glycogen phosphorylase deficiency Muscle phosphorylase deficiency Myophosphorylase deficiency PYGM deficiency GTR C0017924 ICD-10-CM E74.04 MeSH D006012 OMIM 232600 SNOMED CT 55912009 2010-07 2020-08-18 Glycogen storage disease type VI https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-vi descriptionGlycogen storage disease type VI (also known as GSDVI or Hers disease) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in liver cells. A lack of glycogen breakdown interferes with the normal function of the liver.The signs and symptoms of GSDVI typically begin in infancy to early childhood. The first sign is usually an enlarged liver (hepatomegaly). During prolonged periods without food (fasting), affected individuals may have low blood sugar (hypoglycemia) or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars are unavailable. Children with GSDVI tend to grow slower than their peers, but they often achieve normal height as adults. Some affected children also have mild delays in the development of motor skills, such as sitting, standing, or walking.The signs and symptoms of GSDVI tend to improve with age; most adults with this condition do not have any related health problems. ar Autosomal recessive PYGL https://medlineplus.gov/genetics/gene/pygl GSD type VI GSD VI GSD6 Hepatic glycogen phosphorylase deficiency Hers disease Liver phosphorylase deficiency syndrome GTR C0017925 ICD-10-CM E74.09 MeSH D006013 OMIM 232700 SNOMED CT 29291001 2010-09 2020-08-18 Glycogen storage disease type VII https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-vii descriptionGlycogen storage disease type VII (GSDVII) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells. A lack of glycogen breakdown interferes with the function of muscle cells.There are four types of GSDVII. They are differentiated by their signs and symptoms and the age at which symptoms first appear.The classical form of GSDVII is the most common form. Its features usually appear in childhood. This form is characterized by muscle pain and cramps, often following moderate exercise; strenuous exercise can lead to nausea and vomiting. During exercise, muscle tissue can be abnormally broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can damage the kidneys and lead to kidney failure. Some people with the classical form of GSDVII develop high levels of a waste product called uric acid in the blood (hyperuricemia) because the damaged kidneys are unable to remove uric acid effectively. Affected individuals may also have elevated levels of a molecule called bilirubin in the blood that can cause yellowing of the skin and whites of the eyes (jaundice). Individuals with classical GSDVII often have elevated levels of an enzyme called creatine kinase in their blood. This finding is a common indicator of muscle disease.Infants with the severe infantile form of GSDVII have low muscle tone (hypotonia) at birth, which leads to muscle weakness (myopathy) that worsens over time. Affected infants have a weakened and enlarged heart (cardiomyopathy) and difficulty breathing normally. Individuals with this form of GSDVII usually do not survive past their first year of life.In the late-onset form of GSDVII, myopathy is typically the only feature. The muscle weakness appears in adulthood, although some individuals have difficulty with sustained exercise starting in childhood. The weakness generally affects the muscles closest to the center of the body (proximal muscles).The hemolytic form of GSDVII is characterized by hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, causing a shortage of red blood cells (anemia). People with the hemolytic form of GSDVII do not experience any signs or symptoms of muscle pain or weakness related to the disorder. ar Autosomal recessive PFKM https://medlineplus.gov/genetics/gene/pfkm Glycogenosis 7 GSD VII GSD7 Muscle phosphofructokinase deficiency PFKM deficiency Phosphofructokinase deficiency Tarui disease GTR C0017926 MeSH D006014 OMIM 232800 SNOMED CT 89597008 2014-04 2023-07-26 Glycoprotein VI deficiency https://medlineplus.gov/genetics/condition/glycoprotein-vi-deficiency descriptionGlycoprotein VI deficiency is a bleeding disorder associated with a decreased ability to form blood clots. Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. Because people with glycoprotein VI deficiency cannot form blood clots normally, they have an increased risk of nosebleeds (epistaxis) and may experience abnormally heavy or prolonged bleeding following minor injury or surgery. In some affected individuals, spontaneous bleeding under the skin causes areas of discoloration (ecchymosis). Women with glycoprotein VI deficiency often have heavy or prolonged menstrual periods (menorrhagia). ar Autosomal recessive GP6 https://medlineplus.gov/genetics/gene/gp6 BDPLT11 Bleeding diathesis due to a collagen receptor defect Bleeding disorder, platelet-type, 11 GP VI deficiency GTR C3280120 MeSH D025861 OMIM 614201 SNOMED CT 234470000 2017-03 2023-07-11 Gnathodiaphyseal dysplasia https://medlineplus.gov/genetics/condition/gnathodiaphyseal-dysplasia descriptionGnathodiaphyseal dysplasia is a disorder that affects the bones. People with this condition have reduced bone mineral density (osteopenia), which causes the bones to be unusually fragile. As a result, affected individuals typically experience multiple bone fractures in childhood, often from mild trauma or with no apparent cause.While most bone tissue is less dense than normal in gnathodiaphyseal dysplasia, the outer layer (cortex) of the shafts of the long bones in the arms and legs is abnormally hard and thick (diaphyseal sclerosis). Bowing of the long bones also occurs in this disorder.Jaw problems are common in gnathodiaphyseal dysplasia; the prefix "gnatho-" in the condition name refers to the jaw. Affected individuals may develop bone infections (osteomyelitis) in the jaw, which can lead to pain, swelling, discharge of pus from the gums, loose teeth, and slow healing after teeth are lost or extracted. Areas of the jawbone may lose the protective coverage of the gums, which can result in deterioration of the exposed bone (osteonecrosis of the jaw). Also, normal bone in areas of the jaw may be replaced by fibrous tissue and a hard material called cementum, which normally surrounds the roots of teeth and anchors them in the jaw. These areas of abnormal bone, called cementoosseous lesions, may be present at birth or develop later in life.When gnathodiaphyseal dysplasia was first described, it was thought to be a variation of another bone disorder called osteogenesis imperfecta, which is also characterized by frequent bone fractures. However, gnathodiaphyseal dysplasia is now generally considered to be a separate condition. Unlike in osteogenesis imperfecta, the fractures in gnathodiaphyseal dysplasia heal normally without causing deformity or loss of height. ad Autosomal dominant ANO5 https://medlineplus.gov/genetics/gene/ano5 GDD Gnathodiaphyseal sclerosis Levin syndrome 2 Osteogenesis imperfecta with unusual skeletal lesions Osteogenesis imperfecta, Levin type GTR C1833736 MeSH D010009 OMIM 166260 SNOMED CT 715568002 2014-12 2023-03-21 Gordon Holmes syndrome https://medlineplus.gov/genetics/condition/gordon-holmes-syndrome descriptionGordon Holmes syndrome is a rare condition characterized by reproductive and neurological problems. One of the key features of the condition is reduced production of hormones that direct sexual development (hypogonadotropic hypogonadism). Many affected individuals have a delay in development of the typical signs of puberty, such as the growth of facial hair and deepening of the voice in males, and the start of monthly periods (menstruation) and breast development in females. Some never undergo puberty. While some people with Gordon Holmes syndrome seem to have normal puberty, they develop other problems with the reproductive system later in life.In early adulthood, individuals with Gordon Holmes syndrome develop neurological problems, usually beginning with speech difficulties (dysarthria). As the condition worsens, affected individuals have problems with balance and coordination (cerebellar ataxia), often leading to difficulties with activities of daily living and a need for wheelchair assistance. Some affected individuals also develop memory problems and a decline in intellectual function (dementia). ar Autosomal recessive PNPLA6 https://medlineplus.gov/genetics/gene/pnpla6 RNF216 https://medlineplus.gov/genetics/gene/rnf216 Cerebellar ataxia and hypogonadotropic hypogonadism Deficiency of luteinizing hormone-releasing hormone with ataxia LHRH deficiency and ataxia GTR C1859305 MeSH D002526 MeSH D007006 OMIM 212840 SNOMED CT 230240004 2017-07 2020-08-18 Gorlin syndrome https://medlineplus.gov/genetics/condition/gorlin-syndrome descriptionGorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors.In people with Gorlin syndrome, the type of cancer diagnosed most often is basal cell carcinoma, which is the most common form of skin cancer. Individuals with Gorlin syndrome typically begin to develop basal cell carcinomas during adolescence or early adulthood. These cancers occur most often on the face, chest, and back. The number of basal cell carcinomas that develop during a person's lifetime varies among affected individuals. Some people with Gorlin syndrome never develop any basal cell carcinomas, while others may develop thousands of these cancers. Individuals with lighter skin are more likely to develop basal cell carcinomas than are people with darker skin. The number of carcinomas may be reduced with ongoing treatment.Most people with Gorlin syndrome also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors. These tumors usually first appear during adolescence, and new tumors form until about age 30. Keratocystic odontogenic tumors rarely develop later in adulthood. If untreated, these tumors may cause painful facial swelling and tooth displacement.Individuals with Gorlin syndrome have a higher risk than the general population of developing other tumors. A small proportion of affected individuals develop a brain tumor called medulloblastoma during childhood. A type of benign tumor called a fibroma can occur in the heart or in a woman's ovaries. Heart (cardiac) fibromas often do not cause any symptoms, but they may obstruct blood flow or cause irregular heartbeats (arrhythmia). Ovarian fibromas are not thought to affect a woman's ability to have children (fertility).Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull. These signs and symptoms are typically apparent from birth or become evident in early childhood. ad Autosomal dominant PTCH1 https://medlineplus.gov/genetics/gene/ptch1 SUFU https://www.ncbi.nlm.nih.gov/gene/51684 Basal cell nevus syndrome BCNS Gorlin-Goltz syndrome NBCCS Nevoid basal cell carcinoma syndrome GTR C0004779 MeSH D001478 OMIM 109400 SNOMED CT 69408002 2012-10 2023-03-28 Gorlin-Chaudhry-Moss syndrome https://medlineplus.gov/genetics/condition/gorlin-chaudhry-moss-syndrome descriptionGorlin-Chaudhry-Moss syndrome is a condition that affects many parts of the body. The signs and symptoms of this disorder are apparent from birth or infancy.Gorlin-Chaudhry-Moss syndrome is characterized by the premature closure of certain bones of the skull (craniosynostosis) during development, which affects the shape of the head and face. Many people with this disorder have a premature fusion of skull bones along the coronal suture, the growth line that goes over the head from ear to ear. These changes can result in a head that is abnormally wide and pointed at the top (acrobrachycephaly). Affected individuals also have distinctive facial characteristics that can include a flat or sunken appearance of the middle of the face (midface hypoplasia), and small eyes (microphthalmia) with narrowed openings (narrowed palpebral fissures). Affected individuals may also have farsightedness (hyperopia) and dental problems such as small teeth (microdontia) or fewer teeth than normal (hypodontia).Many people with Gorlin-Chaudhry-Moss syndrome have a lack of fatty tissue under the skin (lipodystrophy). The lack of fat, together with thin, wrinkled, loose skin and veins visible beneath the skin, makes affected individuals look older than their biological age. This appearance of premature aging is sometimes described as progeroid.Affected individuals also have excessive hair growth (hypertrichosis) on their face and body. They have a low hairline on the forehead and their scalp hair is often coarse. People with Gorlin-Chaudhry-Moss syndrome also have shortened bones at the ends of the fingers and toes (short distal phalanges). Affected females have unusually small external genital folds (hypoplasia of the labia majora).Some individuals with Gorlin-Chaudhry-Moss syndrome have mild developmental delay but intelligence is usually normal in this disorder, as is life expectancy. ad Autosomal dominant SLC25A24 https://medlineplus.gov/genetics/gene/slc25a24 Craniofacial dysostosis, hypertrichosis, hypoplasia of labia majora, dental and eye anomalies, patent ductus arteriosus, and normal intelligence Craniofacial dysostosis, patent ductus arteriosus, hypertrichosis, hypoplasia of labia majora, dental and eye anomalies GCM syndrome GCMS Gorlin Chaudhry Moss syndrome GTR C2676780 MeSH D003398 MeSH D006983 OMIM 612289 SNOMED CT 205800003 2018-02 2020-08-18 Gout https://medlineplus.gov/genetics/condition/gout descriptionGout is a type of arthritis, which is a group of related disorders caused by episodes of abnormal inflammation in the joints. People with gout have high levels of a substance called urate in the blood (hyperuricemia). Gout develops when hyperuricemia leads to the formation of urate crystals in joints, triggering an inflammatory response from the immune system.In people with gout, the first episode of inflammation (called a flare) usually affects the big toe or other joints in the foot or ankle. If urate levels remain high, flares can recur, affecting additional joints throughout the body. The time between flares varies among affected individuals; however, most people who experience multiple flares have their second one within a year of their first.Flares usually begin at night and can last several days. It is unclear what causes a flare to stop; the body likely turns off the inflammation response after a certain period of time. During a flare, individuals can experience throbbing or burning pain, swelling, warmth, redness, and difficulty moving the affected joint. Fevers may occur, after which the skin over the affected joint can begin to peel. Without treatment, people with gout can experience frequent flares and joint pain and damage, which can limit mobility and decrease quality of life.In about 15 percent of people with gout, urate accumulates in the kidneys and forms kidney stones. As the condition worsens, urate crystals can also be deposited under the skin or in other soft tissue, forming a nodule called a tophus (plural: tophi). These tophi often form in the hands, elbows, or feet. Tophi do not typically cause pain, but they can become inflamed, infected, or ooze fluid. Depending on their location, tophi can interfere with movements such as walking or gripping objects.Many people with gout also have other health conditions. Most affected individuals have high blood pressure (hypertension), chronic kidney disease, or obesity. Some also have diabetes, heart disease, or a history of stroke. It is unclear whether gout is the cause of a person's increased risk for these conditions, or whether the conditions cause the development of gout, or whether both of these situations occur to influence disease. u Pattern unknown SLC2A9 https://medlineplus.gov/genetics/gene/slc2a9 ABCG2 https://medlineplus.gov/genetics/gene/abcg2 Arthritis, gouty Articular gout Gouty arthritis Gouty arthropathy ICD-10-CM M10.9 MeSH D006073 OMIM 138900 OMIM 612076 SNOMED CT 90560007 2018-08 2020-09-29 Grange syndrome https://medlineplus.gov/genetics/condition/grange-syndrome descriptionGrange syndrome is a rare condition that primarily affects the blood vessels. It is characterized by narrowing (stenosis) or blockage (occlusion) of arteries that supply blood to various organs and tissues, including the kidneys, brain, and heart. Stenosis or occlusion of the arteries that supply blood to the kidneys (renal arteries) can result in chronic high blood pressure (hypertension). Blockage of the arteries that carry blood to the brain (cerebral arteries) can cause a stroke.Additional features of Grange syndrome can include short fingers and toes (brachydactyly), fusion of some of the fingers or toes (syndactyly), fragile bones that are prone to breakage, and learning disabilities. Most people with this disorder also have heart defects that are present from birth. ar Autosomal recessive YY1AP1 https://medlineplus.gov/genetics/gene/yy1ap1 Arterial occlusive disease, progressive, with hypertension, heart defects, bone fragility, and brachysyndactyly Grange occlusive arterial syndrome GRNG GTR C1865267 MeSH D001157 MeSH D006330 OMIM 602531 SNOMED CT 717824007 2017-07 2020-08-18 Granulomatosis with polyangiitis https://medlineplus.gov/genetics/condition/granulomatosis-with-polyangiitis descriptionGranulomatosis with polyangiitis (GPA) is a condition that causes inflammation that primarily affects the respiratory tract (including the lungs and airways) and the kidneys. This disorder is formerly known as Wegener granulomatosis. A characteristic feature of GPA is inflammation of blood vessels (vasculitis), particularly the small- and medium-sized blood vessels in the lungs, nose, sinuses, windpipe, and kidneys, although vessels in any organ can be involved. Polyangiitis refers to the inflammation of multiple types of vessels, such as small arteries and veins. Vasculitis causes scarring and tissue death in the vessels and impedes blood flow to tissues and organs.Another characteristic feature of GPA is the formation of granulomas, which are small areas of inflammation composed of immune cells that aid in the inflammatory reaction. The granulomas usually occur in the lungs or airways of people with this condition, although they can occur in the eyes or other organs. As granulomas grow, they can invade surrounding areas, causing tissue damage.The signs and symptoms of GPA vary based on the tissues and organs affected by vasculitis. Many people with this condition experience a vague feeling of discomfort (malaise), fever, weight loss, or other general symptoms of the body's immune reaction. In most people with GPA, inflammation begins in the vessels of the respiratory tract, leading to nasal congestion, frequent nosebleeds, shortness of breath, or coughing. Severe inflammation in the nose can lead to a hole in the tissue that separates the two nostrils (nasal septum perforation) or a collapse of the septum, causing a sunken bridge of the nose (saddle nose).The kidneys are commonly affected in people with GPA. Tissue damage caused by vasculitis in the kidneys can lead to decreased kidney function, which may cause increased blood pressure or blood in the urine, and life-threatening kidney failure. Inflammation can also occur in other regions of the body, including the eyes, middle and inner ear structures, skin, joints, nerves, heart, and brain. Depending on which systems are involved, additional symptoms can include skin rashes, inner ear pain, swollen and painful joints, and numbness or tingling in the limbs.GPA is most common in middle-aged adults, although it can occur at any age. If untreated, the condition is usually fatal within 2 years of diagnosis. Even after treatment, vasculitis can return. u Pattern unknown HLA-DPB1 https://medlineplus.gov/genetics/gene/hla-dpb1 GPA ICD-10-CM M31.3 ICD-10-CM M31.30 ICD-10-CM M31.31 MeSH D014890 OMIM 608710 SNOMED CT 195353004 2013-07 2020-08-18 Graves' disease https://medlineplus.gov/genetics/condition/graves-disease descriptionGraves' disease is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. In people with Graves' disease, the thyroid is overactive and makes more hormones than the body needs. The condition usually appears in mid-adulthood, although it may occur at any age.Excess thyroid hormones can cause a variety of signs and symptoms. These include nervousness or anxiety, extreme tiredness (fatigue), a rapid and irregular heartbeat, hand tremors, frequent bowel movements or diarrhea, increased sweating and difficulty tolerating hot conditions, trouble sleeping, and weight loss in spite of an increased appetite. Affected women may have menstrual irregularities, such as an unusually light menstrual flow and infrequent periods. Some people with Graves' disease develop an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing.Between 25 and 50 percent of people with Graves' disease have eye abnormalities, which are known as Graves' ophthalmopathy. These eye problems can include swelling and inflammation, redness, dryness, puffy eyelids, and a gritty sensation like having sand or dirt in the eyes. Some people develop bulging of the eyes caused by inflammation of tissues behind the eyeball and "pulling back" (retraction) of the eyelids. Rarely, affected individuals have more serious eye problems, such as pain, double vision, and pinching (compression) of the optic nerve connecting the eye and the brain, which can cause vision loss.A small percentage of people with Graves' disease develop a skin abnormality called pretibial myxedema or Graves' dermopathy. This abnormality causes the skin on the front of the lower legs and the tops of the feet to become thick, lumpy, and red. It is not usually painful. u Pattern unknown TSHR https://medlineplus.gov/genetics/gene/tshr TG https://medlineplus.gov/genetics/gene/tg PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 CD40 https://www.ncbi.nlm.nih.gov/gene/958 CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 IL2RA https://www.ncbi.nlm.nih.gov/gene/3559 SCGB3A2 https://www.ncbi.nlm.nih.gov/gene/117156 Autoimmune hyperthyroidism Basedow disease Basedow's disease Exophthalmic goiter Graves' disease Toxic diffuse goiter GTR C1848795 ICD-10-CM E05.0 ICD-10-CM E05.00 ICD-10-CM E05.01 MeSH D006111 OMIM 275000 OMIM 300351 OMIM 603388 SNOMED CT 353295004 2013-07 2025-12-22 Gray platelet syndrome https://medlineplus.gov/genetics/condition/gray-platelet-syndrome descriptionGray platelet syndrome is a bleeding disorder associated with abnormal platelets, which are small blood cells involved in blood clotting. People with this condition tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or extended bleeding following surgery, dental work, or minor trauma. Women with gray platelet syndrome often have irregular, heavy periods (menometrorrhagia). These bleeding problems are usually mild to moderate, but they have been life-threatening in a few affected individuals.A condition called myelofibrosis, which is a buildup of scar tissue (fibrosis) in the bone marrow, is another common feature of gray platelet syndrome. Bone marrow is the spongy tissue in the center of long bones that produces most of the blood cells the body needs, including platelets. The scarring associated with myelofibrosis damages bone marrow, preventing it from making enough blood cells. Other organs, particularly the spleen, start producing more blood cells to compensate; this process often leads to an enlarged spleen (splenomegaly). ar Autosomal recessive ad Autosomal dominant NBEAL2 https://medlineplus.gov/genetics/gene/nbeal2 BDPLT4 Bleeding disorder, platelet-type, 4 Deficient alpha granule syndrome GPS Grey platelet syndrome Platelet alpha granule deficiency Platelet alpha-granule deficiency Platelet granule defect GTR C0272302 ICD-10-CM D69.1 MeSH D055652 OMIM 139090 SNOMED CT 51720005 2014-09 2020-08-18 Greenberg dysplasia https://medlineplus.gov/genetics/condition/greenberg-dysplasia descriptionGreenberg dysplasia is a severe condition characterized by specific bone abnormalities in the developing fetus. This condition is fatal before birth.The bones of affected individuals do not develop properly, causing a distinctive spotted appearance called moth-eaten bone, which is visible on x-ray images. In addition, the bones have abnormal calcium deposits (ectopic calcification). Affected individuals have extremely short bones in the arms and legs and abnormally flat vertebrae (platyspondyly). Other skeletal abnormalities may include short ribs and extra fingers (polydactyly). In addition, affected fetuses have extensive swelling of the body caused by fluid accumulation (hydrops fetalis). Greenberg dysplasia is also called hydrops-ectopic calcification-moth-eaten skeletal dysplasia (HEM), which reflects the condition's most common features. ar Autosomal recessive LBR https://medlineplus.gov/genetics/gene/lbr Chondrodystrophy, hydropic and prenatally lethal type Greenberg skeletal dysplasia HEM dysplasia HEM skeletal dysplasia Hydrops - ectopic calcification - moth-eaten skeletal dysplasia Moth-eaten skeletal dysplasia GTR C2931048 MeSH D010009 OMIM 215140 SNOMED CT 389261002 2012-02 2020-08-18 Greig cephalopolysyndactyly syndrome https://medlineplus.gov/genetics/condition/greig-cephalopolysyndactyly-syndrome descriptionGreig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux). The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures, delayed development, and intellectual disability. ad Autosomal dominant GLI3 https://medlineplus.gov/genetics/gene/gli3 7 https://medlineplus.gov/genetics/chromosome/7 Cephalopolysyndactyly syndrome GCPS GTR C0265306 MeSH D017689 OMIM 175700 SNOMED CT 32985001 2006-03 2020-09-08 Griscelli syndrome https://medlineplus.gov/genetics/condition/griscelli-syndrome descriptionGriscelli syndrome is an inherited condition characterized by unusually light (hypopigmented) skin and light silvery-gray hair starting in infancy. Researchers have identified three types of this disorder, which are distinguished by their genetic cause and pattern of signs and symptoms.Griscelli syndrome type 1 involves severe problems with brain function in addition to the distinctive skin and hair coloring. Affected individuals typically have delayed development, intellectual disability, seizures, weak muscle tone (hypotonia), and eye and vision abnormalities. Another condition called Elejalde disease has many of the same signs and symptoms, and some researchers have proposed that Griscelli syndrome type 1 and Elejalde disease are actually the same disorder.People with Griscelli syndrome type 2 have immune system abnormalities in addition to having hypopigmented skin and hair. Affected individuals are prone to recurrent infections. They also develop an immune condition called hemophagocytic lymphohistiocytosis (HLH), in which the immune system produces too many activated immune cells called T-lymphocytes and macrophages (histiocytes). Overactivity of these cells can damage organs and tissues throughout the body, causing life-threatening complications if the condition is untreated. People with Griscelli syndrome type 2 do not have the neurological abnormalities of type 1.Unusually light skin and hair coloring are the only features of Griscelli syndrome type 3. People with this form of the disorder do not have neurological abnormalities or immune system problems. ar Autosomal recessive MLPH https://medlineplus.gov/genetics/gene/mlph MYO5A https://medlineplus.gov/genetics/gene/myo5a RAB27A https://medlineplus.gov/genetics/gene/rab27a GS Hypopigmentation immunodeficiency disease Partial albinism with immunodeficiency GTR C1836573 GTR C1859194 GTR C1868679 MeSH D017496 OMIM 214450 OMIM 256710 OMIM 607624 OMIM 609227 SNOMED CT 37548006 2013-09 2020-08-18 Guanidinoacetate methyltransferase deficiency https://medlineplus.gov/genetics/condition/guanidinoacetate-methyltransferase-deficiency descriptionGuanidinoacetate methyltransferase deficiency is an inherited disorder that primarily affects the brain and muscles. Without early treatment, people with this disorder have neurological problems that are usually severe. These problems include intellectual disability, speech development limited to a few words, and recurrent seizures (epilepsy). Affected individuals may also exhibit autistic behaviors that affect communication and social interaction or self-injurious behaviors such as head-banging. Other features of this disorder can include involuntary movements (extrapyramidal dysfunction) such as tremors or facial tics.People with guanidinoacetate methyltransferase deficiency may have weak muscle tone and delayed development of motor skills such as sitting or walking. In severe cases they may lose previously acquired skills such as the ability to support their head or to sit unsupported. ar Autosomal recessive GAMT https://medlineplus.gov/genetics/gene/gamt Creatine deficiency syndrome due to GAMT deficiency Deficiency of guanidinoacetate methyltransferase GAMT deficiency GTR C0574080 MeSH D008661 OMIM 612736 SNOMED CT 124239003 2011-06 2020-08-18 Guillain-Barré syndrome https://medlineplus.gov/genetics/condition/guillain-barre-syndrome descriptionGuillain-Barré syndrome is an autoimmune disorder that affects the nerves. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. In Guillain-Barré syndrome, the immune response damages peripheral nerves, which are the nerves that connect the central nervous system (the brain and spinal cord) to the limbs and organs. Specifically, the immune response affects a particular part of peripheral nerves called axons, which are the extensions of nerve cells (neurons) that transmit nerve impulses. Guillain-Barré syndrome can affect the neurons that control muscle movement (motor neurons); the neurons that transmit sensory signals such as pain, temperature, and touch (sensory neurons); or both. As a result, affected individuals can experience muscle weakness or lose the ability to feel certain sensations.Muscle weakness or paralysis are the characteristic features of Guillain-Barré syndrome. The weakness often begins in the legs and spreads to the arms, torso, and face and is commonly accompanied by numbness, tingling, or pain. Additional signs and symptoms of the condition include difficulty swallowing and difficulty breathing. Occasionally, the nerves that control involuntary functions of the body such as blood pressure and heart rate are affected, which can lead to fluctuating blood pressure or an abnormal heartbeat (cardiac arrhythmia).There are several types of Guillain-Barré syndrome, classified by the part of the peripheral nerve involved in the condition. The most common type of Guillain-Barré syndrome is acute inflammatory demyelinating polyradiculoneuropathy (AIDP). In AIDP, the immune response damages myelin, which is the covering that protects axons and promotes the efficient transmission of nerve impulses. In two other types of Guillain-Barré syndrome, acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN), the axons themselves are damaged by the immune response. In AMAN, only the axons of motor neurons are damaged. In AMSAN, the axons of sensory neurons are also damaged. Because of sensory nerve damage, affected individuals can lose the ability to sense the position of their limbs and can have abnormal or absent reflexes (areflexia).Miller Fisher syndrome, another type of Guillain-Barré syndrome, involves cranial nerves, which extend from the brain to various areas of the head and neck. Miller Fisher syndrome is characterized by three features: weakness or paralysis of the muscles that move the eyes (ophthalmoplegia), problems with balance and coordination (ataxia), and areflexia. People with this condition can have other signs and symptoms common in Guillain-Barré syndrome, such as muscle weakness.Guillain-Barré syndrome occurs in people of all ages. The development of the condition usually follows a pattern. Prior to developing the condition, most people with Guillain-Barré syndrome have a bacterial or viral infection. The first phase of Guillain-Barré syndrome, during which signs and symptoms of the condition worsen, can last up to four weeks, although the peak of the illness is usually reached in one to two weeks. During the second phase, called the plateau, signs and symptoms of Guillain-Barré syndrome stabilize. This phase can last weeks or months. During the recovery phase, symptoms improve. However, some people with Guillain-Barré syndrome never fully recover and can still experience excessive tiredness (fatigue), muscle weakness, or muscle pain. u Pattern unknown TNF https://www.ncbi.nlm.nih.gov/gene/7124 Acute infectious polyneuritis Acute inflammatory polyneuropathy Fisher syndrome GBS Guillain-Barre syndrome Landry-Guillain-Barre syndrome GTR C4083008 ICD-10-CM G61.0 ICD-10-CM G65.0 MeSH D020275 OMIM 139393 SNOMED CT 40956001 2011-09 2020-08-18 Gyrate atrophy of the choroid and retina https://medlineplus.gov/genetics/condition/gyrate-atrophy-of-the-choroid-and-retina descriptionGyrate atrophy of the choroid and retina, which is often shortened to gyrate atrophy, is an inherited disorder characterized by progressive vision loss. People with this disorder have an ongoing loss of cells (atrophy) in the retina, which is the specialized light-sensitive tissue that lines the back of the eye, and in a nearby tissue layer called the choroid. During childhood, they begin experiencing nearsightedness (myopia), difficulty seeing in low light (night blindness), and loss of side (peripheral) vision. Over time, their field of vision continues to narrow, resulting in tunnel vision. Many people with gyrate atrophy also develop clouding of the lens of the eyes (cataracts). These progressive vision changes lead to blindness by about the age of 50.Most people with gyrate atrophy have no symptoms other than vision loss, but some have additional features of the disorder. Occasionally, newborns with gyrate atrophy develop excess ammonia in the blood (hyperammonemia), which may lead to poor feeding, vomiting, seizures, or coma. Neonatal hyperammonemia associated with gyrate atrophy generally responds quickly to treatment and does not recur after the newborn period.Gyrate atrophy usually does not affect intelligence; however, abnormalities may be observed in brain imaging or other neurological testing. In some cases, mild to moderate intellectual disability is associated with gyrate atrophy.Gyrate atrophy may also cause disturbances in the nerves connecting the brain and spinal cord to muscles and sensory cells (peripheral nervous system). In some people with the disorder these abnormalities lead to numbness, tingling, or pain in the hands or feet, while in others they are detectable only by electrical testing of the nerve impulses.In some people with gyrate atrophy, a particular type of muscle fibers (type II fibers) break down over time. While this muscle abnormality usually causes no symptoms, it may result in mild weakness. ar Autosomal recessive OAT https://medlineplus.gov/genetics/gene/oat Gyrate atrophy HOGA Hyperornithinemia with gyrate atrophy of choroid and retina OAT deficiency OKT deficiency Ornithine aminotransferase deficiency Ornithine keto acid aminotransferase deficiency Ornithine-delta-aminotransferase deficiency Ornithinemia with gyrate atrophy GTR C0599035 ICD-10-CM H31.23 MeSH D015799 OMIM 258870 SNOMED CT 314467007 2009-08 2020-08-18 HIVEP2-related intellectual disability https://medlineplus.gov/genetics/condition/hivep2-related-intellectual-disability descriptionHIVEP2-related intellectual disability is a neurological disorder characterized by moderate to severe developmental delay and intellectual disability and mild physical abnormalities (dysmorphic features). Early symptoms of the condition include weak muscle tone (hypotonia) and delayed development of motor skills, such as sitting, standing, and walking. After learning to walk, many affected individuals continue to have difficulty with this activity; their walking style (gait) is often unbalanced and wide-based. Speech is also delayed, and some people with this condition never learn to talk. Most people with HIVEP2-related intellectual disability also have unusual physical features, such as widely spaced eyes (hypertelorism), a broad nasal bridge, or fingers with tapered ends, although there is no characteristic pattern of such features among affected individuals. Many people with the condition exhibit neurodevelopmental disorders, such as hyperactivity, attention deficit disorder, aggression, anxiety, and autism spectrum disorder, which is a group of developmental disorders characterized by impaired communication and social interaction.Other features of HIVEP2-related intellectual disability include mild abnormalities in the structure of the brain and an abnormally small brain and head size (microcephaly). Less common health problems include seizures; recurrent ear infections; and eye disorders, such as eyes that do not look in the same direction (strabismus), "lazy eye" (amblyopia), and farsightedness (hyperopia). Some people with HIVEP2-related intellectual disability have gastrointestinal problems, which can include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and constipation. ad Autosomal dominant HIVEP2 https://medlineplus.gov/genetics/gene/hivep2 Mental retardation, autosomal dominant 43 MRD43 GTR C4707429 MeSH D008607 OMIM 616977 2017-01 2023-08-02 HSD10 disease https://medlineplus.gov/genetics/condition/hsd10-disease descriptionHSD10 disease is a disorder that affects the nervous system, vision, and heart. It is typically more severe in males than in females. Most affected males have a form of HSD10 disease in which early development seems normal, followed by a stage in which affected individuals rapidly lose skills they have acquired. This developmental regression often occurs between the ages of 1 and 2 and results in severe intellectual disability and loss of communication skills and motor skills such as sitting, standing, and walking. This form of the disorder is referred to as the infantile type. Less commonly, affected males have severe neurological problems from birth and never develop motor skills. This form is called the neonatal type. Males with the infantile or neonatal type frequently have weak muscle tone (hypotonia), recurrent seizures (epilepsy), and vision loss that gradually gets worse. Weakening of the heart muscle (cardiomyopathy) also occurs and is a common cause of death in males with severe HSD10 disease. Many affected males do not survive beyond early childhood.Females with HSD10 disease may have developmental delay, learning problems, or intellectual disability, but they do not experience developmental regression. Some affected females have additional features of this condition, such as epilepsy, movement problems, and hearing loss. Affected females appear to have a normal life expectancy. x X-linked HSD17B10 https://medlineplus.gov/genetics/gene/hsd17b10 17β-hydroxysteroid dehydrogenase type 10 deficiency 2-methyl-3-hydroxybutyric aciduria 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency 2M3HBA 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency 3H2MBD deficiency HSD10 deficiency Hydroxyacyl-CoA dehydrogenase II deficiency MHBD deficiency GTR C3266731 MeSH D028361 OMIM 300438 SNOMED CT 791000124107 SNOMED CT 801000124108 2018-01 2020-08-18 Hailey-Hailey disease https://medlineplus.gov/genetics/condition/hailey-hailey-disease descriptionHailey-Hailey disease, also known as benign chronic pemphigus, is a rare skin condition that usually appears in early adulthood. The disorder is characterized by red, raw, and blistered areas of skin that occur most often in skin folds, such as the groin, armpits, neck, and under the breasts. These inflamed areas can become crusty or scaly and may itch and burn. The skin problems tend to worsen with exposure to moisture (such as sweat), friction, and hot weather.The severity of Hailey-Hailey disease varies from relatively mild episodes of skin irritation to widespread, persistent areas of raw and blistered skin that interfere with daily activities. Affected skin may become infected with bacteria or fungi, leading to pain and odor. Although the condition is described as "benign" (noncancerous), in rare cases the skin lesions may develop into a form of skin cancer called squamous cell carcinoma.Many affected individuals also have white lines running the length of their fingernails. These lines do not cause any problems, but they can be useful for diagnosing Hailey-Hailey disease. ad Autosomal dominant ATP2C1 https://medlineplus.gov/genetics/gene/atp2c1 Benign chronic pemphigus Benign familial pemphigus Familial benign chronic pemphigus Pemphigus, benign familial GTR C0085106 MeSH D016506 OMIM 169600 SNOMED CT 79468000 2013-05 2021-01-14 Hajdu-Cheney syndrome https://medlineplus.gov/genetics/condition/hajdu-cheney-syndrome descriptionHajdu-Cheney syndrome is a rare disorder that can affect many parts of the body, particularly the bones. Bone loss from the tips of the fingers and toes (acroosteolysis) is a characteristic feature of the condition. The fingers and toes may appear short and rounded, and they may become shorter over time as the bone continues to break down. In people with Hajdu-Cheney syndrome, the fingers are more likely to be affected than the toes. Bone loss in the fingers can interfere with fine motor skills, such as picking up small objects.The signs and symptoms of Hajdu-Cheney syndrome vary greatly among affected individuals, even among members of the same family. Many of the disorder's features, including acroosteolysis, are not present at birth but become apparent in childhood or later.Additional bone abnormalities are common in people with Hajdu-Cheney syndrome. Affected individuals typically develop osteoporosis, which causes the bones to be brittle and prone to fracture. Many affected individuals experience a type of fracture called a compression fracture in the spinal bones (vertebrae). Some develop an abnormal curvature of the spine (scoliosis or kyphosis). Hajdu-Cheney syndrome can also affect the shape and strength of the long bones in the arms and legs. The bone abnormalities that are associated with this condition often lead to short stature.Hajdu-Cheney syndrome can also involve the bones of the skull. The shape of the skull is often dolichocephalic, which means it is elongated from back to front. In many affected individuals, the bone at the back of the skull bulges outward, causing a bump called a prominent occiput. Serious complications of Hajdu-Cheney syndrome include abnormalities known as platybasia and basilar invagination. Platybasia is a flattening of the base of the skull that is caused by thinning and softening of the skull bones. Basilar invagination occurs when the softened bones allow part of the spine to protrude through the opening at the bottom of the skull and push into the lower parts of the brain. These abnormalities can lead to severe neurological problems, such as a buildup of fluid in the brain (hydrocephalus) or spinal cord (syringomyelia) and breathing difficulties. In some cases, these abnormalities can be life-threatening.Additional signs and symptoms can include a small lower jaw (micrognathia) and an opening in the roof of the mouth called a cleft palate.  Adults with Hajdu-Cheney syndrome may have facial features that are described as "coarse."  These facial features can include widely spaced and downward-slanting eyes, eyebrows that grow together in the middle (synophrys), low-set ears, and a large space between the nose and upper lip (a long philtrum).Other features of Hajdu-Cheney syndrome can include joint abnormalities, particularly an unusually large range of joint movement (hypermobility); dental problems; hearing loss; and a deep, gravelly voice. Affected individuals may also have recurrent childhood infections, heart defects, and kidney abnormalities that include the growth of multiple fluid-filled cysts (polycystic kidneys). Some people with this condition have delayed development in childhood, but the delays are usually mild. ad Autosomal dominant+New variant NOTCH2 https://medlineplus.gov/genetics/gene/notch2 Acroosteolysis dominant type Acroosteolysis with osteoporosis and changes in skull and mandible Arthrodentoosteodysplasia Cheney syndrome Hajdu-cheney syndrome-notch2 HJCYS Serpentine fibula polycystic kidney syndrome SFPKS GTR C0917715 MeSH D031845 OMIM 102500 SNOMED CT 63122002 2025-12 2025-12-16 Hand-foot-genital syndrome https://medlineplus.gov/genetics/condition/hand-foot-genital-syndrome descriptionHand-foot-genital syndrome is a rare condition that affects the development of the hands and feet, the urinary tract, and the reproductive system. People with this condition have abnormally short thumbs and first (big) toes, small fifth fingers that curve inward (clinodactyly), and short feet. The bones in the wrists and ankles may be fused in people with this condition, or hardening of these bones may be delayed. The other bones in the arms and legs are normal.Abnormalities of the genitals and urinary tract can vary among affected individuals. Many people with hand-foot-genital syndrome have defects in the ureters, which are tubes that carry urine from each kidney to the bladder, or in the urethra, which carries urine from the bladder to the outside of the body. Recurrent urinary tract infections and an inability to control the flow of urine (urinary incontinence) have been reported. About half of males with this disorder have the urethra opening on the underside of the penis (hypospadias).People with hand-foot-genital syndrome are usually able to have children (fertile). In some affected females, problems in the early development of the uterus can later increase the risk of pregnancy loss, premature labor, and stillbirth. ad Autosomal dominant HOXA13 https://medlineplus.gov/genetics/gene/hoxa13 Hand-foot-uterus syndrome HFG syndrome HFGS HFU syndrome GTR C1841679 MeSH D005532 MeSH D006228 MeSH D014564 OMIM 140000 SNOMED CT 702425002 2023-10 2023-10-12 Harlequin ichthyosis https://medlineplus.gov/genetics/condition/harlequin-ichthyosis descriptionHarlequin ichthyosis is a severe genetic disorder that affects the skin. Infants with this condition are born prematurely with very hard, thick skin covering most of their bodies. The skin forms large, diamond-shaped plates that are separated by deep cracks (fissures). These skin abnormalities affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties and respiratory failure in babies with harlequin ichthyosis. Affected infants also have feeding problems.The skin normally forms a protective barrier between the body and its surrounding environment. The skin abnormalities associated with harlequin ichthyosis disrupt this barrier, making it difficult for affected infants to control water loss, regulate their body temperature, and fight infections. Infants with harlequin ichthyosis often experience an excessive loss of fluids (dehydration) and develop life-threatening infections in the first few weeks of life. Following the newborn period, the hard, skin plates are shed and the skin develops widespread scales and redness.It used to be very rare for affected infants to survive the newborn period. However, with intensive medical support and improved treatment, babies with this disorder now have a better chance of living into childhood and early adulthood. ar Autosomal recessive ABCA12 https://medlineplus.gov/genetics/gene/abca12 Autosomal recessive congenital ichthyosis 4B Harlequin baby syndrome HI Ichthyosis congenita, harlequin fetus type GTR C0598226 ICD-10-CM Q80.4 MeSH D016113 OMIM 242500 SNOMED CT 205548006 SNOMED CT 268245001 2008-11 2022-01-07 Hartnup disease https://medlineplus.gov/genetics/condition/hartnup-disease descriptionHartnup disease is a condition caused by the body's inability to absorb certain protein building blocks (amino acids) from the diet. As a result, affected individuals are not able to use these amino acids to produce other substances, such as vitamins and proteins. Most people with Hartnup disease are able to get the vitamins and other substances they need with a well-balanced diet.People with Hartnup disease have high levels of various amino acids in their urine (aminoaciduria). For most affected individuals, this is the only sign of the condition. However, some people with Hartnup disease have episodes during which they exhibit other signs, which can include skin rashes; difficulty coordinating movements (cerebellar ataxia); and psychiatric symptoms, such as depression or psychosis. These episodes are typically temporary and are often triggered by illness, stress, nutrient-poor diet, or fever. These features tend to go away once the trigger is remedied, although the aminoaciduria remains. In affected individuals, signs and symptoms most commonly occur in childhood. ar Autosomal recessive SLC6A19 https://medlineplus.gov/genetics/gene/slc6a19 Hartnup disorder Hartnup's disease Neutral amino acid transport defect GTR C0018609 ICD-10-CM E72.02 MeSH D006250 OMIM 234500 SNOMED CT 80902009 2016-05 2020-08-18 Hartsfield syndrome https://medlineplus.gov/genetics/condition/hartsfield-syndrome descriptionHartsfield syndrome is a rare condition characterized by holoprosencephaly, which is an abnormality of brain development, and a malformation of the hands and feet called ectrodactyly.During early development before birth, the brain normally divides into two halves, the right and left hemispheres. Holoprosencephaly occurs when the brain fails to divide properly. In the most severe forms of holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe holoprosencephaly die before birth or soon after. In less severe cases of holoprosencephaly, the brain is partially divided. The life expectancy of these affected individuals depends on the severity of signs and symptoms.People with Hartsfield syndrome often have other brain abnormalities associated with holoprosencephaly. Affected individuals may have a malfunctioning pituitary, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. These include diabetes insipidus, which disrupts the balance between fluid intake and urine excretion; a shortage (deficiency) of growth hormone, leading to slow or delayed growth; and hypogonadotropic hypogonadism, which affects the production of hormones that direct sexual development. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature and sleep patterns. People with Hartsfield syndrome have delayed development that ranges from mild to severe.The other hallmark feature of Hartsfield syndrome is ectrodactyly. Ectrodactyly is a deep split in the hands, feet, or both, with missing fingers or toes and partial fusion of the remaining digits. It can affect the hands and feet on one or both sides. Other features that have been described in people with Hartsfield syndrome include premature fusion of certain bones of the skull (craniosynostosis), heart defects, abnormalities of the bones of the spine (vertebrae), and abnormal genitalia. Some affected individuals have distinctive facial features, including eyes that are widely spaced (hypertelorism) or closely spaced (hypotelorism), ears that are abnormally small or unusually shaped, and a split in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). ad Autosomal dominant ar Autosomal recessive FGFR1 https://medlineplus.gov/genetics/gene/fgfr1 Hartsfield-Bixler-Demyer syndrome HHES Holoprosencephaly and split hand/foot syndrome Holoprosencephaly, ectrodactyly, and bilateral cleft lip/palate Holoprosencephaly, hypertelorism, and ectrodactyly syndrome GTR C1845146 MeSH D006228 MeSH D016142 OMIM 615465 2016-10 2020-08-18 Hashimoto's disease https://medlineplus.gov/genetics/condition/hashimotos-disease descriptionHashimoto's disease is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. Hashimoto's disease is a form of chronic inflammation that can damage the thyroid, reducing its ability to produce hormones.One of the first signs of Hashimoto's disease is an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing. As damage to the thyroid continues, the gland can shrink over a period of years and the goiter may eventually disappear.Other signs and symptoms resulting from an underactive thyroid can include excessive tiredness (fatigue), weight gain or difficulty losing weight, hair that is thin and dry, a slow heart rate, joint or muscle pain, and constipation. People with Hashimoto's disease may also have a pale, puffy face and feel cold even when others around them are warm. Affected women can have heavy or irregular menstrual periods and difficulty conceiving a child (impaired fertility). Difficulty concentrating and depression can also be signs of a shortage of thyroid hormones.Hashimoto's disease usually appears in mid-adulthood, although it can occur earlier or later in life. Its signs and symptoms tend to develop gradually over months or years. u Pattern unknown SLC26A4 https://medlineplus.gov/genetics/gene/slc26a4 TG https://medlineplus.gov/genetics/gene/tg FOXP3 https://medlineplus.gov/genetics/gene/foxp3 PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 Autoimmune chronic lymphocytic thyroiditis Autoimmune thyroiditis Chronic lymphocytic thyroiditides Chronic lymphocytic thyroiditis Hashimoto disease Hashimoto struma Hashimoto syndrome Hashimoto thyroidosis Lymphocytic thyroiditis GTR C0677607 ICD-10-CM E06.3 MeSH D050031 OMIM 140300 SNOMED CT 21983002 2013-07 2025-12-22 Head and neck squamous cell carcinoma https://medlineplus.gov/genetics/condition/head-and-neck-squamous-cell-carcinoma descriptionSquamous cell carcinoma is a cancer that arises from particular cells called squamous cells. Squamous cells are found in the outer layer of skin and in the mucous membranes, which are the moist tissues that line body cavities such as the airways and intestines. Head and neck squamous cell carcinoma (HNSCC) develops in the mucous membranes of the mouth, nose, and throat.HNSCC is classified by its location: it can occur in the mouth (oral cavity), the middle part of the throat near the mouth (oropharynx), the space behind the nose (nasal cavity and paranasal sinuses), the upper part of the throat near the nasal cavity (nasopharynx), the voicebox (larynx), or the lower part of the throat near the larynx (hypopharynx). Depending on the location, the cancer can cause abnormal patches or open sores (ulcers) in the mouth and throat, unusual bleeding or pain in the mouth, sinus congestion that does not clear, sore throat, earache, pain when swallowing or difficulty swallowing, a hoarse voice, difficulty breathing, or enlarged lymph nodes.HNSCC can spread (metastasize) to other parts of the body, such as the lymph nodes or lungs. If it spreads, the cancer has a worse prognosis and can be fatal. About half of affected individuals survive more than five years after diagnosis. n Not inherited HRAS https://medlineplus.gov/genetics/gene/hras TP53 https://medlineplus.gov/genetics/gene/tp53 PTEN https://medlineplus.gov/genetics/gene/pten PIK3CA https://medlineplus.gov/genetics/gene/pik3ca NOTCH1 https://medlineplus.gov/genetics/gene/notch1 CDKN2A https://medlineplus.gov/genetics/gene/cdkn2a FAT1 https://www.ncbi.nlm.nih.gov/gene/2195 HNSCC SCCHN Squamous cell carcinoma of the head and neck GTR C1168401 MeSH D002294 MeSH D006258 OMIM 275355 SNOMED CT 405822008 SNOMED CT 408649007 SNOMED CT 419842002 2014-12 2020-08-18 Hemophilia https://medlineplus.gov/genetics/condition/hemophilia descriptionHemophilia is a bleeding disorder that slows the blood clotting process. People with this condition experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases of hemophilia, continuous bleeding occurs after minor trauma or even when there is no obvious injury (sometimes called spontaneous bleeding). Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of hemophilia do not necessarily involve spontaneous bleeding, and the condition may not become apparent until abnormal bleeding occurs following surgery or a serious injury.The major types of this condition are hemophilia A (also known as classic hemophilia or factor VIII deficiency) and hemophilia B (also known as Christmas disease or factor IX deficiency). Although the two types have very similar signs and symptoms, they are caused by variants (also known as mutations) in different genes. People with an unusual form of hemophilia B, known as hemophilia B Leyden, experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty. xr X-linked recessive F8 https://medlineplus.gov/genetics/gene/f8 F9 https://medlineplus.gov/genetics/gene/f9 Haemophilia Hemophilia, familial Hemophilia, hereditary GTR C0008533 GTR C0019069 GTR C0684275 GTR CN043453 ICD-10-CM D66 ICD-10-CM D67 ICD-10-CM D68.311 ICD-10-CM M36.2 ICD-10-CM Z14.01 ICD-10-CM Z14.02 MeSH D002836 MeSH D006467 OMIM 306700 OMIM 306900 SNOMED CT 41788008 SNOMED CT 90935002 2010-05 2022-05-06 Hennekam syndrome https://medlineplus.gov/genetics/condition/hennekam-syndrome descriptionHennekam syndrome is an inherited disorder that is characterized by abnormalities of the lymphatic system, which is part of both the circulatory system and the immune system. The lymphatic system is a network of vessels that transport white blood cells (lymphocytes), nutrients, and proteins in a fluid called lymph. In people with Hennekam syndrome, the lymphatic vessels are often dilated (lymphangiectasia), which can slow down the flow of lymph and cause the vessels to leak. As a result, people with this condition experience puffiness or swelling that is caused by a buildup of fluid within certain tissues (lymphedema). The affected vessels may also break open (rupture).The lymphedema in people with Hennekam syndrome is typically present at birth and often affects the legs and genitalia. Severely affected infants may have extensive swelling caused by fluid buildup before birth (hydrops fetalis). People with Hennekam syndrome may have lymphangiectasia in the kidneys, lungs, and the membrane covering the heart (pericardium). Many affected infants have intestinal lymphangiectasia, which affects the vessels that transport lymph to and from the intestines. This can cause lymph to leak into the intestines, which can interfere with the absorption of proteins and other nutrients. Affected individuals may also have a buildup of lymph in the abdomen, which can cause swelling (chylous ascites). The lymphedema that is seen in individuals with Hennekam syndrome may affect one side of the body more severely than the other.Distinctive facial features are common among people with Hennekam syndrome. Affected individuals often have a flattened appearance to the middle of the face and the bridge of the nose, puffy eyelids, widely spaced eyes (hypertelorism), low-set ears, and a small mouth with overgrowth of the gums (gingival hypertrophy). Some individuals with Hennekam syndrome have intellectual disabilities, and these can range from mild to severe. Seizures and growth delays may also occur.The skeletal abnormalities that can be seen in people with Hennekam syndrome include a premature fusion of the skull bones (craniosynostosis), permanently bent fingers and toes (camptodactyly), and a fusion of the skin between the fingers and toes (cutaneous syndactyly). Affected individuals may also have inward- and upward-turning feet (clubfeet), a narrow upper chest that may have a sunken appearance (pectus excavatum), and an abnormal side-to-side curvature of the spine (scoliosis).Additional features can include structural abnormalities of the heart, kidneys, or genitals; a soft out-pouching around the belly-button (umbilical hernia); hearing loss; and excessive body hair (hirsutism).The signs and symptoms of Hennekam syndrome vary widely, even among members of the same family. Because of the potentially serious complications, the life expectancy of individuals with Hennekam syndrome also varies.  ar Autosomal recessive CCBE1 https://medlineplus.gov/genetics/gene/ccbe1 FAT4 https://medlineplus.gov/genetics/gene/fat4 ADAMTS3 https://www.ncbi.nlm.nih.gov/gene/9508 Hennekam lymphangiectasia-lymphedema syndrome HKLLS Lymphedema-lymphangiectasia-intellectual disability syndrome GTR C4012050 GTR C4014939 GTR C4748408 MeSH D008201 OMIM 235510 OMIM 616006 OMIM 618154 SNOMED CT 234146006 2026-03 2026-03-20 Hepatic lipase deficiency https://medlineplus.gov/genetics/condition/hepatic-lipase-deficiency descriptionHepatic lipase deficiency is a disorder that affects the body's ability to break down fats (lipids). People with this disorder have increased amounts of certain fats, known as triglycerides and cholesterol, in the blood. These individuals also have increased amounts of molecules known as high-density lipoproteins (HDLs) and decreased amounts of molecules called low-density lipoproteins (LDL). These molecules transport triglycerides and cholesterol throughout the body. In people with hepatic lipase deficiency, the LDL molecules are often abnormally large.Normally, high levels of HDL (known as "good cholesterol") and low levels of LDL (known as "bad cholesterol") are protective against an accumulation of fatty deposits on the artery walls (atherosclerosis) and heart disease. However, some individuals with hepatic lipase deficiency, who have this imbalance of HDL and LDL, develop atherosclerosis and heart disease in mid-adulthood, while others do not. It is unknown whether people with hepatic lipase deficiency have a greater risk of developing atherosclerosis or heart disease than individuals in the general population. Similarly, it is unclear how increased blood triglycerides and cholesterol levels affect the risk of atherosclerosis and heart disease in people with hepatic lipase deficiency. ar Autosomal recessive LIPC https://medlineplus.gov/genetics/gene/lipc HL deficiency Hyperlipidemia due to hepatic triglyceride lipase deficiency LIPC deficiency GTR C3151466 MeSH D008052 OMIM 614025 SNOMED CT 720940008 2015-11 2020-08-18 Hepatic veno-occlusive disease with immunodeficiency https://medlineplus.gov/genetics/condition/hepatic-veno-occlusive-disease-with-immunodeficiency descriptionHepatic veno-occlusive disease with immunodeficiency (VODI) is a disorder of the liver and immune system. Its signs and symptoms typically appear before six months of age.Hepatic veno-occlusive disease is a condition that blocks (occludes) small veins in the liver, disrupting blood flow in this organ. This condition can lead to enlargement of the liver (hepatomegaly), a buildup of scar tissue (hepatic fibrosis), and liver failure.Children with VODI have immune systems that do not function normally. They are vulnerable to recurrent infections that are caused by certain bacteria, viruses, and fungi. Affected individuals experience frequent colds or bouts of pneumonia. The infections are likely related to lower-than-normal levels of immune system cells, including special proteins called antibodies or immunoglobulins, particularly immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA). Antibodies attach to specific foreign particles, marking them for destruction. These infections are usually serious and may be life-threatening. In most people with VODI, infections occur before hepatic veno-occlusive disease becomes evident.Some children with VODI have neurological problems due to blocked blood flow in the brain.If untreated, children with VODI do not survive past infancy. With treatment, many people with VODI can live into childhood and sometimes into their teens. ar Autosomal recessive SP110 https://medlineplus.gov/genetics/gene/sp110 Familial veno-occlusive disease with immunodeficiency Hepatic venoocclusive disease with immunodeficiency Veno-occlusive disease and immunodeficiency syndrome VODI GTR C1856128 ICD-10-CM K76.5 MeSH D006504 OMIM 235550 SNOMED CT 65617004 2024-12 2024-12-02 Hereditary angioedema https://medlineplus.gov/genetics/condition/hereditary-angioedema descriptionHereditary angioedema is a disorder characterized by recurrent episodes of severe swelling (angioedema). The parts of the body that are most often affected by swelling are the limbs, face, intestinal tract, and airway. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway. About one-third of people with this condition develop a non-itchy rash called erythema marginatum during an attack.Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty.  On average, untreated individuals have swelling episodes every 1 to 2 weeks, and most episodes last for about 3 to 4 days. The frequency and duration of attacks vary greatly among people with hereditary angioedema, even among people in the same family.Hereditary angioedema is broadly divided into two types, which are distinguished by levels of a protein called C1 inhibitor (C1-INH) in the blood. These types are known as hereditary angioedema due to C1-INH deficiency and hereditary angioedema with normal C1-INH. Hereditary angioedema due to C1-INH deficiency is further divided into two types: type I occurs when C1-INH levels are low, and type II occurs when the C1-INH protein is not functioning correctly. The different types of hereditary angioedema have similar signs and symptoms.  ad Autosomal dominant+Inherited or new variant SERPING1 https://medlineplus.gov/genetics/gene/serping1 F12 https://medlineplus.gov/genetics/gene/f12 PLG https://medlineplus.gov/genetics/gene/plg ANGPT1 https://www.ncbi.nlm.nih.gov/gene/284 KNG1 https://www.ncbi.nlm.nih.gov/gene/3827 MYOF https://www.ncbi.nlm.nih.gov/gene/26509 HS3ST6 https://www.ncbi.nlm.nih.gov/gene/64711 C1 esterase inhibitor deficiency C1 inhibitor deficiency HAE HANE Hereditary angioneurotic edema GTR C0019243 GTR C0398776 GTR C1857728 GTR C5543526 MeSH D054179 OMIM 106100 OMIM 610618 OMIM 619360 OMIM 619361 OMIM 619363 OMIM 619367 SNOMED CT 82966003 SNOMED CT 846575004 2024-03 2026-03-04 Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome https://medlineplus.gov/genetics/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome descriptionHereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. In people with HANAC syndrome, angiopathy affects several parts of the body. The blood vessels as well as thin sheet-like structures called basement membranes that separate and support cells are weakened and more susceptible to breakage.People with HANAC syndrome develop kidney disease (nephropathy). Fragile or damaged blood vessels or basement membranes in the kidneys can lead to blood in the urine (hematuria). Cysts can also form in one or both kidneys, and the cysts may grow larger over time.Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). However, in people with HANAC syndrome, these aneurysms typically do not burst. About half of people with this condition also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. Any muscle may be affected, and cramps usually last from a few seconds to a few minutes, although in some cases they can last for several hours. Muscle cramps can be spontaneous or triggered by exercise.Individuals with HANAC syndrome also experience a variety of eye problems. All individuals with this condition have arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eyes (arterial retinal tortuosity). This blood vessel abnormality can cause episodes of bleeding within the eyes following any minor trauma to the eyes, leading to temporary vision loss. Other eye problems associated with HANAC syndrome include a clouding of the lens of the eye (cataract) and an abnormality called Axenfeld-Rieger anomaly. Axenfeld-Rieger anomaly is associated with various other eye abnormalities, including underdevelopment and eventual tearing of the colored part of the eye (iris), and a pupil that is not in the center of the eye.Rarely, affected individuals will have a condition called Raynaud phenomenon in which the blood vessels in the fingers and toes temporarily narrow, restricting blood flow to the fingertips and the ends of the toes. As a result, the skin around the affected area may turn white or blue for a brief period of time and the area may tingle or throb. Raynaud phenomenon is typically triggered by changes in temperature and usually causes no long term damage. ad Autosomal dominant COL4A1 https://medlineplus.gov/genetics/gene/col4a1 Autosomal dominant familial hematuria, retinal arteriolar tortuosity, contractures HANAC HANAC syndrome Hereditary angiopathy with nephropathy, aneurysm, and muscle cramps syndrome GTR C2673195 MeSH D002561 OMIM 611773 SNOMED CT 702428000 2011-09 2023-03-21 Hereditary antithrombin deficiency https://medlineplus.gov/genetics/condition/hereditary-antithrombin-deficiency descriptionHereditary antithrombin deficiency is a disorder of blood clotting. People with this condition are at higher than average risk for developing abnormal blood clots, particularly a type of clot that occurs in the deep veins of the legs. This type of clot is called a deep vein thrombosis (DVT). Affected individuals also have an increased risk of developing a pulmonary embolism (PE), which is a clot that travels through the bloodstream and lodges in the lungs. In hereditary antithrombin deficiency, abnormal blood clots usually form only in veins, although they may rarely occur in arteries.About half of people with hereditary antithrombin deficiency will develop at least one abnormal blood clot during their lifetime. These clots usually develop after adolescence.Other factors can increase the risk of abnormal blood clots in people with hereditary antithrombin deficiency. These factors include increasing age, surgery, or immobility. The combination of hereditary antithrombin deficiency and other inherited disorders of blood clotting can also influence risk. Women with hereditary antithrombin deficiency are at increased risk of developing an abnormal blood clot during pregnancy or soon after delivery. They also may have an increased risk for pregnancy loss (miscarriage) or stillbirth. ad Autosomal dominant SERPINC1 https://medlineplus.gov/genetics/gene/serpinc1 Antithrombin III deficiency Congenital antithrombin III deficiency GTR C0272375 MeSH D020152 OMIM 107300 SNOMED CT 36351005 SNOMED CT 439699000 2009-08 2021-04-07 Hereditary cerebral amyloid angiopathy https://medlineplus.gov/genetics/condition/hereditary-cerebral-amyloid-angiopathy descriptionHereditary cerebral amyloid angiopathy is a condition characterized by an abnormal buildup of protein clumps called amyloid deposits in the blood vessels in the brain, causing vascular disease (angiopathy). People with hereditary cerebral amyloid angiopathy often have progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. Due to neurological decline, this condition is typically fatal in one's sixties, although there is variation depending on the severity of the signs and symptoms. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer.There are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause, which determines whether areas of the brain other than blood vessels are affected, and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed.The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy).People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia.The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties.Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus).Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type also have clouding of the lens of the eyes (cataracts) and deafness. ad Autosomal dominant APP https://medlineplus.gov/genetics/gene/app CST3 https://medlineplus.gov/genetics/gene/cst3 ITM2B https://medlineplus.gov/genetics/gene/itm2b Autosomal dominant cerebrovascular amyloidosis CAA, familial Cerebral amyloid angiopathy, familial Cerebral amyloid angiopathy, genetic HCHWA-D HCHWA-I Hereditary cerebral hemorrhage with amyloidosis-Dutch type Hereditary cerebral hemorrhage with amyloidosis-Icelandic type GTR C0085220 GTR C1527338 GTR C1861735 GTR C2751536 ICD-10-CM I68.0 MeSH D028243 OMIM 105150 OMIM 117300 OMIM 176500 OMIM 605714 SNOMED CT 230724001 SNOMED CT 237867001 SNOMED CT 45639009 SNOMED CT 56453003 SNOMED CT 703220002 2022-04 2022-04-11 Hereditary diffuse gastric cancer https://medlineplus.gov/genetics/condition/hereditary-diffuse-gastric-cancer descriptionHereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach(gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones.Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones.In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent.Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50. ad Autosomal dominant CDH1 https://medlineplus.gov/genetics/gene/cdh1 CTNNA1 https://www.ncbi.nlm.nih.gov/gene/1495 E-cadherin-associated hereditary gastric cancer Familial diffuse gastric cancer FDGC HDGC Hereditary diffuse gastric adenocarcinoma GTR C1708349 MeSH D013274 OMIM 137215 SNOMED CT 716859000 2014-01 2023-03-21 Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis https://medlineplus.gov/genetics/condition/hereditary-fibrosing-poikiloderma-with-tendon-contractures-myopathy-and-pulmonary-fibrosis descriptionHereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (abbreviated POIKTMP), is a disorder that affects many parts of the body, particularly the skin, muscles, lungs, and pancreas. Signs and symptoms vary among affected individuals.People with POIKTMP have patchy changes in skin coloring and small clusters of blood vessels just under the skin (telangiectases), a combination known as poikiloderma. These skin changes begin in infancy and occur primarily on the face. They can also have red, scaly skin patches and mild swelling (lymphedema) of the arms and legs; thickened skin on the palms of the hands and soles of the feet (palmoplantar keratoderma); and abnormal hardening (sclerosis) of tissues in the fingers and toes. People with this disorder usually have sparse scalp hair, and their eyelashes and eyebrows can also be sparse or absent. Affected individuals have a decreased ability to sweat (hypohidrosis), which impairs their ability to tolerate heat.Reduced movement of joints (contractures) caused by shortening of the connective tissues that attach muscles to bone (tendons) usually develops during childhood in people with POIKTMP. These contractures often affect the calf, resulting in turning in (valgus deformity) of the feet. Contractures can also affect the elbows and wrists. In addition, people with POIKTMP usually develop muscle weakness (myopathy) in the arms and legs, and medical imaging shows abnormal fatty tissue in the muscles.Adults with POIKTMP can develop a condition called pulmonary fibrosis, in which scar tissue forms in the lungs. Pulmonary fibrosis eventually causes difficulty breathing and can be life-threatening within a few years after symptoms begin.In addition to the skin, muscle, and lung problems that give this condition its name, people with POIKTMP can also have a shortage (deficiency) of enzymes produced by the pancreas to aid in the digestion of fats. This deficiency can lead to diarrhea and poor absorption of fats and fat-soluble vitamins. Liver problems, short stature, and delayed puberty can also occur in affected individuals. Intellectual development is not affected by this disorder. ad Autosomal dominant FAM111B https://medlineplus.gov/genetics/gene/fam111b Hereditary sclerosing poikiloderma with tendon and pulmonary involvement HFP POIKTMP GTR C3810325 MeSH D012873 OMIM 615704 SNOMED CT 402769003 2017-02 2021-08-17 Hereditary folate malabsorption https://medlineplus.gov/genetics/condition/hereditary-folate-malabsorption descriptionHereditary folate malabsorption is a disorder that interferes with the body's ability to use certain vitamins from food. During digestion, the body cannot take in (absorb) certain B vitamins called folates. Folates are important for cell growth and function and blood cell formation.Infants with hereditary folate malabsorption are born with normal amounts of folates in their body because they get these vitamins through the placenta before birth. Affected babies generally begin to show signs and symptoms of the disorder within the first few months of life when they cannot use the folates they get from food.Infants with hereditary folate malabsorption often experience feeding difficulties, diarrhea, and swelling or irritation on the inside of the mouth (oral mucositis). These babies also do not gain weight and grow at the expected rate (failure to thrive). Affected individuals usually develop a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). People with hereditary folate malabsorption may also have fewer white blood cells (leukopenia), making them more susceptible to infections. In addition, some affected individuals have fewer platelets (thrombocytopenia), which means they can bruise easily.Without treatment, affected individuals may develop neurological problems such as developmental delays, intellectual disabilities, seizures, and difficulty coordinating movements (ataxia). Abnormal deposits of calcium (calcification) in the brain may also occur.Pregnant women with hereditary folate malabsorption who are receiving treatment for the vitamin deficiency do not appear to have an increased risk of having children with birth defects caused by folate deficiency, such as spina bifida or anencephaly. ar Autosomal recessive SLC46A1 https://medlineplus.gov/genetics/gene/slc46a1 Congenital defect of folate absorption Congenital folate malabsorption Folic acid transport defect GTR C0342705 ICD-10-CM MeSH D008286 OMIM 229050 SNOMED CT 62578003 2024-05 2025-01-31 Hereditary fructose intolerance https://medlineplus.gov/genetics/condition/hereditary-fructose-intolerance descriptionHereditary fructose intolerance is a condition that affects a person's ability to digest the sugar fructose. Fructose is a simple sugar found primarily in fruits. Affected individuals develop signs and symptoms of the disorder in infancy when fruits, juices, or other foods containing fructose are introduced into the diet. After ingesting fructose, individuals with hereditary fructose intolerance may experience nausea, bloating, abdominal pain, diarrhea, vomiting, and low blood sugar (hypoglycemia). Affected infants may fail to grow and gain weight at the expected rate (failure to thrive).Repeated ingestion of fructose-containing foods can lead to liver and kidney damage. The liver damage can result in a yellowing of the skin and whites of the eyes (jaundice), an enlarged liver (hepatomegaly), and chronic liver disease (cirrhosis). Continued exposure to fructose may result in seizures, coma, and ultimately death from liver and kidney failure. Due to the severity of symptoms experienced when fructose is ingested, most people with hereditary fructose intolerance develop a dislike for fruits, juices, and other foods containing fructose.Hereditary fructose intolerance should not be confused with a condition called fructose malabsorption. In people with fructose malabsorption, the cells of the intestine cannot absorb fructose normally, leading to bloating, diarrhea or constipation, flatulence, and stomach pain. Fructose malabsorption is thought to affect approximately 40 percent of individuals in the Western hemisphere; its cause is unknown. ar Autosomal recessive ALDOB https://medlineplus.gov/genetics/gene/aldob ALDOB deficiency Aldolase B deficiency Fructose aldolase B deficiency Fructose intolerance Fructose-1,6-biphosphate aldolase deficiency Fructose-1-phosphate aldolase deficiency Fructosemia GTR C0016751 ICD-10-CM E74.12 MeSH D005633 OMIM 229600 SNOMED CT 20052008 2011-06 2025-04-03 Hereditary hemochromatosis https://medlineplus.gov/genetics/condition/hereditary-hemochromatosis descriptionHereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hereditary hemochromatosis is also called an iron overload disorder.Early symptoms of hereditary hemochromatosis may include extreme tiredness (fatigue), joint pain, abdominal pain, weight loss, and loss of sex drive. As the condition worsens, affected individuals may develop arthritis, liver disease (cirrhosis) or liver cancer, diabetes, heart abnormalities, or skin discoloration. The appearance and severity of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.There are four types of hereditary hemochromatosis, which are classified depending on the age of onset and other factors such as genetic cause and mode of inheritance.Type 1, the most common form of the disorder, and type 4 (also called ferroportin disease) begin in adulthood. Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause.Type 2 hemochromatosis is known as a juvenile-onset disorder because symptoms often begin in childhood. By age 20, iron accumulation causes decreased or absent secretion of sex hormones. Affected females usually begin menstruation normally but menses stop after a few years. Males may experience delayed puberty or symptoms related to a shortage of sex hormones. If type 2 hemochromatosis is untreated, potentially fatal heart disease becomes evident by age 30.The onset of type 3 hemochromatosis is usually intermediate between types 1 and 2 with symptoms generally beginning before age 30. ar Autosomal recessive ad Autosomal dominant HFE https://medlineplus.gov/genetics/gene/hfe HJV https://medlineplus.gov/genetics/gene/hjv TFR2 https://medlineplus.gov/genetics/gene/tfr2 HAMP https://medlineplus.gov/genetics/gene/hamp SLC40A1 https://medlineplus.gov/genetics/gene/slc40a1 Bronze diabetes Bronzed cirrhosis Familial hemochromatosis Genetic hemochromatosis Haemochromatosis HC Hemochromatosis Hereditary haemochromatosis HH HLAH Iron storage disorder Pigmentary cirrhosis Primary hemochromatosis Troisier-Hanot-Chauffard syndrome Von Recklenhausen-Applebaum disease GTR C0392514 ICD-10-CM E83.11 ICD-10-CM E83.110 ICD-10-CM E83.118 ICD-10-CM E83.119 MeSH D006432 OMIM 235200 OMIM 602390 OMIM 604250 OMIM 606069 OMIM 613313 SNOMED CT 35400008 SNOMED CT 399126000 SNOMED CT 399144008 SNOMED CT 399170009 SNOMED CT 50855007 SNOMED CT 6160004 SNOMED CT 838361004 2006-10 2025-04-03 Hereditary hemorrhagic telangiectasia https://medlineplus.gov/genetics/condition/hereditary-hemorrhagic-telangiectasia descriptionHereditary hemorrhagic telangiectasia is a disorder that results in the development of multiple abnormalities in the blood vessels.In the circulatory system, blood carrying oxygen from the lungs is normally pumped by the heart into the arteries at high pressure. The pressure allows the blood to make its way through the arteries to the smaller vessels (arterioles and capillaries) that supply oxygen to the body's tissues. By the time blood reaches the capillaries, the pressure is much lower. The blood then proceeds from the capillaries into veins, through which it eventually returns to the heart.In hereditary hemorrhagic telangiectasia, some arterial vessels flow directly into veins rather than into the capillaries. These abnormalities are called arteriovenous malformations. When they occur in vessels near the surface of the skin, where they are visible as red markings, they are known as telangiectases (the singular is telangiectasia).Without the normal buffer of the capillaries, the blood moves from the arteries at high pressure into the thinner walled, less elastic veins. The extra pressure tends to strain and enlarge these blood vessels, and may result in compression or irritation of adjacent tissues and frequent episodes of severe bleeding (hemorrhage). Nosebleeds are very common in people with hereditary hemorrhagic telangiectasia, and more serious problems may arise from hemorrhages in the brain, liver, lungs, or other organs.There are several forms of hereditary hemorrhagic telangiectasia, distinguished mainly by their genetic cause but with some differences in patterns of signs and symptoms. People with type 1 tend to develop symptoms earlier than those with type 2, and are more likely to have blood vessel malformations in the lungs and brain. Type 2 and type 3 may be associated with a higher risk of liver involvement. Women are more likely than men to develop blood vessel malformations in the lungs with type 1, and are also at higher risk of liver involvement with both type 1 and type 2. Individuals with any form of hereditary hemorrhagic telangiectasia, however, can have any of these problems.Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is a condition that involves both arteriovenous malformations and a tendency to develop growths (polyps) in the gastrointestinal tract. Hereditary hemorrhagic telangiectasia types 1, 2 and 3 do not appear to increase the likelihood of such polyps. ad Autosomal dominant ENG https://medlineplus.gov/genetics/gene/eng ACVRL1 https://medlineplus.gov/genetics/gene/acvrl1 SMAD4 https://medlineplus.gov/genetics/gene/smad4 GDF2 https://www.ncbi.nlm.nih.gov/gene/2658 HHT Osler-Weber-Rendu syndrome GTR C1832774 GTR C1832942 GTR C1838163 GTR C4551861 ICD-10-CM I78.0 MeSH D013683 OMIM 175050 OMIM 187300 OMIM 600376 OMIM 610655 SNOMED CT 21877004 2007-02 2021-05-20 Hereditary hyperekplexia https://medlineplus.gov/genetics/condition/hereditary-hyperekplexia descriptionHereditary hyperekplexia is a condition in which affected infants have increased muscle tone (hypertonia) and an exaggerated startle reaction to unexpected stimuli, especially loud noises. Following the startle reaction, infants experience a brief period in which they are very rigid and unable to move. During these rigid periods, some infants stop breathing, which, if prolonged, can be fatal. Infants with hereditary hyperekplexia have hypertonia at all times, except when they are sleeping.Other signs and symptoms of hereditary hyperekplexia can include muscle twitches when falling asleep (hypnagogic myoclonus) and movements of the arms or legs while asleep. Some infants, when tapped on the nose, extend their head forward and have spasms of the limb and neck muscles. Rarely, infants with hereditary hyperekplexia experience recurrent seizures (epilepsy).The signs and symptoms of hereditary hyperekplexia typically fade by age 1. However, older individuals with hereditary hyperekplexia may still startle easily and have periods of rigidity, which can cause them to fall down. They may also continue to have hypnagogic myoclonus or movements during sleep. As they get older, individuals with this condition may have a low tolerance for crowded places and loud noises. People with hereditary hyperekplexia who have epilepsy have the seizure disorder throughout their lives.Hereditary hyperekplexia may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of unexplained death in babies younger than 1 year. ar Autosomal recessive ad Autosomal dominant GLRA1 https://medlineplus.gov/genetics/gene/glra1 GLRB https://www.ncbi.nlm.nih.gov/gene/2743 SLC6A5 https://www.ncbi.nlm.nih.gov/gene/9152 Congenital stiff-man syndrome Congenital stiff-person syndrome Familial hyperekplexia Hyperekplexia Startle syndrome STHE Stiff-baby syndrome GTR C0234166 GTR C3553288 GTR C3553291 GTR C4551954 ICD-10-CM G25.82 MeSH D016750 OMIM 149400 OMIM 614618 OMIM 614619 SNOMED CT 724351008 2010-04 2020-08-18 Hereditary leiomyomatosis and renal cell cancer https://medlineplus.gov/genetics/condition/hereditary-leiomyomatosis-and-renal-cell-cancer descriptionHereditary leiomyomatosis and renal cell cancer (HLRCC) is a disorder in which affected individuals tend to develop benign tumors containing smooth muscle tissue (leiomyomas) in the skin and, in females, the uterus. This condition also increases the risk of kidney cancer.In this disorder, growths on the skin (cutaneous leiomyomas) typically develop in the third decade of life. Most of these growths arise from the tiny muscles around the hair follicles that cause "goosebumps". They appear as bumps or nodules on the trunk, arms, legs, and occasionally on the face. Cutaneous leiomyomas may be the same color as the surrounding skin, or they may be darker. Some affected individuals have no cutaneous leiomyomas or only a few, but the growths tend to increase in size and number over time. Cutaneous leiomyomas are often more sensitive than the surrounding skin to cold or light touch, and may be painful.Most women with HLRCC also develop uterine leiomyomas (fibroids). While uterine fibroids are very common in the general population, women with HLRCC tend to have numerous large fibroids that appear earlier than in the general population.Approximately 10 percent to 16 percent of people with HLRCC develop a type of kidney cancer called renal cell cancer. The signs and symptoms of renal cell cancer may include lower back pain, blood in the urine, or a mass in the kidney that can be felt upon physical examination. Some people with renal cell cancer have no symptoms until the disease is advanced. People with HLRCC are commonly diagnosed with kidney cancer in their forties.This disorder, especially if it appears in individuals or families without renal cell cancer, is also sometimes called multiple cutaneous leiomyomatosis (MCL) or multiple cutaneous and uterine leiomyomatosis (MCUL). ad Autosomal dominant FH https://medlineplus.gov/genetics/gene/fh Hereditary leiomyomatosis and renal cell carcinoma HLRCC Leiomyomatosis and renal cell cancer LRCC MCL MCUL Multiple cutaneous and uterine leiomyomata Multiple cutaneous leiomyoma Reed's syndrome GTR C1708350 MeSH D009386 OMIM 150800 SNOMED CT 404043000 2008-04 2023-03-28 Hereditary multiple osteochondromas https://medlineplus.gov/genetics/condition/hereditary-multiple-osteochondromas descriptionHereditary multiple osteochondromas is a condition in which people develop multiple benign (noncancerous) bone tumors called osteochondromas. The number of osteochondromas and the bones on which they are located vary greatly among affected individuals. The osteochondromas are not present at birth, but approximately 96 percent of affected people develop multiple osteochondromas by the time they are 12 years old. Osteochondromas typically form at the end of long bones and on flat bones such as the hip and shoulder blade.Multiple osteochondromas can disrupt bone growth and can cause growth disturbances of the arms, hands, and legs, leading to short stature. Often these problems with bone growth do not affect the right and left limb equally, resulting in uneven limb lengths (limb length discrepancy). Bowing of the forearm or ankle and abnormal development of the hip joints (hip dysplasia) caused by osteochondromas can lead to difficulty walking and general discomfort. Multiple osteochondromas may also result in pain, limited range of joint movement, and pressure on nerves, blood vessels, the spinal cord, and tissues surrounding the osteochondromas.Osteochondromas are typically benign; however, in some instances these tumors become malignant (cancerous). Researchers estimate that people with hereditary multiple osteochondromas have a 1 in 20 to 1 in 200 lifetime risk of developing cancerous osteochondromas (called sarcomas). ad Autosomal dominant EXT1 https://medlineplus.gov/genetics/gene/ext1 EXT2 https://medlineplus.gov/genetics/gene/ext2 Bessel-Hagen disease Diaphyseal aclasis Exostoses, multiple hereditary Familial exostoses Hereditary multiple exostoses Multiple cartilaginous exostoses Multiple congenital exostosis Multiple hereditary exostoses Multiple osteochondromas Multiple osteochondromatosis GTR C0015306 GTR C1851413 ICD-10-CM Q78.6 MeSH D005097 OMIM 133700 OMIM 133701 SNOMED CT 254044004 2007-12 2020-08-18 Hereditary myopathy with early respiratory failure https://medlineplus.gov/genetics/condition/hereditary-myopathy-with-early-respiratory-failure descriptionHereditary myopathy with early respiratory failure (HMERF) is an inherited disease that affects muscles used for movement (skeletal muscles) and muscles that are needed for breathing (respiratory muscles).The major signs and symptoms of HMERF usually appear in adulthood, often in the mid-thirties. Among the earliest signs of the condition are breathing problems and difficulty walking. Weakness of the respiratory muscles, particularly the diaphragm (the muscle that separates the organs in the abdomen from those in the chest), causes breathing problems. This weakness worsens over time and can lead to life-threatening respiratory failure. Some affected individuals have weakness of muscles of the lower leg and foot, which makes it difficult to lift the toes while walking, a condition known as foot drop. Other muscles that become weak in people with HMERF include those of the hips, thighs, upper arms, and neck.When viewed under a microscope, muscle fibers from affected individuals contain abnormal structures called cytoplasmic bodies. In many cases, the cytoplasmic bodies are arranged side-by-side in a ring inside the muscle fiber, resembling a necklace (necklace cytoplasmic bodies). ad Autosomal dominant TTN https://medlineplus.gov/genetics/gene/ttn Edstrom myopathy HMERF Myopathy, proximal, with early respiratory muscle involvement GTR C1863599 MeSH D009135 MeSH D012131 OMIM 603689 SNOMED CT 702373006 2018-08 2023-11-10 Hereditary neuralgic amyotrophy https://medlineplus.gov/genetics/condition/hereditary-neuralgic-amyotrophy descriptionHereditary neuralgic amyotrophy is a disorder characterized by episodes of severe pain and muscle wasting (amyotrophy) in one or both shoulders and arms. Pain is felt along the path of one or more nerves (neuralgia) and often has no obvious physical cause. The network of nerves involved in hereditary neuralgic amyotrophy, called the brachial plexus, controls movement and sensation in the shoulders and arms.People with hereditary neuralgic amyotrophy usually begin experiencing pain episodes in their twenties, but pain episodes have occurred in children as young as 1 year old. The episodes may be spontaneous, or they may be triggered by stress such as strenuous exercise, childbirth, surgery, exposure to cold, infections, immunization, or emotional disturbance. While the frequency of the episodes tends to decrease with age, affected individuals are often left with residual problems, such as chronic pain and impaired movement, that accumulate over time.Typically, an attack begins with severe pain on one or both sides of the body; the pain most commonly occurs on the right side of the body. About one-third of individuals with hereditary neuralgic amyotrophy have pain in both shoulders or arms. The pain typically starts out sharp and may become more of an ache over time, and the pain lasts about a month. It may be difficult to control the pain with medication. Over a period of a few hours to a couple of weeks, the muscles in the affected area begin to weaken and waste away (atrophy), and movement becomes difficult. Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) stick out from the back, a common sign known as scapular winging. Additional features of hereditary neuralgic amyotrophy may include decreased sensation (hypoesthesia) and abnormal sensations in the skin such as numbness or tingling (paresthesias). Areas other than the shoulder and arm may also be involved.In a few affected families, individuals with hereditary neuralgic amyotrophy also have unusual physical characteristics including short stature, excess skin folds on the neck and arms, an opening in the roof of the mouth (cleft palate), a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula), and partially webbed or fused fingers or toes (partial syndactyly). They may also have distinctive facial features including eyes set close together (ocular hypotelorism), a narrow opening of the eyelids (short palpebral fissures) with a skin fold that covers the inner corner of the eye (epicanthal fold), a long nasal bridge, a narrow mouth, and differences between one side of the face and the other (facial asymmetry). ad Autosomal dominant SEPTIN9 https://medlineplus.gov/genetics/gene/septin9 Amyotrophic neuralgia Brachial neuralgia Brachial neuritis Brachial plexus neuritis Familial brachial plexus neuritis Hereditary brachial plexus neuropathy Heredofamilial neuritis with brachial plexus predilection HNA NAPB Neuralgic amyotrophy Neuritis with brachial predilection Shoulder girdle neuropathy GTR C1834304 ICD-10-CM G54.5 MeSH D020968 OMIM 162100 SNOMED CT 26609002 2024-08 2024-08-20 Hereditary neuropathy with liability to pressure palsies https://medlineplus.gov/genetics/condition/hereditary-neuropathy-with-liability-to-pressure-palsies descriptionHereditary neuropathy with liability to pressure palsies is a disorder that affects peripheral nerves. These nerves connect the brain and spinal cord to muscles and sensory cells that detect touch, pain, and temperature. In people with this disorder, the peripheral nerves are unusually sensitive to pressure, such as the pressure that occurs when carrying heavy grocery bags, leaning on an elbow, or sitting without changing position, particularly with crossed legs. These activities would not normally cause sensation problems in people without the disorder.Hereditary neuropathy with liability to pressure palsies is characterized by recurrent episodes of numbness, tingling, and loss of muscle function (palsy) in the region associated with the affected nerve, usually an arm, hand, leg, or foot. An episode can last from several minutes to several months, but recovery is usually complete. Repeated incidents, however, can cause permanent muscle weakness or loss of sensation. This disorder is also associated with pain in the limbs, especially the hands.A pressure palsy episode results from pressure on a single nerve, and any peripheral nerve can be affected. Although episodes often recur, they can affect different nerves. The most common problem sites involve nerves in the wrists, elbows, and knees. The fingers, shoulders, hands, feet, and scalp can also be affected. Many people with this disorder experience carpal tunnel syndrome, which occurs when a nerve in the wrist (the median nerve) is involved. Carpal tunnel syndrome is characterized by numbness, tingling, and weakness in the hand and fingers. An episode in the hand may affect fine motor activities such as writing, opening jars, and fastening buttons. An episode of nerve compression in the knee can lead to a condition called foot drop, which makes walking, climbing stairs, or driving difficult or impossible.The symptoms of hereditary neuropathy with liability to pressure palsies usually begin during adolescence or early adulthood but may develop anytime from childhood to late adulthood. Symptoms vary in severity; many people never realize they have the disorder, while some people experience prolonged disability. Hereditary neuropathy with liability to pressure palsies does not affect life expectancy. ad Autosomal dominant PMP22 https://medlineplus.gov/genetics/gene/pmp22 Compression neuropathy Entrapment neuropathy Familial pressure sensitive neuropathy Hereditary motor and sensory neuropathy Hereditary pressure sensitive neuropathy HNPP Inherited tendency to pressure palsies Tomaculous neuropathy GTR C0393814 MeSH D006211 MeSH D015417 OMIM 162500 SNOMED CT 230558006 2007-04 2023-03-21 Hereditary pancreatitis https://medlineplus.gov/genetics/condition/hereditary-pancreatitis descriptionHereditary pancreatitis is a genetic condition characterized by recurrent episodes of inflammation of the pancreas (pancreatitis). The pancreas produces enzymes that help digest food, and it also produces insulin, a hormone that controls levels of blood glucose, also called blood sugar. Episodes of pancreatitis can lead to permanent tissue damage and loss of pancreatic function.Signs and symptoms of this condition usually begin in late childhood with an episode of acute pancreatitis. A sudden (acute) attack can cause abdominal pain, fever, nausea, or vomiting. An episode typically lasts from one to three days, although some people may experience severe episodes that last longer. Hereditary pancreatitis progresses to recurrent acute pancreatitis with multiple episodes of acute pancreatitis that recur over a period of at least a year; the number of episodes a person experiences varies. Recurrent acute pancreatitis leads to chronic pancreatitis, which occurs when the pancreas is persistently inflamed. Chronic pancreatitis usually develops by early adulthood in affected individuals. Signs and symptoms of chronic pancreatitis include occasional or frequent abdominal pain of varying severity, flatulence, and bloating. Many individuals with hereditary pancreatitis also develop abnormal calcium deposits in the pancreas (pancreatic calcifications) by early adulthood.Years of inflammation damage the pancreas, causing the formation of scar tissue (fibrosis) in place of functioning pancreatic tissue. Pancreatic fibrosis leads to the loss of pancreatic function in many affected individuals. This loss of function can impair the production of digestive enzymes and disrupt normal digestion, leading to fatty stool (steatorrhea), weight loss, and protein and vitamin deficiencies. Because of a decrease in insulin production due to a loss of pancreatic function, about a quarter of individuals with hereditary pancreatitis will develop type 1 diabetes mellitus by mid-adulthood; the risk of developing diabetes increases with age.Chronic pancreatic inflammation and damage to the pancreas increase the risk of developing pancreatic cancer. The risk is particularly high in people with hereditary pancreatitis who also smoke, use alcohol, have type 1 diabetes mellitus, or have a family history of cancer. In affected individuals who develop pancreatic cancer, it is typically diagnosed in mid-adulthood.Complications from pancreatic cancer and type 1 diabetes mellitus are the most common causes of death in individuals with hereditary pancreatitis, although individuals with this condition are thought to have a normal life expectancy. ad Autosomal dominant CFTR https://medlineplus.gov/genetics/gene/cftr PRSS1 https://medlineplus.gov/genetics/gene/prss1 SPINK1 https://www.ncbi.nlm.nih.gov/gene/6690 CTRC https://www.ncbi.nlm.nih.gov/gene/11330 Autosomal dominant hereditary pancreatitis Familial pancreatitis Hereditary chronic pancreatitis HP GTR C0238339 ICD-10-CM K86.1 MeSH D050500 OMIM 167800 SNOMED CT 235949005 SNOMED CT 235956004 SNOMED CT 68072000 2012-10 2023-07-26 Hereditary paraganglioma-pheochromocytoma https://medlineplus.gov/genetics/condition/hereditary-paraganglioma-pheochromocytoma descriptionHereditary paraganglioma-pheochromocytoma is an inherited condition characterized by the growth of tumors in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are located on top of each kidney and produce hormones in response to stress. Other types of paraganglioma are usually found in the head, neck, or trunk. People with hereditary paraganglioma-pheochromocytoma develop one or more paragangliomas, which may include pheochromocytomas.Pheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Sympathetic paragangliomas found outside the adrenal glands, usually in the abdomen, are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.Most paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.Paragangliomas and pheochromocytomas are typically considered an undetermined tumor type, meaning they can be noncancerous (benign) or become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.Researchers have identified several types of hereditary paraganglioma-pheochromocytoma. Each type is distinguished by its genetic cause. People with types 1, 2, and 3 typically develop paragangliomas in the head or neck region. People with type 4 usually develop extra-adrenal paragangliomas in the abdomen and are at higher risk for malignant tumors that metastasize. The other types are very rare. Hereditary paraganglioma-pheochromocytoma is typically diagnosed in a person's 30s.Paragangliomas and pheochromocytomas can occur in individuals with other inherited disorders, such as von Hippel-Lindau syndrome, Carney-Stratakis syndrome, and certain types of multiple endocrine neoplasia. These other disorders feature additional tumor types and have different genetic causes. Some paragangliomas and pheochromocytomas occur in people with no history of the tumors in their families and appear not to be inherited. These cases are designated as sporadic. ad Autosomal dominant SDHD https://medlineplus.gov/genetics/gene/sdhd SDHAF2 https://medlineplus.gov/genetics/gene/sdhaf2 SDHC https://medlineplus.gov/genetics/gene/sdhc SDHB https://medlineplus.gov/genetics/gene/sdhb SDHA https://medlineplus.gov/genetics/gene/sdha Familial paraganglioma syndrome Familial paraganglioma-pheochromocytoma syndromes FPGL FPGL/PHEO Hereditary paraganglioma-pheochromocytoma syndromes Hereditary pheochromocytoma-paraganglioma Paragangliomas 1 Paragangliomas 2 Paragangliomas 3 Paragangliomas 4 GTR C1854336 GTR C1861848 GTR C1866552 GTR C1868633 GTR C3279992 MeSH D010235 OMIM 115310 OMIM 168000 OMIM 601650 OMIM 605373 OMIM 614165 SNOMED CT 716857003 2011-06 2023-11-08 Hereditary sensory and autonomic neuropathy type IE https://medlineplus.gov/genetics/condition/hereditary-sensory-and-autonomic-neuropathy-type-ie descriptionHereditary sensory and autonomic neuropathy type IE (HSAN IE) is a disorder that affects the nervous system. It is characterized by three main features: hearing loss, a decline of intellectual function (dementia), and a worsening loss of sensation in the feet and legs (peripheral neuropathy).People with HSAN IE develop hearing loss that is caused by abnormalities in the inner ear (sensorineural hearing loss). The hearing loss, which affects both ears, gets worse over time and usually progresses to moderate or severe deafness between the ages of 20 and 35.Affected individuals experience dementia typically beginning in their thirties. In some people with HSAN IE, changes in personality, such as irritability, apathy, or lack of impulse control, become apparent before problems with thinking skills.Peripheral neuropathy is caused by impaired function of nerve cells called sensory neurons, which transmit information about sensations such as pain, temperature, and touch. Loss of sensation in the feet and legs, which usually begins in adolescence or early adulthood in people with HSAN IE and worsens over time, can cause difficulty walking. Affected individuals may not be aware of injuries to their feet, which can lead to complications such as open sores and infections. If these complications are severe, amputation of the affected areas may be required.Some people with HSAN IE also experience recurrent seizures (epilepsy) and sleep problems. The severity of the signs and symptoms of HSAN IE and their age of onset are variable, even among affected members of the same family. ad Autosomal dominant DNMT1 https://medlineplus.gov/genetics/gene/dnmt1 DNMT1-complex disorder DNMT1-related dementia, deafness, and sensory neuropathy Hereditary sensory and autonomic neuropathy type 1 with dementia and hearing loss Hereditary sensory neuropathy type IE HSAN1E HSN IE HSNIE GTR C3279885 MeSH D009477 OMIM 614116 SNOMED CT 397734008 2017-06 2020-08-18 Hereditary sensory and autonomic neuropathy type II https://medlineplus.gov/genetics/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii descriptionHereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch to the brain. These sensations are impaired in people with HSAN2. In some affected people, the condition may also cause mild abnormalities of the autonomic neurons, which control involuntary body functions such as heart rate, digestion, and breathing. The sensory and autonomic neurons are part of the body's peripheral nervous system, which comprises the nerves outside the brain and spinal cord. HSAN2 is considered a form of peripheral neuropathy.The signs and symptoms of HSAN2 typically begin in infancy or early childhood. The first sign of the condition is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. In people with HSAN2, unnoticed injuries often lead to open sores (ulcers) on the hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may require amputation of the affected area. People with HSAN2 often injure themselves unintentionally, typically by biting the tongue, lips, or fingers. These injuries may lead to loss of the affected areas, such as the tip of the tongue. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are damaged.The effects of HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux) or slow eye-blink or gag reflexes. Affected individuals may also have weak deep-tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.Some people with HSAN2 lose a type of taste bud on the tip of the tongue called lingual fungiform papillae and have a diminished sense of taste. ar Autosomal recessive SCN9A https://medlineplus.gov/genetics/gene/scn9a WNK1 https://medlineplus.gov/genetics/gene/wnk1 RETREG1 https://medlineplus.gov/genetics/gene/retreg1 KIF1A https://www.ncbi.nlm.nih.gov/gene/547 Congenital sensory neuropathy Hereditary sensory and autonomic neuropathy type 2 HSAN type II HSAN2 HSAN2A HSAN2B HSAN2C HSAN2D HSANII HSN type II Morvan disease GTR C2751092 GTR C2752089 MeSH D009477 OMIM 201300 OMIM 613115 SNOMED CT 398148000 SNOMED CT 860809000 SNOMED CT 860810005 2017-04 2023-08-18 Hereditary sensory and autonomic neuropathy type V https://medlineplus.gov/genetics/condition/hereditary-sensory-and-autonomic-neuropathy-type-v descriptionHereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN5.The signs and symptoms of HSAN5 appear early, usually at birth or during infancy. People with HSAN5 lose the ability to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ligaments, or muscles, is especially affected in people with HSAN5. Because of the inability to feel deep pain, affected individuals suffer repeated severe injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed. ar Autosomal recessive NGF https://medlineplus.gov/genetics/gene/ngf Congenital insensitivity to pain Congenital sensory neuropathy with selective loss of small myelinated fibers Hereditary sensory and autonomic neuropathy, type 5 HSAN type V HSAN V HSAN5 GTR C0020075 MeSH D009477 OMIM 608654 SNOMED CT 128206006 2011-07 2020-08-18 Hereditary sensory neuropathy type IA https://medlineplus.gov/genetics/condition/hereditary-sensory-neuropathy-type-ia descriptionHereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition experience prickling or tingling sensations (paresthesias), numbness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, joints, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older. Weakness in the ankle muscles can make walking difficult. As the condition progresses, some people with hereditary sensory neuropathy type IA require wheelchair assistance.Individuals with hereditary sensory neuropathy type IA typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected individuals cannot feel the pain of these sores, they may not seek immediate treatment. Without treatment, the ulcers can become infected and may require amputation of the surrounding area or limb.Some people with hereditary sensory neuropathy type IA develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). Hearing loss typically develops in middle to late adulthood.The signs and symptoms of hereditary sensory neuropathy type IA can begin anytime between adolescence and late adulthood. While the features of this condition tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are properly treated. ad Autosomal dominant SPTLC1 https://medlineplus.gov/genetics/gene/sptlc1 Autosomal dominant hereditary sensory radicular neuropathy, type 1A Hereditary sensory and autonomic neuropathy, type IA HSAN IA HSAN1A HSN IA HSN1A GTR C0020071 ICD-10-CM G60.8 MeSH D009477 OMIM 162400 SNOMED CT 397734008 2015-02 2020-08-18 Hereditary spherocytosis https://medlineplus.gov/genetics/condition/hereditary-spherocytosis descriptionHereditary spherocytosis is a condition that affects red blood cells. People with this condition typically experience a shortage of red blood cells (anemia), yellowing of the eyes and skin (jaundice), and an enlarged spleen (splenomegaly). Most newborns with hereditary spherocytosis have severe anemia, although it improves after the first year of life. Splenomegaly can occur anytime from early childhood to adulthood. About half of affected individuals develop hard deposits in the gallbladder called gallstones, which typically occur from late childhood to mid-adulthood.There are four forms of hereditary spherocytosis, which are distinguished by the severity of signs and symptoms. They are known as the mild form, the moderate form, the moderate/severe form, and the severe form. It is estimated that 20 to 30 percent of people with hereditary spherocytosis have the mild form, 60 to 70 percent have the moderate form, 10 percent have the moderate/severe form, and 3 to 5 percent have the severe form.People with the mild form may have very mild anemia or sometimes have no symptoms. People with the moderate form typically have anemia, jaundice, and splenomegaly. Many also develop gallstones. The signs and symptoms of moderate hereditary spherocytosis usually appear in childhood. Individuals with the moderate/severe form have all the features of the moderate form but also have severe anemia. Those with the severe form have life-threatening anemia that requires frequent blood transfusions to replenish their red blood cell supply. They also have severe splenomegaly, jaundice, and a high risk for developing gallstones. Some individuals with the severe form have short stature, delayed sexual development, and skeletal abnormalities. ad Autosomal dominant ar Autosomal recessive ANK1 https://medlineplus.gov/genetics/gene/ank1 SLC4A1 https://medlineplus.gov/genetics/gene/slc4a1 EPB42 https://www.ncbi.nlm.nih.gov/gene/2038 SPTA1 https://www.ncbi.nlm.nih.gov/gene/6708 SPTB https://www.ncbi.nlm.nih.gov/gene/6710 Congenital spherocytic hemolytic anemia Congenital spherocytosis HS Spherocytic anemia Spherocytosis, type 1 GTR C0037889 GTR C2674219 GTR C2675192 GTR C2675212 GTR C2678338 ICD-10-CM D58.0 MeSH D013103 OMIM 182870 OMIM 182900 OMIM 270970 OMIM 612653 OMIM 612690 SNOMED CT 55995005 2010-10 2020-08-18 Hereditary xanthinuria https://medlineplus.gov/genetics/condition/hereditary-xanthinuria descriptionHereditary xanthinuria is a condition that most often affects the kidneys. It is characterized by high levels of a compound called xanthine and very low levels of another compound called uric acid in the blood and urine. The excess xanthine can accumulate in the kidneys and other tissues. In the kidneys, xanthine forms tiny crystals that occasionally build up to create kidney stones. These stones can impair kidney function and ultimately cause kidney failure. Related signs and symptoms can include abdominal pain, recurrent urinary tract infections, and blood in the urine (hematuria). Less commonly, xanthine crystals build up in the muscles, causing pain and cramping. In some people with hereditary xanthinuria, the condition does not cause any health problems.Researchers have described two major forms of hereditary xanthinuria, types I and II. The types are distinguished by the enzymes involved; they have the same signs and symptoms. ar Autosomal recessive MOCOS https://medlineplus.gov/genetics/gene/mocos XDH https://medlineplus.gov/genetics/gene/xdh Combined deficiency of xanthine dehydrogenase and aldehyde oxidase Xanthine dehydrogenase deficiency Xanthine oxidase deficiency Xanthinuria XDH deficiency GTR C0268118 GTR C1863688 MeSH D008661 OMIM 278300 OMIM 603592 SNOMED CT 124147007 SNOMED CT 29692004 SNOMED CT 54627004 SNOMED CT 72682008 SNOMED CT 836343001 2015-12 2020-08-18 Hermansky-Pudlak syndrome https://medlineplus.gov/genetics/condition/hermansky-pudlak-syndrome descriptionHermansky-Pudlak syndrome is a disorder characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and white or light-colored hair. People with this disorder have a higher than average risk of skin damage and skin cancers caused by long-term sun exposure. Oculocutaneous albinism reduces pigmentation of the colored part of the eye (iris) and the light-sensitive tissue at the back of the eye (retina). Reduced vision, rapid and involuntary eye movements (nystagmus), and increased sensitivity to light (photophobia) are also common in oculocutaneous albinism. In Hermansky-Pudlak syndrome, these vision problems usually remain stable after early childhood.People with Hermansky-Pudlak syndrome also have problems with blood clotting (coagulation) that lead to easy bruising and prolonged bleeding.Some individuals with Hermansky-Pudlak syndrome develop breathing problems due to a lung disease called pulmonary fibrosis, which causes scar tissue to form in the lungs. The symptoms of pulmonary fibrosis usually appear during an individual's early thirties and rapidly worsen. Individuals with Hermansky-Pudlak syndrome who develop pulmonary fibrosis often do not live for more than a decade after they begin to experience breathing problems.Other, less common features of Hermansky-Pudlak syndrome include inflammation of the large intestine (granulomatous colitis) and kidney failure.There are nine different types of Hermansky-Pudlak syndrome, which can be distinguished by their signs and symptoms and underlying genetic cause. Types 1 and 4 are the most severe forms of the disorder. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with type 3, 5, or 6 have the mildest symptoms. Little is known about the signs, symptoms, and severity of types 7, 8, and 9. ar Autosomal recessive HPS1 https://medlineplus.gov/genetics/gene/hps1 HPS3 https://medlineplus.gov/genetics/gene/hps3 AP3B1 https://www.ncbi.nlm.nih.gov/gene/8546 HPS5 https://www.ncbi.nlm.nih.gov/gene/11234 BLOC1S6 https://www.ncbi.nlm.nih.gov/gene/26258 HPS6 https://www.ncbi.nlm.nih.gov/gene/79803 DTNBP1 https://www.ncbi.nlm.nih.gov/gene/84062 HPS4 https://www.ncbi.nlm.nih.gov/gene/89781 BLOC1S3 https://www.ncbi.nlm.nih.gov/gene/388552 HPS GTR C0079504 GTR C2931875 ICD-10-CM E70.331 MeSH D022861 OMIM 203300 SNOMED CT 9311003 2014-05 2020-08-18 Heterotaxy syndrome https://medlineplus.gov/genetics/condition/heterotaxy-syndrome descriptionHeterotaxy syndrome is a condition in which the internal organs are abnormally arranged in the chest and abdomen. The term "heterotaxy" is from the Greek words "heteros," meaning "other than," and "taxis," meaning "arrangement." Individuals with this condition have complex birth defects affecting the heart, lungs, liver, spleen, intestines, and other organs.In the normal body, most of the organs in the chest and abdomen have a particular location on the right or left side. For example, the heart, spleen, and pancreas are on the left side of the body, and most of the liver is on the right. This normal arrangement of the organs is known as "situs solitus." Rarely, the orientation of the internal organs is completely flipped from right to left, a situation known as "situs inversus." This mirror-image orientation usually does not cause any health problems, unless it occurs as part of a syndrome affecting other parts of the body. Heterotaxy syndrome is an arrangement of internal organs somewhere between situs solitus and situs inversus; this condition is also known as "situs ambiguus." Unlike situs inversus, the abnormal arrangement of organs in heterotaxy syndrome often causes serious health problems.Heterotaxy syndrome can alter the structure of the heart, including the attachment of the large blood vessels that carry blood to and from the rest of the body. It can also affect the structure of the lungs, such as the number of lobes in each lung and the length of the tubes (called bronchi) that lead from the windpipe to the lungs. In the abdomen, the condition can cause a person to have no spleen (asplenia) or multiple small, poorly functioning spleens (polysplenia). The liver may lie across the middle of the body instead of being in its normal position to the right of the stomach. Some affected individuals also have intestinal malrotation, which is an abnormal twisting of the intestines that occurs in the early stages of development before birth.Depending on the organs involved, signs and symptoms of heterotaxy syndrome can include a bluish appearance of the skin or lips (cyanosis, which is due to a shortage of oxygen), breathing difficulties, an increased risk of infections, and problems with digesting food. The most serious complications are generally caused by critical congenital heart disease, a group of complex heart defects that are present from birth. Biliary atresia, a problem with the bile ducts in the liver, can also cause severe health problems in infancy.The severity of heterotaxy syndrome varies depending on the specific abnormalities involved. Some affected individuals have only mild health problems related to the condition. At the other end of the spectrum, heterotaxy syndrome can be life-threatening in infancy or childhood, even with treatment. x X-linked ad Autosomal dominant n Not inherited ar Autosomal recessive DNAI1 https://medlineplus.gov/genetics/gene/dnai1 DNAH5 https://medlineplus.gov/genetics/gene/dnah5 DNAH11 https://medlineplus.gov/genetics/gene/dnah11 ACVR2B https://www.ncbi.nlm.nih.gov/gene/93 NKX2-5 https://www.ncbi.nlm.nih.gov/gene/1482 GATA4 https://www.ncbi.nlm.nih.gov/gene/2626 GDF1 https://www.ncbi.nlm.nih.gov/gene/2657 SMAD2 https://www.ncbi.nlm.nih.gov/gene/4087 NODAL https://www.ncbi.nlm.nih.gov/gene/4838 LEFTY2 https://www.ncbi.nlm.nih.gov/gene/7044 ZIC3 https://www.ncbi.nlm.nih.gov/gene/7547 FOXH1 https://www.ncbi.nlm.nih.gov/gene/8928 CITED2 https://www.ncbi.nlm.nih.gov/gene/10370 SESN1 https://www.ncbi.nlm.nih.gov/gene/27244 NAT10 https://www.ncbi.nlm.nih.gov/gene/55226 CFC1 https://www.ncbi.nlm.nih.gov/gene/55997 SHROOM3 https://www.ncbi.nlm.nih.gov/gene/57619 CRELD1 https://www.ncbi.nlm.nih.gov/gene/78987 MMP21 https://www.ncbi.nlm.nih.gov/gene/118856 CFAP53 https://www.ncbi.nlm.nih.gov/gene/220136 Heterotaxy HTX Ivemark syndrome Left isomerism Right isomerism Situs ambiguus Situs ambiguus viscerum Visceral heterotaxy GTR C1415817 GTR C1844020 GTR C1853509 GTR C3151057 GTR C3178805 GTR C3495537 GTR C3553676 ICD-10-CM Q89.3 MeSH D059446 OMIM 208530 OMIM 270100 OMIM 306955 OMIM 605376 OMIM 606217 OMIM 606325 OMIM 613751 OMIM 614779 SNOMED CT 14821001 SNOMED CT 8641000119101 2016-01 2025-09-22 Hidradenitis suppurativa https://medlineplus.gov/genetics/condition/hidradenitis-suppurativa descriptionHidradenitis suppurativa, also known as acne inversa, is a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin. The nodules become inflamed and painful. They tend to break open (rupture), causing abscesses that drain fluid and pus. As the abscesses heal, they produce significant scarring of the skin.The signs and symptoms of hidradenitis suppurativa typically appear after puberty, usually in a person's teens or twenties, although they can begin earlier in puberty, particularly in affected females. Nodules are most likely to form in the armpits and groin. They may also develop around the anus, on the buttocks, or under the breasts. In some cases, nodules appear in other areas, such as the nape of the neck, waist, and inner thighs.The recurrent nodules and abscesses cause chronic pain and can lead to self-consciousness, social isolation, and depression. Rarely, long-term (chronic) abscesses on the buttocks can develop into a type of skin cancer called squamous cell carcinoma. ad Autosomal dominant PSEN1 https://medlineplus.gov/genetics/gene/psen1 NCSTN https://medlineplus.gov/genetics/gene/ncstn PSENEN https://medlineplus.gov/genetics/gene/psenen Acne inversa Apocrinitis Hidradenitides, suppurative Hidradenitis, suppurative Suppurative hidradenitides Suppurative hidradenitis GTR C1840560 ICD-10-CM L73.2 MeSH D017497 OMIM 142690 OMIM 613736 OMIM 613737 SNOMED CT 59393003 2013-12 2024-09-19 Hirschsprung disease https://medlineplus.gov/genetics/condition/hirschsprung-disease descriptionHirschsprung disease is an intestinal disorder characterized by the absence of nerves in parts of the intestine. This condition occurs when the nerves in the intestine (enteric nerves) do not form properly during development before birth (embryonic development). This condition is usually identified in the first two months of life, although less severe cases may be diagnosed later in childhood.Enteric nerves trigger the muscle contractions that move stool through the intestine. Without these nerves in parts of the intestine, the material cannot be pushed through, causing severe constipation or complete blockage of the intestine in people with Hirschsprung disease. Other signs and symptoms of this condition include vomiting, abdominal pain or swelling, diarrhea, poor feeding, malnutrition, and slow growth. People with this disorder are at risk of developing more serious conditions such as inflammation of the intestine (enterocolitis) or a hole in the wall of the intestine (intestinal perforation), which can cause serious infection and may be fatal.There are two main types of Hirschsprung disease, known as short-segment disease and long-segment disease, which are defined by the region of the intestine lacking nerve cells. In short-segment disease, nerve cells are missing from only the last segment of the large intestine (colon). This type is most common, occurring in approximately 80 percent of people with Hirschsprung disease. For unknown reasons, short-segment disease is four times more common in men than in women. Long-segment disease occurs when nerve cells are missing from most of the large intestine and is the more severe type. Long-segment disease is found in approximately 20 percent of people with Hirschsprung disease and affects men and women equally. Very rarely, nerve cells are missing from the entire large intestine and sometimes part of the small intestine (total colonic aganglionosis) or from all of the large and small intestine (total intestinal aganglionosis).Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic. ad Autosomal dominant SOX10 https://medlineplus.gov/genetics/gene/sox10 EDNRB https://medlineplus.gov/genetics/gene/ednrb EDN3 https://medlineplus.gov/genetics/gene/edn3 RET https://medlineplus.gov/genetics/gene/ret GDNF https://www.ncbi.nlm.nih.gov/gene/2668 NRG1 https://www.ncbi.nlm.nih.gov/gene/3084 NRTN https://www.ncbi.nlm.nih.gov/gene/4902 SEMA3D https://www.ncbi.nlm.nih.gov/gene/10511 SEMA3C https://www.ncbi.nlm.nih.gov/gene/10512 NRG3 https://www.ncbi.nlm.nih.gov/gene/10718 Aganglionic megacolon Congenital intestinal aganglionosis Congenital megacolon Hirschsprung's disease HSCR GTR C1838564 GTR C3150974 GTR C3150975 GTR C3888239 ICD-10-CM Q43.1 MeSH D006627 OMIM 142623 OMIM 600155 OMIM 613711 OMIM 613712 SNOMED CT 204739008 SNOMED CT 253780003 2012-08 2020-08-18 Histidinemia https://medlineplus.gov/genetics/condition/histidinemia descriptionHistidinemia is an inherited condition characterized by elevated levels of histidine in blood, urine, and the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). Histidine is an amino acid that acts as a building block for many different proteins. In most cases, histidinemia does not cause health problems. Most people with elevated histidine levels are unaware that they have this condition. Rarely, people with histidinemia have intellectual disabilities, learning disabilities, or behavioral problems. Having a medical complication during or soon after birth might increase the risk of developmental problems in people with histidinemia.  ar Autosomal recessive HAL https://medlineplus.gov/genetics/gene/hal HAL deficiency HIS deficiency Histidase deficiency Histidine ammonia-lyase deficiency Histidinuria Hyperhistidinemia GTR C0220992 ICD-10-CM E70.41 MeSH D000592 OMIM 235800 SNOMED CT 124628005 SNOMED CT 410058007 2024-06 2024-06-03 Histiocytosis-lymphadenopathy plus syndrome https://medlineplus.gov/genetics/condition/histiocytosis-lymphadenopathy-plus-syndrome descriptionHistiocytosis-lymphadenopathy plus syndrome (also known as SLC29A3 spectrum disorder) is a group of conditions with overlapping signs and symptoms that affect many parts of the body. This group of disorders includes H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID), Faisalabad histiocytosis, and familial Rosai-Dorfman disease (RDD). These conditions were once thought to be distinct disorders; however, because of the overlapping features and shared genetic cause, they are now considered to be part of the same disease spectrum. While some affected individuals have signs and symptoms characteristic of one of the conditions, others have a range of features from two or more of the conditions. The pattern of signs and symptoms can vary even within the same family.A feature common to the disorders in this spectrum is histiocytosis, which is the overgrowth of immune system cells called histiocytes. The cells abnormally accumulate in one or more tissues in the body, which can lead to organ or tissue damage. The buildup often occurs in the lymph nodes, leading to swelling of the lymph nodes (lymphadenopathy). Other areas of cell accumulation can include the skin, kidneys, brain and spinal cord (central nervous system), or digestive tract.This spectrum is known as histiocytosis-lymphadenopathy plus syndrome because the disorders that make up the spectrum can have additional signs and symptoms. A characteristic feature of H syndrome is abnormal patches of skin (lesions), typically on the lower body. These lesions are unusually dark (hyperpigmented) and have excessive hair growth (hypertrichosis). In addition, histiocytes accumulate at the site of the skin lesions. Other features of H syndrome include enlargement of the liver (hepatomegaly), heart abnormalities, hearing loss, reduced amounts of hormones that direct sexual development (hypogonadism), and short stature.Like H syndrome, PHID causes patches of hyperpigmented skin with hypertrichosis. PHID is also characterized by the development of type 1 diabetes (also known as insulin-dependent diabetes mellitus), which usually begins in childhood. Type 1 diabetes occurs when the body does not produce enough of the hormone insulin, leading to dysregulation of levels of blood glucose, also called blood sugar.Faisalabad histiocytosis typically causes lymphadenopathy and swelling of the eyelids due to accumulation of histiocytes. Affected individuals can also have joint deformities called contractures in their fingers or toes and hearing loss.The most common feature of familial RDD is lymphadenopathy, usually affecting lymph nodes in the neck. Histiocytes can also accumulate in other parts of the body. (Familial RDD is one of several forms of RDD; the other forms are not considered part of histiocytosis-lymphadenopathy plus syndrome.) ar Autosomal recessive SLC29A3 https://medlineplus.gov/genetics/gene/slc29a3 SLC29A3 disorder SLC29A3 spectrum disorder GTR C1864445 MeSH D015614 OMIM 602782 SNOMED CT 711159002 2014-12 2023-07-26 Holocarboxylase synthetase deficiency https://medlineplus.gov/genetics/condition/holocarboxylase-synthetase-deficiency descriptionHolocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, which is a group of disorders characterized by impaired activity of certain enzymes that depend on biotin.The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management with biotin supplements may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases. ar Autosomal recessive HLCS https://medlineplus.gov/genetics/gene/hlcs Biotin-(propionyl-CoA-carboxylase) ligase deficiency Biotin-(propionyl-coenzyme A-carboxylase) ligase deficiency Early-onset biotin-responsive multiple carboxylase deficiency Early-onset combined carboxylase deficiency HLCS deficiency Infantile multiple carboxylase deficiency GTR C0268581 ICD-10-CM D81.818 MeSH D028922 OMIM 253270 SNOMED CT 15307001 2020-05 2020-08-18 Holt-Oram syndrome https://medlineplus.gov/genetics/condition/holt-oram-syndrome descriptionHolt-Oram syndrome is characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems.People with Holt-Oram syndrome have abnormally developed bones in their upper limbs. At least one abnormality in the bones of the wrist (carpal bones) is present in affected individuals. Often, these wrist bone abnormalities can be detected only by x-ray. Individuals with Holt-Oram syndrome may have additional bone abnormalities including a missing thumb, a long thumb that looks like a finger, partial or complete absence of bones in the forearm, an underdeveloped bone of the upper arm, and abnormalities of the collar bone or shoulder blades. These skeletal abnormalities may affect one or both of the upper limbs. If both upper limbs are affected, the bone abnormalities can be the same or different on each side. In cases where the skeletal abnormalities are not the same on both sides of the body, the left side is usually more severely affected than the right side.About 75 percent of individuals with Holt-Oram syndrome have heart (cardiac) problems, which can be life-threatening. The most common problem is a defect in the muscular wall (septum) that separates the right and left sides of the heart. A hole in the septum between the upper chambers of the heart (atria) is called an atrial septal defect (ASD), and a hole in the septum between the lower chambers of the heart (ventricles) is called a ventricular septal defect (VSD). Some people with Holt-Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slower-than-normal heart rate (bradycardia) or a rapid and uncoordinated contraction of the heart muscle (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as ASD or VSD) or as the only heart problem in people with Holt-Oram syndrome.The features of Holt-Oram syndrome are similar to those of a condition called Duane-radial ray syndrome; however, these two disorders are caused by mutations in different genes. ad Autosomal dominant TBX5 https://medlineplus.gov/genetics/gene/tbx5 Atrio-digital syndrome Atriodigital dysplasia Cardiac-limb syndrome Heart-hand syndrome, type 1 HOS Ventriculo-radial syndrome GTR C0265264 MeSH D006330 MeSH D038062 OMIM 142900 SNOMED CT 19092004 2009-12 2020-08-18 Homocystinuria https://medlineplus.gov/genetics/condition/homocystinuria descriptionHomocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. The most common form of homocystinuria, called classic homocystinuria, is characterized by tall stature, nearsightedness (myopia), dislocation of the lens at the front of the eye, a higher risk of blood clotting disorders, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems.Less common forms of homocystinuria can cause intellectual disability, slower growth and weight gain (failure to thrive), seizures, and problems with movement. They can also cause and a blood disorder called megaloblastic anemia, which occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic).The signs and symptoms of homocystinuria typically develop during childhood, although some mildly affected people may not show signs and symptoms until adulthood. ar Autosomal recessive CBS https://medlineplus.gov/genetics/gene/cbs MTHFR https://medlineplus.gov/genetics/gene/mthfr MTRR https://medlineplus.gov/genetics/gene/mtrr MTR https://medlineplus.gov/genetics/gene/mtr MMADHC https://medlineplus.gov/genetics/gene/mmadhc Cystathionine beta synthase deficiency Homocysteinemia GTR C0019880 GTR C0751202 GTR C1848553 GTR C1856061 ICD-10-CM E72.11 ICD-10-CM E72.12 MeSH D006712 OMIM 236200 OMIM 236250 OMIM 236270 OMIM 250940 OMIM 277410 SNOMED CT 11282001 SNOMED CT 24308003 SNOMED CT 28093001 SNOMED CT 360373000 2023-05 2023-05-01 Horizontal gaze palsy with progressive scoliosis https://medlineplus.gov/genetics/condition/horizontal-gaze-palsy-with-progressive-scoliosis descriptionHorizontal gaze palsy with progressive scoliosis (HGPPS) is a disorder that affects the eyes and the spine. Individuals with this condition are unable to move their eyes side-to-side (horizontally) from birth, although the problem may not be diagnosed until later in infancy. As a result, affected individuals must track moving objects by turning their head instead of moving their eyes. Up-and-down (vertical) eye movements are typically normal.In people with HGPPS, an abnormal side-to-side curvature of the spine (scoliosis) develops between infancy and childhood. It tends to be moderate to severe and worsens over time. The abnormal spine position can be painful and can interfere with movement. In severe cases, it may impede breathing. It may require external support, such as bracing, and is often treated with surgery early in life.People with HGPPS have structural abnormalities along the midline of the brain that can only be seen with medical imaging. This imaging shows distinctive malformations that include underdevelopment of brain structures called the pons and cerebellar peduncles and a notch or cleft in the midline of the brain. While most people with HGPPS have a normal intellect, mild intellectual disabilities can occur. ar Autosomal recessive ROBO3 https://medlineplus.gov/genetics/gene/robo3 Familial horizontal gaze palsy with progressive scoliosis Familial infantile scoliosis associated with bilateral paralysis of conjugate gaze HGPPS Progressive external ophthalmoplegia and scoliosis GTR C4551964 MeSH D012600 MeSH D015785 OMIM 607313 SNOMED CT 702381007 2025-04 2025-04-07 Horner syndrome https://medlineplus.gov/genetics/condition/horner-syndrome descriptionHorner syndrome is a disorder that affects the eye and surrounding tissues on one side of the face and results from paralysis of certain nerves. Horner syndrome can appear at any time of life; in about 5 percent of affected individuals, the disorder is present from birth (congenital).Horner syndrome is characterized by drooping of the upper eyelid (ptosis) on the affected side, a constricted pupil in the affected eye (miosis) resulting in unequal pupil size (anisocoria), and absent sweating (anhidrosis) on the affected side of the face. Sinking of the eye into its cavity (enophthalmos) and a bloodshot eye often occur in this disorder. In people with Horner syndrome that occurs before the age of 2, the colored part (iris) of the eyes may differ in color (iris heterochromia), with the iris of the affected eye being lighter in color than that of the unaffected eye. Individuals who develop Horner syndrome after age 2 do not generally have iris heterochromia.The abnormalities in the eye area related to Horner syndrome do not generally affect vision or health. However, the nerve damage that causes Horner syndrome may result from other health problems, some of which can be life-threatening. ad Autosomal dominant Bernard-Horner syndrome Horner's syndrome Oculosympathetic palsy Von Passow syndrome ICD-10-CM G90.2 MeSH D006732 OMIM 143000 SNOMED CT 164018003 SNOMED CT 192915005 SNOMED CT 271730003 2013-04 2020-08-18 Huntington's disease https://medlineplus.gov/genetics/condition/huntingtons-disease descriptionHuntington's disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition).Adult-onset Huntington's disease, the most common form of this disorder, usually appears in a person's thirties or forties. Early signs and symptoms can include irritability, depression, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many people with Huntington's disease develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these movements become more pronounced. Affected individuals may have trouble walking, speaking, and swallowing. People with this disorder also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with the adult-onset form of Huntington's disease usually live about 15 to 20 years after signs and symptoms begin.A less common form of Huntington's disease known as the juvenile form begins in childhood or adolescence. It also involves movement problems and mental and emotional changes. Additional signs of the juvenile form include slow movements, clumsiness, frequent falling, rigidity, slurred speech, and drooling. School performance declines as thinking and reasoning abilities become impaired. Seizures occur in 30 percent to 50 percent of children with this condition. Juvenile Huntington's disease tends to progress more quickly than the adult-onset form; affected individuals usually live 10 to 15 years after signs and symptoms appear. ad Autosomal dominant+1 affected parent HTT https://medlineplus.gov/genetics/gene/htt Huntington chorea Huntington chronic progressive hereditary chorea Huntington disease Huntington's chorea GTR C0020179 GTR C0751208 ICD-10-CM G10 MeSH D006816 OMIM 143100 SNOMED CT 230299004 SNOMED CT 230300007 SNOMED CT 58756001 2020-07 2023-10-12 Huntington's disease-like https://medlineplus.gov/genetics/condition/huntingtons-disease-like descriptionHuntington's disease-like (HDL) is a group of related neurological conditions. As the name suggests, HDLs resembles Huntington's disease. HDLs and Huntington's disease are both characterized by uncontrolled movements, emotional problems, and loss of thinking ability. In both conditions these signs and symptoms worsen over time. HDLs occurs in people with the characteristic features of Huntington's disease who do not have a variant (also called mutation) in the gene typically associated with that disorder. Researchers have described four HDLs that are designated Huntington's disease-like 1 (HDL1) through Huntington's disease-like 4 (HDL4). Sometimes, HDL4 is also known as spinocerebellar ataxia type 17 (SCA17).HDL1, HDL2, and HDL4 usually begin in early to mid-adulthood, although they can start earlier or later. The first signs and symptoms of these conditions often include irritability, emotional problems, small involuntary movements (dyskinesia), poor coordination, and trouble learning new information or making decisions. Many people with an HDL develop involuntary jerking or twitching movements known as chorea. Over time, these abnormal movements worsen. Affected individuals may develop problems with walking (bradykinesia), speaking (dysarthria), and swallowing (dysphagia). People with these disorders also experience changes in personality and a decline in thinking and reasoning abilities (dementia). Individuals with an HDL syndrome can live for 10 to 20 years after signs and symptoms begin, though this can vary between the types of HDL syndromes.HDL3 begins much earlier in life than the other HDLs (usually around age 3 or 4). Affected children experience a decline in thinking ability, difficulties with movement and speech, and seizures. Because HDL3 has some different signs and symptoms and a different pattern of inheritance, researchers are unsure whether it belongs in the same category as the other HDLs. ad Autosomal dominant+1 affected parent ar Autosomal recessive PRNP https://medlineplus.gov/genetics/gene/prnp JPH3 https://medlineplus.gov/genetics/gene/jph3 TBP https://medlineplus.gov/genetics/gene/tbp HDL HDL syndrome Huntington disease-like syndrome Huntington disease-like syndromes Huntington's disease phenocopies Huntington's disease phenocopy syndromes Huntington's disease-like syndrome Huntington's disease-like syndromes GTR C1846707 GTR C1847987 GTR C1864112 MeSH D006816 MeSH D020271 OMIM 603218 OMIM 604802 OMIM 606438 OMIM 607136 SNOMED CT 702376003 2024-06 2024-06-28 Hutchinson-Gilford progeria syndrome https://medlineplus.gov/genetics/condition/hutchinson-gilford-progeria-syndrome descriptionHutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected rate (failure to thrive). They develop a characteristic facial appearance including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears. Hutchinson-Gilford progeria syndrome also causes hair loss (alopecia), aged-looking skin, joint abnormalities, and a loss of fat under the skin (subcutaneous fat). This condition does not affect intellectual development or the development of motor skills such as sitting, standing, and walking.People with Hutchinson-Gilford progeria syndrome experience severe hardening of the arteries (arteriosclerosis) beginning in childhood. This condition greatly increases the chances of having a heart attack or stroke at a young age. These serious complications can worsen over time and are life-threatening for affected individuals. ad Autosomal dominant LMNA https://medlineplus.gov/genetics/gene/lmna HGPS Hutchinson-Gilford syndrome Progeria Progeria of childhood GTR C0033300 GTR C2750285 MeSH D011371 OMIM 176670 SNOMED CT 238870004 2007-07 2020-08-18 Hyaline fibromatosis syndrome https://medlineplus.gov/genetics/condition/hyaline-fibromatosis-syndrome descriptionHyaline fibromatosis syndrome is a disorder in which a clear (hyaline) substance abnormally accumulates in body tissues. This disorder affects many areas of the body, including the skin, joints, bones, and internal organs. The severity of the signs and symptoms of hyaline fibromatosis syndrome fall along a spectrum. In more severe cases (previously diagnosed as infantile systemic hyalinosis), signs and symptoms are present at birth or begin within the first few months of life and can be life-threatening. In milder cases (previously diagnosed as juvenile hyaline fibromatosis), signs and symptoms begin in childhood and affect fewer body systems.One of the main features of hyaline fibromatosis syndrome is the growth of noncancerous masses of tissue (nodules) under the skin, very commonly on the scalp. In more severely affected individuals, nodules also grow in the muscles and internal organs, causing pain and complications. Some severely affected individuals develop a condition called protein-losing enteropathy due to the formation of nodules in their intestines. This condition results in severe diarrhea, failure to gain weight and grow at the expected rate, and general wasting and weight loss (cachexia).Another common feature of hyaline fibromatosis syndrome is painful skin bumps that frequently appear on the hands, neck, scalp, ears, and nose. They can also develop in joint creases and the genital region. These skin bumps are described as white or pink and pearly. They may be large or small and often increase in number over time.In some affected individuals, especially those with more severe signs and symptoms, the skin covering joints, such as the ankles, wrists, elbows, and finger joints, is unusually dark (hyperpigmented). Hyaline fibromatosis syndrome is also characterized by overgrowth of the gums (gingival hypertrophy), and some affected individuals have thickened skin.Joint stiffness and pain are common in hyaline fibromatosis syndrome, and many affected individuals develop joint deformities called contractures that limit movement. By adulthood, some people with the condition require a wheelchair for mobility. Bone abnormalities can also occur in hyaline fibromatosis syndrome.Although individuals with hyaline fibromatosis syndrome have severe physical limitations, mental development is typically normal. People with milder signs and symptoms live into adulthood, while the most severely affected individuals often do not survive beyond early childhood due to chronic diarrhea and recurrent infections. ar Autosomal recessive ANTXR2 https://medlineplus.gov/genetics/gene/antxr2 Inherited systemic hyalinosis Molluscum fibrosum Murray syndrome Puretic syndrome GTR C2745948 MeSH D057770 OMIM 228600 SNOMED CT 238861002 SNOMED CT 238867003 2019-03 2023-11-08 Hyperferritinemia-cataract syndrome https://medlineplus.gov/genetics/condition/hyperferritinemia-cataract-syndrome descriptionHyperferritinemia-cataract syndrome is a disorder characterized by an excess of an iron storage protein called ferritin in the blood (hyperferritinemia) and tissues of the body. A buildup of this protein begins early in life, leading to clouding of the lenses of the eyes (cataracts). In affected individuals, cataracts usually develop in infancy, rather than after age 60 as typically occurs in the general population. Cataracts that are not removed surgically cause progressive dimming and blurriness of vision because the clouded lenses reduce and distort incoming light.Although the hyperferritinemia in this disorder does not usually cause any health problems other than cataracts, the elevated ferritin levels in the blood can be mistaken for a sign of certain liver disorders. These conditions result in excess iron in the body and may be treated by blood-drawing. However, individuals with hyperferritinemia-cataract syndrome do not have an excess of iron, and with repeated blood draws will develop reduced iron levels leading to a low number of red blood cells (anemia). Therefore, correct diagnosis of hyperferritinemia-cataract syndrome is important to avoid unnecessary treatments or invasive test procedures such as liver biopsies. ad Autosomal dominant FTL https://medlineplus.gov/genetics/gene/ftl Bonneau-Beaumont syndrome Hereditary hyperferritinemia with congenital cataracts Hereditary hyperferritinemia-cataract syndrome HHCS GTR C1833213 MeSH D019189 OMIM 600886 SNOMED CT 702398007 2012-08 2020-08-18 Hyperkalemic periodic paralysis https://medlineplus.gov/genetics/condition/hyperkalemic-periodic-paralysis descriptionHyperkalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness or paralysis, usually beginning in infancy or early childhood. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Episodes tend to increase in frequency until mid-adulthood, after which they occur less frequently in many people with the condition. Factors that can trigger attacks include rest after exercise, potassium-rich foods such as bananas and potatoes, stress, fatigue, alcohol, pregnancy, exposure to hot or cold temperatures, certain medications, and periods without food (fasting). Muscle strength usually returns to normal between attacks, although many affected people continue to experience mild stiffness (myotonia), particularly in muscles of the face and hands.Most people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. Hyperkalemia results when the weak or paralyzed muscles release potassium ions into the bloodstream. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not go up. ad Autosomal dominant SCN4A https://medlineplus.gov/genetics/gene/scn4a Adynamia episodica hereditaria Familial hyperkalemic periodic paralysis Gamstorp disease Gamstorp episodic adynamy HyperKPP HyperPP Primary hyperkalemic periodic paralysis GTR C0238357 ICD-10-CM G72.3 MeSH D020513 OMIM 170500 SNOMED CT 304737009 2013-08 2023-08-22 Hyperlysinemia https://medlineplus.gov/genetics/condition/hyperlysinemia descriptionHyperlysinemia is an inherited condition that is characterized by elevated blood levels of lysine, which is one of the building blocks (amino acids) of proteins. Amino acids are not stored in the body and must be broken down when they are no longer needed. When the body's ability to break down lysine is impaired, lysine can build up and cause hyperlysinemia. Hyperlysinemia is classified as either type I or type II, depending on which steps of lysine breakdown are interrupted. The signs and symptoms of hyperlysinemia can vary widely, even among members of the same family. The features that have been reported in people with hyperlysinemia have included short stature, speech and language delays, intellectual disabilities, behavioral abnormalities, abnormal muscle stiffness (spasticity), and seizures. However, some researchers have suggested that as many as half of all people with hyperlysinemia are asymptomatic, which means that they do not have any signs or symptoms of the disorder. These people may not even be aware that they have the condition.Because the signs and symptoms of hyperlysinemia can vary and because hyperlysinemia is very rare, it is difficult for researchers to determine whether these features are caused by the condition itself or by other factors. People with a condition called 2,4-dienoyl-CoA reductase (DECR) deficiency may also have hyperlysinemia. Additional features of DECR deficiency may include an inability to grow and gain weight as expected (failure to thrive), developmental delays, abnormal brain function (encephalopathy), and eye abnormalities such as degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). ar Autosomal recessive AASS https://medlineplus.gov/genetics/gene/aass Alpha-aminoadipic semialdehyde synthase deficiency Familial hyperlysinemia Lysine alpha-ketoglutarate reductase deficiency Saccharopine dehydrogenase deficiency Saccharopinuria GTR C0268553 GTR C0268556 ICD-10-CM E72.3 MeSH D020167 OMIM 238700 OMIM 268700 SNOMED CT 111397004 SNOMED CT 340519003 SNOMED CT 341536001 SNOMED CT 342553006 SNOMED CT 58558003 SNOMED CT 66002008 2025-06 2025-06-26 Hypermanganesemia with dystonia https://medlineplus.gov/genetics/condition/hypermanganesemia-with-dystonia descriptionHypermanganesemia with dystonia is an inherited disorder in which excessive amounts of the element manganese accumulate in the body (hypermanganesemia). One place manganese builds up in particular is in a region of the brain responsible for the coordination of movement, causing neurological problems that make controlling movement difficult. Consequently, the condition is characterized by involuntary, sustained muscle contractions (dystonia) and other uncontrolled movements. Two types of hypermanganesemia with dystonia, called hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC) and hypermanganesemia with dystonia 2, have been identified. They are distinguished by their genetic causes and certain specific features.In HMDPC (also known as hypermanganesemia with dystonia 1), manganese accumulates in the blood, brain, and liver. Signs and symptoms of the condition can begin in childhood (early-onset), typically between ages 2 and 15, or in adulthood (adult-onset). Most children with the early-onset form of HMDPC experience dystonia in the arms and legs, which often leads to a characteristic high-stepping walk described as a "cock-walk gait." Other neurological symptoms in affected children include involuntary trembling (tremor), unusually slow movement (bradykinesia), and slurred speech (dysarthria). The adult-onset form of HMDPC is characterized by a pattern of movement abnormalities known as parkinsonism, which includes bradykinesia, tremor, muscle rigidity, and an inability to hold the body upright and balanced (postural instability).Individuals with HMDPC have an increased number of red blood cells (polycythemia) and low levels of iron stored in the body. Additional features of HMDPC can include an enlarged liver (hepatomegaly) due to manganese accumulation in the organ, scarring (fibrosis) in the liver, and irreversible liver disease (cirrhosis).In hypermanganesemia with dystonia 2, manganese accumulates in the blood and brain. Signs and symptoms of this type of the disorder usually begin between ages 6 months and 3 years. Development of motor skills, such as sitting and walking, may be delayed, or if already learned, they may be lost. Dystonia can affect any part of the body and worsens over time. By late childhood, the sustained muscle contractions often result in joints that are permanently bent (contractures) and an inability to walk unassisted. Some affected individuals have an abnormal curvature of the spine (scoliosis). People with hypermanganesemia with dystonia 2 can have other neurological problems similar to those in HMDPC, such as tremor, bradykinesia, parkinsonism, and dysarthria. Unlike in HMDPC, individuals with hypermanganesemia with dystonia 2 do not develop polycythemia or liver problems. ar Autosomal recessive SLC30A10 https://medlineplus.gov/genetics/gene/slc30a10 SLC39A14 https://medlineplus.gov/genetics/gene/slc39a14 Familial manganese-induced neurotoxicity HMNDYT GTR C4310765 MeSH D008664 OMIM 613280 OMIM 617013 SNOMED CT 702377007 2017-09 2020-08-18 Hypermethioninemia https://medlineplus.gov/genetics/condition/hypermethioninemia descriptionHypermethioninemia is an excess of a particular protein building block (amino acid), called methionine, in the blood. This condition can occur when methionine is not broken down (metabolized) properly in the body.People with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit intellectual disability and other neurological problems; delays in motor skills such as standing or walking; sluggishness; muscle weakness; liver problems; unusual facial features; and their breath, sweat, or urine may have a smell resembling boiled cabbage.Hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia, and galactosemia, which also involve the faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula. The condition is called primary hypermethioninemia when it is not associated with other metabolic disorders or excess methionine in the diet. ad Autosomal dominant ar Autosomal recessive MAT1A https://medlineplus.gov/genetics/gene/mat1a AHCY https://medlineplus.gov/genetics/gene/ahcy GNMT https://medlineplus.gov/genetics/gene/gnmt Deficiency of methionine adenosyltransferase Glycine N-methyltransferase deficiency GNMT deficiency Hepatic methionine adenosyltransferase deficiency MAT deficiency MET Methionine adenosyltransferase deficiency Methioninemia S-adenosylhomocysteine hydrolase deficiency GTR C0268621 GTR C1847720 GTR C3151058 MeSH D000592 OMIM 250850 OMIM 606664 OMIM 613752 SNOMED CT 124283007 SNOMED CT 43123004 2007-04 2021-08-06 Hyperparathyroidism-jaw tumor syndrome https://medlineplus.gov/genetics/condition/hyperparathyroidism-jaw-tumor-syndrome descriptionHyperparathyroidism-jaw tumor syndrome is a condition characterized by overactivity of the parathyroid glands (hyperparathyroidism). The four parathyroid glands are located in the neck and secrete a hormone that regulates the body's use of calcium. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of the bones (osteoporosis), nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue. About 95 percent of people with hyperparathyroidism-jaw tumor syndrome will develop hyperparathyroidism during their lifetime.In people with hyperparathyroidism-jaw tumor syndrome, hyperparathyroidism is caused by tumors that form in the parathyroid glands. Typically, only one of the four parathyroid glands is affected, but in some people, tumors are found in more than one gland. The tumors are usually a noncancerous (benign) type of tumor called an adenoma. Approximately 15 percent of people with hyperparathyroidism-jaw tumor syndrome develop a cancerous tumor called parathyroid carcinoma. People with hyperparathyroidism-jaw tumor syndrome may also have a type of benign tumor called a fibroma in the jaw. Even though jaw tumors are specified in the name of this condition, it is estimated that only 11 to 40 percent of affected individuals have this symptom.Other tumors, both benign and cancerous, are often seen in people with hyperparathyroidism-jaw tumor syndrome. For example, tumors of the uterus occur in up to 50 percent of people with this condition. Uterine tumors are typically benign, but they can cause heavy menstrual bleeding or other symptoms. The kidneys are affected in about 20 percent of people with hyperparathyroidism-jaw tumor syndrome. Benign kidney cysts are the most common kidney feature, but a rare cancerous tumor called Wilms tumor and other types of kidney tumor have also been found.Regular medical screening may assist in the early detection of the features of hyperparathyroidism-jaw tumor syndrome. ad Autosomal dominant CDC73 https://medlineplus.gov/genetics/gene/cdc73 CDC73-related disorders Familial cystic parathyroid adenomatosis Familial primary hyperparathyroidism with multiple ossifying jaw fibromas Hereditary hyperparathyroidism-jaw tumor syndrome HPT-JT Hyperparathyroidism 2 GTR C1704981 MeSH D049950 OMIM 145001 SNOMED CT 702378002 2024-10 2024-10-03 Hyperphosphatemic familial tumoral calcinosis https://medlineplus.gov/genetics/condition/hyperphosphatemic-familial-tumoral-calcinosis descriptionHyperphosphatemic familial tumoral calcinosis (HFTC) is a condition characterized by an increase in the levels of phosphate in the blood (hyperphosphatemia) and abnormal deposits of phosphate and calcium (calcinosis) in the body's tissues. Calcinosis typically develops in early childhood to early adulthood, although in some people the deposits first appear in infancy or in late adulthood. Calcinosis usually occurs in and just under skin tissue around the joints, most often the hips, shoulders, and elbows. Calcinosis may also develop in the soft tissue of the feet, legs, and hands. Rarely, calcinosis occurs in blood vessels or in the brain and can cause serious health problems. The deposits develop over time and vary in size. Larger deposits form masses that are noticeable under the skin and can interfere with the function of joints and impair movement. These large deposits may appear tumor-like (tumoral), but they are not tumors or cancerous. The number and frequency of deposits varies among affected individuals; some develop few deposits during their lifetime, while others may develop many in a short period of time.Other features of HFTC include eye abnormalities such as calcium buildup in the clear front covering of the eye (corneal calcification) or angioid streaks that occur when tiny breaks form in the layer of tissue at the back of the eye called Bruch's membrane. Inflammation of the long bones (diaphysis) or excessive bone growth (hyperostosis) may occur. Some affected individuals have dental abnormalities. In males, small crystals of cholesterol can accumulate (microlithiasis) in the testicles, which usually causes no health problems.A similar condition called hyperphosphatemia-hyperostosis syndrome (HHS) results in increased levels of phosphate in the blood, excessive bone growth, and bone lesions. This condition used to be considered a separate disorder, but it is now thought to be a mild variant of HFTC. ar Autosomal recessive FGF23 https://medlineplus.gov/genetics/gene/fgf23 GALNT3 https://medlineplus.gov/genetics/gene/galnt3 KL https://medlineplus.gov/genetics/gene/kl HFTC Hyperphosphatemia hyperostosis Hyperphosphatemia hyperostosis syndrome Hyperphosphatemia tumoral calcinosis Primary hyperphosphatemic tumoral calcinosis GTR C4692564 GTR C4693863 GTR C4693864 MeSH D054559 OMIM 211900 OMIM 617993 OMIM 617994 SNOMED CT 20165001 SNOMED CT 61778004 SNOMED CT 860796007 2012-08 2020-08-18 Hyperprolinemia https://medlineplus.gov/genetics/condition/hyperprolinemia descriptionHyperprolinemia is an excess of a particular protein building block (amino acid), called proline, in the blood. This condition generally occurs when proline is not broken down properly by the body. There are two forms of hyperprolinemia, called type I and type II.People with hyperprolinemia type I often do not show any symptoms, although they have proline levels in their blood between 3 and 10 times the normal level. Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems.Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This form of the disorder is more likely than type I to involve seizures or intellectual disability that vary in severity.Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of a chemical called lactic acid in the blood (lactic acidosis) may have hyperprolinemia as well, because lactic acid stops (inhibits) the breakdown of proline. ar Autosomal recessive ALDH4A1 https://medlineplus.gov/genetics/gene/aldh4a1 PRODH https://medlineplus.gov/genetics/gene/prodh Proline oxidase deficiency Prolinemia Pyrroline carboxylate dehydrogenase deficiency Pyrroline-5-carboxylate dehydrogenase deficiency GTR C0268529 GTR C2931835 MeSH D000592 OMIM 239500 OMIM 239510 SNOMED CT 59655002 2007-06 2021-08-27 Hypertension https://medlineplus.gov/genetics/condition/hypertension descriptionHypertension is abnormally high blood pressure in the arteries, which are the blood vessels that carry blood from the heart to the rest of the body. As the heart beats, it forces blood through the arteries to deliver nutrients and oxygen to the rest of the body. The strength of the blood pushing against the artery walls is blood pressure, which is measured in units called millimeters of mercury (mmHg). The top number in a blood pressure reading is the pressure when the heart pumps (systolic blood pressure), and the bottom number is the pressure between heart beats (diastolic blood pressure). In adults, a normal blood pressure measurement is about 120/80 mmHg. Blood pressure is considered high when the measurement is 130/80 mmHg or greater.Hypertension usually has no symptoms, and many affected individuals do not know they have the condition. However, hypertension is a major risk factor for heart disease, stroke, kidney failure, and eye problems. When blood pressure is elevated, the heart and arteries have to work harder than normal to pump blood through the body. The extra work thickens the muscles of the heart and arteries and hardens or damages artery walls. As a result, the flow of blood and oxygen to the heart and other organs is reduced. Damage to the heart caused by the extra work and a lack of oxygen causes heart disease. In addition, damage to the arteries increases the risk of blood clots that block the flow of blood to the heart, causing a heart attack, or to the brain, causing a type of stroke known as an ischemic stroke. Another type of stroke, called a hemorrhagic stroke, can occur when a weakened blood vessel in the brain bursts. Damage to blood vessels in the kidneys impairs their ability to filter waste and remove fluid, leading to kidney failure. Problems with blood flow in the arteries of the eyes can lead to vision loss.In rare cases, dangerously high blood pressure can cause severe headaches, confusion, shortness of breath, chest pain, or nosebleeds.In about 95 percent of cases, the cause of hypertension is unknown. These cases are classified as essential hypertension. When hypertension results from an underlying condition, such as blood vessel defects that reduce blood flow; kidney disorders, which alter the amount of fluids and salts in the body; or problems with hormone-producing glands called the adrenal glands or the thyroid gland, it is classified as secondary hypertension. Hypertension is a key feature of some rare genetic disorders, including familial hyperaldosteronism, pseudohypoaldosteronism type 2, Liddle syndrome, and tumors known as paragangliomas. u Pattern unknown AGT https://medlineplus.gov/genetics/gene/agt AGTR1 https://medlineplus.gov/genetics/gene/agtr1 ATP2B1 https://www.ncbi.nlm.nih.gov/gene/490 EDNRA https://www.ncbi.nlm.nih.gov/gene/1909 NOS2 https://www.ncbi.nlm.nih.gov/gene/4843 NOS3 https://www.ncbi.nlm.nih.gov/gene/4846 PTGIS https://www.ncbi.nlm.nih.gov/gene/5740 SELE https://www.ncbi.nlm.nih.gov/gene/6401 Essential hypertension High blood pressure Primary hypertension GTR C0085580 ICD-10-CM I10 MeSH D000075222 OMIM 145500 OMIM 603918 OMIM 604329 OMIM 607329 OMIM 608742 OMIM 610261 OMIM 610262 OMIM 610948 OMIM 611014 SNOMED CT 38341003 SNOMED CT 59621000 2019-01 2023-11-08 Hypochondroplasia https://medlineplus.gov/genetics/condition/hypochondroplasia descriptionHypochondroplasia is a form of short-limbed dwarfism. This condition affects the conversion of cartilage into bone (a process called ossification), particularly in the long bones of the arms and legs. Hypochondroplasia is similar to another skeletal disorder called achondroplasia, but the features tend to be milder.All people with hypochondroplasia have short stature. The adult height for men with this condition ranges from 138 centimeters to 165 centimeters (4 feet, 6 inches to 5 feet, 5 inches). The height range for adult women is 128 centimeters to 151 centimeters (4 feet, 2 inches to 4 feet, 11 inches).People with hypochondroplasia have short arms and legs and broad, short hands and feet. Other characteristic features include a a large head (macrocephaly), limited range of motion at the elbows, a sway of the lower back (lordosis), and bowed legs. These signs are generally less pronounced than those seen in people with achondroplasia and may not be noticeable until early or middle childhood. Affected individuals have a small increased risk of a seizure disorder known as temporal lobe epilepsy. Some studies have reported that a small percentage of people with hypochondroplasia have mild to moderate intellectual disability or learning problems, but other studies have produced conflicting results.  ad Autosomal dominant FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 HCH Hypochondrodysplasia GTR C0410529 ICD-10-CM Q77.4 MeSH D004392 OMIM 146000 SNOMED CT 205468002 2023-06 2023-05-29 Hypochromic microcytic anemia with iron overload https://medlineplus.gov/genetics/condition/hypochromic-microcytic-anemia-with-iron-overload descriptionHypochromic microcytic anemia with iron overload is a condition that impairs the normal transport of iron in cells. Iron is an essential component of hemoglobin, which is the substance that red blood cells use to carry oxygen to cells and tissues throughout the body. In this condition, red blood cells cannot access iron in the blood, so there is a decrease of red blood cell production (anemia) that is apparent at birth. The red blood cells that are produced are abnormally small (microcytic) and pale (hypochromic). Hypochromic microcytic anemia with iron overload can lead to pale skin (pallor), tiredness (fatigue), and slow growth.In hypochromic microcytic anemia with iron overload, the iron that is not used by red blood cells accumulates in the liver, which can impair its function over time. The liver problems typically become apparent in adolescence or early adulthood. ar Autosomal recessive SLC11A2 https://medlineplus.gov/genetics/gene/slc11a2 Microcytic anemia and hepatic iron overload Microcytic anemia with liver iron overload GTR C3806153 MeSH D000747 OMIM 206100 SNOMED CT 711161006 2014-11 2020-08-18 Hypohidrotic ectodermal dysplasia https://medlineplus.gov/genetics/condition/hypohidrotic-ectodermal-dysplasia descriptionHypohidrotic ectodermal dysplasia is one of more than 100 types of ectodermal dysplasia. Starting before birth, these disorders result in the abnormal development of ectodermal tissues, particularly the skin, hair, nails, teeth, and sweat glands.Most people with hypohidrotic ectodermal dysplasia have a reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly. Sweating is a major way that the body controls its temperature; as sweat evaporates from the skin, it cools the body. Reduced sweating can lead to a dangerously high body temperature (hyperthermia), particularly in hot weather. In some cases, hyperthermia can cause life-threatening health problems.Affected individuals tend to have sparse scalp and body hair (hypotrichosis). The hair is often light-colored, brittle, and slow-growing. Hypohidrotic ectodermal dysplasia is also characterized by several missing teeth (hypodontia) or teeth that are malformed. The teeth that are present erupt from the gums later than usual and are frequently small and pointed.Some people with hypohidrotic ectodermal dysplasia have distinctive facial features, including a prominent forehead, thick lips, and a flattened bridge of the nose. Additional features of this condition can include thin, wrinkled, and dark-colored skin around the eyes; chronic skin problems such as eczema; and a bad-smelling discharge from the nostrils (ozena).Intellectual ability and growth are typically normal in people with hypohidrotic ectodermal dysplasia. ad Autosomal dominant x X-linked ar Autosomal recessive EDA https://medlineplus.gov/genetics/gene/eda EDARADD https://medlineplus.gov/genetics/gene/edaradd EDAR https://medlineplus.gov/genetics/gene/edar WNT10A https://medlineplus.gov/genetics/gene/wnt10a Anhidrotic ectodermal dysplasia Christ-Siemens-Touraine syndrome CST syndrome HED GTR C0162359 GTR C3887494 GTR C3888065 ICD-10-CM Q82.4 MeSH D053358 MeSH D053359 MeSH D053360 OMIM 129490 OMIM 224900 OMIM 305100 OMIM 614940 OMIM 614941 SNOMED CT 239007005 SNOMED CT 27025001 SNOMED CT 7731005 2018-11 2020-08-18 Hypokalemic periodic paralysis https://medlineplus.gov/genetics/condition/hypokalemic-periodic-paralysis descriptionHypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, some develop persistent muscle weakness later in life.People with hypokalemic periodic paralysis typically have reduced levels of potassium in their blood (hypokalemia) during episodes of muscle weakness. Researchers are investigating how low potassium levels may be related to the muscle abnormalities in this condition. ad Autosomal dominant SCN4A https://medlineplus.gov/genetics/gene/scn4a CACNA1S https://medlineplus.gov/genetics/gene/cacna1s Familial hypokalemic periodic paralysis HOKPP HypoKPP HypoPP Primary hypokalemic periodic paralysis Westphall disease GTR C0238358 GTR C2750061 GTR C3714580 ICD-10-CM G72.3 MeSH D020514 OMIM 170400 OMIM 613345 SNOMED CT 82732003 2007-04 2021-04-07 Hypomagnesemia with secondary hypocalcemia https://medlineplus.gov/genetics/condition/hypomagnesemia-with-secondary-hypocalcemia descriptionHypomagnesemia with secondary hypocalcemia is an inherited condition caused by the body's inability to absorb and retain magnesium that is taken in through the diet. As a result, magnesium levels in the blood are severely low (hypomagnesemia).Hypomagnesemia impairs the function of the parathyroid glands, which are small hormone-producing glands located in the neck. Normally, the parathyroid glands release a hormone that increases blood calcium levels when they are low. Magnesium is required for the production and release of parathyroid hormone, so when magnesium is too low, insufficient parathyroid hormone is produced and blood calcium levels are also reduced (hypocalcemia). The hypocalcemia is described as "secondary" because it occurs as a consequence of hypomagnesemia.Shortages of magnesium and calcium can cause neurological problems that begin in infancy, including painful muscle spasms (tetany) and seizures. If left untreated, hypomagnesemia with secondary hypocalcemia can lead to developmental delay, intellectual disability, a failure to gain weight and grow at the expected rate (failure to thrive), and heart failure. ar Autosomal recessive TRPM6 https://medlineplus.gov/genetics/gene/trpm6 Familial primary hypomagnesemia with hypocalcuria HOMG HSH Hypomagnesemic tetany Intestinal hypomagnesemia 1 Intestinal hypomagnesemia with secondary hypocalcemia GTR C1865974 MeSH D006996 OMIM 602014 SNOMED CT 711151004 2015-01 2020-08-18 Hypomyelination and congenital cataract https://medlineplus.gov/genetics/condition/hypomyelination-and-congenital-cataract descriptionHypomyelination and congenital cataract is an inherited condition that affects the nervous system and the eyes. This disease is one of a group of genetic disorders called leukoencephalopathies. Leukoencephalopathies involve abnormalities of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. Hypomyelination and congenital cataract is caused by a reduced ability to form myelin (hypomyelination). Additionally, people with this disorder are typically born with a clouding of the lens (cataract) in both eyes.People with this condition usually have normal development throughout the first year of life. Development slows around the age of 1. Most affected children learn to walk between the ages of 1 and 2, although they usually need some type of support. Over time they experience muscle weakness and wasting (atrophy) in their legs, and many affected people eventually require wheelchair assistance. Weakness in the muscles of the trunk and a progressive abnormal curvature of the spine (scoliosis) further impair walking in some individuals. Most people with hypomyelination and congenital cataract have reduced sensation in their arms and legs (peripheral neuropathy). In addition, affected individuals typically have speech difficulties (dysarthria) and mild to moderate intellectual disability. ar Autosomal recessive HYCC1 https://medlineplus.gov/genetics/gene/hycc1 HCC GTR C1864663 MeSH D020279 OMIM 610532 SNOMED CT 702379005 2009-07 2024-07-11 Hypomyelination with brainstem and spinal cord involvement and leg spasticity https://medlineplus.gov/genetics/condition/hypomyelination-with-brainstem-and-spinal-cord-involvement-and-leg-spasticity descriptionHypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) is a condition that affects the brain and spinal cord (central nervous system). In particular, the condition affects nerves in specific regions (called tracts) within the spinal cord and the brainstem, which is the part of the brain that connects to the spinal cord. HBSL is a form of leukodystrophy, which is a group of conditions that involve abnormalities of the nervous system's white matter. The white matter consists of nerve fibers covered by a fatty substance, called myelin, that insulates the fibers and promotes the rapid transmission of nerve impulses. In HBSL, the nervous system has a reduced ability to form myelin (hypomyelination).In HBSL, early development of motor skills (such as rolling over and sitting) may be normal, but movement problems typically begin within the infant's first year. However, in some individuals, these problems do not appear until adolescence. The characteristic feature of HBSL is muscle stiffness (spasticity) in the legs that worsens over time. Most people with HBSL are unable to walk independently. Other neurological problems in affected individuals can include abnormal side-to-side movements of the eyes (nystagmus), weak muscle tone (hypotonia) in the torso, and mild intellectual disability.Distinct changes in the brains of people with HBSL can be seen using magnetic resonance imaging (MRI). These characteristic abnormalities typically involve specific regions (called tracts) within the brainstem and spinal cord, especially the pyramidal tract, lateral corticospinal tract, and the dorsal column. ar Autosomal recessive DARS1 https://medlineplus.gov/genetics/gene/dars1 Aspartyl-tRNA synthetase deficiency HBSL Hypomyelination with brain stem and spinal cord involvement and leg spasticity GTR C4755254 MeSH D056784 OMIM 615281 2019-02 2023-08-18 Hypophosphatasia https://medlineplus.gov/genetics/condition/hypophosphatasia descriptionHypophosphatasia is an inherited disorder that affects the development of bones and teeth. This condition disrupts a process called mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.The signs and symptoms of hypophosphatasia vary widely and can appear anywhere from before birth to adulthood. The most severe forms of the disorder tend to occur before birth and in early infancy. Hypophosphatasia weakens and softens the bones, causing skeletal abnormalities similar to another childhood bone disorder called rickets. Affected infants are born with short limbs, an abnormally shaped chest, and soft skull bones. Additional complications in infancy include poor feeding and a failure to gain weight, respiratory problems, and high levels of calcium in the blood (hypercalcemia), which can lead to recurrent vomiting and kidney problems. These complications are life-threatening in some cases.The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. Early loss of primary (baby) teeth is one of the first signs of the condition in children. Affected children may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. Adult forms of hypophosphatasia are characterized by a softening of the bones known as osteomalacia. In adults, recurrent fractures in the foot and thigh bones can lead to chronic pain. Affected adults may lose their secondary (adult) teeth prematurely and are at increased risk for joint pain and inflammation.The mildest form of this condition, called odontohypophosphatasia, only affects the teeth. People with this disorder typically experience abnormal tooth development and premature tooth loss, but do not have the skeletal abnormalities seen in other forms of hypophosphatasia. ar Autosomal recessive ad Autosomal dominant ALPL https://medlineplus.gov/genetics/gene/alpl Deficiency of alkaline phosphatase Phosphoethanolaminuria GTR C0020630 GTR C0220743 GTR C0268412 GTR C0268413 MeSH D007014 OMIM 146300 OMIM 241500 OMIM 241510 SNOMED CT 190859005 SNOMED CT 20756002 SNOMED CT 30174008 SNOMED CT 360792001 SNOMED CT 55236002 2007-09 2024-09-19 Hystrix-like ichthyosis with deafness https://medlineplus.gov/genetics/condition/hystrix-like-ichthyosis-with-deafness descriptionHystrix-like ichthyosis with deafness (HID) is a disorder characterized by dry, scaly skin (ichthyosis) and hearing loss that is usually profound. Hystrix-like means resembling a porcupine; in this type of ichthyosis, the scales may be thick and spiky, giving the appearance of porcupine quills.Newborns with HID typically develop reddened skin. The skin abnormalities worsen over time, and the ichthyosis eventually covers most of the body, although the palms of the hands and soles of the feet are usually only mildly affected. Breaks in the skin may occur and in severe cases can lead to life-threatening infections. Affected individuals have an increased risk of developing a type of skin cancer called squamous cell carcinoma, which can also affect mucous membranes such as the inner lining of the mouth. People with HID may also have patchy hair loss caused by scarring on particular areas of skin. ad Autosomal dominant GJB2 https://medlineplus.gov/genetics/gene/gjb2 HID syndrome Ichthyosis, hystrix-like, with deafness GTR C1865234 MeSH D007057 OMIM 602540 SNOMED CT 254173004 2012-11 2020-08-18 IMAGe syndrome https://medlineplus.gov/genetics/condition/image-syndrome descriptionThe combination of intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies is commonly known by the acronym IMAGe. This rare syndrome has signs and symptoms that affect many parts of the body.Most affected individuals grow slowly before birth (intrauterine growth restriction) and are small in infancy. They have skeletal abnormalities that often become apparent in early childhood, although these abnormalities are usually mild and can be difficult to recognize on x-rays. The most common bone changes are metaphyseal dysplasia and epiphyseal dysplasia; these are malformations of the ends of long bones in the arms and legs. Some affected individuals also have an abnormal side-to-side curvature of the spine (scoliosis) or thinning of the bones (osteoporosis).Adrenal hypoplasia congenita is the most severe feature of IMAGe syndrome. The adrenal glands are a pair of small glands on top of each kidney. They produce a variety of hormones that regulate many essential functions in the body. Underdevelopment (hypoplasia) of these glands prevents them from producing enough hormones, a condition known as adrenal insufficiency. The signs of adrenal insufficiency begin shortly after birth and include vomiting, difficulty with feeding, dehydration, extremely low blood glucose (hypoglycemia), and shock. If untreated, these complications can be life-threatening.The genital abnormalities associated with IMAGe syndrome occur only in affected males. They include an unusually small penis (micropenis), undescended testes (cryptorchidism), and the opening of the urethra on the underside of the penis (hypospadias).Several additional signs and symptoms have been reported in people with IMAGe syndrome. Some affected individuals have distinctive facial features, such as a prominent forehead, low-set ears, and a short nose with a flat nasal bridge. Less commonly, people with this condition have premature fusion of certain bones of the skull (craniosynostosis), a split in the soft flap of tissue that hangs from the back of the mouth (cleft or bifid uvula), a high-arched roof of the mouth (palate), and a small chin (micrognathia). Other possible features of IMAGe syndrome include high levels of calcium in the blood (hypercalcemia) or urine (hypercalcuria) and a shortage of growth hormone in childhood that results in short stature. ad Autosomal dominant CDKN1C https://medlineplus.gov/genetics/gene/cdkn1c IMAGe anomaly IMAGe association IMAGe syndrome Intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies GTR C1846009 MeSH D000015 OMIM 614732 SNOMED CT 702384004 2013-04 2025-03-05 IRAK-4 deficiency https://medlineplus.gov/genetics/condition/irak-4-deficiency descriptionIRAK-4 deficiency is an inherited disorder of the immune system (primary immunodeficiency). This immunodeficiency leads to recurrent infections by a subset of bacteria known as pyogenic bacteria but not by other infectious agents. (Infection with pyogenic bacteria causes the production of pus.) The most common infections in IRAK-4 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent with age.Most people with IRAK-4 deficiency have invasive bacterial infections, which can involve the blood (septicemia), the membrane covering the brain and spinal cord (meningitis), or the joints (leading to inflammation and arthritis). Invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, affected individuals can have localized infections of the upper respiratory tract, skin, or eyes. Although fever is a common reaction to bacterial infections, many people with IRAK-4 deficiency do not at first develop a high fever in response to these infections, even if the infection is severe. ar Autosomal recessive IRAK4 https://medlineplus.gov/genetics/gene/irak4 Interleukin-1 receptor-associated kinase 4 deficiency IRAK4 deficiency GTR C1843256 MeSH D007153 OMIM 607676 SNOMED CT 699869003 2011-11 2020-08-18 Ichthyosis with confetti https://medlineplus.gov/genetics/condition/ichthyosis-with-confetti descriptionIchthyosis with confetti is a disorder of the skin. Individuals with this condition are born with red, scaly skin all over the body, which can be itchy in some people. In childhood or adolescence, hundreds to thousands of small patches of normal skin appear, usually on the torso. The numerous pale spots surrounded by red skin look like confetti, giving the condition its name. The patches of normal skin increase in number and size over time.In addition to red, scaly skin, people with ichthyosis with confetti typically have abnormally thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Many affected individuals have excess hair (hirsutism) on some parts of the body, particularly on the arms and legs. Because of their skin abnormalities, people with ichthyosis with confetti are at increased risk of developing skin infections. ad Autosomal dominant KRT10 https://medlineplus.gov/genetics/gene/krt10 Congenital reticular ichthyosiform erythroderma CRIE Ichthyosis variegata IWC GTR C1836681 MeSH D016113 OMIM 609165 SNOMED CT 703504006 2014-02 2020-08-18 Idiopathic infantile hypercalcemia https://medlineplus.gov/genetics/condition/idiopathic-infantile-hypercalcemia descriptionIdiopathic infantile hypercalcemia is a condition characterized by high levels of calcium in the blood (hypercalcemia). Two types of idiopathic infantile hypercalcemia have been identified and are distinguished by their genetic causes: infantile hypercalcemia 1 and infantile hypercalcemia 2. In infants with either type, hypercalcemia can cause vomiting, increased urine production (polyuria), dehydration, constipation, poor feeding, weight loss, and an inability to grow and gain weight as expected (failure to thrive). As they age, affected babies usually have delayed development of mental and movement abilities (psychomotor delay). Individuals with infantile hypercalcemia 1 or 2 may also have high levels of calcium in their urine (hypercalciuria) and deposits of calcium in their kidneys (nephrocalcinosis).With treatment, the outward symptoms of hypercalcemia, such as vomiting, dehydration, failure to thrive, and psychomotor delay, usually improve in childhood. However, affected children still tend to have higher-than-normal amounts of calcium in their blood and urine and calcium deposits in their kidneys. By adulthood, long-term hypercalcemia and hypercalciuria can lead to the formation of kidney stones (nephrolithiasis) and may damage the kidneys and impair their function. Affected adults may also develop calcium deposits in the joints or in the clear outer covering of the eye (the cornea), and some have low bone mineral density (osteoporosis).In rare cases, affected individuals do not have symptoms of hypercalcemia in infancy, and the condition begins in later childhood or adulthood. These individuals usually develop hypercalciuria, nephrocalcinosis, and nephrolithiasis, although the features may not cause any obvious health problems.Although most signs and symptoms are similar between the two known types of idiopathic infantile hypercalcemia, individuals with infantile hypercalcemia 2 have low levels of a mineral called phosphate in the blood (hypophosphatemia), while phosphate levels are typically normal in people with infantile hypercalcemia 1. ar Autosomal recessive CYP24A1 https://medlineplus.gov/genetics/gene/cyp24a1 SLC34A1 https://medlineplus.gov/genetics/gene/slc34a1 Autosomal recessive infantile hypercalcemia IIH Vitamin D hypersensitivity GTR C4329374 MeSH D006934 OMIM 143880 OMIM 616963 SNOMED CT 34225008 2017-12 2023-03-21 Idiopathic inflammatory myopathy https://medlineplus.gov/genetics/condition/idiopathic-inflammatory-myopathy descriptionIdiopathic inflammatory myopathy is a group of disorders characterized by inflammation of the muscles used for movement (skeletal muscles). Idiopathic inflammatory myopathy usually appears in adults between ages 40 and 60 or in children between ages 5 and 15, though it can occur at any age.The primary symptom of idiopathic inflammatory myopathy is muscle weakness, which develops gradually over a period of weeks to months or even years. Other symptoms include joint pain and general tiredness (fatigue).There are several forms of idiopathic inflammatory myopathy, including polymyositis, dermatomyositis, and sporadic inclusion body myositis.Polymyositis and dermatomyositis involve weakness of the muscles closest to the center of the body (proximal muscles), such as the muscles of the hips and thighs, upper arms, and neck. People with these forms of idiopathic inflammatory myopathy may find it difficult to climb stairs, get up from a seated position, or lift items above their head. In some cases, muscle weakness may make swallowing or breathing difficult.Polymyositis and dermatomyositis have similar symptoms, but dermatomyositis is distinguished by a reddish or purplish rash on the eyelids, elbows, knees, or knuckles. Sometimes, abnormal calcium deposits form hard, painful bumps under the skin (calcinosis).In sporadic inclusion body myositis, the muscles most affected are those of the wrists and fingers and the front of the thigh. Affected individuals may frequently stumble while walking and find it difficult to grasp items. As in dermatomyositis and polymyositis, swallowing can be difficult. u Pattern unknown IL1A https://medlineplus.gov/genetics/gene/il1a PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 HLA-DQA1 https://medlineplus.gov/genetics/gene/hla-dqa1 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 TNF https://www.ncbi.nlm.nih.gov/gene/7124 Idiopathic inflammatory myopathies Idiopathic inflammatory myositis Inflammatory myopathy, idiopathic GTR C0027121 GTR C0238190 MeSH D009220 OMIM 147421 OMIM 160750 SNOMED CT 702380008 2011-02 2025-12-22 Idiopathic pulmonary fibrosis https://medlineplus.gov/genetics/condition/idiopathic-pulmonary-fibrosis descriptionIdiopathic pulmonary fibrosis is a chronic, progressive lung disease. This condition causes scar tissue (fibrosis) to build up in the lungs, which makes the lungs unable to transport oxygen into the bloodstream effectively. The disease usually affects people between the ages of 50 and 70. Idiopathic pulmonary fibrosis belongs to a group of conditions called interstitial lung diseases (also known as ILD), which describes lung diseases that involve inflammation or scarring in the lung.The most common signs and symptoms of idiopathic pulmonary fibrosis are shortness of breath and a persistent dry, hacking cough. Many affected individuals also experience a loss of appetite and gradual weight loss. Some people with idiopathic pulmonary fibrosis develop widened and rounded tips of the fingers and toes (clubbing) resulting from a shortage of oxygen. These features are relatively nonspecific; not everyone with these health problems has idiopathic pulmonary fibrosis. Other respiratory diseases, some of which are less serious, can cause similar signs and symptoms.In people with idiopathic pulmonary fibrosis, scarring of the lungs increases over time until the lungs can no longer provide enough oxygen to the body's organs and tissues. Some people with idiopathic pulmonary fibrosis develop other serious lung conditions, including lung cancer, blood clots in the lungs (pulmonary emboli), pneumonia, or high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Most affected individuals survive 3 to 5 years after their diagnosis. However, the course of the disease is highly variable; some affected people become seriously ill within a few months, while others may live with the disease for a decade or longer.In most cases, idiopathic pulmonary fibrosis occurs in only one person in a family. These cases are described as sporadic. However, a small percentage of people with this disease have at least one other affected family member. When idiopathic pulmonary fibrosis occurs in multiple members of the same family, it is known as familial pulmonary fibrosis. ad Autosomal dominant IVD https://medlineplus.gov/genetics/gene/ivd TGFB1 https://medlineplus.gov/genetics/gene/tgfb1 MAPT https://medlineplus.gov/genetics/gene/mapt TERC https://medlineplus.gov/genetics/gene/terc TERT https://medlineplus.gov/genetics/gene/tert DKC1 https://medlineplus.gov/genetics/gene/dkc1 TINF2 https://medlineplus.gov/genetics/gene/tinf2 SFTPC https://medlineplus.gov/genetics/gene/sftpc ABCA3 https://medlineplus.gov/genetics/gene/abca3 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 DSP https://medlineplus.gov/genetics/gene/dsp MICA https://www.ncbi.nlm.nih.gov/gene/4276 MUC5B https://www.ncbi.nlm.nih.gov/gene/4587 PARN https://www.ncbi.nlm.nih.gov/gene/5073 TLR3 https://www.ncbi.nlm.nih.gov/gene/7098 FAM13A https://www.ncbi.nlm.nih.gov/gene/10144 AKAP13 https://www.ncbi.nlm.nih.gov/gene/11214 ATP11A https://www.ncbi.nlm.nih.gov/gene/23250 RTEL1 https://www.ncbi.nlm.nih.gov/gene/51750 TOLLIP https://www.ncbi.nlm.nih.gov/gene/54472 STN1 https://www.ncbi.nlm.nih.gov/gene/79991 DPP9 https://www.ncbi.nlm.nih.gov/gene/91039 ELMOD2 https://www.ncbi.nlm.nih.gov/gene/255520 SFTPA1 https://www.ncbi.nlm.nih.gov/gene/653509 SFTPA2 https://www.ncbi.nlm.nih.gov/gene/729238 Cryptogenic fibrosing alveolitis Idiopathic fibrosing alveolitis, chronic form IPF Usual interstitial pneumonia GTR C1800706 ICD-10-CM J84.10 ICD-10-CM J84.11 ICD-10-CM J84.111 ICD-10-CM J84.112 ICD-10-CM J84.113 ICD-10-CM J84.114 ICD-10-CM J84.115 ICD-10-CM J84.116 ICD-10-CM J84.117 MeSH D054990 OMIM 178500 SNOMED CT 426437004 SNOMED CT 700250006 2010-10 2020-08-18 Imerslund-Gräsbeck syndrome https://medlineplus.gov/genetics/condition/imerslund-grasbeck-syndrome descriptionImerslund-Gräsbeck syndrome is an inherited condition that is characterized by problems with the body's ability to take in (absorb) vitamin B12 (also called cobalamin). Most people with Imerslund-Gräsbeck syndrome have a blood disorder called megaloblastic anemia, which occurs when a person has a low number of red blood cells (anemia) and the remaining red blood cells are larger than normal (megaloblastic). Many people with Imerslund-Gräsbeck syndrome have a high level of protein in the urine (proteinuria), but this is less common in affected individuals from Finland. Although proteinuria can be an indication of kidney problems, people with Imerslund-Gräsbeck syndrome typically have normal kidney function.The signs and symptoms of Imerslund-Gräsbeck syndrome usually begin in early childhood. Megaloblastic anemia leads to many of these signs and symptoms, including an inability to grow and gain weight at the expected rate (failure to thrive), pale skin (pallor), and fatigue. Additional signs and symptoms can include mouth ulcers and gastrointestinal problems, such as vomiting and diarrhea.  Affected individuals may also have recurring respiratory infections.Imerslund-Gräsbeck syndrome can also cause neurological problems, such as a lack of energy (lethargy); weak muscle tone (hypotonia); developmental delays; problems with movement and balance (ataxia); or abnormal sensations, such as numbness or tingling in the hands and feet. Some affected individuals have more severe neurological signs and symptoms, such as seizures or a decline in intellectual abilities.Abnormalities of the organs or tissues that make up the urinary tract have been reported in some individuals with Imerslund-Gräsbeck syndrome, but the cause of these problems is not well understood.  ar Autosomal recessive AMN https://medlineplus.gov/genetics/gene/amn CUBN https://medlineplus.gov/genetics/gene/cubn Enterocyte cobalamin malabsorption Gräsbeck-imerslund disease Imerslund's syndrome Imerslund-Grasbeck anemia Imerslund-grasbeck disease Imerslund-najman-grasbeck syndrome Juvenile pernicious anemia with proteinuria due to selective intestinal malabsorption of vitamin B12 Selective cobalamin malabsorption with proteinuria GTR C4016819 GTR C4016948 GTR C4551825 MeSH D000749 OMIM 261100 OMIM 618882 SNOMED CT 26333003 2026-04 2026-04-09 Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome https://medlineplus.gov/genetics/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome descriptionImmune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome primarily affects males and is caused by problems with the immune system. The immune system normally protects the body from foreign invaders, such as bacteria and viruses, by recognizing and attacking these invaders and clearing them from the body. However, the immune system can malfunction and attack the body's own tissues and organs instead, which is known as autoimmunity. IPEX syndrome is characterized by the development of multiple autoimmune disorders in affected individuals. Although IPEX syndrome can affect many different areas of the body, autoimmune disorders involving the intestines, skin, and hormone-producing (endocrine) glands occur most often. IPEX syndrome can be life-threatening in early childhood.Almost all individuals with IPEX syndrome develop a disorder of the intestines called autoimmune enteropathy. Autoimmune enteropathy occurs when certain cells in the intestines are destroyed by a person's immune system. It causes severe diarrhea, which is usually the first symptom of IPEX syndrome. Autoimmune enteropathy typically begins in the first few months of life. It can cause failure to gain weight and grow at the expected rate (failure to thrive) and general wasting and weight loss (cachexia).People with IPEX syndrome frequently develop inflammation of the skin, called dermatitis. Eczema is the most common type of dermatitis that occurs in this syndrome, and it causes abnormal patches of red, irritated skin. Other skin disorders that cause similar symptoms are sometimes present in IPEX syndrome.The term polyendocrinopathy is used in IPEX syndrome because individuals can develop multiple disorders of the endocrine glands. Type 1 diabetes mellitus is an autoimmune condition involving the pancreas and is the most common endocrine disorder present in people with IPEX syndrome. It usually develops within the first few months of life and prevents the body from properly controlling the amount of sugar in the blood. Autoimmune thyroid disease may also develop in people with IPEX syndrome. The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones. This gland is commonly underactive (hypothyroidism) in individuals with this disorder, but may become overactive (hyperthyroidism).Individuals with IPEX syndrome typically develop other types of autoimmune disorders in addition to those that involve the intestines, skin, and endocrine glands. Autoimmune blood disorders are common; about half of affected individuals have low levels of red blood cells (anemia), platelets (thrombocytopenia), or certain white blood cells (neutropenia) because these cells are attacked by the immune system. In some individuals, IPEX syndrome involves the liver and kidneys. xr X-linked recessive FOXP3 https://medlineplus.gov/genetics/gene/foxp3 Autoimmunity-immunodeficiency syndrome, X-linked Diabetes mellitus, congenital insulin-dependent, with fatal secretory diarrhea Diarrhea, polyendocrinopathy, fatal infection syndrome, X-linked Enteropathy, autoimmune, with hemolytic anemia and polyendocrinopathy IDDM-secretory diarrhea syndrome Immunodeficiency, polyendocrinopathy, and enteropathy, X-linked Insulin-dependent diabetes mellitus secretory diarrhea syndrome IPEX syndrome Polyendocrinopathy, immune dysfunction, and diarrhea, X-linked X-linked autoimmunity-allergic dysregulation syndrome XLAAD GTR C0342288 MeSH D040181 OMIM 304790 SNOMED CT 237618001 2017-05 2023-02-21 Immune thrombocytopenia https://medlineplus.gov/genetics/condition/immune-thrombocytopenia descriptionImmune thrombocytopenia is a disorder characterized by a blood abnormality called thrombocytopenia, which is a shortage of blood cells called platelets that are needed for normal blood clotting.Affected individuals can develop red or purple spots on the skin caused by bleeding just under the skin's surface. Small spots of bleeding under the skin are called purpura and larger spots are called ecchymoses. People with immune thrombocytopenia can have significant bleeding episodes, such as nose bleeds (epistaxis) or bleeding in the moist lining (mucosae) of the mouth. In severe cases, individuals may have gastrointestinal bleeding or blood in the urine or stool, or heavy and prolonged menstrual bleeding (menorrhagia). In very rare instances, bleeding inside the skull (intracranial hemorrhage) can occur, which can be life-threatening. A greater reduction in platelet numbers is often associated with more frequent bleeding episodes and an increased risk of severe bleeding.While immune thrombocytopenia can be diagnosed at any age, there are two periods when the condition is most likely to develop: early childhood and late adulthood. In children, the reduction in platelets is often sudden, but platelet levels usually return to normal levels within weeks to months. Immune thrombocytopenia in children is often preceded by a minor infection, such as an upper respiratory infection, but the relationship between the infection and immune thrombocytopenia is not clear. In adults, the development of immune thrombocytopenia is usually gradual and the condition tends to persist throughout life. u Pattern unknown Autoimmune thrombocytopenia Autoimmune thrombocytopenic purpura Idiopathic thrombocytopenic purpura Immune thrombocytopenic purpura ITP Werlhof disease GTR C0398650 ICD-10-CM D69.3 MeSH D016553 OMIM 188030 SNOMED CT 2897005 2016-08 2020-08-18 Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia https://medlineplus.gov/genetics/condition/inclusion-body-myopathy-with-early-onset-paget-disease-and-frontotemporal-dementia descriptionInclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD) is a condition that can affect the muscles, bones, and brain.The first symptom of IBMPFD is often muscle weakness (myopathy), which typically appears in mid-adulthood. Weakness first occurs in muscles of the hips and shoulders, making it difficult to climb stairs and raise the arms above the shoulders. As the disorder progresses, weakness develops in other muscles in the arms and legs.  Muscle weakness can also affect respiratory and heart (cardiac) muscles, leading to life-threatening breathing difficulties and heart failure.About half of all adults with IBMPFD develop a disorder called Paget disease of bone. This disorder causes bones to grow larger and weaker than normal.Paget disease of bone most often affects bones of the hips, spine, and skull, and the long bones of the arms and legs. Bone pain, particularly in the hips and spine, is usually the major symptom of Paget disease. Other complications of Paget disease of bone depend on which bones are affected.Rarely, this condition can weaken bones so much that they break (fracture).In about one-third of people with IBMPFD, the disorder also affects the brain. IBMPFD is associated with a brain condition called frontotemporal dementia, which becomes noticeable in a person's forties or fifties. People with frontotemporal dementia initially may have trouble speaking, remembering words and names (dysnomia), and using numbers (dyscalculia). Over time, the condition damages parts of the brain that control reasoning, personality, social skills, speech, and language. Personality changes, loss of judgment, and inappropriate social behavior are also hallmarks of the disease. As the dementia worsens, affected people ultimately become unable to speak, read, or care for themselves.Additional features that rarely occur in IBMPFD include a severe and progressive muscular disease called amyotrophic lateral sclerosis and progressive problems with movement and balance(Parkinson's disease).People with IBMPFD usually live into their fifties or sixties. ad Autosomal dominant VCP https://medlineplus.gov/genetics/gene/vcp HNRNPA1 https://www.ncbi.nlm.nih.gov/gene/3178 HNRNPA2B1 https://www.ncbi.nlm.nih.gov/gene/3181 IBMPFD Inclusion body myopathy with early-onset Paget disease of bone and/or frontotemporal dementia Inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia Lower motor neuron degeneration with Paget-like bone disease Multisystem proteinopathy Muscular dystrophy, limb-girdle, with Paget disease of bone Pagetoid amyotrophic lateral sclerosis Pagetoid neuroskeletal syndrome GTR C1833662 MeSH D010001 MeSH D018979 MeSH D057180 OMIM 167320 OMIM 615422 OMIM 615424 SNOMED CT 703544004 2008-12 2023-07-17 Incontinentia pigmenti https://medlineplus.gov/genetics/condition/incontinentia-pigmenti descriptionIncontinentia pigmenti is a condition that can affect many body systems, particularly the skin. This condition occurs much more often in females than in males.Incontinentia pigmenti is characterized by skin abnormalities that typically evolve throughout childhood and young adulthood. Many affected infants have a blistering rash at birth and in early infancy. Though this blistering heals spontaneously, it can recur during illnesses with high fever. This blistering stage is followed by the development of wart-like (verrucous) lesions that also heal spontaneously. The blisters and wart-like lesions primarily occur on the arms and legs. In infancy and early childhood, the skin develops grey or brown patches (hyperpigmentation) that occur in a swirled pattern. These patches, which can occur anywhere on the body, fade with time. Adults with incontinentia pigmenti usually have lines of unusually light-colored skin (hypopigmentation) on their arms and legs. These markings follow the paths along which cells migrate as the skin develops before birth (called the lines of Blaschko).Individuals with incontinentia pigmenti are at risk of stroke and vision loss, especially within the first year of life. These risks are due to abnormalities in blood vessels in the brain and  in the light-sensitive tissue that lines the back of the eye (retina). Affected individuals at risk often have developmental delays, intellectual disabilities, seizures, or other neurological problems. In the absence of stroke or another brain abnormality, most people with incontinentia pigmenti have normal intelligence. Other signs and symptoms of incontinentia pigmenti can include hair loss (alopecia) on the scalp and other parts of the body, dental abnormalities (such as small teeth or few teeth), and lined or pitted fingernails and toenails. The features of incontinentia pigmenti may be mild or gone by the time affected individuals reach adulthood.  xd X-linked dominant IKBKG https://medlineplus.gov/genetics/gene/ikbkg Bloch-Siemens syndrome Bloch-Siemens-Sulzberger Syndrome Bloch-Sulzberger Syndrome IP GTR C0021171 ICD-10-CM Q82.3 MeSH D007184 OMIM 308300 SNOMED CT 367520004 2023-03 2023-03-13 Infantile neuroaxonal dystrophy https://medlineplus.gov/genetics/condition/infantile-neuroaxonal-dystrophy descriptionInfantile neuroaxonal dystrophy is a disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills (developmental regression). In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. They generally have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding. Muscle weakness can also result in breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the nerve that carries information from the eye to the brain (the optic nerve) often occur in infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and they eventually lose awareness of their surroundings.Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia. The relationship of these features to the symptoms of infantile neuroaxonal dystrophy is unknown. ar Autosomal recessive PLA2G6 https://medlineplus.gov/genetics/gene/pla2g6 INAD NBIA, PLA2G6-related Neurodegeneration with brain iron accumulation, PLA2G6-related Seitelberger disease Seitelberger's disease GTR C0270724 MeSH D019150 OMIM 256600 SNOMED CT 230365004 SNOMED CT 52713000 2012-09 2023-07-18 Infantile-onset ascending hereditary spastic paralysis https://medlineplus.gov/genetics/condition/infantile-onset-ascending-hereditary-spastic-paralysis descriptionInfantile-onset ascending hereditary spastic paralysis is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and eventual paralysis of the lower limbs (paraplegia). The spasticity and paraplegia result from degeneration (atrophy) of motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only the lower limbs, while the complicated types involve additional areas of the nervous system, affecting the upper limbs and other areas of the body. Infantile-onset ascending hereditary spastic paralysis starts as a pure hereditary spastic paraplegia, with spasticity and weakness in the legs only, but as the disorder progresses, the muscles in the arms, neck, and head become involved and features of the disorder are more characteristic of the complicated type.Affected infants are typically normal at birth, then within the first 2 years of life, the initial symptoms of infantile-onset ascending hereditary spastic paralysis appear. Early symptoms include exaggerated reflexes (hyperreflexia) and recurrent muscle spasms in the legs. As the condition progresses, affected children develop abnormal tightness and stiffness in the leg muscles and weakness in the legs and arms. Over time, muscle weakness and stiffness travels up (ascends) the body from the legs to the head and neck. Muscles in the head and neck usually weaken during adolescence; symptoms include slow eye movements and difficulty with speech and swallowing. Affected individuals may lose the ability to speak (anarthria). The leg and arm muscle weakness can become so severe as to lead to paralysis; as a result affected individuals require wheelchair assistance by late childhood or early adolescence. Intelligence is not affected in this condition.A condition called juvenile primary lateral sclerosis shares many of the features of infantile-onset ascending hereditary spastic paralysis. Both conditions have the same genetic cause and significantly impair movement beginning in childhood; however, the pattern of nerve degeneration is different. Because of their similarities, these conditions are sometimes considered the same disorder. ar Autosomal recessive ALS2 https://medlineplus.gov/genetics/gene/als2 IAHSP Infantile onset ascending spastic paralysis Infantile-onset ascending hereditary spastic paraplegia GTR C0037773 GTR C2931441 MeSH D010264 MeSH D015419 OMIM 607225 SNOMED CT 703543005 2016-04 2021-04-27 Infantile-onset spinocerebellar ataxia https://medlineplus.gov/genetics/condition/infantile-onset-spinocerebellar-ataxia descriptionInfantile-onset spinocerebellar ataxia (IOSCA) is a progressive disorder that affects the nervous system. Babies with IOSCA develop normally during the first year of life. During early childhood, however, they begin experiencing difficulty coordinating movements (ataxia); very weak muscle tone (hypotonia); involuntary writhing movements of the limbs (athetosis); and decreased reflexes. By their teenage years affected individuals require wheelchair assistance.People with IOSCA often develop problems with the autonomic nervous system, which controls involuntary body functions. As a result, they may experience excessive sweating, difficulty controlling urination, and severe constipation.IOSCA also leads to vision and hearing problems that begin by about age 7. Children with this disorder develop weakness in the muscles that control eye movement (ophthalmoplegia). In their teenage years they experience degeneration of the nerves that carry information from the eyes to the brain (optic atrophy), which can result in vision loss. Hearing loss caused by nerve damage (sensorineural hearing loss) typically occurs during childhood and progresses to profound deafness.Individuals with IOSCA may have recurrent seizures (epilepsy). These seizures can lead to severe brain dysfunction (encephalopathy).Most people with IOSCA survive into adulthood. However, a few individuals with IOSCA have an especially severe form of the disorder involving liver damage and encephalopathy that develops during early childhood. These children do not generally live past age 5. ar Autosomal recessive TWNK https://medlineplus.gov/genetics/gene/twnk IOSCA Ohaha syndrome Ophthalmoplegia, hypotonia, ataxia, hypacusis, and athetosis GTR C1849096 MeSH D020754 OMIM 271245 SNOMED CT 129609000 2010-03 2023-11-13 Inherited thyroxine-binding globulin deficiency https://medlineplus.gov/genetics/condition/inherited-thyroxine-binding-globulin-deficiency descriptionInherited thyroxine-binding globulin deficiency is a genetic condition that typically does not cause health problems.Thyroxine-binding globulin is one of three major proteins in the bloodstream that carries hormones made by the thyroid gland, a butterfly-shaped tissue in the lower neck. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Thyroxine is the primary hormone produced by the thyroid gland. In the bloodstream, thyroxine and other thyroid hormones are typically attached (bound) to thyroxine-binding globulin and similar proteins. A shortage (deficiency) of thyroxine-binding globulin reduces the total amount of thyroxine in the blood.Researchers have identified two forms of inherited thyroxine-binding globulin deficiency: the partial form and the complete form. The partial form reduces the amount of functioning thyroxine-binding globulin. The complete form causes a more significant loss of functioning thyroxine-binding globulin. These conditions typically do not cause problems with thyroid function and are usually identified when bloodwork is performed to rule out other conditions.Although inherited thyroxine-binding globulin deficiency typically does not cause health problems, it can be mistaken for more serious thyroid disorders, such as hypothyroidism. Therefore, it is important to correctly diagnose the condition to avoid unnecessary treatments. x X-linked SERPINA7 https://medlineplus.gov/genetics/gene/serpina7 TBG deficiency TBGQTL Thyroxine-binding globulin quantitative trait locus GTR C1839141 MeSH D013959 OMIM 300932 SNOMED CT 2241003 SNOMED CT 41300001 2025-03 2025-03-13 Intervertebral disc disease https://medlineplus.gov/genetics/condition/intervertebral-disc-disease descriptionIntervertebral disc disease is a common condition characterized by the breakdown (degeneration) of one or more of the discs that separate the bones of the spine (vertebrae), causing pain in the back or neck and frequently in the legs and arms. The intervertebral discs provide cushioning between vertebrae and absorb pressure put on the spine.While the discs in the lower (lumbar) region of the spine are most often affected in intervertebral disc disease, any part of the spine can have disc degeneration. Depending on the location of the affected disc or discs, intervertebral disc disease can cause periodic or chronic pain in the back or neck. Pain is often worse when sitting, bending, twisting, or lifting objects.Degenerated discs are prone to out-pouching (herniation); the protruding disc can press against one of the spinal nerves that run from the spinal cord to the rest of the body. This pressure causes pain, weakness, and numbness in the back and legs. Herniated discs often cause nerve pain called sciatica that travels along the sciatic nerve, which runs from the lower back down the length of each leg.As a disc degenerates, small bony outgrowths (bone spurs) may form at the edges of the affected vertebrae. These bone spurs may pinch (compress) the spinal nerves, leading to weakness or numbness in the arms or legs. If the bone spurs compress the spinal cord, affected individuals can develop problems with walking and bladder and bowel control. Over time, a degenerating disc may break down completely and leave no space between vertebrae, which can result in impaired movement, pain, and nerve damage. u Pattern unknown COL1A1 https://medlineplus.gov/genetics/gene/col1a1 COL11A1 https://medlineplus.gov/genetics/gene/col11a1 COL9A2 https://medlineplus.gov/genetics/gene/col9a2 COL9A3 https://medlineplus.gov/genetics/gene/col9a3 IL1A https://medlineplus.gov/genetics/gene/il1a ACAN https://medlineplus.gov/genetics/gene/acan MMP2 https://medlineplus.gov/genetics/gene/mmp2 IGF1R https://www.ncbi.nlm.nih.gov/gene/3480 MMP9 https://www.ncbi.nlm.nih.gov/gene/4318 THBS2 https://www.ncbi.nlm.nih.gov/gene/7058 CILP https://www.ncbi.nlm.nih.gov/gene/8483 ASPN https://www.ncbi.nlm.nih.gov/gene/54829 Discogenic disease Discogenic disorder Disorder of intervertebral disc IDD Intervertebral disc degeneration Intervertebral disc disorder Intervertebral disk degeneration GTR C0158252 ICD-10-CM M50.3 ICD-10-CM M50.9 ICD-10-CM M51 ICD-10-CM M51.3 ICD-10-CM M51.8 MeSH D055959 OMIM 603932 SNOMED CT 77547008 2016-10 2026-03-16 Intestinal pseudo-obstruction https://medlineplus.gov/genetics/condition/intestinal-pseudo-obstruction descriptionIntestinal pseudo-obstruction is a condition characterized by impairment of the muscle contractions that move food through the digestive tract. It can occur at any time of life, and its symptoms range from mild to severe. The condition may arise from abnormalities of the gastrointestinal muscles themselves (myogenic) or from problems with the nerves that control the muscle contractions (neurogenic).Intestinal pseudo-obstruction leads to a buildup of partially digested food in the intestines. This buildup can cause abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those of an intestinal blockage (obstruction), but in intestinal pseudo-obstruction no blockage is found.Depending on the cause of intestinal pseudo-obstruction, affected individuals can have additional signs and symptoms. Some people with intestinal pseudo-obstruction have bladder dysfunction such as an inability to pass urine. Other, additional features may include decreased muscle tone (hypotonia) or stiffness (spasticity) of the torso and limbs, weakness in the muscles that control eye movement (ophthalmoplegia), intellectual disability, seizures, unusual facial features, or recurrent infections.When intestinal pseudo-obstruction occurs without additional features, it is called primary or idiopathic intestinal pseudo-obstruction. When the disorder occurs along with other signs and symptoms or as a complication of another health condition, it is called secondary intestinal pseudo-obstruction. The condition can occur once in a while (acute) or steadily (chronic). ar Autosomal recessive ad Autosomal dominant x X-linked FLNA https://medlineplus.gov/genetics/gene/flna MYH11 https://medlineplus.gov/genetics/gene/myh11 ACTG2 https://medlineplus.gov/genetics/gene/actg2 MYLK https://www.ncbi.nlm.nih.gov/gene/4638 LMOD1 https://www.ncbi.nlm.nih.gov/gene/25802 X https://medlineplus.gov/genetics/chromosome/x Chronic idiopathic intestinal pseudo-obstruction CIIP CIPO Congenital short bowel syndrome Enteric neuropathy Familial visceral myopathy Familial visceral neuropathy IPO Paralytic ileus Pseudo-obstruction of intestine Pseudointestinal obstruction syndrome Pseudoobstructive syndrome GTR C1855733 GTR C1864996 GTR C2746068 ICD-10-CM K56.0 MeSH D007418 OMIM 243180 OMIM 243185 OMIM 277320 OMIM 300048 OMIM 609629 SNOMED CT 235825006 SNOMED CT 55525008 SNOMED CT 715201005 2017-12 2026-02-12 Intrahepatic cholestasis of pregnancy https://medlineplus.gov/genetics/condition/intrahepatic-cholestasis-of-pregnancy descriptionIntrahepatic cholestasis of pregnancy (also called ICP) is a liver disorder that typically occurs during the second half of pregnancy. Cholestasis is a condition that impairs the release of a digestive fluid called bile, which is made and released by the liver. In people with cholestasis, bile builds up in the liver, impairing its function. Because the problems with bile release occur within the liver (intrahepatic), the condition is described as intrahepatic cholestasis.Severe itchiness (pruritus) is typically one of the first symptoms of intrahepatic cholestasis of pregnancy. The itchiness usually begins on the palms of the hands and the soles of the feet before spreading to other parts of the body. Women with intrahepatic cholestasis of pregnancy have a buildup of bile acids in the blood. Bile acids are a component of bile and are produced when the liver processes cholesterol. Bile acid levels in the blood are normally low, but they can increase in people with liver disease. Occasionally, women with intrahepatic cholestasis of pregnancy have yellowing of the skin and whites of the eyes (jaundice). Women with intrahepatic cholestasis of pregnancy typically do not continue to have signs and symptoms of the condition after having the baby, though they may have an increased risk of developing disorders of the gallbladder, liver, or heart later in life. Intrahepatic cholestasis of pregnancy can cause problems for the baby. This condition is associated with an increased risk of premature delivery and breathing problems in the newborn (meconium aspiration). Some infants born to women with intrahepatic cholestasis of pregnancy experience a slow heart rate and a lack of oxygen during delivery (fetal distress). Women with higher levels of bile acids in their blood also have an increased risk of stillbirth.  ad Autosomal dominant ABCC2 https://medlineplus.gov/genetics/gene/abcc2 ATP8B1 https://medlineplus.gov/genetics/gene/atp8b1 ABCB11 https://medlineplus.gov/genetics/gene/abcb11 ABCB4 https://medlineplus.gov/genetics/gene/abcb4 NR1H4 https://www.ncbi.nlm.nih.gov/gene/9971 Gestational cholestasis Obstetric cholestasis Pregnancy-related cholestasis Recurrent intrahepatic cholestasis of pregnancy GTR C3549845 ICD-10-CM MeSH D002780 OMIM 147480 SNOMED CT 235888006 2024-05 2025-01-31 Intranuclear rod myopathy https://medlineplus.gov/genetics/condition/intranuclear-rod-myopathy descriptionIntranuclear rod myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with intranuclear rod myopathy have severe muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body. Signs and symptoms of this condition are apparent in infancy and include feeding and swallowing difficulties, a weak cry, and difficulty with controlling head movements. Affected babies are sometimes described as "floppy" and may be unable to move on their own.The severe muscle weakness that occurs in intranuclear rod myopathy also affects the muscles used for breathing. Individuals with this disorder may take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Frequent respiratory infections and life-threatening breathing difficulties can occur. Because of the respiratory problems, most affected individuals do not survive past infancy. Those who do survive have delayed development of motor skills such as sitting, crawling, standing, and walking.The name intranuclear rod myopathy comes from characteristic abnormal rod-shaped structures that can be seen in the nucleus of muscle cells when muscle tissue is viewed under a microscope. n Not inherited ad Autosomal dominant ACTA1 https://medlineplus.gov/genetics/gene/acta1 Intranuclear nemaline rod myopathy Nemaline myopathy with exclusively intranuclear rods GTR C3711389 MeSH D017696 OMIM 161800 SNOMED CT 129621001 2012-04 2020-08-18 Iron-refractory iron deficiency anemia https://medlineplus.gov/genetics/condition/iron-refractory-iron-deficiency-anemia descriptionIron-refractory iron deficiency anemia is one of many types of anemia, which is a group of conditions characterized by a shortage of healthy red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues.Iron-refractory iron deficiency anemia results from an inadequate amount (deficiency) of iron in the bloodstream. It is described as "iron-refractory" because the condition is totally resistant (refractory) to treatment with iron given orally and partially resistant to iron given in other ways, such as intravenously (by IV). In people with this form of anemia, red blood cells are abnormally small (microcytic) and pale (hypochromic). The symptoms of iron-refractory iron deficiency anemia can include tiredness (fatigue), weakness, pale skin, and other complications. These symptoms are most pronounced during childhood, although they tend to be mild. Affected individuals usually have normal growth and development. ar Autosomal recessive TMPRSS6 https://medlineplus.gov/genetics/gene/tmprss6 Anemia, hypochromic microcytic, with defect in iron metabolism IRIDA IRIDA syndrome Iron-handling disorder, hereditary GTR C0085576 MeSH D018798 OMIM 206200 SNOMED CT 722005000 2014-07 2020-08-18 Isobutyryl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/isobutyryl-coa-dehydrogenase-deficiency descriptionIsobutyryl-CoA dehydrogenase (IBD) deficiency is a condition that disrupts the breakdown of certain proteins. Normally, proteins from food are broken down into amino acids. Amino acids can be further processed to provide energy for growth and development. People with IBD deficiency have problems breaking down the amino acid valine.Most people with IBD deficiency are asymptomatic, which means that they do not have any signs or symptoms of the condition. If signs or symptoms do appear, they typically show early in life and only last for a short period of time. These signs and symptoms can include weak muscle tone (hypotonia), developmental delays, slow growth, a low number of red blood cells (anemia), and seizures. Because IBD deficiency is rare and often does not cause signs and symptoms, it is difficult to know if the health problems seen in affected individuals are caused by this condition or if those health problems are unrelated to the condition. It is also unclear whether IBD deficiency causes health problems later in life.Newborn screening, which identifies abnormal levels of certain compounds in the blood, can detect IBD deficiency. People with IBD deficiency have high levels of a compound called carnitine (specifically a form called C4-acylcarnitine). Cells use carnitine, a natural substance that is acquired mostly through the diet, to process fats and produce energy. ar Autosomal recessive ACAD8 https://medlineplus.gov/genetics/gene/acad8 ACAD8 deficiency IBD deficiency Isobutyryl-CoA dehydrogenase deficiency Isobutyryl-coenzyme A dehydrogenase deficiency Isobutyrylglycinuria GTR C1969809 MeSH D000592 OMIM 611283 SNOMED CT 445274004 2025-03 2025-03-31 Isolated Duane retraction syndrome https://medlineplus.gov/genetics/condition/isolated-duane-retraction-syndrome descriptionIsolated Duane retraction syndrome is a disorder of eye movement. This condition prevents outward movement of the eye (toward the ear), and in some cases it may also limit inward eye movement (toward the nose). In people with this condition, the eyeball pulls back (retracts) into its socket and the eyelid opening narrows as the eye moves inward. Due to these movement limitations, the eyes often do not look in the same direction (strabismus). Instead, affected individuals may need to turn their head to track objects with both eyes.Normally, only one eye is affected (most commonly the left eye) in people with isolated Duane retraction syndrome. About 10 percent of people with this condition also develop amblyopia ("lazy eye"), a condition that causes vision loss in the affected eye.About 70 percent of all cases of Duane retraction syndrome are isolated, which means they occur without other signs and symptoms. The remaining cases of Duane retraction syndrome occur as part of syndromes that affect other areas of the body. For example, Duane-radial ray syndrome is characterized by this eye disorder and abnormalities of bones in the arms and hands.Researchers have identified three forms of isolated Duane retraction syndrome, designated types I, II, and III. The types are differentiated by which eye movements are most severely restricted (inward, outward, or both). All three types are characterized by a retraction of the eyeball as the eye moves inward. ad Autosomal dominant ar Autosomal recessive CHN1 https://medlineplus.gov/genetics/gene/chn1 MAFB https://www.ncbi.nlm.nih.gov/gene/9935 Co-contractive retraction syndrome Duane anomaly, isolated Duane retraction syndrome Duane syndrome Duane's syndrome Ocular retraction syndrome Stilling-Turk-Duane syndrome GTR C0013261 ICD-10-CM H50.81 ICD-10-CM H50.811 ICD-10-CM H50.812 MeSH D004370 OMIM 126800 OMIM 604356 OMIM 617041 SNOMED CT 60318001 2024-05 2024-05-31 Isolated Pierre Robin sequence https://medlineplus.gov/genetics/condition/isolated-pierre-robin-sequence descriptionPierre Robin sequence is a set of abnormalities affecting the head and face, consisting of a small lower jaw (micrognathia), a tongue that is placed further back than normal (glossoptosis), and blockage (obstruction) of the airways. Most people with Pierre Robin sequence are also born with an opening in the roof of the mouth (a cleft palate). This feature is not generally considered necessary for diagnosis of the condition, although there is some disagreement among doctors.Some people have the features of Pierre Robin sequence as part of a syndrome that affects other organs and tissues in the body, such as Stickler syndrome or campomelic dysplasia. These instances are described as syndromic. When Pierre Robin sequence occurs by itself, it is described as nonsyndromic or isolated. Approximately 20 to 40 percent of cases of Pierre Robin sequence are isolated.This condition is described as a "sequence" because one of its features, underdevelopment of the lower jaw (mandible), sets off a sequence of events before birth that cause the other signs and symptoms. Specifically, having an abnormally small jaw affects placement of the tongue, and the abnormally positioned tongue can block the airways. In addition, micrognathia and glossoptosis affect formation of the palate during development before birth, which often leads to cleft palate.The combination of features characteristic of Pierre Robin sequence can lead to difficulty breathing and problems eating early in life. As a result, some affected babies have an inability to grow and gain weight at the expected rate (failure to thrive). In some children with Pierre Robin sequence, growth of the mandible catches up, and as adults these individuals have normal-sized chins. ad Autosomal dominant SOX9 https://medlineplus.gov/genetics/gene/sox9 Glossoptosis, micrognathia, and cleft palate Pierre Robin syndrome Pierre-Robin syndrome Robin sequence Robin syndrome GTR C0031900 MeSH D010855 OMIM 261800 SNOMED CT 4602007 2016-12 2020-08-18 Isolated congenital asplenia https://medlineplus.gov/genetics/condition/isolated-congenital-asplenia descriptionIsolated congenital asplenia is a condition in which affected individuals are missing their spleen (asplenia) but have no other developmental abnormalities. While most individuals with this condition have no spleen at all, some people have a very small, nonfunctional spleen (hyposplenism).The spleen plays an important role in the immune system. This organ is part of the lymphatic system, which produces and transports fluids and immune cells throughout the body. The spleen produces certain immune system cells called phagocytes that help remove bacteria from the blood in order to prevent infections. The spleen also stores particular blood cells that fight foreign invaders until they are needed and filters old blood cells for removal. Because people with isolated congenital asplenia lack these immune functions, they are highly susceptible to bacterial infections.People with isolated congenital asplenia are prone to developing severe, recurrent infections. Infections most commonly affect the whole body (sepsis), the membrane covering the brain and spinal cord (meningitis), or the ears (otitis media). Infections are most often caused by the Streptococcus pneumoniae bacteria.Without preventative care and proper treatment, the frequent infections caused by isolated congenital asplenia can be life-threatening. ad Autosomal dominant u Pattern unknown RPSA https://medlineplus.gov/genetics/gene/rpsa Asplenia, familial Asplenia, isolated congenital Congenital hypoplasia of spleen Hypoplasia of spleen Hyposplenia, isolated congenital ICAS Spenlic hypoplasia GTR C0685889 ICD-10-CM Q89.01 MeSH D013158 OMIM 271400 SNOMED CT 726708009 2019-04 2020-08-18 Isolated ectopia lentis https://medlineplus.gov/genetics/condition/isolated-ectopia-lentis descriptionIsolated ectopia lentis is a condition that affects the positioning of the lens in the eyes. The lens is a clear structure at the front of the eye that helps focus light. In people with isolated ectopia lentis, the lens in one or both eyes is out of place (ectopic) instead of centrally positioned. Isolated ectopia lentis is often present at birth but may become apparent during childhood. The lens may drift further out of place over time.Vision problems are common in people with isolated ectopia lentis. These problems often include nearsightedness (myopia) and double vision (diplopia). The lens or the structure that covers the front of the eye (the cornea) can have an irregular curvature, which causes blurred vision (astigmatism). Affected individuals may also develop clouding of the lenses (cataracts) or increased pressure in the eyes (glaucoma) at an earlier age than other adults. A small number of people with isolated ectopia lentis experience tearing in the lining at the back of the eye (retinal detachment), which can lead to further vision problems and blindness.In individuals with isolated ectopia lentis, each eye can be affected differently. In addition, the eye problems vary among affected individuals, even those within the same family.Ectopia lentis is classified as isolated when it occurs without signs and symptoms that affect other body systems. Ectopia lentis can also be classified as syndromic when it is part of a syndrome that affects multiple parts of the body. Ectopia lentis is a common feature of genetic syndromes such as Marfan syndrome and Weill-Marchesani syndrome.Ectopia lentis can also occur in individuals who experience injury or trauma to the head or eye. Traumatic ectopia lentis is not genetic, can occur at any age, and is the most common cause of ectopia lentis. ar Autosomal recessive ad Autosomal dominant+Inherited or new variant FBN1 https://medlineplus.gov/genetics/gene/fbn1 ADAMTSL4 https://medlineplus.gov/genetics/gene/adamtsl4 Congenital ectopia lentis Ectopia lentis Lens subluxation Subluxation of lens GTR C3541474 GTR C3541518 ICD-10-CM H27.11 ICD-10-CM H27.111 ICD-10-CM H27.112 ICD-10-CM H27.113 ICD-10-CM H27.119 MeSH D004479 OMIM 129600 OMIM 225100 SNOMED CT 65814009 SNOMED CT 74969002 2026-04 2026-04-01 Isolated growth hormone deficiency https://medlineplus.gov/genetics/condition/isolated-growth-hormone-deficiency descriptionIsolated growth hormone deficiency is a condition caused by a severe shortage or absence of growth hormone. Growth hormone is a protein that is necessary for the normal growth of the body's bones and tissues. Because they do not have enough of this hormone, people with isolated growth hormone deficiency commonly experience a failure to grow at the expected rate and have unusually short stature. This condition is usually apparent by early childhood.There are four types of isolated growth hormone deficiency differentiated by the severity of the condition, the gene involved, and the inheritance pattern.Isolated growth hormone deficiency type IA is caused by an absence of growth hormone and is the most severe of all the types. In people with type IA, growth failure is evident in infancy as affected babies are shorter than normal at birth.People with isolated growth hormone deficiency type IB produce very low levels of growth hormone. As a result, type IB is characterized by short stature, but this growth failure is typically not as severe as in type IA. Growth failure in people with type IB is usually apparent in early to mid-childhood.Individuals with isolated growth hormone deficiency type II have very low levels of growth hormone and short stature that varies in severity. Growth failure in these individuals is usually evident in early to mid-childhood. It is estimated that nearly half of the individuals with type II have underdevelopment of the pituitary gland (pituitary hypoplasia). The pituitary gland is located at the base of the brain and produces many hormones, including growth hormone.Isolated growth hormone deficiency type III is similar to type II in that affected individuals have very low levels of growth hormone and short stature that varies in severity. Growth failure in type III is usually evident in early to mid-childhood. People with type III may also have a weakened immune system and are prone to frequent infections. They produce very few B cells, which are specialized white blood cells that help protect the body against infection (agammaglobulinemia). ad Autosomal dominant ar Autosomal recessive xr X-linked recessive BTK https://medlineplus.gov/genetics/gene/btk GHRHR https://medlineplus.gov/genetics/gene/ghrhr GH1 https://medlineplus.gov/genetics/gene/gh1 Dwarfism, growth hormone deficiency Dwarfism, pituitary Growth hormone deficiency dwarfism Isolated GH deficiency Isolated HGH deficiency Isolated human growth hormone deficiency Isolated somatotropin deficiency Isolated somatotropin deficiency disorder GTR C0271567 GTR C0342573 GTR C0472813 GTR C2748571 ICD-10-CM D80.0 ICD-10-CM E23.0 MeSH D004393 OMIM 173100 OMIM 262400 OMIM 307200 OMIM 612781 SNOMED CT 18200000 SNOMED CT 2109003 SNOMED CT 234533006 SNOMED CT 237687003 SNOMED CT 7990002 2012-02 2020-08-18 Isolated hyperCKemia https://medlineplus.gov/genetics/condition/isolated-hyperckemia descriptionIsolated hyperCKemia is a condition characterized by elevated levels of an enzyme called creatine kinase in the blood. In affected individuals, levels of this enzyme are typically 3 to 10 times higher than normal. While elevated creatine kinase often accompanies various muscle diseases, individuals with isolated hyperCKemia have no muscle weakness or other symptoms. Some people with this condition have abnormalities of muscle cells that can be seen with a microscope, such as unusual variability in the size of muscle fibers, but these changes do not affect the function of the muscle. ad Autosomal dominant CAV3 https://medlineplus.gov/genetics/gene/cav3 Elevated serum CPK Elevated serum creatine phosphokinase H-CK Idiopathic hyperCKemia Idiopathic persistent elevation of serum creatine kinase GTR C5679790 MeSH D009135 OMIM 123320 SNOMED CT 432352001 2014-05 2023-02-21 Isolated hyperchlorhidrosis https://medlineplus.gov/genetics/condition/isolated-hyperchlorhidrosis descriptionIsolated hyperchlorhidrosis is characterized by the excessive loss of salt (sodium chloride or NaCl) in sweat. In particular, "hyperchlorhidrosis" refers to the high levels of chloride found in sweat, although both sodium and chloride are released. Because the salt is abnormally released from the body in sweat, there are lower than normal levels of sodium in fluids inside the body (hyponatremia). Most infants with isolated hyperchlorhidrosis experience one or more episodes of dehydration with low levels of sodium in the blood (hyponatremic dehydration), which can require hospitalization. These episodes typically follow a mild illness that causes vomiting or diarrhea. Affected infants also have poor feeding and an inability to grow and gain weight at the expected rate (failure to thrive). By early childhood, though, weight and height usually catch up to normal, although the abnormal loss of salt still remains. These individuals may still experience dangerous hyponatremia when they sweat excessively, for example in warm temperatures or when exercising.While hyperchlorhidrosis can occur as one of several features of other conditions, such as cystic fibrosis, people with isolated hyperchlorhidrosis do not have the additional signs and symptoms of these other conditions. ar Autosomal recessive CA12 https://medlineplus.gov/genetics/gene/ca12 Carbonic anhydrase XII deficiency MeSH D014883 OMIM 143860 SNOMED CT 709413001 2014-05 2020-08-18 Isolated lissencephaly sequence https://medlineplus.gov/genetics/condition/isolated-lissencephaly-sequence descriptionIsolated lissencephaly sequence (ILS) is a condition that affects brain development before birth. Normally, the cells that make up the exterior of the brain (cerebral cortex) are well-organized, multi-layered, and arranged into many folds and grooves (gyri). In people with ILS, the cells of the cerebral cortex are disorganized, and the brain surface is abnormally smooth with an absence (agyria) or reduction (pachygyria) of folds and grooves. In most cases, these abnormalities impair brain growth, causing the brain to be smaller than normal (microcephaly). This underdevelopment of the brain causes severe intellectual disability, delayed development, and recurrent seizures (epilepsy) in individuals with ILS.More than 90 percent of individuals with ILS develop epilepsy, often within the first year of life. Up to 80 percent of infants with ILS have a type of seizure called infantile spasms, these seizures can be severe enough to cause brain dysfunction (epileptic encephalopathy). After the first months of life, most children with ILS develop a variety of seizure types, including persisting infantile spasms, short periods of loss of consciousness (absence seizures); sudden episodes of weak muscle tone (drop attacks); rapid, uncontrolled muscle jerks (myoclonic seizures); and episodes of muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures).Infants with ILS may have poor muscle tone (hypotonia) and difficulty feeding, which leads to poor growth overall. Hypotonia also affects the muscles used for breathing, which often causes breathing problems that can lead to a life-threatening bacterial lung infection known as aspiration pneumonia. Children with ILS often develop muscle stiffness (spasticity) in their arms and legs and an abnormal side-to-side curvature of the spine (scoliosis). Rarely, the muscle stiffness will progress to paralysis (spastic paraplegia). Individuals with ILS cannot walk and rarely crawl. Most children with ILS do not develop communication skills. xd X-linked dominant ad Autosomal dominant DCX https://medlineplus.gov/genetics/gene/dcx PAFAH1B1 https://medlineplus.gov/genetics/gene/pafah1b1 TUBA1A https://medlineplus.gov/genetics/gene/tuba1a TUBB2B https://medlineplus.gov/genetics/gene/tubb2b Classical lissencephaly ILS LIS1 Lissencephaly type 1 Lissencephaly, classic Type 1 lissencephaly GTR C0431375 GTR C1969029 GTR C4551968 ICD-10-CM Q04.3 MeSH D054221 OMIM 300067 OMIM 607432 OMIM 611603 SNOMED CT 253147000 SNOMED CT 715780008 2013-06 2020-08-18 Isolated sulfite oxidase deficiency https://medlineplus.gov/genetics/condition/isolated-sulfite-oxidase-deficiency descriptionIsolated sulfite oxidase deficiency (ISOD) is a disorder of the nervous system, with a severe "classic" form that starts in the newborn period and a milder, late-onset form that begins later in infancy or early childhood.Classic ISOD appears within the first few days after birth with signs and symptoms of brain dysfunction (encephalopathy) that quickly get worse. Babies with classic ISOD have seizures that are difficult to treat and feeding difficulties. They have muscle stiffness that results in paralysis of the arms and legs (spastic quadriplegia) and episodes of muscle spasms that cause backward arching of the spine (opisthotonus). Because development of the brain is impaired, the head does not grow at the same rate as the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Abnormalities in facial features also become increasingly pronounced with lack of normal head growth. These facial differences include a relatively long and narrow face; deep-set, widely-spaced eyes; elongated openings of the eyes (palpebral fissures); puffy cheeks; a small nose; a large space between the nose and upper lip (a long philtrum); and thick lips.Babies with classic ISOD do not respond to their environment except to startle easily in response to noises, and they do not develop any motor skills such as turning over or sitting up. They usually do not live for more than a few months. Affected individuals who survive past infancy usually develop displacement of the lenses of the eyes (ectopia lentis). Because these individuals do not react to visual stimuli (are behaviorally blind) due to the brain damage associated with classic ISOD, the ectopia lentis has no further impact on their vision.Late-onset ISOD usually begins between the ages of 6 and 18 months, often after an illness involving fever. Individuals with this form of the disorder may not have the seizures and ectopia lentis that usually occur in the classic form. They have developmental delay and may lose skills that they had already developed (developmental regression). Movement problems occur in this form of the disorder, including muscle tensing (dystonia), uncontrolled movements of the limbs (choreoathetosis), and difficulty with coordination (ataxia). The signs and symptoms of late-onset ISOD can gradually get worse (progress), or they can be episodic, which means that they come and go. Some individuals with this form of ISOD survive into childhood or adolescence; because of the rarity of this disorder, their life expectancy is unknown. ar Autosomal recessive SUOX https://medlineplus.gov/genetics/gene/suox Encephalopathy due to sulfite oxidase deficiency ISOD Sulfocysteinuria MeSH D000592 OMIM 272300 SNOMED CT 40873003 SNOMED CT 715980003 2018-01 2020-08-18 Isovaleric acidemia https://medlineplus.gov/genetics/condition/isovaleric-acidemia descriptionIsovaleric acidemia is a rare disorder in which the body is unable to properly break down a particular protein building block (amino acid). The condition is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with isovaleric acidemia have inadequate levels of an enzyme that helps break down a particular amino acid called leucine.Health problems related to isovaleric acidemia range from very mild to life-threatening. In severe cases, the features of isovaleric acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, seizures, and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including seizures, coma, and possibly death. A characteristic sign of isovaleric acidemia is a distinctive odor of sweaty feet during acute illness. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.In other cases, the signs and symptoms of isovaleric acidemia appear during childhood and may come and go over time. Children with this condition may fail to gain weight and grow at the expected rate (failure to thrive) and often have delayed development. In these children, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), infections, or eating an increased amount of protein-rich foods.Some people with gene mutations that cause isovaleric acidemia are asymptomatic, which means they never experience any signs or symptoms of the condition. ar Autosomal recessive IVD https://medlineplus.gov/genetics/gene/ivd Isovaleric acid-CoA dehydrogenase deficiency Isovaleryl-CoA dehydrogenase deficiency IVA IVD deficiency GTR C0268575 ICD-10-CM E71.110 MeSH D000592 OMIM 243500 SNOMED CT 87827003 2020-03 2020-08-18 JAK3-deficient severe combined immunodeficiency https://medlineplus.gov/genetics/condition/jak3-deficient-severe-combined-immunodeficiency descriptionJAK3-deficient severe combined immunodeficiency (SCID) is an inherited disorder of the immune system. Individuals with JAK3-deficient SCID lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with JAK3-deficient SCID are described as opportunistic because they ordinarily do not cause illness in healthy people. Affected infants typically develop chronic diarrhea, a fungal infection in the mouth called oral thrush, pneumonia, and skin rashes. Persistent illness also causes affected individuals to grow more slowly than other children. Without treatment, people with JAK3-deficient SCID usually live only into early childhood. ar Autosomal recessive JAK3 https://medlineplus.gov/genetics/gene/jak3 Autosomal recessive T cell-negative, B cell-positive, NK cell-negative severe combined immunodeficiency Autosomal recessive T-B+NK- SCID JAK3 SCID T cell-negative, B cell-positive, NK cell-negative SCID T-B+ severe combined immunodeficiency due to JAK3 deficiency GTR C1833275 MeSH D016511 OMIM 600802 SNOMED CT 718107000 2017-08 2020-08-18 Jackson-Weiss syndrome https://medlineplus.gov/genetics/condition/jackson-weiss-syndrome descriptionJackson-Weiss syndrome is a genetic disorder characterized by foot abnormalities and the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.Many of the characteristic facial features of Jackson-Weiss syndrome result from premature fusion of the skull bones. Abnormal growth of these bones leads to a misshapen skull, widely spaced eyes, and a bulging forehead.Foot abnormalities are the most consistent features of Jackson-Weiss syndrome. The first (big) toes are short and wide, and they bend away from the other toes. Additionally, the bones of some toes may be fused together (syndactyly) or abnormally shaped. The hands are almost always normal.Some individuals with Jackson-Weiss syndrome have hearing impairment. People with Jackson-Weiss syndrome usually have normal intelligence and a normal life span. ad Autosomal dominant FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 JWS GTR C0795998 MeSH D003398 OMIM 123150 SNOMED CT 709105005 2008-02 2020-08-18 Jacobsen syndrome https://medlineplus.gov/genetics/condition/jacobsen-syndrome descriptionJacobsen syndrome is a condition caused by a loss (deletion) of genetic material from chromosome 11. Because this deletion most commonly occurs at the end (terminus) of the long (q) arm of chromosome 11, Jacobsen syndrome is also known as 11q terminal deletion disorder.The signs and symptoms of Jacobsen syndrome vary considerably. Most affected individuals experience delayed development of certain skills, including speech and motor skills (such as sitting, standing, and walking). Most also have cognitive impairment and learning difficulties. Behavioral problems have been reported, including compulsive behavior (such as shredding paper), a short attention span, and easy distractibility. Many people with Jacobsen syndrome have been diagnosed with attention-deficit/hyperactivity disorder (ADHD). Jacobsen syndrome is also associated with an increased likelihood of autism spectrum disorder, which is characterized by impaired communication and socialization skills.Jacobsen syndrome is also characterized by distinctive facial features. These include small and low-set ears, widely set eyes (hypertelorism) with droopy eyelids (ptosis), skin folds covering the inner corner of the eyes (epicanthal folds), a broad nasal bridge, downturned corners of the mouth, a thin upper lip, and a small lower jaw. Affected individuals often have a large head size (macrocephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance.More than 90 percent of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. This condition causes a lifelong risk of abnormal bleeding and easy bruising. Paris-Trousseau syndrome is a disorder of platelets, which are blood cells that are necessary for blood clotting.Other features of Jacobsen syndrome can include heart defects, such as underdevelopment of the left side of the heart (hypoplastic left heart syndrome); feeding difficulties in infancy; short stature; frequent ear and sinus infections; and skeletal abnormalities. The disorder can also affect the digestive system, kidneys, and genitalia. The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood. Complex heart defects are a leading cause of death in people with Jacobsen syndrome. Bleeding episodes and infections can also be life-threatening in people with Jacobsen syndrome. n Not inherited FLI1 https://medlineplus.gov/genetics/gene/fli1 ETS1 https://www.ncbi.nlm.nih.gov/gene/2113 NRGN https://www.ncbi.nlm.nih.gov/gene/4900 ARHGAP32 https://www.ncbi.nlm.nih.gov/gene/9743 BSX https://www.ncbi.nlm.nih.gov/gene/390259 11 https://medlineplus.gov/genetics/chromosome/11 11q deletion disorder 11q deletion syndrome 11q terminal deletion disorder 11q- deletion syndrome 11q23 deletion disorder Jacobsen thrombocytopenia GTR C0795841 MeSH D054868 OMIM 147791 SNOMED CT 4325000 2023-08 2023-08-02 Jansen-de Vries syndrome https://medlineplus.gov/genetics/condition/jansen-de-vries-syndrome descriptionJansen-de Vries syndrome is a developmental disorder that affects many parts of the body. Features of this condition include unique facial features, intellectual disability, certain personality characteristics, behavioral changes, and gastrointestinal problems. The signs and symptoms of Jansen-de Vries syndrome typically begin soon after birth. Affected infants often have low muscle tone (hypotonia) and feeding difficulties. Children with this disorder are often slow to develop speech and language skills, They may also be slow to acquire motor skills, such as standing or walking. People with Jansen-de Vries syndrome also tend to have intellectual disability, which can range from mild to severe.  Additional features seen in people with Jansen-de Vries syndrome may include short stature, small hands and feet, and differences in facial features. The facial features that are common in people with this condition include a broad forehead, thin upper lip, low-set ears that are rotated backwards, and downturned corners of the mouth. Gastrointestinal problems, such as constipation, are also common in people with Jansen-de Vries syndrome. Many affected individuals experience recurrent episodes of nausea and vomiting (cyclic vomiting).Though people with Jansen-de Vries syndrome tend to be very social with outgoing and friendly personalities, affected individuals may experience behavioral differences, such as anxiety disorders and attention-deficit hyperactivity disorder. Some people with Jansen-de Vries syndrome have autism-spectrum disorder, a developmental disorder that affects communication and social skills.Other signs and symptoms of Jansen-de Vries syndrome include vision problems, an increased sensitivity to sound (hyperacusis), and a higher-than-normal pain threshold. Less commonly, people with Jansen-de Vries syndrome can have congenital heart defects. These may include openings in the wall (septum) that separates the upper or lower chambers of the heart (atrial or ventricular septal defects). ad Autosomal dominant+New variant PPM1D https://medlineplus.gov/genetics/gene/ppm1d IDDGIP Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold JDVS OMIM 617450 2025-03 2025-09-10 Jervell and Lange-Nielsen syndrome https://medlineplus.gov/genetics/condition/jervell-and-lange-nielsen-syndrome descriptionJervell and Lange-Nielsen syndrome is a condition that causes profound hearing loss from birth and a disruption of the heart's normal rhythm (arrhythmia). This disorder is a form of long QT syndrome, which is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. Beginning in early childhood, the irregular heartbeats increase the risk of fainting (syncope) and sudden death. ar Autosomal recessive KCNQ1 https://medlineplus.gov/genetics/gene/kcnq1 KCNE1 https://medlineplus.gov/genetics/gene/kcne1 Autosomal recessive long QT syndrome (LQTS) Cardio-auditory-syncope syndrome Cardioauditory syndrome of Jervell and Lange-Nielsen Deafness, congenital, and functional heart disease Jervell-Lange Nielsen syndrome JLNS Prolonged QT interval in EKG and sudden death Surdo-cardiac syndrome GTR C0022387 GTR C2676723 GTR C4551509 ICD-10-CM I45.81 MeSH D029593 OMIM 220400 OMIM 612347 SNOMED CT 373905003 2006-04 2020-08-18 Joubert syndrome https://medlineplus.gov/genetics/condition/joubert-syndrome descriptionJoubert syndrome is a condition that affects the development of the brain. This condition can also impact many other parts of the body. The signs and symptoms seen in people with Joubert syndrome can vary, even among members of the same family.The hallmark feature of Joubert syndrome is a combination of brain abnormalities called the molar tooth sign, which can be seen using magnetic resonance imaging (MRI). The molar tooth sign occurs when structures near the back of the brain, including the brainstem and the central part of the cerebellum (vermis), develop abnormally. This sign got its name because these brain abnormalities resemble the shape or outline of a molar tooth when seen on an MRI scan.Infants with Joubert syndrome often have low muscle tone (hypotonia) and may experience breathing problems, with episodes of unusually fast (hyperpnea) or slow (apnea) breathing. Abnormal eye movements, which can include rapid, involuntary eye movements (nystagmus) or problems with side-to-side movements of the eyes (oculomotor apraxia), are also common.Most individuals with Joubert syndrome have intellectual disabilities, which can range from mild to severe. Children with Joubert syndrome often have delayed development of speech and motor skills, such as sitting and walking. Problems with coordination and balance (ataxia) are common, but ataxia may become less severe over time. Most children with Joubert syndrome learn to walk on their own, although some affected individuals require walking support or wheelchair assistance.Additional signs and symptoms that are seen in people with Joubert syndrome can include seizures, difficulty regulating body temperature, and behavioral problems. People with Joubert syndrome may have a broad range of other signs and symptoms. Kidney disease, liver disease, skeletal abnormalities (such as the presence of extra fingers and toes), or hormone (endocrine) problems may occur in affected individuals. Eye abnormalities may also be present and can include the breakdown of the light-sensitive tissue at the back of the eye (retinal dystrophy), which can cause vision loss.In the past, individuals with the molar tooth sign were separated into different subgroups of Joubert syndrome based on their additional features. The term “Joubert syndrome and related disorders” (JSRD) was used to refer to these subgroups. Today, all people with the molar tooth sign, including those with additional signs and symptoms, are considered to have Joubert syndrome. x X-linked ad Autosomal dominant ar Autosomal recessive OFD1 https://medlineplus.gov/genetics/gene/ofd1 CEP290 https://medlineplus.gov/genetics/gene/cep290 NPHP1 https://medlineplus.gov/genetics/gene/nphp1 KIF7 https://medlineplus.gov/genetics/gene/kif7 ARL3 https://www.ncbi.nlm.nih.gov/gene/403 MKS1 https://www.ncbi.nlm.nih.gov/gene/4290 PDE6D https://www.ncbi.nlm.nih.gov/gene/5147 CEP104 https://www.ncbi.nlm.nih.gov/gene/9731 KIAA0586 https://www.ncbi.nlm.nih.gov/gene/9786 KIAA0753 https://www.ncbi.nlm.nih.gov/gene/9851 PIBF1 https://www.ncbi.nlm.nih.gov/gene/10464 TOGARAM1 https://www.ncbi.nlm.nih.gov/gene/23116 KATNIP https://www.ncbi.nlm.nih.gov/gene/23247 RPGRIP1L https://www.ncbi.nlm.nih.gov/gene/23322 C2CD3 https://www.ncbi.nlm.nih.gov/gene/26005 TCTN3 https://www.ncbi.nlm.nih.gov/gene/26123 IFT172 https://www.ncbi.nlm.nih.gov/gene/26160 B9D1 https://www.ncbi.nlm.nih.gov/gene/27077 CEP83 https://www.ncbi.nlm.nih.gov/gene/51134 TMEM216 https://www.ncbi.nlm.nih.gov/gene/51259 TMEM138 https://www.ncbi.nlm.nih.gov/gene/51524 SUFU https://www.ncbi.nlm.nih.gov/gene/51684 AHI1 https://www.ncbi.nlm.nih.gov/gene/54806 INPP5E https://www.ncbi.nlm.nih.gov/gene/56623 CC2D2A https://www.ncbi.nlm.nih.gov/gene/57545 TMEM237 https://www.ncbi.nlm.nih.gov/gene/65062 CPLANE1 https://www.ncbi.nlm.nih.gov/gene/65250 TMEM231 https://www.ncbi.nlm.nih.gov/gene/79583 TCTN1 https://www.ncbi.nlm.nih.gov/gene/79600 TXNDC15 https://www.ncbi.nlm.nih.gov/gene/79770 CSPP1 https://www.ncbi.nlm.nih.gov/gene/79848 TCTN2 https://www.ncbi.nlm.nih.gov/gene/79867 IFT74 https://www.ncbi.nlm.nih.gov/gene/80173 ARMC9 https://www.ncbi.nlm.nih.gov/gene/80210 B9D2 https://www.ncbi.nlm.nih.gov/gene/80776 TMEM107 https://www.ncbi.nlm.nih.gov/gene/84314 TMEM67 https://www.ncbi.nlm.nih.gov/gene/91147 CEP41 https://www.ncbi.nlm.nih.gov/gene/95681 CEP120 https://www.ncbi.nlm.nih.gov/gene/153241 ARL13B https://www.ncbi.nlm.nih.gov/gene/200894 HYLS1 https://www.ncbi.nlm.nih.gov/gene/219844 TMEM218 https://www.ncbi.nlm.nih.gov/gene/219854 NPHP4 https://www.ncbi.nlm.nih.gov/gene/261734 FAM149B1 https://www.ncbi.nlm.nih.gov/gene/317662 Cerebellooculorenal disorder Cerebellooculorenal syndrome 1 Cerebelloparenchymal disorder CORS CPD Familial aplasia of the vermis JBTS Joubert Syndrome and Related Disorders Joubert-Bolthauser syndrome JSRD GTR C5679612 GTR C5979921 MeSH D000015 OMIM 213300 OMIM 300804 OMIM 608091 OMIM 608629 OMIM 609583 OMIM 610188 OMIM 610688 OMIM 611560 OMIM 612285 OMIM 612291 OMIM 614173 OMIM 614424 OMIM 614464 OMIM 614465 OMIM 614615 OMIM 614815 OMIM 614844 OMIM 614970 OMIM 615636 OMIM 615665 OMIM 616490 OMIM 616654 OMIM 616781 OMIM 616784 OMIM 617120 OMIM 617121 OMIM 617622 OMIM 617757 OMIM 617761 OMIM 617767 OMIM 618161 OMIM 618763 OMIM 619185 OMIM 619476 OMIM 619562 OMIM 619582 SNOMED CT 253175003 2026-02 2026-02-25 Junctional epidermolysis bullosa https://medlineplus.gov/genetics/condition/junctional-epidermolysis-bullosa descriptionJunctional epidermolysis bullosa (JEB) is a major form of epidermolysis bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and areas of skin loss (erosions) form in response to minor injury or friction, such as rubbing or scratching. Researchers classify junctional epidermolysis bullosa into two main types: JEB generalized severe (formerly known as Herlitz JEB) and JEB generalized intermediate (formerly known as non-Herlitz JEB). Although the types differ in severity, their features overlap significantly, and they can be caused by mutations in the same genes.JEB generalized severe is the more serious form of the condition. From birth or early infancy, affected individuals have blistering over large regions of the body. Blistering also affects the mucous membranes, such as the moist lining of the mouth and digestive tract, which can make it difficult to eat and digest food. As a result, many affected children are undernourished and grow slowly. The extensive blistering leads to scarring and the formation of red, bumpy patches called granulation tissue. Granulation tissue bleeds easily and profusely, making affected infants susceptible to serious infections and loss of necessary proteins, minerals, and fluids. Additionally, a buildup of granulation tissue in the airway can lead to a weak, hoarse cry and difficulty breathing.Other complications of JEB generalized severe can include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that limit movement, hair loss (alopecia), and thinning of the protective outer layer (enamel) of the teeth. Because the signs and symptoms of JEB generalized severe are so serious, infants with this condition usually do not survive beyond the first year of life.The milder form of junctional epidermolysis bullosa is called JEB generalized intermediate. The blistering associated with JEB generalized intermediate may be limited to the hands, feet, knees, and elbows, and it often improves after the newborn period. Other characteristic features of this form of the condition include hair loss, abnormal fingernails and toenails, and irregular tooth enamel. Most affected individuals do not have extensive scarring or granulation tissue formation, so breathing difficulties and other severe complications are rare. JEB generalized intermediate is typically associated with a normal lifespan. ar Autosomal recessive LAMB3 https://medlineplus.gov/genetics/gene/lamb3 LAMC2 https://medlineplus.gov/genetics/gene/lamc2 LAMA3 https://medlineplus.gov/genetics/gene/lama3 COL17A1 https://medlineplus.gov/genetics/gene/col17a1 ITGB4 https://medlineplus.gov/genetics/gene/itgb4 Epidermolysis bullosa, junctional JEB GTR C0079301 GTR C0079683 GTR C0268374 ICD-10-CM Q81.8 MeSH D016109 OMIM 226650 OMIM 226700 SNOMED CT 33662006 SNOMED CT 399971009 SNOMED CT 400140006 SNOMED CT 79855003 2009-09 2025-04-03 Juvenile Paget disease https://medlineplus.gov/genetics/condition/juvenile-paget-disease descriptionJuvenile Paget disease is a disorder that affects bone growth. This disease causes bones to be abnormally large, misshapen, and easily broken (fractured). The specific signs and symptoms and the severity of the condition can vary among affected individuals.The features of juvenile Paget disease appear in infancy or childhood. As bones grow, they become weaker and misshapen. These abnormalities usually become more severe during the adolescent growth spurt, when bones grow very quickly.Juvenile Paget disease affects the entire skeleton, resulting in widespread bone and joint pain. The bones of the skull tend to grow unusually large and thick, which can increase the size of the head (circumference). The abnormal growth of the skull bones can damage the bones in the ear, leading to hearing loss. The disease can also cause an abnormal curvature of the spine (kyphosis). Additionally, the weight-bearing long bones in the legs tend to bow and fracture easily, which can interfere with the ability to stand and walk.Other features of juvenile Paget disease can include short stature; developmental delays; dental problems, such as the delayed appearance (eruption) of teeth or the early (premature) loss of teeth; and vision problems, which can include abnormalities of the light-sensing tissue at the back of the eye (retina). Affected individuals may also have an abnormal accumulation of calcium (calcification) in the walls of blood vessels. Rarely, people with juvenile Paget disease have a bulge (aneurysm) in the wall of the vessel that carries blood to the brain, face, and neck (internal carotid artery). If an aneurysm grows large, it can burst and cause dangerous bleeding. ar Autosomal recessive TNFRSF11B https://medlineplus.gov/genetics/gene/tnfrsf11b Chronic congenital idiopathic hyperphosphatasemia Familial Hyperphosphatasemia Familial hyperphosphatasia Familial idiopathic hyperphosphatasia Familial osteoectasia Hereditary hyperphosphatasia Hyperostosis corticalis deformans juvenilis Idiopathic hyperphosphatasia JPD Paget disease of bone 5 GTR C0268414 MeSH D010001 OMIM 239000 SNOMED CT 9723006 2025-11 2025-11-20 Juvenile idiopathic arthritis https://medlineplus.gov/genetics/condition/juvenile-idiopathic-arthritis descriptionJuvenile idiopathic arthritis refers to a group of conditions involving joint inflammation (arthritis) that first appears before the age of 16. This condition is an autoimmune disorder, which means that the immune system malfunctions and attacks the body's organs and tissues, in this case the joints.Researchers have described seven types of juvenile idiopathic arthritis. The types are distinguished by their signs and symptoms, the number of joints affected, the results of laboratory tests, and the family history.Systemic juvenile idiopathic arthritis causes inflammation in one or more joints. A high daily fever that lasts at least 2 weeks either precedes or accompanies the arthritis. Individuals with systemic arthritis may also have a skin rash or enlargement of the lymph nodes (lymphadenopathy), liver (hepatomegaly), or spleen (splenomegaly).Oligoarticular juvenile idiopathic arthritis (also known as oligoarthritis) is marked by the occurrence of arthritis in four or fewer joints in the first 6 months of the disease. It is divided into two subtypes depending on the course of disease. If the arthritis is confined to four or fewer joints after 6 months, then the condition is classified as persistent oligoarthritis. If more than four joints are affected after 6 months, this condition is classified as extended oligoarthritis. Individuals with oligoarthritis are at increased risk of developing inflammation of the eye (uveitis).Rheumatoid factor positive polyarticular juvenile idiopathic arthritis (also known as polyarthritis, rheumatoid factor positive) causes inflammation in five or more joints within the first 6 months of the disease. Individuals with this condition also have a positive blood test for proteins called rheumatoid factors. This type of arthritis closely resembles rheumatoid arthritis as seen in adults.Rheumatoid factor negative polyarticular juvenile idiopathic arthritis (also known as polyarthritis, rheumatoid factor negative) is also characterized by arthritis in five or more joints within the first 6 months of the disease. Individuals with this type, however, test negative for rheumatoid factor in the blood.Psoriatic juvenile idiopathic arthritis involves arthritis that usually occurs in combination with a skin disorder called psoriasis. Psoriasis is a condition characterized by patches of red, irritated skin that are often covered by flaky white scales. Some affected individuals develop psoriasis before arthritis while others first develop arthritis. Other features of psoriatic arthritis include abnormalities of the fingers and nails or eye problems.Enthesitis-related juvenile idiopathic arthritis is characterized by tenderness where the bone meets a tendon, ligament, or other connective tissue. The most commonly affected places are the hips, knees, and feet. This tenderness, known as enthesitis, accompanies the joint inflammation of arthritis. Enthesitis-related arthritis may also involve inflammation in parts of the body other than the joints.The last type of juvenile idiopathic arthritis is called undifferentiated arthritis. This classification is given to affected individuals who do not fit into any of the above types or who fulfill the criteria for more than one type of juvenile idiopathic arthritis. u Pattern unknown HLA-B https://medlineplus.gov/genetics/gene/hla-b FAS https://medlineplus.gov/genetics/gene/fas PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 HLA-DQB1 https://medlineplus.gov/genetics/gene/hla-dqb1 HLA-DQA1 https://medlineplus.gov/genetics/gene/hla-dqa1 STAT4 https://medlineplus.gov/genetics/gene/stat4 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 CCN6 https://medlineplus.gov/genetics/gene/ccn6 HLA-DPB1 https://medlineplus.gov/genetics/gene/hla-dpb1 RUNX1 https://medlineplus.gov/genetics/gene/runx1 ZFP36L1 https://www.ncbi.nlm.nih.gov/gene/677 CD247 https://www.ncbi.nlm.nih.gov/gene/919 CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 HLA-A https://www.ncbi.nlm.nih.gov/gene/3105 HLA-G https://www.ncbi.nlm.nih.gov/gene/3135 IL2RA https://www.ncbi.nlm.nih.gov/gene/3559 IL2RB https://www.ncbi.nlm.nih.gov/gene/3560 IL6 https://www.ncbi.nlm.nih.gov/gene/3569 MIF https://www.ncbi.nlm.nih.gov/gene/4282 PTPN2 https://www.ncbi.nlm.nih.gov/gene/5771 SLC11A1 https://www.ncbi.nlm.nih.gov/gene/6556 TNF https://www.ncbi.nlm.nih.gov/gene/7124 TNFAIP3 https://www.ncbi.nlm.nih.gov/gene/7128 TRAF1 https://www.ncbi.nlm.nih.gov/gene/7185 TYK2 https://www.ncbi.nlm.nih.gov/gene/7297 UBE2L3 https://www.ncbi.nlm.nih.gov/gene/7332 ANKRD55 https://www.ncbi.nlm.nih.gov/gene/79722 LACC1 https://www.ncbi.nlm.nih.gov/gene/144811 Arthritis, juvenile rheumatoid JIA JRA Juvenile chronic arthritis Juvenile RA Juvenile rheumatoid arthritis Systemic juvenile rheumatoid arthritis GTR C1858558 ICD-10-CM M08 ICD-10-CM M08.0 ICD-10-CM M08.00 ICD-10-CM M08.01 ICD-10-CM M08.011 ICD-10-CM M08.012 ICD-10-CM M08.019 ICD-10-CM M08.02 ICD-10-CM M08.021 ICD-10-CM M08.022 ICD-10-CM M08.029 ICD-10-CM M08.03 ICD-10-CM M08.031 ICD-10-CM M08.032 ICD-10-CM M08.039 ICD-10-CM M08.04 ICD-10-CM M08.041 ICD-10-CM M08.042 ICD-10-CM M08.049 ICD-10-CM M08.05 ICD-10-CM M08.051 ICD-10-CM M08.052 ICD-10-CM M08.059 ICD-10-CM M08.06 ICD-10-CM M08.061 ICD-10-CM M08.062 ICD-10-CM M08.069 ICD-10-CM M08.07 ICD-10-CM M08.071 ICD-10-CM M08.072 ICD-10-CM M08.079 ICD-10-CM M08.08 ICD-10-CM M08.09 ICD-10-CM M08.2 ICD-10-CM M08.20 ICD-10-CM M08.21 ICD-10-CM M08.211 ICD-10-CM M08.212 ICD-10-CM M08.219 ICD-10-CM M08.22 ICD-10-CM M08.221 ICD-10-CM M08.222 ICD-10-CM M08.229 ICD-10-CM M08.23 ICD-10-CM M08.231 ICD-10-CM M08.232 ICD-10-CM M08.239 ICD-10-CM M08.24 ICD-10-CM M08.241 ICD-10-CM M08.242 ICD-10-CM M08.249 ICD-10-CM M08.25 ICD-10-CM M08.251 ICD-10-CM M08.252 ICD-10-CM M08.259 ICD-10-CM M08.26 ICD-10-CM M08.261 ICD-10-CM M08.262 ICD-10-CM M08.269 ICD-10-CM M08.27 ICD-10-CM M08.271 ICD-10-CM M08.272 ICD-10-CM M08.279 ICD-10-CM M08.28 ICD-10-CM M08.29 ICD-10-CM M08.3 ICD-10-CM M08.4 ICD-10-CM M08.40 ICD-10-CM M08.41 ICD-10-CM M08.411 ICD-10-CM M08.412 ICD-10-CM M08.419 ICD-10-CM M08.42 ICD-10-CM M08.421 ICD-10-CM M08.422 ICD-10-CM M08.429 ICD-10-CM M08.43 ICD-10-CM M08.431 ICD-10-CM M08.432 ICD-10-CM M08.439 ICD-10-CM M08.44 ICD-10-CM M08.441 ICD-10-CM M08.442 ICD-10-CM M08.449 ICD-10-CM M08.45 ICD-10-CM M08.451 ICD-10-CM M08.452 ICD-10-CM M08.459 ICD-10-CM M08.46 ICD-10-CM M08.461 ICD-10-CM M08.462 ICD-10-CM M08.469 ICD-10-CM M08.47 ICD-10-CM M08.471 ICD-10-CM M08.472 ICD-10-CM M08.479 ICD-10-CM M08.48 ICD-10-CM M08.8 ICD-10-CM M08.80 ICD-10-CM M08.81 ICD-10-CM M08.811 ICD-10-CM M08.812 ICD-10-CM M08.819 ICD-10-CM M08.82 ICD-10-CM M08.821 ICD-10-CM M08.822 ICD-10-CM M08.829 ICD-10-CM M08.83 ICD-10-CM M08.831 ICD-10-CM M08.832 ICD-10-CM M08.839 ICD-10-CM M08.84 ICD-10-CM M08.841 ICD-10-CM M08.842 ICD-10-CM M08.849 ICD-10-CM M08.85 ICD-10-CM M08.851 ICD-10-CM M08.852 ICD-10-CM M08.859 ICD-10-CM M08.86 ICD-10-CM M08.861 ICD-10-CM M08.862 ICD-10-CM M08.869 ICD-10-CM M08.87 ICD-10-CM M08.871 ICD-10-CM M08.872 ICD-10-CM M08.879 ICD-10-CM M08.88 ICD-10-CM M08.89 ICD-10-CM M08.9 ICD-10-CM M08.90 ICD-10-CM M08.91 ICD-10-CM M08.911 ICD-10-CM M08.912 ICD-10-CM M08.919 ICD-10-CM M08.92 ICD-10-CM M08.921 ICD-10-CM M08.922 ICD-10-CM M08.929 ICD-10-CM M08.93 ICD-10-CM M08.931 ICD-10-CM M08.932 ICD-10-CM M08.939 ICD-10-CM M08.94 ICD-10-CM M08.941 ICD-10-CM M08.942 ICD-10-CM M08.949 ICD-10-CM M08.95 ICD-10-CM M08.951 ICD-10-CM M08.952 ICD-10-CM M08.959 ICD-10-CM M08.96 ICD-10-CM M08.961 ICD-10-CM M08.962 ICD-10-CM M08.969 ICD-10-CM M08.97 ICD-10-CM M08.971 ICD-10-CM M08.972 ICD-10-CM M08.979 ICD-10-CM M08.98 ICD-10-CM M08.99 MeSH D001171 OMIM 604302 SNOMED CT 201796004 SNOMED CT 239796000 SNOMED CT 410502007 2011-08 2024-10-02 Juvenile myoclonic epilepsy https://medlineplus.gov/genetics/condition/juvenile-myoclonic-epilepsy descriptionJuvenile myoclonic epilepsy is a condition characterized by recurrent seizures (epilepsy). This condition begins in childhood or adolescence, usually between ages 12 and 18, and lasts into adulthood. The most common type of seizure in people with this condition is myoclonic seizures, which cause rapid, uncontrolled muscle jerks. People with this condition may also have generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Sometimes, affected individuals have absence seizures, which cause loss of consciousness for a short period that appears as a staring spell. Typically, people with juvenile myoclonic epilepsy develop the characteristic myoclonic seizures in adolescence, then develop generalized tonic-clonic seizures a few years later. Although seizures can happen at any time, they occur most commonly in the morning, shortly after awakening. Seizures can be triggered by a lack of sleep, extreme tiredness, stress, or alcohol consumption. ar Autosomal recessive ad Autosomal dominant EFHC1 https://medlineplus.gov/genetics/gene/efhc1 GABRA1 https://medlineplus.gov/genetics/gene/gabra1 CLCN2 https://medlineplus.gov/genetics/gene/clcn2 CACNB4 https://www.ncbi.nlm.nih.gov/gene/785 GABRD https://www.ncbi.nlm.nih.gov/gene/2563 Adolescent myoclonic epilepsy Janz syndrome Petit mal, impulsive GTR C0270853 GTR C2750887 GTR C2750893 GTR C2751603 GTR C4013473 ICD-10-CM G40.B01 ICD-10-CM G40.B09 ICD-10-CM G40.B11 ICD-10-CM G40.B19 MeSH D020190 OMIM 254770 OMIM 607628 OMIM 607682 OMIM 611136 OMIM 613060 OMIM 614280 SNOMED CT 6204001 2012-06 2023-04-28 Juvenile polyposis syndrome https://medlineplus.gov/genetics/condition/juvenile-polyposis-syndrome descriptionJuvenile polyposis syndrome is a disorder characterized by multiple noncancerous (benign) growths called juvenile polyps. People with juvenile polyposis syndrome typically develop polyps before age 20; however, in the name of this condition "juvenile" refers to the characteristics of the tissues that make up the polyp, not the age of the affected individual. These growths occur in the gastrointestinal tract, typically in the large intestine (colon). The number of polyps varies from only a few to hundreds, even among affected members of the same family. Polyps may cause gastrointestinal bleeding, a shortage of red blood cells (anemia), abdominal pain, and diarrhea. Approximately 15 percent of people with juvenile polyposis syndrome have other abnormalities, such as a twisting of the intestines (intestinal malrotation), heart or brain abnormalities, an opening in the roof of the mouth (cleft palate), extra fingers or toes (polydactyly), and abnormalities of the genitalia or urinary tract.Juvenile polyposis syndrome is diagnosed when a person has any one of the following: (1) more than five juvenile polyps of the colon or rectum; (2) juvenile polyps in other parts of the gastrointestinal tract; or (3) any number of juvenile polyps and one or more affected family members. Single juvenile polyps are relatively common in children and are not characteristic of juvenile polyposis syndrome.Three types of juvenile polyposis syndrome have been described, based on the signs and symptoms of the disorder. Juvenile polyposis of infancy is characterized by polyps that occur throughout the gastrointestinal tract during infancy. Juvenile polyposis of infancy is the most severe form of the disorder and is associated with the poorest outcome. Children with this type may develop a condition called protein-losing enteropathy. This condition results in severe diarrhea, failure to gain weight and grow at the expected rate (failure to thrive), and general wasting and weight loss (cachexia). Another type called generalized juvenile polyposis is diagnosed when polyps develop throughout the gastrointestinal tract. In the third type, known as juvenile polyposis coli, affected individuals develop polyps only in their colon. People with generalized juvenile polyposis and juvenile polyposis coli typically develop polyps during childhood.Most juvenile polyps are benign, but there is a chance that polyps can become cancerous (malignant). It is estimated that people with juvenile polyposis syndrome have a 10 to 50 percent risk of developing a cancer of the gastrointestinal tract. The most common type of cancer seen in people with juvenile polyposis syndrome is colorectal cancer. ad Autosomal dominant SMAD4 https://medlineplus.gov/genetics/gene/smad4 BMPR1A https://medlineplus.gov/genetics/gene/bmpr1a JIP JPS Juvenile intestinal polyposis GTR C0345893 ICD-10-CM D12.6 MeSH D044483 OMIM 174900 SNOMED CT 9273005 2009-05 2020-08-18 Juvenile primary lateral sclerosis https://medlineplus.gov/genetics/condition/juvenile-primary-lateral-sclerosis descriptionJuvenile primary lateral sclerosis is a rare disorder characterized by progressive weakness and tightness (spasticity) of muscles in the arms, legs, and face. The features of this disorder are caused by damage to motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement.Symptoms of juvenile primary lateral sclerosis begin in early childhood and progress slowly over many years. Early symptoms include clumsiness, muscle weakness and spasticity in the legs, and difficulty with balance. As symptoms progress, the spasticity spreads to the arms and hands and individuals develop slurred speech, drooling, difficulty swallowing, and an inability to walk. ar Autosomal recessive ALS2 https://medlineplus.gov/genetics/gene/als2 ERLIN2 https://www.ncbi.nlm.nih.gov/gene/11160 JPLS Juvenile PLS PLSJ Primary lateral sclerosis, juvenile GTR C1853396 MeSH D016472 OMIM 606353 SNOMED CT 717964007 2007-05 2020-08-18 Juvenile primary osteoporosis https://medlineplus.gov/genetics/condition/juvenile-primary-osteoporosis descriptionJuvenile primary osteoporosis is a skeletal disorder characterized by thinning of the bones (osteoporosis) that begins in childhood. Osteoporosis is caused by a shortage of calcium and other minerals in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple fractures in the long bones of the arms and legs, especially in the regions where new bone forms (metaphyses). They also have fractures in the bones that form the spine (vertebrae), which can cause collapse of the affected vertebrae (compressed vertebrae). Multiple fractures can cause bone pain and lead to movement problems. ad Autosomal dominant LRP5 https://medlineplus.gov/genetics/gene/lrp5 Childhood-onset primary osteoporosis Idiopathic juvenile osteoporosis GTR C1866079 MeSH D010024 SNOMED CT 240156000 2013-01 2020-08-18 KBG syndrome https://medlineplus.gov/genetics/condition/kbg-syndrome descriptionKBG syndrome is a rare disorder that affects several body systems. "KBG" represents the surname initials of the first families diagnosed with the disorder. Common signs and symptoms in individuals with this condition include unusual facial features, skeletal abnormalities, and intellectual disability.A characteristic feature of KBG syndrome is unusually large upper front teeth (macrodontia). Other distinctive facial features include a wide, short skull (brachycephaly), a triangular face shape, widely spaced eyes (hypertelorism), wide eyebrows that may grow together in the middle (synophrys), a prominent nasal bridge, a long space between the nose and upper lip (long philtrum), and a thin upper lip.A common skeletal abnormality in people with KBG syndrome is slowed mineralization of bones (delayed bone age); for example, an affected 3-year-old child may have bones more typical of a child of 2. In addition, affected individuals can have abnormalities of the bones of the spine (vertebrae) and ribs. They can also have abnormalities of the bones of the hands or feet, including unusually short or curved fifth (pinky) fingers (brachydactyly or clinodactyly, respectively) and flat feet (pes planus). Most affected individuals are shorter than average from birth.Development of mental and movement abilities is also delayed in KBG syndrome. Most affected individuals learn to speak and walk later than normal and have mild to moderate intellectual disability. Most people with this condition have neurodevelopmental disorders, such as hyperactivity; anxiety; or autism spectrum disorder, which is characterized by impaired communication and social interactions.Less common features of KBG syndrome include hearing loss, seizures, and heart defects. ad Autosomal dominant ANKRD11 https://medlineplus.gov/genetics/gene/ankrd11 Macrodontia, mental retardation, characteristic facies, short stature, and skeletal anomalies Short stature, characteristic facies, macrodontia, mental retardation, and skeletal anomalies Short stature-characteristic facies-mental retardation-macrodontia-skeletal anomalies syndrome GTR C0220687 MeSH D000015 OMIM 148050 SNOMED CT 711156009 2015-01 2023-08-02 KCNK9 imprinting syndrome https://medlineplus.gov/genetics/condition/kcnk9-imprinting-syndrome descriptionKCNK9 imprinting syndrome is a rare condition characterized by weak muscle tone (hypotonia) from birth. As a result, affected infants have a lack of energy (lethargy), a weak cry, and they move less than normal. Facial weakness and a poor ability to suck cause feeding difficulties, which can lead to an inability to grow and gain weight (failure to thrive). Difficulty swallowing (dysphagia) often lasts into adolescence. While muscle tone may improve over time, affected individuals usually have some weakness into adulthood. The weakness can lead to permanently bent joints (contractures) and abnormal curvature of the spine (scoliosis).KCNK9 imprinting syndrome is also characterized by intellectual disability and delayed development of speech and motor skills, such as sitting and walking. Many affected individuals have limited speech throughout life.This condition is associated with unusual facial features, including an elongated face that narrows at the temples; an upper lip that points outward (called a tented lip); a short, broad space between the lip and the nose (philtrum); a small lower jaw (micrognathia); and abnormally shaped eyebrows. Some affected individuals have an opening in the roof of the mouth (cleft palate). In addition to unusual facial features, some people with KCNK9 imprinting syndrome have a long neck, a narrow chest, and tapered fingers. ad Autosomal dominant KCNK9 https://medlineplus.gov/genetics/gene/kcnk9 Birk-Barel mental retardation dysmorphism syndrome Birk-Barel syndrome Intellectual disability, Birk-Barel type Intellectual disability-hypotonia-facial dysmorphism syndrome Mental retardation with hypotonia and facial dysmorphism GTR C2676770 MeSH D008607 OMIM 612292 2017-06 2020-08-18 Kabuki syndrome https://medlineplus.gov/genetics/condition/kabuki-syndrome descriptionKabuki syndrome is a disorder that can affect many parts of the body. It is characterized by distinctive facial features including arched eyebrows; long eyelashes; long openings of the eyelids (long palpebral fissures) with the lower lids turned out (everted) at the outside edges; a flat, broadened tip of the nose; and large protruding earlobes. The name of this disorder comes from the resemblance of its characteristic facial appearance to stage makeup used in traditional Japanese Kabuki theater.People with Kabuki syndrome may have mild to severe developmental delay and intellectual disability. Affected individuals may also have seizures, an unusually small head size (microcephaly), or weak muscle tone (hypotonia). Some have eye problems such as rapid, involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).Other characteristic features of Kabuki syndrome include short stature and skeletal abnormalities such as abnormal side-to-side curvature of the spine (scoliosis), short fifth (pinky) fingers, or problems with the hip and knee joints. The roof of the mouth may have an abnormal opening (cleft palate) or be high and arched, and dental problems are common in affected individuals. People with Kabuki syndrome may also have fingerprints with unusual features and fleshy pads at the tips of the fingers. These prominent finger pads are called fetal finger pads because they normally occur in human fetuses; in most people they disappear before birth.A wide variety of other health problems occur in some people with Kabuki syndrome. Among the most commonly reported are heart abnormalities, frequent ear infections (otitis media), hearing loss, and early puberty. ad Autosomal dominant KMT2D https://medlineplus.gov/genetics/gene/kmt2d KDM6A https://medlineplus.gov/genetics/gene/kdm6a Kabuki make-up syndrome Kabuki makeup syndrome KMS Niikawa-Kuroki syndrome GTR C3275495 GTR CN030661 MeSH D000015 OMIM 147920 OMIM 300867 SNOMED CT 313426007 2013-10 2022-11-01 Kallmann syndrome https://medlineplus.gov/genetics/condition/kallmann-syndrome descriptionKallmann syndrome is a condition characterized by delayed or absent puberty and an impaired sense of smell.This disorder is a form of hypogonadotropic hypogonadism, which is a condition resulting from a lack of production of certain hormones that direct sexual development. These hormones are normally made in a part of the brain called the hypothalamus. Males born with hypogonadotropic hypogonadism often have an unusually small penis (micropenis) and undescended testes (cryptorchidism). At puberty, most affected individuals do not develop secondary sex characteristics, such as the growth of facial hair and deepening of the voice in males, the start of monthly periods (menstruation) and breast development in females, and a growth spurt in both sexes. Without treatment, most affected men and women are unable to have biological children (infertile).In Kallmann syndrome, the sense of smell is either diminished (hyposmia) or completely absent (anosmia). This feature distinguishes Kallmann syndrome from most other forms of hypogonadotropic hypogonadism, which do not affect the sense of smell. Many people with Kallmann syndrome are not aware that they are unable to detect odors until the impairment is discovered through testing.Kallmann syndrome can have a wide variety of additional signs and symptoms. These include a failure of one kidney to develop (unilateral renal agenesis), abnormalities of bones in the fingers or toes, a cleft lip with or without an opening in the roof of the mouth (a cleft palate), abnormal eye movements, hearing loss, and abnormalities of tooth development. Some affected individuals have a feature called bimanual synkinesis, in which the movements of one hand are mirrored by the other hand. Bimanual synkinesis can make it difficult to do tasks that require the hands to move separately, such as playing a musical instrument. ad Autosomal dominant ar Autosomal recessive xr X-linked recessive FGFR1 https://medlineplus.gov/genetics/gene/fgfr1 SOX10 https://medlineplus.gov/genetics/gene/sox10 ANOS1 https://medlineplus.gov/genetics/gene/anos1 PROKR2 https://medlineplus.gov/genetics/gene/prokr2 PROK2 https://medlineplus.gov/genetics/gene/prok2 CHD7 https://medlineplus.gov/genetics/gene/chd7 FGF8 https://medlineplus.gov/genetics/gene/fgf8 AXL https://www.ncbi.nlm.nih.gov/gene/558 DUSP6 https://www.ncbi.nlm.nih.gov/gene/1848 SEMA7A https://www.ncbi.nlm.nih.gov/gene/8482 FGF17 https://www.ncbi.nlm.nih.gov/gene/8822 HS6ST1 https://www.ncbi.nlm.nih.gov/gene/9394 SEMA3A https://www.ncbi.nlm.nih.gov/gene/10371 FLRT3 https://www.ncbi.nlm.nih.gov/gene/23767 NSMF https://www.ncbi.nlm.nih.gov/gene/26012 IL17RD https://www.ncbi.nlm.nih.gov/gene/54756 WDR11 https://www.ncbi.nlm.nih.gov/gene/55717 SPRY4 https://www.ncbi.nlm.nih.gov/gene/81848 CCDC141 https://www.ncbi.nlm.nih.gov/gene/285025 FEZF1 https://www.ncbi.nlm.nih.gov/gene/389549 Anosmic hypogonadism Anosmic idiopathic hypogonadotropic hypogonadism Hypogonadism with anosmia Hypogonadotropic hypogonadism and anosmia Hypogonadotropic hypogonadism-anosmia syndrome Kallman's syndrome GTR C0162809 GTR C1563719 GTR C1563720 GTR C3550478 GTR C3552343 GTR C3552553 GTR C3552574 MeSH D017436 OMIM 147950 OMIM 244200 OMIM 308700 OMIM 308750 OMIM 610628 SNOMED CT 93559003 2016-12 2020-08-18 Kaufman oculocerebrofacial syndrome https://medlineplus.gov/genetics/condition/kaufman-oculocerebrofacial-syndrome descriptionKaufman oculocerebrofacial syndrome is a disorder characterized by eye problems (oculo-), intellectual disability (-cerebro-), and a distinctive pattern of facial features (-facial).Most individuals with Kaufman oculocerebrofacial syndrome have an unusually small head size (microcephaly), and some have structural abnormalities of the brain. Affected individuals have weak muscle tone (hypotonia), and are delayed in developing motor skills such as walking. Intellectual disability is severe or profound. Most affected individuals never acquire the ability to speak.Eye abnormalities and their effect on vision vary among people with Kaufman oculocerebrofacial syndrome. Some people with this disorder have abnormally small or poorly developed eyes (microphthalmia); microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved; missing pieces of tissue in structures that form the eye (coloboma); or underdevelopment of the nerves that carry signals between the eyes and the brain (optic nerve hypoplasia). Eyes that do not look in the same direction (strabismus), nearsightedness (myopia) or farsightedness (hyperopia), or an inward turning of the lower eyelid (entropion) can also occur.Individuals with Kaufman oculocerebrofacial syndrome typically have a characteristic pattern of facial features. These include highly arched eyebrows, an increased distance between the inner corners of the eyes (telecanthus), a narrowing of the eye opening (blepharophimosis), skin folds covering the inner corner of the eyes (epicanthal folds), droopy eyelids (ptosis), and outside corners of the eyes that point upward (upslanting palpebral fissures). Ear abnormalities include low-set ears with small lobes and growths of skin (skin tags) in front of the ear (preauricular tags). The nose has a narrow bridge, a wide base, and nostrils that open to the front rather than downward (anteverted nares). Affected individuals may also have flat cheeks; a space between the nose and upper lip (philtrum) that is unusually long and smooth; a narrow mouth; and an unusually small jaw (micrognathia).Other signs and symptoms that can occur in people with this disorder include short stature; hearing loss; and abnormalities of the heart, respiratory tract, gastrointestinal tract, kidneys, genitals, or skeleton. Affected individuals can live into adulthood; however, their average life expectancy is unknown because of the small number of people who have been diagnosed with this disorder. ar Autosomal recessive UBE3B https://medlineplus.gov/genetics/gene/ube3b Blepharophimosis-ptosis-intellectual disability syndrome BPIDS KOS Oculocerebrofacial syndrome, Kaufman type GTR C1855663 MeSH D000015 OMIM 244450 SNOMED CT 722056009 2017-01 2020-08-18 Kawasaki disease https://medlineplus.gov/genetics/condition/kawasaki-disease descriptionKawasaki disease is a sudden and time-limited (acute) illness that affects infants and young children. Affected children develop a prolonged fever lasting several days, a skin rash, and swollen lymph nodes in the neck (cervical lymphadenopathy). They also develop redness in the whites of the eyes (conjunctivitis) and redness (erythema) of the lips, lining of the mouth (oral mucosa), tongue, palms of the hands, and soles of the feet.Without treatment, 15 to 25 percent of individuals with Kawasaki disease develop bulging and thinning of the walls of the arteries that supply blood to the heart muscle (coronary artery aneurysms) or other damage to the coronary arteries, which can be life-threatening. u Pattern unknown ITPKC https://medlineplus.gov/genetics/gene/itpkc Acute febrile mucocutaneous lymph node syndrome Kawasaki syndrome KD Mucocutaneous lymph node syndrome GTR C0026691 ICD-10-CM M30.3 MeSH D009080 OMIM 611775 SNOMED CT 75053002 2011-06 2020-08-18 Kearns-Sayre syndrome https://medlineplus.gov/genetics/condition/kearns-sayre-syndrome descriptionKearns-Sayre syndrome is a condition that affects many parts of the body, especially the eyes. The features of Kearns-Sayre syndrome usually appear before age 20, and the condition is diagnosed by a few characteristic signs and symptoms. People with Kearns-Sayre syndrome have progressive external ophthalmoplegia, which is weakness or paralysis of the eye muscles that impairs eye movement and causes drooping eyelids (ptosis). Affected individuals also have an eye condition called pigmentary retinopathy, which results from breakdown (degeneration) of the light-sensing tissue at the back of the eye (the retina) that gives it a speckled and streaked appearance. The retinopathy may cause loss of vision. In addition, people with Kearns-Sayre syndrome have at least one of the following signs or symptoms: abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects), problems with coordination and balance that cause unsteadiness while walking (ataxia), or abnormally high levels of protein in the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF).People with Kearns-Sayre syndrome may also experience muscle weakness in their limbs, deafness, kidney problems, or a deterioration of cognitive functions (dementia). Affected individuals often have short stature. In addition, diabetes mellitus is occasionally seen in people with Kearns-Sayre syndrome.When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. The abnormal muscle cells contain an excess of structures called mitochondria and are known as ragged-red fibers.A related condition called ophthalmoplegia-plus may be diagnosed if an individual has many of the signs and symptoms of Kearns-Sayre syndrome but not all the criteria are met. m mitochondrial mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Kearns-Sayre mitochondrial cytopathy KSS GTR C0022541 ICD-10-CM H49.81 ICD-10-CM H49.811 ICD-10-CM H49.812 ICD-10-CM H49.813 ICD-10-CM H49.819 MeSH D007625 OMIM 530000 SNOMED CT 25792000 2011-12 2020-09-08 Keratitis-ichthyosis-deafness syndrome https://medlineplus.gov/genetics/condition/keratitis-ichthyosis-deafness-syndrome descriptionKeratitis-ichthyosis-deafness (KID) syndrome is characterized by eye problems, skin abnormalities, and hearing loss.People with KID syndrome usually have keratitis, which is inflammation of the front surface of the eye (the cornea). The keratitis may cause pain, increased sensitivity to light (photophobia), abnormal blood vessel growth over the cornea (neovascularization), and scarring. Over time, affected individuals experience a loss of sharp vision (reduced visual acuity); in severe cases the keratitis can lead to blindness.Most people with KID syndrome have thick, hard skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Affected individuals also have thick, reddened patches of skin (erythrokeratoderma) that are dry and scaly (ichthyosis). These dry patches can occur anywhere on the body, although they most commonly affect the neck, groin, and armpits. Breaks in the skin often occur and may lead to infections. In severe cases these infections can be life-threatening, especially in infancy. Approximately 12 percent of people with KID syndrome develop a type of skin cancer called squamous cell carcinoma, which may also affect mucous membranes such as the lining of the mouth.Partial hair loss is a common feature of KID syndrome, and often affects the eyebrows and eyelashes. Affected individuals may also have small, abnormally formed nails.Hearing loss in this condition is usually profound, but occasionally is less severe. ar Autosomal recessive ad Autosomal dominant GJB2 https://medlineplus.gov/genetics/gene/gjb2 Ichthyosiform erythroderma, corneal involvement, and deafness Keratitis, ichthyosis, and deafness KID syndrome GTR C0265336 GTR C1275089 MeSH D007634 OMIM 148210 OMIM 242150 SNOMED CT 239059004 SNOMED CT 403780007 2012-11 2020-08-18 Keratoconus https://medlineplus.gov/genetics/condition/keratoconus descriptionKeratoconus is an eye condition that affects the shape of the cornea, which is the clear outer covering of the eye. In this condition, the cornea thins and bulges outward, eventually resembling a cone shape. These corneal abnormalities, which worsen over time, can lead to nearsightedness (myopia), blurred vision that cannot be improved with corrective lenses (irregular astigmatism), and vision loss.Other corneal changes typical of keratoconus that can be seen during an eye exam include iron deposits in the cornea that form a yellow-to-brownish ring, called the Fleischer ring, surrounding the colored part of the eye (iris). Affected individuals may also develop Vogt's striae, which are thin, vertical, white lines in the tissue at the back of the cornea.Keratoconus may affect only one eye at first, but eventually the corneas of both eyes become misshapen, although they might not be affected with the same severity. As keratoconus worsens, people with this condition can develop corneal scarring, often caused by exposure of the abnormally thin cornea to prolonged contact lens use or excessive eye rubbing.The eye changes characteristic of keratoconus typically begin in adolescence and slowly worsen until mid-adulthood at which point the shape of the cornea remains stable. ar Autosomal recessive n Not inherited ad Autosomal dominant COL5A1 https://medlineplus.gov/genetics/gene/col5a1 COL4A3 https://medlineplus.gov/genetics/gene/col4a3 COL4A4 https://medlineplus.gov/genetics/gene/col4a4 IL1A https://medlineplus.gov/genetics/gene/il1a TGFBI https://medlineplus.gov/genetics/gene/tgfbi RAB3GAP1 https://medlineplus.gov/genetics/gene/rab3gap1 WNT10A https://medlineplus.gov/genetics/gene/wnt10a CAST https://www.ncbi.nlm.nih.gov/gene/831 FOXO1 https://www.ncbi.nlm.nih.gov/gene/2308 HGF https://www.ncbi.nlm.nih.gov/gene/3082 IL1RN https://www.ncbi.nlm.nih.gov/gene/3557 LOX https://www.ncbi.nlm.nih.gov/gene/4015 ZEB1 https://www.ncbi.nlm.nih.gov/gene/6935 DOCK9 https://www.ncbi.nlm.nih.gov/gene/23348 VSX1 https://www.ncbi.nlm.nih.gov/gene/30813 FNDC3B https://www.ncbi.nlm.nih.gov/gene/64778 SLC4A11 https://www.ncbi.nlm.nih.gov/gene/83959 ZNF469 https://www.ncbi.nlm.nih.gov/gene/84627 MIR184 https://www.ncbi.nlm.nih.gov/gene/406960 Bulging cornea Conical cornea KC GTR C1835677 ICD-10-CM H18.6 MeSH D007640 OMIM 148300 OMIM 608586 OMIM 608932 OMIM 609271 OMIM 614622 OMIM 614623 OMIM 614628 OMIM 614629 SNOMED CT 65636009 2017-07 2020-08-18 Keratoderma with woolly hair https://medlineplus.gov/genetics/condition/keratoderma-with-woolly-hair descriptionKeratoderma with woolly hair is a group of related conditions that affect the skin and hair and in many cases increase the risk of potentially life-threatening heart problems. People with these conditions have hair that is unusually coarse, dry, fine, and tightly curled. In some cases, the hair is also sparse. The woolly hair texture typically affects only scalp hair and is present from birth. Starting early in life, affected individuals also develop palmoplantar keratoderma, a condition that causes skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused.Cardiomyopathy, which is a disease of the heart muscle, is a life-threatening health problem that can develop in people with keratoderma with woolly hair. Unlike the other features of this condition, signs and symptoms of cardiomyopathy may not appear until adolescence or later. Complications of cardiomyopathy can include an abnormal heartbeat (arrhythmia), heart failure, and sudden death.Keratoderma with woolly hair comprises several related conditions with overlapping signs and symptoms. Researchers have recently proposed classifying keratoderma with woolly hair into four types, based on the underlying genetic cause. Type I, also known as Naxos disease, is characterized by palmoplantar keratoderma, woolly hair, and a form of cardiomyopathy called arrhythmogenic right ventricular cardiomyopathy (ARVC). Type II, also known as Carvajal syndrome, has hair and skin abnormalities similar to type I but features a different form of cardiomyopathy, called dilated left ventricular cardiomyopathy. Type III also has signs and symptoms similar to those of type I, including ARVC, although the hair and skin abnormalities are often milder. Type IV is characterized by palmoplantar keratoderma and woolly and sparse hair, as well as abnormal fingernails and toenails. Type IV does not appear to cause cardiomyopathy. ar Autosomal recessive DSC2 https://medlineplus.gov/genetics/gene/dsc2 DSP https://medlineplus.gov/genetics/gene/dsp JUP https://medlineplus.gov/genetics/gene/jup KANK2 https://medlineplus.gov/genetics/gene/kank2 KWWH GTR C1832600 GTR C1864850 GTR C4014393 GTR C4015202 MeSH D006201 MeSH D007645 MeSH D009202 OMIM 601214 OMIM 605676 OMIM 610476 OMIM 615821 OMIM 616099 SNOMED CT 52564001 2015-11 2024-10-02 Kidney stones https://medlineplus.gov/genetics/condition/kidney-stones descriptionKidney stones (also called renal stones or urinary stones) are small, hard deposits that form in one or both kidneys; the stones are made up of minerals or other compounds found in urine. Kidney stones vary in size, shape, and color. To be cleared from the body (or "passed"), the stones need to travel through ducts that carry urine from the kidneys to the bladder (ureters) and be excreted. Depending on their size, kidney stones generally take days to weeks to pass out of the body.Kidney stones can cause abdominal or back pain (known as renal colic). Renal colic usually begins sporadically but then becomes constant and can lead to nausea and vomiting. The site of pain can change as the stone moves through the urinary tract. Some small stones pass through the kidney and urinary tract with little discomfort, while larger ones can block the flow of urine and impair kidney function. Kidney stones can also result in blood in the urine (hematuria) or kidney or urinary tract infections. Unusually large stones or stones that are difficult to pass can be medically removed.Although there are many types of kidney stones, four main types are classified by the material they are made of. Up to 75 percent of all kidney stones are composed primarily of calcium. Stones can also be made up of uric acid (a normal waste product), cystine (a protein building block), or struvite (a phosphate mineral). Stones form when there is more of the compound in the urine than can be dissolved. This imbalance can occur when there is an increased amount of the material in the urine, a reduced amount of liquid urine, or a combination of both.People are most likely to develop kidney stones between ages 40 and 60, though the stones can appear at any age. Research shows that 35 to 50 percent of people who have one kidney stone will develop additional stones, usually within 10 years of the first stone. u Pattern unknown n Not inherited FGF23 https://medlineplus.gov/genetics/gene/fgf23 CASR https://medlineplus.gov/genetics/gene/casr KL https://medlineplus.gov/genetics/gene/kl IL1RN https://www.ncbi.nlm.nih.gov/gene/3557 SPP1 https://www.ncbi.nlm.nih.gov/gene/6696 SLC26A1 https://www.ncbi.nlm.nih.gov/gene/10861 CLDN14 https://www.ncbi.nlm.nih.gov/gene/23562 ORAI1 https://www.ncbi.nlm.nih.gov/gene/84876 Calculus of kidney Calculus, kidney Calculus, renal Kidney calculi Kidney stone Nephrolith Nephrolithiasis Renal calculi Renal calculus Renal lithiasis Renal stones Urinary stones Urolithiasis GTR CN580796 ICD-10-CM N20.0 MeSH D007669 OMIM 167030 SNOMED CT 95570007 2019-01 2026-03-16 Kindler epidermolysis bullosa https://medlineplus.gov/genetics/condition/kindler-epidermolysis-bullosa descriptionKindler epidermolysis bullosa (or Kindler EB) is a rare type of epidermolysis bullosa, which is a group of genetic conditions that cause the skin to be very fragile and to blister easily.From early infancy, people with Kindler EB have skin blistering, particularly on the backs of the hands and the tops of the feet. The blisters occur less frequently over time, although repeated blistering on the hands can cause scarring that fuses the skin between the fingers and between the toes. Affected individuals also develop thin, papery skin starting on the hands and feet and later affecting other parts of the body; changes in skin coloring; and small clusters of visible blood vessels just under the skin (telangiectases). This combination of features is known as poikiloderma. In some affected individuals, the skin on the palms of the hands and soles of the feet thickens and hardens (hyperkeratosis). Kindler EB can also cause people to be highly sensitive to ultraviolet (UV) rays from the sun and to sunburn easily.Kindler EB can also affect the moist lining (mucosae) of the mouth, eyes, esophagus, intestines, genitals, and urinary system, causing these tissues to be very fragile and easily damaged. Affected individuals commonly develop severe gum disease that can lead to early tooth loss. The moist tissues that line the eyelids and the white part of the eyes (the conjunctiva) can become inflamed (conjunctivitis), and damage to the clear outer covering of the eye (the cornea) can affect vision. Narrowing (stenosis) of the esophagus, which is the tube that carries food from the mouth to the stomach, causes difficulty with swallowing that worsens over time. Some affected individuals develop health problems related to inflammation of the colon (colitis) or damage to the mucosa in the vagina, the anus, or the tube that carries urine from the bladder out of the body (the urethra).Kindler EB increases the risk of developing a form of cancer called squamous cell carcinoma. This type of cancer arises from squamous cells, which are found in the outer layer of skin (the epidermis) and in the mucosae. In people with Kindler EB, squamous cell carcinoma occurs most often on the skin, lips, and the lining of the mouth (oral mucosa). ar Autosomal recessive FERMT1 https://medlineplus.gov/genetics/gene/fermt1 Congenital bullous poikiloderma Kindler syndrome Kindler's syndrome Poikiloderma of Kindler GTR C0406557 ICD-10-CM MeSH D004820 OMIM 173650 SNOMED CT 238836000 2016-06 2023-03-17 Kleefstra syndrome https://medlineplus.gov/genetics/condition/kleefstra-syndrome descriptionKleefstra syndrome is a disorder that involves many parts of the body. Characteristic features of Kleefstra syndrome include developmental delay and intellectual disability, severely limited or absent speech, and weak muscle tone (hypotonia). Affected individuals also have an unusually small head size (microcephaly) and a wide, short skull (brachycephaly). Distinctive facial features include eyebrows that grow together in the middle (synophrys), widely spaced eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), nostrils that open to the front rather than downward (anteverted nares), a protruding jaw (prognathism), rolled out (everted) lips, and a large tongue (macroglossia). Affected individuals may have a high birth weight and childhood obesity.People with Kleefstra syndrome may also have structural brain abnormalities, congenital heart defects, genitourinary abnormalities, seizures, and a tendency to develop severe respiratory infections. During childhood they may exhibit features of autism or related developmental disorders affecting communication and social interaction. In adolescence, they may develop a general loss of interest and enthusiasm (apathy) or unresponsiveness (catatonia). ad Autosomal dominant EHMT1 https://medlineplus.gov/genetics/gene/ehmt1 9 https://medlineplus.gov/genetics/chromosome/9 9q subtelomeric deletion syndrome 9q- syndrome 9q34.3 deletion syndrome 9q34.3 microdeletion syndrome Chromosome 9q deletion syndrome GTR C0795833 MeSH D025063 OMIM 610253 SNOMED CT 724207001 2011-02 2020-09-08 Klinefelter syndrome https://medlineplus.gov/genetics/condition/klinefelter-syndrome descriptionKlinefelter syndrome, also called 47,XXY, is a chromosomal condition that affects male development. The signs and symptoms of Klinefelter syndrome vary. In some cases, the features are so mild that the condition is not diagnosed until puberty or adulthood. Researchers believe that up to 65 percent of people with Klinefelter syndrome are never diagnosed.Individuals with Klinefelter syndrome typically have small testes that produce a reduced amount of testosterone (primary testicular insufficiency). Testosterone is the hormone that directs male sexual development before birth and during puberty. A small percentage of affected individuals are born with undescended testes (cryptorchidism). Without treatment, the shortage of testosterone can lead to delayed or incomplete puberty, breast enlargement (gynecomastia), decreased muscle mass, decreased bone density, a reduced amount of facial and body hair, and fatigue. Klinefelter syndrome can make it difficult for people with this condition to have biological children (a condition called infertility), but up to half of people with Klinefelter syndrome may be able to have children using assisted reproductive technologies.. The other physical changes associated with Klinefelter syndrome are usually subtle. Most commonly, affected individuals are taller than average and 2 to 3 inches taller than would be expected for their family. Other features can include curved pinky fingers (fifth finger clinodactyly), flat feet (pes planus), and, less commonly, abnormal fusion of certain bones in the forearm (radioulnar synostosis).Children with Klinefelter syndrome may have low muscle tone (hypotonia), difficulty coordinating movements, and mild delays of certain developmental skills, such as rolling over or walking. Affected children have an increased risk of mild delays in speech and language development. People with Klinefelter syndrome tend to have better receptive language skills (the ability to understand speech) than expressive language skills (vocabulary and the production of speech) and may have difficulty communicating and expressing themselves. Affected individuals have an increased risk for learning disabilities, most commonly problems with reading (dyslexia) and written expression. People with Klinefelter syndrome very rarely have intellectual disabilities. Individuals with Klinefelter syndrome may have have anxiety, depression,  impaired social skills, or behavioral differences, such as emotional immaturity during childhood or difficulty with frustration. Affected individuals also have an increased risk for attention-deficit/hyperactivity disorder (ADHD), though they tend to have problems with attention and distractability rather than hyperactivity. People with Klinefelter syndrome are more likely than those without Klinefelter syndrome to have autism spectrum disorder, which is a developmental disorder that affects communication and social interaction.People with Klinefelter syndrome have an increased risk of developing metabolic syndrome, which is a group of conditions that include high blood glucose levels during prolonged periods without food (fasting), high blood pressure (hypertension), increased belly fat, and high levels of fats (lipids) such as cholesterol and triglycerides in the blood. Compared with unaffected people, adults with Klinefelter syndrome also have an increased risk of developing involuntary trembling (tremors) in their arms or hands, breast cancer (if gynecomastia develops), thinning and weakening of the bones (osteoporosis), and autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. Autoimmune disorders are a large group of conditions that occur when the immune system attacks the body's own tissues and organs. n Not inherited X https://medlineplus.gov/genetics/chromosome/x 47,XXY syndrome Klinefelter syndrome (KS) Klinefelter's syndrome XXY syndrome XXY trisomy GTR C0022735 ICD-10-CM Q98.0 ICD-10-CM Q98.1 ICD-10-CM Q98.4 MeSH D007713 SNOMED CT 205700008 SNOMED CT 22053006 SNOMED CT 405769009 2023-07 2025-03-06 Klippel-Feil syndrome https://medlineplus.gov/genetics/condition/klippel-feil-syndrome descriptionKlippel-Feil syndrome is a bone disorder that is characterized by the abnormal joining (fusion) of two or more spinal bones in the neck (cervical vertebrae). The vertebral fusion is present from birth. Cases of Klippel-Feil syndrome may be classified using the Samartzis classification system. This system divides the condition into three types based on the number of fused vertebrae and whether the fused vertebrae are next to each other (contiguous). According to the Samartzis classification, type I involves a single fusion of two vertebrae, type II involves multiple fused vertebrae that are not contiguous, and type III involves multiple fused vertebrae that are contiguous.Klippel-Feil syndrome has been described as having three classic features: a short neck, the appearance of a low hairline at the back of the head, and a limited range of motion in the neck. However, less than half of the individuals who have been diagnosed with Klippel-Feil syndrome have all three features. People with Klippel-Feil syndrome may have additional signs and symptoms, and these can vary greatly among affected individuals. Some people with Klippel-Feil syndrome do not have any signs or symptoms.The fused vertebrae in people with Klippel-Feil syndrome can cause health problems. These include chronic headaches; muscle pain; and an involuntary tensing of the neck, which causes the head to tilt or turn (torticollis). Because some of the cervical vertebrae are fused, this region of the neck can become unstable, which increases the risk of damage to the spinal cord. The fused area of the spine may be more susceptible to trauma, such as a fall or car accident. Some individuals with Klippel-Feil syndrome have a narrowing of the spinal canal (spinal stenosis) in the neck, which can put pressure on the spinal cord and nerves. This may be more common in those with Klippel-Feil syndrome type III.People with Klippel-Feil syndrome may have additional skeletal features, such as rib abnormalities or an abnormal side-to-side curvature of the spine (scoliosis). Approximately 20 to 30 percent of affected individuals have a skeletal condition called Sprengel deformity, in which the shoulder blades are underdeveloped and sit abnormally high on the back.Additional signs and symptoms seen in people with Klippel-Feil syndrome may include a difference in the size and shape of the right and left sides of the face (facial asymmetry), hearing loss, eye abnormalities, or an opening in the roof of the mouth (cleft palate). Abnormalities of the heart or kidneys may also be present. Some people with Klippel-Feil syndrome have neurological issues, which can include a type of birth defect that occurs during the development of the brain and spinal cord (neural tube defect) and a condition in which intentional movements of one side of the body are mirrored by involuntary movements of the other side (synkinesia).Klippel-Feil syndrome may occur as a feature of other disorders, such as Wildervanck syndrome or hemifacial microsomia. In these instances, affected individuals have the signs and symptoms of both Klippel-Feil syndrome and the additional disorder. ar Autosomal recessive ad Autosomal dominant GDF6 https://medlineplus.gov/genetics/gene/gdf6 GDF3 https://medlineplus.gov/genetics/gene/gdf3 MEOX1 https://medlineplus.gov/genetics/gene/meox1 MYO18B https://www.ncbi.nlm.nih.gov/gene/84700 Cervical vertebral fusion Congenital cervical vertebral fusion Congenital fused cervical segments KFS Klippel-Feil malformation Klippel-Feil sequence GTR C0022738 GTR C1859209 GTR C1861689 GTR C3150967 GTR C4225285 ICD-10-CM Q76.1 MeSH D007714 OMIM 118100 OMIM 214300 OMIM 613702 OMIM 616549 SNOMED CT 5601008 2025-09 2025-09-24 Klippel-Trenaunay syndrome https://medlineplus.gov/genetics/condition/klippel-trenaunay-syndrome descriptionKlippel-Trenaunay syndrome is a condition that affects the development of blood vessels, soft tissues (such as skin and muscles), and bones. The disorder has three characteristic features: a red birthmark called a port-wine stain, abnormal overgrowth of soft tissues and bones, and vein malformations.Most people with Klippel-Trenaunay syndrome are born with a port-wine stain. This type of birthmark is caused by swelling of small blood vessels near the surface of the skin. Port-wine stains are typically flat and can vary from pale pink to deep maroon in color. In people with Klippel-Trenaunay syndrome, the port-wine stain usually covers part of one limb. The affected area may become lighter or darker with age. Occasionally, port-wine stains develop small red blisters that break open and bleed easily.Klippel-Trenaunay syndrome is also associated with overgrowth of bones and soft tissues beginning in infancy. Usually this abnormal growth is limited to one limb, most often one leg. However, overgrowth can also affect the arms or, rarely, the torso. The abnormal growth can cause pain, a feeling of heaviness, and reduced movement in the affected area. If the overgrowth causes one leg to be longer than the other, it can also lead to problems with walking.Malformations of veins are the third major feature of Klippel-Trenaunay syndrome. These abnormalities include varicose veins, which are swollen and twisted veins near the surface of the skin that often cause pain. Varicose veins usually occur on the sides of the upper legs and calves. Veins deep in the limbs can also be abnormal in people with Klippel-Trenaunay syndrome. Malformations of deep veins increase the risk of a type of blood clot called a deep vein thrombosis (DVT). If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening blood clot known as a pulmonary embolism (PE).Other complications of Klippel-Trenaunay syndrome can include a type of skin infection called cellulitis, swelling caused by a buildup of fluid (lymphedema), and internal bleeding from abnormal blood vessels. Less commonly, this condition is also associated with fusion of certain fingers or toes (syndactyly) or the presence of extra digits (polydactyly). n Not inherited PIK3CA https://medlineplus.gov/genetics/gene/pik3ca Angio-osteohypertrophy syndrome Congenital dysplastic angiopathy Klippel-Trenaunay disease KTS GTR C0022739 MeSH D007715 OMIM 149000 SNOMED CT 721105004 2016-07 2021-05-17 Kniest dysplasia https://medlineplus.gov/genetics/condition/kniest-dysplasia descriptionKniest dysplasia is a skeletal disorder that is characterized by short stature, joint disease, and problems with vision and hearing. People with Kniest dysplasia are born with a short torso and short arms and legs. Adult height ranges from approximately 42 to 57 inches. Other skeletal problems may include a rounded upper back that also curves to the side (kyphoscoliosis), flattened bones of the spine (platyspondyly), dumbbell-shaped bones in the legs, and inward- and upward-turning feet (clubfeet). A distinguishing feature of Kniest dysplasia is abnormal cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development; most cartilage is later converted to bone. People with Kniest dysplasia have tiny holes in their cartilage, which makes the cartilage look like Swiss cheese when seen with medical imaging. Individuals with Kniest dysplasia often have distinctive facial features, which include a round, flat face with prominent and wide-set eyes.  Some affected infants are born with an opening in the roof of the mouth (cleft palate). Infants with Kniest dysplasia may also have breathing problems due to a windpipe that is too flexible. Enlarged joints that cause pain and restrict movement are another sign of Kniest dysplasia. These joint problems typically lead to early-onset arthritis. Many people with Kniest dysplasia also have hearing loss and problems with vision, such as severe nearsightedness (myopia) and tearing of the light-sensitive tissue at the back of the eye (retinal detachment). ad Autosomal dominant+New variant ad Autosomal dominant COL2A1 https://medlineplus.gov/genetics/gene/col2a1 Kniest chondrodystrophy Kniest dysplasia, COL2A1-related Kniest syndrome GTR C0265279 MeSH D003095 MeSH D010009 OMIM 156550 SNOMED CT 53974002 2024-12 2024-12-19 Knobloch syndrome https://medlineplus.gov/genetics/condition/knobloch-syndrome descriptionKnobloch syndrome is a rare condition characterized by severe vision problems and a skull defect.A characteristic feature of Knobloch syndrome is extreme nearsightedness (high myopia). In addition, several other eye abnormalities are common in people with this condition. Most affected individuals have vitreoretinal degeneration, which is breakdown (degeneration) of two structures in the eye called the vitreous and the retina. The vitreous is the gelatin-like substance that fills the eye, and the retina is the light-sensitive tissue at the back of the eye. Vitreoretinal degeneration often leads to separation of the retina from the back of the eye (retinal detachment). Affected individuals may also have abnormalities in the central area of the retina, called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Due to abnormalities in the vitreous, retina, and macula, people with Knobloch syndrome often develop blindness in one or both eyes.Another characteristic feature of Knobloch syndrome is a skull defect called an occipital encephalocele, which is a sac-like protrusion of the brain (encephalocele) through a defect in the bone at the base of the skull (occipital bone). Some affected individuals have been diagnosed with a different skull defect in the occipital region, and it is unclear whether the defect is always a true encephalocele. In other conditions, encephaloceles may be associated with intellectual disability; however, most people with Knobloch syndrome have normal intelligence. ar Autosomal recessive COL18A1 https://medlineplus.gov/genetics/gene/col18a1 Retinal detachment and occipital encephalocele GTR C4551775 MeSH D012164 OMIM 267750 SNOMED CT 703542000 2011-06 2020-08-18 Koolen-de Vries syndrome https://medlineplus.gov/genetics/condition/koolen-de-vries-syndrome descriptionKoolen-de Vries syndrome is a disorder characterized by developmental delay and mild to moderate intellectual disability. People with this disorder typically have a disposition that is described as cheerful, sociable, and cooperative. They usually have weak muscle tone (hypotonia) in childhood. About half have recurrent seizures (epilepsy).Affected individuals often have distinctive facial features including a high, broad forehead; droopy eyelids (ptosis); a narrowing of the eye openings (blepharophimosis); outer corners of the eyes that point upward (upward-slanting palpebral fissures); skin folds covering the inner corner of the eyes (epicanthal folds); a bulbous nose; and prominent ears. Males with Koolen-de Vries syndrome often have undescended testes (cryptorchidism). Defects in the walls between the chambers of the heart (septal defects) or other cardiac abnormalities, kidney problems, and skeletal anomalies such as foot deformities occur in some affected individuals. ad Autosomal dominant KANSL1 https://medlineplus.gov/genetics/gene/kansl1 17 https://medlineplus.gov/genetics/chromosome/17 17q21.31 deletion syndrome 17q21.31 microdeletion syndrome Chromosome 17q21.31 microdeletion syndrome KANSL1-related intellectual disability syndrome KDVS Koolen syndrome Microdeletion 17q21.31 syndrome Monosomy 17q21.31 GTR C1864871 MeSH D025063 OMIM 610443 SNOMED CT 717338006 2013-03 2020-09-08 Krabbe disease https://medlineplus.gov/genetics/condition/krabbe-disease descriptionKrabbe disease (also called globoid cell leukodystrophy) is a severe neurological condition. It is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination) in the nervous system. Myelin is the protective covering around nerve cells that ensures the rapid transmission of nerve signals. Krabbe disease is also characterized by abnormal cells in the brain called globoid cells, which are large cells that usually have more than one nucleus.The most common form of Krabbe disease, called the infantile form, usually begins before the age of 1. Initial signs and symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture, and delayed mental and physical development. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and seizures. Because of the severity of the condition, individuals with the infantile form of Krabbe disease rarely survive beyond the age of 2.Less commonly, Krabbe disease begins in childhood, adolescence, or adulthood (late-onset forms). Vision problems and walking difficulties are the most common initial symptoms in these forms of the disorder, however, signs and symptoms vary considerably among affected individuals. Individuals with late-onset Krabbe disease may survive many years after the condition begins. ar Autosomal recessive GALC https://medlineplus.gov/genetics/gene/galc Diffuse globoid body sclerosis Galactosylceramidase deficiency disease Galactosylceramide lipidosis Galactosylcerebrosidase deficiency Galactosylsphingosine lipidosis GALC deficiency GCL GLD Psychosine lipidosis GTR C0023521 ICD-10-CM E75.23 MeSH D007965 OMIM 245200 SNOMED CT 189979005 SNOMED CT 192782005 SNOMED CT 41142009 2017-12 2020-08-18 Kuskokwim syndrome https://medlineplus.gov/genetics/condition/kuskokwim-syndrome descriptionKuskokwim syndrome is characterized by joint deformities called contractures that restrict the movement of affected joints. This condition has been found only in a population of Alaska Natives known as Yup'ik Eskimos, who live in and around a region of southwest Alaska known as the Kuskokwim River Delta.In Kuskokwim syndrome, contractures most commonly affect the knees, ankles, and elbows, although other joints, particularly of the lower body, can be affected. The contractures are usually present at birth and worsen during childhood. They tend to stabilize after childhood, and they remain throughout life.Some individuals with this condition have other bone abnormalities, most commonly affecting the spine, pelvis, and feet. Affected individuals can develop an inward curve of the lower back (lordosis), a spine that curves to the side (scoliosis), wedge-shaped spinal bones, or an abnormality of the collarbones (clavicles) described as clubbing. Affected individuals are typically shorter than their peers and they may have an abnormally large head (macrocephaly). ar Autosomal recessive FKBP10 https://medlineplus.gov/genetics/gene/fkbp10 Arthrogryposis-like syndrome Bruck syndrome 1 Kuskokwim disease GTR C1850168 MeSH D001176 OMIM 259450 SNOMED CT 702447002 2013-11 2020-09-28 L1 syndrome https://medlineplus.gov/genetics/condition/l1-syndrome descriptionL1 syndrome describes a group of conditions that primarily affect the nervous system and occur almost exclusively in males. These conditions vary in severity and include, from most severe to least, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), MASA syndrome, spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis.HSAS is an acronym for the characteristic features of the condition: a buildup of fluid in the brain (hydrocephalus) that is often present from before birth, muscle stiffness (spasticity), thumbs that are permanently bent toward the palms (adducted thumbs), and narrowing (stenosis) of a passageway in the brain called the aqueduct of Sylvius. In individuals with HSAS, stenosis of the aqueduct of Sylvius causes hydrocephalus by impeding the flow of cerebrospinal fluid (CSF) out of fluid-filled cavities called ventricles. Individuals with HSAS often have severe intellectual disability and may have seizures.MASA syndrome is also named for the characteristic features of the condition, which are intellectual disability (mental retardation) that can range from mild to moderate, delayed speech (aphasia), spasticity, and adducted thumbs. Individuals with MASA syndrome may have mild enlargement of the ventricles.Spastic paraplegia type 1 is characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the limbs (paraplegia). Affected individuals also have mild to moderate intellectual disability. People with spastic paraplegia type 1 do not usually have major abnormalities in structures of the brain.X-linked complicated corpus callosum agenesis is defined by underdevelopment (hypoplasia) or absence (agenesis) of the tissue that connects the left and right halves of the brain (the corpus callosum). People with this condition can have spastic paraplegia and mild to moderate intellectual disability.The life expectancy of individuals with L1 syndrome varies depending on the severity of the signs and symptoms. Severely affected individuals may survive only a short time after birth, while those with mild features live into adulthood.The conditions that make up L1 syndrome were once thought to be distinct disorders, but since they were found to share a genetic cause, they are now considered to be part of the same syndrome. Family members with L1 syndrome caused by the same mutation may have different forms of the condition. x X-linked L1CAM https://medlineplus.gov/genetics/gene/l1cam Adducted thumbs-mental retardation syndrome Corpus callosum hypoplasia, mental retardation, adducted thumbs, spastic paraplegia, hydrocephalus syndrome CRASH syndrome Mental retardation-clasped thumb syndrome X-linked hydrocephalus syndrome GTR C0265216 GTR C0795953 GTR C1839909 GTR C5779710 MeSH D015419 OMIM 303350 OMIM 304100 OMIM 307000 SNOMED CT 302882002 SNOMED CT 716996008 SNOMED CT 71779008 SNOMED CT 838441009 2017-04 2021-06-10 LAMA2-related muscular dystrophy https://medlineplus.gov/genetics/condition/lama2-related-muscular-dystrophy descriptionLAMA2-related muscular dystrophy is a disorder that causes weakness and wasting (atrophy) of muscles used for movement (skeletal muscles). This condition varies in severity, from a severe, early-onset type to a milder, late-onset form.Early-onset LAMA2-related muscular dystrophy is apparent at birth or within the first few months of life. It is considered part of a class of muscle disorders called congenital muscular dystrophies and is sometimes called congenital muscular dystrophy type 1A. Affected infants may have severe muscle weakness, lack of muscle tone (hypotonia), little spontaneous movement, and joint deformities (contractures). Weakness of the muscles in the face and throat can result in feeding difficulties and an inability to grow and gain weight at the expected rate. Respiratory insufficiency, which occurs when muscles in the chest are weakened, causes a weak cry and breathing problems that can lead to frequent, potentially life-threatening lung infections.As affected children grow, they often develop an abnormal, gradually worsening side-to-side curvature of the spine (scoliosis) and inward curvature of the back (lordosis). Children with early-onset LAMA2-related muscular dystrophy often do not develop the ability to walk. Difficulty with speech may result from weakness of the facial muscles and an enlarged tongue. Seizures occur in about a third of individuals with early-onset LAMA2-related muscular dystrophy; rarely, heart complications occur in this form of the disorder.Symptoms of late-onset LAMA2-related muscular dystrophy become evident later in childhood or adulthood, and are similar to those of a group of muscle disorders classified as limb-girdle muscular dystrophies. In late-onset LAMA2-related muscular dystrophy, the muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs. Children with late-onset LAMA2-related muscular dystrophy sometimes have delayed development of motor skills such as walking, but generally achieve the ability to walk without assistance. Over time, they may develop rigidity of the back, joint contractures, scoliosis, and breathing problems. However, most affected individuals retain the ability to walk and climb stairs. ar Autosomal recessive LAMA2 https://medlineplus.gov/genetics/gene/lama2 LAMA2 MD Laminin alpha 2 deficiency Laminin alpha-2 deficient muscular dystrophy MDC1A Merosin-deficient muscular dystrophy Muscular dystrophy due to LAMA2 deficiency GTR C1263858 GTR C1842898 MeSH D009136 OMIM 607855 SNOMED CT 111503008 2013-09 2020-08-18 LMNA-related congenital muscular dystrophy https://medlineplus.gov/genetics/condition/lmna-related-congenital-muscular-dystrophy descriptionLMNA-related congenital muscular dystrophy (L-CMD) is a condition that primarily affects muscles used for movement (skeletal muscles). It is part of a group of genetic conditions called congenital muscular dystrophies, which cause weak muscle tone (hypotonia) and muscle wasting (atrophy) beginning very early in life.In people with L-CMD, muscle weakness becomes apparent in infancy or early childhood and can worsen quickly. The most severely affected infants develop few motor skills, and they are never able to hold up their heads, roll over, or sit. Less severely affected children may learn to sit, stand, and walk before muscle weakness becomes apparent. First the neck muscles weaken, causing the head to fall forward (dropped-head syndrome). As other skeletal muscles become weaker, these children may ultimately lose the ability to sit, stand, and walk unassisted.Other features of L-CMD often include spinal rigidity and abnormal curvature of the spine (scoliosis and lordosis); joint deformities (contractures) that restrict movement, particularly in the hips and legs; and an inward-turning foot. People with L-CMD also have an increased risk of heart rhythm abnormalities (arrhythmias).Over time, muscle weakness causes most infants and children with L-CMD to have trouble eating and breathing. The breathing problems result from restrictive respiratory insufficiency, which occurs when muscles in the chest are weakened and the ribcage becomes increasingly rigid. This problem can be life-threatening, and many affected children require support with a machine to help them breathe (mechanical ventilation). ad Autosomal dominant LMNA https://medlineplus.gov/genetics/gene/lmna L-CMD LMNA-related CMD MDCL Muscular dystrophy, congenital, LMNA-related GTR C2750785 MeSH D009136 OMIM 613205 2018-05 2020-08-18 Lacrimo-auriculo-dento-digital syndrome https://medlineplus.gov/genetics/condition/lacrimo-auriculo-dento-digital-syndrome descriptionLacrimo-auriculo-dento-digital (LADD) syndrome is a genetic disorder that mainly affects the eyes, ears, mouth, and hands. LADD syndrome is characterized by defects in the tear-producing lacrimal system (lacrimo-), ear problems (auriculo-), dental abnormalities (dento-), and deformities of the fingers (digital).The lacrimal system consists of structures in the eye that produce and secrete tears. Lacrimal system malformations that can occur with LADD syndrome include an underdeveloped or absent opening to the tear duct at the edge of the eyelid (lacrimal puncta) and blockage of the channel (nasolacrimal duct) that connects the inside corner of the eye where tears gather (tear sac) to the nasal cavity. These malformations of the lacrimal system can lead to chronic tearing (epiphora), inflammation of the tear sac (dacryocystitis), inflammation of the front surface of the eye (keratoconjunctivitis), or an inability to produce tears.Ears that are low-set and described as cup-shaped, often accompanied by hearing loss, are a common feature of LADD syndrome. The hearing loss may be mild to severe and can be caused by changes in the inner ear (sensorineural deafness), changes in the middle ear (conductive hearing loss), or both (mixed hearing loss).People with LADD syndrome may have underdeveloped or absent salivary glands, which impairs saliva production. A decrease in saliva leads to dry mouth (xerostomia) and a greater susceptibility to cavities. Individuals with LADD syndrome often have small, underdeveloped teeth with thin enamel and peg-shaped front teeth (incisors).Hand deformities are also a frequent feature of LADD syndrome. Affected individuals may have abnormally small or missing thumbs. Alternatively, the thumb might be duplicated, fused with the index finger (syndactyly), abnormally placed, or have three bones instead of the normal two and resemble a finger. Abnormalities of the fingers include syndactyly of the second and third fingers, extra or missing fingers, and curved pinky fingers (fifth finger clinodactyly). Sometimes, the forearm is also affected. It can be shorter than normal with abnormal wrist and elbow joint development that limits movement.People with LADD syndrome may also experience other signs and symptoms. They can have kidney problems that include hardening of the kidneys (nephrosclerosis) and urine accumulation in the kidneys (hydronephrosis), which can impair kidney function. Recurrent urinary tract infections and abnormalities of the genitourinary system can also occur. Some people with LADD syndrome have an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). The signs and symptoms of this condition vary widely, even among affected family members. ad Autosomal dominant FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 FGF10 https://medlineplus.gov/genetics/gene/fgf10 Lacrimoauriculodentodigital syndrome LADD syndrome Levy-Hollister syndrome GTR C0265269 MeSH D019465 OMIM 149730 SNOMED CT 23817003 2013-06 2020-08-18 Lactate dehydrogenase deficiency https://medlineplus.gov/genetics/condition/lactate-dehydrogenase-deficiency descriptionLactate dehydrogenase deficiency is a condition that affects how the body breaks down sugar to use as energy in cells, primarily muscle cells.There are two types of this condition: lactate dehydrogenase-A deficiency (sometimes called glycogen storage disease XI) and lactate dehydrogenase-B deficiency.People with lactate dehydrogenase-A deficiency experience fatigue, muscle pain, and cramps during exercise (exercise intolerance). In some people with lactate dehydrogenase-A deficiency, high-intensity exercise or other strenuous activity leads to the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure. Some people with lactate dehydrogenase-A deficiency develop skin rashes. The severity of the signs and symptoms among individuals with lactate dehydrogenase-A deficiency varies greatly.People with lactate dehydrogenase-B deficiency typically do not have any signs or symptoms of the condition. They do not have difficulty with physical activity or any specific physical features related to the condition. Affected individuals are usually discovered only when routine blood tests reveal reduced lactate dehydrogenase activity. ar Autosomal recessive LDHA https://medlineplus.gov/genetics/gene/ldha LDHB https://medlineplus.gov/genetics/gene/ldhb Deficiency of lactate dehydrogenase Lactate dehydrogenase subunit deficiencies LDH deficiency GTR C2931743 GTR C3279904 MeSH D002239 OMIM 612933 OMIM 614128 SNOMED CT 124115002 SNOMED CT 124116001 SNOMED CT 124141008 SNOMED CT 237982007 SNOMED CT 55783001 2012-02 2023-08-18 Lactose intolerance https://medlineplus.gov/genetics/condition/lactose-intolerance descriptionLactose intolerance is a condition that makes it difficult to digest lactose, a sugar found in milk and several other dairy products. Lactose is normally broken down by an enzyme called lactase, which is produced by cells in the lining of the small intestine. Lack or loss of lactase has both genetic and non-genetic causes.Congenital lactase deficiency, also called congenital alactasia, is a disorder in which infants are unable to break down the lactose in breast milk or formula. This form of lactose intolerance results in very severe diarrhea. If affected infants are not given a lactose-free infant formula, they may experience severe dehydration and weight loss.Lactose intolerance in adulthood can be caused by the reduced production of lactase after infancy (lactase nonpersistence). If individuals with lactose intolerance consume lactose-containing dairy products, they may experience abdominal pain, bloating, flatulence, nausea, and diarrhea beginning 30 minutes to 2 hours later.Most people with lactase nonpersistence retain some lactase activity and can include varying amounts of lactose in their diets without experiencing symptoms. Often, affected individuals have difficulty digesting fresh milk but can eat certain dairy products such as cheese or yogurt without discomfort. These foods are made using fermentation processes that break down much of the lactose in milk. ad Autosomal dominant ar Autosomal recessive LCT https://medlineplus.gov/genetics/gene/lct MCM6 https://medlineplus.gov/genetics/gene/mcm6 Alactasia Hypolactasia Lactose malabsorption Milk sugar intolerance GTR C0268179 GTR C0268181 ICD-10-CM E73 ICD-10-CM E73.0 ICD-10-CM E73.1 ICD-10-CM E73.8 ICD-10-CM E73.9 MeSH D007787 OMIM 223000 OMIM 223100 SNOMED CT 267425008 SNOMED CT 38032004 SNOMED CT 5388008 2023-03 2025-04-03 Lafora progressive myoclonus epilepsy https://medlineplus.gov/genetics/condition/lafora-progressive-myoclonus-epilepsy descriptionLafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures (epilepsy) and a decline in intellectual function. The signs and symptoms of the disorder usually appear in late childhood or adolescence and worsen with time.Myoclonus is a term used to describe episodes of sudden, involuntary muscle jerking or twitching that can affect part of the body or the entire body. Myoclonus can occur when an affected person is at rest, and it is made worse by motion, excitement, or flashing light (photic stimulation). In the later stages of Lafora progressive myoclonus epilepsy, myoclonus often occurs continuously and affects the entire body.Several types of seizures commonly occur in people with Lafora progressive myoclonus epilepsy. Generalized tonic-clonic seizures (also known as grand mal seizures) affect the entire body, causing muscle rigidity, convulsions, and loss of consciousness. Affected individuals may also experience occipital seizures, which can cause temporary blindness and visual hallucinations. Over time, the seizures worsen and become more difficult to treat. A life-threatening seizure condition called status epilepticus may also develop. Status epilepticus is a continuous state of seizure activity lasting longer than several minutes.About the same time seizures begin, intellectual function starts to decline. Behavioral changes, depression, confusion, and speech difficulties (dysarthria) are among the early signs and symptoms of this disorder. As the condition worsens, a continued loss of intellectual function (dementia) impairs memory, judgment, and thought. Affected people lose the ability to perform the activities of daily living by their mid-twenties, and they ultimately require comprehensive care. People with Lafora progressive myoclonus epilepsy generally survive up to 10 years after symptoms first appear. ar Autosomal recessive EPM2A https://medlineplus.gov/genetics/gene/epm2a NHLRC1 https://medlineplus.gov/genetics/gene/nhlrc1 Epilepsy, progressive myoclonic, Lafora Lafora body disease Lafora disease Lafora progressive myoclonic epilepsy Lafora type progressive myoclonic epilepsy Myoclonic epilepsy of Lafora Progressive myoclonic epilepsy type 2 Progressive myoclonus epilepsy, Lafora type GTR C0751783 MeSH D020192 OMIM 254780 SNOMED CT 230425004 2009-07 2020-08-18 Laing distal myopathy https://medlineplus.gov/genetics/condition/laing-distal-myopathy descriptionLaing distal myopathy is a condition that affects skeletal muscles, which are muscles that the body uses for movement. This disorder causes progressive muscle weakness that appears in childhood. The first sign of Laing distal myopathy is usually weakness in certain muscles in the feet and ankles. This weakness leads to tightening of the Achilles tendon (the band that connects the heel of the foot to the calf muscles), an inability to lift the first (big) toe, and a high-stepping walk. Months to years later, muscle weakness develops in the hands and wrists. Weakness in these muscles makes it difficult to lift the fingers, particularly the third and fourth fingers. Many affected people also experience hand tremors.In addition to muscle weakness in the hands and feet, Laing distal myopathy causes weakness in several muscles of the neck and face. A decade or more after the onset of symptoms, mild weakness also spreads to muscles in the legs, hips, and shoulders. Laing distal myopathy progresses very gradually, and most affected people remain mobile throughout life. Life expectancy is normal in people with this condition. ad Autosomal dominant MYH7 https://medlineplus.gov/genetics/gene/myh7 Distal myopathy 1 Laing early-onset distal myopathy MPD1 GTR C4552004 MeSH D049310 OMIM 160500 SNOMED CT 193230001 2008-08 2020-08-18 Lamellar ichthyosis https://medlineplus.gov/genetics/condition/lamellar-ichthyosis descriptionLamellar ichthyosis is a condition that mainly affects the skin. Infants with this condition are typically born with a tight, clear sheath covering their skin called a collodion membrane. This membrane usually dries and peels off during the first few weeks of life, and then it becomes obvious that affected babies have scaly skin, and eyelids and lips that are turned outward. People with lamellar ichthyosis typically have large, dark, plate-like scales covering their skin on most of their body. Infants with lamellar ichthyosis may develop infections, an excessive loss of fluids (dehydration), and respiratory problems. Affected individuals may also have hair loss (alopecia), abnormally formed fingernails and toenails (nail dystrophy), a decreased ability to sweat (hypohidrosis), an increased sensitivity to heat, and a thickening of the skin on the palms of the hands and soles of the feet (keratoderma). Less frequently, affected individuals have reddened skin (erythema) and joint deformities (contractures). ar Autosomal recessive ABCA12 https://medlineplus.gov/genetics/gene/abca12 TGM1 https://medlineplus.gov/genetics/gene/tgm1 CYP4F22 https://www.ncbi.nlm.nih.gov/gene/126410 NIPAL4 https://www.ncbi.nlm.nih.gov/gene/348938 LIPN https://www.ncbi.nlm.nih.gov/gene/643418 Collodion baby Collodion baby syndrome Ichthyoses, lamellar Ichthyosis, lamellar LI GTR C0020758 GTR C1832550 GTR C1858133 GTR C3539888 GTR C3553029 ICD-10-CM Q80.2 MeSH D017490 OMIM 242300 OMIM 601277 OMIM 604777 OMIM 606545 SNOMED CT 205550003 SNOMED CT 254163001 SNOMED CT 403777006 2010-08 2020-08-18 Langer mesomelic dysplasia https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia descriptionLanger mesomelic dysplasia is a disorder of bone growth. Affected individuals typically have extreme shortening of the long bones in the arms and legs (mesomelia). As a result of the shortened leg bones, people with Langer mesomelic dysplasia have very short stature. A bone in the forearm called the ulna and a bone in the lower leg called the fibula are often underdeveloped or absent, while other bones in the forearm (the radius) and lower leg (the tibia) are unusually short, thick, and curved. Some people with Langer mesomelic dysplasia also have an abnormality of the wrist and forearm bones called Madelung deformity, which may cause pain and limit wrist movement. Additionally, some affected individuals have mild underdevelopment of the lower jaw bone (mandible). xr X-linked recessive ar Autosomal recessive SHOX https://medlineplus.gov/genetics/gene/shox Dyschondrosteosis homozygous Langer mesomelic dwarfism LMD Mesomelic dwarfism of the hypoplastic ulna, fibula, and mandible type GTR C0432230 MeSH D009139 OMIM 249700 SNOMED CT 38494008 2012-01 2023-03-28 Langerhans cell histiocytosis https://medlineplus.gov/genetics/condition/langerhans-cell-histiocytosis descriptionLangerhans cell histiocytosis is a disorder in which excess immune system cells called Langerhans cells build up in the body. Langerhans cells, which help regulate the immune system, are normally found throughout the body, especially in the skin, lymph nodes, spleen, lungs, liver, and bone marrow. In Langerhans cell histiocytosis, excess immature Langerhans cells usually form tumors called granulomas. Many researchers now consider Langerhans cell histiocytosis to be a form of cancer, but this classification remains controversial.In approximately 80 percent of affected individuals, one or more granulomas develop in the bones, causing pain and swelling. The granulomas, which usually occur in the skull or the long bones of the arms or legs, may cause the bone to fracture.Granulomas also frequently occur in the skin, appearing as blisters, reddish bumps, or rashes which can be mild to severe. The pituitary gland may also be affected; this gland is located at the base of the brain and produces hormones that control many important body functions. Without hormone supplementation, affected individuals may experience delayed or absent puberty or an inability to have children (infertility). In addition, pituitary gland damage may result in the production of excessive amounts of urine (diabetes insipidus) and dysfunction of another gland called the thyroid. Thyroid dysfunction can affect the rate of chemical reactions in the body (metabolism), body temperature, skin and hair texture, and behavior.In 15 to 20 percent of cases, Langerhans cell histiocytosis affects the lungs, liver, or blood-forming (hematopoietic) system; damage to these organs and tissues may be life-threatening. Lung involvement, which appears as swelling of the small airways (bronchioles) and blood vessels of the lungs, results in stiffening of the lung tissue, breathing problems, and increased risk of infection. Hematopoietic involvement, which occurs when the Langerhans cells crowd out blood-forming cells in the bone marrow, leads to a general reduction in the number of blood cells (pancytopenia). Pancytopenia results in fatigue due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia).Other signs and symptoms that may occur in Langerhans cell histiocytosis, depending on which organs and tissues have Langerhans cell deposits, include swollen lymph nodes, abdominal pain, yellowing of the skin and whites of the eyes (jaundice), delayed puberty, protruding eyes, dizziness, irritability, and seizures. About 1 in 50 affected individuals experience deterioration of neurological function (neurodegeneration).Langerhans cell histiocytosis is often diagnosed in childhood, usually between ages 2 and 3, but can appear at any age. Most individuals with adult-onset Langerhans cell histiocytosis are current or past smokers; in about two-thirds of adult-onset cases the disorder affects only the lungs.The severity of Langerhans cell histiocytosis, and its signs and symptoms, vary widely among affected individuals. Certain presentations or forms of the disorder were formerly considered to be separate diseases. Older names that were sometimes used for forms of Langerhans cell histiocytosis include eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease.In many people with Langerhans cell histiocytosis, the disorder eventually goes away with appropriate treatment. It may even disappear on its own, especially if the disease occurs only in the skin. However, some complications of the condition, such as diabetes insipidus or other effects of tissue and organ damage, may be permanent. u Pattern unknown BRAF https://medlineplus.gov/genetics/gene/braf MAP2K1 https://medlineplus.gov/genetics/gene/map2k1 MAP3K1 https://medlineplus.gov/genetics/gene/map3k1 Hashimoto-Pritzger disease Histiocytosis X Langerhans cell granulomatosis LCH GTR C0019621 ICD-10-CM C96.0 ICD-10-CM C96.5 ICD-10-CM C96.6 ICD-10-CM J84.82 MeSH D006646 OMIM 604856 SNOMED CT 65399007 2011-08 2021-05-28 Laron syndrome https://medlineplus.gov/genetics/condition/laron-syndrome descriptionLaron syndrome is a rare form of short stature that results from the body's inability to use growth hormone, a substance produced by the brain's pituitary gland that helps promote growth. Affected individuals are close to normal size at birth, but they experience slow growth from early childhood that results in very short stature. If the condition is not treated, adult males typically reach a maximum height of about 4.5 feet; adult females may be just over 4 feet tall.Other features of untreated Laron syndrome include reduced muscle strength and endurance, low blood glucose levels (hypoglycemia) in infancy, small genitals and delayed puberty, hair that is thin and fragile, and dental abnormalities. Many affected individuals have a distinctive facial appearance, including a protruding forehead, a sunken bridge of the nose (saddle nose), and a blue tint to the whites of the eyes (blue sclerae). Affected individuals have short limbs compared to the size of their torso, as well as small hands and feet. Adults with this condition tend to develop obesity. However, the signs and symptoms of Laron syndrome vary, even among affected members of the same family.Studies suggest that people with Laron syndrome have a significantly reduced risk of cancer and type 2 diabetes. Affected individuals appear to develop these common diseases much less frequently than their unaffected relatives, despite having obesity (a risk factor for both cancer and type 2 diabetes). However, people with Laron syndrome do not seem to have an increased lifespan compared with their unaffected relatives. ar Autosomal recessive ad Autosomal dominant GHR https://medlineplus.gov/genetics/gene/ghr GH-R deficiency Growth hormone insensitivity syndrome Growth hormone receptor defect Growth hormone receptor deficiency Laron dwarfism Laron-type dwarfism Laron-type isolated somatotropin defect Laron-type pituitary dwarfism Laron-type short stature Pituitary dwarfism II Primary GH resistance Primary growth hormone resistance Severe GH insensitivity GTR C0271568 ICD-10-CM E34.3 MeSH D046150 OMIM 262500 SNOMED CT 38196001 2015-04 2023-07-25 Larsen syndrome https://medlineplus.gov/genetics/condition/larsen-syndrome descriptionLarsen syndrome is a disorder that affects the development of bones throughout the body. The signs and symptoms of Larsen syndrome vary widely even within the same family. Affected individuals are usually born with dislocations of the hips, knees, or elbows. Foot abnormalities, such as inward- and upward-turning feet (clubfeet), are also common. Affected individuals generally have small extra bones in their wrists and ankles that are visible on x-ray images. The tips of their fingers, especially the thumbs, are typically blunt and square-shaped (spatulate).Characteristic facial features in people with Larsen syndrome include a prominent forehead (frontal bossing), flattening of the bridge of the nose and middle of the face (midface hypoplasia), and wide-set eyes (ocular hypertelorism). Many people with Larsen syndrome have an opening in the roof of the mouth (a cleft palate). Affected individuals may also have hearing loss caused by malformations in tiny bones in the ears (ossicles).Short stature is a common feature of Larsen syndrome. In addition, people with the condition may have an unusually large range of joint movement (hypermobility) or joint deformities (contractures) that restrict movement. People with Larsen syndrome can also have abnormal curvature of the spine (kyphosis or scoliosis) that can impair breathing or compress the spinal cord and lead to weakness of the limbs. Some affected individuals experience respiratory problems, such as partial closing of the airways, short pauses in breathing (apnea), and frequent respiratory infections. Heart and kidney problems can also occur in people with Larsen syndrome. People with this condition can survive into adulthood. Their intellectual function is usually unaffected. ad Autosomal dominant FLNB https://medlineplus.gov/genetics/gene/flnb LRS GTR C0175778 MeSH D010009 OMIM 150250 SNOMED CT 63387002 2011-09 2023-08-18 Laryngo-onycho-cutaneous syndrome https://medlineplus.gov/genetics/condition/laryngo-onycho-cutaneous-syndrome descriptionLaryngo-onycho-cutaneous (LOC) syndrome is a disorder that leads to abnormalities of the voicebox (laryngo-), finger- and toenails (onycho-), and skin (cutaneous). Many of the condition's signs and symptoms are related to the abnormal growth of granulation tissue in different parts of the body. This red, bumpy tissue is normally produced during wound healing and is usually replaced by skin cells as healing continues. However, in people with LOC syndrome, this tissue grows even when there is no major injury.One of the first symptoms in infants with LOC syndrome is a hoarse cry due to ulcers or overgrowth of granulation tissue in the voicebox (the larynx). Excess granulation tissue can also block the airways, leading to life-threatening breathing problems; as a result many affected individuals do not survive past childhood.In LOC syndrome, granulation tissue also grows in the eyes, specifically the conjunctiva, which are the moist tissues that line the eyelids and the white part of the eyes. Affected individuals often have impairment or complete loss of vision due to the tissue overgrowth.Another common feature of LOC syndrome is missing patches of skin (cutaneous erosions). The erosions heal slowly and may become infected. People with LOC syndrome can also have malformed nails and small, abnormal teeth. The hard, white material that forms the protective outer layer of each tooth (enamel) is thin, which contributes to frequent cavities.LOC syndrome is typically considered a subtype of another skin condition called junctional epidermolysis bullosa, which is characterized by fragile skin that blisters easily. While individuals with junctional epidermolysis bullosa can have some of the features of LOC syndrome, they do not usually have overgrowth of granulation tissue in the conjunctiva. ar Autosomal recessive LAMA3 https://medlineplus.gov/genetics/gene/lama3 JEB-LOC Laryngoonychocutaneous syndrome LOC syndrome LOCS LOGIC syndrome Shabbir syndrome GTR C1328355 MeSH D016109 OMIM 245660 SNOMED CT 722675000 2014-09 2020-08-18 Lateral meningocele syndrome https://medlineplus.gov/genetics/condition/lateral-meningocele-syndrome descriptionLateral meningocele syndrome is a disorder that affects the nervous system, the bones and muscles, and other body systems. The condition is characterized by abnormalities known as lateral meningoceles. Lateral meningoceles are protrusions of the membranes surrounding the spinal cord (known as the meninges) through gaps in the bones of the spine (vertebrae). The protrusions are most common and typically larger in the lower spine.The meningoceles associated with this disorder may damage the nerves that spread from the spine to the rest of the body. Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. Prickling or tingling sensations (paresthesias), progressive stiffness and weakness in the legs (paraparesis), and back pain can also occur. Delayed development of motor skills in infancy, such as sitting and crawling, often occurs in this disorder; intelligence is usually unaffected.Other features of lateral meningocele syndrome can include low muscle tone (hypotonia) during infancy, decreased muscle bulk, loose (hyperextensible) joints that can lead to dislocations, and protrusion of organs through gaps in muscles (hernias). Spinal abnormalities are also common, including side-to-side curvature of the spine (scoliosis), abnormal joining (fusion) of two or more vertebrae, and vertebrae that are unusually shaped (scalloped).People with lateral meningocele syndrome typically have a particular pattern of facial features that may include high arched eyebrows, widely spaced eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), and droopy eyelids (ptosis). Affected individuals may have a flat appearance of the middle of the face and cheekbones (midface and malar hypoplasia); low-set ears; a long area between the nose and mouth (long philtrum); a thin upper lip; a high, narrow roof of the mouth, occasionally with an abnormal opening (a cleft palate); a small jaw (micrognathia); coarse hair; and a low hairline at the back of the neck.Other signs and symptoms that can occur in lateral meningocele syndrome include a high and nasal voice, hearing loss, abnormalities of the heart or the genitourinary system, poor feeding, difficulty swallowing (dysphagia), and backflow of stomach acids into the esophagus (called gastroesophageal reflux or GERD). ad Autosomal dominant NOTCH3 https://medlineplus.gov/genetics/gene/notch3 Lehman syndrome LMS GTR C1851710 MeSH D000015 MeSH D008588 OMIM 130720 SNOMED CT 253166000 2016-07 2020-08-18 Lattice corneal dystrophy type I https://medlineplus.gov/genetics/condition/lattice-corneal-dystrophy-type-i descriptionLattice corneal dystrophy type I is an eye disorder that affects the clear, outer covering of the eye called the cornea. The cornea must remain clear for an individual to see properly; however, in lattice corneal dystrophy type I, protein clumps known as amyloid deposits cloud the cornea, which leads to vision impairment. The cornea is made up of several layers of tissue, and in lattice corneal dystrophy type I, the deposits form in the stromal layer. The amyloid deposits form as delicate, branching fibers that create a lattice pattern.Affected individuals often have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another. Corneal erosions are very painful and can cause sensitivity to bright light (photophobia). Lattice corneal dystrophy type I is usually bilateral, which means it affects both eyes. The condition becomes apparent in childhood or adolescence and leads to vision problems by early adulthood. ad Autosomal dominant TGFBI https://medlineplus.gov/genetics/gene/tgfbi Biber-Haab-Dimmer dystrophy GTR C1690006 ICD-10-CM H18.54 MeSH D003317 OMIM 122200 SNOMED CT 419197009 2012-04 2020-08-18 Lattice corneal dystrophy type II https://medlineplus.gov/genetics/condition/lattice-corneal-dystrophy-type-ii descriptionLattice corneal dystrophy type II is characterized by an accumulation of protein clumps called amyloid deposits in tissues throughout the body. The deposits frequently occur in blood vessel walls and basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. Amyloid deposits lead to characteristic signs and symptoms involving the eyes, nerves, and skin that worsen with age.The earliest sign of this condition, which is usually identified in a person's twenties, is accumulation of amyloid deposits in the cornea (lattice corneal dystrophy). The cornea is the clear, outer covering of the eye. It is made up of several layers of tissue, and in lattice corneal dystrophy type II, the amyloid deposits form in the stromal layer. The amyloid deposits form as delicate, branching fibers that create a lattice pattern. Because these protein deposits cloud the cornea, they often lead to vision impairment. In addition, affected individuals can have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another. Corneal erosions are very painful and can cause sensitivity to bright light (photophobia). Amyloid deposits and corneal erosions are usually bilateral, which means they affect both eyes.As lattice corneal dystrophy type II progresses, the nerves become involved, typically starting in a person's forties. It is thought that the amyloid deposits disrupt nerve function. Dysfunction of the nerves in the head and face (cranial nerves) can cause paralysis of facial muscles (facial palsy); decreased sensations in the face (facial hypoesthesia); and difficulty speaking, chewing, and swallowing. Dysfunction of the nerves that connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat (peripheral nerves) can cause loss of sensation and weakness in the limbs (peripheral neuropathy). Peripheral neuropathy usually occurs in the lower legs and arms, leading to muscle weakness, clumsiness, and difficulty sensing vibrations.The skin is also commonly affected in people with lattice corneal dystrophy type II, typically beginning in a person's forties. People with this condition may have thickened, sagging skin, especially on the scalp and forehead, and a condition called cutis laxa, which is characterized by loose skin that lacks elasticity. The skin can also be dry and itchy. Because of loose skin and muscle paralysis in the face, individuals with lattice corneal dystrophy type II can have a facial expression that appears sad. ad Autosomal dominant GSN https://medlineplus.gov/genetics/gene/gsn Amyloid cranial neuropathy with lattice corneal dystrophy Amyloidosis due to mutant gelsolin Amyloidosis V Amyloidosis, Finnish type Amyloidosis, Meretoja type Familial amyloid polyneuropathy type IV Familial amyloidosis, Finnish type Gelsolin-related amyloidosis Kymenlaakso syndrome Lattice corneal dystrophy, gelsolin type Meretoja syndrome GTR C1622345 ICD-10-CM H18.54 MeSH D028226 OMIM 105120 SNOMED CT 419087002 SNOMED CT 419398009 2012-04 2020-08-18 Leber congenital amaurosis https://medlineplus.gov/genetics/condition/leber-congenital-amaurosis descriptionLeber congenital amaurosis, also known as LCA, is an eye disorder that is present from birth (congenital). This condition primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this disorder typically have severe visual impairment beginning at birth or shortly afterward. The visual impairment tends to be severe and may worsen over time.Leber congenital amaurosis is also associated with other vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). The pupils, which usually expand and contract in response to the amount of light entering the eye, do not react normally to light. Instead, they expand and contract more slowly than normal, or they may not respond to light at all.A specific behavior called Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of affected individuals poking, pressing, and rubbing their eyes with a knuckle or finger. Poking their eyes often results in the sensation of flashes of light called phosphenes. Researchers suspect that this behavior may contribute to deep-set eyes in affected children.In very rare cases, delayed development and intellectual disability have been reported in people with the features of Leber congenital amaurosis. Because of the visual loss, affected children may become isolated. Providing children with opportunities to play, hear, touch, understand and other early educational interventions may prevent developmental delays in children with Leber congenital amaurosis.At least 20 genetic types of Leber congenital amaurosis have been described. The types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities. ad Autosomal dominant ar Autosomal recessive PRPH2 https://medlineplus.gov/genetics/gene/prph2 CEP290 https://medlineplus.gov/genetics/gene/cep290 CRB1 https://medlineplus.gov/genetics/gene/crb1 GUCY2D https://medlineplus.gov/genetics/gene/gucy2d RPE65 https://medlineplus.gov/genetics/gene/rpe65 GDF6 https://medlineplus.gov/genetics/gene/gdf6 CRX https://medlineplus.gov/genetics/gene/crx IMPDH1 https://www.ncbi.nlm.nih.gov/gene/3614 KCNJ13 https://www.ncbi.nlm.nih.gov/gene/3769 TULP1 https://www.ncbi.nlm.nih.gov/gene/7287 LRAT https://www.ncbi.nlm.nih.gov/gene/9227 IQCB1 https://www.ncbi.nlm.nih.gov/gene/9657 AIPL1 https://www.ncbi.nlm.nih.gov/gene/23746 LCA5 https://www.ncbi.nlm.nih.gov/gene/30828 SPATA7 https://www.ncbi.nlm.nih.gov/gene/55812 RPGRIP1 https://www.ncbi.nlm.nih.gov/gene/57096 NMNAT1 https://www.ncbi.nlm.nih.gov/gene/64802 USP45 https://www.ncbi.nlm.nih.gov/gene/85015 RDH12 https://www.ncbi.nlm.nih.gov/gene/145226 RD3 https://www.ncbi.nlm.nih.gov/gene/343035 Amaurosis, Leber congenital Congenital amaurosis of retinal origin Congenital retinal blindness CRB Dysgenesis neuroepithelialis retinae Hereditary epithelial dysplasia of retina Hereditary retinal aplasia Heredoretinopathia congenitalis LCA Leber abiotrophy Leber congenital tapetoretinal degeneration Leber's amaurosis GTR C0339527 GTR C1837873 GTR C1840284 GTR C1854260 GTR C1857743 GTR C1857821 GTR C1858301 GTR C1858386 GTR C1858677 GTR C1859844 GTR C2675186 GTR C2750063 GTR C2931258 GTR C3151192 GTR C3151202 GTR C3151206 GTR C3280062 GTR C3715164 GTR C4013102 MeSH D057130 OMIM 204000 OMIM 204100 OMIM 604232 OMIM 604393 OMIM 604537 OMIM 608553 OMIM 610612 OMIM 611755 OMIM 612712 OMIM 613341 OMIM 613826 OMIM 613829 OMIM 613835 OMIM 613837 OMIM 613843 OMIM 614186 OMIM 615360 OMIM 618513 SNOMED CT 193413001 2022-10 2022-10-06 Leber hereditary optic neuropathy https://medlineplus.gov/genetics/condition/leber-hereditary-optic-neuropathy descriptionLeber hereditary optic neuropathy (LHON) is an inherited form of vision loss. Although this condition usually begins in a person's teens or twenties, rare cases may appear in early childhood or later in adulthood. For unknown reasons, males are affected much more often than females.Blurring and clouding of vision are usually the first symptoms of LHON. These vision problems may begin in one eye or simultaneously in both eyes; if vision loss starts in one eye, the other eye is usually affected within several weeks or months. Over time, vision in both eyes worsens with a severe loss of sharpness (visual acuity) and color vision. This condition mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Vision loss results from the death of cells in the nerve that relays visual information from the eyes to the brain (the optic nerve). Although central vision gradually improves in a small percentage of cases, in most cases the vision loss is profound and permanent.Vision loss is typically the only symptom of LHON; however, some families with additional signs and symptoms have been reported. In these individuals, the condition is described as "LHON plus." In addition to vision loss, the features of LHON plus can include movement disorders, tremors, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). Some affected individuals develop features similar to multiple sclerosis, which is a chronic disorder characterized by muscle weakness, poor coordination, numbness, and a variety of other health problems. m mitochondrial MT-ND1 https://medlineplus.gov/genetics/gene/mt-nd1 MT-ND4 https://medlineplus.gov/genetics/gene/mt-nd4 MT-ND4L https://medlineplus.gov/genetics/gene/mt-nd4l MT-ND6 https://medlineplus.gov/genetics/gene/mt-nd6 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Hereditary optic neuroretinopathy Leber hereditary optic atrophy Leber optic atrophy Leber's hereditary optic neuropathy Leber's optic atrophy Leber's optic neuropathy LHON GTR C0917796 ICD-10-CM H47.22 MeSH D029242 OMIM 308905 OMIM 535000 SNOMED CT 58610003 2006-08 2020-09-08 Left ventricular noncompaction https://medlineplus.gov/genetics/condition/left-ventricular-noncompaction descriptionLeft ventricular noncompaction is a heart (cardiac) muscle disorder that occurs when the lower left chamber of the heart (left ventricle), which helps the heart pump blood, does not develop correctly. Instead of the muscle being smooth and firm, the cardiac muscle in the left ventricle is thick and appears spongy. The abnormal cardiac muscle is weak and has an impaired ability to pump blood because it either cannot completely contract or it cannot completely relax. For the heart to pump blood normally, cardiac muscle must contract and relax fully.Some individuals with left ventricular noncompaction experience no symptoms at all; others have heart problems that can include sudden cardiac death. Additional signs and symptoms include abnormal blood clots, irregular heart rhythm (arrhythmia), a sensation of fluttering or pounding in the chest (palpitations), extreme fatigue during exercise (exercise intolerance), shortness of breath (dyspnea), fainting (syncope), swelling of the legs (lymphedema), and trouble laying down flat. Some affected individuals have features of other heart defects. Left ventricular noncompaction can be diagnosed at any age, from birth to late adulthood. Approximately two-thirds of individuals with left ventricular noncompaction develop heart failure. ad Autosomal dominant xr X-linked recessive ar Autosomal recessive LMNA https://medlineplus.gov/genetics/gene/lmna SCN5A https://medlineplus.gov/genetics/gene/scn5a TAFAZZIN https://medlineplus.gov/genetics/gene/tafazzin MYH7 https://medlineplus.gov/genetics/gene/myh7 LDB3 https://medlineplus.gov/genetics/gene/ldb3 TNNT2 https://medlineplus.gov/genetics/gene/tnnt2 MYBPC3 https://medlineplus.gov/genetics/gene/mybpc3 HCN4 https://medlineplus.gov/genetics/gene/hcn4 ACTC1 https://www.ncbi.nlm.nih.gov/gene/70 DTNA https://www.ncbi.nlm.nih.gov/gene/1837 TPM1 https://www.ncbi.nlm.nih.gov/gene/7168 MIB1 https://www.ncbi.nlm.nih.gov/gene/57534 PRDM16 https://www.ncbi.nlm.nih.gov/gene/63976 Fetal myocardium Honeycomb myocardium Hypertrabeculation syndrome Isolated noncompaction of the ventricular myocardium Left ventricular hypertrabeculation Left ventricular myocardial noncompaction cardiomyopathy Left ventricular non-compaction LVHT LVNC Non-compaction of the left ventricular myocardium Noncompaction cardiomyopathy Spongy myocardium GTR C1832243 GTR C1858725 GTR C1960469 GTR C3554496 GTR C3715165 GTR C3809288 ICD-10-CM MeSH D056830 OMIM 601493 OMIM 601494 OMIM 604169 OMIM 609470 OMIM 611878 OMIM 613424 OMIM 613426 OMIM 615092 OMIM 615373 OMIM 615396 SNOMED CT 447935001 2017-06 2022-06-22 Legius syndrome https://medlineplus.gov/genetics/condition/legius-syndrome descriptionLegius syndrome is a condition characterized by changes in skin coloring (pigmentation). Almost all affected individuals have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Another pigmentation change, freckles in the armpits and groin, may occur in some affected individuals.Other signs and symptoms of Legius syndrome may include an abnormally large head (macrocephaly) and unusual facial characteristics. Although most people with Legius syndrome have normal intelligence, some affected individuals have been diagnosed with learning disabilities, attention-deficit disorder (ADD), or attention-deficit/hyperactivity disorder (ADHD).Many of the signs and symptoms of Legius syndrome also occur in a similar disorder called neurofibromatosis type 1. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life. ad Autosomal dominant SPRED1 https://medlineplus.gov/genetics/gene/spred1 Neurofibromatosis type 1-like syndrome NFLS GTR C1969623 MeSH D019080 OMIM 611431 SNOMED CT 703541007 2011-02 2022-12-02 Leigh syndrome https://medlineplus.gov/genetics/condition/leigh-syndrome descriptionLeigh syndrome is a severe neurological disorder that usually becomes apparent in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly.The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia), which disrupts eating. These problems often result in an inability to grow and gain weight at the expected rate (failure to thrive). Severe muscle and movement problems are common in Leigh syndrome. Affected individuals may develop weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia). Loss of sensation and weakness in the limbs (peripheral neuropathy), common in people with Leigh syndrome, may also make movement difficult.Several other features may occur in people with Leigh syndrome. Many individuals with this condition develop weakness or paralysis of the muscles that move the eyes (ophthalmoparesis); rapid, involuntary eye movements (nystagmus); or degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). Severe breathing problems are common, and these problems can worsen until they cause acute respiratory failure. Some affected individuals develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. In addition, a substance called lactate can build up in the body, and excessive amounts are often found in the blood, urine, or the fluid that surrounds and protects the brain and spinal cord (cerebrospinal fluid) of people with Leigh syndrome.The signs and symptoms of Leigh syndrome are caused in part by patches of damaged tissue (lesions) that develop in the brains of people with this condition. A medical procedure called magnetic resonance imaging (MRI) reveals characteristic lesions in certain regions of the brain. These regions include the basal ganglia, which help control movement; the cerebellum, which controls the ability to balance and coordinates movement; and the brainstem, which connects the brain to the spinal cord and controls functions such as swallowing and breathing. The brain lesions are often accompanied by loss of the myelin coating around nerves (demyelination), which reduces the ability of the nerves to activate muscles used for movement or relay sensory information from the rest of the body back to the brain. xr X-linked recessive ar Autosomal recessive n Not inherited m mitochondrial BTD https://medlineplus.gov/genetics/gene/btd DLD https://medlineplus.gov/genetics/gene/dld ETHE1 https://medlineplus.gov/genetics/gene/ethe1 MT-ND1 https://medlineplus.gov/genetics/gene/mt-nd1 MT-ND4 https://medlineplus.gov/genetics/gene/mt-nd4 MT-ND6 https://medlineplus.gov/genetics/gene/mt-nd6 MT-ATP6 https://medlineplus.gov/genetics/gene/mt-atp6 MT-TL1 https://medlineplus.gov/genetics/gene/mt-tl1 MT-ND5 https://medlineplus.gov/genetics/gene/mt-nd5 MT-TV https://medlineplus.gov/genetics/gene/mt-tv SLC25A19 https://medlineplus.gov/genetics/gene/slc25a19 MT-TK https://medlineplus.gov/genetics/gene/mt-tk SUCLG1 https://medlineplus.gov/genetics/gene/suclg1 SUCLA2 https://medlineplus.gov/genetics/gene/sucla2 POLG https://medlineplus.gov/genetics/gene/polg SDHA https://medlineplus.gov/genetics/gene/sdha SURF1 https://medlineplus.gov/genetics/gene/surf1 PDHA1 https://medlineplus.gov/genetics/gene/pdha1 PDHB https://medlineplus.gov/genetics/gene/pdhb PDHX https://medlineplus.gov/genetics/gene/pdhx DLAT https://medlineplus.gov/genetics/gene/dlat SLC19A3 https://medlineplus.gov/genetics/gene/slc19a3 BCS1L https://medlineplus.gov/genetics/gene/bcs1l SERAC1 https://medlineplus.gov/genetics/gene/serac1 EARS2 https://medlineplus.gov/genetics/gene/ears2 FBXL4 https://medlineplus.gov/genetics/gene/fbxl4 GFM1 https://medlineplus.gov/genetics/gene/gfm1 COX10 https://www.ncbi.nlm.nih.gov/gene/1352 COX15 https://www.ncbi.nlm.nih.gov/gene/1355 ECHS1 https://www.ncbi.nlm.nih.gov/gene/1892 MT-CO3 https://www.ncbi.nlm.nih.gov/gene/4514 MT-ND2 https://www.ncbi.nlm.nih.gov/gene/4536 MT-ND3 https://www.ncbi.nlm.nih.gov/gene/4537 MT-TI https://www.ncbi.nlm.nih.gov/gene/4565 MT-TW https://www.ncbi.nlm.nih.gov/gene/4578 NDUFA1 https://www.ncbi.nlm.nih.gov/gene/4694 NDUFA2 https://www.ncbi.nlm.nih.gov/gene/4695 COXFA4 https://www.ncbi.nlm.nih.gov/gene/4697 NDUFA9 https://www.ncbi.nlm.nih.gov/gene/4704 NDUFA10 https://www.ncbi.nlm.nih.gov/gene/4705 NDUFS1 https://www.ncbi.nlm.nih.gov/gene/4719 NDUFS2 https://www.ncbi.nlm.nih.gov/gene/4720 NDUFS3 https://www.ncbi.nlm.nih.gov/gene/4722 NDUFV1 https://www.ncbi.nlm.nih.gov/gene/4723 NDUFS4 https://www.ncbi.nlm.nih.gov/gene/4724 NDUFS7 https://www.ncbi.nlm.nih.gov/gene/4727 NDUFS8 https://www.ncbi.nlm.nih.gov/gene/4728 NDUFV2 https://www.ncbi.nlm.nih.gov/gene/4729 AIFM1 https://www.ncbi.nlm.nih.gov/gene/9131 SCO2 https://www.ncbi.nlm.nih.gov/gene/9997 TSFM https://www.ncbi.nlm.nih.gov/gene/10102 LRPPRC https://www.ncbi.nlm.nih.gov/gene/10128 FARS2 https://www.ncbi.nlm.nih.gov/gene/10667 LIAS https://www.ncbi.nlm.nih.gov/gene/11019 HIBCH https://www.ncbi.nlm.nih.gov/gene/26275 TPK1 https://www.ncbi.nlm.nih.gov/gene/27010 UQCRQ https://www.ncbi.nlm.nih.gov/gene/27089 TACO1 https://www.ncbi.nlm.nih.gov/gene/51204 LIPT1 https://www.ncbi.nlm.nih.gov/gene/51601 TTC19 https://www.ncbi.nlm.nih.gov/gene/54902 FOXRED1 https://www.ncbi.nlm.nih.gov/gene/55572 TRMU https://www.ncbi.nlm.nih.gov/gene/55687 IARS2 https://www.ncbi.nlm.nih.gov/gene/55699 NDUFA12 https://www.ncbi.nlm.nih.gov/gene/55967 PDSS2 https://www.ncbi.nlm.nih.gov/gene/57107 NDUFAF5 https://www.ncbi.nlm.nih.gov/gene/79133 NARS2 https://www.ncbi.nlm.nih.gov/gene/79731 GFM2 https://www.ncbi.nlm.nih.gov/gene/84340 GTPBP3 https://www.ncbi.nlm.nih.gov/gene/84705 PNPT1 https://www.ncbi.nlm.nih.gov/gene/87178 MTRFR https://www.ncbi.nlm.nih.gov/gene/91574 NDUFAF2 https://www.ncbi.nlm.nih.gov/gene/91942 MTFMT https://www.ncbi.nlm.nih.gov/gene/123263 NDUFA11 https://www.ncbi.nlm.nih.gov/gene/126328 NDUFAF6 https://www.ncbi.nlm.nih.gov/gene/137682 SDHAF1 https://www.ncbi.nlm.nih.gov/gene/644096 PET100 https://www.ncbi.nlm.nih.gov/gene/100131801 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Infantile subacute necrotizing encephalopathy Juvenile subacute necrotizing encephalopathy Leigh disease Leigh's disease Subacute necrotizing encephalomyelopathy GTR C1857355 GTR C2931891 GTR CN043625 GTR CN230159 ICD-10-CM G31.82 MeSH D007888 OMIM 161700 OMIM 220111 OMIM 256000 SNOMED CT 29570005 2016-05 2025-03-06 Lennox-Gastaut syndrome https://medlineplus.gov/genetics/condition/lennox-gastaut-syndrome descriptionLennox-Gastaut syndrome is a severe condition characterized by repeated seizures (epilepsy) that begin early in life. Affected individuals have multiple types of seizures, developmental delays, and particular patterns of brain activity measured by a test called an electroencephalogram (EEG). An EEG shows a slow spike-and-wave pattern during wakefulness and generalized paroxysmal fast activity during sleep.In people with Lennox-Gastaut syndrome, epilepsy begins in early childhood, usually between ages 3 and 5. The most common seizure type is tonic seizures, which cause the muscles to stiffen (contract) uncontrollably. These seizures typically occur during sleep; they may also occur during wakefulness. Also common are atonic seizures, which are caused by a sudden loss of muscle tone. Tonic and atonic seizures can cause sudden falls that can result in serious or life-threatening injuries. Additionally, many affected individuals have atypical absence seizures, which cause a very brief partial or complete loss of consciousness. Other types of seizures have been reported less frequently in people with Lennox-Gastaut syndrome. Seizures associated with Lennox-Gastaut syndrome often do not respond well to therapy with anti-epileptic medications.Although each seizure episode associated with Lennox-Gastaut syndrome is usually brief, more than two-thirds of affected individuals experience prolonged periods of seizure activity (known as status epilepticus) or episodes of many seizures that occur in a cluster.About one-third of people with Lennox-Gastaut syndrome have normal intellectual development before seizures begin. The remainder have intellectual disability or learning problems even before seizures arise. Intellectual problems may worsen over time, particularly if seizures are very frequent or severe. Some affected children develop additional neurological abnormalities and behavioral problems. Many are also slow to develop motor skills such as sitting and crawling. As a result of their seizures and intellectual disability, most people with Lennox-Gastaut syndrome require help with daily activities. However, a small percentage of affected adults can live independently.People with Lennox-Gastaut syndrome have a higher risk of death than their peers of the same age. Although the increased risk is not fully understood, it is partly due to poorly controlled seizures, pneumonia resulting from inhaling saliva (aspiration pneumonia) during a seizure, and injuries from falls. In addition, individuals with Lennox-Gastaut syndrome are at risk of sudden unexpected death in epilepsy (SUDEP), which describes sudden death with no known cause in someone with epilepsy; it is not the direct result of a seizure. u Pattern unknown SCN1A https://medlineplus.gov/genetics/gene/scn1a FOXG1 https://medlineplus.gov/genetics/gene/foxg1 CHD2 https://medlineplus.gov/genetics/gene/chd2 STXBP1 https://medlineplus.gov/genetics/gene/stxbp1 SCN8A https://medlineplus.gov/genetics/gene/scn8a DNM1 https://www.ncbi.nlm.nih.gov/gene/1759 GABRB3 https://www.ncbi.nlm.nih.gov/gene/2562 ALG13 https://www.ncbi.nlm.nih.gov/gene/55849 LGS GTR C3807541 ICD-10-CM G40.811 ICD-10-CM G40.812 ICD-10-CM G40.813 ICD-10-CM G40.814 MeSH D065768 OMIM 606369 SNOMED CT 230418006 2023-05 2023-05-03 Leprosy https://medlineplus.gov/genetics/condition/leprosy descriptionLeprosy, also called Hansen disease, is a disorder known since ancient times. It is caused by bacteria called Mycobacterium leprae and is contagious, which means that it can be passed from person to person. It is usually contracted by breathing airborne droplets from affected individuals' coughs and sneezes, or by coming into contact with their nasal fluids. However, it is not highly transmissible, and approximately 95 percent of individuals who are exposed to Mycobacterium leprae never develop leprosy. The infection can be contracted at any age, and signs and symptoms can take anywhere from several months to 20 years to appear.Leprosy affects the skin and the peripheral nerves, which connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat. Most affected individuals have areas of skin damage (cutaneous lesions) and problems with nerve function (peripheral neuropathy); however, the severity and extent of the problems vary widely. Leprosy occurs on a spectrum, in which the most severe form is called multibacillary or lepromatous, and the least severe form is called paucibacillary or tuberculoid. Patterns of signs and symptoms intermediate between these forms are sometimes called borderline forms.Multibacillary leprosy usually involves a large number of cutaneous lesions, including both surface damage and lumps under the skin (nodules). The moist tissues that line body openings such as the eyelids and the inside of the nose and mouth (mucous membranes) can also be affected, which can lead to vision loss, destruction of nasal tissue, or impaired speech. Some affected individuals have damage to internal organs and tissues. The nerve damage that occurs in multibacillary leprosy often results in a lack of sensation in the hands and feet. Repeated injuries that go unnoticed and untreated because of this lack of sensation can lead to reabsorption of affected fingers or toes by the body, resulting in the shortening or loss of these digits.Paucibacillary leprosy typically involves a small number of surface lesions on the skin. There is generally loss of sensation in these areas, but the other signs and symptoms that occur in multibacillary leprosy are less likely to develop in this form of the disorder.In any form of leprosy, episodes called reactions can occur, and can lead to further nerve damage. These episodes can include reversal reactions, which involve pain and swelling of the skin lesions and the nerves in the hands and feet. People with the more severe forms of leprosy can develop a type of reaction called erythema nodosum leprosum (ENL). These episodes involve fever and painful skin nodules. In addition, painful, swollen nerves can occur. ENL can also lead to inflammation of the joints, eyes, and the testicles in men.Leprosy has long been stigmatized because of its infectious nature and the disfigurement it can cause. This stigma can cause social and emotional problems for affected individuals. However, modern treatments can prevent leprosy from getting worse and spreading to other people. While the infection is curable, nerve and tissue damage that occurred before treatment is generally permanent. u Pattern unknown PRKN https://medlineplus.gov/genetics/gene/prkn LTA https://www.ncbi.nlm.nih.gov/gene/4049 TLR1 https://www.ncbi.nlm.nih.gov/gene/7096 TLR2 https://www.ncbi.nlm.nih.gov/gene/7097 PACRG https://www.ncbi.nlm.nih.gov/gene/135138 Hansen disease Hansen's disease Infection due to Mycobacterium leprae GTR C1843632 GTR C1968668 GTR C1970254 GTR C2750733 ICD-10-CM A30.0 ICD-10-CM A30.1 ICD-10-CM A30.3 ICD-10-CM A30.5 ICD-10-CM A30.9 MeSH D007918 OMIM 246300 OMIM 607572 OMIM 609888 OMIM 610988 OMIM 613223 OMIM 613407 SNOMED CT 81004002 2018-02 2026-03-16 Leptin receptor deficiency https://medlineplus.gov/genetics/condition/leptin-receptor-deficiency descriptionLeptin receptor deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. The extreme hunger leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret.People with leptin receptor deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Affected individuals experience delayed puberty or do not go through puberty, and they may be unable to conceive children (infertile). ar Autosomal recessive LEPR https://medlineplus.gov/genetics/gene/lepr Congenital deficiency of the leptin receptor Leptin receptor-related monogenic obesity Obesity due to leptin receptor gene deficiency Obesity, morbid, due to leptin receptor deficiency Obesity, morbid, nonsyndromic 2 GTR C3554225 MeSH D009767 OMIM 614963 2013-10 2020-08-18 Lesch-Nyhan syndrome https://medlineplus.gov/genetics/condition/lesch-nyhan-syndrome descriptionLesch-Nyhan syndrome is a condition that occurs almost exclusively in males. It is characterized by neurological and behavioral abnormalities and the overproduction of uric acid. Uric acid is a waste product of normal chemical processes and is found in blood and urine. Excess uric acid can be released from the blood and build up under the skin and cause gouty arthritis (arthritis caused by an accumulation of uric acid in the joints). Uric acid accumulation can also cause kidney and bladder stones.The nervous system and behavioral disturbances experienced by people with Lesch-Nyhan syndrome include abnormal involuntary muscle movements, such as tensing of various muscles (dystonia), jerking movements (chorea), and flailing of the limbs (ballismus). People with Lesch-Nyhan syndrome usually cannot walk, require assistance sitting, and generally use a wheelchair. Self-injury (including biting and head banging) is the most common and distinctive behavioral problem in individuals with Lesch-Nyhan syndrome. xr X-linked recessive HPRT1 https://medlineplus.gov/genetics/gene/hprt1 Choreoathetosis self-mutilation syndrome Complete HPRT deficiency Complete hypoxanthine-guanine phosphoribosyltransferase deficiency Deficiency of guanine phosphoribosyltransferase Deficiency of hypoxanthine phosphoribosyltransferase HGPRT deficiency Hypoxanthine guanine phosphoribosyltransferase deficiency Hypoxanthine phosphoribosyltransferase deficiency Juvenile gout, choreoathetosis, mental retardation syndrome Juvenile hyperuricemia syndrome Lesch-Nyhan disease LND LNS Primary hyperuricemia syndrome Total HPRT deficiency Total hypoxanthine-guanine phosphoribosyl transferase deficiency X-linked hyperuricemia X-linked primary hyperuricemia X-linked uric aciduria enzyme defect GTR C0023374 ICD-10-CM E79.1 MeSH D007926 OMIM 300322 OMIM 300323 SNOMED CT 10406007 SNOMED CT 124275001 2007-12 2020-08-18 Leukocyte adhesion deficiency type 1 https://medlineplus.gov/genetics/condition/leukocyte-adhesion-deficiency-type-1 descriptionLeukocyte adhesion deficiency type 1 is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as viruses, bacteria, and fungi. Starting from birth, people with leukocyte adhesion deficiency type 1 develop serious bacterial and fungal infections.One of the first signs of leukocyte adhesion deficiency type 1 is a delay in the detachment of the umbilical cord stump after birth. In newborns, the stump normally falls off within the first two weeks of life; but, in infants with leukocyte adhesion deficiency type 1, this separation usually occurs at three weeks or later. In addition, affected infants often have inflammation of the umbilical cord stump (omphalitis) due to a bacterial infection.In leukocyte adhesion deficiency type 1, bacterial and fungal infections most commonly occur on the skin and mucous membranes such as the moist lining of the nose and mouth. In childhood, people with this condition develop severe inflammation of the gums (gingivitis) and other tissue around the teeth (periodontitis), which often results in the loss of both primary and permanent teeth. These infections often spread to cover a large area. A hallmark of leukocyte adhesion deficiency type 1 is the lack of pus formation at the sites of infection. In people with this condition, wounds are slow to heal, which can lead to additional infection.Life expectancy in individuals with leukocyte adhesion deficiency type 1 is often severely shortened. Due to repeat infections, affected individuals may not survive past infancy. ar Autosomal recessive ITGB2 https://medlineplus.gov/genetics/gene/itgb2 LAD1 Leucocyte adhesion deficiency type 1 Leukocyte adhesion molecule deficiency type 1 GTR C0398738 MeSH D018370 OMIM 116920 SNOMED CT 234582006 2014-04 2020-08-18 Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation descriptionLeukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (commonly referred to as LBSL) is a progressive disorder that affects the brain and spinal cord. Leukoencephalopathy refers to abnormalities in the white matter of the brain, which is tissue containing nerve cell fibers (axons) that transmit nerve impulses.Most affected individuals begin to develop movement problems during childhood or adolescence. However, in some individuals, these problems do not develop until adulthood. People with LBSL have abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). In addition, affected individuals lose the ability to sense the position of their limbs or vibrations with their limbs. These movement and sensation problems affect the legs more than the arms, making walking difficult. Most affected individuals eventually require wheelchair assistance, sometimes as early as their teens, although the age varies.People with LBSL can have other signs and symptoms of the condition. Some affected individuals develop recurrent seizures (epilepsy), speech difficulties (dysarthria), learning problems, or mild deterioration of mental functioning. Some people with this disorder are particularly vulnerable to severe complications following minor head trauma, which may trigger a loss of consciousness, other reversible neurological problems, or fever.Distinct changes in the brains of people with LBSL can be seen using magnetic resonance imaging (MRI). These characteristic abnormalities typically involve particular parts of the white matter of the brain and specific regions (called tracts) within the brainstem and spinal cord, especially the pyramidal tract and the dorsal column. In addition, most affected individuals have a high level of a substance called lactate in the white matter of the brain, which is identified using another test called magnetic resonance spectroscopy (MRS). ar Autosomal recessive DARS2 https://medlineplus.gov/genetics/gene/dars2 LBSL Mitochondrial aspartyl-tRNA synthetase deficiency GTR C1970180 MeSH D056784 OMIM 611105 SNOMED CT 703537008 2011-08 2020-08-18 Leukoencephalopathy with thalamus and brainstem involvement and high lactate https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate descriptionLeukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a disorder that affects the brain. LTBL is one of a group of genetic disorders called leukodystrophies, which feature abnormalities of the nervous system's white matter. White matter consists of nerve fibers covered by a fatty substance, called myelin, that insulates nerve fibers and promotes the rapid transmission of nerve impulses.LTBL is characterized by distinct changes in the brain, which can be seen using magnetic resonance imaging (MRI). These abnormalities typically involve white matter in regions of the brain known as the cerebrum and cerebellum. Abnormalities can also be seen in other regions of the brain, including the brainstem, which is the part that connects to the spinal cord. Affected brain regions include the thalamus, midbrain, pons, and medulla oblongata. Thinning of the tissue that connects the left and right halves of the brain (the corpus callosum) also occurs in people with LTBL. In addition, most affected individuals have a high level of a substance called lactate in the brain and elsewhere in the body.The severity of the condition varies. Mildly affected individuals usually develop signs and symptoms after the age of 6 months. Loss of mental and movement abilities (psychomotor regression), muscle stiffness (spasticity), and extreme irritability are common, and some people with mild LTBL develop seizures. However, after age 2, the signs and symptoms of the condition improve: affected children regain some psychomotor abilities, seizures are reduced or disappear, MRI results become more normal, and lactate levels drop.Severely affected individuals have features that begin soon after birth. These infants typically have delayed development of mental and movement abilities (psychomotor delay), weak muscle tone (hypotonia), involuntary muscle tensing (dystonia), muscle spasticity, and seizures. Some have extremely high levels of lactate (lactic acidosis), which can cause serious breathing problems and an abnormal heartbeat. Liver failure occurs in some severely affected infants. In severe cases, the signs and symptoms do not improve and can be life-threatening. In some people with LTBL, the features fall between mild and severe. ar Autosomal recessive EARS2 https://medlineplus.gov/genetics/gene/ears2 Combined oxidative phosphorylation deficiency 12 COXPD12 LTBL GTR C4706421 MeSH D056784 OMIM 614924 2016-09 2023-11-10 Leukoencephalopathy with vanishing white matter https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-vanishing-white-matter descriptionLeukoencephalopathy with vanishing white matter is a progressive disorder that mainly affects the brain and spinal cord (central nervous system). This disorder causes deterioration of the central nervous system's white matter, which consists of nerve fibers covered by myelin. Myelin is the fatty substance that insulates and protects nerves.In most cases, people with leukoencephalopathy with vanishing white matter show no signs or symptoms of the disorder at birth. Affected children may have slightly delayed development of motor skills such as crawling or walking. During early childhood, most affected individuals begin to develop motor symptoms, including abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). There may also be some deterioration of mental functioning, but this is not usually as pronounced as the motor symptoms. Some affected females may have abnormal development of the ovaries (ovarian dysgenesis). Specific changes in the brain as seen using magnetic resonance imaging (MRI) are characteristic of leukoencephalopathy with vanishing white matter, and may be visible before the onset of symptoms.While childhood onset is the most common form of leukoencephalopathy with vanishing white matter, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood, when behavioral or psychiatric problems may be the first signs of the disease. Some females with milder forms of leukoencephalopathy with vanishing white matter who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.Progression of leukoencephalopathy with vanishing white matter is generally uneven, with periods of relative stability interrupted by episodes of rapid decline. People with this disorder are particularly vulnerable to stresses such as infection, mild head trauma or other injury, or even extreme fright. These stresses may trigger the first symptoms of the condition or worsen existing symptoms, and can cause affected individuals to become lethargic or comatose. ar Autosomal recessive EIF2B1 https://medlineplus.gov/genetics/gene/eif2b1 EIF2B2 https://medlineplus.gov/genetics/gene/eif2b2 EIF2B3 https://medlineplus.gov/genetics/gene/eif2b3 EIF2B4 https://medlineplus.gov/genetics/gene/eif2b4 EIF2B5 https://medlineplus.gov/genetics/gene/eif2b5 CACH syndrome Childhood ataxia with central nervous system hypomyelination Cree leukoencephalopathy Myelinosis centralis diffusa Vanishing white matter disease Vanishing white matter leukodystrophy GTR C1858991 MeSH D020279 MeSH D056784 OMIM 603896 SNOMED CT 447351004 2007-10 2020-08-18 Leydig cell hypoplasia https://medlineplus.gov/genetics/condition/leydig-cell-hypoplasia descriptionLeydig cell hypoplasia is a condition that affects male sexual development. It is characterized by underdevelopment (hypoplasia) of Leydig cells in the testes. Leydig cells secrete male sex hormones (androgens) that are important for normal male sexual development before birth and during puberty.In Leydig cell hypoplasia, affected individuals with a typical male chromosomal pattern (46,XY) may have a range of genital abnormalities. Affected males may have a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), or a scrotum divided into two lobes (bifid scrotum). Because of these abnormalities, the external genitalia may not look clearly male or clearly female.In more severe cases of Leydig cell hypoplasia, people with a typical male chromosomal pattern (46,XY) have female external genitalia. They have small testes that are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. People with this form of the disorder do not develop secondary sex characteristics, such as increased body hair, at puberty. Some researchers refer to this form of Leydig cell hypoplasia as type 1 and designate less severe cases as type 2. ar Autosomal recessive LHCGR https://medlineplus.gov/genetics/gene/lhcgr 46,XY disorder of sex development due to LH defects LCH Leydig cell agenesis LH resistance due to LH receptor deactivation Male hypergonadotropic hypogonadism due to LHCGR defect GTR C0266432 ICD-10-CM MeSH D058490 OMIM 238320 SNOMED CT 56212008 2010-04 2023-10-26 Li-Fraumeni syndrome https://medlineplus.gov/genetics/condition/li-fraumeni-syndrome descriptionLi-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different. ad Autosomal dominant TP53 https://medlineplus.gov/genetics/gene/tp53 CHEK2 https://www.ncbi.nlm.nih.gov/gene/11200 LFS Sarcoma family syndrome of Li and Fraumeni Sarcoma, breast, leukemia, and adrenal gland (SBLA) syndrome SBLA syndrome GTR C0085390 GTR C1835398 GTR C5882668 ICD-10-CM Z15.01 MeSH D016864 OMIM 151623 OMIM 609265 SNOMED CT 428850001 2007-01 2020-08-18 Liddle syndrome https://medlineplus.gov/genetics/condition/liddle-syndrome descriptionLiddle syndrome is an inherited form of high blood pressure (hypertension). This condition is characterized by severe hypertension that begins unusually early in life, often in childhood, although some affected individuals are not diagnosed until adulthood. Some people with Liddle syndrome have no additional signs or symptoms, especially in childhood. Over time, however, untreated hypertension can lead to heart disease or stroke, which may be fatal.In addition to hypertension, affected individuals can have low levels of potassium in the blood (hypokalemia). Signs and symptoms of hypokalemia include muscle weakness or pain, fatigue, constipation, or heart palpitations. The shortage of potassium can also raise the pH of the blood, a condition known as metabolic alkalosis. ad Autosomal dominant SCNN1B https://medlineplus.gov/genetics/gene/scnn1b SCNN1G https://medlineplus.gov/genetics/gene/scnn1g Pseudoaldosteronism Pseudoprimary hyperaldosteronism GTR C0221043 MeSH D056929 OMIM 177200 SNOMED CT 707747007 2013-03 2023-03-21 Liebenberg syndrome https://medlineplus.gov/genetics/condition/liebenberg-syndrome descriptionLiebenberg syndrome is a condition that is characterized by abnormal development of the elbows, wrists, and hands. Joint deformities (contractures) that limit the movement of these structures are common. The signs and symptoms and the severity of Liebenberg syndrome can vary among affected individuals.In people with Liebenberg syndrome, the bones and tissues of the elbows typically resemble those of the knees, and the arm bones near the elbow are shaped more like related structures in the leg. These changes limit the range of motion in the elbows.Individuals with Liebenberg syndrome may have bones in the wrists that are joined together (fused), resembling related structures in the ankles and heels. This fusion can cause the hand to bend permanently toward the thumb (radial deviation).Abnormalities of the hands and fingers may also be seen in individuals with Liebenberg syndrome. The bones in the hand that connect the wrist to the fingers (metacarpals) tend to be longer than normal, resembling the bones in the foot that connect the ankle to the toes. People with Liebenberg syndrome typically have fingers that are short (brachydactyly). Some affected individuals have a little finger that is permanently bent (camptodactyly) or fingers that are fused together (syndactyly).Individuals with Liebenberg syndrome typically have no other signs and symptoms that are related to this condition. The development of the legs and feet is not affected. ad Autosomal dominant PITX1 https://medlineplus.gov/genetics/gene/pitx1 5 https://medlineplus.gov/genetics/chromosome/5 Brachydactyly with joint dysplasia Brachydactyly-elbow wrist dysplasia syndrome Brachydactyly-joint dysplasia syndrome Carpal synostosis with dysplastic elbow joints and brachydactyly LBNBG GTR C1861313 MeSH D038062 OMIM 186550 2026-01 2026-01-12 Limb-girdle muscular dystrophy https://medlineplus.gov/genetics/condition/limb-girdle-muscular-dystrophy descriptionThe limb-girdle muscular dystrophies are a group of diseases that cause muscle weakness (myopathy) and wasting (atrophy). The muscles that are most affected are those closest to the center of the body (proximal muscles), specifically the muscles of the shoulders, upper arms, hips, and thighs. Signs and symptoms may appear as early as childhood and typically worsen over time.The severity, age of onset, and specific features of limb-girdle muscle dystrophy vary among affected individuals, even among members of the same family. In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet. Walking this way for an extended period of time can cause overgrowth (hypertrophy) of the calf muscles. Affected individuals may also have difficulty running. They may need to use their arms to push themselves up from a squatting position because of their weak thigh muscles. Over time, as myopathy and atrophy worsen, people with limb-girdle muscular dystrophy may require wheelchair assistance.Muscle atrophy may cause changes in posture or in the appearance of the shoulders, back, and arms. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Weak back muscles may also cause an affected individual to have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some affected individuals develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. A weakening of the heart muscle (cardiomyopathy) occurs in some people with limb-girdle muscular dystrophy. If the weakness affects the muscles needed for breathing, affected individuals may have mild to severe breathing problems. In some cases, affected individuals need a machine to help them breathe (mechanical ventilation).Intelligence is generally not affected in people with limb-girdle muscular dystrophy. However, developmental delays and intellectual disabilities have been reported in some affected individuals who have signs and symptoms that are more severe or that appear earlier in life. ad Autosomal dominant ar Autosomal recessive PLEC https://medlineplus.gov/genetics/gene/plec FKTN https://medlineplus.gov/genetics/gene/fktn TTN https://medlineplus.gov/genetics/gene/ttn COL6A1 https://medlineplus.gov/genetics/gene/col6a1 COL6A2 https://medlineplus.gov/genetics/gene/col6a2 COL6A3 https://medlineplus.gov/genetics/gene/col6a3 SGCA https://medlineplus.gov/genetics/gene/sgca SGCB https://medlineplus.gov/genetics/gene/sgcb SGCG https://medlineplus.gov/genetics/gene/sgcg SGCD https://medlineplus.gov/genetics/gene/sgcd CAPN3 https://medlineplus.gov/genetics/gene/capn3 DYSF https://medlineplus.gov/genetics/gene/dysf ANO5 https://medlineplus.gov/genetics/gene/ano5 POMT1 https://medlineplus.gov/genetics/gene/pomt1 POMT2 https://medlineplus.gov/genetics/gene/pomt2 FKRP https://medlineplus.gov/genetics/gene/fkrp CRPPA https://medlineplus.gov/genetics/gene/crppa LAMA2 https://medlineplus.gov/genetics/gene/lama2 POGLUT1 https://medlineplus.gov/genetics/gene/poglut1 DAG1 https://www.ncbi.nlm.nih.gov/gene/1605 TCAP https://www.ncbi.nlm.nih.gov/gene/8557 HNRNPDL https://www.ncbi.nlm.nih.gov/gene/9987 DNAJB6 https://www.ncbi.nlm.nih.gov/gene/10049 POPDC1 https://www.ncbi.nlm.nih.gov/gene/11149 TRIM32 https://www.ncbi.nlm.nih.gov/gene/22954 TNPO3 https://www.ncbi.nlm.nih.gov/gene/23534 GMPPB https://www.ncbi.nlm.nih.gov/gene/29925 POMGNT1 https://www.ncbi.nlm.nih.gov/gene/55624 TRAPPC11 https://www.ncbi.nlm.nih.gov/gene/60684 POPDC3 https://www.ncbi.nlm.nih.gov/gene/64208 POMGNT2 https://www.ncbi.nlm.nih.gov/gene/84892 LGMD Limb-girdle syndrome Myopathic limb-girdle syndrome GTR C0686353 MeSH D049288 OMIM 253600 OMIM 253601 OMIM 253700 OMIM 254110 OMIM 601287 OMIM 601954 OMIM 603511 OMIM 604286 OMIM 607155 OMIM 608099 OMIM 608423 OMIM 608807 OMIM 609115 OMIM 609308 OMIM 611307 OMIM 611588 OMIM 613157 OMIM 613158 OMIM 613530 OMIM 613723 OMIM 613818 OMIM 615352 OMIM 615356 OMIM 616052 OMIM 616094 OMIM 617232 OMIM 618129 OMIM 618135 SNOMED CT 240056002 SNOMED CT 240064008 SNOMED CT 93153005 2025-11 2025-12-12 Lipoid proteinosis https://medlineplus.gov/genetics/condition/lipoid-proteinosis descriptionLipoid proteinosis is a condition that results from the formation of numerous small clumps (deposits) of proteins and other molecules in various tissues throughout the body. These tiny clumps appear in the skin, upper respiratory tract, the moist tissues that line body openings such as the eyelids and the inside of the mouth (mucous membranes), and other areas.The first symptom of this condition is usually a hoarse voice, which is due to deposits in the vocal cords. In infancy the hoarseness is expressed as a weak cry. The voice abnormalities persist throughout life and can ultimately cause difficulty speaking or complete loss of speech. Involvement of the throat, tonsils, and lips can result in breathing problems and upper respiratory tract infections. Deposits in the tongue can result in a thick and shortened tongue. They can also thicken the band of tissue that connects the tongue to the bottom of the mouth (frenulum), making it difficult to extend the tongue. The tongue may also have a smooth appearance due to damage to the taste buds.A characteristic feature of lipoid proteinosis is the presence of multiple tiny, bead-like bumps lining the upper and lower eyelids along the lash line. These bumps are known as moniliform blepharosis. They may cause eyeball irritation or itching but generally do not impair vision.The skin and mucous membranes are often fragile in children with lipoid proteinosis, leading to bleeding and scabbing following minor trauma. These problems often first appear in infancy in the mouth and on the face and limbs. Over time, these scabs form blisters and scars. Deposits accumulate in the skin, which causes the skin to become thickened and yellowish in color. Skin damage appears more frequently on areas that experience friction, such as the hands, elbows, knees, buttocks, and armpits. Some people with this condition have hair loss (alopecia) affecting their scalp, eyelashes, and eyebrows.Neurologic features are also common in people with lipoid proteinosis. Affected individuals may have recurrent seizures (epilepsy) or behavioral and neurological problems, which can include headaches, aggressive behaviors, paranoia, hallucinations, short-term memory loss, and absence of fear. These features are thought to be associated with the presence of deposits and an accumulation of calcium (calcification) in areas of the brain called the temporal lobes. The temporal lobes help process hearing, speech, memory, and emotion. The brain abnormalities and neurological features do not always occur together, so the cause of the neurological features is still unclear.Deposits can be found in some internal organs, including the stomach, a section of the small intestine called the duodenum, and the colon. The deposits in these tissues often do not cause any symptoms and may disappear over time. ar Autosomal recessive ECM1 https://medlineplus.gov/genetics/gene/ecm1 Hyalinosis cutis et mucosae Lipid proteinosis Lipoglycoproteinosis Lipoid proteinosis of Urbach and Wiethe Lipoidosis cutis et mucosae Lipoidproteinosis Lipoproteinosis Urbach-Wiethe disease Urbach-Wiethe lipoid proteinosis Urbach-Wiethe syndrome GTR C0023795 MeSH D008065 OMIM 247100 SNOMED CT 38692000 2016-07 2020-08-18 Lissencephaly with cerebellar hypoplasia https://medlineplus.gov/genetics/condition/lissencephaly-with-cerebellar-hypoplasia descriptionLissencephaly with cerebellar hypoplasia (LCH) affects brain development, resulting in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. In addition, the part of the brain that coordinates movement is unusually small and underdeveloped (cerebellar hypoplasia). Other parts of the brain are also often underdeveloped in LCH, including the hippocampus, which plays a role in learning and memory, and the part of the brain that is connected to the spinal cord (the brainstem).Individuals with LCH have moderate to severe intellectual disability and delayed development. They have few or no communication skills, extremely poor muscle tone (hypotonia), problems with coordination and balance (ataxia), and difficulty sitting or standing without support. Most affected children experience recurrent seizures (epilepsy) that begin within the first months of life. Some affected individuals have nearsightedness (myopia), involuntary eye movements (nystagmus), or puffiness or swelling caused by a buildup of fluids in the body's tissues (lymphedema). ad Autosomal dominant ar Autosomal recessive TUBA1A https://medlineplus.gov/genetics/gene/tuba1a RELN https://medlineplus.gov/genetics/gene/reln LCH LIS2 LIS3 Lissencephaly 2 Lissencephaly 3 Lissencephaly syndrome, Norman-Roberts type Norman-Roberts syndrome GTR C0796089 GTR C1969029 ICD-10-CM Q04.3 MeSH D054221 OMIM 257320 OMIM 611603 SNOMED CT 715817007 SNOMED CT 717977003 2013-08 2020-08-18 Loeys-Dietz syndrome https://medlineplus.gov/genetics/condition/loeys-dietz-syndrome descriptionLoeys-Dietz syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, and blood vessels.There are five types of Loeys-Dietz syndrome, labelled types I through V, which are distinguished by their genetic cause. Regardless of the type, signs and symptoms of Loeys-Dietz syndrome can become apparent anytime from childhood through adulthood, and the severity is variable.Loeys-Dietz syndrome is characterized by enlargement of the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. The aorta can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection). People with Loeys-Dietz syndrome can also have aneurysms or dissections in arteries throughout the body and have arteries with abnormal twists and turns (arterial tortuosity).Individuals with Loeys-Dietz syndrome often have skeletal problems including premature fusion of the skull bones (craniosynostosis), an abnormal side-to-side curvature of the spine (scoliosis), either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum), an inward- and upward-turning foot (clubfoot), flat feet (pes planus), or elongated limbs with joint deformities called contractures that restrict the movement of certain joints. A membrane called the dura, which surrounds the brain and spinal cord, can be abnormally enlarged (dural ectasia). In individuals with Loeys-Dietz syndrome, dural ectasia typically does not cause health problems. Malformation or instability of the spinal bones (vertebrae) in the neck is a common feature of Loeys-Dietz syndrome and can lead to injuries to the spinal cord. Some affected individuals have joint inflammation (osteoarthritis) that commonly affects the knees and the joints of the hands, wrists, and spine.People with Loeys-Dietz syndrome may bruise easily and develop abnormal scars after wound healing. The skin is frequently described as translucent, often with stretch marks (striae) and visible underlying veins. Some individuals with Loeys-Dietz syndrome develop an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung (spontaneous pneumothorax) or a protrusion of organs through gaps in muscles (hernias). Other characteristic features include widely spaced eyes (hypertelorism), eyes that do not point in the same direction (strabismus), a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula), and an opening in the roof of the mouth (cleft palate).Individuals with Loeys-Dietz syndrome frequently develop immune system-related problems such as food allergies, asthma, or inflammatory disorders such as eczema or inflammatory bowel disease. ad Autosomal dominant TGFBR2 https://medlineplus.gov/genetics/gene/tgfbr2 TGFBR1 https://medlineplus.gov/genetics/gene/tgfbr1 SMAD3 https://medlineplus.gov/genetics/gene/smad3 TGFB2 https://medlineplus.gov/genetics/gene/tgfb2 TGFB3 https://medlineplus.gov/genetics/gene/tgfb3 LDS Loeys-Dietz aortic aneurysm syndrome GTR C2674574 GTR C2697932 GTR C3151087 GTR C3553762 GTR C3810012 GTR C4551955 MeSH D055947 OMIM 609192 OMIM 610168 OMIM 613795 OMIM 614816 OMIM 615582 SNOMED CT 446263001 SNOMED CT 838364007 2017-03 2020-08-18 Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency descriptionLong-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).Signs and symptoms of LCHAD deficiency typically appear during infancy or early childhood. Many affected infants have feeding difficulties, such as an extreme dislike of certain foods  or of eating at all (food or feeding aversion), nausea, and vomiting. Other signs and symptoms include lack of energy (lethargy), low blood glucose (hypoglycemia), weak muscle tone (hypotonia), delayed development of milestones, liver problems, and abnormalities in the light-sensitive tissue at the back of the eye (retina). Affected individuals can have impaired vision or difficulty seeing things far away (myopia) or in low light (night blindness). These vision problems worsen over time. Later in childhood, people with this condition may experience muscle pain, breakdown of muscle tissue (rhabdomyolysis), and a loss of sensation in their arms and legs (peripheral neuropathy). Infants and children with LCHAD deficiency are also at risk of serious heart problems, such as a weakened heart (cardiomyopathy) and heart failure; breathing difficulties; coma; and sudden death.Problems related to LCHAD deficiency can be triggered when the body is under stress, for example during periods of fasting, illnesses such as viral infections, or weather extremes. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. ar Autosomal recessive HADHA https://medlineplus.gov/genetics/gene/hadha 3-hydroxyacyl-CoA dehydrogenase, long chain, deficiency LCHAD deficiency Long-chain 3-hydroxy acyl CoA dehydrogenase deficiency Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency Long-chain 3-OH acyl-CoA dehydrogenase deficiency Trifunctional protein deficiency, type 1 GTR C3711645 MeSH D008052 OMIM 609016 SNOMED CT 307127004 2023-02 2023-07-26 Lowe syndrome https://medlineplus.gov/genetics/condition/lowe-syndrome descriptionLowe syndrome is a condition that primarily affects the eyes, brain, and kidneys. This disorder occurs almost exclusively in males.Infants with Lowe syndrome are born with thick clouding of the lenses in both eyes (congenital cataracts), often with other eye abnormalities that can impair vision. About half of affected infants develop an eye disease called infantile glaucoma, which is characterized by increased pressure within the eyes.Many individuals with Lowe syndrome have delayed development, and intellectual ability ranges from normal to severely impaired. Behavioral problems and seizures have also been reported in children with this condition. Most affected children have weak muscle tone from birth (neonatal hypotonia), which can contribute to feeding difficulties, problems with breathing, and delayed development of motor skills such as sitting, standing, and walking.Kidney (renal) abnormalities, most commonly a condition known as renal Fanconi syndrome, frequently develop in individuals with Lowe syndrome. The kidneys play an essential role in maintaining the right amounts of minerals, salts, water, and other substances in the body. In individuals with renal Fanconi syndrome, the kidneys are unable to reabsorb important nutrients into the bloodstream. Instead, the nutrients are excreted in the urine. These kidney problems lead to increased urination, dehydration, and abnormally acidic blood (metabolic acidosis). A loss of salts and nutrients may also impair growth and result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. Progressive kidney problems in older children and adults with Lowe syndrome can lead to life-threatening renal failure and end-stage renal disease (ESRD). xr X-linked recessive OCRL https://medlineplus.gov/genetics/gene/ocrl Cerebrooculorenal syndrome Lowe oculocerebrorenal syndrome Oculocerebrorenal syndrome Oculocerebrorenal syndrome of Lowe Phosphatidylinositol-4,5-bisphosphate-5-phosphatase deficiency GTR C0028860 ICD-10-CM E72.03 MeSH D009800 OMIM 309000 SNOMED CT 79385002 2008-05 2020-08-18 Lujan syndrome https://medlineplus.gov/genetics/condition/lujan-syndrome descriptionLujan syndrome is a condition characterized by intellectual disability, behavioral problems, and certain physical features. It occurs almost exclusively in males.The intellectual disability associated with Lujan syndrome is usually mild to moderate. Behavioral problems can include hyperactivity, aggressiveness, extreme shyness, and excessive attention-seeking. Some affected individuals have features of autism or related developmental disorders affecting communication and social interaction. A few have been diagnosed with psychiatric problems such as delusions and hallucinations.Characteristic physical features of Lujan syndrome include a tall, thin body and an unusually large head (macrocephaly). Affected individuals also have a long, thin face with distinctive facial features such as a prominent top of the nose (high nasal root); a short space between the nose and the upper lip (philtrum); a narrow roof of the mouth (palate); crowded teeth; and a small chin (micrognathia). Almost all people with this condition have weak muscle tone (hypotonia).Additional signs and symptoms of Lujan syndrome can include abnormal speech, heart defects, and abnormalities of the genitourinary system. Many affected individuals have long fingers and toes with an unusually large range of joint movement (hyperextensibility). Seizures and abnormalities of the tissue that connects the left and right halves of the brain (corpus callosum) have also been reported in people with this condition. xr X-linked recessive MED12 https://medlineplus.gov/genetics/gene/med12 LFS Lujan-Fryns syndrome X-linked intellectual deficit with marfanoid habitus X-linked mental retardation with marfanoid habitus XLMR with marfanoid features GTR C0796022 MeSH D038901 OMIM 309520 SNOMED CT 422437002 2012-12 2020-08-18 Lung cancer https://medlineplus.gov/genetics/condition/lung-cancer descriptionLung cancer is a disease in which certain cells in the lungs become abnormal and multiply uncontrollably to form a tumor. Lung cancer may not cause signs or symptoms in its early stages. Some people with lung cancer have chest pain, frequent coughing, blood in the mucus, breathing problems, trouble swallowing or speaking, loss of appetite and weight loss, fatigue, or swelling in the face or neck. Additional symptoms can develop if the cancer spreads (metastasizes) into other tissues. Lung cancer occurs most often in adults in their sixties or seventies. Most people who develop lung cancer have a history of long-term tobacco smoking; however, the condition can occur in people who have never smoked.Lung cancer is generally divided into two types, small cell lung cancer and non-small cell lung cancer, based on the size of the affected cells when viewed under a microscope. Non-small cell lung cancer accounts for 85 percent of lung cancer, while small cell lung cancer accounts for the remaining 15 percent.Small cell lung cancer grows quickly and in more than half of cases the cancer has spread beyond the lung by the time the condition is diagnosed. Small cell lung cancer often metastasizes, most commonly to the liver, brain, bones, and adrenal glands (small hormone-producing glands located on top of each kidney). After diagnosis, most people with small cell lung cancer survive for about 1 year; less than seven percent survive 5 years.Non-small cell lung cancer is divided into three main subtypes: adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Adenocarcinoma arises from the cells that line the small air sacs (alveoli) located throughout the lungs. Squamous cell carcinoma arises from squamous cells that line the passages leading from the windpipe (trachea) to the lungs (bronchi). Large cell carcinoma arises from epithelial cells that line the lungs. Large cell carcinoma encompasses non-small cell lung cancers that do not appear to be adenocarcinomas or squamous cell carcinomas. The 5-year survival rate for people with non-small cell lung cancer is usually between 11 and 17 percent; it can be lower or higher depending on the subtype and stage of the cancer. n Not inherited ad Autosomal dominant RB1 https://medlineplus.gov/genetics/gene/rb1 TP53 https://medlineplus.gov/genetics/gene/tp53 PTEN https://medlineplus.gov/genetics/gene/pten STK11 https://medlineplus.gov/genetics/gene/stk11 NF1 https://medlineplus.gov/genetics/gene/nf1 PRKN https://medlineplus.gov/genetics/gene/prkn RET https://medlineplus.gov/genetics/gene/ret KRAS https://medlineplus.gov/genetics/gene/kras BRAF https://medlineplus.gov/genetics/gene/braf MAP2K1 https://medlineplus.gov/genetics/gene/map2k1 NRAS https://medlineplus.gov/genetics/gene/nras ALK https://medlineplus.gov/genetics/gene/alk SMARCA4 https://medlineplus.gov/genetics/gene/smarca4 PIK3CA https://medlineplus.gov/genetics/gene/pik3ca CDKN2A https://medlineplus.gov/genetics/gene/cdkn2a EGFR https://medlineplus.gov/genetics/gene/egfr RIT1 https://medlineplus.gov/genetics/gene/rit1 MAP3K8 https://www.ncbi.nlm.nih.gov/gene/1326 ERBB2 https://www.ncbi.nlm.nih.gov/gene/2064 NRG1 https://www.ncbi.nlm.nih.gov/gene/3084 IRF1 https://www.ncbi.nlm.nih.gov/gene/3659 MET https://www.ncbi.nlm.nih.gov/gene/4233 DDR2 https://www.ncbi.nlm.nih.gov/gene/4921 SLC67A1 https://www.ncbi.nlm.nih.gov/gene/5002 PPP2R1B https://www.ncbi.nlm.nih.gov/gene/5519 ROS1 https://www.ncbi.nlm.nih.gov/gene/6098 KEAP1 https://www.ncbi.nlm.nih.gov/gene/9817 DLEC1 https://www.ncbi.nlm.nih.gov/gene/9940 RASSF1 https://www.ncbi.nlm.nih.gov/gene/11186 Cancer of bronchus Cancer of the lung Lung malignancies Lung malignant tumors Lung neoplasms Malignant lung tumor Malignant neoplasm of lung Malignant tumor of lung Pulmonary cancer Pulmonary carcinoma Pulmonary neoplasms Respiratory carcinoma GTR C0684249 ICD-10-CM C34 ICD-10-CM C34.0 ICD-10-CM C34.00 ICD-10-CM C34.01 ICD-10-CM C34.02 ICD-10-CM C34.1 ICD-10-CM C34.10 ICD-10-CM C34.11 ICD-10-CM C34.12 ICD-10-CM C34.2 ICD-10-CM C34.3 ICD-10-CM C34.30 ICD-10-CM C34.31 ICD-10-CM C34.32 ICD-10-CM C34.9 ICD-10-CM C34.90 ICD-10-CM C34.91 ICD-10-CM C34.92 MeSH D002289 MeSH D008175 MeSH D055752 OMIM 211980 SNOMED CT 363358000 SNOMED CT 830151004 2017-12 2020-08-18 Lyme disease https://medlineplus.gov/genetics/condition/lyme-disease descriptionLyme disease is an infectious disease caused by Borrelia burgdorferi bacteria. The bacteria are transferred to humans by tick bite, specifically by blacklegged ticks (commonly known as deer ticks). The condition is named for the location in which it was first described, the town of Lyme, Connecticut.If not treated with antibiotics, Lyme disease follows three stages: early localized, early disseminated, and late disseminated infection. A small percentage of individuals have symptoms that persist months or years after treatment, which is called post-treatment Lyme disease syndrome.A characteristic feature of Lyme disease, and the key feature of early localized infection, is a slowly expanding red rash on the skin (called erythema migrans) at the site of the tick bite; the rash is often bull's-eye shaped. Flu-like symptoms and enlarged lymph nodes (lymphadenopathy) are also early signs of infection. Most people who are treated at this stage never develop further symptoms.The early disseminated stage of Lyme disease occurs as the bacteria is carried throughout the body in the bloodstream. This stage occurs a few weeks after the tick bite. Signs and symptoms can include additional rashes on other parts of the body, flu-like symptoms, and lymphadenopathy. Some affected individuals develop neurologic problems (referred to as neuroborreliosis), such as paralyzed muscles in the face (facial palsy); pain, numbness, or weakness in the hands or feet; difficulty concentrating; or memory problems. Rarely, the heart is affected (Lyme carditis), causing a sensation of fluttering or pounding in the chest (palpitations) or an irregular heartbeat.The late disseminated stage of Lyme disease can occur months to years after the tick bite. The most common feature of this stage, Lyme arthritis, is characterized by episodes of joint pain and swelling, usually affecting the knees. In rare cases, the late disseminated stage also involves neurological problems.Individuals with post-treatment Lyme disease syndrome report ongoing exhaustion (fatigue), muscle and joint achiness, headache, or difficulty concentrating even after treatment with antibiotics, when there is no evidence of the bacteria in the body. Very rarely, individuals have joint pain and swelling for months or years after successful antibiotic treatment. This complication is called antibiotic-refractory Lyme arthritis. n Not inherited u Pattern unknown HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 TLR1 https://www.ncbi.nlm.nih.gov/gene/7096 B. burgdorferi infection Borrelia burgdorferi infection Borreliosis, Lyme Infection by Borrelia burgdorferi Infection due to Borrelia burgdorferi sensu lato Lyme borreliosis ICD-10-CM A69.2 ICD-10-CM A69.20 ICD-10-CM A69.21 ICD-10-CM A69.22 ICD-10-CM A69.23 MeSH D008193 SNOMED CT 23502006 2018-06 2023-11-08 Lymphangioleiomyomatosis https://medlineplus.gov/genetics/condition/lymphangioleiomyomatosis descriptionLymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body. Lymph fluid helps exchange immune cells, proteins, and other substances between the blood and tissues.LAM is found almost exclusively in women. It often occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM.Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation.Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas. n Not inherited TSC1 https://medlineplus.gov/genetics/gene/tsc1 TSC2 https://medlineplus.gov/genetics/gene/tsc2 LAM Lymphangiomyomatosis GTR C0751674 ICD-10-CM J84.81 MeSH D018192 OMIM 606690 SNOMED CT 277844007 2010-06 2020-08-18 Lymphedema-distichiasis syndrome https://medlineplus.gov/genetics/condition/lymphedema-distichiasis-syndrome descriptionLymphedema-distichiasis syndrome is a condition that affects the normal function of the lymphatic system, which is a part of the circulatory and immune systems. The lymphatic system produces and transports fluids and immune cells throughout the body. People with lymphedema-distichiasis syndrome develop puffiness or swelling (lymphedema) of the limbs, typically the legs and feet. Another characteristic of this syndrome is the growth of extra eyelashes (distichiasis), ranging from a few extra eyelashes to a full extra set on both the upper and lower lids. These eyelashes do not grow along the edge of the eyelid, but out of its inner lining. When the abnormal eyelashes touch the eyeball, they can cause damage to the clear covering of the eye (cornea). Related eye problems can include an irregular curvature of the cornea causing blurred vision (astigmatism) or scarring of the cornea. Other health problems associated with this disorder include swollen and knotted (varicose) veins, droopy eyelids (ptosis), heart abnormalities, and an opening in the roof of the mouth (a cleft palate).All people with lymphedema-distichiasis syndrome have extra eyelashes present at birth. The age of onset of lymphedema varies, but it most often begins during puberty. Males usually develop lymphedema earlier than females, but all affected individuals will develop lymphedema by the time they are in their forties. ad Autosomal dominant FOXC2 https://medlineplus.gov/genetics/gene/foxc2 Distichiasis-lymphedema syndrome Lymphedema with distichiasis GTR C0265345 MeSH D008209 OMIM 153400 SNOMED CT 8634009 2008-02 2020-08-18 Lynch syndrome https://medlineplus.gov/genetics/condition/lynch-syndrome descriptionLynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer. This includes cancers of the colon and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, urinary tract, brain, and skin. Additionally, women with this disorder have an increased risk of cancer of the ovaries and the lining of the uterus (endometrial cancer). Women with Lynch syndrome have a higher overall risk of developing cancer than men with the condition because of these cancers of the female reproductive system. In individuals with Lynch syndrome who develop cancer, the cancer typically occurs in their 40s or 50s.People with Lynch syndrome may occasionally have noncancerous (benign) growths in the colon, called colon polyps. In individuals with this disorder, colon polyps occur at a younger age but not in greater numbers than they do in the general population. ad Autosomal dominant MLH1 https://medlineplus.gov/genetics/gene/mlh1 MSH2 https://medlineplus.gov/genetics/gene/msh2 MSH6 https://medlineplus.gov/genetics/gene/msh6 PMS2 https://medlineplus.gov/genetics/gene/pms2 EPCAM https://medlineplus.gov/genetics/gene/epcam Cancer family syndrome Familial nonpolyposis colon cancer Hereditary nonpolyposis colorectal cancer Hereditary nonpolyposis colorectal neoplasms HNPCC GTR C1333990 GTR C1333991 GTR C1833477 GTR C1838333 GTR C2750471 GTR C2936783 MeSH D003123 OMIM 114500 OMIM 120435 SNOMED CT 716318002 2013-05 2025-05-09 Lysinuric protein intolerance https://medlineplus.gov/genetics/condition/lysinuric-protein-intolerance descriptionLysinuric protein intolerance is a disorder caused by the body's inability to digest and use certain protein building blocks (amino acids), namely lysine, arginine, and ornithine. Because the body cannot absorb these amino acids, which are found in many protein-rich foods, nausea and vomiting are typically experienced after ingesting protein.People with lysinuric protein intolerance have a variety of features, such as an enlarged liver and spleen (hepatosplenomegaly), short stature, muscle weakness, impaired immune function, and brittle bones that are prone to fracture (osteoporosis). A lung disorder called pulmonary alveolar proteinosis may also develop. This disorder is characterized by protein deposits in the lungs, which interfere with lung function and can be life-threatening. An accumulation of amino acids in the kidneys can cause end-stage renal disease (ESRD), in which the kidneys become unable to filter fluids and waste products from the body effectively. A lack of certain amino acids can cause elevated levels of ammonia in the blood. If ammonia levels are too high for too long, they can cause coma and intellectual disability.The signs and symptoms of lysinuric protein intolerance typically appear after infants are weaned and receive greater amounts of protein from solid foods. ar Autosomal recessive SLC7A7 https://medlineplus.gov/genetics/gene/slc7a7 Congenital lysinuria Hyperdibasic aminoaciduria LPI GTR C0268647 ICD-10-CM MeSH D020157 OMIM 222700 SNOMED CT 303852004 SNOMED CT 50056009 SNOMED CT 71751002 2023-03 2023-03-10 Lysosomal acid lipase deficiency https://medlineplus.gov/genetics/condition/lysosomal-acid-lipase-deficiency descriptionLysosomal acid lipase deficiency is an inherited condition characterized by problems with the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of fats (lipids) accumulate in cells and tissues throughout the body, which typically causes liver disease. There are two forms of the condition. The most severe and rarest form begins in infancy. The less severe form can begin from childhood to late adulthood.In the severe, early-onset form of lysosomal acid lipase deficiency, lipids accumulate throughout the body, particularly in the liver, within the first weeks of life. This accumulation of lipids leads to several health problems, including an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, fatty stool (steatorrhea), and poor absorption of nutrients from food (malabsorption). In addition, affected infants often have calcium deposits in small hormone-producing glands on top of each kidney (adrenal glands), low amounts of iron in the blood (anemia), and developmental delay. Scar tissue quickly builds up in the liver, leading to liver disease (cirrhosis). Infants with this form of lysosomal acid lipase deficiency develop multi-organ failure and severe malnutrition and generally do not survive past 1 year.In the later-onset form of lysosomal acid lipase deficiency, signs and symptoms vary and usually begin in mid-childhood, although they can appear anytime up to late adulthood. Nearly all affected individuals develop an enlarged liver (hepatomegaly); an enlarged spleen (splenomegaly) may also occur. About two-thirds of individuals have liver fibrosis, eventually leading to cirrhosis. Approximately one-third of individuals with the later-onset form have malabsorption, diarrhea, vomiting, and steatorrhea. Individuals with this form of lysosomal acid lipase deficiency may have increased liver enzymes and high cholesterol levels, which can be detected with blood tests.Some people with this later-onset form of lysosomal acid lipase deficiency develop an accumulation of fatty deposits on the artery walls (atherosclerosis). Although these deposits are common in the general population, they usually begin at an earlier age in people with lysosomal acid lipase deficiency. The deposits narrow the arteries, increasing the chance of heart attack or stroke. The expected lifespan of individuals with later-onset lysosomal acid lipase deficiency depends on the severity of the associated health problems.The two forms of lysosomal acid lipase deficiency were once thought to be separate disorders. The early-onset form was known as Wolman disease, and the later-onset form was known as cholesteryl ester storage disease. Although these two disorders have the same genetic cause and are now considered to be forms of a single condition, these names are still sometimes used to distinguish between the forms of lysosomal acid lipase deficiency. ar Autosomal recessive LIPA https://medlineplus.gov/genetics/gene/lipa Acid esterase deficiency Acid lipase deficiency Familial visceral xanthomatosis Familial xanthomatosis LAL deficiency LIPA deficiency Primary familial xanthomatosis Primary familial xanthomatosis with adrenal calcification GTR C0043208 MeSH D015223 OMIM 278000 SNOMED CT 715923003 2017-02 2020-08-18 Léri-Weill dyschondrosteosis https://medlineplus.gov/genetics/condition/leri-weill-dyschondrosteosis descriptionLéri-Weill dyschondrosteosis is a disorder of bone growth. Affected individuals typically have shortening of the long bones in the arms and legs (mesomelia). As a result of the shortened leg bones, people with Leri-Weill dyschondrosteosis typically have short stature. Most people with the condition also have an abnormality of the wrist and forearm bones called Madelung deformity, which may cause pain and limit wrist movement. This abnormality usually appears in childhood or early adolescence. Other features of Léri-Weill dyschondrosteosis can include increased muscle mass (muscle hypertrophy); bowing of a bone in the lower leg called the tibia; a greater-than-normal angling of the elbow away from the body (increased carrying angle); and a high arched palate.Léri-Weill dyschondrosteosis occurs in both males and females, although its signs and symptoms tend to be more severe in females. Researchers believe that the more severe features may result from hormonal differences. xd X-linked dominant ac Autosomal codominant SHOX https://medlineplus.gov/genetics/gene/shox DCO Dyschondrosteosis Leri-Weill dyschondrosteosis LWD GTR C0265309 MeSH D009139 OMIM 127300 SNOMED CT 17818006 2012-01 2020-08-18 MBD5-associated neurodevelopmental disorder https://medlineplus.gov/genetics/condition/mbd5-associated-neurodevelopmental-disorder descriptionMBD5-associated neurodevelopmental disorder (MAND) is a condition that affects neurological and physical development.Children with MAND have mild to severe intellectual disability and developmental delay. They often have poor coordination and do not walk until age 2 or 3. Their walking style (gait) is often unbalanced and wide-based. Language skills, both the production of speech and the ability to understand speech, are very limited in affected individuals. By age 2, most children with MAND develop recurring seizures (epilepsy). Most affected children have feeding problems due to weak muscle tone (hypotonia). Constipation also frequently occurs.Sleep problems are common in MAND and include night terrors, waking frequently during the night, and waking early in the morning. As a result, many affected individuals are extremely tired during the day due to lack of sleep and poor-quality sleep. Most people with MAND have features similar to autism spectrum disorder, a developmental condition that affects communication and social interaction. They have a short attention span; perform repetitive hand movements (stereotypies), such as clapping, hand licking, and hand sucking; and grind their teeth.People with MAND tend to have subtle facial features, including a broad forehead, thick and highly arched eyebrows, abnormalities of the outer ear, a short nose, a wide or depressed nasal bridge, downturned corners of the mouth, an upper lip that points outward (called a tented lip), and a full lower lip. Some affected individuals have mild skeletal abnormalities including small hands and feet, short fingers (brachydactyly), curved pinky fingers (fifth-finger clinodactyly), or a wide gap between the first and second toes (known as a sandal gap). Rarely, individuals with MAND have heart abnormalities. n Not inherited ad Autosomal dominant MBD5 https://medlineplus.gov/genetics/gene/mbd5 2 https://medlineplus.gov/genetics/chromosome/2 2q23.1 microdeletion syndrome 2q23.1 microduplication syndrome MAND MBD5 haploinsufficiency GTR C1969562 MeSH D025063 MeSH D065886 OMIM 156200 SNOMED CT 719657001 2018-09 2023-07-12 MDA5 deficiency https://medlineplus.gov/genetics/condition/mda5-deficiency descriptionMDA5 deficiency is a disorder of the immune system (immunodeficiency) that leads to recurrent, severe infections of the lungs and airways (respiratory tract) beginning in infancy. These infections are most frequently caused by rhinovirus (the virus that causes the common cold). Respiratory syncytial virus (RSV) and the influenza (flu) virus may also cause recurrent infections in affected individuals. While infection by these viruses is common in all children, it usually causes mild symptoms and lasts only a short time before being cleared by a healthy immune system. In contrast, individuals with MDA5 deficiency frequently require hospitalization due to the severity of the symptoms caused by the infection. Repeated infections can contribute to chronic lung disease.Infections usually become less frequent with age in people with MDA5 deficiency, as the body's immune system matures and develops other mechanisms for fighting viruses. ar Autosomal recessive ad Autosomal dominant IFIH1 https://medlineplus.gov/genetics/gene/ifih1 IFIH1 deficiency MeSH D007153 2017-11 2020-08-18 MECP2 duplication syndrome https://medlineplus.gov/genetics/condition/mecp2-duplication-syndrome descriptionMECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Most people with this condition also have weak muscle tone in infancy, feeding difficulties, poor or absent speech, or muscle stiffness (rigidity). Individuals with MECP2 duplication syndrome have delayed development of motor skills such as sitting and walking. About half of individuals have seizures, often of the tonic-clonic type. This type of seizure involves a loss of consciousness, muscle rigidity, and convulsions and may not respond to medication. Some affected individuals experience the loss of previously acquired skills (developmental regression). Approximately half of individuals learn to walk, and about one-third of people with this condition require assistance when walking. Many individuals with MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections are a major cause of death in affected individuals, with only half surviving past age 25. x X-linked MECP2 https://medlineplus.gov/genetics/gene/mecp2 Lubs X-linked mental retardation syndrome Trisomy Xq28 GTR C1846058 MeSH D038901 OMIM 300260 SNOMED CT 702816000 2017-03 2023-08-02 MECP2-related severe neonatal encephalopathy https://medlineplus.gov/genetics/condition/mecp2-related-severe-neonatal-encephalopathy descriptionMECP2-related severe neonatal encephalopathy is a neurological disorder that primarily affects males and causes brain dysfunction (encephalopathy). Affected males have a small head size (microcephaly), poor muscle tone (hypotonia) in infancy, movement disorders, rigidity, and seizures. Infants with this condition appear normal at birth but then develop severe encephalopathy within the first week of life. These babies experience poor feeding, leading to a failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MECP2-related severe neonatal encephalopathy have severe to profound intellectual disability. Affected males have breathing problems, with some having episodes in which breathing slows or stops for short periods (apnea). As the child ages, the apnea episodes tend to last longer, especially during sleep, and affected babies often require use of a machine to help regulate their breathing (mechanical ventilation). Most males with MECP2-related severe neonatal encephalopathy do not live past the age of 2 because of respiratory failure.MECP2-related severe neonatal encephalopathy is the most severe condition in a spectrum of disorders with the same genetic cause. The mildest is PPM-X syndrome, followed by MECP2 duplication syndrome, then Rett syndrome (which exclusively affects females), and finally MECP2-related severe neonatal encephalopathy. x X-linked MECP2 https://medlineplus.gov/genetics/gene/mecp2 Methyl-cytosine phosphate guanine binding protein 2 related severe neonatal encephalopathy Severe congenital encephalopathy due to MECP2 mutation Severe neonatal encephalopathy due to MECP2 mutations GTR C1968556 MeSH D001925 OMIM 300673 SNOMED CT 711487002 2011-10 2023-03-21 MED13L syndrome https://medlineplus.gov/genetics/condition/med13l-syndrome descriptionMED13L syndrome is a developmental disorder characterized by developmental delay, intellectual disability, and minor differences in facial features. Additionally, some people with this condition have recurrent seizures (epilepsy) or heart abnormalities that are present from birth (congenital heart defects).Intellectual disability and developmental delay are usually moderate to severe in people with MED13L syndrome. Weak muscle tone (hypotonia) and delayed development of motor skills, such as sitting, standing, and walking, are early symptoms of the condition. After learning to walk, some affected individuals continue to have difficulty with coordination and balance (ataxia). Speech is also delayed, and most people with this condition develop only a few words or never learn to talk. People with MED13L syndrome may exhibit characteristics typical of autism spectrum disorder, including repetitive actions and difficulty with social interactions.Most people with MED13L syndrome have unusual facial features that consist of a depressed nasal bridge, a bulbous nasal tip, straight eyebrows, outside corners of the eyes that point upward (upslanting palpebral fissures), full cheeks, and an open mouth. Other facial features that sometimes occur are a pronounced double curve of the upper lip (Cupid's bow), and a deep space between the nose and upper lip (philtrum).Different congenital heart defects can occur in MED13L syndrome. Affected individuals may have transposition of the great arteries, which is abnormal positioning of the large blood vessel that distributes blood from the heart to the rest of the body (aorta) and the artery that carries blood from the heart to the lungs (the pulmonary artery). Other congenital heart defects in MED13L syndrome include a hole between the two lower chambers of the heart (ventricular septal defect), a hole between the two upper chambers of the heart (patent foramen ovale), or a particular combination of heart defects known as tetralogy of Fallot. ad Autosomal dominant MED13L https://medlineplus.gov/genetics/gene/med13l Asadollahi-Rauch syndrome ASRAS Cardiac anomalies-developmental delay-facial dysmorphism syndrome Developmental delay-facial dysmorphism syndrome due to MED13L deficiency Intellectual disability and distinctive facial features with or without cardiac defects MED13L haploinsufficiency syndrome MED13L-related intellectual disability MRFACD GTR C5192431 MeSH D008607 OMIM 616789 2019-05 2024-10-02 MEGDEL syndrome https://medlineplus.gov/genetics/condition/megdel-syndrome descriptionMEGDEL syndrome is an inherited disorder that affects multiple body systems. It is named for several of its features: 3-methylglutaconic aciduria (MEG), deafness (D), encephalopathy (E), and Leigh-like disease (L).MEGDEL syndrome is characterized by abnormally high levels of an acid, called 3-methylglutaconic acid, in the urine (3-methylglutaconic aciduria). MEGDEL syndrome is one of a group of metabolic disorders that can be diagnosed by presence of this feature. People with MEGDEL syndrome also have high urine levels of another acid called 3-methylglutaric acid.In infancy, individuals with MEGDEL syndrome develop hearing loss caused by changes in the inner ear (sensorineural deafness); the hearing problems gradually worsen over time.Another feature of MEGDEL syndrome is brain dysfunction (encephalopathy). In infancy, encephalopathy leads to difficulty feeding, an inability to grow and gain weight at the expected rate (failure to thrive), and weak muscle tone (hypotonia). Infants with MEGDEL syndrome later develop involuntary muscle tensing (dystonia) and muscle stiffness (spasticity), which worsen over time. Because of these brain and muscle problems, affected babies have delayed development of mental and movement abilities (psychomotor delay), or they may lose skills they already developed. Individuals with MEGDEL syndrome have intellectual disability and never learn to speak.People with MEGDEL syndrome have changes in the brain that resemble those in another condition called Leigh syndrome. These changes, which can be seen with medical imaging, are referred to as Leigh-like disease.Other features that occur commonly in MEGDEL syndrome include low blood glucose (hypoglycemia) in affected newborns; liver problems (hepatopathy) in infancy, which can be serious but improve by early childhood; and episodes of abnormally high amounts of lactic acid in the blood (lactic acidosis).The life expectancy of individuals with MEGDEL syndrome is unknown. Because of the severe health problems caused by the disorder, some affected individuals do not survive past infancy. ar Autosomal recessive SERAC1 https://medlineplus.gov/genetics/gene/serac1 3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy, and Leigh-like syndrome 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome MEGDHEL syndrome SERAC1 defect GTR C4040739 ICD-10-CM E71.111 MeSH D008052 OMIM 614739 SNOMED CT 711409002 2014-07 2023-08-22 MPV17-related hepatocerebral mitochondrial DNA depletion syndrome https://medlineplus.gov/genetics/condition/mpv17-related-hepatocerebral-mitochondrial-dna-depletion-syndrome descriptionMPV17-related hepatocerebral mitochondrial DNA depletion syndrome is an inherited disorder that can cause liver disease and neurological problems. The signs and symptoms of this condition begin in infancy and typically include vomiting, diarrhea, and an inability to grow or gain weight at the expected rate (failure to thrive). Many affected infants have a buildup of a chemical called lactic acid in the body (lactic acidosis) and low blood glucose (hypoglycemia). Within the first weeks of life, infants develop liver disease that quickly progresses to liver failure. The liver is frequently enlarged (hepatomegaly) and liver cells often have a reduced ability to release a digestive fluid called bile (cholestasis). Rarely, affected children develop liver cancer. After the onset of liver disease, many affected infants develop neurological problems, which can include developmental delay, weak muscle tone (hypotonia), and reduced sensation in the limbs (peripheral neuropathy). Individuals with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome typically survive only into infancy or early childhood.MPV17-related hepatocerebral mitochondrial DNA depletion syndrome is most frequently seen in the Navajo population of the southwestern United States. In this population, the condition is known as Navajo neurohepatopathy. People with Navajo neurohepatopathy tend to have a longer life expectancy than those with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. In addition to the signs and symptoms described above, people with Navajo neurohepatopathy may have problems with sensing pain that can lead to painless bone fractures and self-mutilation of the fingers or toes. Individuals with Navajo neurohepatopathy may lack feeling in the clear front covering of the eye (corneal anesthesia), which can lead to open sores and scarring on the cornea, resulting in impaired vision. The cause of these additional features is unknown. ar Autosomal recessive MPV17 https://medlineplus.gov/genetics/gene/mpv17 Mitochondrial DNA depletion syndrome 6 MPV17-associated hepatocerebral MDS MTDPS6 Navajo familial neurogenic arthropathy Navajo neurohepatopathy Navajo neuropathy NNH GTR C1850406 MeSH D028361 OMIM 256810 SNOMED CT 237995002 2013-01 2023-07-26 MUTYH-associated polyposis https://medlineplus.gov/genetics/condition/mutyh-associated-polyposis descriptionMUTYH-associated polyposis (MAP) is an inherited disorder that is characterized by a greatly increased risk of cancer of the large intestine (colon) and rectum (collectively known as colorectal cancer). Most people with MAP develop multiple noncancerous (benign) growths (polyps) in the colon by around age 50 years. Polyps can also occur in the small intestine or the stomach. Individuals with this condition can develop ten to hundreds of polyps. Without monitoring and prompt follow-up, affected individuals have an 80 to 90 percent risk of developing colorectal cancer in their lifetimes. However, people with MAP who do not have polyps can also develop cancer.While colorectal cancer is the most common type of cancer in people with MAP, cancer can develop in other places in the body, including a section of the small intestine known as the duodenum, the breasts, the ovaries, the lining of the uterus (the endometrium), and the bladder. While cancers in other tissues have occurred in people with MAP, it is unclear if the risk for those cancers is higher than the risk for the general population. ar Autosomal recessive MUTYH https://medlineplus.gov/genetics/gene/mutyh Familial adenomatous polyposis 2 MUTYH-related attenuated familial adenomatous polyposis MYH-associated polyposis GTR C3272841 OMIM 608456 2025-08 2025-09-10 MYH9-related disorder https://medlineplus.gov/genetics/condition/myh9-related-disorder descriptionMYH9-related disorder is a condition that can have many signs and symptoms, including bleeding problems, hearing loss, kidney (renal) disease, and clouding of the lens of the eyes (cataracts).The bleeding problems in people with MYH9-related disorder are due to thrombocytopenia. Thrombocytopenia is a reduced level of circulating platelets, which are small cells that normally assist with blood clotting. People with MYH9-related disorder typically experience easy bruising, and affected women have excessive bleeding during menstruation (menorrhagia). The platelets in people with MYH9-related disorder are larger than normal. These enlarged platelets have difficulty moving into tiny blood vessels like capillaries. As a result, the platelet level is even lower in these small vessels, further impairing clotting.Some people with MYH9-related disorder develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). Hearing loss may be present from birth or can develop anytime into late adulthood.An estimated 30 to 70 percent of people with MYH9-related disorder develop renal disease, usually beginning in early adulthood. The first sign of renal disease in MYH9-related disorder is typically protein or blood in the urine. Renal disease in these individuals particularly affects structures called glomeruli, which are clusters of tiny blood vessels that help filter waste products from the blood. The resulting damage to the kidneys can lead to kidney failure and end-stage renal disease (ESRD).Some affected individuals develop cataracts in early adulthood that worsen over time.Not everyone with MYH9-related disorder has all of the major features. All individuals with MYH9-related disorder have thrombocytopenia and enlarged platelets. Most commonly, affected individuals will also have hearing loss and renal disease. Cataracts are the least common sign of this disorder.MYH9-related disorder was previously thought to be four separate disorders: May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian syndrome. All of these disorders involved thrombocytopenia and enlarged platelets and were distinguished by some combination of hearing loss, renal disease, and cataracts. When it was discovered that these four conditions all had the same genetic cause, they were combined and renamed MYH9-related disorder. ad Autosomal dominant MYH9 https://medlineplus.gov/genetics/gene/myh9 Autosomal dominant MYH9 spectrum disorders MYH9-related macrothrombocytopenias MYH9RD GTR C5200934 ICD-10-CM D72.0 MeSH D013921 OMIM 155100 SNOMED CT 234484005 SNOMED CT 234485006 SNOMED CT 236422008 2011-04 2023-08-22 Mabry syndrome https://medlineplus.gov/genetics/condition/mabry-syndrome descriptionMabry syndrome is a condition characterized by intellectual disability, distinctive facial features, increased levels of an enzyme called alkaline phosphatase in the blood (hyperphosphatasia), and other signs and symptoms.People with Mabry syndrome have intellectual disability that is often moderate to severe. They typically have little to no speech development and are delayed in the development of motor skills (such as sitting, crawling, and walking). Many affected individuals have low muscle tone (hypotonia) and develop recurrent seizures (epilepsy) in early childhood. Seizures are usually the generalized tonic-clonic type, which involve muscle rigidity, convulsions, and loss of consciousness.Individuals with Mabry syndrome have distinctive facial features that include wide-set eyes (hypertelorism), long openings of the eyelids (long palpebral fissures), a nose with a broad bridge and a rounded tip, downturned corners of the mouth, and a thin upper lip. These facial features usually become less pronounced over time.Hyperphosphatasia begins within the first year of life in people with Mabry syndrome. There are many different types of alkaline phosphatase found in tissues; the type that is increased in Mabry syndrome is called the tissue non-specific type and is found throughout the body. In affected individuals, alkaline phosphatase levels in the blood are usually increased by one to two times the normal amount, but can be up to 20 times higher than normal. The elevated enzyme levels remain relatively stable over a person's lifetime. Hyperphosphatasia appears to cause no negative health effects, but this finding can help health professionals diagnose Mabry syndrome.Another common feature of Mabry syndrome is shortened bones at the ends of fingers (brachytelephalangy), which can be seen on x-ray imaging. Underdeveloped fingernails (nail hypoplasia) may also occur. Sometimes, individuals with Mabry syndrome have abnormalities of the digestive system, including narrowing or blockage of the anus (anal stenosis or anal atresia) or Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine. Rarely, affected individuals experience hearing loss.The signs and symptoms of Mabry syndrome vary among affected individuals. Those who are least severely affected have only intellectual disability and hyperphosphatasia, without distinctive facial features or the other health problems listed above. ar Autosomal recessive PIGV https://medlineplus.gov/genetics/gene/pigv PIGO https://medlineplus.gov/genetics/gene/pigo PGAP2 https://medlineplus.gov/genetics/gene/pgap2 Hyperphosphatasia with mental retardation syndrome Hyperphosphatasia with seizures and neurologic deficit GTR C1855923 GTR C3280153 GTR C3553637 GTR C4551502 MeSH D054559 OMIM 239300 OMIM 614207 OMIM 614749 SNOMED CT 33982008 2013-07 2020-08-18 Macrozoospermia https://medlineplus.gov/genetics/condition/macrozoospermia descriptionMacrozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility).In affected males, almost all sperm cells have abnormally large and misshapen heads. The head of the sperm cell contains the male's genetic information that is to be passed on to the next generation. Normally, the head of a sperm cell contains one copy of each chromosome. In men with macrozoospermia, the sperm cell head contains extra chromosomes, usually four copies of each instead of the usual one. This additional genetic material accounts for the larger head size of the sperm cell. Additionally, instead of having one tail (flagellum) per sperm cell, affected sperm have multiple flagella, most often four.Because of the additional genetic material, if one of these abnormal sperm cells combines with an egg cell, the embryo will not develop or the pregnancy will result in miscarriage. ar Autosomal recessive AURKC https://medlineplus.gov/genetics/gene/aurkc Infertility associated with multi-tailed spermatozoa and excessive DNA Large-headed multiflagellar polyploid spermatozoa Spermatogenic failure 5 GTR C0403812 MeSH D000072660 OMIM 243060 SNOMED CT 236817003 2015-01 2020-08-18 Maffucci syndrome https://medlineplus.gov/genetics/condition/maffucci-syndrome descriptionMaffucci syndrome is a disorder that primarily affects the bones and skin. It is characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures.The signs and symptoms of Maffucci syndrome may be detectable at birth, although they generally do not become apparent until around the age of 5. Enchondromas develop near the ends of bones, where normal growth occurs, and they frequently stop forming after affected individuals stop growing in early adulthood. As a result of the bone deformities associated with Maffucci syndrome, people with this disorder generally have short stature and underdeveloped muscles.Maffucci syndrome is distinguished from a similar disorder that involves enchondromas (Ollier disease) by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas). In addition to hemangiomas, individuals with Maffucci syndrome occasionally also have lymphangiomas, which are masses made up of the thin tubes that carry lymph fluid (lymphatic vessels). These growths may appear anywhere on the body.Although the enchondromas associated with Maffucci syndrome start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Maffucci syndrome also have an increased risk of other cancers, such as ovarian or liver cancer.People with Maffucci syndrome usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities. n Not inherited IDH2 https://medlineplus.gov/genetics/gene/idh2 IDH1 https://medlineplus.gov/genetics/gene/idh1 Chondrodysplasia with hemangioma Chondroplasia angiomatosis Dyschondroplasia and cavernous hemangioma Enchondromatosis with hemangiomata Hemangiomata with dyschondroplasia Hemangiomatosis chondrodystrophica Kast syndrome Multiple angiomas and endochondromas GTR C0024454 MeSH D004687 OMIM 614569 SNOMED CT 46041001 2016-02 2020-08-18 Mainzer-Saldino syndrome https://medlineplus.gov/genetics/condition/mainzer-saldino-syndrome descriptionMainzer-Saldino syndrome is a disorder characterized by kidney disease, eye problems, and skeletal abnormalities.People with Mainzer-Saldino syndrome have chronic kidney disease that begins in childhood and gets worse over time. The rate at which the kidney disease worsens is variable, but the condition eventually leads to kidney failure in most affected individuals.Degeneration of the light-sensitive tissue at the back of the eye (the retina) almost always occurs in this disorder, but the age at which this feature develops varies. Some affected individuals are blind or have severe vision impairment beginning in infancy, with the pattern of vision loss resembling a condition called Leber congenital amaurosis. In other people with Mainzer-Saldino syndrome, the retinal degeneration begins in childhood, but some vision is retained into early adulthood. The vision loss in these affected individuals resembles a category of retinal disorders called rod-cone dystrophies. The most common rod-cone dystrophy is called retinitis pigmentosa, and the vision problems in Mainzer-Saldino syndrome are sometimes referred to as such. However, the abnormal deposits of pigment in the retina from which retinitis pigmentosa gets its name are often not found in Mainzer-Saldino syndrome. As a result, some researchers use terms such as "atypical retinitis pigmentosa without pigment" to describe the retinal degeneration that occurs in Mainzer-Saldino syndrome.The skeletal abnormality most characteristic of Mainzer-Saldino syndrome consists of cone-shaped ends of the bones (epiphyses) in the fingers (phalanges) that can be seen on x-ray images after the first year of life. Affected individuals may also have abnormalities of the thigh bones that occur in the epiphyses and adjacent areas where bone growth occurs (the metaphyses). Occasionally, other skeletal abnormalities occur, including short stature and premature fusion of certain skull bones (craniosynostosis) that affects the shape of the head and face. Affected individuals may also have a small rib cage, which sometimes causes breathing problems in infancy, but the breathing problems are usually mild.A small number of individuals with this disorder have additional problems affecting other organs. These can include liver disease resulting in a buildup of scar tissue in the liver (hepatic fibrosis); cerebellar ataxia, which is difficulty with coordination and balance arising from problems with a part of the brain called the cerebellum; and mild intellectual disability. ar Autosomal recessive IFT140 https://medlineplus.gov/genetics/gene/ift140 Conorenal dysplasia Conorenal syndrome Mainzer-Saldino chondrodysplasia Mainzer-Saldino disease MZSDS Renal dysplasia, retinal pigmentary dystrophy, cerebellar ataxia, and skeletal dysplasia Saldino-Mainzer dysplasia Saldino-Mainzer syndrome Short-rib thoracic dysplasia 9 SRTD9 GTR C1849437 MeSH D052177 OMIM 266920 SNOMED CT 254092004 2013-05 2023-03-21 Majeed syndrome https://medlineplus.gov/genetics/condition/majeed-syndrome descriptionMajeed syndrome is a rare condition that is characterized by recurrent episodes of fever and inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, Majeed syndrome causes abnormal inflammation that can damage the body's tissues, particularly the bones and, less commonly, the skin. The signs and symptoms of Majeed syndrome typically appear in infancy or early childhood and can vary from person to person.One of the major features of Majeed syndrome is an inflammatory bone condition known as chronic recurrent multifocal osteomyelitis (CRMO). This condition causes recurrent episodes of bone pain and joint swelling. These symptoms continue into adulthood, although they may improve for short periods. CRMO can lead to complications such as slow growth and the development of joint deformities called contractures, which restrict the movement of certain joints.Another feature of Majeed syndrome is a blood disorder called congenital dyserythropoietic anemia. This disorder is one of many types of anemia, all of which involve a shortage of red blood cells. Without enough of these cells, the blood cannot carry an adequate supply of oxygen to the body's tissues. This can cause tiredness (fatigue), weakness, pale skin, and shortness of breath. The complications of congenital dyserythropoietic anemia can range from mild to severe.Some people with Majeed syndrome develop an inflammatory disorder of the skin known as Sweet syndrome. The symptoms of Sweet syndrome include fever and the development of painful bumps or blisters on the face, neck, back, and arms. ar Autosomal recessive LPIN2 https://medlineplus.gov/genetics/gene/lpin2 Chronic recurrent multifocal osteomyelitis 1, with congenital dyserythropoietic anemia, with or without neutrophilic dermatosis Chronic recurrent multifocal osteomyelitis-congenital dyserythropoietic anemia-neutrophilic dermatosis syndrome CRM01 MJDS GTR C1864997 ICD-10-CM MeSH D010019 OMIM 609628 SNOMED CT 703540008 2024-07 2024-07-05 Mal de Meleda https://medlineplus.gov/genetics/condition/mal-de-meleda descriptionMal de Meleda is a rare skin disorder that begins in early infancy. Affected individuals have a condition known as palmoplantar keratoderma, in which the skin of the palms of the hands and soles of the feet becomes thick, hard, and callused. In mal de Meleda, the thickened skin is also found on the back of the hands and feet and on the wrists and ankles. In addition, affected individuals may have rough, thick pads on the joints of the fingers and toes and on the elbows and knees. Some people with mal de Meleda have recurrent fungal infections in the thickened skin, which can lead to a strong odor. Other features of this disorder can include short fingers and toes (brachydactyly), nail abnormalities, red skin around the mouth, and excessive sweating (hyperhidrosis). ar Autosomal recessive SLURP1 https://medlineplus.gov/genetics/gene/slurp1 Acroerythrokeratoderma Keratosis palmoplantaris transgrediens of Siemens Meleda disease Transgrediens palmoplantar keratoderma of Siemens GTR C0025221 MeSH D007645 OMIM 248300 SNOMED CT 239069005 2014-11 2020-08-18 Malignant hyperthermia https://medlineplus.gov/genetics/condition/malignant-hyperthermia descriptionMalignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate and body temperature (hyperthermia), abnormally fast breathing, muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). Without prompt treatment and cessation of the drugs, the body's reaction can cause multiple organs to be unable to function, including the heart (cardiac arrest) and kidneys (renal failure), and it can cause a blood clotting abnormality called disseminated intravascular coagulation. These complications may be life-threatening. (In medicine, the term malignant refers to conditions that are dangerous to one's health.)People at increased risk of this disorder are said to have malignant hyperthermia susceptibility. Affected individuals may never know they have the condition unless they have a severe reaction to anesthesia during a surgical procedure or they undergo testing (for instance, if susceptibility is suspected because a family member had a severe reaction). Malignant hyperthermia may not occur every time anesthesia is used. Many individuals who develop a severe reaction have previously been exposed to a triggering drug and not had a reaction.Affected individuals may be at increased risk for "awake" malignant hyperthermia, in which the severe reaction occurs in response to physical activity, often while sick, rather than in reaction to exposure to a triggering drug.While malignant hyperthermia often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease, multiminicore disease, and STAC3 disorder) are associated with malignant hyperthermia susceptibility. ad Autosomal dominant CACNA1S https://medlineplus.gov/genetics/gene/cacna1s RYR1 https://medlineplus.gov/genetics/gene/ryr1 Anesthesia related hyperthermia Hyperpyrexia, malignant Hyperthermia, malignant Malignant hyperpyrexia MHS GTR C1838102 GTR C1866076 GTR C1866077 GTR C2930980 ICD-10-CM T88.3 MeSH D008305 OMIM 145600 OMIM 154275 OMIM 154276 OMIM 600467 OMIM 601887 OMIM 601888 SNOMED CT 213026003 SNOMED CT 405501007 2020-03 2020-08-18 Malonyl-CoA decarboxylase deficiency https://medlineplus.gov/genetics/condition/malonyl-coa-decarboxylase-deficiency descriptionMalonyl-CoA decarboxylase deficiency is a condition that prevents the body from converting certain fats to energy. The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency. ar Autosomal recessive MLYCD https://medlineplus.gov/genetics/gene/mlycd Deficiency of malonyl-CoA decarboxylase Malonic aciduria Malonyl-coenzyme A decarboxylase deficiency MCD deficiency GTR C0342793 MeSH D008661 OMIM 248360 SNOMED CT 124594007 2010-01 2023-07-25 Mandibuloacral dysplasia https://medlineplus.gov/genetics/condition/mandibuloacral-dysplasia descriptionMandibuloacral dysplasia is a condition that causes a variety of abnormalities involving bone development, skin coloring (pigmentation), and fat distribution. People with this condition may grow slowly after birth. Most affected individuals are born with an underdeveloped lower jaw bone (mandible) and small collar bones (clavicles), leading to the characteristic features of a small chin and sloped shoulders. Other bone problems include loss of bone from the tips of the fingers (acroosteolysis), which causes bulbous finger tips; delayed closure of certain skull bones; and joint deformities (contractures).People with mandibuloacral dysplasia can have mottled or patchy skin pigmentation or other skin abnormalities. Some people with this condition have features of premature aging (a condition called progeria), such as thin skin, loss of teeth, loss of hair, and a beaked nose. Some individuals with mandibuloacral dysplasia have metabolic problems, such as diabetes.A common feature of mandibuloacral dysplasia is a lack of fatty tissue under the skin (lipodystrophy) in certain regions of the body. The two types of this disorder, mandibuloacral dysplasia with type A lipodystrophy (MADA) and mandibuloacral dysplasia with type B lipodystrophy (MADB) are distinguished by the pattern of fat distribution throughout the body. Type A is described as partial lipodystrophy; affected individuals have a loss of fatty tissue from the torso and limbs, but it may build up around the neck and shoulders. Type B is a generalized lipodystrophy, with loss of fatty tissue in the face, torso, and limbs.MADA usually begins in adulthood, although children can be affected. MADB begins earlier, often just after birth. Many babies with MADB are born prematurely. ar Autosomal recessive LMNA https://medlineplus.gov/genetics/gene/lmna ZMPSTE24 https://medlineplus.gov/genetics/gene/zmpste24 Mandibuloacral dysostosis GTR C0432291 GTR C1837756 MeSH D008060 OMIM 248370 OMIM 608612 SNOMED CT 109419009 2013-08 2020-08-18 Mandibulofacial dysostosis with microcephaly https://medlineplus.gov/genetics/condition/mandibulofacial-dysostosis-with-microcephaly descriptionMandibulofacial dysostosis with microcephaly (MFDM) is a disorder that causes abnormalities of the head and face.  People with this disorder often have an unusually small head at birth, and the head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Affected individuals have developmental delay and intellectual disability that can range from mild to severe. Speech and language problems are also common in this disorder.Facial abnormalities that occur in MFDM include underdevelopment of the middle of the face and the cheekbones (midface and malar hypoplasia) and an unusually small lower jaw (mandibular hypoplasia, also called micrognathia). The external ears are small and abnormally shaped, and they may have skin growths in front of them called preauricular tags. There may also be abnormalities of the ear canal, the tiny bones in the ears (ossicles), or a part of the inner ear called the semicircular canals. These ear abnormalities lead to hearing loss in most affected individuals. Some people with MFDM have an opening in the roof of the mouth (cleft palate), which may also contribute to hearing loss by increasing the risk of ear infections. Affected individuals can also have a blockage of the nasal passages (choanal atresia) that can cause respiratory problems.Heart problems, abnormalities of the thumbs, and short stature are other features that can occur in MFDM. Some people with this disorder also have blockage of the esophagus (esophageal atresia). In esophageal atresia, the upper esophagus does not connect to the lower esophagus and stomach. Most babies born with esophageal atresia (EA) also have a tracheoesophageal fistula (TEF), in which the esophagus and the trachea are abnormally connected, allowing fluids from the esophagus to get into the airways and interfere with breathing. Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a life-threatening condition; without treatment, it prevents normal feeding and can cause lung damage from repeated exposure to esophageal fluids. ad Autosomal dominant EFTUD2 https://medlineplus.gov/genetics/gene/eftud2 Mandibulofacial dysostosis, Guion-Almeida type MFDGA MFDM GTR C1864652 ICD-10-CM Q75.4 MeSH D008342 OMIM 610536 SNOMED CT 711543008 2014-09 2024-05-24 Manitoba oculotrichoanal syndrome https://medlineplus.gov/genetics/condition/manitoba-oculotrichoanal-syndrome descriptionManitoba oculotrichoanal syndrome is a condition involving several characteristic physical features, particularly affecting the eyes (oculo-), hair (tricho-), and anus (-anal).People with Manitoba oculotrichoanal syndrome have widely spaced eyes (hypertelorism). They may also have other eye abnormalities including small eyes (microphthalmia), a notched or partially absent upper eyelid (upper eyelid coloboma), eyelids that are attached to the front surface of the eye (corneopalpebral synechiae), or eyes that are completely covered by skin and usually malformed (cryptophthalmos). These abnormalities may affect one or both eyes.Individuals with Manitoba oculotrichoanal syndrome usually have abnormalities of the front hairline, such as hair growth extending from the temple to the eye on one or both sides of the face. One or both eyebrows may be completely or partially missing. Most people with this disorder also have a wide nose with a notched tip; in some cases this notch extends up from the tip so that the nose appears to be divided into two halves (bifid nose).About 20 percent of people with Manitoba oculotrichoanal syndrome have defects in the abdominal wall, such as a soft out-pouching around the belly-button (an umbilical hernia) or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. Another characteristic feature of Manitoba oculotrichoanal syndrome is a narrow anus (anal stenosis) or an anal opening farther forward than usual. Umbilical wall defects or anal malformations may require surgical correction. Some affected individuals also have malformations of the kidneys.The severity of the features of Manitoba oculotrichoanal syndrome may vary even within the same family. With appropriate treatment, affected individuals generally have normal growth and development, intelligence, and life expectancy. ar Autosomal recessive FREM1 https://medlineplus.gov/genetics/gene/frem1 Marles Greenberg Persaud syndrome Marles syndrome Marles-Greenberg-Persaud syndrome MOTA GTR C1855425 MeSH D000015 OMIM 248450 SNOMED CT 703539006 2011-05 2020-08-18 Mannose-binding lectin deficiency https://medlineplus.gov/genetics/condition/mannose-binding-lectin-deficiency descriptionMannose-binding lectin deficiency is a condition that affects the immune system. People with this condition have low levels (deficiency) of an immune system protein called mannose-binding lectin in their blood. Whether this deficiency makes affected individuals prone to recurrent infections is not clear.People with mannose-binding lectin deficiency can develop infections of the upper respiratory tract and other body systems. Individuals with this condition may also contract more serious infections such as pneumonia and meningitis. Depending on the type of infection, the symptoms caused by the infections vary in frequency and severity.Infants and young children with mannose-binding lectin deficiency seem to be more susceptible to infections than affected adults, but adults can also develop recurrent infections. In addition, affected individuals undergoing chemotherapy or taking drugs that suppress the immune system are especially prone to infections. u Pattern unknown MBL2 https://medlineplus.gov/genetics/gene/mbl2 Mannose-binding lectin protein deficiency Mannose-binding protein deficiency MBL deficiency MBL2 deficiency MBP deficiency GTR C3280586 MeSH D007153 OMIM 614372 SNOMED CT 703538003 2012-03 2024-09-19 Maple syrup urine disease https://medlineplus.gov/genetics/condition/maple-syrup-urine-disease descriptionMaple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine. It is also characterized by poor feeding, vomiting, lack of energy (lethargy), abnormal movements, and delayed development. If untreated, maple syrup urine disease can lead to seizures, coma, and death.Maple syrup urine disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still lead to delayed development and other health problems if not treated. ar Autosomal recessive BCKDHA https://medlineplus.gov/genetics/gene/bckdha BCKDHB https://medlineplus.gov/genetics/gene/bckdhb DBT https://medlineplus.gov/genetics/gene/dbt PPM1K https://www.ncbi.nlm.nih.gov/gene/152926 BCKD deficiency Branched-chain alpha-keto acid dehydrogenase deficiency Branched-chain ketoaciduria Ketoacidemia MSUD GTR C0024776 GTR C0268568 ICD-10-CM E71.0 MeSH D008375 OMIM 248600 OMIM 615135 SNOMED CT 27718001 SNOMED CT 31368008 SNOMED CT 405287008 SNOMED CT 405288003 SNOMED CT 54064006 2008-12 2025-04-03 Marfan syndrome https://medlineplus.gov/genetics/condition/marfan-syndrome descriptionMarfan syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. The signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression.Because connective tissue is found throughout the body, Marfan syndrome can affect many systems, often causing abnormalities in the heart, blood vessels, eyes, bones, and joints. The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and defects in the large blood vessel that distributes blood from the heart to the rest of the body (the aorta). The aorta can weaken and stretch, which may lead to a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may cause the aortic valve to leak, which can lead to a sudden tearing of the layers in the aorta wall (aortic dissection). Aortic aneurysm and dissection can be life threatening.Many people with Marfan syndrome have additional heart problems including a leak in the valve that connects two of the four chambers of the heart (mitral valve prolapse) or the valve that regulates blood flow from the heart into the aorta (aortic valve regurgitation). Leaks in these valves can cause shortness of breath, fatigue, and an irregular heartbeat felt as skipped or extra beats (palpitations).Individuals with Marfan syndrome are usually tall and slender, have elongated fingers and toes (arachnodactyly), loose joints, and have an arm span that exceeds their body height. Other common features include a long and narrow face, crowded teeth, an abnormal curvature of the spine (scoliosis or kyphosis), stretch marks (striae) not related to weight gain or loss, and either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some individuals develop an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung (spontaneous pneumothorax). A membrane called the dura, which surrounds the brain and spinal cord, can be abnormally enlarged (dural ectasia) in people with Marfan syndrome. Dural ectasia can cause pain in the back, abdomen, legs, or head. Most individuals with Marfan syndrome have some degree of nearsightedness (myopia). Clouding of the lens (cataract) may occur in mid-adulthood, and increased pressure within the eye (glaucoma) occurs more frequently in people with Marfan syndrome than in those without the condition.The features of Marfan syndrome can become apparent anytime between infancy and adulthood. Depending on the onset and severity of signs and symptoms, Marfan syndrome can be fatal early in life; however, with proper treatment, many affected individuals have normal lifespans. ad Autosomal dominant FBN1 https://medlineplus.gov/genetics/gene/fbn1 Marfan's syndrome MFS GTR C0024796 ICD-10-CM Q87.4 ICD-10-CM Q87.40 ICD-10-CM Q87.41 ICD-10-CM Q87.410 ICD-10-CM Q87.418 ICD-10-CM Q87.42 ICD-10-CM Q87.43 MeSH D008382 OMIM 154700 SNOMED CT 19346006 SNOMED CT 234035006 SNOMED CT 57201002 2012-03 2023-11-08 Marinesco-Sjögren syndrome https://medlineplus.gov/genetics/condition/marinesco-sjogren-syndrome descriptionMarinesco-Sjögren syndrome is a condition that has a variety of signs and symptoms affecting many tissues. People with Marinesco-Sjögren syndrome have clouding of the lens of the eyes (cataracts) that usually develops soon after birth or in early childhood. Affected individuals also have muscle weakness (myopathy) and difficulty coordinating movements (ataxia), which may impair their ability to walk. People with Marinesco-Sjögren syndrome may experience further decline in muscle function later in life.Most people with Marinesco-Sjögren syndrome have mild to moderate intellectual disability. They also have skeletal abnormalities including short stature and a spine that curves to the side (scoliosis). Other features of Marinesco-Sjögren syndrome include eyes that do not look in the same direction (strabismus), involuntary eye movements (nystagmus), and impaired speech (dysarthria).Affected individuals may have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, puberty is either delayed or absent. ar Autosomal recessive SIL1 https://medlineplus.gov/genetics/gene/sil1 Garland-Moorhouse syndrome Hereditary oligophrenic cerebello-lental degeneration Marinesco-Garland syndrome MSS GTR C0024814 MeSH D013132 OMIM 248800 SNOMED CT 80734006 2008-09 2020-08-18 Maternally inherited diabetes and deafness https://medlineplus.gov/genetics/condition/maternally-inherited-diabetes-and-deafness descriptionMaternally inherited diabetes and deafness (MIDD) is a form of diabetes that is often accompanied by hearing loss, especially of high tones. The diabetes in MIDD is characterized by high blood sugar (glucose) levels, known as hyperglycemia. This results from a shortage of the hormone insulin, which regulates the amount of glucose in the blood. In MIDD, the diabetes and hearing loss usually develop in mid-adulthood, although the age that they occur varies from childhood to late adulthood. Typically, hearing loss occurs before diabetes.Some people with MIDD develop an eye disorder called macular retinal dystrophy, which is characterized by colored patches in the light-sensitive tissue that lines the back of the eye (the retina). This disorder does not usually cause vision problems in people with MIDD. Individuals with MIDD also may experience muscle cramps or weakness, particularly during exercise; heart problems; kidney disease; and constipation. Individuals with MIDD are often shorter than their peers. m mitochondrial MT-TL1 https://medlineplus.gov/genetics/gene/mt-tl1 MT-TK https://medlineplus.gov/genetics/gene/mt-tk MT-TE https://medlineplus.gov/genetics/gene/mt-te mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Ballinger-Wallace syndrome Diabetes mellitus, type II, with deafness Maternally transmitted diabetes-deafness syndrome MIDD Mitochondrial inherited diabetes and deafness NIDDM with deafness Noninsulin-dependent diabetes mellitus with deafness GTR C0342289 ICD-10-CM E13.69 MeSH D003920 OMIM 520000 SNOMED CT 237619009 2012-10 2023-07-19 Maturity-onset diabetes of the young https://medlineplus.gov/genetics/condition/maturity-onset-diabetes-of-the-young descriptionMaturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels of blood glucose, also called blood sugar. These forms of diabetes typically begin before age 30, although they can occur later in life. In MODY, elevated blood glucose arises from reduced production of insulin, which is a hormone produced in the pancreas that helps regulate blood glucose levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source.The different types of MODY are distinguished by their genetic causes. The most common types are HNF1A-MODY (also known as MODY3), accounting for 50 to 70 percent of cases, and GCK-MODY (MODY2), accounting for 30 to 50 percent of cases. Less frequent types include HNF4A-MODY (MODY1) and renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5), which each account for 5 to 10 percent of cases. At least ten other types have been identified, and these are very rare.HNF1A-MODY and HNF4A-MODY have similar signs and symptoms that develop slowly over time. Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time uncontrolled high blood glucose can damage small blood vessels in the eyes and kidneys. Damage to the light-sensitive tissue at the back of the eye (the retina) causes a condition known as diabetic retinopathy that can lead to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) can lead to kidney failure and end-stage renal disease (ESRD). While these two types of MODY are very similar, certain features are particular to each type. For example, babies with HNF4A-MODY tend to weigh more than average or have abnormally low blood glucose at birth, even though other signs of the condition do not occur until childhood or young adulthood. People with HNF1A-MODY have a higher-than-average risk of developing noncancerous (benign) liver tumors known as hepatocellular adenomas.GCK-MODY is a very mild type of the condition. People with this type have slightly elevated blood glucose levels, particularly in the morning before eating (fasting blood glucose). However, affected individuals often have no symptoms related to the disorder, and diabetes-related complications are extremely rare.RCAD is associated with a combination of diabetes and kidney or urinary tract abnormalities (unrelated to the elevated blood glucose), most commonly fluid-filled sacs (cysts) in the kidneys. However, the signs and symptoms are variable, even within families, and not everyone with RCAD has both features. Affected individuals may have other features unrelated to diabetes, such as abnormalities of the pancreas or liver or a form of arthritis called gout. ad Autosomal dominant ABCC8 https://medlineplus.gov/genetics/gene/abcc8 KCNJ11 https://medlineplus.gov/genetics/gene/kcnj11 INS https://medlineplus.gov/genetics/gene/ins HNF1B https://medlineplus.gov/genetics/gene/hnf1b HNF1A https://medlineplus.gov/genetics/gene/hnf1a GCK https://medlineplus.gov/genetics/gene/gck HNF4A https://medlineplus.gov/genetics/gene/hnf4a APPL1 https://www.ncbi.nlm.nih.gov/gene/352 BLK https://www.ncbi.nlm.nih.gov/gene/640 CEL https://www.ncbi.nlm.nih.gov/gene/1056 PDX1 https://www.ncbi.nlm.nih.gov/gene/3651 NEUROD1 https://www.ncbi.nlm.nih.gov/gene/4760 PAX4 https://www.ncbi.nlm.nih.gov/gene/5078 KLF11 https://www.ncbi.nlm.nih.gov/gene/8462 MODY GTR C0342276 GTR C0342277 GTR C1833382 GTR C1838100 GTR C1852093 GTR C1853297 GTR C1853371 GTR C1864839 GTR C2677132 GTR C3150617 GTR C3150618 GTR C4225299 GTR C4225365 MeSH D003920 OMIM 125850 OMIM 125851 OMIM 137920 OMIM 600496 SNOMED CT 14052004 SNOMED CT 609561005 SNOMED CT 717048002 SNOMED CT 717182006 SNOMED CT 721234004 2020-07 2023-11-08 Mayer-Rokitansky-Küster-Hauser syndrome https://medlineplus.gov/genetics/condition/mayer-rokitansky-kuster-hauser-syndrome descriptionMayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder that causes the vagina and uterus to be underdeveloped or absent. Because of this, affected women do not have menstrual periods. Often, the first noticeable sign of MRKH syndrome is that menstruation does not begin by age 15 (primary amenorrhea).Girls and women with MRKH syndrome have a 46,XX chromosome pattern. They have normal external genitalia and functioning ovaries. They also have normal breast and pubic hair development. Women with this condition cannot carry a pregnancy; some may be unable to have biological children (infertile), while others may be able to have children with medical support.MRKH syndrome is often divided into two types. MRKH syndrome type 1 affects only the reproductive organs. MRKH syndrome type 2 also affects other parts of the body. In this form of the condition, the kidneys may be abnormally formed or positioned, or one kidney may fail to develop (unilateral renal agenesis). Additionally, hearing loss, heart defects, or skeletal abnormalities, particularly of the spinal bones (vertebrae), can occur in those with MRKH syndrome type 2. u Pattern unknown ad Autosomal dominant Congenital absence of the uterus and vagina (CAUV) Genital renal ear syndrome (GRES) MRKH syndrome Mullerian agenesis Mullerian aplasia Mullerian dysgenesis Rokitansky Kuster Hauser syndrome Rokitansky syndrome GTR C0431648 MeSH D058489 OMIM 277000 OMIM 601076 SNOMED CT 253828000 2025-05 2026-03-13 McCune-Albright syndrome https://medlineplus.gov/genetics/condition/mccune-albright-syndrome descriptionMcCune-Albright syndrome is a disorder that affects the bones, skin, and several hormone-producing (endocrine) tissues.People with McCune-Albright syndrome develop areas of abnormal scar-like (fibrous) tissue in their bones, a condition called polyostotic fibrous dysplasia. Polyostotic means the abnormal areas (lesions) may occur in many bones; often they are confined to one side of the body. Replacement of bone with fibrous tissue may lead to fractures, uneven growth, and deformity. When lesions occur in the bones of the skull and jaw it can result in uneven (asymmetric) growth of the face. Asymmetry may also occur in the long bones; uneven growth of leg bones may cause limping. Abnormal curvature of the spine (scoliosis) may also occur. Bone lesions may become cancerous, but this happens in fewer than 1 percent of people with McCune-Albright syndrome.In addition to bone abnormalities, affected individuals usually have light brown patches of skin called café-au-lait spots, which may be present from birth. The irregular borders of the café-au-lait spots in McCune-Albright syndrome are often compared to a map of the coast of Maine. By contrast, café-au-lait spots in other disorders have smooth borders, which are compared to the coast of California. Like the bone lesions, the café-au-lait spots in McCune-Albright syndrome may appear on only one side of the body.Girls with McCune-Albright syndrome may reach puberty early. These girls often have menstrual bleeding by age 2. This early onset of menstruation is believed to be caused by excess estrogen, a female sex hormone, produced by cysts that develop in one of the ovaries. Less commonly, boys with McCune-Albright syndrome may also experience early puberty.Other endocrine problems may also occur in people with McCune-Albright syndrome. The thyroid gland, a butterfly-shaped organ at the base of the neck, may become enlarged (a condition called a goiter) or develop masses called nodules. About 50 percent of affected individuals produce excessive amounts of thyroid hormone (hyperthyroidism), resulting in a fast heart rate, high blood pressure, weight loss, tremors, sweating, and other symptoms. The pituitary gland (a structure at the base of the brain that makes several hormones) may produce too much growth hormone. Excess growth hormone can result in acromegaly, a condition characterized by large hands and feet, arthritis, and distinctive facial features that are often described as "coarse." Excess growth hormone secretion may also lead to increased expansion of the fibrous dysplasia in the bones, most visibly in the skull. Rarely, affected individuals develop Cushing syndrome, an excess of the hormone cortisol produced by the adrenal glands, which are small glands located on top of each kidney. Cushing syndrome causes weight gain in the face and upper body, slowed growth in children, fragile skin, fatigue, and other health problems. In people with McCune-Albright syndrome, Cushing syndrome occurs only before age 2.Problems in other organs and systems, such as noncancerous (benign) gastrointestinal growths called polyps and other abnormalities, can also occur in McCune-Albright syndrome. n Not inherited GNAS https://medlineplus.gov/genetics/gene/gnas Albright syndrome Albright's disease Albright's disease of bone Albright's syndrome Albright's syndrome with precocious puberty Albright-McCune-Sternberg syndrome Albright-Sternberg syndrome Fibrous dysplasia with pigmentary skin changes and precocious puberty MAS Osteitis fibrosa disseminata PFD POFD Polyostotic fibrous dysplasia GTR C0242292 ICD-10-CM Q78.1 MeSH D005359 OMIM 174800 SNOMED CT 36517007 2009-01 2020-08-18 McKusick-Kaufman syndrome https://medlineplus.gov/genetics/condition/mckusick-kaufman-syndrome descriptionMcKusick-Kaufman syndrome is a condition that affects the development of the hands, feet, heart, and reproductive system. It is characterized by a combination of three features: extra fingers and/or toes (polydactyly), congenital heart defects, and genital abnormalities. The most common genital abnormality is hydrometrocolpos, an accumulation of fluid in the vagina and uterus.In people with McKusick-Kaufman syndrome, the extra digits are typically on the same side of the hand or foot as the pinky or little toe (postaxial polydactyly). The congenital heart defects in individuals with McKusick-Kaufman syndrome can include an atrial septal defect or a ventricular septal defect, which are openings in the wall (septum) that separates the upper or lower chambers of the heart. A genital abnormality called hydrometrocolpos is common in individuals with McKusick-Kaufman syndrome. Hydrometrocolpos can occur if part of the vagina  fails to develop (vaginal agenesis) or if a membrane blocks the opening of the vagina. The blockage allows fluid to build up in the vagina and uterus, stretching these organs and leading to a fluid-filled mass. Other genital abnormalities associated with McKusick-Kaufman syndrome can include a urethral opening on the underside of the penis (hypospadias), a downward-curving penis (chordee), and undescended testes (cryptorchidism).The signs and symptoms of McKusick-Kaufman syndrome overlap significantly with those of another genetic disorder, Bardet-Biedl syndrome. However, Bardet-Biedl syndrome has several features that are not typically seen in people with McKusick-Kaufman syndrome. These include a gradual loss of vision, developmental disabilities, kidney abnormalities, and obesity. Because some of these features are not apparent at birth, the two conditions can be difficult to tell apart in infancy and early childhood.Both McKusick-Kaufman syndrome and Bardet-Biedl syndrome belong to a group of conditions called ciliopathies. Ciliopathies are inherited disorders that affect the structure or function of cilia, the microscopic, finger-like projections found on the surface of cells. Cilia are involved in signaling pathways that transmit information between cells. ar Autosomal recessive MKKS https://medlineplus.gov/genetics/gene/mkks HMCS Hydrometrocolpos syndrome Hydrometrocolpos, postaxial polydactyly, and congenital heart malformation Hydrometrocolpos-postaxial polydactyly syndrome Kaufman-McKusick syndrome MKS GTR C0948368 ICD-10-CM MeSH D006330 MeSH D017689 MeSH D052202 OMIM 236700 SNOMED CT 702407009 2024-04 2024-04-16 McLeod neuroacanthocytosis syndrome https://medlineplus.gov/genetics/condition/mcleod-neuroacanthocytosis-syndrome descriptionMcLeod neuroacanthocytosis syndrome is primarily a neurological disorder that occurs almost exclusively in boys and men. This disorder affects movement in many parts of the body. People with McLeod neuroacanthocytosis syndrome also have abnormal star-shaped red blood cells (acanthocytosis). This condition is one of a group of disorders called neuroacanthocytoses that involve neurological problems and abnormal red blood cells.McLeod neuroacanthocytosis syndrome affects the brain and spinal cord (central nervous system). Affected individuals have involuntary movements, including jerking motions (chorea), particularly of the arms and legs, and muscle tensing (dystonia) in the face and throat, which can cause grimacing and vocal tics (such as grunting and clicking noises). Dystonia of the tongue can lead to swallowing difficulties. Seizures occur in approximately half of all people with McLeod neuroacanthocytosis syndrome. Individuals with this condition may develop difficulty processing, learning, and remembering information (cognitive impairment). They may also develop psychiatric disorders, such as depression, bipolar disorder, psychosis, or obsessive-compulsive disorder.People with McLeod neuroacanthocytosis syndrome also have problems with their muscles, including muscle weakness (myopathy) and muscle degeneration (atrophy). Sometimes, nerves that connect to muscles atrophy (neurogenic atrophy), leading to loss of muscle mass and impaired movement. Individuals with McLeod neuroacanthocytosis syndrome may also have reduced sensation and weakness in their arms and legs (peripheral neuropathy). Life-threatening heart problems such as irregular heartbeats (arrhythmia) and a weakened and enlarged heart (dilated cardiomyopathy) are common in individuals with this disorder.The signs and symptoms of McLeod neuroacanthocytosis syndrome usually begin in mid-adulthood. Behavioral changes, such as lack of self-restraint, the inability to take care of oneself, anxiety, depression, and changes in personality may be the first signs of this condition. While these behavioral changes are typically not progressive, the movement and muscle problems and intellectual impairments tend to worsen with age. xr X-linked recessive XK https://medlineplus.gov/genetics/gene/xk McLeod syndrome GTR C0398568 MeSH D054546 OMIM 300842 SNOMED CT 724172004 2008-05 2020-08-18 Meckel syndrome https://medlineplus.gov/genetics/condition/meckel-syndrome descriptionMeckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver.Other signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia.Because of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure. ar Autosomal recessive CEP290 https://medlineplus.gov/genetics/gene/cep290 MKS1 https://www.ncbi.nlm.nih.gov/gene/4290 RPGRIP1L https://www.ncbi.nlm.nih.gov/gene/23322 B9D1 https://www.ncbi.nlm.nih.gov/gene/27077 TMEM216 https://www.ncbi.nlm.nih.gov/gene/51259 CC2D2A https://www.ncbi.nlm.nih.gov/gene/57545 B9D2 https://www.ncbi.nlm.nih.gov/gene/80776 TMEM67 https://www.ncbi.nlm.nih.gov/gene/91147 Dysencephalia splanchnocystica Meckel-Gruber syndrome MKS GTR C1846357 GTR C1864148 GTR C1969052 GTR C1970161 GTR C2673885 GTR C2676790 GTR C3280036 GTR C3280155 GTR C3714506 GTR C3836857 MeSH D000015 OMIM 249000 OMIM 267010 OMIM 603194 OMIM 607361 OMIM 611134 OMIM 611561 OMIM 612284 OMIM 613885 OMIM 614175 OMIM 614209 SNOMED CT 29076005 2012-05 2020-08-18 Medium-chain acyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/medium-chain-acyl-coa-dehydrogenase-deficiency descriptionMedium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).Signs and symptoms of MCAD deficiency typically appear during infancy or early childhood and can include vomiting, lack of energy (lethargy), and low blood glucose (hypoglycemia). In rare cases, symptoms of this disorder are not recognized early in life, and the condition is not diagnosed until adulthood. People with MCAD deficiency are at risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden death.Problems related to MCAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. ar Autosomal recessive ACADM https://medlineplus.gov/genetics/gene/acadm ACADM deficiency MCAD deficiency MCADD MCADH deficiency Medium chain acyl-CoA dehydrogenase deficiency Medium-chain acyl-coenzyme A dehydrogenase deficiency GTR C0220710 ICD-10-CM E71.311 MeSH D008052 OMIM 201450 SNOMED CT 128596003 2009-11 2023-07-26 Medullary cystic kidney disease type 1 https://medlineplus.gov/genetics/condition/medullary-cystic-kidney-disease-type-1 descriptionMedullary cystic kidney disease type 1 (MCKD1) is an inherited condition that affects the kidneys. It leads to scarring (fibrosis) and impaired function of the kidneys, usually beginning in adulthood. The kidneys filter fluid and waste products from the body. They also reabsorb needed nutrients and release them back into the blood. As MCKD1 progresses, the kidneys are less able to function, resulting in kidney failure.Declining kidney function in people with MCKD1 leads to the signs and symptoms of the condition. The features are variable, even among members of the same family. Many individuals with MCKD1 develop high blood pressure (hypertension), especially as kidney function worsens. Some develop high levels of a waste product called uric acid in the blood (hyperuricemia) because the damaged kidneys are unable to remove uric acid effectively. In a small number of affected individuals, the buildup of this waste product can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints.Although the condition is named medullary cystic kidney disease, only about 40 percent of affected individuals have medullary cysts, which are fluid filled pockets found in a particular region of the kidney. When present, the cysts are usually found in the inner part of the kidney (the medullary region) or the border between the inner and outer parts (corticomedullary region). These cysts are visible by tests such as ultrasound or CT scan. ad Autosomal dominant MUC1 https://medlineplus.gov/genetics/gene/muc1 Autosomal dominant interstitial kidney disease Autosomal dominant medullary cystic kidney disease Polycystic kidneys, medullary type GTR C1868139 ICD-10-CM Q61.5 MeSH D007674 OMIM 174000 SNOMED CT 726017001 2013-06 2020-08-18 Meesmann corneal dystrophy https://medlineplus.gov/genetics/condition/meesmann-corneal-dystrophy descriptionMeesmann corneal dystrophy is an eye disease that affects the cornea, which is the clear front covering of the eye. This condition is characterized by the formation of tiny round cysts in the outermost layer of the cornea, called the corneal epithelium. This part of the cornea acts as a barrier to help prevent foreign materials, such as dust and bacteria, from entering the eye.In people with Meesmann corneal dystrophy, cysts can appear as early as the first year of life. They usually affect both eyes and increase in number over time. The cysts usually do not cause any symptoms until late adolescence or adulthood, when they start to break open (rupture) on the surface of the cornea and cause irritation. The resulting symptoms typically include increased sensitivity to light (photophobia), twitching of the eyelids (blepharospasm), increased tear production, the sensation of having a foreign object in the eye, and an inability to tolerate wearing contact lenses. Some affected individuals also have temporary episodes of blurred vision. ad Autosomal dominant KRT12 https://medlineplus.gov/genetics/gene/krt12 KRT3 https://medlineplus.gov/genetics/gene/krt3 Corneal dystrophy, juvenile epithelial of Meesmann Corneal dystrophy, Meesmann epithelial Juvenile hereditary epithelial dystrophy MECD Meesman's corneal dystrophy Meesmann corneal epithelial dystrophy Meesmann epithelial corneal dystrophy GTR C0339277 ICD-10-CM H18.52 MeSH D053559 OMIM 122100 SNOMED CT 1674008 2012-08 2020-08-18 Megacystis-microcolon-intestinal hypoperistalsis syndrome https://medlineplus.gov/genetics/condition/megacystis-microcolon-intestinal-hypoperistalsis-syndrome descriptionMegacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a severe disorder affecting the muscles that line the bladder and intestines. It is characterized by impairment of the muscle contractions that move food through the digestive tract (peristalsis) and empty the bladder.Some of the major features of MMIHS can be recognized before birth using ultrasound imaging. Affected fetuses have an enlarged bladder (megacystis) because it does not empty. In addition, the large intestine (colon) is abnormally narrow (microcolon) because of a shortage of functional muscle lining it. Intestinal and bladder problems persist throughout life.After birth, the continued impairment of peristalsis (hypoperistalsis) often causes a digestive condition called intestinal pseudo-obstruction. This condition, which mimics a physical blockage (obstruction) of the intestines but without an actual blockage, leads to a buildup of partially digested food in the intestines. This buildup can cause abdominal swelling (distention) and pain, nausea, and vomiting. The vomit usually contains a green or yellow digestive fluid called bile. Because digestion is impeded and the body does not get the nutrients from food, nutritional support is usually needed, which is given through intravenous feedings (parenteral nutrition). While some affected individuals rely solely on intravenous feedings, others require it only on occasion. Long-term use of parenteral nutrition can lead to liver problems.The reduced ability to pass urine also contributes to painful distention of the abdomen. Many people with MMIHS require placement of a tube (urinary catheter) to remove urine from the bladder.Another abnormality in some people with MMIHS is intestinal malrotation, in which the intestines do not fold properly. Instead, they twist abnormally, often causing a blockage. Individuals with MMIHS can also develop problems with the kidneys or the ureters, which are the ducts that carry urine from the kidneys to the bladder.The life expectancy of people with MMIHS is shorter than normal, often due to malnutrition, overwhelming infection (sepsis), or the failure of multiple organs. ar Autosomal recessive ad Autosomal dominant MYH11 https://medlineplus.gov/genetics/gene/myh11 ACTG2 https://medlineplus.gov/genetics/gene/actg2 MYLK https://www.ncbi.nlm.nih.gov/gene/4638 LMOD1 https://www.ncbi.nlm.nih.gov/gene/25802 Berdon syndrome Megacystis, microcolon, hypoperistalsis syndrome MMIH syndrome MMIHS GTR C5542316 GTR C5543476 GTR C5543513 GTR C5543636 MeSH D005767 OMIM 155310 OMIM 619350 SNOMED CT 253781004 2017-10 2024-10-02 Megalencephalic leukoencephalopathy with subcortical cysts https://medlineplus.gov/genetics/condition/megalencephalic-leukoencephalopathy-with-subcortical-cysts descriptionMegalencephalic leukoencephalopathy with subcortical cysts is a progressive condition that affects brain development and function. Individuals with this condition typically have an enlarged brain (megalencephaly) that is evident at birth or within the first year of life. Megalencephaly leads to an increase in the size of the head (macrocephaly). Affected people also have leukoencephalopathy, an abnormality of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve cells (neurons) and promotes the rapid transmission of nerve impulses. In megalencephalic leukoencephalopathy with subcortical cysts, the myelin is swollen and contains numerous fluid-filled pockets (vacuoles). Over time, the swelling decreases and the myelin begins to waste away (atrophy). Individuals affected with this condition may develop cysts in the brain; because these cysts form below an area of the brain called the cerebral cortex, they are called subcortical cysts. These cysts can grow in size and number.The brain abnormalities in people with megalencephalic leukoencephalopathy with subcortical cysts affect the use of muscles and lead to movement problems. Affected individuals typically experience muscle stiffness (spasticity) and difficulty coordinating movements (ataxia). Walking ability varies greatly among those affected. Some people lose the ability to walk early in life and need wheelchair assistance, while others are able to walk unassisted well into adulthood. Minor head trauma can further impair movements and may lead to coma. Affected individuals may also develop uncontrolled muscle tensing (dystonia), involuntary writhing movements of the limbs (athetosis), difficulty swallowing (dysphagia), and impaired speech (dysarthria). More than half of all people with this condition have recurrent seizures (epilepsy). Despite the widespread brain abnormalities, people with this condition typically have only mild to moderate intellectual disability.There are three types of megalencephalic leukoencephalopathy with subcortical cysts, which are distinguished by their signs and symptoms and genetic cause. Types 1 and 2A have different genetic causes but are nearly identical in signs and symptoms. Types 2A and 2B have the same genetic cause but the signs and symptoms of type 2B often begin to improve after one year. After improvement, individuals with type 2B usually have macrocephaly and may have intellectual disability. ar Autosomal recessive ad Autosomal dominant MLC1 https://medlineplus.gov/genetics/gene/mlc1 HEPACAM https://medlineplus.gov/genetics/gene/hepacam Infantile leukoencephalopathy and megalencephaly Leukoencephalopathy with swelling and a discrepantly mild course Leukoencephalopathy with swelling and cysts LVM MLC Vacuolating leukoencephalopathy Vacuolating megalencephalic leukoencephalopathy with subcortical cysts Van der Knaap disease GTR C1858854 GTR C5779875 MeSH D020279 OMIM 604004 OMIM 613925 OMIM 613926 SNOMED CT 703536004 2015-03 2020-08-18 Megalencephaly-capillary malformation syndrome https://medlineplus.gov/genetics/condition/megalencephaly-capillary-malformation-syndrome descriptionMegalencephaly-capillary malformation syndrome (MCAP) is a disorder characterized by overgrowth of several tissues in the body. Its primary features are a large brain (megalencephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).In individuals with MCAP, megalencephaly leads to an unusually large head size (macrocephaly), which is typically evident at birth. After birth, the brain and head continue to grow at a fast rate for the first few years of life; then, the growth slows to a normal rate, although the head remains larger than average. Additional brain abnormalities are common in people with MCAP; these can include excess fluid within the brain (hydrocephalus) and abnormalities in the brain's structure, such as those known as Chiari malformation and polymicrogyria. Abnormal brain development leads to intellectual disability in most affected individuals and can also cause seizures or weak muscle tone (hypotonia). In particular, polymicrogyria is associated with speech delays and difficulty chewing and swallowing.The capillary malformations characteristic of MCAP are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations usually look like pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, particularly the nose, the upper lip, and the area between the nose and upper lip (the philtrum). In other people with MCAP, the malformations appear as patches spread over the body or as a reddish net-like pattern on the skin (cutis marmorata).In some people with MCAP, excessive growth affects not only the brain but other individual parts of the body, which is known as segmental overgrowth. This can lead to one arm or leg that is bigger or longer than the other or a few oversized fingers or toes. Some affected individuals have fusion of the skin between two or more fingers or toes (cutaneous syndactyly).Additional features of MCAP can include flexible joints and skin that stretches easily. Some affected individuals are said to have doughy skin because the tissue under the skin is unusually thick and soft.The gene involved in MCAP is also associated with several types of cancer. Only a small number of individuals with MCAP have developed tumors (in particular, a childhood form of kidney cancer known as Wilms tumor and noncancerous tumors in the nervous system known as meningiomas). n Not inherited PIK3CA https://medlineplus.gov/genetics/gene/pik3ca M-CM Macrocephaly cutis marmorata telangiectatica congenita Macrocephaly-capillary malformation syndrome MCAP MCMTC Megalencephaly cutis marmorata telangiectatica congenita Megalencephaly-capillary malformation-polymicrogyria syndrome GTR C1865285 MeSH D054079 MeSH D058627 OMIM 602501 SNOMED CT 703370002 2014-02 2020-08-18 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome https://medlineplus.gov/genetics/condition/megalencephaly-polymicrogyria-polydactyly-hydrocephalus-syndrome descriptionMegalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare disorder that primarily affects the development of the brain. Affected individuals are born with an unusually large brain and head size (megalencephaly). The head and brain continue to grow rapidly during the first 2 years of life. MPPH syndrome is also associated with a brain abnormality called bilateral perisylvian polymicrogyria (BPP). The surface of the brain normally has many ridges or folds, called gyri. In people with BPP, an area of the brain called the perisylvian region develops too many gyri, and the folds are irregular and unusually small. Other brain abnormalities, including a buildup of fluid in the brain (hydrocephalus), have also been reported in people with MPPH syndrome.The problems with brain development cause a variety of neurological signs and symptoms. People with MPPH syndrome have delayed development and intellectual disability that ranges from mild to severe. About half of affected individuals develop recurrent seizures (epilepsy) beginning early in childhood. People with MPPH syndrome also have difficulty coordinating movements of the mouth and tongue (known as oromotor dysfunction), which leads to drooling, difficulty swallowing (dysphagia), and a delay in the production of speech (expressive language).About half of people with MPPH syndrome have an extra finger or toe on one or more of their hands or feet (polydactyly). The polydactyly is described as postaxial because it occurs on the same side of the hand or foot as the pinky finger or little toe.The brain abnormalities characteristic of MPPH syndrome are also found in a closely related condition called megalencephaly-capillary malformation syndrome (MCAP). However, MCAP includes abnormalities of small blood vessels in the skin (capillary malformations) and several other features that are not usually part of MPPH syndrome. ad Autosomal dominant AKT3 https://medlineplus.gov/genetics/gene/akt3 CCND2 https://medlineplus.gov/genetics/gene/ccnd2 PIK3R2 https://medlineplus.gov/genetics/gene/pik3r2 MEG-PMG-POLY-HYD Megalencephaly-postaxial polydactyly-polymicrogyria-hydrocephalus syndrome MPPH MPPH syndrome GTR C4012727 GTR C4014738 GTR C4014742 MeSH D006849 MeSH D017689 MeSH D058627 MeSH D065706 OMIM 603387 OMIM 615937 OMIM 615938 SNOMED CT 722036008 2017-01 2020-08-18 Meier-Gorlin syndrome https://medlineplus.gov/genetics/condition/meier-gorlin-syndrome descriptionMeier-Gorlin syndrome is a condition primarily characterized by short stature. It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation). After birth, affected individuals continue to grow at a slow rate. Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly). Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect.Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age).Most people with Meier-Gorlin syndrome have distinctive facial features. In addition to being abnormally small, the ears may be low-set or rotated backward. Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge.Abnormalities in sexual development may also occur in Meier-Gorlin syndrome. In some males with this condition, the testes are small or undescended (cryptorchidism). Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair.Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems. ar Autosomal recessive CDC6 https://medlineplus.gov/genetics/gene/cdc6 CDT1 https://medlineplus.gov/genetics/gene/cdt1 ORC1 https://medlineplus.gov/genetics/gene/orc1 ORC4 https://medlineplus.gov/genetics/gene/orc4 ORC6 https://medlineplus.gov/genetics/gene/orc6 Ear, patella, short stature syndrome Microtia, absent patellae, micrognathia syndrome GTR C1868684 GTR C3151097 GTR C3151113 GTR C3151120 GTR C3151126 MeSH D004392 OMIM 224690 OMIM 613800 OMIM 613803 OMIM 613804 OMIM 613805 SNOMED CT 703508009 2014-02 2020-08-18 Meige disease https://medlineplus.gov/genetics/condition/meige-disease descriptionMeige disease is a condition that affects the normal function of the lymphatic system. The lymphatic system consists of a network of vessels that transport lymphatic fluid and immune cells throughout the body. Meige disease is characterized by the abnormal transport of lymphatic fluid. When this fluid builds up abnormally, it causes swelling (lymphedema) in the lower limbs.Meige disease is classified as a primary lymphedema, which means it is a form of lymphedema that is not caused by other health conditions. In Meige disease, the lymphatic system abnormalities are present from birth (congenital), although the swelling is not usually apparent until puberty. The swelling often begins in the feet and ankles and progresses up the legs to the knees. Some affected individuals develop non-contagious skin infections called cellulitis or erysipelas in the legs, which can further damage the vessels that carry lymphatic fluid. ad Autosomal dominant Hereditary lymphedema II Late-onset lymphedema LMPH2 Lymphedema praecox Meige lymphedema GTR C4746631 ICD-10-CM Q82.0 MeSH D008209 OMIM 153200 SNOMED CT 400040008 SNOMED CT 77123007 2015-07 2020-08-18 Melanoma https://medlineplus.gov/genetics/condition/melanoma descriptionMelanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. This cancer typically occurs in areas that are only occasionally sun-exposed; tumors are most commonly found on the back in men and on the legs in women. Melanoma usually occurs on the skin (cutaneous melanoma), but in about 5 percent of cases it develops in melanocytes in other tissues, including the eyes (uveal melanoma) or mucous membranes that line the body's cavities, such as the moist lining of the mouth (mucosal melanoma). Melanoma can develop at any age, but it most frequently occurs in people in their fifties to seventies and is becoming more common in teenagers and young adults.Melanoma may develop from an existing mole or other normal skin growth that becomes cancerous (malignant); however, many melanomas are new growths. Melanomas often have ragged edges and an irregular shape. They can range from a few millimeters to several centimeters across. They can also be a variety of colors: brown, black, red, pink, blue, or white.Most melanomas affect only the outermost layer of skin (the epidermis). If a melanoma becomes thicker and involves multiple layers of skin, it can spread to other parts of the body (metastasize).A large number of moles or other pigmented skin growths on the body, generally more than 25, is associated with an increased risk of developing melanoma. Melanoma is also a common feature of genetic syndromes affecting the skin such as xeroderma pigmentosum. Additionally, individuals who have previously had melanoma are nearly nine times more likely than the general population to develop melanoma again. It is estimated that about 90 percent of individuals with melanoma survive at least 5 years after being diagnosed. n Not inherited ad Autosomal dominant TP53 https://medlineplus.gov/genetics/gene/tp53 ATM https://medlineplus.gov/genetics/gene/atm MITF https://medlineplus.gov/genetics/gene/mitf OCA2 https://medlineplus.gov/genetics/gene/oca2 TYR https://medlineplus.gov/genetics/gene/tyr TYRP1 https://medlineplus.gov/genetics/gene/tyrp1 SLC45A2 https://medlineplus.gov/genetics/gene/slc45a2 MC1R https://medlineplus.gov/genetics/gene/mc1r PLA2G6 https://medlineplus.gov/genetics/gene/pla2g6 BRAF https://medlineplus.gov/genetics/gene/braf TERT https://medlineplus.gov/genetics/gene/tert NRAS https://medlineplus.gov/genetics/gene/nras CDKN2A https://medlineplus.gov/genetics/gene/cdkn2a BAP1 https://medlineplus.gov/genetics/gene/bap1 ASIP https://www.ncbi.nlm.nih.gov/gene/434 CASP8 https://www.ncbi.nlm.nih.gov/gene/841 CDK4 https://www.ncbi.nlm.nih.gov/gene/1019 EGF https://www.ncbi.nlm.nih.gov/gene/1950 IRF4 https://www.ncbi.nlm.nih.gov/gene/3662 KITLG https://www.ncbi.nlm.nih.gov/gene/4254 MTAP https://www.ncbi.nlm.nih.gov/gene/4507 MX2 https://www.ncbi.nlm.nih.gov/gene/4600 SLC2A4 https://www.ncbi.nlm.nih.gov/gene/6517 XRCC3 https://www.ncbi.nlm.nih.gov/gene/7517 CDK10 https://www.ncbi.nlm.nih.gov/gene/8558 HERC2 https://www.ncbi.nlm.nih.gov/gene/8924 POT1 https://www.ncbi.nlm.nih.gov/gene/25913 MYH7B https://www.ncbi.nlm.nih.gov/gene/57644 PIGU https://www.ncbi.nlm.nih.gov/gene/128869 TPCN2 https://www.ncbi.nlm.nih.gov/gene/219931 Cutaneous melanoma Malignant melanoma GTR C0025202 GTR C0151779 GTR C1512419 ICD-10-CM C43 MeSH D008545 OMIM 155600 OMIM 155601 OMIM 608035 OMIM 609048 OMIM 612263 OMIM 613099 OMIM 613972 OMIM 614456 OMIM 615134 OMIM 615848 SNOMED CT 372244006 SNOMED CT 830150003 SNOMED CT 830195005 2018-07 2021-05-28 Melnick-Needles syndrome https://medlineplus.gov/genetics/condition/melnick-needles-syndrome descriptionMelnick-Needles syndrome is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, frontometaphyseal dysplasia, and terminal osseous dysplasia. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits).Melnick-Needles syndrome is usually the most severe of the otopalatodigital spectrum disorders. People with this condition are usually of short stature, have an abnormal curvature of the spine (scoliosis), partial dislocation (subluxation) of certain joints, and unusually long fingers and toes. They may have bowed limbs; underdeveloped, irregular ribs that can cause problems with breathing; and other abnormal or absent bones.Characteristic facial features may include bulging eyes with prominent brow ridges, excess hair growth on the forehead, round cheeks, a very small lower jaw and chin (micrognathia), and misaligned teeth. One side of the face may appear noticeably different from the other (facial asymmetry). Some individuals with this disorder have hearing loss.In addition to skeletal abnormalities, individuals with Melnick-Needles syndrome may have obstruction of the ducts between the kidneys and bladder (ureters) or heart defects.Males with Melnick-Needles syndrome generally have much more severe signs and symptoms than do females, and in almost all cases die before or soon after birth. xd X-linked dominant FLNA https://medlineplus.gov/genetics/gene/flna Melnick-Needles osteodysplasty MNS Osteodysplasty of Melnick and Needles GTR C0025237 MeSH D010009 OMIM 309350 SNOMED CT 13449007 2007-11 2021-08-26 Melorheostosis https://medlineplus.gov/genetics/condition/melorheostosis descriptionMelorheostosis is a rare bone disease. It causes the abnormal growth of new bone tissue on the surface of existing bones. The new bone has a characteristic appearance on x-rays, often described as "flowing" or like dripping candle wax. The excess bone growth typically occurs on the bones in one arm or leg, although it can also affect the pelvis, breastbone (sternum), ribs, or other bones. (The term "melorheostosis" is derived from the Greek words "melos," which means limb; "rheos," which means flow; and "ostosis," which refers to bone formation.) The abnormal bone growth associated with melorheostosis is noncancerous (benign), and it does not spread from one bone to another.The signs and symptoms of melorheostosis usually appear in childhood or adolescence. The condition can cause long-lasting (chronic) pain, permanent joint deformities (contractures), and a limited range of motion of the affected body part. In some people, the limb may appear thickened or enlarged, and the skin overlying the affected area can become red, thick, and shiny.Another rare disease, Buschke-Ollendorff syndrome, can include melorheostosis. Buschke-Ollendorff syndrome is characterized by skin growths called connective tissue nevi and areas of increased bone density called osteopoikilosis. A small percentage of affected individuals also have melorheostosis or other bone abnormalities. Scientists originally speculated that melorheostosis that occurs without the other features of Buschke-Ollendorff syndrome might have the same genetic cause as that syndrome. However, it has since been determined that Buschke-Ollendorff syndrome and melorheostosis that occurs alone are caused by mutations in different genes, and the two conditions are considered separate disorders. n Not inherited MAP2K1 https://medlineplus.gov/genetics/gene/map2k1 Candle wax disease Flowing hyperostosis Hyperostosis, monomelic Leri syndrome Leri's disease Melorheostoses Melorheostosis of Leri Melorheostosis, isolated Periostitis; monomelic Rheostosis GTR C3149631 MeSH D008557 OMIM 155950 SNOMED CT 44697002 2018-05 2020-08-18 Menkes syndrome https://medlineplus.gov/genetics/condition/menkes-syndrome descriptionMenkes syndrome is a disorder that affects copper levels in the body. It is characterized by sparse, kinky hair; failure to gain weight and grow at the expected rate (failure to thrive); and deterioration of the nervous system. Additional signs and symptoms include weak muscle tone (hypotonia), sagging facial features, seizures, developmental delay, and intellectual disability. Children with Menkes syndrome typically begin to develop symptoms during infancy and often do not live past age 3. Early treatment with copper may improve the prognosis in some affected individuals. In rare cases, symptoms begin later in childhood.Occipital horn syndrome (sometimes called X-linked cutis laxa) is a less severe form of Menkes syndrome that begins in early to middle childhood. It is characterized by wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose skin and joints. xr X-linked recessive ATP7A https://medlineplus.gov/genetics/gene/atp7a Copper transport disease Hypocupremia, congenital Kinky hair syndrome Menkea syndrome Menkes disease MK MNK Steely hair syndrome X-linked copper deficiency GTR C0022716 MeSH D007706 OMIM 304150 OMIM 309400 SNOMED CT 59178007 2009-03 2021-04-07 Metabolic dysfunction-associated steatotic liver disease https://medlineplus.gov/genetics/condition/metabolic-dysfunction-associated-steatotic-liver-disease descriptionMetabolic dysfunction-associated steatotic liver disease (MASLD) is a condition that is characterized by a buildup of fat in the liver, which can lead to liver damage. The liver is part of the digestive system, and it helps break down food, store energy, and remove waste products. If more than 5 percent of the liver contains fat, the liver is considered to be fatty (steatotic).MASLD is most common among middle-aged or older people, although younger people, including children, may also be affected. People with MASLD have liver steatosis along with at least one of the following features: higher body weight, type 2 diabetes, or one of several metabolic abnormalities. The abnormalities that are included in the diagnosis of MASLD are pre-diabetes (insulin resistance), high levels of fats (lipids) such as cholesterol and triglycerides in the blood, or high blood pressure (hypertension). MASLD is estimated to occur in up to 75 percent of adults with obesity or high levels of lipids in the blood and in up to 65 percent of adults with type 2 diabetes.In people with MASLD, the fat deposits in the liver can cause increased levels of liver enzymes that can be detected during routine blood tests. Some affected individuals have abdominal pain or fatigue. During a physical examination, the liver may be found to be slightly enlarged. In people with MASLD, the liver problems are not caused by alcohol use disorder.MASLD is slow to worsen, or it may not worsen at all. In many affected individuals, the buildup of fat in the liver can be reduced by adopting healthy habits. However, up to 30 percent of people with MASLD develop inflammation of the liver (metabolic dysfunction-associated steatohepatitis, also known as MASH), which can damage the liver. In people with long-term liver damage, normal liver tissue may be replaced with scar tissue (fibrosis), resulting in permanent liver disease (cirrhosis) and, eventually, liver failure. People with MASLD, MASH, and cirrhosis have a higher risk of developing liver cancer (hepatocellular cancer). People with MASLD are also at increased risk of developing additional health problems such as heart (cardiovascular) disease. u Pattern unknown PNPLA3 https://medlineplus.gov/genetics/gene/pnpla3 APOC3 https://www.ncbi.nlm.nih.gov/gene/345 GCKR https://www.ncbi.nlm.nih.gov/gene/2646 TRIB1 https://www.ncbi.nlm.nih.gov/gene/10221 TM6SF2 https://www.ncbi.nlm.nih.gov/gene/53345 MBOAT7 https://www.ncbi.nlm.nih.gov/gene/79143 MASLD NAFLD Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis GTR C2750440 GTR C3150651 ICD-10-CM K75.81 MeSH D065626 OMIM 613282 OMIM 613387 SNOMED CT 197315008 2026-04 2026-04-01 Metachromatic leukodystrophy https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy descriptionMetachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system).In people with metachromatic leukodystrophy, white matter damage causes progressive deterioration of intellectual functions and motor skills, such as the ability to walk. Affected individuals also develop loss of sensation in the extremities (peripheral neuropathy), incontinence, seizures, paralysis, an inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. While neurological problems are the primary feature of metachromatic leukodystrophy, effects of sulfatide accumulation on other organs and tissues have been reported, most often involving the gallbladder.The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood.In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis.The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcohol use disorder, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline.Metachromatic leukodystrophy gets its name from the way cells with an accumulation of sulfatides appear when viewed under a microscope. The sulfatides form granules that are described as metachromatic, which means they pick up color differently than surrounding cellular material when stained for examination. ar Autosomal recessive ARSA https://medlineplus.gov/genetics/gene/arsa PSAP https://medlineplus.gov/genetics/gene/psap ARSA deficiency Arylsulfatase A deficiency disease Cerebral sclerosis, diffuse, metachromatic form Cerebroside sulphatase deficiency disease Greenfield disease Metachromatic leukoencephalopathy MLD Sulfatide lipidosis Sulfatidosis GTR C0023522 GTR C0268262 ICD-10-CM E75.25 MeSH D007966 OMIM 249900 OMIM 250100 SNOMED CT 238031009 SNOMED CT 24326000 SNOMED CT 396338004 SNOMED CT 40802007 SNOMED CT 44359008 SNOMED CT 68390005 2007-09 2023-04-12 Metatropic dysplasia https://medlineplus.gov/genetics/condition/metatropic-dysplasia descriptionMetatropic dysplasia is a skeletal disorder characterized by short stature (dwarfism) with other skeletal abnormalities. The term "metatropic" is derived from the Greek word "metatropos," which means "changing patterns." This name reflects the fact that the skeletal abnormalities associated with the condition change over time.Affected infants are born with a narrow chest and unusually short arms and legs with dumbbell-shaped long bones. Beginning in early childhood, people with this condition develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). The curvature worsens with time and tends to be resistant to treatment. Because of the severe kyphoscoliosis, affected individuals may ultimately have a very short torso in relation to the length of their arms and legs.Some people with metatropic dysplasia are born with an elongated tailbone known as a coccygeal tail; it is made of a tough but flexible tissue called cartilage. The coccygeal tail usually shrinks over time. Other skeletal problems associated with metatropic dysplasia include flattened bones of the spine (platyspondyly); excessive movement of spinal bones in the neck that can damage the spinal cord; either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum); and joint deformities called contractures that restrict the movement of joints in the shoulders, elbows, hips, and knees. Beginning early in life, affected individuals can also develop a degenerative form of arthritis that causes joint pain and further restricts movement.The signs and symptoms of metatropic dysplasia can vary from relatively mild to life-threatening. In the most severe cases, the narrow chest and spinal abnormalities prevent the lungs from expanding fully, which restricts breathing. Researchers formerly recognized several distinct forms of metatropic dysplasia based on the severity of the condition's features. The forms included a mild type, a classic type, and a lethal type. However, all of these forms are now considered to be part of a single condition with a spectrum of overlapping signs and symptoms. ad Autosomal dominant TRPV4 https://medlineplus.gov/genetics/gene/trpv4 Metatropic dwarfism Metatropic dysplasia type 1 GTR C0265281 MeSH D004392 OMIM 156530 SNOMED CT 22764001 2012-04 2020-08-18 Methemoglobinemia, beta-globin type https://medlineplus.gov/genetics/condition/methemoglobinemia-beta-globin-type descriptionMethemoglobinemia, beta-globin type is a condition that affects the function of red blood cells. Specifically, it alters a molecule called hemoglobin within these cells. Hemoglobin within red blood cells attaches (binds) to oxygen molecules in the lungs, which it carries through the bloodstream, then releases in tissues throughout the body. Instead of normal hemoglobin, people with methemoglobinemia, beta-globin type have an abnormal form called methemoglobin, which is unable to efficiently deliver oxygen to the body's tissues. In methemoglobinemia, beta-globin type, the abnormal hemoglobin gives the blood a brown color. It also causes a bluish appearance of the skin, lips, and nails (cyanosis), which usually first appears around the age of 6 months. The signs and symptoms of methemoglobinemia, beta-globin type are generally limited to cyanosis, which does not cause any health problems. However, in rare cases, severe methemoglobinemia, beta-globin type can cause headaches, weakness, and fatigue. ad Autosomal dominant HBB https://medlineplus.gov/genetics/gene/hbb Blue baby syndrome Congenital methemoglobinemia Hemoglobin M disease GTR C1840779 ICD-10-CM D74.0 MeSH D008708 OMIM 141900 SNOMED CT 267550008 2015-06 2025-04-03 Methylmalonic acidemia https://medlineplus.gov/genetics/condition/methylmalonic-acidemia descriptionMethylmalonic acidemia is a group of inherited disorders that prevent the body from breaking down proteins and fats (lipids) properly. The effects of methylmalonic acidemia, which usually appear in early infancy, vary from mild to life-threatening. Affected infants can experience vomiting, dehydration, weak muscle tone (hypotonia), developmental delays, excessive tiredness (lethargy), an enlarged liver (hepatomegaly), and failure to gain weight and grow at the expected rate (failure to thrive). Long-term complications can include feeding problems, intellectual disabilities, movement problems, chronic kidney disease, and inflammation of the pancreas (pancreatitis). People with methylmalonic acidemia can have frequent episodes of excess acid in the blood (metabolic acidosis) that cause serious health complications.Without treatment, this disorder can lead to coma and death in some cases. ar Autosomal recessive MMUT https://medlineplus.gov/genetics/gene/mmut MMAA https://medlineplus.gov/genetics/gene/mmaa MMAB https://medlineplus.gov/genetics/gene/mmab MCEE https://medlineplus.gov/genetics/gene/mcee MMADHC https://medlineplus.gov/genetics/gene/mmadhc Isolated methylmalonic acidemia Methylmalonic aciduria MMA GTR C0268583 GTR C1855100 GTR C1855102 GTR C1855109 GTR C1855114 ICD-10-CM E71.120 MeSH D008661 OMIM 251000 OMIM 251100 OMIM 251110 OMIM 251120 OMIM 277410 SNOMED CT 42393006 SNOMED CT 69614003 SNOMED CT 73843004 SNOMED CT 82245003 2023-07 2023-07-17 Methylmalonic acidemia with homocystinuria https://medlineplus.gov/genetics/condition/methylmalonic-acidemia-with-homocystinuria descriptionMethylmalonic acidemia with homocystinuria is a disorder in which the body is unable to correctly process certain protein building blocks (amino acids), fat building blocks (fatty acids), and  cholesterol. The body is also unable to convert the amino acid homocysteine to another amino acid, methionine. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria. There are several forms of this combined condition, and the different forms have different genetic causes and signs and symptoms. The most common and best understood form, called cblC type (or cobalamin C disease), occurs in about 80 percent of affected individuals. The signs and symptoms of methylmalonic acidemia with homocystinuria usually develop in infancy, although they can begin at any age. When the condition begins early in life, affected individuals typically grow more slowly than expected. This sign is sometimes iedentified before the baby is born. These infants can also have difficulty feeding and have an abnormally pale appearance (pallor). Eye abnormalities and neurological problems, including weak muscle tone (hypotonia) and seizures, are also common in people with methylmalonic acidemia with homocystinuria. Many infants and children with this condition have delayed development and intellectual disability, and some have an unusually small head size (microcephaly). Some people with methylmalonic acidemia with homocystinuria develop a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The signs and symptoms of early-onset methylmalonic acidemia with homocystinuria worsen over time, and the condition can be life-threatening if it is not treated.When methylmalonic acidemia with homocystinuria begins in adolescence or adulthood, it may change an affected person's behavior and personality; the person may become less social and may experience hallucinations, delirium, and psychosis. In addition, these individuals can begin to lose previously acquired mental and physical abilities, resulting in a decline in school or work performance, difficulty controlling movements, memory problems, speech difficulties, a decline in intellectual function (dementia), or an extreme lack of energy (lethargy). Some people with methylmalonic acidemia with homocystinuria whose signs and symptoms begin later in life develop a condition called subacute combined degeneration of the spinal cord, which leads to numbness and weakness in the lower limbs, difficulty walking, and frequent falls. xr X-linked recessive ar Autosomal recessive MMADHC https://medlineplus.gov/genetics/gene/mmadhc ABCD4 https://medlineplus.gov/genetics/gene/abcd4 HCFC1 https://medlineplus.gov/genetics/gene/hcfc1 LMBRD1 https://medlineplus.gov/genetics/gene/lmbrd1 MMACHC https://medlineplus.gov/genetics/gene/mmachc PRDX1 https://medlineplus.gov/genetics/gene/prdx1 ZNF143 https://www.ncbi.nlm.nih.gov/gene/7702 THAP11 https://www.ncbi.nlm.nih.gov/gene/57215 Methylmalonic acidemia and homocystinemia Methylmalonic acidemia and homocystinuria Methylmalonic aciduria and homocystinuria Vitamin B12 metabolic defect with combined deficiency of methylmalonyl-coA mutase and homocysteine:methyltetrahydrofolate methyltransferase Vitamin B12 metabolic defect with combined deficiency of methylmalonyl-coA mutase and methionine synthase activities GTR C1848552 GTR C1848561 GTR C1848578 GTR C3553915 MeSH D000592 OMIM 277380 OMIM 277400 OMIM 277410 OMIM 614857 SNOMED CT 4409006 2023-05 2023-05-16 Mevalonate kinase deficiency https://medlineplus.gov/genetics/condition/mevalonate-kinase-deficiency descriptionMevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often.Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA).During episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why some people with HIDS have high levels of IgD and IgA and some do not. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy.People with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, problems with movement and balance (ataxia), recurrent seizures (epilepsy), progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy. ar Autosomal recessive MVK https://medlineplus.gov/genetics/gene/mvk Hyper IgD syndrome Hyperimmunoglobulin D with periodic fever Hyperimmunoglobulinemia D Mevalonic aciduria Mevalonicaciduria Periodic fever, Dutch type GTR C0398691 GTR C1959626 MeSH D054078 OMIM 260920 OMIM 610377 SNOMED CT 124327008 SNOMED CT 234538002 2011-04 2026-03-04 Microcephalic osteodysplastic primordial dwarfism type II https://medlineplus.gov/genetics/condition/microcephalic-osteodysplastic-primordial-dwarfism-type-ii descriptionMicrocephalic osteodysplastic primordial dwarfism type II (MOPDII) is a condition characterized by short stature (dwarfism) with other skeletal abnormalities (osteodysplasia) and an unusually small head size (microcephaly). The growth problems in MOPDII are primordial, meaning they begin before birth, with affected individuals showing slow prenatal growth (intrauterine growth retardation). After birth, affected individuals continue to grow at a very slow rate. The final adult height of people with this condition ranges from 20 inches to 40 inches. Other skeletal abnormalities in MOPDII include abnormal development of the hip joints (hip dysplasia), thinning of the bones in the arms and legs, an abnormal side-to-side curvature of the spine (scoliosis), and shortened wrist bones. In people with MOPDII head growth slows over time; affected individuals have an adult brain size comparable to that of a 3-month-old infant. However, intellectual development is typically normal.People with this condition have a high-pitched, nasal voice and some have a narrowing of the voicebox (subglottic stenosis). Facial features characteristic of MOPDII include a prominent nose, full cheeks, a long midface, and a small jaw. Other signs and symptoms seen in some people with MOPDII include small teeth (microdontia) and farsightedness. Over time, affected individuals may develop areas of abnormally light or dark skin coloring (pigmentation).Many individuals with MOPDII have blood vessel abnormalities. For example, some affected individuals develop a bulge in one of the blood vessels at the center of the brain (intracranial aneurysm). These aneurysms are dangerous because they can burst, causing bleeding within the brain. Some affected individuals have Moyamoya disease, in which arteries at the base of the brain are narrowed, leading to restricted blood flow. These vascular abnormalities are often treatable, though they increase the risk of stroke and reduce the life expectancy of affected individuals. ar Autosomal recessive PCNT https://medlineplus.gov/genetics/gene/pcnt Majewski osteodysplastic primordial dwarfism type II MOPD2 MOPDII Osteodysplastic primordial dwarfism type II GTR C0432246 MeSH D004392 OMIM 210720 SNOMED CT 254103003 2011-01 2023-02-27 Microcephaly, seizures, and developmental delay https://medlineplus.gov/genetics/condition/microcephaly-seizures-and-developmental-delay descriptionMicrocephaly, seizures, and developmental delay (MCSZ) is a condition characterized by an abnormally small head size (microcephaly) and neurological problems related to impaired brain development before birth. Affected individuals typically have recurrent seizures (epilepsy) beginning in infancy and delayed development of motor skills, such as sitting and walking. Speech is also delayed, and some affected individuals are never able to speak. Intellectual disability and behavior problems, primarily hyperactivity, are also common features of MCSZ. Rarely, individuals with MCSZ also have poor balance and coordination (ataxia). ar Autosomal recessive PNKP https://medlineplus.gov/genetics/gene/pnkp EIEE10 Epileptic encephalopathy, early infantile, 10 MCSZ GTR C3150667 MeSH D065886 OMIM 613402 2018-06 2020-08-18 Microcephaly-capillary malformation syndrome https://medlineplus.gov/genetics/condition/microcephaly-capillary-malformation-syndrome descriptionMicrocephaly-capillary malformation syndrome is an inherited disorder characterized by an abnormally small head size (microcephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).In people with microcephaly-capillary malformation syndrome, microcephaly begins before birth and is associated with an unusually small brain and multiple brain abnormalities. Affected individuals develop seizures that can occur many times per day and are difficult to treat (intractable epilepsy). The problems with brain development and epilepsy lead to profound developmental delay and intellectual impairment. Most affected individuals do not develop skills beyond those of a 1- or 2-month-old infant. For example, most children with this condition are never able to control their head movements or sit unassisted.Capillary malformations are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations look like pink or red spots on the skin. People with microcephaly-capillary malformation syndrome are born with anywhere from a few to hundreds of these spots, which can occur anywhere on the body. The spots are usually round or oval-shaped and range in size from the head of a pin to a large coin.Other signs and symptoms of microcephaly-capillary malformation syndrome include abnormal movements, feeding difficulties, slow growth, and short stature. Most affected individuals have abnormalities of the fingers and toes, including digits with tapered ends and abnormally small or missing fingernails and toenails. Some affected children also have distinctive facial features and an unusual pattern of hair growth on the scalp. ar Autosomal recessive STAMBP https://medlineplus.gov/genetics/gene/stambp MIC-CAP syndrome GTR C3280296 MeSH D008831 MeSH D054079 OMIM 614261 SNOMED CT 703369003 2014-02 2024-05-24 Microphthalmia with linear skin defects syndrome https://medlineplus.gov/genetics/condition/microphthalmia-with-linear-skin-defects-syndrome descriptionMicrophthalmia with linear skin defects syndrome is a disorder that mainly affects females. In people with this condition, one or both eyes may be very small or poorly developed (microphthalmia). Affected individuals also typically have unusual linear skin markings on the head and neck. These markings follow the paths along which cells migrate as the skin develops before birth (lines of Blaschko). The skin defects generally improve over time and leave variable degrees of scarring.The signs and symptoms of microphthalmia with linear skin defects syndrome vary widely, even among affected individuals within the same family. In addition to the characteristic eye problems and skin markings, this condition can cause abnormalities in the brain, heart, and genitourinary system. A hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia, may occur in people with this disorder. Affected individuals may also have short stature and fingernails and toenails that do not grow normally (nail dystrophy). xd X-linked dominant HCCS https://medlineplus.gov/genetics/gene/hccs X https://medlineplus.gov/genetics/chromosome/x MCOPS7 Microphthalmia syndromic 7 Microphthalmia with linear skin lesions syndrome Microphthalmia, dermal aplasia, and sclerocornea Microphthalmia, syndromic 7 MIDAS syndrome MLS syndrome Syndromic microphthalmia-7 GTR C0796070 MeSH D008850 OMIM 309801 SNOMED CT 721879006 2009-10 2020-09-08 Microvillus inclusion disease https://medlineplus.gov/genetics/condition/microvillus-inclusion-disease descriptionMicrovillus inclusion disease is a condition characterized by chronic, watery, life-threatening diarrhea typically beginning in the first hours to days of life. Rarely, the diarrhea starts around age 3 or 4 months. Food intake increases the frequency of diarrhea.Microvillus inclusion disease prevents the absorption of nutrients from food during digestion, resulting in malnutrition and dehydration. Affected infants often have difficulty gaining weight and growing at the expected rate (failure to thrive), developmental delay, liver and kidney problems, and thinning of the bones (osteoporosis). Some affected individuals develop cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to irreversible liver disease (cirrhosis).In individuals with microvillus inclusion disease, lifelong nutritional support is needed and given through intravenous feedings (parenteral nutrition).A variant of microvillus inclusion disease with milder diarrhea often does not require full-time parenteral nutrition. Individuals with the variant type frequently live past childhood. ar Autosomal recessive MYO5B https://medlineplus.gov/genetics/gene/myo5b STX3 https://www.ncbi.nlm.nih.gov/gene/6809 Congenital enteropathy Congenital familial protracted diarrhea with enterocyte brush-border abnormalities Congenital microvillous atrophy Davidson disease Familial protracted enteropathy Intractable diarrhea of infancy Microvillous atrophy Microvillous inclusion disease Microvillus atrophy with diarrhea 2 MVID GTR C0341306 MeSH D008286 OMIM 251850 SNOMED CT 235729009 2014-07 2020-08-18 Migraine https://medlineplus.gov/genetics/condition/migraine descriptionA migraine is a type of headache that typically causes intense, throbbing pain usually in one area of the head. People can experience migraines once a year to multiple times a week. A person is considered to have chronic migraines if they experience 15 or more headache days a month with eight of those days involving migraine headaches. Migraines typically first start during a person's teens to early twenties, but they can begin anytime from early childhood to late-adulthood.A migraine usually has three stages: the period leading up to the headache (known as the premonitory or prodromal phase), the migraine itself (the headache phase), and the period following the headache (known as the postdromal phase).The premonitory phase can start from several hours up to several days before the headache appears. In this phase, affected individuals can experience extreme tiredness (fatigue), concentration problems, and muscle stiffness in the neck. A wide variety of additional signs and symptoms can occur including excessive yawning, food cravings, irritability, depression, sensitivity to light, and nausea. About one-third of people with migraine experience a temporary pattern of neurological symptoms called an aura. An aura typically develops gradually over a few minutes and lasts between 5 and 60 minutes. Auras commonly include temporary visual changes such as blind spots (scotomas), flashing lights, and zig-zagging lines of color. Additional features of aura can include numbness, difficulty with speech and language, episodes of extreme dizziness (vertigo), and double vision. During an aura, affected individuals might experience abnormal sensations including tingling or numbness, usually of the hands or mouth. An aura usually starts within one hour of the start of a migraine. In some cases, an aura can occur without a subsequent migraine.In the headache phase, the pain may last from a few hours to a few days. Affected individuals tend to experience nausea, vomiting, dizziness, and sensitivity to light and sound in addition to headache. Some have changes in their vision or sensitivity to odors and touch.The postdromal phase usually lasts a few hours but can linger for more than a day. In this phase, the headache pain is gone but individuals can experience fatigue, drowsiness, decreased energy, concentration problems, irritability, nausea, or sensitivity to light. Affected individuals may also have brief episodes of head pain when moving their head.People with migraine, particularly women who have migraine with aura, have an increased risk of a type of stroke that is caused by a lack of blood flow to the brain (ischemic stroke), but this is a rare occurrence.There are many migraine disorders that usually include additional signs and symptoms. For example, familial hemiplegic migraine and sporadic hemiplegic migraine are characterized by migraine with associated temporary weakness that affects one side of the body (hemiparesis). Additionally, cyclic vomiting syndrome is a migraine disorder usually found in children that causes episodes of nausea and vomiting in addition to headaches. u Pattern unknown HPSE2 https://medlineplus.gov/genetics/gene/hpse2 RNF213 https://medlineplus.gov/genetics/gene/rnf213 MPPED2 https://www.ncbi.nlm.nih.gov/gene/744 MEF2D https://www.ncbi.nlm.nih.gov/gene/4209 KCNK5 https://www.ncbi.nlm.nih.gov/gene/8645 NRP1 https://www.ncbi.nlm.nih.gov/gene/8829 IRAG1 https://www.ncbi.nlm.nih.gov/gene/10335 YAP1 https://www.ncbi.nlm.nih.gov/gene/10413 CFDP1 https://www.ncbi.nlm.nih.gov/gene/10428 IGSF9B https://www.ncbi.nlm.nih.gov/gene/22997 ASTN2 https://www.ncbi.nlm.nih.gov/gene/23245 PLCE1 https://www.ncbi.nlm.nih.gov/gene/51196 SLC24A3 https://www.ncbi.nlm.nih.gov/gene/56225 PRDM16 https://www.ncbi.nlm.nih.gov/gene/63976 SUGCT https://www.ncbi.nlm.nih.gov/gene/79783 CARF https://www.ncbi.nlm.nih.gov/gene/79800 PHACTR1 https://www.ncbi.nlm.nih.gov/gene/221692 Classic migraine Common migraine Disorder, migraine Headache migraine Headache migrainous Migraine disorder Migraine headache Migraine syndrome Migraines GTR C3887485 ICD-10-CM G43 MeSH D020325 MeSH D020326 OMIM 157300 OMIM 300125 OMIM 607498 OMIM 607501 OMIM 607508 OMIM 607516 OMIM 609179 OMIM 609570 OMIM 609670 OMIM 610208 OMIM 610209 OMIM 611706 OMIM 613656 SNOMED CT 37796009 2019-01 2020-08-18 Miller syndrome https://medlineplus.gov/genetics/condition/miller-syndrome descriptionMiller syndrome is a rare condition that mainly affects the development of the face, arms, and legs. The severity of this disorder can vary among affected individuals.Individuals with Miller syndrome typically have facial differences, which can include underdeveloped cheek bones (malar hypoplasia), a small lower jaw (micrognathia), and an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). These facial differences can cause feeding problems in infants with Miller syndrome. In some affected individuals, micrognathia may restrict the airway, which can also lead to breathing problems. Other facial features can include eyes that slant downward, eyelids that turn outward so the inner surface is exposed (ectropion), and a notch in the lower eyelids called an eyelid coloboma. Many individuals with Miller syndrome also have small, cup-shaped ears. Some affected individuals have hearing loss caused by defects in the middle ear (conductive hearing loss), which can lead to a delay in speech development.  The bones of the arms and legs often develop abnormally in people with Miller syndrome. The most common problem is the absence of the fifth (pinky) fingers and toes. Affected individuals may also have webbed or fused fingers or toes (syndactyly) and underdeveloped bones in the forearms. Another feature of Miller syndrome is the presence of extra nipples. Abnormalities of the heart have also been reported in individuals with this condition.  ar Autosomal recessive DHODH https://medlineplus.gov/genetics/gene/dhodh Acrofacial dysostosis, Genee-Wiedemann type Genee-Wiedemann acrofacial dysostosis Genee-Wiedemann syndrome Mandibulfacial dysostosis with postaxial limb anomalies Postaxial acrofacial dysostosis (POADS) GTR C0265257 MeSH D003394 OMIM 263750 SNOMED CT 66038001 2025-03 2025-03-13 Miller-Dieker syndrome https://medlineplus.gov/genetics/condition/miller-dieker-syndrome descriptionMiller-Dieker syndrome is a condition characterized by a pattern of abnormal brain development called lissencephaly. Normally, the surface of the brain (cerebral cortex) has folds and grooves. Lissencephaly causes the surface of the brain to be abnormally smooth, with fewer folds and grooves. In people with Miller-Dieker syndrome, lissencephaly is typically associated with severe intellectual disabilities, developmental delays, weak muscle tone (hypotonia), and seizures. Seizures usually begin in the first few months of life.  People with Miller-Dieker syndrome often have distinctive facial features that include a prominent forehead; a sunken appearance in the middle of the face (midface hypoplasia); a small, upturned nose; low-set and abnormally shaped ears; a small jaw; and a thick upper lip.  Some individuals with this condition also grow more slowly than their peers. Less often, affected individuals have heart problems, kidney abnormalities, or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. Because of these severe health issues, most individuals with Miller-Dieker syndrome do not survive beyond early childhood. n Not inherited ad Autosomal dominant PAFAH1B1 https://medlineplus.gov/genetics/gene/pafah1b1 YWHAE https://medlineplus.gov/genetics/gene/ywhae CRK https://www.ncbi.nlm.nih.gov/gene/1398 17 https://medlineplus.gov/genetics/chromosome/17 Lissencephaly due to 17p13.3 deletion MDLS MDS Miller-Dieker lissencephaly syndrome Monosomy 17p13.3 Telomeric deletion 17p GTR C0265219 MeSH D054221 OMIM 247200 SNOMED CT 253148005 2024-11 2024-11-14 Milroy disease https://medlineplus.gov/genetics/condition/milroy-disease descriptionMilroy disease is a condition that affects the normal function of the lymphatic system. The lymphatic system produces and transports fluids and immune cells throughout the body. Impaired transport with accumulation of lymph fluid can cause swelling (lymphedema). Individuals with Milroy disease typically have lymphedema in their lower legs and feet at birth or develop it in infancy. The lymphedema typically occurs on both sides of the body and may worsen over time.Milroy disease is associated with other features in addition to lymphedema. Males with Milroy disease are sometimes born with an accumulation of fluid in the scrotum (hydrocele). Males and females may have upslanting toenails, deep creases in the toes, wart-like growths (papillomas), and prominent leg veins. Some individuals develop non-contagious skin infections called cellulitis that can damage the thin tubes that carry lymph fluid (lymphatic vessels). Episodes of cellulitis can cause further swelling in the lower limbs. ad Autosomal dominant FLT4 https://medlineplus.gov/genetics/gene/flt4 Congenital familial lymphedema Hereditary lymphedema type I Milroy's disease Nonne-Milroy lymphedema GTR C1704423 ICD-10-CM Q82.0 MeSH D008209 OMIM 153100 SNOMED CT 399889006 2008-05 2024-10-02 Mitochondrial complex I deficiency https://medlineplus.gov/genetics/condition/mitochondrial-complex-i-deficiency descriptionMitochondrial complex I deficiency is a shortage (deficiency) of a protein complex called complex I or a loss of its function. Complex I is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex I is the first of five mitochondrial complexes that carry out a multi-step process called oxidative phosphorylation, through which cells derive much of their energy.Mitochondrial complex I deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system, the heart, and the muscles used for movement (skeletal muscles). These signs and symptoms can appear at any time from birth to adulthood.People with mitochondrial complex I deficiency typically have neurological problems, such as abnormal brain function (encephalopathy), recurrent seizures (epilepsy), intellectual disability, difficulty coordinating movements (ataxia), or involuntary movements (dystonia). Affected individuals may have low muscle tone (hypotonia), muscle pain (myalgia), and extreme fatigue in response to physical activity (exercise intolerance). They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. In severe cases, lactic acidosis can be life-threatening.People with mitochondrial complex I deficiency sometimes have heart, liver, or kidney problems. Vision problems due to abnormal eye movement or breakdown (degeneration) of the nerves that carry signals from the eyes to the brain (optic nerves) can also occur.Some people with mitochondrial complex I deficiency have groups of signs and symptoms that are classified as a specific syndrome. For example, a condition called Leigh syndrome is most commonly caused by mitochondrial complex I deficiency. Leigh syndrome is characterized by progressive loss of mental and movement abilities (developmental or psychomotor regression) and typically results in death within 2 to 3 years from the onset of symptoms. Another condition that can be caused by mitochondrial complex I deficiency, Leber hereditary optic neuropathy, is associated mainly with vision problems due to optic nerve degeneration. These syndromes can also have other causes. x X-linked m mitochondrial ar Autosomal recessive MT-ND1 https://medlineplus.gov/genetics/gene/mt-nd1 MT-ND4 https://medlineplus.gov/genetics/gene/mt-nd4 MT-ND4L https://medlineplus.gov/genetics/gene/mt-nd4l MT-ND6 https://medlineplus.gov/genetics/gene/mt-nd6 MT-TL1 https://medlineplus.gov/genetics/gene/mt-tl1 MT-ND5 https://medlineplus.gov/genetics/gene/mt-nd5 ACAD9 https://medlineplus.gov/genetics/gene/acad9 MT-ND2 https://www.ncbi.nlm.nih.gov/gene/4536 MT-ND3 https://www.ncbi.nlm.nih.gov/gene/4537 NDUFA1 https://www.ncbi.nlm.nih.gov/gene/4694 NDUFA2 https://www.ncbi.nlm.nih.gov/gene/4695 NDUFA9 https://www.ncbi.nlm.nih.gov/gene/4704 NDUFA10 https://www.ncbi.nlm.nih.gov/gene/4705 NDUFB3 https://www.ncbi.nlm.nih.gov/gene/4709 NDUFB9 https://www.ncbi.nlm.nih.gov/gene/4715 NDUFB10 https://www.ncbi.nlm.nih.gov/gene/4716 NDUFS1 https://www.ncbi.nlm.nih.gov/gene/4719 NDUFS2 https://www.ncbi.nlm.nih.gov/gene/4720 NDUFS3 https://www.ncbi.nlm.nih.gov/gene/4722 NDUFV1 https://www.ncbi.nlm.nih.gov/gene/4723 NDUFS4 https://www.ncbi.nlm.nih.gov/gene/4724 NDUFS6 https://www.ncbi.nlm.nih.gov/gene/4726 NDUFS7 https://www.ncbi.nlm.nih.gov/gene/4727 NDUFS8 https://www.ncbi.nlm.nih.gov/gene/4728 NDUFV2 https://www.ncbi.nlm.nih.gov/gene/4729 NDUFAF3 https://www.ncbi.nlm.nih.gov/gene/25915 PPA2 https://www.ncbi.nlm.nih.gov/gene/27068 NDUFAF4 https://www.ncbi.nlm.nih.gov/gene/29078 NDUFA13 https://www.ncbi.nlm.nih.gov/gene/51079 NDUFAF1 https://www.ncbi.nlm.nih.gov/gene/51103 TIMMDC1 https://www.ncbi.nlm.nih.gov/gene/51300 NDUFB11 https://www.ncbi.nlm.nih.gov/gene/54539 FOXRED1 https://www.ncbi.nlm.nih.gov/gene/55572 TMEM126B https://www.ncbi.nlm.nih.gov/gene/55863 NDUFA12 https://www.ncbi.nlm.nih.gov/gene/55967 ELAC2 https://www.ncbi.nlm.nih.gov/gene/60528 NDUFAF5 https://www.ncbi.nlm.nih.gov/gene/79133 NUBPL https://www.ncbi.nlm.nih.gov/gene/80224 NDUFAF2 https://www.ncbi.nlm.nih.gov/gene/91942 MTFMT https://www.ncbi.nlm.nih.gov/gene/123263 NDUFA11 https://www.ncbi.nlm.nih.gov/gene/126328 NDUFAF6 https://www.ncbi.nlm.nih.gov/gene/137682 NADH-coenzyme Q reductase deficiency NADH:Q(1) oxidoreductase deficiency MeSH D028361 OMIM 252010 SNOMED CT 237988006 SNOMED CT 725046003 2017-10 2020-08-18 Mitochondrial complex III deficiency https://medlineplus.gov/genetics/condition/mitochondrial-complex-iii-deficiency descriptionMitochondrial complex III deficiency is a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and the muscles used for movement (skeletal muscles). Signs and symptoms of mitochondrial complex III deficiency usually begin in infancy but can appear later.The severity of mitochondrial complex III deficiency varies widely among affected individuals. People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). More severely affected individuals have problems with multiple body systems, such as liver disease that can lead to liver failure, kidney abnormalities (tubulopathy), and brain dysfunction (encephalopathy). Encephalopathy can cause delayed development of mental and motor skills (psychomotor delay), movement problems, weak muscle tone (hypotonia), and difficulty with communication. Some affected individuals have a form of heart disease called cardiomyopathy, which can lead to heart failure. Most people with mitochondrial complex III deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis). Some affected individuals also have buildup of molecules called ketones (ketoacidosis) or high blood glucose levels (hyperglycemia). Abnormally high levels of these chemicals in the body can be life-threatening.Mitochondrial complex III deficiency can be fatal in childhood, although individuals with mild signs and symptoms can survive into adolescence or adulthood. ar Autosomal recessive m mitochondrial BCS1L https://medlineplus.gov/genetics/gene/bcs1l MT-CYB https://medlineplus.gov/genetics/gene/mt-cyb CYC1 https://www.ncbi.nlm.nih.gov/gene/1537 UQCRB https://www.ncbi.nlm.nih.gov/gene/7381 UQCRC2 https://www.ncbi.nlm.nih.gov/gene/7385 UQCRQ https://www.ncbi.nlm.nih.gov/gene/27089 TTC19 https://www.ncbi.nlm.nih.gov/gene/54902 UQCC2 https://www.ncbi.nlm.nih.gov/gene/84300 LYRM7 https://www.ncbi.nlm.nih.gov/gene/90624 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Isolated CoQ-cytochrome c reductase deficiency Ubiquinone-cytochrome c oxidoreductase deficiency GTR C3541471 GTR C3554605 GTR C3554606 GTR C3554607 GTR C3554608 GTR C3809553 GTR C4014440 MeSH D028361 OMIM 124000 OMIM 615157 OMIM 615158 OMIM 615159 OMIM 615160 OMIM 615453 SNOMED CT 709414007 2014-04 2023-07-26 Mitochondrial complex V deficiency https://medlineplus.gov/genetics/condition/mitochondrial-complex-v-deficiency descriptionMitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function. Complex V is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex V is the last of five mitochondrial complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy.Mitochondrial complex V deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system and the heart. The disorder can be life-threatening in infancy or early childhood. Affected individuals may have feeding problems, slow growth, low muscle tone (hypotonia), extreme fatigue (lethargy), and developmental delay. They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. High levels of ammonia in the blood (hyperammonemia) can also occur in affected individuals, and in some cases result in abnormal brain function (encephalopathy) and damage to other organs.Another common feature of mitochondrial complex V deficiency is hypertrophic cardiomyopathy. This condition is characterized by thickening (hypertrophy) of the heart (cardiac) muscle that can lead to heart failure. People with mitochondrial complex V deficiency may also have a characteristic pattern of facial features, including a high forehead, curved eyebrows, outside corners of the eyes that point downward (downslanting palpebral fissures), a prominent bridge of the nose, low-set ears, thin lips, and a small chin (micrognathia).Some people with mitochondrial complex V deficiency have groups of signs and symptoms that are classified as a specific syndrome. For example, mitochondrial complex V deficiency can cause a condition called neuropathy, ataxia, and retinitis pigmentosa (NARP). NARP causes a variety of signs and symptoms chiefly affecting the nervous system. Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have cognitive impairment and an eye disorder called retinitis pigmentosa that causes vision loss.A condition called Leigh syndrome can also be caused by mitochondrial complex V deficiency. Leigh syndrome is characterized by progressive loss of mental and movement abilities (developmental or psychomotor regression) and typically results in death within 2 to 3 years after the onset of symptoms. Both NARP and Leigh syndrome can also have other causes. ar Autosomal recessive m mitochondrial MT-ATP6 https://medlineplus.gov/genetics/gene/mt-atp6 TMEM70 https://medlineplus.gov/genetics/gene/tmem70 ATP5F1A https://www.ncbi.nlm.nih.gov/gene/498 ATP5F1E https://www.ncbi.nlm.nih.gov/gene/514 MT-ATP8 https://www.ncbi.nlm.nih.gov/gene/4509 ATPAF2 https://www.ncbi.nlm.nih.gov/gene/91647 ATP synthase deficiency GTR C3808899 MeSH D028361 OMIM 604273 OMIM 614052 OMIM 614053 OMIM 615228 SNOMED CT 237992004 2017-10 2024-10-02 Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes https://medlineplus.gov/genetics/condition/mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-episodes descriptionMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). The signs and symptoms of this disorder most often appear in childhood following a period of normal development, although they can begin at any age. Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia).Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. Less commonly, people with MELAS may experience involuntary muscle spasms (myoclonus), impaired muscle coordination (ataxia), hearing loss, heart and kidney problems, diabetes, and hormonal imbalances. m mitochondrial MT-ND1 https://medlineplus.gov/genetics/gene/mt-nd1 MT-TL1 https://medlineplus.gov/genetics/gene/mt-tl1 MT-TH https://medlineplus.gov/genetics/gene/mt-th MT-ND5 https://medlineplus.gov/genetics/gene/mt-nd5 MT-TV https://medlineplus.gov/genetics/gene/mt-tv mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna MELAS MELAS syndrome Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes Mitochondrial myopathy, lactic acidosis, stroke-like episode Myopathy, mitochondrial-encephalopathy-lactic acidosis-stroke GTR C0162671 ICD-10-CM E88.41 MeSH D017241 OMIM 540000 SNOMED CT 39925003 2006-11 2020-09-08 Mitochondrial membrane protein-associated neurodegeneration https://medlineplus.gov/genetics/condition/mitochondrial-membrane-protein-associated-neurodegeneration descriptionMitochondrial membrane protein-associated neurodegeneration (MPAN) is a disorder of the nervous system. The condition typically begins in childhood or early adulthood and worsens (progresses) over time.MPAN commonly begins with difficulty walking. As the condition progresses, affected individuals usually develop other movement problems, including muscle stiffness (spasticity) and involuntary muscle cramping (dystonia). Many people with MPAN have a pattern of movement abnormalities known as parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, involuntary trembling (tremors), and an inability to hold the body upright and balanced (postural instability).Other neurological problems that occur in individuals with MPAN include degeneration of the nerve cells that carry visual information from the eyes to the brain (optic atrophy), which can impair vision; problems with speech (dysarthria); difficulty swallowing (dysphagia); and, in later stages of the condition, an inability to control the bowels or the flow of urine (incontinence). Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, mood swings, hyperactivity, and depression.MPAN is characterized by an abnormal buildup of iron in certain regions of the brain. Because of these deposits, MPAN is considered part of a group of conditions known as neurodegeneration with brain iron accumulation (NBIA). ar Autosomal recessive C19orf12 https://medlineplus.gov/genetics/gene/c19orf12 Mitochondrial membrane protein-associated neurodegeneration due to C19orf12 mutation Mitochondrial protein-associated neurodegeneration MPAN NBIA4 Neurodegeneration with brain iron accumulation 4 GTR C3280371 MeSH D019150 OMIM 614298 SNOMED CT 709415008 2014-04 2020-08-18 Mitochondrial neurogastrointestinal encephalopathy disease https://medlineplus.gov/genetics/condition/mitochondrial-neurogastrointestinal-encephalopathy-disease descriptionMitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is a condition that affects several parts of the body, particularly the digestive system and nervous system. The major features of MNGIE disease can appear anytime from infancy to adulthood, but signs and symptoms most often begin by age 20. The medical problems associated with this disorder worsen over time.Almost all people with MNGIE disease have a condition known as gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently. The resulting digestive problems include feelings of fullness (satiety) after eating only a small amount, trouble swallowing (dysphagia), nausea and vomiting after eating, episodes of abdominal pain, diarrhea, and intestinal blockage. These gastrointestinal problems lead to extreme weight loss and reduced muscle mass (cachexia).MNGIE disease is also characterized by abnormalities of the nervous system, although these tend to be milder than the gastrointestinal problems. Affected individuals experience tingling, numbness, and weakness in their limbs (peripheral neuropathy), particularly in the hands and feet. Additional neurological signs and symptoms can include droopy eyelids (ptosis), weakness of the muscles that control eye movement (ophthalmoplegia), and hearing loss. Leukoencephalopathy, which is the deterioration of a type of brain tissue known as white matter, is a hallmark of MNGIE disease. These changes in the brain can be seen with magnetic resonance imaging (MRI), though they usually do not cause symptoms in people with this disorder. ar Autosomal recessive TYMP https://medlineplus.gov/genetics/gene/tymp POLG https://medlineplus.gov/genetics/gene/polg RRM2B https://medlineplus.gov/genetics/gene/rrm2b MEPOP Mitochondrial myopathy with sensorimotor polyneuropathy, ophthalmoplegia, and pseudo-obstruction Mitochondrial neurogastrointestinal encephalopathy syndrome MNGIE disease MNGIE syndrome Myoneurogastrointestinal encephalopathy syndrome Oculogastrointestinal muscular dystrophy OGIMD POLIP Polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction Thymidine phosphorylase deficiency GTR C2749861 GTR C3150914 GTR C4551995 ICD-10-CM E88.49 MeSH D028361 OMIM 603041 OMIM 612075 OMIM 613662 SNOMED CT 124273008 2023-09 2023-09-20 Mitochondrial trifunctional protein deficiency https://medlineplus.gov/genetics/condition/mitochondrial-trifunctional-protein-deficiency descriptionMitochondrial trifunctional protein deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).Signs and symptoms of mitochondrial trifunctional protein deficiency may begin during infancy or later in life. Features that occur during infancy include feeding difficulties, lack of energy (lethargy), low blood glucose (hypoglycemia), weak muscle tone (hypotonia), and liver problems. Infants with this disorder are also at high risk for serious heart problems, breathing difficulties, coma, and sudden death. Signs and symptoms of mitochondrial trifunctional protein deficiency that may begin after infancy include hypotonia, muscle pain, a breakdown of muscle tissue, and a loss of sensation in the extremities (peripheral neuropathy).Problems related to mitochondrial trifunctional protein deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. ar Autosomal recessive HADHA https://medlineplus.gov/genetics/gene/hadha HADHB https://medlineplus.gov/genetics/gene/hadhb MTP deficiency TFP deficiency TPA deficiency Trifunctional protein deficiency, type 2 GTR C1969443 MeSH D008052 OMIM 609015 SNOMED CT 237999008 2009-07 2023-07-26 Miyoshi myopathy https://medlineplus.gov/genetics/condition/miyoshi-myopathy descriptionMiyoshi myopathy is a muscle disorder that begins with weakness in the muscles that are located away from the center of the body (distal muscles), such as those in the legs. During early to mid-adulthood, affected individuals typically begin to experience muscle weakness and wasting (atrophy) in one or both calves. If only one leg is affected, the calves appear different in size (asymmetrical). Calf weakness can make it difficult to stand on tiptoe.As Miyoshi myopathy slowly worsens, the muscle weakness and atrophy spread up the leg to the muscles in the thigh and buttock and can also involve the upper arm and shoulder muscles. Eventually, affected individuals may have difficulty climbing stairs or walking for an extended period of time. Some people with Miyoshi myopathy may eventually need wheelchair assistance.Rarely, abnormal heart rhythms (arrhythmias) have developed in people with Miyoshi myopathy. Individuals with Miyoshi myopathy have highly elevated levels of an enzyme called creatine kinase (CK) in their blood, which often indicates muscle disease. ar Autosomal recessive DYSF https://medlineplus.gov/genetics/gene/dysf ANO5 https://medlineplus.gov/genetics/gene/ano5 Distal muscular dystrophy, Miyoshi type Miyoshi distal myopathy Miyoshi muscular dystrophy MMD GTR C2750076 GTR C4551973 MeSH D049310 OMIM 254130 OMIM 613319 SNOMED CT 111506000 2014-04 2023-08-22 Moebius syndrome https://medlineplus.gov/genetics/condition/moebius-syndrome descriptionMoebius syndrome is a rare neurological condition that primarily affects the muscles that control facial expression and eye movement. The signs and symptoms of this condition are present from birth.Weakness or paralysis of the facial muscles is one of the most common features of Moebius syndrome. Affected individuals lack facial expressions; they cannot smile, frown, or raise their eyebrows. The muscle weakness also causes problems with feeding that become apparent in early infancy.Many people with Moebius syndrome are born with a small chin (micrognathia) and a small mouth (microstomia) with a short or unusually shaped tongue. The roof of the mouth may have an abnormal opening (cleft palate) or be high and arched. These abnormalities contribute to problems with speech, which occur in many children with Moebius syndrome. Dental abnormalities, including missing and misaligned teeth, are also common.Moebius syndrome also affects muscles that control back-and-forth eye movement. Affected individuals must move their head from side to side to read or follow the movement of objects. People with this disorder have difficulty making eye contact, and their eyes may not look in the same direction (strabismus). Additionally, the eyelids may not close completely when blinking or sleeping, which can result in dry or irritated eyes.Other features of Moebius syndrome can include bone abnormalities in the hands and feet, weak muscle tone (hypotonia), and hearing loss. Affected children often experience delayed development of motor skills (such as crawling and walking), although most eventually acquire these skills.Some research studies have suggested that children with Moebius syndrome are more likely than unaffected children to have characteristics of autism spectrum disorders, which are a group of conditions characterized by impaired communication and social interaction. However, recent studies have questioned this association. Because people with Moebius syndrome have difficulty with eye contact and speech due to their physical differences, autism spectrum disorders can be difficult to diagnose in these individuals. Moebius syndrome may also be associated with a somewhat increased risk of intellectual disability; however, most affected individuals have normal intelligence. u Pattern unknown Congenital facial diplegia Congenital ophthalmoplegia and facial paresis Mobius syndrome Moebius congenital oculofacial paralysis Moebius sequence Moebius spectrum Möbius sequence GTR C0221060 MeSH D020331 OMIM 157900 SNOMED CT 89444000 2010-07 2020-08-18 Molybdenum cofactor deficiency https://medlineplus.gov/genetics/condition/molybdenum-cofactor-deficiency descriptionMolybdenum cofactor deficiency is a rare condition characterized by brain dysfunction (encephalopathy) that worsens over time. Babies with this condition appear normal at birth, but within a week they have difficulty feeding and develop seizures that do not improve with treatment (intractable seizures). Brain abnormalities, including deterioration (atrophy) of brain tissue, lead to severe developmental delay; affected individuals usually do not learn to sit unassisted or to speak. A small percentage of affected individuals have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli such as loud noises. Other features of molybdenum cofactor deficiency can include a small head size (microcephaly) and facial features that are described as "coarse."Tests reveal that affected individuals have high levels of chemicals called sulfite, S-sulfocysteine, xanthine, and hypoxanthine in the urine and low levels of a chemical called uric acid in the blood.Because of the serious health problems caused by molybdenum cofactor deficiency, affected individuals usually do not survive past early childhood. ar Autosomal recessive MOCS1 https://medlineplus.gov/genetics/gene/mocs1 MOCS2 https://medlineplus.gov/genetics/gene/mocs2 GPHN https://medlineplus.gov/genetics/gene/gphn Combined deficiency of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase Combined molybdoflavoprotein enzyme deficiency Combined xanthine oxidase and sulfite oxidase and aldehyde oxidase deficiency Deficiency of molybdenum cofactor MOCOD GTR C0268119 GTR C1854988 GTR C1854989 GTR C1854990 MeSH D020739 OMIM 252150 OMIM 252160 OMIM 615501 SNOMED CT 29692004 2014-03 2020-08-18 Monilethrix https://medlineplus.gov/genetics/condition/monilethrix descriptionMonilethrix is a condition that affects hair growth. Its most characteristic feature is that individual strands of hair have a beaded appearance like the beads of a necklace. The name monilethrix comes from the Latin word for necklace (monile) and the Greek word for hair (thrix). Noticeable when viewed under a microscope, the beaded appearance is due to periodic narrowing of the hair shaft. People with monilethrix also have sparse hair growth (hypotrichosis) and short, brittle hair that breaks easily.Affected individuals usually have normal hair at birth, but the hair abnormalities develop within the first few months of life. In mild cases of monilethrix, only hair on the back of the head (occiput) or nape of the neck is affected. In more severe cases, hair over the whole scalp can be affected, as well as pubic hair, underarm hair, eyebrows, eyelashes, or hair on the arms and legs.Occasionally, the skin and nails are involved in monilethrix. Some affected individuals have a skin condition called keratosis pilaris, which causes small bumps on the skin, especially on the scalp, neck, and arms. Affected individuals may also have abnormal fingernails or toenails. ar Autosomal recessive ad Autosomal dominant KRT81 https://medlineplus.gov/genetics/gene/krt81 KRT86 https://medlineplus.gov/genetics/gene/krt86 DSG4 https://medlineplus.gov/genetics/gene/dsg4 KRT83 https://medlineplus.gov/genetics/gene/krt83 Beaded hair GTR C0546966 MeSH D056734 OMIM 158000 SNOMED CT 69488000 2012-03 2020-08-18 Monoamine oxidase A deficiency https://medlineplus.gov/genetics/condition/monoamine-oxidase-a-deficiency descriptionMonoamine oxidase A deficiency is a rare disorder that occurs almost exclusively in males. It is characterized by mild intellectual disability and behavioral problems beginning in early childhood.Most boys with monoamine oxidase A deficiency are less able to control their impulses than their peers, causing aggressive or violent outbursts. In addition, affected individuals may have features of other neurodevelopmental disorders, including autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD). These features can include obsessive behaviors, difficulty forming friendships, and problems focusing attention. Sleep problems, such as trouble falling asleep or night terrors, can also occur in monoamine oxidase A deficiency.Some people with monoamine oxidase A deficiency have episodes of skin flushing, sweating, headaches, or diarrhea. Similar episodes can occur in female family members of males with monoamine oxidase A deficiency, although females do not experience other signs or symptoms of the condition.In some cases, certain foods, such as cheese, appear to worsen symptoms of monoamine oxidase A deficiency. xr X-linked recessive MAOA https://medlineplus.gov/genetics/gene/maoa Brunner syndrome Deficiency of monoamine oxidase A X-linked monoamine oxidase deficiency GTR C0796275 MeSH D008607 MeSH D040181 OMIM 300615 SNOMED CT 718210003 2017-04 2023-07-12 Mosaic variegated aneuploidy syndrome https://medlineplus.gov/genetics/condition/mosaic-variegated-aneuploidy-syndrome descriptionMosaic variegated aneuploidy (MVA) syndrome is a rare disorder in which some cells in the body have an abnormal number of chromosomes instead of the usual 46 chromosomes, a situation known as aneuploidy. Most commonly, cells have an extra chromosome, which is called trisomy, or are missing a chromosome, which is known as monosomy. In MVA syndrome, some cells are aneuploid and others have the normal number of chromosomes, which is a phenomenon known as mosaicism. Typically, at least one-quarter of cells in affected individuals have an abnormal number of chromosomes. Because the additional or missing chromosomes vary among the abnormal cells, the aneuploidy is described as variegated.In MVA syndrome, growth before birth is slow (intrauterine growth restriction). After birth, affected individuals continue to grow at a slow rate and are shorter than average. In addition, they typically have an unusually small head size (microcephaly). Another common feature of MVA syndrome is an increased risk of developing cancer in childhood. Cancers that occur most frequently in affected individuals include a cancer of muscle tissue called rhabdomyosarcoma, a form of kidney cancer known as Wilms tumor, and a cancer of the blood-forming tissue known as leukemia.Less commonly, people with MVA syndrome have eye abnormalities or distinctive facial features, such as a broad nasal bridge and low-set ears. Some affected individuals have brain abnormalities, the most common of which is called Dandy-Walker malformation. Intellectual disability, seizures, and other health problems can also occur in people with MVA syndrome.There are at least three types of MVA syndrome, each with a different genetic cause. Type 1 is the most common and displays the classic signs and symptoms described above. Type 2 appears to have slightly different signs and symptoms than type 1, although the small number of affected individuals makes it difficult to define its characteristic features. Individuals with MVA syndrome type 2 grow slowly before and after birth; however, their head size is typically normal. Some people with MVA syndrome type 2 have unusually short arms. Individuals with MVA syndrome type 2 do not seem to have an increased risk of cancer. Another form of MVA syndrome is characterized by a high risk of developing Wilms tumor. Individuals with this form may also have other signs and symptoms typical of MVA syndrome type 1. ar Autosomal recessive BUB1B https://medlineplus.gov/genetics/gene/bub1b CEP57 https://medlineplus.gov/genetics/gene/cep57 TRIP13 https://medlineplus.gov/genetics/gene/trip13 Mosaic variegated aneuplody microcephaly syndrome MVA syndrome Warburton-Anyane-Yeboa syndrome GTR C1850343 GTR C3279843 MeSH D000782 OMIM 257300 OMIM 614114 SNOMED CT 700056005 2017-06 2023-02-27 Motion sickness https://medlineplus.gov/genetics/condition/motion-sickness descriptionMotion sickness is a common condition characterized by a feeling of unwellness brought on by certain kinds of movement. The usual symptoms include dizziness, pale skin (pallor), and sweating, followed by nausea and vomiting. Affected individuals may also experience rapid breathing (hyperventilation), headache, restlessness, and drowsiness. These symptoms can be triggered by many kinds of motion, particularly traveling in a car, bus, train, airplane, or boat. Amusement park rides, skiing, and virtual reality environments can also induce motion sickness. u Pattern unknown Airsickness Carsickness Riders' vertigo Seasickness ICD-10-CM T75.3 MeSH D009041 OMIM 158280 SNOMED CT 37031009 2018-05 2023-07-26 Mowat-Wilson syndrome https://medlineplus.gov/genetics/condition/mowat-wilson-syndrome descriptionMowat-Wilson syndrome is a genetic condition that affects many parts of the body. Major signs of this disorder frequently include distinctive facial features, intellectual disability, delayed development, an intestinal disorder called Hirschsprung disease, and other birth defects.Children with Mowat-Wilson syndrome have a square-shaped face with deep-set, widely spaced eyes. They also have a broad nasal bridge with a rounded nasal tip; a prominent and pointed chin; large, flaring eyebrows; and uplifted earlobes with a dimple in the middle. These facial features become more distinctive with age, and adults with Mowat-Wilson syndrome have an elongated face with heavy eyebrows and a pronounced chin and jaw. Affected people tend to have a smiling, open-mouthed expression, and they typically have friendly and happy personalities.Mowat-Wilson syndrome is often associated with an unusually small head (microcephaly), structural brain abnormalities, and intellectual disability ranging from moderate to severe. Speech is absent or severely impaired, and affected people may learn to speak only a few words. Many people with this condition can understand others' speech, however, and some use sign language to communicate. If speech develops, it is delayed until mid-childhood or later. Children with Mowat-Wilson syndrome also have delayed development of motor skills such as sitting, standing, and walking.More than half of people with Mowat-Wilson syndrome are born with an intestinal disorder called Hirschsprung disease that causes severe constipation, intestinal blockage, and enlargement of the colon. Chronic constipation also occurs frequently in people with Mowat-Wilson syndrome who have not been diagnosed with Hirschsprung disease.Other features of Mowat-Wilson syndrome include short stature, seizures, heart defects, and abnormalities of the urinary tract and genitalia. Less commonly, this condition also affects the eyes, teeth, hands, and skin coloring (pigmentation). Although many different medical issues have been associated with Mowat-Wilson syndrome, not every individual with this condition has all of these features. ad Autosomal dominant ZEB2 https://medlineplus.gov/genetics/gene/zeb2 Hirschsprung disease-mental retardation syndrome Microcephaly, mental retardation, and distinct facial features, with or without Hirschsprung disease MWS GTR C1856113 MeSH D000015 MeSH D006627 OMIM 235730 SNOMED CT 703535000 2007-12 2020-08-18 Moyamoya disease https://medlineplus.gov/genetics/condition/moyamoya-disease descriptionMoyamoya disease is a disorder of blood vessels in the brain, specifically the internal carotid arteries and the arteries that branch from them. These vessels, which provide oxygen-rich blood to the brain, narrow over time. Narrowing of these vessels reduces blood flow in the brain. In an attempt to compensate, new networks of small, fragile blood vessels form. These networks, visualized by a particular test called an angiogram, resemble puffs of smoke, which is how the condition got its name: "moyamoya" is an expression meaning "something hazy like a puff of smoke" in Japanese.Moyamoya disease commonly begins either around age 5 or in a person's thirties or forties. A lack of blood supply to the brain leads to several symptoms of the disorder, including temporary stroke-like episodes (transient ischemic attacks), strokes, and seizures. In addition, the fragile blood vessels that grow can develop bulges (aneurysms), or they can break open, leading to bleeding (hemorrhage) in the brain. Affected individuals may develop recurrent headaches, involuntary jerking movements (chorea), or a decline in thinking ability. The symptoms of moyamoya disease often worsen over time if the condition is not treated.Some people have the blood vessel changes characteristic of moyamoya disease in addition to features of another disorder, such as neurofibromatosis type 1, sickle cell disease, or Graves' disease. These individuals are said to have moyamoya syndrome. ad Autosomal dominant u Pattern unknown RNF213 https://medlineplus.gov/genetics/gene/rnf213 Cerebrovascular moyamoya disease Moya-moya disease Progressive intracranial arterial occlusion Progressive intracranial occlusive arteropathy Spontaneous occlusion of the Circle of Willis GTR C0026654 GTR C1846689 GTR C3279690 ICD-10-CM I67.5 MeSH D009072 OMIM 252350 OMIM 607151 OMIM 608796 OMIM 614042 SNOMED CT 69116000 2015-04 2023-07-11 Mucolipidosis II alpha/beta https://medlineplus.gov/genetics/condition/mucolipidosis-ii-alpha-beta descriptionMucolipidosis II alpha/beta (also known as I-cell disease) is a progressively debilitating disorder that affects many parts of the body. Most affected individuals do not survive past early childhood.At birth, children with mucolipidosis II alpha/beta are small and have weak muscle tone (hypotonia) and a weak cry. Affected individuals grow slowly after birth and usually stop growing during the second year of life. Development is delayed, particularly the development of speech and motor skills such as sitting and standing.Children with mucolipidosis II alpha/beta typically have several bone abnormalities, many of which are present at birth. Affected individuals may have an abnormally rounded upper back (kyphosis), feet that are abnormally rotated (clubfeet), dislocated hips, unusually shaped long bones, and short hands and fingers. People with this condition also have joint deformities (contractures) that significantly affect mobility. Most children with mucolipidosis II alpha/beta do not develop the ability to walk independently. Affected individuals have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray.Other features of mucolipidosis II alpha/beta include a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia), heart valve abnormalities, distinctive-looking facial features that are described as "coarse," and overgrowth of the gums (gingival hypertrophy). Vocal cords can stiffen, resulting in a hoarse voice. The airway is narrow, which can contribute to prolonged or recurrent respiratory infections. Affected individuals may also have recurrent ear infections, which can lead to hearing loss. ar Autosomal recessive GNPTAB https://medlineplus.gov/genetics/gene/gnptab I-cell disease Inclusion cell disease MLII Mucolipidosis II Mucolipidosis type II GTR C2673377 ICD-10-CM E77.0 MeSH D009081 OMIM 252500 SNOMED CT 70199000 2009-08 2020-08-18 Mucolipidosis III alpha/beta https://medlineplus.gov/genetics/condition/mucolipidosis-iii-alpha-beta descriptionMucolipidosis III alpha/beta is a disorder that affects many parts of the body. Signs and symptoms of this condition typically appear around age 3 and worsen slowly over time.Individuals with mucolipidosis III alpha/beta grow slowly and have short stature. They also have stiff joints and dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Many affected individuals develop low bone mineral density (osteoporosis), which weakens the bones and makes them prone to fracture. Osteoporosis and progressive joint problems also cause bone pain that becomes more severe over time in people with mucolipidosis III alpha/beta.People with mucolipidosis III alpha/beta often have heart valve abnormalities and mild clouding of the clear covering of the eye (cornea). Their facial features become slightly thickened or "coarse" over time. Affected individuals may also develop frequent ear and respiratory infections. About half of people with this condition have mild intellectual disability or learning problems. Individuals with mucolipidosis III alpha/beta generally survive into adulthood, but they may have a shortened lifespan. ar Autosomal recessive GNPTAB https://medlineplus.gov/genetics/gene/gnptab ML III ML IIIA Mucolipidosis III Mucolipidosis III, variant Mucolipidosis IIIA Pseudo-Hurler polydystrophy GTR C0033788 ICD-10-CM E77.0 MeSH D009081 OMIM 252600 SNOMED CT 65764006 2009-08 2024-10-02 Mucolipidosis III gamma https://medlineplus.gov/genetics/condition/mucolipidosis-iii-gamma descriptionMucolipidosis III gamma is a slowly progressive disorder that affects many parts of the body. Signs and symptoms of this condition typically appear around age 3.Individuals with mucolipidosis III gamma grow slowly and have short stature. They also have stiff joints and dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Many affected individuals develop low bone mineral density (osteoporosis), which weakens the bones and makes them prone to fracture. Osteoporosis and progressive joint problems in people with mucolipidosis III gamma also cause pain, which becomes more severe over time.People with mucolipidosis III gamma often have heart valve abnormalities and mild clouding of the clear covering of the eye (cornea). Their facial features become slightly thickened or "coarse" as they get older. A small percentage of people with this condition have mild intellectual disability or learning problems. Individuals with mucolipidosis III gamma generally survive into adulthood, but they may have a shortened lifespan. ar Autosomal recessive GNPTG https://medlineplus.gov/genetics/gene/gnptg ML IIIC Mucolipidosis III Mucolipidosis III, variant Mucolipidosis IIIC Mucolipidosis type III Pseudo-Hurler polydystrophy GTR C1854896 ICD-10-CM E77.0 MeSH D009081 OMIM 252605 SNOMED CT 65764006 2009-08 2020-08-18 Mucolipidosis type IV https://medlineplus.gov/genetics/condition/mucolipidosis-type-iv descriptionMucolipidosis type IV is an inherited disorder characterized by delayed development and vision impairment that worsens over time. The severe form of the disorder is called typical mucolipidosis type IV, and the mild form is called atypical mucolipidosis type IV.Approximately 95 percent of individuals with this condition have the severe form. People with typical mucolipidosis type IV have delayed development of mental and motor skills (psychomotor delay). Motor skills include sitting, standing, walking, grasping objects, and writing. Psychomotor delay is moderate to severe and usually becomes apparent during the first year of life. Affected individuals have intellectual disability, limited or absent speech, difficulty chewing and swallowing, weak muscle tone (hypotonia) that gradually turns into abnormal muscle stiffness (spasticity), and problems controlling hand movements. Most people with typical mucolipidosis type IV are unable to walk independently. In about 15 percent of affected individuals, the psychomotor problems worsen over time.Vision may be normal at birth in people with typical mucolipidosis type IV, but it becomes increasingly impaired during the first decade of life. Individuals with this condition develop clouding of the clear covering of the eye (cornea) and progressive breakdown of the light-sensitive layer at the back of the eye (retina). By their early teens, affected individuals have severe vision loss or blindness.People with typical mucolipidosis type IV also have impaired production of stomach acid (achlorhydria). Achlorhydria does not cause any symptoms in these individuals, but it does result in unusually high levels of gastrin in the blood. Gastrin is a hormone that regulates the production of stomach acid. Individuals with mucolipidosis type IV may not have enough iron in their blood, which can lead to a shortage of red blood cells (anemia). People with the severe form of this disorder usually survive to adulthood; however, they may have a shortened lifespan.About 5 percent of affected individuals have atypical mucolipidosis type IV. These individuals usually have mild psychomotor delay and may develop the ability to walk. People with atypical mucolipidosis type IV tend to have milder eye abnormalities than those with the severe form of the disorder. Achlorhydria also may be present in mildly affected individuals. ar Autosomal recessive MCOLN1 https://medlineplus.gov/genetics/gene/mcoln1 Ganglioside sialidase deficiency ML4 MLIV Sialolipidosis GTR C0238286 ICD-10-CM E75.11 MeSH D009081 OMIM 252650 SNOMED CT 725296006 2009-05 2025-04-03 Mucopolysaccharidosis type I https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-i descriptionMucopolysaccharidosis type I (MPS I) is a condition that affects many parts of the body. This disorder was once divided into three separate syndromes: Hurler syndrome (MPS I-H), Hurler-Scheie syndrome (MPS I-H/S), and Scheie syndrome (MPS I-S), listed from most to least severe. Because there is so much overlap between each of these three syndromes, MPS I is currently divided into the severe and attenuated types.Children with MPS I often have no signs or symptoms of the condition at birth, although some have a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with severe MPS I generally begin to show other signs and symptoms of the disorder within the first year of life, while those with the attenuated form have milder features that develop later in childhood.Individuals with MPS I may have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), heart valve abnormalities, distinctive-looking facial features that are described as "coarse," an enlarged liver and spleen (hepatosplenomegaly), and a large tongue (macroglossia). Vocal cords can also enlarge, resulting in a deep, hoarse voice. The airway may become narrow in some people with MPS I, causing frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea).People with MPS I often develop clouding of the clear covering of the eye (cornea), which can cause significant vision loss. Affected individuals may also have hearing loss and recurrent ear infections.Some individuals with MPS I have short stature and joint deformities (contractures) that affect mobility. Most people with the severe form of the disorder also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord.While both forms of MPS I can affect many different organs and tissues, people with severe MPS I experience a decline in intellectual function and a more rapid disease progression. Developmental delay is usually present by age 1, and severely affected individuals eventually lose basic functional skills (developmentally regress). Children with this form of the disorder usually have a shortened lifespan, sometimes living only into late childhood. Individuals with attenuated MPS I typically live into adulthood and may or may not have a shortened lifespan. Some people with the attenuated type have learning disabilities, while others have no intellectual impairments. Heart disease and airway obstruction are major causes of death in people with both types of MPS I. ar Autosomal recessive IDUA https://medlineplus.gov/genetics/gene/idua Hurler syndrome Hurler-Scheie syndrome IDUA deficiency MPS I MPS I H MPS I H-S MPS I S Mucopolysaccharidosis I Scheie syndrome GTR C0023786 ICD-10-CM E76.0 ICD-10-CM E76.01 ICD-10-CM E76.02 ICD-10-CM E76.03 MeSH D008059 OMIM 607014 OMIM 607015 OMIM 607016 SNOMED CT 26745009 SNOMED CT 73123008 SNOMED CT 75610003 2008-12 2023-02-27 Mucopolysaccharidosis type II https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-ii descriptionMucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a condition that affects many different parts of the body. The condition occurs almost exclusively in boys, although it has been reported in a few girls. It is a progressively debilitating disorder; however, the rate of progression varies among affected individuals.At birth, individuals with MPS II do not display any features of the condition. Between ages 2 and 4, they develop full lips; large, rounded cheeks; a broad nose; and an enlarged tongue (macroglossia). The vocal cords also enlarge, which results in a deep, hoarse voice. Narrowing of the airway causes frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). As the disorder progresses, individuals need medical assistance to keep their airway open.Many other organs and tissues are affected in people with MPS II. Individuals with this disorder often have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), a short neck, an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with MPS II usually have thick skin that is not very stretchy. Some affected individuals also have distinctive white skin growths that look like pebbles. Most people with this disorder develop hearing loss. Some individuals with MPS II develop problems with the light-sensitive tissue in the back of the eye (retina) and have reduced vision. Carpal tunnel syndrome commonly occurs in children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord. The heart is also significantly affected by MPS II, and many individuals develop heart valve problems. Heart valve abnormalities can cause the heart to become enlarged (ventricular hypertrophy) and can eventually lead to abnormalities in the heart's rhythm (arrhythmia) and heart failure.Children with MPS II grow steadily until about age 5, and then their growth slows and they develop short stature. Individuals with this condition have joint deformities (contractures) that significantly affect mobility. Most people with MPS II also have dysostosis multiplex, which refers to multiple skeletal abnormalities that can be seen on x-rays. Dysostosis multiplex includes a generalized thickening of certain bones, particularly the ribs.There are two types of MPS II: the neuropathic form, which is more severe, and the non-neuropathic form, which is less severe. While both types affect many different organs and tissues as described above, people with neuropathic MPS II also experience a decline in intellectual function and a more rapid disease progression. Individuals with this form begin to lose basic functional skills (developmentally regress) between the ages of 6 and 8. Their life expectancy is 10 to 20 years. Individuals with non-neuropathic MPS II also have a shortened lifespan, but they typically live into adulthood, and their intelligence is not affected. Heart disease and airway obstruction are major causes of death in people with both types of MPS II. xr X-linked recessive IDS https://medlineplus.gov/genetics/gene/ids Hunter syndrome I2S deficiency Iduronate 2-sulfatase deficiency MPS II GTR C0026705 ICD-10-CM E76.1 MeSH D016532 OMIM 309900 SNOMED CT 5667009 SNOMED CT 70737009 SNOMED CT 73146005 2023-10 2025-03-06 Mucopolysaccharidosis type III https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-iii descriptionMucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a disorder that primarily affects the brain and spinal cord (central nervous system). It is characterized by deterioration of neurological function (neurodegeneration), resulting in many of the features of the condition. Other body systems can also be involved, although the physical features are usually mild in the early stages.People with MPS III generally do not display any features of the condition at birth, but they begin to show signs and symptoms of the disorder during early childhood. Early signs and symptoms of MPS III can include frequent ear and throat infections or bowel problems, though most common are mild developmental delay or delayed speech. Behavioral problems often worsen with affected children becoming restless, hyperactive, destructive, anxious, impulsive, fearless, or aggressive. Some affected children display features of autism spectrum disorder, which is a condition characterized by difficulty with social interactions and communication. Children with MPS III may have an increased tendency to chew on objects or put things in their mouth (be hyperoral). Sleep disturbances are also very common in children with MPS III. This condition causes progressive intellectual disability and the loss of previously acquired skills (developmental regression or dementia). In later stages of the disorder, people with MPS III may develop seizures, loss of mobility, and movement disorders.The physical features of MPS III are less pronounced than those of other types of mucopolysaccharidosis. Individuals with MPS III typically have mildly "coarse" facial features, a prominent forehead, a large head (macrocephaly), and thick hair and eyebrows. Some people with MPS III have short stature, joint stiffness, or mild dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. People with MPS III often have a slightly enlarged liver (mild hepatomegaly) or spleen (mild splenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Cardiac abnormalities may also occur in this condition, including weakening of the heart muscle (cardiomyopathy), disruption of the heart's normal rhythm (arrhythmia), or problems with the heart's valves. Affected individuals often experience chronic diarrhea and recurrent upper respiratory and ear infections. People with MPS III may also have hearing loss and vision problems.MPS III is divided into types IIIA, IIIB, IIIC, and IIID, which are distinguished by their genetic cause. The different types of MPS III have similar signs and symptoms, although the features of MPS IIIA typically appear earlier in life and progress more rapidly. People with MPS III usually live into adolescence or early to mid-adulthood. ar Autosomal recessive SGSH https://medlineplus.gov/genetics/gene/sgsh GNS https://medlineplus.gov/genetics/gene/gns HGSNAT https://medlineplus.gov/genetics/gene/hgsnat NAGLU https://medlineplus.gov/genetics/gene/naglu MPS III Mucopolysaccharidosis III Sanfilippo syndrome GTR C0086647 GTR C0086648 GTR C0086649 GTR C0086650 ICD-10-CM E76.22 MeSH D009084 OMIM 252900 OMIM 252920 OMIM 252930 OMIM 252940 SNOMED CT 15892005 SNOMED CT 41572006 SNOMED CT 59990008 SNOMED CT 75238000 SNOMED CT 88393000 2010-08 2022-11-07 Mucopolysaccharidosis type IV https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-iv descriptionMucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a progressive condition that mainly affects the skeleton. The rate at which symptoms worsen varies among affected individuals.The first signs and symptoms of MPS IV usually become apparent during early childhood. Affected individuals develop various skeletal abnormalities, including short stature, knock knees, and abnormalities of the ribs, chest, spine, hips, and wrists. People with MPS IV often have joints that are loose and very flexible (hypermobile), but they may also have restricted movement in certain joints. A characteristic feature of this condition is underdevelopment (hypoplasia) of a peg-like bone in the neck called the odontoid process. The odontoid process helps stabilize the spinal bones in the neck (cervical vertebrae). Odontoid hypoplasia can lead to misalignment of the cervical vertebrae, which may compress and damage the spinal cord, resulting in paralysis or death.In people with MPS IV, the clear covering of the eye (cornea) typically becomes cloudy, which can cause vision loss. Some affected individuals have recurrent ear infections and hearing loss. The airway may become narrow in some people with MPS IV, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). Other common features of this condition include mildly "coarse" facial features, thin tooth enamel, multiple cavities, heart valve abnormalities, a mildly enlarged liver (hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Unlike some other types of mucopolysaccharidosis, MPS IV does not affect intelligence.The life expectancy of individuals with MPS IV depends on the severity of symptoms. Severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced. Spinal cord compression and airway obstruction are major causes of death in people with MPS IV. ar Autosomal recessive GALNS https://medlineplus.gov/genetics/gene/galns GLB1 https://medlineplus.gov/genetics/gene/glb1 Morquio disease Morquio syndrome Morquio's disease Morquio's syndrome Morquio-Brailsford disease MPS IV Mucopolysaccharidosis (MPS) IV (A, B) GTR C0026707 GTR C0086651 GTR C0086652 ICD-10-CM E76.21 ICD-10-CM E76.210 ICD-10-CM E76.211 ICD-10-CM E76.219 MeSH D009085 OMIM 253000 OMIM 253010 SNOMED CT 130197005 SNOMED CT 238044004 SNOMED CT 378007 SNOMED CT 7259005 2010-06 2021-04-07 Mucopolysaccharidosis type VI https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-vi descriptionMucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a progressive condition that causes many tissues and organs to enlarge, become inflamed or scarred, and eventually waste away (atrophy). Skeletal abnormalities are also common in this condition. The rate at which symptoms worsen varies among affected individuals.People with MPS VI generally do not display any features of the condition at birth. They often begin to show signs and symptoms of MPS VI during early childhood. The features of MPS VI affect many bodily systems, including  skeletal, cardiac, and respiratory.MPS VI causes various skeletal abnormalities, including a large head (macrocephaly) with a buildup of fluid in the brain (hydrocephalus), distinctive-looking facial features that are described as "coarse," and a large tongue (macroglossia). Other skeletal features include short stature, joint deformities (contractures) that affect mobility, and dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with MPS VI and is characterized by numbness, tingling, and weakness in the hands and fingers. People with MPS VI may develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord. Cardiac problems in people with MPS VI typically includes heart valve abnormalities. Respiratory abnormalities in this condition may involve the airway becoming narrow, which leads to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). Other features of MPS VI include an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). The clear covering of the eye (cornea) typically becomes cloudy, which can cause significant vision loss. People with MPS VI may also have recurrent ear infections and hearing loss. Unlike other types of mucopolysaccharidosis, MPS VI does not affect intelligence.The life expectancy of individuals with MPS VI depends on the severity of symptoms. Without treatment, severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced. Heart disease and airway obstruction are major causes of death in people with MPS VI. ar Autosomal recessive ARSB https://medlineplus.gov/genetics/gene/arsb Arylsulfatase B deficiency Maroteaux-Lamy syndrome MPS VI MPS6 Mucopolysaccharidosis 6 Mucopolysaccharidosis VI Polydystrophic dwarfism GTR C0026709 MeSH D009087 OMIM 253200 SNOMED CT 52677002 2010-06 2023-03-28 Mucopolysaccharidosis type VII https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-vii descriptionMucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, is a progressive condition that affects most tissues and organs. The severity of MPS VII varies widely among affected individuals.The most severe cases of MPS VII are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth. Other people with MPS VII typically begin to show signs and symptoms of the condition during early childhood. The features of MPS VII include a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), distinctive-looking facial features that are described as "coarse," and a large tongue (macroglossia). Affected individuals also frequently develop an enlarged liver and spleen (hepatosplenomegaly), heart valve abnormalities, and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). The airway may become narrow in some people with MPS VII, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). The clear covering of the eye (cornea) becomes cloudy, which can cause significant vision loss. People with MPS VII may also have recurrent ear infections and hearing loss. Affected individuals may have developmental delay and progressive intellectual disability, although intelligence is unaffected in some people with this condition.MPS VII causes various skeletal abnormalities that become more pronounced with age, including short stature and joint deformities (contractures) that affect mobility. Individuals with this condition may also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with MPS VII and is characterized by numbness, tingling, and weakness in the hands and fingers. People with MPS VII may develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord.The life expectancy of individuals with MPS VII depends on the severity of symptoms. Some affected individuals do not survive infancy, while others may live into adolescence or adulthood. Heart disease and airway obstruction are major causes of death in people with MPS VII. ar Autosomal recessive GUSB https://medlineplus.gov/genetics/gene/gusb Beta-glucuronidase deficiency GUSB deficiency MPS VII MPS7 Mucopolysaccharidosis 7 Mucopolysaccharidosis VII Sly Syndrome GTR C0085132 MeSH D016538 OMIM 253220 SNOMED CT 124470009 SNOMED CT 43916004 2010-08 2023-02-27 Muenke syndrome https://medlineplus.gov/genetics/condition/muenke-syndrome descriptionMuenke syndrome is a condition characterized by the premature closure of certain bones of the skull (craniosynostosis) during development, which affects the shape of the head and face.Many people with this disorder have a premature fusion of skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may also be malformed. These changes can result in an abnormally shaped head, wide-set eyes, and flattened cheekbones. About 5 percent of affected individuals have an enlarged head (macrocephaly). People with Muenke syndrome may also have mild abnormalities of the hands or feet, and hearing loss has been observed in some cases. Most people with this condition have normal intellect, but developmental delay and learning problems are possible.The signs and symptoms of Muenke syndrome vary among affected people, and some features overlap with those seen in other craniosynostosis syndromes. A small percentage of people with the gene mutation associated with Muenke syndrome do not have any of the characteristic features of the disorder. ad Autosomal dominant FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 FGFR3-associated coronal synostosis Muenke nonsyndromic coronal craniosynostosis GTR C1864436 MeSH D003398 OMIM 602849 SNOMED CT 440350001 2006-06 2020-08-18 Multicentric osteolysis, nodulosis, and arthropathy https://medlineplus.gov/genetics/condition/multicentric-osteolysis-nodulosis-and-arthropathy descriptionMulticentric osteolysis, nodulosis, and arthropathy (MONA) describes a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. MONA includes a condition formerly called nodulosis-arthropathy-osteolysis (NAO) syndrome. It may also include a similar disorder called Torg syndrome, although it is unknown whether Torg syndrome is actually part of MONA or a separate disorder caused by a mutation in a different gene.In most cases of MONA, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities can later spread to other areas of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with MONA develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature.Many affected individuals develop subcutaneous nodules, which are firm lumps of noncancerous tissue underneath the skin, especially on the soles of the feet. Some affected individuals also have skin abnormalities including patches of dark, thick, and leathery skin. Other features of MONA can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as "coarse." ar Autosomal recessive MMP2 https://medlineplus.gov/genetics/gene/mmp2 Al-Aqeel Sewairi syndrome Hereditary multicentric osteolysis MONA NAO syndrome Nodulosis-arthropathy-osteolysis syndrome Torg syndrome Torg-Winchester syndrome GTR C1850155 MeSH D010014 OMIM 259600 SNOMED CT 254151006 SNOMED CT 254152004 2013-11 2020-08-18 Multiminicore disease https://medlineplus.gov/genetics/condition/multiminicore-disease descriptionMultiminicore disease is a disorder that primarily affects muscles used for movement (skeletal muscles). This condition causes muscle weakness and related health problems that range from mild to life-threatening.Researchers have identified at least four forms of multiminicore disease, which can be distinguished by their characteristic signs and symptoms. The forms of multiminicore disease are the classic form, the progressive form with hand involvement, the antenatal form with arthrogryposis, and the ophthalmoplegic form.The classic form accounts for about 75 percent of cases of multiminicore disease. This form causes muscle weakness beginning in infancy or early childhood. The muscles of the torso and neck (axial muscles) are most affected with arm and leg muscles less so. Muscle weakness causes affected infants to appear "floppy" (hypotonic) and they may have feeding problems early in life. Muscle weakness can delay the development of motor skills such as sitting, standing, and walking. In this form, the muscles of the ribcage and spine become stiff. In addition, the muscles needed for breathing are weak. This combination of muscle weakness and stiffness leads to severe or life-threatening respiratory problems. Almost all children with the classic form develop an abnormal curvature of the spine (scoliosis), which appears during childhood and steadily worsens over time.The progressive form with hand involvement causes muscle weakness and looseness of the joints (joint laxity) in the arms and hands. Individuals with this form may experience muscle pain (myalgia) or extreme fatigue in response to physical activity (exercise intolerance). This form accounts for about 10 percent of cases of multiminicore disease.The antenatal form with arthrogryposis is characterized by stiff, rigid joints throughout the body (arthrogryposis) and distinctive facial features. Weakness in the muscles needed for breathing can result in breathing problems for affected individuals. This form also accounts for about 10 percent of cases of multiminicore disease.The ophthalmoplegic form of multiminicore disease is characterized by paralysis of the eye muscles (external ophthalmoplegia). This can lead to abnormal eye movements and droopy eyelids (ptosis). This form of the condition can also cause weakness in the muscles close to the center of the body (proximal muscles), such as those of the upper arms and legs. The ophthalmoplegic form accounts for 5 to 10 percent of cases of multiminicore disease.Many people with multiminicore disease also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate (tachycardia) and body temperature (hyperthermia), abnormally fast breathing (tachypnea), muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.Multiminicore disease gets its name from small, disorganized areas called minicores, which are found in skeletal muscle cells of many affected individuals. These abnormal regions can only been seen when muscle tissue is viewed under a microscope. Minicores are often present in cells with few or no mitochondria, which are the energy-producing centers within cells. Although the presence of minicores can help doctors diagnose multiminicore disease, it is unclear how they are related to muscle weakness and the other features of this condition. ar Autosomal recessive RYR1 https://medlineplus.gov/genetics/gene/ryr1 SELENON https://medlineplus.gov/genetics/gene/selenon Minicore disease Minicore myopathy MmD Multi-core congenital myopathy Multi-core disease Multi-minicore disease Multicore disease Multicore myopathy Multiminicore myopathy GTR C1850674 MeSH D020512 OMIM 255320 OMIM 602771 SNOMED CT 55133004 2007-10 2024-10-02 Multiple cutaneous and mucosal venous malformations https://medlineplus.gov/genetics/condition/multiple-cutaneous-and-mucosal-venous-malformations descriptionMultiple cutaneous and mucosal venous malformations (also known as VMCM) are bluish patches (lesions) on the skin (cutaneous) and the mucous membranes, such as the lining of the mouth and nose. These lesions represent areas where the underlying veins and other blood vessels did not develop properly (venous malformations). The lesions can be painful, especially when they extend from the skin into the muscles and joints, or when a calcium deposit forms within the lesion causing inflammation and swelling.Most people with VMCM are born with at least one venous malformation. As affected individuals age, the lesions present from birth usually become larger and new lesions often appear. The size, number, and location of venous malformations vary among affected individuals, even among members of the same family. ad Autosomal dominant TEK https://medlineplus.gov/genetics/gene/tek Mucocutaneous venous malformations VMCM VMCM1 GTR C1838437 MeSH D017445 OMIM 600195 SNOMED CT 699301008 2009-08 2020-08-18 Multiple endocrine neoplasia https://medlineplus.gov/genetics/condition/multiple-endocrine-neoplasia descriptionMultiple endocrine neoplasia is a group of disorders that affect the body's network of hormone-producing glands called the endocrine system. Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia typically involves tumors (neoplasia) in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, the condition can be life-threatening.The major forms of multiple endocrine neoplasia are called type 1, type 2, and type 4. These types are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid glands, the pituitary gland, and the pancreas. Tumors in these glands can lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid glands (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is an adrenal gland tumor that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B (formerly called type 3), and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A, and medullary thyroid carcinoma is the only feature of FMTC. The signs and symptoms of multiple endocrine neoplasia type 2 are relatively consistent within any one family.Multiple endocrine neoplasia type 4 appears to have signs and symptoms similar to those of type 1, although it is caused by mutations in a different gene. Hyperparathyroidism is the most common feature, followed by tumors of the pituitary gland, additional endocrine glands, and other organs. ad Autosomal dominant RET https://medlineplus.gov/genetics/gene/ret MEN1 https://medlineplus.gov/genetics/gene/men1 CDKN1B https://medlineplus.gov/genetics/gene/cdkn1b Adenomatosis, familial endocrine Endocrine neoplasia, multiple Familial endocrine adenomatosis MEA MEN Multiple endocrine adenomatosis Multiple endocrine neoplasms GTR C0025267 GTR C0025268 GTR C0025269 GTR C1833921 GTR C1970712 ICD-10-CM E31.2 ICD-10-CM E31.20 ICD-10-CM E31.21 ICD-10-CM E31.22 ICD-10-CM E31.23 ICD-10-CM Z15.81 ICD-10-CM Z83.41 MeSH D009377 OMIM 131100 OMIM 155240 OMIM 162300 OMIM 171400 OMIM 610755 SNOMED CT 30664006 SNOMED CT 46724008 SNOMED CT 61530001 SNOMED CT 61808009 2013-08 2020-08-18 Multiple epiphyseal dysplasia https://medlineplus.gov/genetics/condition/multiple-epiphyseal-dysplasia descriptionMultiple epiphyseal dysplasia is a disorder of cartilage and bone development primarily affecting the ends of the long bones in the arms and legs (epiphyses). There are two types of multiple epiphyseal dysplasia, which can be distinguished by their pattern of inheritance. Both the dominant and recessive types have relatively mild signs and symptoms, including joint pain that most commonly affects the hips and knees, early-onset arthritis, and a waddling walk. Although some people with multiple epiphyseal dysplasia have mild short stature as adults, most are of normal height. The majority of individuals are diagnosed during childhood; however, some mild cases may not be diagnosed until adulthood.Recessive multiple epiphyseal dysplasia is distinguished from the dominant type by malformations of the hands, feet, and knees and abnormal curvature of the spine (scoliosis). About 50 percent of individuals with recessive multiple epiphyseal dysplasia are born with at least one abnormal feature, including an inward- and upward-turning foot (clubfoot), an opening in the roof of the mouth (cleft palate), an unusual curving of the fingers or toes (clinodactyly), or ear swelling. An abnormality of the kneecap called a double-layered patella is also relatively common. ad Autosomal dominant ar Autosomal recessive SLC26A2 https://medlineplus.gov/genetics/gene/slc26a2 COMP https://medlineplus.gov/genetics/gene/comp COL9A1 https://medlineplus.gov/genetics/gene/col9a1 COL9A2 https://medlineplus.gov/genetics/gene/col9a2 COL9A3 https://medlineplus.gov/genetics/gene/col9a3 MATN3 https://medlineplus.gov/genetics/gene/matn3 EDM1 EDM2 EDM3 EDM4 EDM5 Epiphyseal dysplasia, Fairbank type Epiphyseal dysplasia, multiple, 1 Epiphyseal dysplasia, multiple, 2 Epiphyseal dysplasia, multiple, 3 Epiphyseal dysplasia, multiple, 4 Epiphyseal dysplasia, multiple, 5 Epiphyseal dysplasia, Ribbing type MED Multiple epiphyseal dysplasia, autosomal dominant Multiple epiphyseal dysplasia, autosomal recessive RMED GTR C1832998 GTR C1838280 GTR C1838429 GTR C1846843 GTR C1847593 GTR C2675767 MeSH D010009 OMIM 120210 OMIM 132400 OMIM 226900 OMIM 600204 OMIM 600969 OMIM 607078 SNOMED CT 313339007 SNOMED CT 59708000 2008-02 2020-08-18 Multiple familial trichoepithelioma https://medlineplus.gov/genetics/condition/multiple-familial-trichoepithelioma descriptionMultiple familial trichoepithelioma is a condition involving multiple skin tumors that develop from structures associated with the skin (skin appendages), such as hair follicles and sweat glands. People with multiple familial trichoepithelioma typically develop large numbers of smooth, round tumors called trichoepitheliomas, which arise from hair follicles. Trichoepitheliomas are generally noncancerous (benign) but occasionally develop into a type of skin cancer called basal cell carcinoma.Individuals with multiple familial trichoepithelioma occasionally also develop other types of tumors, including growths called spiradenomas and cylindromas. Spiradenomas develop in sweat glands. The origin of cylindromas has been unclear; while previously thought to derive from sweat glands, they are now generally believed to begin in hair follicles. Affected individuals are also at increased risk of developing tumors in tissues other than skin appendages, particularly benign or malignant tumors of the salivary glands.People with multiple familial trichoepithelioma typically begin developing tumors during childhood or adolescence. The tumors mostly appear on the face, especially in the folds in the skin between the nose and lips (nasolabial folds, sometimes called smile lines), but may also occur on the neck, scalp, or trunk. They may grow larger and increase in number over time.In severe cases, the tumors may get in the way of the eyes, ears, nose, or mouth and affect vision, hearing, or other functions. The growths can be disfiguring and may contribute to depression or other psychological problems. For reasons that are unclear, females with multiple familial trichoepithelioma are often more severely affected than males. ad Autosomal dominant CYLD https://medlineplus.gov/genetics/gene/cyld Brooke-Fordyce trichoepitheliomas EAC Epithelioma adenoides cysticum of Brooke Familial multiple trichoepitheliomata Hereditary multiple benign cystic epithelioma MFT GTR C1275122 MeSH D012878 OMIM 601606 OMIM 612099 SNOMED CT 403825008 2012-06 2023-11-08 Multiple mitochondrial dysfunctions syndrome https://medlineplus.gov/genetics/condition/multiple-mitochondrial-dysfunctions-syndrome descriptionMultiple mitochondrial dysfunctions syndrome is characterized by impairment of cellular structures called mitochondria, which are the energy-producing centers of cells. While certain mitochondrial disorders are caused by impairment of a single stage of energy production, individuals with multiple mitochondrial dysfunctions syndrome have reduced function of more than one stage. The signs and symptoms of this severe condition begin early in life, and affected individuals usually do not live past infancy.Affected infants typically have severe brain dysfunction (encephalopathy), which can contribute to weak muscle tone (hypotonia), seizures, and delayed development of mental and movement abilities (psychomotor delay). These infants often have difficulty growing and gaining weight at the expected rate (failure to thrive). Most affected babies have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can be life-threatening. They may also have high levels of a molecule called glycine (hyperglycinemia) or elevated levels of sugar (hyperglycemia) in the blood. Some babies with multiple mitochondrial dysfunctions syndrome have high blood pressure in the blood vessels that connect to the lungs (pulmonary hypertension) or weakening of the heart muscle (cardiomyopathy). ar Autosomal recessive BOLA3 https://medlineplus.gov/genetics/gene/bola3 NFU1 https://medlineplus.gov/genetics/gene/nfu1 MMDS Multiple mitochondrial dysfunction syndrome GTR C3276432 GTR C3280378 GTR C3809165 MeSH D028361 OMIM 605711 OMIM 614299 OMIM 615330 SNOMED CT 720827002 2015-05 2020-08-18 Multiple myeloma https://medlineplus.gov/genetics/condition/multiple-myeloma descriptionMultiple myeloma is a cancer that develops in the bone marrow, the spongy tissue found in the center of most bones. The bone marrow produces red blood cells, which carry oxygen throughout the body; white blood cells, which form the body's defenses (immune system); and platelets, which are necessary for blood clotting.Multiple myeloma is characterized by abnormalities in plasma cells, a type of white blood cell. These abnormal cells multiply out of control, increasing from about one percent of cells in the bone marrow to the majority of bone marrow cells. The abnormal cells form tumors within the bone, causing bone pain and an increased risk of fractures. If the tumors interfere with nerves near the bones, numbness or weakness in the arms or legs can occur. Affected individuals may also experience a loss of bone tissue, particularly in the skull, spine, ribs, and pelvis. The deterioration of bone can result in an excess of calcium in the blood (hypercalcemia), which can lead to nausea and loss of appetite, excessive thirst, fatigue, muscle weakness, and confusion.The abnormal plasma cells in multiple myeloma produce proteins that impair the development of normal blood cells. As a result, affected individuals may have a reduced number of red blood cells (anemia), which can cause fatigue, weakness, and unusually pale skin (pallor); a low number of white blood cells (leukopenia), which can result in a weakened immune system and frequent infections such as pneumonia; and a reduced number of platelets (thrombocytopenia), which can lead to abnormal bleeding and bruising. Kidney problems can also occur in this disorder, caused by hypercalcemia or by toxic proteins produced by the abnormal plasma cells.People with multiple myeloma typically develop the disorder around age 65. Over time, affected individuals can develop life-threatening complications, but the rate at which this happens varies widely. Some affected individuals are diagnosed incidentally when tests are done for other purposes and do not experience symptoms for years. n Not inherited u Pattern unknown FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 BRAF https://medlineplus.gov/genetics/gene/braf CCND1 https://www.ncbi.nlm.nih.gov/gene/595 IRF4 https://www.ncbi.nlm.nih.gov/gene/3662 LIG4 https://www.ncbi.nlm.nih.gov/gene/3981 MAF https://www.ncbi.nlm.nih.gov/gene/4094 FCRL4 https://www.ncbi.nlm.nih.gov/gene/83417 PWWP3A https://www.ncbi.nlm.nih.gov/gene/84939 14 https://medlineplus.gov/genetics/chromosome/14 Kahler disease Kahler's disease Kahler-Bozzolo disease Medullary plasmacytoma Myelomatosis Plasma cell dyscrasia Plasma cell myelomas GTR C0026764 ICD-10-CM C90.0 ICD-10-CM C90.00 ICD-10-CM C90.01 ICD-10-CM C90.02 MeSH D009101 OMIM 254500 SNOMED CT 109989006 2016-05 2020-09-18 Multiple pterygium syndrome https://medlineplus.gov/genetics/condition/multiple-pterygium-syndrome descriptionMultiple pterygium syndrome is a condition that is evident before birth with webbing of the skin (pterygium) at the joints and a lack of muscle movement (akinesia) before birth. Akinesia frequently results in muscle weakness and joint deformities called contractures that restrict the movement of joints (arthrogryposis). As a result, multiple pterygium syndrome can lead to further problems with movement such as arms and legs that cannot fully extend.The two forms of multiple pterygium syndrome are differentiated by the severity of their symptoms. Multiple pterygium syndrome, Escobar type (sometimes referred to as Escobar syndrome) is the milder of the two types. Lethal multiple pterygium syndrome is fatal before birth or very soon after birth.In people with multiple pterygium syndrome, Escobar type, the webbing typically affects the skin of the neck, fingers, forearms, inner thighs, and backs of the knee. People with this type may also have arthrogryposis. A side-to-side curvature of the spine (scoliosis) is sometimes seen. Affected individuals may also have respiratory distress at birth due to underdeveloped lungs (lung hypoplasia). People with multiple pterygium syndrome, Escobar type usually have distinctive facial features including droopy eyelids (ptosis), outside corners of the eyes that point downward (downslanting palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), a small jaw, and low-set ears. Males with this condition can have undescended testes (cryptorchidism). This condition does not worsen after birth, and affected individuals typically do not have muscle weakness later in life.Lethal multiple pterygium syndrome has many of the same signs and symptoms as the Escobar type. In addition, affected fetuses may develop a buildup of excess fluid in the body (hydrops fetalis) or a fluid-filled sac typically found on the back of the neck (cystic hygroma). Individuals with this type have severe arthrogryposis. Lethal multiple pterygium syndrome is associated with abnormalities such as underdevelopment (hypoplasia) of the heart, lung, or brain; twisting of the intestines (intestinal malrotation); kidney abnormalities; an opening in the roof of the mouth (a cleft palate); and an unusually small head size (microcephaly). Affected individuals may also develop a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), a condition called a congenital diaphragmatic hernia. Lethal multiple pterygium syndrome is typically fatal in the second or third trimester of pregnancy. ar Autosomal recessive CHRNG https://medlineplus.gov/genetics/gene/chrng RAPSN https://medlineplus.gov/genetics/gene/rapsn CHRNA1 https://www.ncbi.nlm.nih.gov/gene/1134 CHRND https://www.ncbi.nlm.nih.gov/gene/1144 Escobar syndrome Familial pterygium syndrome Pterygium syndrome GTR C0265261 GTR C1854678 MeSH D012873 OMIM 253290 OMIM 265000 SNOMED CT 205819008 SNOMED CT 60192008 SNOMED CT 80773006 2011-11 2020-08-18 Multiple sclerosis https://medlineplus.gov/genetics/condition/multiple-sclerosis descriptionMultiple sclerosis is a condition characterized by areas of damage (lesions) on the brain and spinal cord. These lesions are associated with destruction of the covering that protects nerves and promotes the efficient transmission of nerve impulses (the myelin sheath) and damage to nerve cells. Multiple sclerosis is considered an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs, in this case tissues of the nervous system.Multiple sclerosis usually begins in early adulthood, between ages 20 and 40. The symptoms vary widely, and affected individuals can experience one or more effects of nervous system damage. Multiple sclerosis often causes sensory disturbances in the limbs, including a prickling or tingling sensation (paresthesia), numbness, pain, and itching. Some people experience Lhermitte sign, which is an electrical shock-like sensation that runs down the back and into the limbs. This sensation usually occurs when the head is bent forward. Problems with muscle control are common in people with multiple sclerosis. Affected individuals may have tremors, muscle stiffness (spasticity), exaggerated reflexes (hyperreflexia), weakness or partial paralysis of the muscles of the limbs, difficulty walking, or poor bladder control. Multiple sclerosis is also associated with vision problems, such as blurred or double vision or partial or complete vision loss. Infections that cause fever can make the symptoms worse.There are several forms of multiple sclerosis: relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive relapsing MS. The most common is the relapsing-remitting form, which affects approximately 80 percent of people with multiple sclerosis. Individuals with this form of the condition have periods during which they experience symptoms, called clinical attacks, followed by periods without any symptoms (remission). The triggers of clinical attacks and remissions are unknown. After about 10 years, relapsing-remitting MS usually develops into another form of the disorder called secondary progressive MS. In this form, there are no remissions, and symptoms of the condition continually worsen.Primary progressive MS is the next most common form, affecting approximately 10 to 20 percent of people with multiple sclerosis. This form is characterized by constant symptoms that worsen over time, with no clinical attacks or remissions. Primary progressive MS typically begins later than the other forms, around age 40.Progressive relapsing MS is a rare form of multiple sclerosis that initially appears like primary progressive MS, with constant symptoms. However, people with progressive relapsing MS also experience clinical attacks of more severe symptoms. u Pattern unknown TNFRSF1A https://medlineplus.gov/genetics/gene/tnfrsf1a HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 IL7R https://medlineplus.gov/genetics/gene/il7r IL2RA https://www.ncbi.nlm.nih.gov/gene/3559 Disseminated sclerosis MS GTR C1868685 ICD-10-CM G35 MeSH D009103 OMIM 126200 SNOMED CT 192928003 SNOMED CT 24700007 2013-04 2026-03-17 Multiple sulfatase deficiency https://medlineplus.gov/genetics/condition/multiple-sulfatase-deficiency descriptionMultiple sulfatase deficiency is a condition that mainly affects the brain, skin, and skeleton. Because the signs and symptoms of multiple sulfatase deficiency vary widely, researchers have split the condition into three types: neonatal, late-infantile, and juvenile.The neonatal type is the most severe form, with signs and symptoms appearing soon after birth. Affected individuals have deterioration of tissue in the nervous system (leukodystrophy), which can contribute to movement problems, seizures, developmental delay, and slow growth. They also have dry, scaly skin (ichthyosis) and excess hair growth (hypertrichosis). Skeletal abnormalities can include abnormal side-to-side curvature of the spine (scoliosis), joint stiffness, and dysostosis multiplex, which refers to a specific pattern of skeletal abnormalities seen on x-ray. Individuals with the neonatal type typically have facial features that can be described as "coarse." Affected individuals may also have hearing loss, heart malformations, and an enlarged liver and spleen (hepatosplenomegaly). Many of the signs and symptoms of neonatal multiple sulfatase deficiency worsen over time.The late-infantile type is the most common form of multiple sulfatase deficiency. It is characterized by normal cognitive development in early childhood followed by a progressive loss of mental abilities and movement (psychomotor regression) due to leukodystrophy or other brain abnormalities. Individuals with this form of the condition do not have as many features as those with the neonatal type, but they often have ichthyosis, skeletal abnormalities, and coarse facial features.The juvenile type is the rarest form of multiple sulfatase deficiency. Signs and symptoms of the juvenile type appear in mid- to late childhood. Affected individuals have normal early cognitive development but then experience psychomotor regression; however, the regression in the juvenile type usually occurs at a slower rate than in the late-infantile type. Ichthyosis is also common in the juvenile type of multiple sulfatase deficiency.Life expectancy is shortened in individuals with all types of multiple sulfatase deficiency. Typically, affected individuals survive only a few years after the signs and symptoms of the condition appear, but life expectancy varies depending on the severity of the condition and how quickly the neurological problems worsen. ar Autosomal recessive SUMF1 https://medlineplus.gov/genetics/gene/sumf1 Austin syndrome Juvenile sulfatidosis, Austin type MSD Mucosulfatidosis GTR C0268263 MeSH D052517 OMIM 272200 SNOMED CT 54898003 2014-07 2021-05-17 Multiple system atrophy https://medlineplus.gov/genetics/condition/multiple-system-atrophy descriptionMultiple system atrophy is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary, such as regulation of blood pressure. The most frequent autonomic symptoms associated with multiple system atrophy are a sudden drop in blood pressure upon standing (orthostatic hypotension), urinary difficulties, and erectile dysfunction in men.Researchers have described two major types of multiple system atrophy, which are distinguished by their major signs and symptoms at the time of diagnosis. In one type, known as MSA-P, a group of movement abnormalities called parkinsonism are predominant. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). The other type of multiple system atrophy, known as MSA-C, is characterized by cerebellar ataxia, which causes problems with coordination and balance. This form of the condition can also include speech difficulties (dysarthria) and problems controlling eye movement.Multiple system atrophy usually occurs in older adults; on average, signs and symptoms appear around age 55. The condition worsens with time, and affected individuals survive an average of 10 years after the signs and symptoms first appear. u Pattern unknown SNCA https://medlineplus.gov/genetics/gene/snca COQ2 https://medlineplus.gov/genetics/gene/coq2 MSA OPCA Progressive autonomic failure with multiple system atrophy SDS Shy-Drager syndrome Sporadic olivopontocerebellar atrophy GTR C3714927 ICD-10-CM G90.3 MeSH D019578 OMIM 146500 SNOMED CT 16576004 SNOMED CT 230297002 2016-07 2024-10-02 MyD88 deficiency https://medlineplus.gov/genetics/condition/myd88-deficiency descriptionMyD88 deficiency is an inherited disorder of the immune system (primary immunodeficiency). This primary immunodeficiency affects the innate immune response, which is the body's early, nonspecific response to foreign invaders (pathogens). MyD88 deficiency leads to abnormally frequent and severe infections by a subset of bacteria known as pyogenic bacteria. (Infection with pyogenic bacteria causes the production of pus.) However, affected individuals have normal resistance to other common bacteria, viruses, fungi, and parasites. The most common infections in MyD88 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent by about age 10.Children with MyD88 deficiency develop invasive bacterial infections, which can involve the blood (septicemia), the membrane covering the brain and spinal cord (meningitis), or the joints (leading to inflammation and arthritis). Invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, affected individuals can have localized infections of the ears, nose, or throat. Although fever is a common reaction to bacterial infections, many people with MyD88 deficiency do not at first develop a high fever in response to these infections, even if the infection is severe. ar Autosomal recessive MYD88 https://medlineplus.gov/genetics/gene/myd88 MYD88 deficiency Pyogenic bacterial infections due to MyD88 deficiency GTR C2677092 MeSH D007153 OMIM 612260 SNOMED CT 718232007 2015-06 2020-08-18 Myasthenia gravis https://medlineplus.gov/genetics/condition/myasthenia-gravis descriptionMyasthenia gravis is a disorder that causes weakness of the skeletal muscles, which are muscles that the body uses for movement. The weakness most often starts in the muscles around the eyes, causing drooping of the eyelids (ptosis) and difficulty coordinating eye movements, which results in blurred or double vision. In a form of the disorder called ocular myasthenia, the weakness remains confined to the eye muscles. In most people with myasthenia gravis, however, additional muscles in the face and neck are affected. Affected individuals may have unusual facial expressions, difficulty holding up the head, speech impairment (dysarthria), and chewing and swallowing problems (dysphagia) that may lead to choking, gagging, or drooling.Other muscles in the body are also affected in some people with myasthenia gravis. The muscles of the arms and legs may be involved, causing affected individuals to have changes in their gait or trouble with lifting objects, rising from a seated position, or climbing stairs. The muscle weakness tends to fluctuate over time; it typically worsens with activity and improves with rest.Weakness of the muscles in the chest wall and the muscle that separates the abdomen from the chest cavity (the diaphragm) can cause breathing problems in some people with myasthenia gravis. About 10 percent of people with this disorder experience a potentially life-threatening complication in which these respiratory muscles weaken to the point that breathing is dangerously impaired, and the affected individual requires ventilation assistance. This respiratory failure, called a myasthenic crisis, may be triggered by stresses such as infections or reactions to medications.People can develop myasthenia gravis at any age. For reasons that are unknown, it is most commonly diagnosed in women younger than age 40 and men older than age 60. It is uncommon in children, but some infants born to women with myasthenia gravis show signs and symptoms of the disorder for the first few days or weeks of life. This temporary occurrence of symptoms is called transient neonatal myasthenia gravis. u Pattern unknown MG GTR C0026896 ICD-10-CM G70.00 ICD-10-CM G70.01 ICD-10-CM P94.0 MeSH D009157 OMIM 159400 OMIM 254200 OMIM 607085 SNOMED CT 91637004 2012-07 2021-11-05 Mycosis fungoides https://medlineplus.gov/genetics/condition/mycosis-fungoides descriptionMycosis fungoides is the most common form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions. Although the skin is involved, the skin cells themselves are not cancerous. Mycosis fungoides usually occurs in adults over age 50, although affected children have been identified.Mycosis fungoides may progress slowly through several stages, although not all people with the condition progress through all stages. Most affected individuals initially develop skin lesions called patches, which are flat, scaly, pink or red areas on the skin that can be itchy. Cancerous T cells, which cause the formation of patches, are found in these lesions. The skin cells themselves are not cancerous; the skin problems result when cancerous T cells move from the blood into the skin. Patches are most commonly found on the lower abdomen, upper thighs, buttocks, and breasts. They can disappear and reappear or remain stable over time. In some affected individuals, patches progress to plaques, the next stage of mycosis fungoides.Plaques are raised lesions that are usually reddish, purplish, or brownish in color and itchy. Plaques commonly occur in the same body regions as patches. While some plaques arise from patches, others develop on their own, and an affected person can have both patches and plaques simultaneously. As with patches, cancerous T cells are found in plaques. Plaques can remain stable or can develop into tumors. Not everyone with patches or plaques develops tumors.The tumors in mycosis fungoides, which are composed of cancerous T cells, are raised nodules that are thicker and deeper than plaques. They can arise from patches or plaques or occur on their own. Mycosis fungoides was so named because the tumors can resemble mushrooms, a type of fungus. Common locations for tumor development include the upper thighs and groin, breasts, armpits, and the crook of the elbow. Open sores may develop on the tumors, often leading to infection.Although rare, the cancerous T cells can spread to other organs, including the lymph nodes, spleen, liver, and lungs. Spread to other organs can occur in any stage of mycosis fungoides but is most common in the tumor stage. In addition, affected individuals have an increased risk of developing another lymphoma or other type of cancer. n Not inherited u Pattern unknown Alibert-Bazin syndrome Granuloma fungoides ICD-10-CM C84.0 ICD-10-CM C84.00 ICD-10-CM C84.01 ICD-10-CM C84.02 ICD-10-CM C84.03 ICD-10-CM C84.04 ICD-10-CM C84.05 ICD-10-CM C84.06 ICD-10-CM C84.07 ICD-10-CM C84.08 ICD-10-CM C84.09 MeSH D009182 OMIM 254400 SNOMED CT 118618005 2013-02 2021-05-17 Myhre syndrome https://medlineplus.gov/genetics/condition/myhre-syndrome descriptionMyhre syndrome is a rare condition that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the body. Myhre syndrome has a variety of signs and symptoms that affect many parts of the body, though not everyone has all the possible features. The features of the condition can range in severity, and some features become more apparent with age.Common signs and symptoms of Myhre syndrome include short stature, skeletal abnormalities, limited joint mobility, characteristic facial features, intellectual and behavioral problems, hearing loss, a tendency for the buildup of scar tissue (fibrosis) in the skin and internal organs, and heart and lung abnormalities.Growth is reduced in most people with Myhre syndrome, beginning before birth and continuing through adolescence. Affected individuals usually have a low birth weight and are generally shorter than about 97 percent of their peers throughout life. They have shortened long bones of the arms and legs, unusually short fingers and toes (brachydactyly), and curved pinky fingers (fifth finger clinodactyly). Other skeletal abnormalities associated with this disorder include thickening of the skull bones, flattened bones of the spine (platyspondyly), broad ribs, and underdevelopment of the wing-shaped structures of the pelvis (hypoplastic iliac wings). Affected individuals often have joint problems (arthropathy), including stiffness and limited mobility.Typical facial features in people with Myhre syndrome include narrow openings of the eyelids (short palpebral fissures), deeply set eyes, a shortened distance between the nose and upper lip (a short philtrum), a narrow mouth with a thin upper lip, an underdeveloped upper jaw, and a protruding lower jaw (prognathism). Some affected individuals are born with an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both. Vision problems are common in this disorder and can include eyes that do not point in the same direction (strabismus), nearsightedness (myopia), farsightedness (hyperopia), an irregular curvature of the front of the eye (astigmatism), clouding of the lenses (cataracts), or rarely, an abnormality of the back of the eye called pseudopapilledema.Children with Myhre syndrome have delayed development, which is noticeable by age 5. Speech and language delay are the most significant. Motor skills such as crawling and walking may be delayed, although children with Myhre syndrome eventually learn to walk. Most affected individuals have intellectual disability that ranges from mild to moderate, yet some are able to have jobs or pursue higher education.People with Myhre syndrome typically have features like those in autism spectrum disorder, which affects communication and social interaction. These problems vary in severity, and they usually improve over time.Hearing loss occurs in most people with Myhre syndrome, usually beginning in childhood and gradually worsening. If not detected promptly, hearing problems can contribute to learning and behavioral problems.Fibrosis in Myhre syndrome can occur in the absence of injury (spontaneously) or develop following surgery or trauma. Affected individuals typically have stiff, thickened skin, usually beginning in childhood. Typically, the skin changes first appear on the palms of the hands, the soles of the feet, the back of the elbows, and the front of the knees. Eventually the skin thickens on other parts of the body. As a result of the thicker skin, affected individuals typically have fewer facial creases (wrinkles) than others of their age. Scars may be more noticeable or become unusually thickened after healing (keloids or hypertrophic scars).Individuals with Myhre syndrome often have problems with the structure of the heart that are present at birth (congenital heart defects). Fibrosis in the heart and blood vessels (cardiovascular system) can lead to the development of additional problems such as high blood pressure (hypertension) and narrowing (stenosis) of the heart valves or blood vessels. Other cardiovascular problems can include swelling and tightening of the pericardium, which is the membrane that surrounds the heart (pericarditis), and rarely, restrictive cardiomyopathy, in which the heart muscle is stiff and cannot fully relax after each contraction. These cardiovascular problems can be life-threatening.Abnormalities of the lungs and airways (respiratory tract) in people with Myhre syndrome include narrowing of the windpipe (laryngotracheal stenosis) and the passages leading from the windpipe to the lungs (bronchi); difficulty filling the lungs with air when inhaling (restrictive pulmonary disease); or widespread lung damage (interstitial lung disease). These respiratory tract problems can be life-threatening.Additional features of Myhre syndrome include problems in the gastrointestinal tract, such as narrowing of the lower part of the stomach (pyloric stenosis) or of the upper part of the small intestine (duodenal strictures) and severe constipation. People with Myhre syndrome also may have an increased risk of developing cancerous or noncancerous tumors, including cancer of the lining of the uterus (endometrial cancer). ad Autosomal dominant SMAD4 https://medlineplus.gov/genetics/gene/smad4 LAPS syndrome Laryngotracheal stenosis, arthropathy, prognathism, and short stature GTR C0796081 MeSH D000015 OMIM 139210 SNOMED CT 699316006 2020-02 2023-07-12 Myoclonic epilepsy myopathy sensory ataxia https://medlineplus.gov/genetics/condition/myoclonic-epilepsy-myopathy-sensory-ataxia descriptionMyoclonic epilepsy myopathy sensory ataxia, commonly called MEMSA, is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. The signs and symptoms of MEMSA typically appear during young adulthood. This condition had previously been known as spinocerebellar ataxia with epilepsy (SCAE).The first symptom of MEMSA is usually cerebellar ataxia, which refers to problems with coordination and balance due to defects in the part of the brain that is involved in coordinating movement (cerebellum). Recurrent seizures (epilepsy) usually develop later, often in combination with uncontrollable muscle jerks (myoclonus). The seizures usually begin in the right arm and spread to become generalized throughout the body. Additionally, affected individuals may have severe brain dysfunction (encephalopathy) or muscle weakness (myopathy). The myopathy can affect muscles close to the center of the body (proximal), such as the muscles of the hips, thighs, upper arms, or neck, or muscles farther away from the center of the body (distal), such as the muscles of the hands or feet. The myopathy may be especially noticeable during exercise (exercise intolerance). ar Autosomal recessive POLG https://medlineplus.gov/genetics/gene/polg MEMSA SCAE Spinocerebellar ataxia with epilepsy GTR C1843852 MeSH D028361 OMIM 607459 SNOMED CT 699328003 2011-06 2020-08-18 Myoclonic epilepsy with ragged-red fibers https://medlineplus.gov/genetics/condition/myoclonic-epilepsy-with-ragged-red-fibers descriptionMyoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family.MERRF is characterized by muscle twitches (myoclonus), weakness (myopathy), and progressive stiffness (spasticity). When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells are called ragged-red fibers. Other features of MERRF include recurrent seizures (epilepsy), difficulty coordinating movements (ataxia), a loss of sensation in the extremities (peripheral neuropathy), and slow deterioration of intellectual function (dementia). People with this condition may also develop hearing loss or optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain. Affected individuals sometimes have short stature and a form of heart disease known as cardiomyopathy. Less commonly, people with MERRF develop fatty tumors, called lipomas, just under the surface of the skin. m mitochondrial MT-TS1 https://medlineplus.gov/genetics/gene/mt-ts1 MT-TL1 https://medlineplus.gov/genetics/gene/mt-tl1 MT-TH https://medlineplus.gov/genetics/gene/mt-th MT-TK https://medlineplus.gov/genetics/gene/mt-tk MT-TF https://www.ncbi.nlm.nih.gov/gene/4558 MT-TP https://www.ncbi.nlm.nih.gov/gene/4571 MT-TS2 https://www.ncbi.nlm.nih.gov/gene/4575 MT-TT https://www.ncbi.nlm.nih.gov/gene/4576 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Fukuhara disease MERRF MERRF syndrome Myoclonic epilepsy associated with ragged-red fibers Myoencephalopathy ragged-red fiber disease GTR C0162672 ICD-10-CM E88.42 MeSH D017243 OMIM 545000 SNOMED CT 230426003 SNOMED CT 57254004 SNOMED CT 68448003 2014-05 2021-04-20 Myoclonus-dystonia https://medlineplus.gov/genetics/condition/myoclonus-dystonia descriptionMyoclonus-dystonia is a movement disorder that typically affects the neck, torso, and arms. Individuals with this condition experience quick, involuntary muscle jerks or twitches (myoclonus). About half of individuals with myoclonus-dystonia develop dystonia, which is involuntary tensing of various muscles that causes unusual positioning. In myoclonus-dystonia, dystonia often affects one or both hands, causing writer's cramp, or the neck, causing the head to turn (torticollis).The movement problems usually first appear in childhood or early adolescence with the development of myoclonus. In most cases, the movement problems remain stable throughout life. In some adults, myoclonus improves with alcohol consumption, which can lead to affected individuals self-medicating and developing alcohol use disorder.People with myoclonus-dystonia often develop psychological disorders such as depression, anxiety, panic attacks, and obsessive-compulsive disorder (OCD). ad Autosomal dominant SGCE https://medlineplus.gov/genetics/gene/sgce RELN https://medlineplus.gov/genetics/gene/reln KCTD17 https://www.ncbi.nlm.nih.gov/gene/79734 Dystonia 11 DYT11 Myoclonus-dystonia syndrome GTR C1834570 MeSH D009207 OMIM 159900 SNOMED CT 439732004 2017-10 2020-08-18 Myofibrillar myopathy https://medlineplus.gov/genetics/condition/myofibrillar-myopathy descriptionMyofibrillar myopathy refers to a group of disorders that are characterized by muscle weakness (myopathy) that worsens over time. Myofibrillar myopathy primarily affects the skeletal muscles, which are the muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected.The signs and symptoms of myofibrillar myopathy vary widely among affected individuals. People with this disorder typically begin to develop myopathy in mid-adulthood. However, the features of this condition can appear anytime between infancy and late adulthood. Myopathy most often begins in the hands, forearms, feet, and lower legs (distal muscles), but some people first experience weakness in the muscles near the center of the body (proximal muscles). The weakness can spread to other muscles. Other signs and symptoms of myofibrillar myopathy can include muscle pain (myalgia) or weakness and loss of sensation in the limbs (peripheral neuropathy). Affected individuals may also have skeletal problems, which can include joint stiffness (contractures) and abnormal side-to-side curvature of the spine (scoliosis). Some people with myofibrillar myopathy develop clouding in the lenses of the eyes (cataracts).Some people with myofibrillar myopathy develop cardiomyopathy, which is a weakening of the heart muscle. In some cases, cardiomyopathy is the first sign of the disorder.In rare cases, the muscles used for speaking, swallowing, or breathing are affected in people with myofibrillar myopathy. When the muscles used for breathing are involved, affected individuals may experience extreme tiredness (fatigue), breathing difficulties, and, in severe cases, respiratory failure.  ad Autosomal dominant+New variant x X-linked TTN https://medlineplus.gov/genetics/gene/ttn HSPB8 https://medlineplus.gov/genetics/gene/hspb8 DES https://medlineplus.gov/genetics/gene/des MYOT https://medlineplus.gov/genetics/gene/myot LDB3 https://medlineplus.gov/genetics/gene/ldb3 CRYAB https://www.ncbi.nlm.nih.gov/gene/1410 FLNC https://www.ncbi.nlm.nih.gov/gene/2318 BAG3 https://www.ncbi.nlm.nih.gov/gene/9531 Myofibrillar myopathies GTR C1832370 GTR C1836050 GTR C1837317 GTR C2678065 GTR C2751831 GTR C3714934 GTR C4310645 GTR C4310711 GTR C4721886 GTR C5436656 GTR C5543038 MeSH D020914 OMIM 601419 OMIM 603689 OMIM 608810 OMIM 609200 OMIM 609452 OMIM 609524 OMIM 612954 OMIM 613869 OMIM 617114 OMIM 617258 OMIM 619040 OMIM 619178 OMIM 619424 OMIM 621078 SNOMED CT 699269005 2025-11 2026-01-05 Myopathy with deficiency of iron-sulfur cluster assembly enzyme https://medlineplus.gov/genetics/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme descriptionMyopathy with deficiency of iron-sulfur cluster assembly enzyme is an inherited disorder that primarily affects muscles used for movement (skeletal muscles). This condition does not usually affect other types of muscle, such as the heart (cardiac) muscle.From early childhood, affected individuals experience extreme fatigue in response to physical activity (exercise intolerance). Mild exertion results in a rapid heartbeat (tachycardia), shortness of breath, and muscle weakness and pain. However, people with this condition typically have normal muscle strength when they are at rest.Prolonged or recurrent physical activity causes more severe signs and symptoms, including a breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure.In most affected individuals, the muscle problems associated with this condition do not worsen with time. However, at least two people with a severe variant of this disorder have experienced progressive muscle weakness and wasting starting in childhood. ar Autosomal recessive ISCU https://medlineplus.gov/genetics/gene/iscu Hereditary myopathy with lactic acidosis HML Iron-sulfur cluster deficiency myopathy Myoglobinuria due to abnormal glycolysis Myopathy with deficiency of ISCU Myopathy with deficiency of succinate dehydrogenase and aconitase Myopathy with exercise intolerance, Swedish type GTR C1850718 MeSH D009135 OMIM 255125 SNOMED CT 699268002 2009-11 2020-08-18 Myosin storage myopathy https://medlineplus.gov/genetics/condition/myosin-storage-myopathy descriptionMyosin storage myopathy is a condition that affects muscle (myopathy). This disorder causes muscle weakness that can worsen slowly over time. The signs and symptoms of myosin storage myopathy often begin in childhood, although they can begin later. The specific features of myosin storage myopathy and the severity of the condition can vary, even among members of the same family. Children with myosin storage myopathy may start walking later than usual and have a waddling gait. They can have trouble climbing stairs and difficulty lifting their arms above shoulder level. Weak shoulder muscles often make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have a spine that curves to the side (scoliosis). Some individuals can also develop weakness of the muscles that control breathing (respiratory insufficiency) or weakness of the heart (cardiac) muscle.Myosin storage myopathy belongs to a group of disorders called congenital myopathies. The signs and symptoms of congenital myopathies are often present at birth (congenital) or soon after. Congenital myopathies may affect the muscles used for movement (skeletal muscle) and, less commonly, the cardiac muscle. ar Autosomal recessive ad Autosomal dominant MYH7 https://medlineplus.gov/genetics/gene/myh7 Hyaline body myopathy MYH7-related skeletal myopathy Myosin storage congenital myopathy GTR C1842160 MeSH D009135 OMIM 255160 OMIM 608358 SNOMED CT 699267007 2026-04 2026-04-10 Myostatin-related muscle hypertrophy https://medlineplus.gov/genetics/condition/myostatin-related-muscle-hypertrophy descriptionMyostatin-related muscle hypertrophy is a rare condition characterized by reduced body fat and increased muscle size. Affected individuals have up to twice the usual amount of muscle mass in their bodies. They also tend to have increased muscle strength. Myostatin-related muscle hypertrophy is not known to cause any medical problems, and affected individuals are intellectually normal. ad Autosomal dominant MSTN https://medlineplus.gov/genetics/gene/mstn Muscle hypertrophy syndrome GTR C2931112 MeSH D009135 OMIM 601788 SNOMED CT 699185005 2008-12 2024-10-02 Myotonia congenita https://medlineplus.gov/genetics/condition/myotonia-congenita descriptionMyotonia congenita is a disorder that affects muscles used for movement (skeletal muscles). Beginning in childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Although myotonia can affect any skeletal muscles, including muscles of the face and tongue, it occurs most often in the legs. Myotonia causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. These muscle problems are particularly noticeable during movement following a period of rest. Many affected individuals find that repeated movements can temporarily alleviate their muscle stiffness, a phenomenon known as the warm-up effect.The two major types of myotonia congenita are known as Thomsen disease and Becker disease. These conditions are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe muscle stiffness, particularly in males. People with Becker disease often experience temporary attacks of muscle weakness, particularly in the arms and hands, brought on by movement after periods of rest. They may also develop mild, permanent muscle weakness over time. This muscle weakness is not seen in people with Thomsen disease. ar Autosomal recessive ad Autosomal dominant CLCN1 https://medlineplus.gov/genetics/gene/clcn1 Congenital myotonia GTR C0027127 GTR C0751360 GTR C2936781 ICD-10-CM G71.12 MeSH D009224 OMIM 160800 OMIM 255700 SNOMED CT 20305008 SNOMED CT 57938005 SNOMED CT 726051002 2020-02 2020-08-18 Myotonic dystrophy https://medlineplus.gov/genetics/condition/myotonic-dystrophy descriptionMyotonic dystrophy is part of a group of inherited disorders called muscular dystrophies. It is the most common form of muscular dystrophy that begins in adulthood.Myotonic dystrophy is characterized by progressive muscle wasting and weakness. People with this disorder often have prolonged muscle contractions (myotonia) and are not able to relax certain muscles after use. For example, a person may have difficulty releasing their grip on a doorknob or handle. Also, affected people may have slurred speech or temporary locking of their jaw.Other signs and symptoms of myotonic dystrophy include clouding of the lens of the eye (cataracts) and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). Some affected individuals develop a condition called diabetes mellitus, in which blood sugar (glucose) levels can become dangerously high. The features of myotonic dystrophy often develop during a person's twenties or thirties, although they can occur at any age. The severity of the condition varies widely among affected people, even among members of the same family.There are two major types of myotonic dystrophy: type 1 and type 2. Their signs and symptoms overlap, although type 2 tends to be milder than type 1. The muscle weakness associated with type 1 particularly affects muscles farthest from the center of the body (distal muscles), such as those of the lower legs, hands, neck, and face. Muscle weakness in type 2 primarily involves muscles close to the center of the body (proximal muscles), such as the those of the neck, shoulders, elbows, and hips. The two types of myotonic dystrophy are caused by mutations in different genes.There are two variations of myotonic dystrophy type 1: the mild and congenital types. Mild myotonic dystrophy is apparent in mid to late adulthood. Affected individuals typically have mild myotonia and cataracts. Congenital myotonic dystrophy is often apparent at birth. Characteristic features include weak muscle tone (hypotonia), an inward- and upward-turning foot (clubfoot), breathing problems, delayed development, and intellectual disability. Some of these health problems can be life-threatening. ad Autosomal dominant CNBP https://medlineplus.gov/genetics/gene/cnbp DMPK https://medlineplus.gov/genetics/gene/dmpk Dystrophia myotonica Myotonia atrophica Myotonia dystrophica GTR C0027126 GTR C2931689 ICD-10-CM G71.11 MeSH D009223 OMIM 160900 OMIM 602668 SNOMED CT 195031006 SNOMED CT 240104008 SNOMED CT 77956009 2010-11 2023-07-26 Ménière disease https://medlineplus.gov/genetics/condition/meniere-disease descriptionMénière disease is a disorder of the inner ear that affects balance and hearing. This condition is characterized by sudden episodes of extreme dizziness (vertigo), a roaring sound in the ears (tinnitus), a feeling of pressure or fullness in the ears, and fluctuations in hearing. Episodes are often associated with nausea and vomiting, and they can severely disrupt activities of daily living.The episodes associated with Ménière disease generally last several hours. Studies suggest that episodes can be triggered by stress, tiredness (fatigue), emotional upset, illness, and dietary factors. The timing of these episodes is unpredictable; affected individuals may experience a cluster of episodes within a short period, followed by months or years without any symptoms.Ménière disease usually appears in adulthood, most often in a person's 40s or 50s. It is much less common in children and young adults. The symptoms of the disorder typically begin in one ear, although they may later involve both ears.Some people with Ménière disease have no symptoms of the disorder between episodes, particularly in the early stages of the disease. Over time, however, many affected individuals develop ongoing problems with unsteadiness, tinnitus, and a feeling of fullness in the ears. Additionally, permanent hearing loss eventually develops in many people with this disorder. ad Autosomal dominant Auditory vertigo Aural vertigo Meniere disease Meniere's disease Meniere's syndrome Ménière's disease Ménière's vertigo Otogenic vertigo Primary endolymphatic hydrops ICD-10-CM H81.0 ICD-10-CM H81.01 ICD-10-CM H81.02 ICD-10-CM H81.03 ICD-10-CM H81.09 MeSH D008575 OMIM 156000 SNOMED CT 13445001 2010-06 2023-11-08 Müllerian aplasia and hyperandrogenism https://medlineplus.gov/genetics/condition/mullerian-aplasia-and-hyperandrogenism descriptionMüllerian aplasia and hyperandrogenism is a condition that affects the reproductive system in females. This condition is caused by abnormal development of the Müllerian ducts, which are structures in the embryo that develop into the uterus, fallopian tubes, cervix, and the upper part of the vagina. Individuals with Müllerian aplasia and hyperandrogenism typically have an underdeveloped or absent uterus and may also have abnormalities of other reproductive organs. Women with this condition have normal female external genitalia, and they develop breasts and pubic hair normally at puberty; however, they do not begin menstruation by age 16 (primary amenorrhea) and will likely never have a menstrual period. Affected women are unable to have children (infertile).Women with Müllerian aplasia and hyperandrogenism have higher-than-normal levels of male sex hormones called androgens in their blood (hyperandrogenism), which can cause acne and excessive facial hair (facial hirsutism). Kidney abnormalities may be present in some affected individuals. ad Autosomal dominant WNT4 https://medlineplus.gov/genetics/gene/wnt4 Biason-Lauber syndrome Mayer-Rokitansky-Küster-Hauser-Biason-Lauber syndrome Mayer-Rokitansky-Küster-Hauser-like syndrome Mullerian aplasia and hyperandrogenism Müllerian duct failure WNT4 deficiency WNT4 Müllerian aplasia WNT4 Müllerian aplasia and ovarian dysfunction GTR C2675014 MeSH D058489 OMIM 158330 SNOMED CT 699275001 2014-07 2023-11-13 N-acetylglutamate synthase deficiency https://medlineplus.gov/genetics/condition/n-acetylglutamate-synthase-deficiency descriptionN-acetylglutamate synthase deficiency is a disorder that causes abnormally high levels of ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The brain is especially sensitive to the effects of excess ammonia.The signs and symptoms of N-acetylglutamate synthase deficiency often become evident in the first few days of life. An infant with this condition may be lacking in energy (lethargic) or unwilling to eat, and have difficulty controlling his or her breathing rate or body temperature. Severely affected babies may experience seizures or unusual body movements, or go into a coma. Complications of N-acetylglutamate synthase deficiency may include developmental delay and intellectual disability.In some affected individuals, signs and symptoms of N-acetylglutamate synthase deficiency do not appear until later in life. Some people with this form of the disorder notice that eating high-protein foods, such as meat, affects how they feel, although they may not know why. In many affected adults, illness or other stress can trigger episodes of vomiting, lack of coordination, headaches, confusion, behavioral changes, or coma. ar Autosomal recessive NAGS https://medlineplus.gov/genetics/gene/nags Hyperammonemia, type III N-acetylglutamate synthetase deficiency NAGS deficiency GTR C0268543 ICD-10-CM E72.29 MeSH D056806 OMIM 237310 SNOMED CT 57119000 2019-07 2020-08-18 NGLY1-congenital disorder of deglycosylation https://medlineplus.gov/genetics/condition/ngly1-congenital-disorder-of-deglycosylation descriptionNGLY1-congenital disorder of deglycosylation (NGLY1-CDDG) is an inherited condition that affects many parts of the body. The severity of the signs and symptoms varies widely among people with the condition.Individuals with NGLY1-CDDG typically develop features of the condition during infancy. They often have delayed development of speech and motor skills, such as sitting and walking, and weak muscle tone (hypotonia). Many affected individuals have movement abnormalities, such as uncontrolled movements of the limbs (choreoathetosis), and some develop seizures that are difficult to treat. Individuals with NGLY1-CDDG may also have problems with liver function. Some affected individuals have eye abnormalities, including degeneration of the nerves that carry information from the eyes to the brain (optic atrophy) and changes in the light-sensing tissue at the back of the eye (the retina). A reduction or absence of tears (hypolacrima or alacrima) is a common feature of NGLY1-CDDG. ar Autosomal recessive NGLY1 https://medlineplus.gov/genetics/gene/ngly1 Congenital disorder of deglycosylation Deficiency of N-glycanase 1 NGLY1-CDDG GTR C3808991 MeSH D002239 OMIM 615273 2017-08 2020-08-18 Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis https://medlineplus.gov/genetics/condition/naegeli-franceschetti-jadassohn-syndrome-dermatopathia-pigmentosa-reticularis descriptionNaegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis (NFJS/DPR) represents a rare type of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of ectodermal tissues including the skin, hair, nails, teeth, and sweat glands. NFJS and DPR were originally described as separate conditions; however, because they have similar features and are caused by mutations in the same gene, they are now often considered forms of the same disorder.Among the most common signs of NFJS/DPR is a net-like pattern of dark brown or gray skin coloring, known as reticulate hyperpigmentation. This darker pigmentation is seen most often on the neck, chest, and abdomen, although it can also occur in and around the eyes and mouth. Reticulate hyperpigmentation appears in infancy or early childhood. It may fade with age or persist throughout life.NFJS/DPR also affects the skin on the hands and feet. The skin on the palms of the hands and soles of the feet often becomes thick, hard, and callused, a condition known as palmoplantar keratoderma. Some affected individuals also have blistering on their palms and soles. Their fingernails and toenails may be malformed, brittle, and either thicker or thinner than usual. Most affected individuals are missing the patterned ridges on the skin of the hands and feet, called dermatoglyphs, that are the basis for each person's unique fingerprints.Additional features of NFJS/DPR can include a reduced ability to sweat (hypohidrosis) or excess sweating (hyperhidrosis) and dental abnormalities. Some affected individuals also have hair loss (alopecia) on the scalp, eyebrows, and underarms. The alopecia is described as noncicatricial because it does not leave scars (cicatrices). ad Autosomal dominant KRT14 https://medlineplus.gov/genetics/gene/krt14 DPR Franceschetti-Jadassohn syndrome Naegeli syndrome Naegeli-Franceschetti-Jadassohn syndrome NFJ syndrome NFJS NFJS/DPR GTR C0343111 GTR C0406778 MeSH D004476 OMIM 125595 OMIM 161000 SNOMED CT 239084001 SNOMED CT 239088003 2013-05 2021-11-24 Nager syndrome https://medlineplus.gov/genetics/condition/nager-syndrome descriptionNager syndrome is a rare condition that mainly affects the development of the face, hands, and arms. The severity of this disorder varies among affected individuals.Children with Nager syndrome are born with underdeveloped cheek bones (malar hypoplasia) and a very small lower jaw (micrognathia). They often have an opening in the roof of the mouth called a cleft palate. These abnormalities frequently cause feeding problems in infants with Nager syndrome. The airway is usually partially blocked due to the micrognathia, which can lead to life-threatening breathing problems.People with Nager syndrome often have eyes that slant downward (downslanting palpebral fissures), no eyelashes, and a notch in the lower eyelids called an eyelid coloboma. Many affected individuals have small or unusually formed ears, and about 60 percent have hearing loss caused by defects in the middle ear (conductive hearing loss). Nager syndrome does not affect a person's intelligence, although speech development may be delayed due to hearing impairment.Individuals with Nager syndrome have bone abnormalities in their hands and arms. The most common abnormality is malformed or absent thumbs. Affected individuals may also have fingers that are unusually curved (clinodactyly) or fused together (syndactyly). Their forearms may be shortened due to the partial or complete absence of a bone called the radius. People with Nager syndrome sometimes have difficulty fully extending their elbows. This condition can also cause bone abnormalities in the legs and feet.Less commonly, affected individuals have abnormalities of the heart, kidneys, genitalia, and urinary tract. ad Autosomal dominant ar Autosomal recessive SF3B4 https://medlineplus.gov/genetics/gene/sf3b4 Acrofacial dysostosis 1, Nager type AFD1 NAFD Nager acrofacial dysostosis Nager acrofacial dysostosis syndrome Preaxial acrofacial dysostosis Preaxial mandibulofacial dysostosis GTR C0265245 MeSH D003394 OMIM 154400 SNOMED CT 35520007 2017-08 2020-08-18 Nail-patella syndrome https://medlineplus.gov/genetics/condition/nail-patella-syndrome descriptionNail-patella syndrome is characterized by abnormalities of the nails, knees, elbows, and pelvis. The features of nail-patella syndrome vary in severity between affected individuals, even among members of the same family.Nail abnormalities are seen in almost all individuals with nail-patella syndrome. The nails may be absent or underdeveloped and discolored, split, ridged, or pitted. The fingernails are more likely to be affected than the toenails, and the thumbnails are usually the most severely affected. In many people with this condition, the areas at the base of the nails (lunulae) are triangular instead of the usual crescent shape.Individuals with nail-patella syndrome also commonly have skeletal abnormalities involving the knees, elbows, and hips. The kneecaps (patellae) are small, irregularly shaped, or absent, and dislocation of the patella is common. Some people with this condition may not be able to fully extend their arms or turn their palms up while keeping their elbows straight. The elbows may also be angled outward (cubitus valgus) or have abnormal webbing. Many individuals with nail-patella syndrome have horn-like outgrowths of the iliac bones of the pelvis (iliac horns). These abnormal projections may be felt through the skin, but they do not cause any symptoms and are usually detected on a pelvic x-ray. Iliac horns are very common in people with nail-patella syndrome and are rarely, if ever, seen in people without this condition.Other areas of the body may also be affected in nail-patella syndrome, particularly the eyes and kidneys. Individuals with this condition are at risk of developing increased pressure within the eyes (glaucoma) at an early age. Some people develop kidney disease, which can progress to kidney failure. ad Autosomal dominant LMX1B https://medlineplus.gov/genetics/gene/lmx1b Fong disease Hereditary onycho-osteodysplasia Hereditary osteo-onychodysplasia Osterreicher syndrome Pelvic horn syndrome Turner-Kieser syndrome GTR C0027341 MeSH D009261 OMIM 137750 OMIM 161200 SNOMED CT 22199006 2008-05 2020-08-18 Nakajo-Nishimura syndrome https://medlineplus.gov/genetics/condition/nakajo-nishimura-syndrome descriptionNakajo-Nishimura syndrome is an inherited condition that affects many parts of the body and has been described only in the Japanese population. Beginning in infancy or early childhood, affected individuals develop red, swollen lumps (nodular erythema) on the skin that occur most often in cold weather; recurrent fevers; and elongated fingers and toes with widened and rounded tips (clubbing).Later in childhood, affected individuals develop joint pain and joint deformities called contractures that limit movement, particularly in the hands, wrists, and elbows. They also experience weakness and wasting of muscles, along with a loss of fatty tissue (lipodystrophy), mainly in the upper body. The combination of muscle and fat loss worsens over time, leading to an extremely thin (emaciated) appearance in the face, chest, and arms.Other signs and symptoms of Nakajo-Nishimura syndrome can include an enlarged liver and spleen (hepatosplenomegaly), a shortage of red blood cells (anemia), a reduced amount of blood cells called platelets (thrombocytopenia), and abnormal deposits of calcium (calcification) in an area of the brain called the basal ganglia. Intellectual disability has been reported in some affected individuals.The signs and symptoms of Nakajo-Nishimura syndrome overlap with those of two other conditions: one called joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP) syndrome; and the other called chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. All three conditions are characterized by skin abnormalities and lipodystrophy. Although they are often considered separate disorders, they are caused by mutations in the same gene, and some researchers believe they may represent different forms of a single condition. ar Autosomal recessive PSMB8 https://medlineplus.gov/genetics/gene/psmb8 ALDD Autoinflammation, lipodystrophy, and dermatosis syndrome Japanese autoinflammatory syndrome with lipodystrophy JASL Nakajo syndrome NKJO GTR C4746851 MeSH D056660 OMIM 256040 SNOMED CT 702449004 2013-11 2026-03-04 Narcolepsy https://medlineplus.gov/genetics/condition/narcolepsy descriptionNarcolepsy is a chronic sleep disorder that disrupts the normal sleep-wake cycle. Although this condition can appear at any age, it most often begins in adolescence.Narcolepsy is characterized by excessive daytime sleepiness. Affected individuals feel tired during the day, and several times a day they may experience an overwhelming urge to sleep. "Sleep attacks" can occur at unusual times, such as during a meal or in the middle of a conversation. They last from a few seconds to a few minutes and often lead to a longer nap, after which affected individuals wake up feeling refreshed.Another common feature of narcolepsy is cataplexy, which is a sudden loss of muscle tone in response to strong emotion (such as laughing, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. Episodes of cataplexy usually last just a few seconds, and they may occur from several times a day to a few times a year. Most people diagnosed with narcolepsy also have cataplexy. However, some do not, which has led researchers to distinguish two major forms of the condition: narcolepsy with cataplexy and narcolepsy without cataplexy.Narcolepsy also affects nighttime sleep. Most affected individuals have trouble sleeping for more than a few hours at night. They often experience vivid hallucinations while falling asleep (hypnogogic hallucinations) or while waking up (hypnopompic hallucinations). Affected individuals often have realistic and distressing dreams, and they may act out their dreams by moving excessively or talking in their sleep. Many people with narcolepsy also experience sleep paralysis, which is an inability to move or speak for a short period while falling asleep or awakening. The combination of hallucinations, vivid dreams, and sleep paralysis is often frightening and unpleasant for affected individuals.Some people with narcolepsy have all of the major features of the disorder, while others have only one or two. Most of the signs and symptoms persist throughout life, although episodes of cataplexy may become less frequent with age and treatment. u Pattern unknown HLA-DQB1 https://medlineplus.gov/genetics/gene/hla-dqb1 HLA-DQA1 https://medlineplus.gov/genetics/gene/hla-dqa1 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 CHKB https://www.ncbi.nlm.nih.gov/gene/1120 CPT1B https://www.ncbi.nlm.nih.gov/gene/1375 P2RY11 https://www.ncbi.nlm.nih.gov/gene/5032 TRA https://www.ncbi.nlm.nih.gov/gene/6955 TNF https://www.ncbi.nlm.nih.gov/gene/7124 TNFRSF1B https://www.ncbi.nlm.nih.gov/gene/7133 Gelineau syndrome Narcoleptic syndrome GTR C0751362 GTR C1834372 GTR C1836907 GTR C1853901 GTR C2676275 GTR C2748508 GTR C3280204 GTR C3280266 ICD-10-CM G47.4 ICD-10-CM G47.41 ICD-10-CM G47.411 ICD-10-CM G47.419 ICD-10-CM G47.42 ICD-10-CM G47.421 ICD-10-CM G47.429 MeSH D009290 OMIM 161400 OMIM 605841 OMIM 609039 OMIM 612417 OMIM 612851 OMIM 614223 OMIM 614250 SNOMED CT 193042000 SNOMED CT 60380001 2010-12 2023-11-08 Nearsightedness https://medlineplus.gov/genetics/condition/nearsightedness descriptionNearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.Nearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.For normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.Nearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.Eye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye. x X-linked u Pattern unknown ar Autosomal recessive ad Autosomal dominant ARR3 https://www.ncbi.nlm.nih.gov/gene/407 LRPAP1 https://www.ncbi.nlm.nih.gov/gene/4043 P4HA2 https://www.ncbi.nlm.nih.gov/gene/8974 SCO2 https://www.ncbi.nlm.nih.gov/gene/9997 ZNF644 https://www.ncbi.nlm.nih.gov/gene/84146 PRIMPOL https://www.ncbi.nlm.nih.gov/gene/201973 SLC39A5 https://www.ncbi.nlm.nih.gov/gene/283375 Close sighted Myopia Myopic Near-sightedness Nearsighted Short-sighted Short-sightedness GTR C0027092 ICD-10-CM H52.1 ICD-10-CM H52.10 ICD-10-CM H52.11 ICD-10-CM H52.12 ICD-10-CM H52.13 MeSH D009216 OMIM 160700 OMIM 255500 OMIM 300613 OMIM 310460 OMIM 603221 OMIM 608367 OMIM 608474 OMIM 608908 OMIM 609256 OMIM 609257 OMIM 609258 OMIM 609259 OMIM 609994 OMIM 609995 OMIM 610320 OMIM 612554 OMIM 612717 OMIM 613969 OMIM 614166 SNOMED CT 57190000 2018-07 2020-08-18 Nemaline myopathy https://medlineplus.gov/genetics/condition/nemaline-myopathy descriptionNemaline myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with nemaline myopathy have muscle weakness (myopathy) throughout the body, but it is typically most severe in the muscles of the face; neck; trunk; and other muscles close to the center of the body (proximal muscles), such as those of the upper arms and legs. This weakness can worsen over time. Affected individuals may have feeding and swallowing difficulties, foot deformities, abnormal curvature of the spine (scoliosis), and joint deformities (contractures). Most people with nemaline myopathy are able to walk, although some affected children may begin walking later than usual. As the condition progresses, some people may require wheelchair assistance. In severe cases, the muscles used for breathing are affected and life-threatening breathing difficulties can occur.Nemaline myopathy is divided into six types. In order of decreasing severity, the types are: severe congenital, Amish, intermediate congenital, typical congenital, childhood-onset, and adult-onset. The types are distinguished by the age when symptoms first appear and the severity of symptoms; however, there is overlap among the various types. The severe congenital type is the most life-threatening. Most individuals with this type do not survive past early childhood due to respiratory failure. The Amish type solely affects the Old Order Amish population of Pennsylvania and is typically fatal in early childhood. The most common type of nemaline myopathy is the typical congenital type, which is characterized by muscle weakness and feeding problems beginning in infancy. Most of these individuals do not have severe breathing problems and can walk unassisted. People with the childhood-onset type usually develop muscle weakness in adolescence. The adult-onset type is the mildest of all the various types. People with this type usually develop muscle weakness between ages 20 and 50. ar Autosomal recessive ad Autosomal dominant ACTA1 https://medlineplus.gov/genetics/gene/acta1 TPM3 https://medlineplus.gov/genetics/gene/tpm3 NEB https://medlineplus.gov/genetics/gene/neb TPM2 https://medlineplus.gov/genetics/gene/tpm2 CFL2 https://www.ncbi.nlm.nih.gov/gene/1073 TNNT1 https://www.ncbi.nlm.nih.gov/gene/7138 KLHL41 https://www.ncbi.nlm.nih.gov/gene/10324 LMOD3 https://www.ncbi.nlm.nih.gov/gene/56203 KLHL40 https://www.ncbi.nlm.nih.gov/gene/131377 KBTBD13 https://www.ncbi.nlm.nih.gov/gene/390594 Myopathies, nemaline Myopathy, nemaline Nemaline body disease Nemaline rod disease Rod body disease Rod myopathy Rod-body myopathy GTR C0206157 GTR C1836447 GTR C1836472 GTR C1850569 GTR C1853154 GTR C1854380 GTR C3711389 GTR C3809209 GTR C3810384 GTR C4015360 GTR C5829889 ICD-10-CM G71.2 MeSH D017696 OMIM 161800 OMIM 256030 OMIM 605355 OMIM 609273 OMIM 609284 OMIM 609285 OMIM 610687 OMIM 615348 OMIM 615731 OMIM 616165 SNOMED CT 75072002 2010-05 2020-08-18 Nephronophthisis https://medlineplus.gov/genetics/condition/nephronophthisis descriptionNephronophthisis is a disorder that affects the kidneys. It is characterized by inflammation and scarring (fibrosis) that impairs kidney function. These abnormalities lead to increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). In addition, affected individuals develop fluid-filled cysts in the kidneys, usually in an area known as the corticomedullary region. Another feature of nephronophthisis is a shortage of red blood cells, a condition known as anemia.Nephronophthisis eventually leads to end-stage renal disease (ESRD), a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. Nephronophthisis can be classified by the approximate age at which ESRD begins: around age 1 (infantile), around age 13 (juvenile), and around age 19 (adolescent).About 85 percent of all cases of nephronophthisis are isolated, which means they occur without other signs and symptoms. Some people with nephronophthisis have additional features, which can include liver fibrosis, heart abnormalities, or mirror image reversal of the position of one or more organs inside the body (situs inversus).Nephronophthisis can occur as part of separate syndromes that affect other areas of the body; these are often referred to as nephronophthisis-associated ciliopathies. For example, Senior-Løken syndrome is characterized by the combination of nephronophthisis and a breakdown of the light-sensitive tissue at the back of the eye (retinal degeneration); Joubert syndrome affects many parts of the body, causing neurological problems and other features, which can include nephronophthisis. ar Autosomal recessive WDR19 https://medlineplus.gov/genetics/gene/wdr19 NPHP1 https://medlineplus.gov/genetics/gene/nphp1 CEP164 https://www.ncbi.nlm.nih.gov/gene/22897 ZNF423 https://www.ncbi.nlm.nih.gov/gene/23090 NPHP3 https://www.ncbi.nlm.nih.gov/gene/27031 INVS https://www.ncbi.nlm.nih.gov/gene/27130 CEP83 https://www.ncbi.nlm.nih.gov/gene/51134 TTC21B https://www.ncbi.nlm.nih.gov/gene/79809 GLIS2 https://www.ncbi.nlm.nih.gov/gene/84662 TMEM67 https://www.ncbi.nlm.nih.gov/gene/91147 ANKS6 https://www.ncbi.nlm.nih.gov/gene/203286 NEK8 https://www.ncbi.nlm.nih.gov/gene/245713 NPHP4 https://www.ncbi.nlm.nih.gov/gene/261734 NPH NPHP GTR C0687120 GTR C1847013 GTR C1855681 GTR C1858392 GTR C1865872 GTR C1969092 GTR C3150796 GTR C3151186 GTR C3151188 GTR C3539071 GTR C3541853 GTR C3809320 GTR C3890591 MeSH D052177 OMIM 256100 OMIM 602088 OMIM 604387 OMIM 606966 OMIM 611498 OMIM 613550 OMIM 613820 OMIM 613824 OMIM 614377 OMIM 614844 OMIM 614845 OMIM 615382 OMIM 615862 SNOMED CT 204958008 2014-09 2023-08-22 Netherton syndrome https://medlineplus.gov/genetics/condition/netherton-syndrome descriptionNetherton syndrome is a disorder that affects the skin, hair, and immune system. Newborns with Netherton syndrome have skin that is red and scaly (ichthyosiform erythroderma), and the skin may leak fluid. Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis), which can be life-threatening. Affected babies may also fail to grow and gain weight at the expected rate (failure to thrive). The health of older children and adults with Netherton syndrome usually improves, although they often remain underweight and of short stature.After infancy, the severity of the skin abnormalities varies among people with Netherton syndrome and can fluctuate over time. The skin may continue to be red and scaly, especially during the first few years of life. Some affected individuals have intermittent redness or experience outbreaks of a distinctive skin abnormality called ichthyosis linearis circumflexa, involving patches of multiple ring-like lesions. The triggers for the outbreaks are not known, but researchers suggest that stress or infections may be involved.Itchiness is a common problem for affected individuals, and scratching can lead to frequent infections. Dead skin cells are shed at an abnormal rate and often accumulate in the ear canals, which can affect hearing if not removed regularly. The skin is abnormally absorbent of substances such as lotions and ointments, which can result in excessive blood levels of some topical medications. Because the ability of the skin to protect against heat and cold is impaired, affected individuals may have difficulty regulating their body temperature.People with Netherton syndrome have hair that is fragile and breaks easily. Some strands of hair vary in diameter, with thicker and thinner spots. This feature is known as bamboo hair, trichorrhexis nodosa, or trichorrhexis invaginata. In addition to the hair on the scalp, the eyelashes and eyebrows may be affected. The hair abnormality in Netherton syndrome may not be noticed in infancy because babies often have sparse hair.Most people with Netherton syndrome have immune system-related problems such as food allergies, hay fever, asthma, or an inflammatory skin disorder called eczema. ar Autosomal recessive SPINK5 https://medlineplus.gov/genetics/gene/spink5 Bamboo hair syndrome Comel-Netherton syndrome Ichthyosiform erythroderma with hypotrichosis and hyper-IgE Ichthyosis linearis circumflexa ILC NETH Netherton disease NS GTR C0265962 MeSH D056770 OMIM 256500 SNOMED CT 312514006 2014-03 2020-08-18 Neuroblastoma https://medlineplus.gov/genetics/condition/neuroblastoma descriptionNeuroblastoma is a type of cancer that most often affects children. Neuroblastoma occurs when immature nerve cells called neuroblasts become abnormal and multiply uncontrollably to form a tumor. Most commonly, the tumor originates in the nerve tissue of the adrenal gland located above each kidney. Other common sites for tumors to form include the nerve tissue in the abdomen, chest, neck, or pelvis. Neuroblastoma can spread (metastasize) to other parts of the body such as the bones, liver, or skin.Individuals with neuroblastoma may develop general signs and symptoms such as irritability, fever, tiredness (fatigue), pain, loss of appetite, weight loss, or diarrhea. More specific signs and symptoms depend on the location of the tumor and where it has spread. A tumor in the abdomen can cause abdominal swelling. A tumor in the chest may lead to difficulty breathing. A tumor in the neck can cause nerve damage known as Horner syndrome, which leads to drooping eyelids, small pupils, decreased sweating, and red skin. Tumor metastasis to the bone can cause bone pain, bruises, pale skin, or dark circles around the eyes. Tumors in the backbone can press on the spinal cord and cause weakness, numbness, or paralysis in the arms or legs. A rash of bluish or purplish bumps that look like blueberries indicates that the neuroblastoma has spread to the skin.In addition, neuroblastoma tumors can release hormones that may cause other signs and symptoms such as high blood pressure, rapid heartbeat, flushing of the skin, and sweating. In rare instances, individuals with neuroblastoma may develop opsoclonus myoclonus syndrome, which causes rapid eye movements and jerky muscle motions. This condition occurs when the immune system malfunctions and attacks nerve tissue.Neuroblastoma occurs most often in children before age 5 and rarely occurs in adults. ad Autosomal dominant n Not inherited KIF1B https://medlineplus.gov/genetics/gene/kif1b PHOX2B https://medlineplus.gov/genetics/gene/phox2b MYCN https://medlineplus.gov/genetics/gene/mycn ALK https://medlineplus.gov/genetics/gene/alk BARD1 https://www.ncbi.nlm.nih.gov/gene/580 ERBB2 https://www.ncbi.nlm.nih.gov/gene/2064 LMO1 https://www.ncbi.nlm.nih.gov/gene/4004 1 https://medlineplus.gov/genetics/chromosome/1 11 https://medlineplus.gov/genetics/chromosome/11 NB GTR C2751681 GTR C2751682 MeSH D009447 OMIM 256700 OMIM 613013 OMIM 613014 SNOMED CT 432328008 SNOMED CT 87364003 2011-03 2020-09-08 Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart https://medlineplus.gov/genetics/condition/neurodevelopmental-disorder-with-or-without-anomalies-of-the-brain-eye-or-heart descriptionNeurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH) is a neurological disorder that can also affect many other body systems. This condition primarily affects neurological development, causing intellectual disability, delayed development of speech and motor skills (such as sitting and walking), or autism spectrum disorder, which is a condition that affects communication and social interaction. Some affected individuals have additional neurological features, such as weak muscle tone (hypotonia), behavioral problems, and seizures.NEDBEH can affect development of many other parts of the body. Some affected individuals have abnormalities of brain structures, such as the tissue that connects the left and right halves of the brain (the corpus callosum), a tissue called white matter, the fluid-filled cavities (ventricles) near the center of the brain, or a structure at the back of the brain known as the cerebellar vermis. Eye abnormalities that can occur include a gap or hole in one of the structures of the eye (coloboma), underdevelopment (hypoplasia) or breakdown (atrophy) of the nerves that carry information from the eyes to the brain (optic nerves), or unusually small eyeballs (microphthalmia). These eye problems can cause vision impairment. Some affected individuals have heart defects, most commonly ventricular septal defect, which is a hole in the muscular wall (septum) that separates the right and left sides of the heart's lower chambers.Less commonly, other systems are affected in NEDBEH, including the kidneys and inner ear. Problems with the inner ear can lead to hearing impairment (sensorineural hearing loss).The signs and symptoms in some people with NEDBEH resemble those of another condition known as CHARGE syndrome; however, people with NEDBEH do not have changes in the gene associated with CHARGE syndrome. ad Autosomal dominant RERE https://medlineplus.gov/genetics/gene/rere NEDBEH RERE-related neurodevelopmental syndrome GTR C5567477 MeSH D001927 MeSH D008607 OMIM 616975 2018-08 2020-08-18 Neuroferritinopathy https://medlineplus.gov/genetics/condition/neuroferritinopathy descriptionNeuroferritinopathy is a disorder in which iron gradually accumulates in the brain. Certain brain regions that help control movement (basal ganglia) are particularly affected. People with neuroferritinopathy have progressive problems with movement that begin at about age 40. These movement problems can include involuntary jerking motions (chorea), rhythmic shaking (tremor), difficulty coordinating movements (ataxia), or uncontrolled tensing of muscles (dystonia). Symptoms of the disorder may be more apparent on one side of the body than on the other. Affected individuals may also have difficulty swallowing (dysphagia) and speaking (dysarthria).Intelligence is unaffected in most people with neuroferritinopathy, but some individuals develop a gradual decline in thinking and reasoning abilities (dementia). Personality changes such as reduced inhibitions and difficulty controlling emotions may also occur as the disorder progresses. ad Autosomal dominant FTL https://medlineplus.gov/genetics/gene/ftl Basal ganglia disease, adult-onset Ferritin-related neurodegeneration Hereditary ferritinopathy NBIA3 Neurodegeneration with brain iron accumulation 3 GTR C1853578 MeSH D001796 OMIM 606159 SNOMED CT 699299001 2008-07 2020-08-18 Neurofibromatosis type 1 https://medlineplus.gov/genetics/condition/neurofibromatosis-type-1 descriptionNeurofibromatosis type 1 is a condition characterized by changes in skin coloring (pigmentation) and the growth of tumors along nerves in the skin, brain, and other parts of the body. The signs and symptoms of this condition vary widely among affected people.Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.Most adults with neurofibromatosis type 1 develop neurofibromas, which are noncancerous (benign) tumors that are usually located on or just under the skin. These tumors may also occur in nerves near the spinal cord or along nerves elsewhere in the body. Some people with neurofibromatosis type 1 develop cancerous tumors that grow along nerves. These tumors, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumors. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumors and cancer of blood-forming tissue (leukemia).During childhood, benign growths called Lisch nodules often appear in the colored part of the eye (the iris). Lisch nodules do not interfere with vision. Some affected individuals also develop tumors that grow along the nerve leading from the eye to the brain (the optic nerve). These tumors, which are called optic gliomas, may lead to reduced vision or total vision loss. In some cases, optic gliomas have no effect on vision.Additional signs and symptoms of neurofibromatosis type 1 vary, but they can include high blood pressure (hypertension), short stature, an unusually large head (macrocephaly), and skeletal abnormalities such as an abnormal curvature of the spine (scoliosis). Although most people with neurofibromatosis type 1 have normal intelligence, learning disabilities and attention-deficit/hyperactivity disorder (ADHD) occur frequently in affected individuals. ad Autosomal dominant NF1 https://medlineplus.gov/genetics/gene/nf1 Neurofibromatosis 1 NF1 Peripheral neurofibromatosis Recklinghausen disease, nerve Von Recklinghausen disease GTR C0027831 ICD-10-CM Q85.0 ICD-10-CM Q85.00 ICD-10-CM Q85.01 MeSH D009456 OMIM 162200 SNOMED CT 92824003 2007-03 2021-04-20 Neurofibromatosis type 2 https://medlineplus.gov/genetics/condition/neurofibromatosis-type-2 descriptionNeurofibromatosis type 2 is a disorder characterized by the growth of noncancerous tumors in the nervous system. The most common tumors associated with neurofibromatosis type 2 are called vestibular schwannomas. These growths develop along the nerve that carries information from the inner ear to the brain (the auditory nerve). Tumors that form on the membrane that covers the brain and spinal cord (meninges) are also common in neurofibromatosis type 2. These tumors are called meningiomas. Tumors can also occur on other nerves or tissues in the brain or spinal cord in people with this condition.The signs and symptoms of neurofibromatosis type 2 usually appear during adolescence or in a person's early twenties, although they can begin at any age. The most frequent early symptoms of vestibular schwannomas are hearing loss, ringing in the ears (tinnitus), and problems with balance. Less commonly, vestibular schwannomas cause facial weakness or paralysis. In most cases, these tumors occur in both ears (bilaterally) by age 30. If tumors develop elsewhere in the nervous system, signs and symptoms vary according to their location. Complications of tumor growth can include changes in vision, numbness or weakness in the arms or legs, and fluid buildup in the brain. Some people with neurofibromatosis type 2 also develop clouding of the lens (cataracts) in one or both eyes, often beginning in childhood. ad Autosomal dominant NF2 https://medlineplus.gov/genetics/gene/nf2 BANF Bilateral acoustic neurofibromatosis Central neurofibromatosis Familial acoustic neuromas Neurofibromatosis 2 Neurofibromatosis type 2 merlin Neurofibromatosis type II NF2 Schwannoma, acoustic, bilateral GTR C0027832 ICD-10-CM Q85.0 ICD-10-CM Q85.00 ICD-10-CM Q85.02 ICD-10-CM Q85.03 MeSH D016518 OMIM 101000 SNOMED CT 92503002 2007-03 2022-12-09 Neuromyelitis optica https://medlineplus.gov/genetics/condition/neuromyelitis-optica descriptionNeuromyelitis optica is an autoimmune disorder that affects the nerves of the eyes and the central nervous system, which includes the brain and spinal cord. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. In neuromyelitis optica, the autoimmune attack causes inflammation of the nerves, and the resulting damage leads to the signs and symptoms of the condition.Neuromyelitis optica is characterized by optic neuritis, which is inflammation of the nerve that carries information from the eye to the brain (optic nerve). Optic neuritis causes eye pain and vision loss, which can occur in one or both eyes.Neuromyelitis optica is also characterized by transverse myelitis, which is inflammation of the spinal cord. The inflammation associated with transverse myelitis damages the spinal cord, causing a lesion that often extends the length of three or more bones of the spine (vertebrae). In addition, myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses, can be damaged. Transverse myelitis causes weakness, numbness, and paralysis of the arms and legs. Other effects of spinal cord damage can include disturbances in sensations, loss of bladder and bowel control, uncontrollable hiccupping, and nausea. In addition, muscle weakness may make breathing difficult and can cause life-threatening respiratory failure in people with neuromyelitis optica.There are two forms of neuromyelitis optica, the relapsing form and the monophasic form. The relapsing form is most common. This form is characterized by recurrent episodes of optic neuritis and transverse myelitis. These episodes can be months or years apart, and there is usually partial recovery between episodes. However, most affected individuals eventually develop permanent muscle weakness and vision impairment that persist even between episodes. For unknown reasons, approximately nine times more women than men have the relapsing form. The monophasic form, which is less common, causes a single episode of neuromyelitis optica that can last several months. People with this form of the condition can also have lasting muscle weakness or paralysis and vision loss. This form affects men and women equally. The onset of either form of neuromyelitis optica can occur anytime from childhood to adulthood, although the condition most frequently begins in a person's forties.Approximately one-quarter of individuals with neuromyelitis optica have signs or symptoms of another autoimmune disorder such as myasthenia gravis, systemic lupus erythematosus, or Sjögren syndrome. Some scientists believe that a condition described in Japanese patients as optic-spinal multiple sclerosis (or opticospinal multiple sclerosis) that affects the nerves of the eyes and central nervous system is the same as neuromyelitis optica. u Pattern unknown Devic disease Devic neuromyelitis optica Devic syndrome Devic's disease Optic-spinal MS Opticospinal MS ICD-10-CM G36.0 MeSH D009471 OMIM 600308 SNOMED CT 25044007 2012-04 2020-08-18 Neuropathy, ataxia, and retinitis pigmentosa https://medlineplus.gov/genetics/condition/neuropathy-ataxia-and-retinitis-pigmentosa descriptionNeuropathy, ataxia, and retinitis pigmentosa (NARP) is a condition that causes a variety of signs and symptoms that mainly affect the nervous system. The condition typically begins in childhood or early adulthood, and the signs and symptoms usually worsen over time. Most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have vision loss caused by changes in the light-sensitive tissue that lines the back of the eye (the retina). In some cases, the vision loss results from a condition called retinitis pigmentosa. This eye disease causes the light-sensing cells of the retina gradually to deteriorate.Learning disabilities and developmental delays are often seen in children with NARP, and older individuals with this condition may experience a loss of intellectual function (dementia). Other features of NARP include seizures, hearing loss, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). These signs and symptoms vary among affected individuals. m mitochondrial MT-ATP6 https://medlineplus.gov/genetics/gene/mt-atp6 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna NARP NARP syndrome Neurogenic muscle weakness, ataxia, and retinitis pigmentosa Neuropathy, ataxia, and retinitis pigmentos GTR C1328349 ICD-10-CM E88.49 MeSH D028361 OMIM 551500 SNOMED CT 237984008 2006-11 2020-09-08 Neutral lipid storage disease with myopathy https://medlineplus.gov/genetics/condition/neutral-lipid-storage-disease-with-myopathy descriptionNeutral lipid storage disease with myopathy is a condition in which fats (lipids) are stored abnormally in organs and tissues throughout the body. People with this condition have muscle weakness (myopathy) due to the accumulation of fats in muscle tissue. Other features of this condition may include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), and type 2 diabetes (the most common form of diabetes). Signs and symptoms of neutral lipid storage disease with myopathy vary greatly among affected individuals. ar Autosomal recessive PNPLA2 https://medlineplus.gov/genetics/gene/pnpla2 Neutral lipid storage disease without ichthyosis NLSDM GTR C1853136 MeSH D008052 OMIM 610717 SNOMED CT 699315005 2008-11 2020-08-18 Nicolaides-Baraitser syndrome https://medlineplus.gov/genetics/condition/nicolaides-baraitser-syndrome descriptionNicolaides-Baraitser syndrome is a condition that affects many body systems. Affected individuals can have a wide variety of signs and symptoms, but the most common are sparse scalp hair, small head size (microcephaly), distinct facial features, short stature, prominent finger joints, unusually short fingers and toes (brachydactyly), recurrent seizures (epilepsy), and moderate to severe intellectual disability with impaired language development.In people with Nicolaides-Baraitser syndrome, the sparse scalp hair is often noticeable in infancy. The amount of hair decreases over time, but the growth rate and texture of the hair that is present is normal. Affected adults generally have very little hair. In rare cases, the amount of scalp hair increases over time. As affected individuals age, their eyebrows may become less full, but their eyelashes almost always remain normal. At birth, the hair on the face may be abnormally thick (hypertrichosis) but thins out over time.Most affected individuals grow slowly, resulting in short stature and microcephaly. Sometimes, growth before birth is unusually slow.The characteristic facial features of people with Nicolaides-Baraitser syndrome include a triangular face, deep-set eyes, a thin nasal bridge, wide nostrils, a pointed nasal tip, and a thick lower lip. Many affected individuals have a lack of fat under the skin (subcutaneous fat) of the face, which may cause premature wrinkling. Throughout their bodies, people with Nicolaides-Baraitser syndrome may have pale skin with veins that are visible on the skin surface due to the lack of subcutaneous fat.In people with Nicolaides-Baraitser syndrome, a lack of subcutaneous fat in the hands makes the finger joints appear larger than normal. Over time, the fingertips become broad and oval shaped. Additionally, there is a wide gap between the first and second toes (known as a sandal gap).Most people with Nicolaides-Baraitser syndrome have epilepsy, which often begins in infancy. Affected individuals can experience multiple seizure types, and the seizures can be difficult to control with medication.Almost everyone with Nicolaides-Baraitser syndrome has moderate to severe intellectual disability. Early developmental milestones, such as crawling and walking, are often normally achieved, but further development is limited, and language development is severely impaired. At least one-third of affected individuals never develop speech, while others lose their verbal communication over time. People with this condition are often described as having a happy demeanor and being very friendly, although they can exhibit moments of aggression and temper tantrums.Other signs and symptoms of Nicolaides-Baraitser syndrome include an inflammatory skin disorder called eczema. About half of individuals with Nicolaides-Baraitser syndrome have a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Some affected individuals have dental abnormalities such as widely spaced teeth, delayed eruption of teeth, and absent teeth (hypodontia). Most affected males have undescended testes (cryptorchidism) and females may have underdeveloped breasts. Nearly half of individuals with Nicolaides-Baraitser syndrome have feeding problems. ad Autosomal dominant SMARCA2 https://medlineplus.gov/genetics/gene/smarca2 NBS NCBRS GTR C1303073 MeSH D000015 MeSH D008607 OMIM 601358 SNOMED CT 401046009 2015-12 2020-08-18 Niemann-Pick disease https://medlineplus.gov/genetics/condition/niemann-pick-disease descriptionNiemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the basis of genetic cause and the signs and symptoms of the condition.Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood.The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood. ar Autosomal recessive SMPD1 https://medlineplus.gov/genetics/gene/smpd1 NPC1 https://medlineplus.gov/genetics/gene/npc1 NPC2 https://medlineplus.gov/genetics/gene/npc2 Lipid histiocytosis Neuronal cholesterol lipidosis Neuronal lipidosis NPD Sphingomyelin lipidosis Sphingomyelin/cholesterol lipidosis Sphingomyelinase deficiency GTR C0028064 GTR C0220756 GTR C0268242 GTR C0268243 GTR C0268247 GTR C1843366 GTR C2675646 GTR C3179455 ICD-10-CM E75.24 ICD-10-CM E75.240 ICD-10-CM E75.241 ICD-10-CM E75.242 ICD-10-CM E75.243 ICD-10-CM E75.248 ICD-10-CM E75.249 MeSH D009542 OMIM 257200 OMIM 257220 OMIM 607616 OMIM 607625 SNOMED CT 18927009 SNOMED CT 39390005 SNOMED CT 52165006 SNOMED CT 58459009 SNOMED CT 66751000 SNOMED CT 73399005 2008-01 2025-04-04 Nijmegen breakage syndrome https://medlineplus.gov/genetics/condition/nijmegen-breakage-syndrome descriptionNijmegen breakage syndrome is a condition characterized by short stature, an unusually small head size (microcephaly), distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, intellectual disability, and other health problems.People with this condition typically grow slowly during infancy and early childhood. After this period of slow growth, affected individuals grow at a normal rate but remain shorter than their peers. Microcephaly is apparent from birth in the majority of affected individuals. The head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Individuals with Nijmegen breakage syndrome have distinctive facial features that include a sloping forehead, a prominent nose, large ears, a small jaw, and outside corners of the eyes that point upward (upslanting palpebral fissures). These facial features typically become apparent by age 3.People with Nijmegen breakage syndrome have a malfunctioning immune system (immunodeficiency) with abnormally low levels of immune system proteins called immunoglobulin G (IgG) and immunoglobulin A (IgA). Affected individuals also have a shortage of immune system cells called T cells. The immune system abnormalities increase susceptibility to recurrent infections, such as bronchitis, pneumonia, sinusitis, and other infections affecting the upper respiratory tract and lungs.Individuals with Nijmegen breakage syndrome have an increased risk of developing cancer, most commonly a cancer of immune system cells called non-Hodgkin lymphoma. About half of individuals with Nijmegen breakage syndrome develop non-Hodgkin lymphoma, usually before age 15. Other cancers seen in people with Nijmegen breakage syndrome include brain tumors such as medulloblastoma and glioma, and a cancer of muscle tissue called rhabdomyosarcoma. People with Nijmegen breakage syndrome are 50 times more likely to develop cancer than people without this condition.Intellectual development is normal in most people with this condition for the first year or two of life, but then development becomes delayed. Skills decline over time, and most affected children and adults have mild to moderate intellectual disability.Most affected woman have premature ovarian failure and do not begin menstruation by age 16 (primary amenorrhea) or have infrequent menstrual periods. Most women with Nijmegen breakage syndrome are unable to have biological children (infertile). ar Autosomal recessive NBN https://medlineplus.gov/genetics/gene/nbn Ataxia-telangiectasia variant 1 Berlin breakage syndrome Microcephaly, normal intelligence and immunodeficiency Seemanova syndrome GTR C0398791 MeSH D049932 OMIM 251260 SNOMED CT 234638009 2011-04 2025-04-03 Nonbullous congenital ichthyosiform erythroderma https://medlineplus.gov/genetics/condition/nonbullous-congenital-ichthyosiform-erythroderma descriptionNonbullous congenital ichthyosiform erythroderma (NBCIE) is a condition that mainly affects the skin. Many infants with this condition are born with a tight, clear sheath covering their skin called a collodion membrane. Constriction by the membrane may cause the lips and eyelids to be turned out so the inner surface is exposed. The collodion membrane is usually shed during the first few weeks of life. Following shedding of the collodion membrane, the skin is red (erythroderma) and covered with fine, white scales (ichthyosis). Infants with NBCIE may develop infections, an excessive loss of fluids (dehydration), and respiratory problems early in life.Some people with NBCIE have thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma), decreased or absent sweating (anhidrosis), and abnormal nails (nail dystrophy). In severe cases, there is an absence of hair growth (alopecia) in certain areas, often affecting the scalp and eyebrows.In individuals with NBCIE, some of the skin problems may improve by adulthood. Life expectancy is normal in people with NBCIE. ar Autosomal recessive ABCA12 https://medlineplus.gov/genetics/gene/abca12 ALOX12B https://medlineplus.gov/genetics/gene/alox12b ALOXE3 https://medlineplus.gov/genetics/gene/aloxe3 CASP14 https://www.ncbi.nlm.nih.gov/gene/23581 CYP4F22 https://www.ncbi.nlm.nih.gov/gene/126410 CERS3 https://www.ncbi.nlm.nih.gov/gene/204219 PNPLA1 https://www.ncbi.nlm.nih.gov/gene/285848 NIPAL4 https://www.ncbi.nlm.nih.gov/gene/348938 Congenital ichthyosiform erythroderma Congenital nonbullous ichthyosiform erythroderma NBCIE NBIE NCIE Nonbullous ichthyosiform erythroderma GTR C1832550 GTR C1858133 GTR C2677065 GTR C3539888 GTR C3554349 GTR C3554355 GTR C3888093 GTR C4310621 MeSH D016113 OMIM 242100 OMIM 601277 OMIM 604777 OMIM 606545 OMIM 612281 OMIM 615023 OMIM 615024 OMIM 617320 SNOMED CT 267372009 2017-07 2020-08-18 Nonketotic hyperglycinemia https://medlineplus.gov/genetics/condition/nonketotic-hyperglycinemia descriptionNonketotic hyperglycinemia is a disorder characterized by abnormally high levels of a molecule called glycine in the body (hyperglycinemia). The excess glycine builds up in tissues and organs, particularly the brain. Affected individuals have serious neurological problems.Nonketotic hyperglycinemia has two forms, the severe form and the attenuated form. Both forms usually begin shortly after birth, although in some cases, signs and symptoms can begin in the first few months of life. Only the attenuated form begins later in infancy. The forms are distinguished by the seriousness of the signs and symptoms. Severe nonketotic hyperglycinemia is more common. Affected babies experience extreme sleepiness (lethargy) that worsens over time and can lead to coma. They can also have weak muscle tone (hypotonia) and life-threatening breathing problems in the first days or weeks of life. Most children who survive these early signs and symptoms develop feeding difficulties, abnormal muscle stiffness (spasticity), profound intellectual disability and seizures that are difficult to control. Most affected children do not achieve normal developmental milestones, such as drinking from a bottle, sitting up, or grabbing objects, and they may lose any acquired skills over time.The signs and symptoms of the attenuated form of nonketotic hyperglycinemia are similar to, but milder than, those of the severe form of the condition. Children with attenuated nonketotic hyperglycinemia typically reach developmental milestones, although the skills they achieve vary widely. Despite delayed development, many affected children eventually learn to walk and are able to interact with others, often using sign language. Some affected children develop seizures; if present, seizures are usually mild and can be treated. Other features can include spasticity, involuntary jerking movements (chorea), or hyperactivity.Individuals with nonketotic hyperglycinemia can also have certain changes in the brain, which can be seen using magnetic resonance imaging (MRI). For example, in children with the severe form of the condition, the tissue that connects the left and right halves of the brain (the corpus callosum) is smaller than average. ar Autosomal recessive GLDC https://medlineplus.gov/genetics/gene/gldc AMT https://medlineplus.gov/genetics/gene/amt Glycine encephalopathy NKH Non-ketotic hyperglycinemia GTR C0751748 ICD-10-CM E72.51 MeSH D020158 OMIM 605899 SNOMED CT 237939006 SNOMED CT 303092001 SNOMED CT 51097006 SNOMED CT 63329001 SNOMED CT 67845009 2020-05 2020-08-18 Nonsyndromic aplasia cutis congenita https://medlineplus.gov/genetics/condition/nonsyndromic-aplasia-cutis-congenita descriptionNonsyndromic aplasia cutis congenita is a condition in which babies are born with localized areas of missing skin (lesions). These areas resemble ulcers or open wounds, although they are sometimes already healed at birth. Lesions most commonly occur on the top of the head (skull vertex), although they can be found on the torso or limbs. In some cases, the bone and other tissues under the skin defect are also underdeveloped.Most affected babies have a single lesion. The lesions vary in size and can be differently shaped: some are round or oval, others rectangular, and still others star-shaped. They usually leave a scar after they heal. When the scalp is involved, there may be an absence of hair growth (alopecia) in the affected area.When the underlying bone and other tissues are involved, affected individuals are at higher risk of infections. If these severe defects occur on the head, the membrane that covers the brain (the dura mater) may be exposed, and life-threatening bleeding may occur from nearby vessels.Skin lesions are typically the only feature of nonsyndromic aplasia cutis congenita, although other skin problems and abnormalities of the bones and other tissues occur rarely. However, the characteristic skin lesions can occur as one of many symptoms in other conditions, including Johanson-Blizzard syndrome and Adams-Oliver syndrome. These instances are described as syndromic aplasia cutis congenita. n Not inherited ad Autosomal dominant ar Autosomal recessive ACC Congenital absence of skin on scalp Congenital defect of the skull and scalp Congenital ulcer of the newborn Scalp defect congenital GTR C0282160 MeSH D004476 OMIM 107600 SNOMED CT 239152005 SNOMED CT 838362006 2013-08 2020-08-18 Nonsyndromic congenital nail disorder 10 https://medlineplus.gov/genetics/condition/nonsyndromic-congenital-nail-disorder-10 descriptionNonsyndromic congenital nail disorder 10 is a condition that affects the fingernails and toenails. Affected individuals have extremely thick nails (onychauxis) that separate from the underlying nail bed (onycholysis) and can appear claw-like. Some fingers and toes may be missing part of the nail (hyponychia).In affected individuals, the nails are often abnormal from birth. However, the abnormalities may not be noticeable until later in childhood because the nails tend to grow more slowly than normal.Individuals with nonsyndromic congenital nail disorder 10 do not have any other health problems related to the condition. ar Autosomal recessive FZD6 https://medlineplus.gov/genetics/gene/fzd6 Claw-shaped nails Nail disorder, nonsyndromic congenital, 10 NDNC10 Onychauxis, hyponychia, and onycholysis GTR C0406443 ICD-10-CM L60.1 ICD-10-CM Q84.5 MeSH D054039 OMIM 161050 SNOMED CT 75789001 SNOMED CT 88103004 2017-03 2023-08-21 Nonsyndromic dilated cardiomyopathy https://medlineplus.gov/genetics/condition/nonsyndromic-dilated-cardiomyopathy descriptionDilated cardiomyopathy is a form of heart disease in which the heart (cardiac) muscle becomes thin and enlarged (dilated). The dilation, which typically starts in the lower left chamber of the heart (left ventricle), makes it harder for the heart to pump blood to the rest of the body. Dilated cardiomyopathy is called nonsyndromic dilated cardiomyopathy when it cannot be explained by other causes, such as a heart attack or damage to the valves of the heart, and is not associated with signs and symptoms that affect other parts of the body.  The signs and symptoms of nonsyndromic dilated cardiomyopathy vary among affected individuals, even among members of the same family. The signs and symptoms typically begin in mid-adulthood, but they can occur at any time from infancy to late adulthood. Affected individuals may have a sensation of fluttering or pounding in the chest (palpitations); shortness of breath, especially when lying down or during physical activity; fatigue; and swelling of the legs and feet. Affected individuals may also have episodes of dizziness or fainting (syncope). Over time, people with nonsyndromic dilated cardiomyopathy may develop life-threatening complications, which can include abnormal heart rhythms (arrhythmias) and heart failure. Although uncommon, sudden death can occur in people with nonsyndromic dilated cardiomyopathy, even if they have no other symptoms of the condition. ad Autosomal dominant+New variant x X-linked ar Autosomal recessive LMNA https://medlineplus.gov/genetics/gene/lmna SCN5A https://medlineplus.gov/genetics/gene/scn5a MYH7 https://medlineplus.gov/genetics/gene/myh7 TTN https://medlineplus.gov/genetics/gene/ttn TNNI3 https://medlineplus.gov/genetics/gene/tnni3 DES https://medlineplus.gov/genetics/gene/des LDB3 https://medlineplus.gov/genetics/gene/ldb3 TNNT2 https://medlineplus.gov/genetics/gene/tnnt2 ACTC1 https://www.ncbi.nlm.nih.gov/gene/70 FLII https://www.ncbi.nlm.nih.gov/gene/2314 FLNC https://www.ncbi.nlm.nih.gov/gene/2318 NRAP https://www.ncbi.nlm.nih.gov/gene/4892 RPL3L https://www.ncbi.nlm.nih.gov/gene/6123 TNNC1 https://www.ncbi.nlm.nih.gov/gene/7134 TPM1 https://www.ncbi.nlm.nih.gov/gene/7168 VCL https://www.ncbi.nlm.nih.gov/gene/7414 BAG5 https://www.ncbi.nlm.nih.gov/gene/9529 BAG3 https://www.ncbi.nlm.nih.gov/gene/9531 PLEKHM2 https://www.ncbi.nlm.nih.gov/gene/23207 PPA2 https://www.ncbi.nlm.nih.gov/gene/27068 TNNI3K https://www.ncbi.nlm.nih.gov/gene/51086 TBX20 https://www.ncbi.nlm.nih.gov/gene/57057 JPH2 https://www.ncbi.nlm.nih.gov/gene/57158 PRDM16 https://www.ncbi.nlm.nih.gov/gene/63976 NEXN https://www.ncbi.nlm.nih.gov/gene/91624 MYLK3 https://www.ncbi.nlm.nih.gov/gene/91807 RBM20 https://www.ncbi.nlm.nih.gov/gene/282996 LMOD2 https://www.ncbi.nlm.nih.gov/gene/442721 MYZAP https://www.ncbi.nlm.nih.gov/gene/100820829 DCM Familial dilated cardiomyopathy Idiopathic dilated cardiomyopathy GTR C0007193 GTR C1832243 GTR C1832244 GTR C1832680 GTR C1834481 GTR C1854159 GTR C1858154 GTR C1858763 GTR C1969639 GTR C2678474 GTR C2678475 GTR C2678476 GTR C2750091 GTR C2750995 GTR C2751084 GTR C3150681 GTR C3150958 GTR C3151293 GTR C3160720 GTR C3808935 GTR C5679590 GTR C5700078 GTR C5979868 ICD-10-CM I42.0 MeSH D002311 OMIM 115200 OMIM 302045 OMIM 600884 OMIM 601154 OMIM 601493 OMIM 601494 OMIM 604145 OMIM 604288 OMIM 604765 OMIM 605362 OMIM 605582 OMIM 606685 OMIM 607482 OMIM 607487 OMIM 608569 OMIM 609909 OMIM 609915 OMIM 611407 OMIM 611878 OMIM 611879 OMIM 611880 OMIM 612158 OMIM 612877 OMIM 613172 OMIM 613252 OMIM 613424 OMIM 613426 OMIM 613694 OMIM 613697 OMIM 613881 OMIM 614672 OMIM 615184 OMIM 615235 OMIM 615248 OMIM 615396 SNOMED CT 52029003 2025-11 2025-12-04 Nonsyndromic hearing loss https://medlineplus.gov/genetics/condition/nonsyndromic-hearing-loss descriptionNonsyndromic hearing loss is a partial or total loss of hearing that is not associated with other signs and symptoms. In contrast, syndromic hearing loss occurs with signs and symptoms affecting other parts of the body.Nonsyndromic hearing loss can be classified in several different ways. One common way is by the condition's pattern of inheritance: autosomal dominant (DFNA), autosomal recessive (DFNB), X-linked (DFNX), or mitochondrial (which does not have a special designation). Each of these types of hearing loss includes multiple subtypes. DFNA, DFNB, and DFNX subtypes are numbered in the order in which they were first described. For example, DFNA1 was the first type of autosomal dominant nonsyndromic hearing loss to be identified.The characteristics of nonsyndromic hearing loss vary among the different types. Hearing loss can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The term "deafness" is often used to describe severe-to-profound hearing loss. Hearing loss can be stable, or it may be progressive, becoming more severe as a person gets older. Particular types of nonsyndromic hearing loss show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones.Most forms of nonsyndromic hearing loss are described as sensorineural, which means they are associated with a permanent loss of hearing caused by damage to structures in the inner ear. The inner ear processes sound and sends the information to the brain in the form of electrical nerve impulses. Less commonly, nonsyndromic hearing loss is described as conductive, meaning it results from changes in the middle ear. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic hearing loss, particularly a type called DFNX2, involve changes in both the inner ear and the middle ear. This combination is called mixed hearing loss.Depending on the type, nonsyndromic hearing loss can become apparent at any time from infancy to old age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual. ar Autosomal recessive ad Autosomal dominant x X-linked m mitochondrial COL11A2 https://medlineplus.gov/genetics/gene/col11a2 MYO7A https://medlineplus.gov/genetics/gene/myo7a CDH23 https://medlineplus.gov/genetics/gene/cdh23 GJB2 https://medlineplus.gov/genetics/gene/gjb2 GJB6 https://medlineplus.gov/genetics/gene/gjb6 GJB3 https://medlineplus.gov/genetics/gene/gjb3 KCNQ4 https://medlineplus.gov/genetics/gene/kcnq4 WFS1 https://medlineplus.gov/genetics/gene/wfs1 TECTA https://medlineplus.gov/genetics/gene/tecta POU3F4 https://medlineplus.gov/genetics/gene/pou3f4 STRC https://medlineplus.gov/genetics/gene/strc SLC26A4 https://medlineplus.gov/genetics/gene/slc26a4 ACTG1 https://medlineplus.gov/genetics/gene/actg1 DSPP https://medlineplus.gov/genetics/gene/dspp MT-TS1 https://medlineplus.gov/genetics/gene/mt-ts1 PRPS1 https://medlineplus.gov/genetics/gene/prps1 BSND https://medlineplus.gov/genetics/gene/bsnd MYH9 https://medlineplus.gov/genetics/gene/myh9 TBC1D24 https://medlineplus.gov/genetics/gene/tbc1d24 ADCY1 https://www.ncbi.nlm.nih.gov/gene/107 COL4A6 https://www.ncbi.nlm.nih.gov/gene/1288 CRYM https://www.ncbi.nlm.nih.gov/gene/1428 GSDME https://www.ncbi.nlm.nih.gov/gene/1687 COCH https://www.ncbi.nlm.nih.gov/gene/1690 DIAPH1 https://www.ncbi.nlm.nih.gov/gene/1729 EPS8 https://www.ncbi.nlm.nih.gov/gene/2059 EYA4 https://www.ncbi.nlm.nih.gov/gene/2070 ESRRB https://www.ncbi.nlm.nih.gov/gene/2103 HGF https://www.ncbi.nlm.nih.gov/gene/3082 TNC https://www.ncbi.nlm.nih.gov/gene/3371 KARS1 https://www.ncbi.nlm.nih.gov/gene/3735 MET https://www.ncbi.nlm.nih.gov/gene/4233 MT-CO1 https://www.ncbi.nlm.nih.gov/gene/4512 MT-RNR1 https://www.ncbi.nlm.nih.gov/gene/4549 MYO6 https://www.ncbi.nlm.nih.gov/gene/4646 OTOG https://www.ncbi.nlm.nih.gov/gene/5011 SERPINB6 https://www.ncbi.nlm.nih.gov/gene/5269 POU4F3 https://www.ncbi.nlm.nih.gov/gene/5459 RDX https://www.ncbi.nlm.nih.gov/gene/5962 USH1C https://www.ncbi.nlm.nih.gov/gene/7394 OTOF https://www.ncbi.nlm.nih.gov/gene/9381 TJP2 https://www.ncbi.nlm.nih.gov/gene/9414 HOMER2 https://www.ncbi.nlm.nih.gov/gene/9455 RIPOR2 https://www.ncbi.nlm.nih.gov/gene/9750 OSBPL2 https://www.ncbi.nlm.nih.gov/gene/9885 CIB2 https://www.ncbi.nlm.nih.gov/gene/10518 TRIOBP https://www.ncbi.nlm.nih.gov/gene/11078 P2RX2 https://www.ncbi.nlm.nih.gov/gene/22953 CLDN14 https://www.ncbi.nlm.nih.gov/gene/23562 PTPRQ https://www.ncbi.nlm.nih.gov/gene/23628 SMPX https://www.ncbi.nlm.nih.gov/gene/23676 WHRN https://www.ncbi.nlm.nih.gov/gene/25861 GPSM2 https://www.ncbi.nlm.nih.gov/gene/29899 MYO15A https://www.ncbi.nlm.nih.gov/gene/51168 DCDC2 https://www.ncbi.nlm.nih.gov/gene/51473 CABP2 https://www.ncbi.nlm.nih.gov/gene/51475 CLIC5 https://www.ncbi.nlm.nih.gov/gene/53405 MYO3A https://www.ncbi.nlm.nih.gov/gene/53904 TSPEAR https://www.ncbi.nlm.nih.gov/gene/54084 BDP1 https://www.ncbi.nlm.nih.gov/gene/55814 DIABLO https://www.ncbi.nlm.nih.gov/gene/56616 TMPRSS3 https://www.ncbi.nlm.nih.gov/gene/64699 PCDH15 https://www.ncbi.nlm.nih.gov/gene/65217 NARS2 https://www.ncbi.nlm.nih.gov/gene/79731 MYH14 https://www.ncbi.nlm.nih.gov/gene/79784 GRHL2 https://www.ncbi.nlm.nih.gov/gene/79977 ESPN https://www.ncbi.nlm.nih.gov/gene/83715 ELMOD3 https://www.ncbi.nlm.nih.gov/gene/84173 PNPT1 https://www.ncbi.nlm.nih.gov/gene/87178 TMC1 https://www.ncbi.nlm.nih.gov/gene/117531 TMEM132E https://www.ncbi.nlm.nih.gov/gene/124842 LOXHD1 https://www.ncbi.nlm.nih.gov/gene/125336 GIPC3 https://www.ncbi.nlm.nih.gov/gene/126326 OTOA https://www.ncbi.nlm.nih.gov/gene/146183 CCDC50 https://www.ncbi.nlm.nih.gov/gene/152137 MARVELD2 https://www.ncbi.nlm.nih.gov/gene/153562 SYNE4 https://www.ncbi.nlm.nih.gov/gene/163183 LRTOMT https://www.ncbi.nlm.nih.gov/gene/220074 LHFPL5 https://www.ncbi.nlm.nih.gov/gene/222662 SLC17A8 https://www.ncbi.nlm.nih.gov/gene/246213 MSRB3 https://www.ncbi.nlm.nih.gov/gene/253827 TMIE https://www.ncbi.nlm.nih.gov/gene/259236 OTOGL https://www.ncbi.nlm.nih.gov/gene/283310 TPRN https://www.ncbi.nlm.nih.gov/gene/286262 ILDR1 https://www.ncbi.nlm.nih.gov/gene/286676 SLC26A5 https://www.ncbi.nlm.nih.gov/gene/375611 CEACAM16 https://www.ncbi.nlm.nih.gov/gene/388551 GRXCR1 https://www.ncbi.nlm.nih.gov/gene/389207 MIR96 https://www.ncbi.nlm.nih.gov/gene/407053 PJVK https://www.ncbi.nlm.nih.gov/gene/494513 GRXCR2 https://www.ncbi.nlm.nih.gov/gene/643226 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Isolated deafness Nonsyndromic deafness Nonsyndromic hearing impairment Nonsyndromic hearing loss and deafness GTR C0236038 GTR C5680182 GTR CN043651 ICD-10-CM H90 ICD-10-CM H90.0 ICD-10-CM H90.1 ICD-10-CM H90.11 ICD-10-CM H90.12 ICD-10-CM H90.2 ICD-10-CM H90.3 ICD-10-CM H90.4 ICD-10-CM H90.41 ICD-10-CM H90.42 ICD-10-CM H90.5 ICD-10-CM H90.6 ICD-10-CM H90.7 ICD-10-CM H90.71 ICD-10-CM H90.72 ICD-10-CM H90.8 ICD-10-CM H91.8 ICD-10-CM H91.8X ICD-10-CM H91.8X1 ICD-10-CM H91.8X2 ICD-10-CM H91.8X3 ICD-10-CM H91.8X9 ICD-10-CM H91.9 ICD-10-CM H91.90 ICD-10-CM H91.91 ICD-10-CM H91.92 ICD-10-CM H91.93 MeSH D003638 MeSH D034381 OMIM 220290 OMIM 300030 OMIM 300066 OMIM 300614 OMIM 300914 OMIM 304400 OMIM 304500 OMIM 580000 OMIM 600060 OMIM 600101 OMIM 600316 OMIM 600652 OMIM 600965 OMIM 600974 OMIM 600994 OMIM 601071 OMIM 601316 OMIM 601317 OMIM 601369 OMIM 601386 OMIM 601412 OMIM 601543 OMIM 601544 OMIM 601868 OMIM 602092 OMIM 602459 OMIM 603010 OMIM 603098 OMIM 603629 OMIM 603720 OMIM 604060 OMIM 604717 OMIM 605192 OMIM 606346 OMIM 606705 OMIM 607084 OMIM 607197 OMIM 607239 OMIM 607821 OMIM 607841 OMIM 608394 OMIM 609006 OMIM 609823 OMIM 610265 SNOMED CT 343087000 SNOMED CT 44057004 SNOMED CT 48758008 SNOMED CT 60700002 SNOMED CT 8531006 SNOMED CT 95820000 SNOMED CT 95821001 2016-01 2025-03-03 Nonsyndromic holoprosencephaly https://medlineplus.gov/genetics/condition/nonsyndromic-holoprosencephaly descriptionNonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family.Nonsyndromic holoprosencephaly can be grouped into four types according to the degree of brain division. From most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In the most severe forms of nonsyndromic holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe nonsyndromic holoprosencephaly die before birth or soon after. In the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). The life expectancy of these affected individuals varies depending on the severity of symptoms.People with nonsyndromic holoprosencephaly often have a small head (microcephaly), although they can develop a buildup of fluid in the brain (hydrocephalus) that causes increased head size (macrocephaly). Other features may include an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip), one central front tooth instead of two (a single maxillary central incisor), and a flat nasal bridge. The eyeballs may be abnormally small (microphthalmia) or absent (anophthalmia).Some individuals with nonsyndromic holoprosencephaly have a distinctive pattern of facial features, including a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). In general, the severity of facial features is directly related to the severity of the brain abnormalities. However, individuals with mildly affected facial features can have severe brain abnormalities. Some people do not have apparent structural brain abnormalities but have some of the facial features associated with this condition. These individuals are considered to have a form of the disorder known as microform holoprosencephaly and are typically identified after the birth of a severely affected family member.Most people with nonsyndromic holoprosencephaly have developmental delay and intellectual disability. Affected individuals also frequently have a malfunctioning pituitary gland, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. Most commonly, people with nonsyndromic holoprosencephaly and pituitary dysfunction develop diabetes insipidus, a condition that disrupts the balance between fluid intake and urine excretion. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature, heart rate, and breathing. The sense of smell may be diminished (hyposmia) or completely absent (anosmia) if the part of the brain that processes smells is underdeveloped or missing. ad Autosomal dominant PTCH1 https://medlineplus.gov/genetics/gene/ptch1 SHH https://medlineplus.gov/genetics/gene/shh SIX3 https://medlineplus.gov/genetics/gene/six3 ZIC2 https://medlineplus.gov/genetics/gene/zic2 TGIF1 https://medlineplus.gov/genetics/gene/tgif1 FGF8 https://medlineplus.gov/genetics/gene/fgf8 GLI2 https://www.ncbi.nlm.nih.gov/gene/2736 NODAL https://www.ncbi.nlm.nih.gov/gene/4838 CRIPTO https://www.ncbi.nlm.nih.gov/gene/6997 FOXH1 https://www.ncbi.nlm.nih.gov/gene/8928 DISP1 https://www.ncbi.nlm.nih.gov/gene/84976 Holoprosencephaly sequence Isolated holoprosencephaly Isolated HPE Non-syndromic, non-chromosomal holoprosencephaly Non-syndromic, non-chromosomal HPE Nonsyndromic HPE GTR C0079541 ICD-10-CM Q04.2 MeSH D016142 OMIM 142945 OMIM 142946 OMIM 157170 OMIM 236100 OMIM 605934 OMIM 609408 OMIM 609637 OMIM 610828 OMIM 610829 SNOMED CT 253136007 SNOMED CT 253137003 SNOMED CT 253138008 SNOMED CT 30915001 2010-09 2023-08-21 Nonsyndromic paraganglioma https://medlineplus.gov/genetics/condition/nonsyndromic-paraganglioma descriptionParaganglioma is a type of noncancerous (benign) tumor that occurs in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. Paragangliomas are usually found in the head, neck, or torso. However, a type of paraganglioma known as pheochromocytoma develops in the adrenal glands. Adrenal glands are located on top of each kidney and produce hormones in response to stress. Most people with paraganglioma develop only one tumor in their lifetime.Some people develop a paraganglioma or pheochromocytoma as part of a hereditary syndrome that may affect other organs and tissues in the body. However, the tumors often are not associated with any syndromes, in which case the condition is called nonsyndromic paraganglioma or pheochromocytoma.Pheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Although most sympathetic paragangliomas are pheochromocytomas, some are found outside the adrenal glands, usually in the abdomen, and are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.Most paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.Although most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma. ad Autosomal dominant KIF1B https://medlineplus.gov/genetics/gene/kif1b VHL https://medlineplus.gov/genetics/gene/vhl RET https://medlineplus.gov/genetics/gene/ret SDHD https://medlineplus.gov/genetics/gene/sdhd SDHB https://medlineplus.gov/genetics/gene/sdhb SDHA https://medlineplus.gov/genetics/gene/sdha TMEM127 https://medlineplus.gov/genetics/gene/tmem127 Chemodectoma GTR C0031511 MeSH D010235 OMIM 171300 SNOMED CT 716857003 2011-09 2023-11-08 Noonan syndrome https://medlineplus.gov/genetics/condition/noonan-syndrome descriptionNoonan syndrome is a condition that affects many areas of the body. It is characterized by mildly unusual facial features, short stature, heart defects, bleeding problems, skeletal malformations, and many other signs and symptoms.People with Noonan syndrome have distinctive facial features such as a deep groove in the area between the nose and mouth (philtrum), widely spaced eyes that are usually pale blue or blue-green in color, and low-set ears that are rotated backward. Affected individuals may have a high arch in the roof of the mouth (high-arched palate), poor teeth alignment, and a small lower jaw (micrognathia). Many children with Noonan syndrome have a short neck, and both children and adults may have excess neck skin (also called webbing) and a low hairline at the back of the neck.Between 50 and 70 percent of individuals with Noonan syndrome have short stature. At birth, they are usually a normal length and weight, but growth slows over time. Abnormal levels of growth hormone, a protein that is necessary for the normal growth of the body's bones and tissues, may contribute to the slow growth.Individuals with Noonan syndrome often have either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some affected people may also have an abnormal side-to-side curvature of the spine (scoliosis).Most people with Noonan syndrome have some form of critical congenital heart disease. The most common heart defect in these individuals is a narrowing of the valve that controls blood flow from the heart to the lungs (pulmonary valve stenosis). Some have hypertrophic cardiomyopathy, which enlarges and weakens the heart muscle.A variety of bleeding disorders have been associated with Noonan syndrome. Some affected individuals have excessive bruising, nosebleeds, or prolonged bleeding following injury or surgery. Rarely, women with Noonan syndrome who have a bleeding disorder have excessive bleeding during menstruation (menorrhagia) or childbirth.Adolescent males with Noonan syndrome typically experience delayed puberty. They go through puberty starting at age 13 or 14 and have a reduced pubertal growth spurt that results in shortened stature. Most males with Noonan syndrome have undescended testes (cryptorchidism), which may contribute to infertility (inability to father a child) later in life. Females with Noonan syndrome can experience delayed puberty but most have normal puberty and fertility.Noonan syndrome can cause a variety of other signs and symptoms. Most children diagnosed with Noonan syndrome have normal intelligence, but a few have special educational needs, and some have intellectual disability. Some affected individuals have vision or hearing problems. Affected infants may have feeding problems, which typically get better by age 1 or 2 years. Infants with Noonan syndrome may be born with puffy hands and feet caused by a buildup of fluid (lymphedema), which can go away on its own. Older individuals can also develop lymphedema, usually in the ankles and lower legs.Some people with Noonan syndrome develop cancer, particularly those involving the blood-forming cells (leukemia). It has been estimated that children with Noonan syndrome have an eightfold increased risk of developing leukemia or other cancers over age-matched peers.Noonan syndrome is one of a group of related conditions, collectively known as RASopathies. These conditions all have similar signs and symptoms and are caused by changes in the same cell signaling pathway. In addition to Noonan syndrome, the RASopathies include cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, Legius syndrome, and Noonan syndrome with multiple lentigines. ad Autosomal dominant PTPN11 https://medlineplus.gov/genetics/gene/ptpn11 KRAS https://medlineplus.gov/genetics/gene/kras SOS1 https://medlineplus.gov/genetics/gene/sos1 RAF1 https://medlineplus.gov/genetics/gene/raf1 BRAF https://medlineplus.gov/genetics/gene/braf MAP2K1 https://medlineplus.gov/genetics/gene/map2k1 NRAS https://medlineplus.gov/genetics/gene/nras RIT1 https://medlineplus.gov/genetics/gene/rit1 LZTR1 https://medlineplus.gov/genetics/gene/lztr1 RASA2 https://www.ncbi.nlm.nih.gov/gene/5922 RRAS https://www.ncbi.nlm.nih.gov/gene/6237 SOS2 https://www.ncbi.nlm.nih.gov/gene/6655 A2ML1 https://www.ncbi.nlm.nih.gov/gene/144568 Familial Turner syndrome Female pseudo-Turner syndrome Male Turner syndrome Noonan's syndrome Noonan-Ehmke syndrome NS Pseudo-Ullrich-Turner syndrome Turner phenotype with normal karyotype Turner syndrome in female with X chromosome Turner-like syndrome Ullrich-Noonan syndrome GTR C0028326 GTR C1853120 GTR C1854469 GTR C1860991 GTR C1969057 GTR C2750732 GTR C3150970 GTR C3809233 GTR C4225280 GTR C4225282 GTR C4551602 ICD-10-CM Q87.1 MeSH D009634 OMIM 163950 OMIM 605275 OMIM 609942 OMIM 610733 OMIM 611553 OMIM 613224 OMIM 613706 OMIM 615355 OMIM 616559 OMIM 616564 SNOMED CT 205824006 2016-05 2020-08-18 Noonan syndrome with multiple lentigines https://medlineplus.gov/genetics/condition/noonan-syndrome-with-multiple-lentigines descriptionNoonan syndrome with multiple lentigines (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. As the condition name suggests, Noonan syndrome with multiple lentigines is very similar to a condition called Noonan syndrome, and it can be difficult to tell the two disorders apart in early childhood. However, the features of these two conditions differ later in life. The characteristic features of Noonan syndrome with multiple lentigines include brown skin spots called lentigines that are similar to freckles, heart defects, widely spaced eyes (ocular hypertelorism), a sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and short stature. These features vary, however, even among affected individuals in the same family. Not all individuals with Noonan syndrome with multiple lentigines have all the characteristic features of this condition.The lentigines seen in Noonan syndrome with multiple lentigines typically first appear in mid-childhood, mostly on the face, neck, and upper body. Affected individuals may have thousands of small dark brown skin spots by the time they reach puberty. Unlike freckles, the appearance of lentigines has nothing to do with sun exposure. In addition to lentigines, people with this condition may have lighter brown skin spots called café-au-lait spots. Café-au-lait spots tend to develop before the lentigines, appearing within the first year of life in most affected people.Of the people with Noonan syndrome with multiple lentigines who have heart defects, about 80 percent have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. The hypertrophic cardiomyopathy most often affects the lower left chamber of the heart (the left ventricle). Up to 20 percent of people with Noonan syndrome with multiple lentigines who have heart problems have a narrowing of the artery from the heart to the lungs (pulmonary stenosis).People with Noonan syndrome with multiple lentigines can have a distinctive facial appearance. In addition to ocular hypertelorism, affected individuals may have droopy eyelids (ptosis), thick lips, and low-set ears. Affected individuals also usually have an abnormal appearance of the chest; they either have pectus excavatum or pectus carinatum.At birth, people with Noonan syndrome with multiple lentigines are typically of normal weight and height, but in some, growth slows over time. This slow growth results in affected individuals being shorter than average, although less than half of people with Noonan syndrome with multiple lentigines have significantly short stature.Other signs and symptoms of Noonan syndrome with multiple lentigines include hearing loss caused by abnormalities in the inner ear (sensorineural deafness), mild intellectual disability, and extra folds of skin on the back of the neck. Affected males often have genital abnormalities, which can include undescended testes (cryptorchidism) and a urethra that opens on the underside of the penis (hypospadias). These abnormalities may reduce the ability to have biological children (decreased fertility). Females with Noonan syndrome with multiple lentigines may have poorly developed ovaries and delayed puberty.Noonan syndrome with multiple lentigines is one of a group of related conditions collectively known as RASopathies. These conditions all have similar signs and symptoms and are caused by changes in the same cell signaling pathway. In addition to Noonan syndrome with multiple lentigines, the RASopathies include Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Legius syndrome. ad Autosomal dominant PTPN11 https://medlineplus.gov/genetics/gene/ptpn11 RAF1 https://medlineplus.gov/genetics/gene/raf1 BRAF https://medlineplus.gov/genetics/gene/braf MAP2K1 https://medlineplus.gov/genetics/gene/map2k1 Cardio-cutaneous syndrome Cardiomyopathic lentiginosis Diffuse lentiginosis Lentiginosis profusa LEOPARD syndrome Moynahan syndrome Multiple lentigines syndrome NSML Progressive cardiomyopathic lentiginosis GTR C0175704 GTR C1969056 GTR C3150971 GTR C4551484 MeSH D044542 OMIM 151100 OMIM 611554 OMIM 613707 SNOMED CT 111306001 SNOMED CT 45167004 2016-06 2022-02-22 Norrie disease https://medlineplus.gov/genetics/condition/norrie-disease descriptionNorrie disease is an inherited eye disorder that leads to blindness in male infants at birth or soon after birth. It causes abnormal development of the retina, the layer of sensory cells that detect light and color, with masses of immature retinal cells accumulating at the back of the eye. As a result, the pupils appear white when light is shone on them, a sign called leukocoria. The irises (colored portions of the eyes) or the entire eyeballs may shrink and deteriorate during the first months of life, and cataracts (cloudiness in the lens of the eye) may eventually develop.About 30 percent of individuals with Norrie disease develop progressive hearing loss, and 30 to 50 percent of people affected experience developmental delays in motor skills such as sitting up and walking. Other problems may include mild to moderate intellectual disability, often with psychosis, and abnormalities that can affect circulation, breathing, digestion, excretion, or reproduction. xr X-linked recessive NDP https://medlineplus.gov/genetics/gene/ndp Anderson-Warburg syndrome Atrophia bulborum hereditaria Congenital progressive oculo-acoustico-cerebral degeneration Episkopi blindness Fetal iritis syndrome Norrie syndrome Norrie's disease Norrie-Warburg syndrome Oligophrenia microphthalmus Pseudoglioma congenita Whitnall-Norman syndrome GTR C0266526 MeSH D015785 OMIM 310600 SNOMED CT 15228007 2020-03 2020-08-18 North American Indian childhood cirrhosis https://medlineplus.gov/genetics/condition/north-american-indian-childhood-cirrhosis descriptionNorth American Indian childhood cirrhosis is a rare liver disorder that occurs in children. The liver malfunction causes yellowing of the skin and whites of the eyes (jaundice) in affected infants. The disorder worsens with age, progressively damaging the liver and leading to chronic, irreversible liver disease (cirrhosis) in childhood or adolescence. Unless it is treated with liver transplantation, North American Indian childhood cirrhosis typically causes life-threatening complications including liver failure. ar Autosomal recessive UTP4 https://medlineplus.gov/genetics/gene/utp4 NAIC GTR C1858051 MeSH D008103 OMIM 604901 SNOMED CT 699189004 2011-03 2020-08-18 Obsessive-compulsive disorder https://medlineplus.gov/genetics/condition/obsessive-compulsive-disorder descriptionObsessive-compulsive disorder (OCD) is a mental health condition characterized by features called obsessions and compulsions. Obsessions are intrusive thoughts, mental images, or urges to perform specific actions. While the particular obsessions vary widely, they often include fear of illness or contamination; a desire for symmetry or getting things "just right;" or intrusive thoughts involving religion, sex, or aggression. Compulsions consist of the repetitive performance of certain actions, such as checking or verifying, washing, counting, arranging, acting out specific routines, or seeking assurance. These behaviors are performed to relieve anxiety, rather than to seek pleasure as in other compulsive behaviors like gambling, eating, or sex.While almost everyone experiences obsessive feelings and compulsive behaviors occasionally or in particular contexts, in OCD they take up more than an hour a day and cause problems with work, school, or social life. People with OCD generally experience anxiety and other distress around their need to accommodate their obsessions or compulsions.About half the time, OCD becomes evident in childhood or adolescence, and most other cases appear in early adulthood. It is unusual for OCD to start after age 40. It tends to appear earlier in males, but by adulthood it is slightly more common in females. Affected individuals can experience periods when their symptoms increase or decrease in severity, but the condition usually does not go away completely.Some people with OCD have additional mental health disorders such as generalized anxiety, depression, phobias, panic disorders, or schizophrenia. OCD can also occur in people with other neurological conditions such as Tourette syndrome and similar disorders, traumatic brain injury, stroke, or dementia. u Pattern unknown HTR2A https://www.ncbi.nlm.nih.gov/gene/3356 SLC6A4 https://www.ncbi.nlm.nih.gov/gene/6532 Anancastic neurosis Anankastic neurosis Obsessive-compulsive neurosis OCD GTR C0028768 ICD-10-CM F42 ICD-10-CM F42.2 ICD-10-CM F42.3 ICD-10-CM F42.4 ICD-10-CM F42.8 ICD-10-CM F42.9 MeSH D009771 OMIM 164230 SNOMED CT 191736004 2018-09 2020-08-18 Obstructive sleep apnea https://medlineplus.gov/genetics/condition/obstructive-sleep-apnea descriptionObstructive sleep apnea is a condition in which individuals experience pauses in breathing (apnea) during sleep, which are associated with partial or complete closure of the throat (pper airway). Complete closure can lead to apnea while partial closure allows breathing but decrease the intake of oxygen (hypopnea).Individuals with obstructive sleep apnea may experience interrupted sleep with frequent awakenings and loud snoring. Repeated pauses in breathing lead to episodes of lower-than-normal oxygen levels (hypoxemia) and a buildup of carbon dioxide (hypercapnia) in the bloodstream. Interrupted and poor quality sleep can lead to daytime sleepiness and fatigue, impaired attention and memory, headaches, depression, and sexual dysfunction. Daytime sleepiness leads to a higher risk of motor vehicle accidents in individuals with obstructive sleep apnea. Obstructive sleep apnea is also associated with an increased risk of developing insulin resistance, which is an inability to regulate blood sugar (glucose) levels effectively; high blood pressure (hypertension); heart disease; and stroke. u Pattern unknown Apnea, obstructive Obstructive apnea Obstructive sleep apnea syndrome OSA OSAHS OSAS SAHS Sleep apnea hypopnea syndrome Sleep apnea syndrome, obstructive Sleep apnea, obstructive Sleep apnea/hypopnea syndrome Upper airway resistance sleep apnea syndrome GTR C0520679 ICD-10-CM G47.33 MeSH D020181 OMIM 107650 SNOMED CT 78275009 2018-03 2023-07-26 Ochoa syndrome https://medlineplus.gov/genetics/condition/ochoa-syndrome descriptionOchoa syndrome is a disorder characterized by urinary problems and unusual facial expressions.The urinary problems associated with Ochoa syndrome typically become apparent in early childhood or adolescence. People with this disorder may have difficulty controlling the flow of urine (incontinence), which can lead to bedwetting. Individuals with Ochoa syndrome may be unable to completely empty the bladder, often resulting in vesicoureteral reflux, a condition in which urine backs up into the ducts that normally carry it from each kidney to the bladder (the ureters). Urine may also accumulate in the kidneys (hydronephrosis). Vesicoureteral reflux and hydronephrosis can lead to frequent infections of the urinary tract and kidney inflammation (pyelonephritis), causing damage that may eventually result in kidney failure.Individuals with Ochoa syndrome also exhibit a characteristic frown-like facial grimace when they try to smile or laugh, often described as inversion of facial expression. While this feature may appear earlier than the urinary tract symptoms, perhaps as early as an infant begins to smile, it is often not brought to medical attention.Approximately two-thirds of individuals with Ochoa syndrome also experience problems with bowel function, such as constipation, loss of bowel control, or muscle spasms of the anus. ar Autosomal recessive HPSE2 https://medlineplus.gov/genetics/gene/hpse2 Hydronephrosis with peculiar facial expression Hydronephrosis-inverted smile Inverted smile and occult neuropathic bladder Inverted smile-neurogenic bladder Partial facial palsy with urinary abnormalities UFS Urofacial Ochoa's syndrome Urofacial syndrome GTR C0403555 MeSH D000015 OMIM 236730 SNOMED CT 236533008 2012-03 2020-08-18 Ocular albinism https://medlineplus.gov/genetics/condition/ocular-albinism descriptionOcular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss. xd X-linked dominant ar Autosomal recessive ad Autosomal dominant GPR143 https://medlineplus.gov/genetics/gene/gpr143 Albinism, ocular OA XLOA GTR C0268505 GTR C0342684 GTR C1845069 ICD-10-CM E70.31 ICD-10-CM E70.310 ICD-10-CM E70.311 ICD-10-CM E70.318 ICD-10-CM E70.319 MeSH D016117 OMIM 300500 OMIM 300650 OMIM 606952 SNOMED CT 26399002 SNOMED CT 78642008 2007-07 2020-08-18 Oculocutaneous albinism https://medlineplus.gov/genetics/condition/oculocutaneous-albinism descriptionOculocutaneous albinism is a group of conditions that affect the color of (pigmentation) of the skin, hair, and eyes. Affected individuals typically have very fair skin and white or light-colored hair. Long-term sun exposure greatly increases the risk of skin damage and skin cancers, including an aggressive form of skin cancer called melanoma, in people with this condition. Oculocutaneous albinism also reduces pigmentation of the colored part of the eye (the iris) and the light-sensitive tissue at the back of the eye (the retina). People with this condition usually have vision problems such as reduced sharpness; rapid, involuntary eye movements (nystagmus); eyes that do not point in the same direction (strabismus); and increased sensitivity to light (photophobia).Researchers have identified multiple types of oculocutaneous albinism, which are distinguished by their specific skin, hair, and eye color changes, and by their genetic cause. Oculocutaneous albinism type 1 is characterized by white hair, very pale skin, and light-colored irises. Type 2 is typically less severe than type 1; the skin is usually pale and hair may be light yellow, blond, or light brown. Type 3 causes reddish-brown skin, ginger or red hair, and hazel or brown irises. Type 3 is often associated with milder vision abnormalities than the other forms of oculocutaneous albinism. Type 4 has signs and symptoms similar to those seen in people with type 2.There are several additional, rare types of oculocutaneous albinism. ar Autosomal recessive OCA2 https://medlineplus.gov/genetics/gene/oca2 TYR https://medlineplus.gov/genetics/gene/tyr TYRP1 https://medlineplus.gov/genetics/gene/tyrp1 SLC45A2 https://medlineplus.gov/genetics/gene/slc45a2 MC1R https://medlineplus.gov/genetics/gene/mc1r DCT https://www.ncbi.nlm.nih.gov/gene/1638 LRMDA https://www.ncbi.nlm.nih.gov/gene/83938 SLC24A5 https://www.ncbi.nlm.nih.gov/gene/283652 Albinism, oculocutaneous OCA GTR C0078918 GTR C0268494 GTR C0268495 GTR C0342683 GTR C1847024 GTR C1847836 GTR C3805375 GTR C3808786 GTR C3888401 GTR C4551504 GTR C5436929 ICD-10-CM E70.32 ICD-10-CM E70.320 ICD-10-CM E70.321 ICD-10-CM E70.328 ICD-10-CM E70.329 MeSH D016115 OMIM 113750 OMIM 203100 OMIM 203200 OMIM 203290 OMIM 606574 OMIM 606952 OMIM 615179 OMIM 615312 OMIM 619165 SNOMED CT 11160000 SNOMED CT 26336006 SNOMED CT 63450009 SNOMED CT 63844009 SNOMED CT 6483008 2024-11 2024-11-22 Oculodentodigital dysplasia https://medlineplus.gov/genetics/condition/oculodentodigital-dysplasia descriptionOculodentodigital dysplasia is a condition that affects many parts of the body, particularly the eyes (oculo-), teeth (dento-), and fingers (digital). The signs and symptoms of the condition vary widely among affected individuals. Some features of oculodentodigital dysplasia are evident at birth, while others become apparent with age.People with oculodentodigital dysplasia often have eye abnormalities that can lead to vision loss. These eye problems can include underdeveloped and small eyes (microphthalmia) and clouding of the lenses of the eyes (cataracts). People with oculodentodigital dysplasia may also have a condition called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved. The tooth abnormalities seen in people with oculodentodigital dysplasia often include missing or small teeth, weak enamel, and early tooth loss. The condition can also affect the fingers and toes. Individuals with oculodentodigital dysplasia may have permanently bent fingers (camptodactyly), fingers that are unusually curved (clinodactyly), webbing of the skin (syndactyly) between the fourth and fifth fingers, and syndactyly of the toes,Individuals who have oculodentodigital dysplasia may also have abnormalities of the head and face (craniofacial anomalies), which can include a narrow nose, a small head size (microcephaly), and an opening in the roof of the mouth (cleft palate).Less common features of oculodentodigital dysplasia include sparse hair growth (hypotrichosis); brittle nails; and a skin condition called palmoplantar keratoderma that causes the skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused.Approximately 30 percent of people with oculodentodigital dysplasia experience neurological problems such as a lack of bladder or bowel control (incontinence), difficulty coordinating movements (ataxia), abnormal muscle stiffness (spasticity), and impaired speech (dysarthria). Some affected individuals develop abnormalities of the brain’s white matter that can be detected with medical imaging (leukodystrophy). Hearing loss and heart problems have also been reported in people with oculodentodigital dysplasia. ar Autosomal recessive ad Autosomal dominant+New variant GJA1 https://medlineplus.gov/genetics/gene/gja1 Meyer-Schwickerath syndrome Meyer-Schwickerath-Weyers syndrome Oculo-dento-digital dysplasia Oculodentodigital dysplasia, autosomal recessive Oculodentodigital syndrome Oculodentodigitalis dysplasia Oculodentoosseous dysplasia ODD syndrome ODDD ODDD syndrome ODDD, autosomal recessive ODOD ODOD syndrome ODOD, autosomal recessive Osseous-oculo-dental dysplasia GTR C0812437 MeSH D004476 OMIM 164200 OMIM 257850 SNOMED CT 254138001 SNOMED CT 254139009 SNOMED CT 38215007 2025-03 2025-03-03 Oculofaciocardiodental syndrome https://medlineplus.gov/genetics/condition/oculofaciocardiodental-syndrome descriptionOculofaciocardiodental (OFCD) syndrome is a condition that affects the development of the eyes (oculo-), facial features (facio-), heart (cardio-), and teeth (dental). The eye abnormalities associated with OFCD syndrome can affect one or both eyes. Many people with this condition are born with eyeballs that are abnormally small (microphthalmia). Other eye problems can include clouding of the lens (cataract) and a high risk of glaucoma, an eye disease that increases the pressure in the eye. These abnormalities can lead to vision loss or blindness.People with OFCD syndrome often have a long, narrow face with distinctive facial features, including deep-set eyes, droopy eyelids (ptosis), and a nose with a high bridge and broad tip. Affected individuals may have a split (cleft) in their nose or in the roof of their mouth (cleft palate).Heart defects are another common feature of OFCD syndrome. Babies with this condition may be born with a hole between two chambers of the heart (an atrial or ventricular septal defect) or a leak in one of the valves that controls blood flow through the heart (mitral valve prolapse).Teeth with very large roots (radiculomegaly) are characteristic of OFCD syndrome. Additional dental abnormalities can include the delayed loss of primary (baby) teeth, missing or abnormally small teeth, delayed teething (dentition), misaligned teeth, and defective tooth enamel.Individuals with OFCD syndrome can have additional features, such as skeletal abnormalities (typically affecting the toes), hearing loss, and intellectual disabilities.  xd X-linked dominant BCOR https://medlineplus.gov/genetics/gene/bcor MCOPS2 Microphthalmia, cataracts, radiculomegaly, and septal heart defects Microphthalmia, syndromic 2 Oculo-facio-cardio-dental syndrome OFCD syndrome GTR C1846265 MeSH D008850 MeSH D015785 OMIM 300166 SNOMED CT 699300009 2024-11 2025-03-06 Oculopharyngeal muscular dystrophy https://medlineplus.gov/genetics/condition/oculopharyngeal-muscular-dystrophy descriptionOculopharyngeal muscular dystrophy is a genetic condition characterized by muscle weakness that begins in adulthood, typically after age 40. The term "oculopharyngeal" refers to the eyes (oculo-) and a part of the throat called the pharynx (-pharyngeal). Affected individuals usually first experience weakness of the muscles in both eyelids that causes droopy eyelids (ptosis). Ptosis can worsen over time, causing the eyelid to impair vision, and in some cases, limit eye movement. Along with ptosis, affected individuals develop weakness of the throat muscles that causes difficulty swallowing (dysphagia). Dysphagia begins with dry food, but over time, liquids can also become difficult to swallow. Dysphagia can cause saliva to accumulate and a wet-sounding voice. Many people with oculopharyngeal muscular dystrophy also have weakness and wasting (atrophy) of the tongue. These problems with food intake may cause malnutrition, choking, or a bacterial lung infection called aspiration pneumonia.Individuals with oculopharyngeal muscular dystrophy frequently have weakness in the muscles near the center of the body (proximal muscles), particularly muscles in the shoulders, upper legs, and hips (limb-girdle muscles). The weakness slowly gets worse, and people may need the aid of a cane or a walker. Rarely, affected individuals need wheelchair assistance.Rarely, individuals have a severe form of oculopharyngeal muscular dystrophy with muscle weakness that begins before age 45, and have trouble walking independently by age 60. These individuals often also have disturbances in nerve function (neuropathy), a gradual loss of intellectual functioning (cognitive decline), and psychiatric symptoms such as depression or strongly held false beliefs (delusions). ad Autosomal dominant PABPN1 https://medlineplus.gov/genetics/gene/pabpn1 Dystrophy, oculopharyngeal muscular Muscular dystrophy, oculopharyngeal Oculopharyngeal dystrophy OPMD Progressive muscular dystrophy, oculopharyngeal type GTR C0270952 ICD-10-CM G71.0 MeSH D039141 OMIM 164300 SNOMED CT 77097004 2018-02 2020-08-18 Ohdo syndrome, Maat-Kievit-Brunner type https://medlineplus.gov/genetics/condition/ohdo-syndrome-maat-kievit-brunner-type descriptionThe Maat-Kievit-Brunner type of Ohdo syndrome is a rare condition characterized by intellectual disability and distinctive facial features. It has only been reported in males.The intellectual disability associated with this condition varies from mild to severe, and the development of motor skills (such as sitting, standing, and walking) is delayed. Some affected individuals also have behavioral problems.Distinctive facial features often seen in this condition include a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), prominent cheeks, a broad nasal bridge, a nose with a rounded tip, a large space between the nose and upper lip (a long philtrum), and a narrow mouth. Some affected individuals also have widely set eyes (hypertelorism), an unusually small chin (micrognathia), and small and low-set ears. As people with the condition get older, these facial characteristics become more pronounced and the face becomes more triangular.Other possible signs of this condition include dental problems, weak muscle tone (hypotonia), and hearing loss. xr X-linked recessive MED12 https://medlineplus.gov/genetics/gene/med12 Blepharophimosis-mental retardation syndrome, Maat-Kievit-Brunner type BMRS, MKB type Ohdo syndrome, MKB type X-linked Ohdo syndrome GTR C3698541 MeSH D000015 OMIM 300895 SNOMED CT 699297004 2013-04 2020-08-18 Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant https://medlineplus.gov/genetics/condition/ohdo-syndrome-say-barber-biesecker-young-simpson-variant descriptionThe Say-Barber-Biesecker-Young-Simpson (SBBYS) variant of Ohdo syndrome is a rare condition characterized by genital abnormalities in males, missing or underdeveloped kneecaps (patellae), intellectual disability, distinctive facial features, and abnormalities affecting other parts of the body.Males with the SBBYS variant of Ohdo syndrome typically have undescended testes (cryptorchidism). Females with this condition have normal genitalia.Missing or underdeveloped patellae is the most common skeletal abnormality associated with the SBBYS variant of Ohdo syndrome. Affected individuals also have joint stiffness involving the hips, knees, and ankles that can impair movement. Although joints in the lower body are stiff, joints in the arms and upper body may be unusually loose (lax). Many people with this condition have long thumbs and first (big) toes.The SBBYS variant of Ohdo syndrome is also associated with delayed development and intellectual disability, which are often severe. Many affected infants have weak muscle tone (hypotonia) that leads to breathing and feeding difficulties.The SBBYS variant of Ohdo syndrome is characterized by a mask-like, non-expressive face. Additionally, affected individuals may have distinctive facial features such as prominent cheeks, a broad nasal bridge or a nose with a rounded tip, a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and abnormalities of the tear (lacrimal) glands. About one-third of affected individuals are born with an opening in the roof of the mouth called a cleft palate. The SBBYS variant of Ohdo syndrome can also be associated with heart defects and dental problems. ad Autosomal dominant KAT6B https://medlineplus.gov/genetics/gene/kat6b Blepharophimosis and mental retardation syndrome, Say-Barber/Biesecker/Young-Simpson type Blepharophimosis-intellectual deficit syndrome, Say-Barber/Biesecker/Young-Simpson type BMRS SBBYS Ohdo syndrome, Say-Barber-Biesecker variant Ohdo syndrome, SBBYS variant Say-Barber-Biesecker-Young-Simpson syndrome Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome SBBYS variant of Ohdo syndrome SBBYSS Young-Simpson syndrome GTR C1863557 MeSH D000015 OMIM 603736 SNOMED CT 699298009 2013-02 2020-08-18 Ollier disease https://medlineplus.gov/genetics/condition/ollier-disease descriptionOllier disease is a disorder characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures.The signs and symptoms of Ollier disease may be detectable at birth, although they generally do not become apparent until around the age of 5. Enchondromas develop near the ends of bones, where normal growth occurs, and they frequently stop forming after affected individuals stop growing in early adulthood. As a result of the bone deformities associated with Ollier disease, people with this disorder generally have short stature and underdeveloped muscles.Although the enchondromas associated with Ollier disease start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Ollier disease also have an increased risk of other cancers, such as ovarian cancer or liver cancer.People with Ollier disease usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities.A related disorder called Maffucci syndrome also involves multiple enchondromas but is distinguished by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas). n Not inherited IDH2 https://medlineplus.gov/genetics/gene/idh2 IDH1 https://medlineplus.gov/genetics/gene/idh1 Dyschondroplasia Enchondromatosis Enchondromatosis, multiple, Ollier type Multiple cartilaginous enchondroses Multiple enchondromatosis Ollier's syndrome GTR C0014084 ICD-10-CM Q78.4 MeSH D004687 OMIM 166000 SNOMED CT 268274005 2016-02 2020-08-18 Omenn syndrome https://medlineplus.gov/genetics/condition/omenn-syndrome descriptionOmenn syndrome is an inherited disorder of the immune system (immunodeficiency). Omenn syndrome is one of several forms of severe combined immunodeficiency (SCID), a group of disorders that cause individuals to have virtually no immune protection from bacteria, viruses, and fungi. Individuals with SCID are prone to repeated and persistent infections that can be very serious or life-threatening. Infants with Omenn syndrome typically experience pneumonia and chronic diarrhea. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people.In addition to immunodeficiency, children with Omenn syndrome develop autoimmunity, in which the immune system attacks the body's own tissues and organs. This abnormal immune reaction can cause very red skin (erythroderma), hair loss (alopecia), and an enlarged liver and spleen (hepatosplenomegaly). In addition, affected individuals have enlargement of tissues that produce infection-fighting white blood cells called lymphocytes. These include the thymus, which is a gland located behind the breastbone, and lymph nodes, which are found throughout the body.If not treated in a way that restores immune function, children with Omenn syndrome usually survive only until age 1 or 2. ar Autosomal recessive IL7R https://medlineplus.gov/genetics/gene/il7r RAG1 https://medlineplus.gov/genetics/gene/rag1 RAG2 https://medlineplus.gov/genetics/gene/rag2 CARD11 https://medlineplus.gov/genetics/gene/card11 LIG4 https://www.ncbi.nlm.nih.gov/gene/3981 DCLRE1C https://www.ncbi.nlm.nih.gov/gene/64421 Familial reticuloendotheliosis Histiocytic medullary reticulosis Omenn's syndrome GTR C2700553 ICD-10-CM D81.2 MeSH D016511 OMIM 603554 SNOMED CT 307650006 SNOMED CT 722067005 2017-02 2020-08-18 Ophthalmo-acromelic syndrome https://medlineplus.gov/genetics/condition/ophthalmo-acromelic-syndrome descriptionOphthalmo-acromelic syndrome is a condition that results in malformations of the eyes, hands, and feet. The features of this condition are present from birth. The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). Usually both eyes are similarly affected in this condition, but if only one eye is small or missing, the other eye may have a defect such as a gap or split in its structures (coloboma).The most common hand and foot malformation seen in ophthalmo-acromelic syndrome is missing fingers or toes (oligodactyly). Other frequent malformations include fingers or toes that are fused together (syndactyly) or extra fingers or toes (polydactyly). These skeletal malformations are often described as acromelic, meaning that they occur in the bones that are away from the center of the body. Additional skeletal abnormalities involving the long bones of the arms and legs or the spinal bones (vertebrae) can also occur. Affected individuals may have distinctive facial features, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), or intellectual disability. ar Autosomal recessive SMOC1 https://medlineplus.gov/genetics/gene/smoc1 Anophthalmia-syndactyly Anophthalmia-Waardenburg syndrome Anophthalmos with limb anomalies Anophthalmos-limb anomalies syndrome Microphthalmia with limb anomalies OAS Ophthalmoacromelic syndrome Syndactyly-anophthalmos syndrome Waardenburg anophthalmia syndrome GTR C0599973 MeSH D000853 OMIM 206920 SNOMED CT 703403003 2014-03 2020-08-18 Opioid addiction https://medlineplus.gov/genetics/condition/opioid-addiction descriptionOpioid addiction is a long-lasting (chronic) disease that can cause major health, social, and economic problems. Opioids are a class of drugs that act in the nervous system to produce feelings of pleasure and pain relief. Some opioids are legally prescribed by healthcare providers to manage severe and chronic pain. Commonly prescribed opioids include oxycodone, fentanyl, buprenorphine, methadone, oxymorphone, hydrocodone, codeine, and morphine. Some other opioids, such as heroin, are illegal drugs of abuse.Opioid addiction is characterized by a powerful, compulsive urge to use opioid drugs, even when they are no longer required medically. Opioids have a high potential for causing addiction in some people, even when the medications are prescribed appropriately and taken as directed. Many prescription opioids are misused or diverted to others. Individuals who become addicted may prioritize getting and using these drugs over other activities in their lives, often negatively impacting their professional and personal relationships. It is unknown why some people are more likely to become addicted than others.Opioids change the chemistry of the brain and lead to drug tolerance, which means that over time the dose needs to be increased to achieve the same effect. Taking opioids over a long period of time produces dependence, such that when people stop taking the drug, they have physical and psychological symptoms of withdrawal (such as muscle cramping, diarrhea, and anxiety). Dependence is not the same thing as addiction; although everyone who takes opioids for an extended period will become dependent, only a small percentage also experience the compulsive, continuing need for the drug that characterizes addiction.Opioid addiction can cause life-threatening health problems, including the risk of overdose. Overdose occurs when high doses of opioids cause breathing to slow or stop, leading to unconsciousness and death if the overdose is not treated immediately. Both legal and illegal opioids carry a risk of overdose if a person takes too much of the drug, or if opioids are combined with other drugs (particularly tranquilizers called benzodiazepines). u Pattern unknown COMT https://medlineplus.gov/genetics/gene/comt BDNF https://medlineplus.gov/genetics/gene/bdnf GRIN2A https://medlineplus.gov/genetics/gene/grin2a OPRM1 https://medlineplus.gov/genetics/gene/oprm1 AVPR1A https://www.ncbi.nlm.nih.gov/gene/552 CSNK1E https://www.ncbi.nlm.nih.gov/gene/1454 CYP2B6 https://www.ncbi.nlm.nih.gov/gene/1555 DRD2 https://www.ncbi.nlm.nih.gov/gene/1813 DRD3 https://www.ncbi.nlm.nih.gov/gene/1814 DRD4 https://www.ncbi.nlm.nih.gov/gene/1815 FKBP5 https://www.ncbi.nlm.nih.gov/gene/2289 GABRG1 https://www.ncbi.nlm.nih.gov/gene/2565 GAD1 https://www.ncbi.nlm.nih.gov/gene/2571 GAL https://www.ncbi.nlm.nih.gov/gene/2586 HTR1B https://www.ncbi.nlm.nih.gov/gene/3351 OPRD1 https://www.ncbi.nlm.nih.gov/gene/4985 OPRK1 https://www.ncbi.nlm.nih.gov/gene/4986 OPRL1 https://www.ncbi.nlm.nih.gov/gene/4987 PDYN https://www.ncbi.nlm.nih.gov/gene/5173 ABCB1 https://www.ncbi.nlm.nih.gov/gene/5243 PNOC https://www.ncbi.nlm.nih.gov/gene/5368 Opiate addiction Opiate dependence Opioid dependence GTR C1864733 ICD-10-CM F11.2 ICD-10-CM F11.20 ICD-10-CM F11.21 ICD-10-CM F11.22 ICD-10-CM F11.220 ICD-10-CM F11.221 ICD-10-CM F11.222 ICD-10-CM F11.229 ICD-10-CM F11.23 ICD-10-CM F11.24 ICD-10-CM F11.25 ICD-10-CM F11.250 ICD-10-CM F11.251 ICD-10-CM F11.259 ICD-10-CM F11.28 ICD-10-CM F11.281 ICD-10-CM F11.282 ICD-10-CM F11.288 ICD-10-CM F11.29 MeSH D009293 OMIM 610064 SNOMED CT 288861000119108 SNOMED CT 75544000 2017-11 2024-05-16 Opitz G/BBB syndrome https://medlineplus.gov/genetics/condition/opitz-g-bbb-syndrome descriptionOpitz G/BBB syndrome is a genetic condition that causes several abnormalities along the midline of the body. "G/BBB" represents the first letters of the last names of the families first diagnosed with this disorder and "Opitz" is the last name of the doctor who first described the signs and symptoms. There are two forms of Opitz G/BBB syndrome, X-linked Opitz G/BBB syndrome and autosomal dominant Opitz G/BBB syndrome. The two forms are distinguished by their genetic causes and patterns of inheritance. The signs and symptoms of the two forms are generally the same.Nearly everyone with Opitz G/BBB syndrome has wide-spaced eyes (ocular hypertelorism). Affected individuals commonly have defects of the voice box (larynx), windpipe (trachea), or esophagus. These throat abnormalities can cause difficulty swallowing or breathing, in some cases resulting in recurrent pneumonia or life-threatening breathing problems. A common defect is a gap between the trachea and esophagus (laryngeal cleft) that allows food or fluids to enter the airway. The cleft can vary in size, and infants may struggle to breathe when feeding. Most males with Opitz G/BBB syndrome have genital abnormalities such as the urethra opening on the underside of the penis (hypospadias), undescended testes (cryptorchidism), an underdeveloped scrotum, or a scrotum divided into two lobes (bifid scrotum). These genital abnormalities can lead to problems in the urinary tract.Mild intellectual disability and developmental delay occur in about 50 percent of people with Opitz G/BBB syndrome. Affected individuals have delayed motor skills, such as walking, speech delay, and learning difficulties. Some people with Opitz G/BBB syndrome have features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills. About half of affected individuals also have an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Some have cleft palate without cleft lip. Less common features of Opitz G/BBB syndrome, affecting less than half of people with this disorder, include minor heart defects, an obstruction of the anal opening (imperforate anus), and brain defects such as a small or absent connection between the left and right halves of the brain (corpus callosum). Distinct facial features that may be seen in this disorder include a prominent forehead, widow's peak hairline, flat nasal bridge, thin upper lip, and low-set ears. These features vary among affected individuals, even within the same family. ad Autosomal dominant x X-linked MID1 https://medlineplus.gov/genetics/gene/mid1 SPECC1L https://medlineplus.gov/genetics/gene/specc1l 22 https://medlineplus.gov/genetics/chromosome/22 Hypertelorism with esophageal abnormalities and hypospadias Hypertelorism-hypospadias sydrome Hypospadias-dysphagia syndrome Opitz BBB syndrome Opitz BBB/G syndrome Opitz G syndrome Opitz syndrome Opitz-Frias syndrome GTR C2936904 GTR CN032444 GTR CN263119 MeSH D004062 MeSH D040181 OMIM 145420 OMIM 300000 SNOMED CT 81771002 2015-01 2023-08-22 Optic atrophy type 1 https://medlineplus.gov/genetics/condition/optic-atrophy-type-1 descriptionOptic atrophy type 1 is a condition that often causes slowly worsening vision, usually beginning in childhood. People with optic atrophy type 1 typically experience a narrowing of their field of vision (tunnel vision). Affected individuals gradually lose their sight as their field of vision becomes smaller. Both eyes are usually affected equally, but the severity of the vision loss varies widely, even among affected members of the same family, ranging from nearly normal vision to complete blindness.In addition to vision loss, people with optic atrophy type 1 frequently have problems with color vision (color vision deficiency) that make it difficult or impossible to distinguish between shades of blue and green.In the early stages of the condition, individuals with optic atrophy type 1 experience a progressive loss of certain cells within the retina, which is a specialized light-sensitive tissue that lines the back of the eye. The loss of these cells (known as retinal ganglion cells) is followed by the degeneration (atrophy) of the nerves that relay visual information from the eye to the brain (optic nerves), which results in further vision loss. Atrophy causes these nerves to have an abnormally pale appearance (pallor), which can be seen during an eye examination. ad Autosomal dominant OPA1 https://medlineplus.gov/genetics/gene/opa1 ADOA Autosomal dominant optic atrophy Autosomal dominant optic atrophy Kjer type DOA Dominant optic atrophy Kjer type optic atrophy Kjer's optic atrophy Optic atrophy, autosomal dominant Optic atrophy, hereditary, autosomal dominant Optic atrophy, juvenile Optic atrophy, Kjer type GTR C0338508 ICD-10-CM H47.21 ICD-10-CM H47.211 ICD-10-CM H47.212 ICD-10-CM H47.213 ICD-10-CM H47.219 ICD-10-CM H47.22 MeSH D029241 OMIM 165500 SNOMED CT 2065009 SNOMED CT 838307002 2017-08 2023-11-08 Oral-facial-digital syndrome https://medlineplus.gov/genetics/condition/oral-facial-digital-syndrome descriptionOral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes).Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder.The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability.Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums.Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism).Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome.Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects. xd X-linked dominant ar Autosomal recessive OFD1 https://medlineplus.gov/genetics/gene/ofd1 Dysplasia linguofacialis OFDS Oro-facio-digital syndrome Orodigitofacial dysostosis Orodigitofacial syndrome Orofaciodigital syndrome GTR C0029294 GTR C0406726 GTR C0406727 GTR C0796101 GTR C1510460 GTR C1868118 GTR C2745997 MeSH D009958 OMIM 165590 OMIM 174300 OMIM 252100 OMIM 258850 OMIM 258860 OMIM 258865 OMIM 277170 OMIM 300484 OMIM 311200 OMIM 608518 OMIM 612913 SNOMED CT 52868006 2010-02 2020-08-18 Orthostatic hypotension https://medlineplus.gov/genetics/condition/orthostatic-hypotension descriptionOrthostatic hypotension is a drop in blood pressure that occurs when moving from a lying-down (supine) position to a standing (upright) position. The word "orthostasis" means to stand up, so the condition is defined as low blood pressure (hypotension) that occurs upon standing.When standing up, gravity moves blood from the upper body to the lower limbs. As a result, there is a temporary reduction in the amount of blood in the upper body for the heart to pump (cardiac output), which decreases blood pressure. Normally, the body quickly counteracts the force of gravity and maintains stable blood pressure and blood flow. In most people, this transient drop in blood pressure goes unnoticed. However, this transient orthostatic hypotension can cause lightheadedness that may result in falls and injury, particularly in older adults.The body has difficulty achieving stable blood pressure in people with orthostatic hypotension, resulting in a prolonged drop in blood pressure that occurs within minutes after moving from lying down to standing. The vast majority of people with orthostatic hypotension do not experience symptoms related to the condition; it may be detected incidentally during routine medical testing. When measuring blood pressure, orthostatic hypotension is defined as a decrease in blood pressure by at least 20mmHg systolic or 10mmHg diastolic within 3 minutes of standing.When signs and symptoms of orthostatic hypotension do occur, they are usually the result of a reduction in blood flow (hypoperfusion) to tissues, particularly the brain. Affected individuals may have fatigue, confusion, dizziness, blurred vision, or fainting episodes (syncope). Less frequently, affected individuals can experience muscle pain in the neck and shoulders (known as "coat hanger pain"), lower back pain, or weakness. During an episode of orthostatic hypotension, symptoms are often increased in severity by physical activity, warm temperatures, eating large meals, or standing for long periods of time.In people with orthostatic hypotension, hypoperfusion to other organs contributes to an increased risk of life-threatening health problems, including heart attack or heart failure, a heart rhythm abnormality called atrial fibrillation, stroke, or chronic kidney failure. Additionally, affected individuals may get injured from falls during fainting episodes. n Not inherited Hypotension, orthostatic Hypotension, postural Postural hypotension ICD-10-CM I95.1 MeSH D007024 SNOMED CT 28651003 2019-03 2025-12-03 Osteoarthritis https://medlineplus.gov/genetics/condition/osteoarthritis descriptionOsteoarthritis is a common disease of the joints that primarily occurs in older adults. This condition is characterized by the breakdown of cartilage, the tough but flexible tissue that covers the ends of the bones at the joints and allows smooth joint movements. One or more parts of the body can be affected, most often the hands, shoulders, spine, knees, or hips.Osteoarthritis usually develops slowly, causing pain, stiffness, and restricted movement as the condition gets worse. Areas of bone no longer cushioned by cartilage rub against each other and start to break down. Further damage is caused as the body attempts to repair and rebuild these tissues. The immune system, which plays a role in healing injuries, targets these areas, and its response leads to inflammation of the joint tissues. Abnormal growths of bone (osteophytes) and other tissue can also occur, and may be visible as enlarged joints. Enlargement of the joints of the fingers is especially noticeable.People with osteoarthritis typically experience stiffness following periods of inactivity such as upon awakening or rising from a chair; the stiffness usually improves as they move around. In some affected individuals, the condition never causes major problems. In others, severe osteoarthritis can impair mobility and the ability to perform daily tasks, affecting quality of life and increasing the risk of other health conditions such as cardiovascular disease.Osteoarthritis is most common in middle age or late adulthood, because the cartilage at the joints naturally begins to thin as people age. However, it can occur earlier in life, especially after injuries affecting the joints such as a type of knee injury called an anterior cruciate ligament (ACL) tear. People who are overweight or whose activities are particularly stressful to the joints are also at increased risk of developing osteoarthritis. u Pattern unknown COL11A1 https://medlineplus.gov/genetics/gene/col11a1 GDF5 https://www.ncbi.nlm.nih.gov/gene/8200 NCOA3 https://www.ncbi.nlm.nih.gov/gene/8202 ALDH1A2 https://www.ncbi.nlm.nih.gov/gene/8854 ASTN2 https://www.ncbi.nlm.nih.gov/gene/23245 MCF2L https://www.ncbi.nlm.nih.gov/gene/23263 DOT1L https://www.ncbi.nlm.nih.gov/gene/84444 Arthritis, degenerative Arthropathy Degenerative joint disease Degenerative polyarthritis Hypertrophic arthritis OA Osteoarthritis deformans Osteoarthrosis GTR C3887876 ICD-10-CM M15 ICD-10-CM M15.0 ICD-10-CM M15.4 MeSH D010003 OMIM 140600 OMIM 165720 OMIM 607850 OMIM 610839 OMIM 612400 OMIM 612401 SNOMED CT 396275006 2017-10 2020-08-18 Osteogenesis imperfecta https://medlineplus.gov/genetics/condition/osteogenesis-imperfecta descriptionOsteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. The term "osteogenesis imperfecta" means imperfect bone formation. People with this condition have bones that break (fracture) easily, often from mild trauma or with no apparent cause. Multiple fractures are common, and in severe cases, can occur even before birth. Milder cases may involve only a few fractures over a person's lifetime.There are at least 19 recognized forms of osteogenesis imperfecta, designated type I through type XIX. Several types are distinguished by their signs and symptoms, although their characteristic features overlap. Increasingly, genetic causes are used to define rarer forms of osteogenesis imperfecta. Type I (also known as classic non-deforming osteogenesis imperfecta with blue sclerae) is the mildest form of osteogenesis imperfecta. Type II (also known as perinatally lethal osteogenesis imperfecta) is the most severe. Other types of this condition, including types III (progressively deforming osteogenesis imperfecta) and IV (common variable osteogenesis imperfecta with normal sclerae), have signs and symptoms that fall somewhere between these two extremes.The milder forms of osteogenesis imperfecta, including type I, are characterized by bone fractures during childhood and adolescence that often result from minor trauma, such as falling while learning to walk. Fractures occur less frequently in adulthood. People with mild forms of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera), and about half develop hearing loss in adulthood. Unlike more severely affected individuals, people with type I are usually of normal or near normal height.Other types of osteogenesis imperfecta are more severe, causing frequent bone fractures that are present at birth and result from little or no trauma. Additional features of these types can include blue sclerae of the eyes, short stature, curvature of the spine (scoliosis), joint deformities (contractures), hearing loss, respiratory problems, and a disorder of tooth development called dentinogenesis imperfecta. Mobility can be reduced in affected individuals, and some may use a walker or wheelchair. The most severe forms of osteogenesis imperfecta, particularly type II, can include an abnormally small, fragile rib cage and underdeveloped lungs. Infants with these abnormalities may have life-threatening problems with breathing and can die shortly after birth. xr X-linked recessive ar Autosomal recessive ad Autosomal dominant COL1A1 https://medlineplus.gov/genetics/gene/col1a1 COL1A2 https://medlineplus.gov/genetics/gene/col1a2 FKBP10 https://medlineplus.gov/genetics/gene/fkbp10 BMP1 https://www.ncbi.nlm.nih.gov/gene/649 SERPINH1 https://www.ncbi.nlm.nih.gov/gene/871 SERPINF1 https://www.ncbi.nlm.nih.gov/gene/5176 PPIB https://www.ncbi.nlm.nih.gov/gene/5479 SPARC https://www.ncbi.nlm.nih.gov/gene/6678 WNT1 https://www.ncbi.nlm.nih.gov/gene/7471 CRTAP https://www.ncbi.nlm.nih.gov/gene/10491 MBTPS2 https://www.ncbi.nlm.nih.gov/gene/51360 TMEM38B https://www.ncbi.nlm.nih.gov/gene/55151 TENT5A https://www.ncbi.nlm.nih.gov/gene/55603 P3H1 https://www.ncbi.nlm.nih.gov/gene/64175 CREB3L1 https://www.ncbi.nlm.nih.gov/gene/90993 SP7 https://www.ncbi.nlm.nih.gov/gene/121340 IFITM5 https://www.ncbi.nlm.nih.gov/gene/387733 Brittle bone disease Fragilitas ossium OI Vrolik disease GTR C0023931 GTR C0029434 GTR C0268362 GTR C0268363 GTR C1850169 GTR C1853162 GTR C1970458 GTR C2931093 GTR C3151211 GTR C3151218 GTR C3151433 GTR C3279564 GTR C3553887 GTR C3554428 GTR C3808844 GTR C4015610 GTR C4225301 GTR C4693736 GTR C4746956 ICD-10-CM Q78.0 MeSH D010013 OMIM 166200 OMIM 166210 OMIM 166220 OMIM 259420 OMIM 259440 OMIM 301014 OMIM 610682 OMIM 610915 OMIM 610967 OMIM 610968 OMIM 613848 OMIM 613849 OMIM 613982 OMIM 614856 OMIM 615066 OMIM 615220 OMIM 616229 OMIM 616507 OMIM 617952 SNOMED CT 205496008 SNOMED CT 205497004 SNOMED CT 254110009 SNOMED CT 385482004 SNOMED CT 385483009 SNOMED CT 78314001 SNOMED CT 86470003 2019-11 2020-08-18 Osteoglophonic dysplasia https://medlineplus.gov/genetics/condition/osteoglophonic-dysplasia descriptionOsteoglophonic dysplasia is a condition characterized by abnormal bone growth that leads to severe head and face (craniofacial) abnormalities, short stature, and other features. The term osteoglophonic refers to the bones (osteo-) having distinctive hollowed-out (-glophonic) areas that appear as lesions or holes on x-ray images. These lesions typically affect the long bones of the arms and legs.In people with osteoglophonic dysplasia, bones in the skull often fuse together too early (craniosynostosis). The craniosynostosis seen in people with this disorder may give the head a flat appearance or a "cloverleaf" shape, depending on which bones fuse first. Characteristic facial features in people with osteoglophonic dysplasia include a prominent forehead, widely spaced eyes (hypertelorism) that are prominent (proptosis), low-set ears, a flattening of the bridge of the nose and  the middle of the face (midface hypoplasia), a protruding jaw (prognathism), a high arch in the roof of the mouth (a high-arched palate), and a short neck. People with this condition usually have no visible teeth because the teeth never emerge from the jaw (clinical anodontia). In addition, the gums are often overgrown (hypertrophic gingiva).Most people with osteoglophonic dysplasia have hollowed lesions in the long bones. These lesions are likely non-ossifying fibromas, which are benign (noncancerous) bone tumors made up of fibrous tissue that does not harden into bone. The lesions appear early in life and gradually increase in size and number during childhood. Later in life, the lesions may get smaller or go away once the bones have stopped growing. Individuals with osteoglophonic dysplasia can also have short, bowed legs and arms. They also have flat feet; overlapping toes; and short, broad hands and fingers.Infants with osteoglophonic dysplasia often experience failure to thrive, which means they do not gain weight and grow at the expected rate. Affected individuals can experience episodes of increased body temperature and excessive sweating.Some people with osteoglophonic dysplasia develop pyloric stenosis, which is a narrowing of the opening from the stomach into the small intestines. Others can develop inguinal hernia, in which the contents of the abdomen causes a soft out-pouching through the lower abdominal wall.The life expectancy of people with osteoglophonic dysplasia depends on the extent of the craniofacial abnormalities. People with abnormalities that obstruct the air passages and affect the mouth and teeth may have respiratory problems and difficulty eating and drinking. Despite the skull abnormalities, intelligence is generally not affected in people with this disorder, but speech delays can occur. ad Autosomal dominant+Inherited or new variant FGFR1 https://medlineplus.gov/genetics/gene/fgfr1 Fairbank-Keats syndrome FGFR1-related osteoglophonic dysplasia OGD Osteoglophonic dwarfism GTR C0432283 ICD-10-CM MeSH D004392 OMIM 166250 SNOMED CT 254144002 2024-05 2024-05-06 Osteopetrosis https://medlineplus.gov/genetics/condition/osteopetrosis descriptionOsteopetrosis is a bone disease that makes bone tissue abnormally compact and dense and also prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant or autosomal recessive. The different types of the disorder can also be distinguished by the severity of their signs and symptoms.Autosomal dominant osteopetrosis (ADO), which is also called Albers-Schönberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In affected people with no symptoms, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. In individuals with ADO who develop signs and symptoms, the major features of the condition include multiple bone fractures after minor injury, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.Autosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis. ad Autosomal dominant ar Autosomal recessive TNFRSF11A https://medlineplus.gov/genetics/gene/tnfrsf11a TCIRG1 https://medlineplus.gov/genetics/gene/tcirg1 CLCN7 https://medlineplus.gov/genetics/gene/clcn7 ITGB3 https://medlineplus.gov/genetics/gene/itgb3 CA2 https://www.ncbi.nlm.nih.gov/gene/760 TNFSF11 https://www.ncbi.nlm.nih.gov/gene/8600 PLEKHM1 https://www.ncbi.nlm.nih.gov/gene/9842 OSTM1 https://www.ncbi.nlm.nih.gov/gene/28962 Congenital osteopetrosis Marble bone disease Osteopetroses GTR C0345407 GTR C1843330 GTR C1850126 GTR C1850127 GTR C1968603 GTR C1969093 GTR C1969106 GTR C2676766 GTR C3179239 ICD-10-CM Q78.2 MeSH D010022 OMIM 166600 OMIM 259700 OMIM 259710 OMIM 259720 OMIM 259730 OMIM 600329 OMIM 611490 OMIM 611497 OMIM 612301 SNOMED CT 1926006 SNOMED CT 254121000 SNOMED CT 254122007 2010-09 2023-03-13 Osteoporosis-pseudoglioma syndrome https://medlineplus.gov/genetics/condition/osteoporosis-pseudoglioma-syndrome descriptionOsteoporosis-pseudoglioma syndrome is a rare condition characterized by severe thinning of the bones (osteoporosis) and eye abnormalities that lead to vision loss. In people with this condition, osteoporosis is usually recognized in early childhood. It is caused by a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple bone fractures, including in the bones that form the spine (vertebrae). Multiple fractures can cause collapse of the affected vertebrae (compressed vertebrae), abnormal side-to-side curvature of the spine (scoliosis), short stature, and limb deformities. Decreased bone mineral density can also cause softening or thinning of the skull (craniotabes).Most affected individuals have impaired vision at birth or by early infancy and are blind by young adulthood. Vision problems are usually caused by one of several eye conditions, grouped together as pseudoglioma, that affect the light-sensitive tissue at the back of the eye (the retina), although other eye conditions have been identified in affected individuals. Pseudogliomas are so named because, on examination, the conditions resemble an eye tumor known as a retinal glioma.Rarely, people with osteoporosis-pseudoglioma syndrome have additional signs or symptoms such as mild intellectual disability, weak muscle tone (hypotonia), abnormally flexible joints, or seizures. ar Autosomal recessive LRP5 https://medlineplus.gov/genetics/gene/lrp5 OPPG Osteogenesis imperfecta, ocular form GTR C0432252 MeSH D010024 OMIM 259770 SNOMED CT 254112001 2013-01 2020-08-18 Otopalatodigital syndrome type 1 https://medlineplus.gov/genetics/condition/otopalatodigital-syndrome-type-1 descriptionOtopalatodigital syndrome type 1 is a disorder primarily involving abnormalities in skeletal development. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 2, frontometaphyseal dysplasia, Melnick-Needles syndrome, and terminal osseous dysplasia. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers or toes (digits).Otopalatodigital syndrome type 1 is usually the mildest of the otopalatodigital spectrum disorders. People with this condition usually have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; and a broad, flat nose. Affected individuals have abnormalities of the fingers and toes, such as blunt, square-shaped (spatulate) fingertips; shortened thumbs and big toes; unusually long second toes; and a wide gap between the first and second toes (known as a sandal gap). Affected individuals also have hearing loss.Infants with otopalatodigital syndrome type 1 may be born with an opening in the roof of the mouth (a cleft palate). Individuals with this condition often have fewer teeth than normal (hypodontia). They may have mild abnormal curvature (bowing) of their limbs, and limited range of motion in some joints. People with otopalatodigital syndrome type 1 may be somewhat shorter than other members of their family.Females with otopalatodigital syndrome type 1 often have more variable signs and symptoms compared to affected males, with females typically having fewer signs and symptoms. x X-linked FLNA https://medlineplus.gov/genetics/gene/flna Cranioorodigital syndrome Faciopalatoosseous syndrome FPO OPD syndrome, type 1 Oto-palato-digital syndrome, type I Taybi syndrome GTR C0265251 MeSH D010009 OMIM 311300 SNOMED CT 54036001 2007-11 2021-07-28 Otopalatodigital syndrome type 2 https://medlineplus.gov/genetics/condition/otopalatodigital-syndrome-type-2 descriptionOtopalatodigital syndrome type 2 is a disorder primarily involving abnormalities in skeletal development. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, frontometaphyseal dysplasia, Melnick-Needles syndrome, and terminal osseous dysplasia. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers or toes (digits). Otopalatodigital syndrome type 2 also tends to cause problems in other areas of the body, such as the brain and heart.People with otopalatodigital syndrome type 2 have characteristic facial features including wide-set and downward-slanting eyes; prominent brow ridges; a broad, flat nose; and a very small lower jaw and chin (micrognathia). Affected individuals often have abnormalities of the fingers and toes, such as unusual curvature of the fingers (camptodactyly) and shortened or absent thumbs and big toes. People with otopalatodigital syndrome type 2 usually have short stature, abnormally curved (bowed) bones in the arms and legs, and other abnormal or absent bones. Underdeveloped ribs can cause problems with breathing in affected individuals. Some people with this condition have an opening in the roof of the mouth (a cleft palate) or hearing loss.In addition to skeletal abnormalities, individuals with otopalatodigital syndrome type 2 may have developmental delay, increased fluid in the center of the brain (hydrocephalus), protrusion of the abdominal organs through the navel (omphalocele), heart defects, chest abnormalities, obstruction of the ducts between the kidneys and bladder (ureters), and, in males, opening of the urethra on the underside of the penis (hypospadias).Males with otopalatodigital syndrome type 2 generally have much more severe signs and symptoms compared to affected females. Males with this condition typically do not survive past infancy because of respiratory failure due to an underdeveloped rib cage. x X-linked FLNA https://medlineplus.gov/genetics/gene/flna Cranioorodigital syndrome Faciopalatoosseous syndrome FPO OPD syndrome, type 2 Oto-palato-digital syndrome, type II Taybi syndrome GTR C1844696 MeSH D010009 OMIM 304120 SNOMED CT 42432003 2007-11 2021-07-28 Otospondylomegaepiphyseal dysplasia https://medlineplus.gov/genetics/condition/otospondylomegaepiphyseal-dysplasia descriptionOtospondylomegaepiphyseal dysplasia (OSMED) is a condition characterized by skeletal abnormalities, distinctive facial features, and severe hearing loss. The term "otospondylomegaepiphyseal" refers to the parts of the body that this condition affects: the ears (oto-), the bones of the spine (spondylo-), and the ends (epiphyses) of long bones in the arms and legs. The features of this condition significantly overlap those of two similar conditions, Weissenbacher-Zweymüller syndrome and Stickler syndrome type III. All of these conditions are caused by mutations in the same gene, and in some cases, it can be difficult to tell the conditions apart. Some researchers believe they represent a single disorder with a range of signs and symptoms.People with OSMED are often shorter than average because the long bones in their legs are unusually short. Other skeletal features include enlarged joints; short arms, hands, and fingers; and flattened bones of the spine (platyspondyly). People with the disorder often experience back and joint pain, limited joint movement, and arthritis that begins early in life.Severe high-frequency hearing loss is common in people with OSMED. Typical facial features include protruding eyes; a flattened bridge of the nose; an upturned nose with a large, rounded tip; and a small lower jaw. Almost all affected infants are born with an opening in the roof of the mouth (a cleft palate). ar Autosomal recessive COL11A2 https://medlineplus.gov/genetics/gene/col11a2 Chondrodystrophy with sensorineural deafness Insley-Astley syndrome Mega-epiphyseal dwarfism Nance-Insley syndrome Nance-Sweeney chondrodysplasia OSMED Oto-spondylo-megaepiphyseal dysplasia GTR C1848488 GTR CN034493 MeSH D003095 OMIM 215150 SNOMED CT 254060000 2016-05 2025-12-16 Otulipenia https://medlineplus.gov/genetics/condition/otulipenia descriptionOtulipenia is characterized by abnormal inflammation throughout the body. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, the uncontrolled inflammation that occurs in otulipenia can damage many of the body's tissues and organs, including the gastrointestinal system, joints, and skin. Disorders such as otulipenia that result from abnormally increased inflammation are known as autoinflammatory diseases.Signs and symptoms of otulipenia usually begin within the first few weeks of life, with recurring episodes of fever; diarrhea; painful, swollen joints; and skin rashes. The skin rashes are due to inflammation of the layer of fatty tissue under the skin (panniculitis), which causes painful red bumps. Some people with otulipenia have an abnormal distribution of fatty tissue in their bodies (lipodystrophy). Affected infants have difficulty growing and gaining weight at the expected rate (failure to thrive). Damage to the body's tissues and organs caused by inflammation is life-threatening if the condition is not treated. ar Autosomal recessive OTULIN https://medlineplus.gov/genetics/gene/otulin AIPDS Autoinflammation, panniculitis, and dermatosis syndrome ORAS OTULIN-related autoinflammatory syndrome GTR C4310614 MeSH D056660 OMIM 617099 2016-12 2026-03-04 Ovarian cancer https://medlineplus.gov/genetics/condition/ovarian-cancer descriptionOvarian cancer is a disease that affects women. In this form of cancer, certain cells in the ovary become abnormal and multiply uncontrollably to form a tumor. The ovaries are the female reproductive organs in which egg cells are produced. In about 90 percent of cases, ovarian cancer occurs after age 40, and most cases occur after age 60.The most common form of ovarian cancer begins in epithelial cells, which are the cells that line the surfaces and cavities of the body. These cancers can arise in the epithelial cells on the surface of the ovary. However, researchers suggest that many or even most ovarian cancers begin in epithelial cells on the fringes (fimbriae) at the end of one of the fallopian tubes, and the cancerous cells migrate to the ovary.Cancer can also begin in epithelial cells that form the lining of the abdomen (the peritoneum). This form of cancer, called primary peritoneal cancer, resembles epithelial ovarian cancer in its origin, symptoms, progression, and treatment. Primary peritoneal cancer often spreads to the ovaries. It can also occur even if the ovaries have been removed. Because cancers that begin in the ovaries, fallopian tubes, and peritoneum are so similar and spread easily from one of these structures to the others, they are often difficult to distinguish. These cancers are so closely related that they are generally considered collectively by experts.In about 10 percent of cases, ovarian cancer develops not in epithelial cells but in germ cells, which are precursors to egg cells, or in hormone-producing ovarian cells called granulosa cells.In its early stages, ovarian cancer usually does not cause noticeable symptoms. As the cancer progresses, signs and symptoms can include pain or a feeling of heaviness in the pelvis or lower abdomen, bloating, feeling full quickly when eating, back pain, vaginal bleeding between menstrual periods or after menopause, or changes in urinary or bowel habits. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a woman has ovarian cancer.In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If ovarian cancer spreads, cancerous tumors most often appear in the abdominal cavity or on the surfaces of nearby organs such as the bladder or colon. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.Some ovarian cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary ovarian cancers tend to develop earlier in life than non-inherited (sporadic) cases.Because it is often diagnosed at a late stage, ovarian cancer can be difficult to treat; it leads to the deaths of about 14,000 women annually in the United States, more than any other gynecological cancer. However, when it is diagnosed and treated early, the 5-year survival rate is high. u Pattern unknown n Not inherited ad Autosomal dominant BRCA1 https://medlineplus.gov/genetics/gene/brca1 BRCA2 https://medlineplus.gov/genetics/gene/brca2 TP53 https://medlineplus.gov/genetics/gene/tp53 STK11 https://medlineplus.gov/genetics/gene/stk11 PRKN https://medlineplus.gov/genetics/gene/prkn NBN https://medlineplus.gov/genetics/gene/nbn CDH1 https://medlineplus.gov/genetics/gene/cdh1 CTNNB1 https://medlineplus.gov/genetics/gene/ctnnb1 AKT1 https://medlineplus.gov/genetics/gene/akt1 PIK3CA https://medlineplus.gov/genetics/gene/pik3ca BARD1 https://www.ncbi.nlm.nih.gov/gene/580 MRE11 https://www.ncbi.nlm.nih.gov/gene/4361 OPCML https://www.ncbi.nlm.nih.gov/gene/4978 RAD51C https://www.ncbi.nlm.nih.gov/gene/5889 RAD51D https://www.ncbi.nlm.nih.gov/gene/5892 RAD50 https://www.ncbi.nlm.nih.gov/gene/10111 CHEK2 https://www.ncbi.nlm.nih.gov/gene/11200 PALB2 https://www.ncbi.nlm.nih.gov/gene/79728 BRIP1 https://www.ncbi.nlm.nih.gov/gene/83990 Cancer of the ovary Malignant neoplasm of the ovary Malignant tumor of the ovary Ovarian carcinoma GTR C1140680 ICD-10-CM C56 ICD-10-CM C56.1 ICD-10-CM C56.2 ICD-10-CM C56.9 MeSH D010051 OMIM 167000 OMIM 604370 OMIM 607893 OMIM 612555 OMIM 613399 OMIM 614291 SNOMED CT 363443007 2015-09 2025-05-08 PACS1 syndrome https://medlineplus.gov/genetics/condition/pacs1-syndrome descriptionPACS1 syndrome is a condition in which all affected individuals have intellectual disability, speech and language problems, and a distinct facial appearance. Many affected individuals have additional neurological, behavioral, and health problems.In PACS1 syndrome, intellectual disability typically ranges from mild to moderate. Individuals with this condition also have problems with producing speech (expressive language). Speech development ranges from limited language to few words or no speech.Individuals with PACS1 syndrome have a distinct facial appearance. Facial features include thick and highly arched eyebrows, long eyelashes, widely set eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), droopy eyelids (ptosis), a rounded nasal tip, a wide mouth with corners that point downward, a thin upper lip, a smooth area between the nose and upper lip (philtrum), widely spaced teeth, and ears that are low-set with fewer folds and grooves than normal (described as "simple"). Abnormalities of other body systems can also occur, such as malformations of the heart, brain, eyes, or other organs. Males may have undescended testes (cryptorchidism).Children with PACS1 syndrome often have problems learning to eat solid food and prefer soft foods. When given solid foods, affected children often swallow without chewing. These food issues tend to persist throughout life. Some affected individuals experience a backflow of stomach acids into the esophagus (gastroesophageal reflux).Additional neurological problems can occur in PACS1 syndrome. Some affected individuals have features of autism spectrum disorder, which is characterized by impaired communication and social interaction. Attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), self-injury, or frustration leading to tantrums can also occur. Most individuals with PACS1 syndrome have seizures that vary in type and age of onset. Some people with PACS1 syndrome have weak muscle tone (hypotonia). Individuals with this condition are often delayed in walking, with some developing an unsteady walking style (gait). Rarely, affected individuals have frequent falls and gradually lose their ability to walk in late childhood, requiring wheelchair assistance. ad Autosomal dominant PACS1 https://medlineplus.gov/genetics/gene/pacs1 Autosomal dominant intellectual disability-17 Intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome PACS1-related syndrome Schuurs-Hoeijmakers syndrome SHMS GTR C3554343 MeSH D007805 MeSH D008607 OMIM 615009 2019-03 2023-02-27 PDGFRA-associated chronic eosinophilic leukemia https://medlineplus.gov/genetics/condition/pdgfra-associated-chronic-eosinophilic-leukemia descriptionPDGFRA-associated chronic eosinophilic leukemia is a form of blood cell cancer characterized by an elevated number of cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRA-associated chronic eosinophilic leukemia.Another characteristic feature of PDGFRA-associated chronic eosinophilic leukemia is organ damage caused by the excess eosinophils. Eosinophils release substances to aid in the immune response, but the release of excessive amounts of these substances causes damage to one or more organs, most commonly the heart, skin, lungs, or nervous system. Eosinophil-associated organ damage can lead to a heart condition known as eosinophilic endomyocardial disease, skin rashes, coughing, difficulty breathing, swelling (edema) in the lower limbs, confusion, changes in behavior, or impaired movement or sensations. People with PDGFRA-associated chronic eosinophilic leukemia can also have an enlarged spleen (splenomegaly) and elevated levels of certain chemicals called vitamin B12 and tryptase in the blood.Some people with PDGFRA-associated chronic eosinophilic leukemia have an increased number of other types of white blood cells, such as neutrophils or mast cells. Occasionally, people with PDGFRA-associated chronic eosinophilic leukemia develop other blood cell cancers, such as acute myeloid leukemia or B-cell or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma.PDGFRA-associated chronic eosinophilic leukemia is often grouped with a related condition called hypereosinophilic syndrome. These two conditions have very similar signs and symptoms; however, the cause of hypereosinophilic syndrome is unknown. n Not inherited PDGFRA https://medlineplus.gov/genetics/gene/pdgfra FIP1L1 https://medlineplus.gov/genetics/gene/fip1l1 4 https://medlineplus.gov/genetics/chromosome/4 Chronic eosinophilic leukemia with FIP1L1-PDGFRA Myeloid and lymphoid neoplasms associated with PDGFRA rearrangement Myeloid and lymphoid neoplasms with PDGFRA rearrangement Myeloid/lymphoid neoplasms with PDGFRA rearrangement PDGFRA-associated myeloproliferative neoplasm GTR C0206141 ICD-10-CM MeSH D017681 OMIM 607685 SNOMED CT 128835008 SNOMED CT 188733003 2012-03 2022-12-14 PDGFRB-associated chronic eosinophilic leukemia https://medlineplus.gov/genetics/condition/pdgfrb-associated-chronic-eosinophilic-leukemia descriptionPDGFRB-associated chronic eosinophilic leukemia is a type of cancer of blood-forming cells. It is characterized by an elevated number of white blood cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRB-associated chronic eosinophilic leukemia. Some people with this condition have an increased number of other types of white blood cells, such as neutrophils or mast cells, in addition to eosinophils. People with this condition can have an enlarged spleen (splenomegaly) or enlarged liver (hepatomegaly). Some affected individuals develop skin rashes, likely as a result of an abnormal immune response due to the increased number of eosinophils. u Pattern unknown PDGFRB https://medlineplus.gov/genetics/gene/pdgfrb ETV6 https://medlineplus.gov/genetics/gene/etv6 5 https://medlineplus.gov/genetics/chromosome/5 12 https://medlineplus.gov/genetics/chromosome/12 Chronic myelomonocytic leukemia with eosinophilia associated with t(5;12) Myeloid neoplasms associated with PDGFRB rearrangement Myeloid neoplasms with PDGFRB rearrangement Myeloid/lymphoid neoplasms with PDGFRB rearrangement GTR C1851585 ICD-10-CM MeSH D017681 OMIM 131440 SNOMED CT 128835008 SNOMED CT 188733003 SNOMED CT 190055003 SNOMED CT 413836008 2013-02 2024-10-02 PGM3-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/pgm3-congenital-disorder-of-glycosylation descriptionPGM3-congenital disorder of glycosylation (PGM3-CDG) is an inherited condition that primarily affects the immune system but can also involve other areas of the body. The pattern and severity of this disorder's signs and symptoms typically vary.Most people with PGM3-CDG have impaired immune function (immune deficiency). Many have a shortage of white blood cells (leukopenia), which normally protect the body from infection. Because affected individuals lack the necessary immune cells to fight off certain bacteria, viruses, and fungi, they are prone to repeated and persistent infections that often occur in the lungs, ears, skin, or gastrointestinal tract. In severe cases of PGM3-CDG, impaired bone marrow function may lead to a decrease in the production of all blood cells, resulting in a condition called bone marrow failure. Affected individuals usually also have allergies, asthma, or an inflammatory skin condition called eczema. People with PGM3-CDG may develop autoimmunity, which occurs when the body attacks its own tissues and organs by mistake. Persistent illness may cause affected children to grow more slowly than other individuals.Additionally, people with PGM3-CDG often have abnormally high levels of immune system proteins called antibodies (also known as immunoglobulins), particularly immunoglobulin E (IgE). Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. The effect of abnormal levels of antibodies in PGM3-CDG is unclear.People with PGM3-CDG often have intellectual disability, delayed development, and weak muscle tone (hypotonia). Many affected individuals have skeletal abnormalities involving the ribs or bones in the hands, feet, or spine. Some people with this condition have distinct facial features, such as a flat or sunken appearance of the middle of the face (midface hypoplasia), small chin (micrognathia), full lips, downturned corners of the mouth, and wide nostrils that open to the front rather than downward. PGM3-CDG can also cause problems in the lungs, gastrointestinal tract, and kidneys.Lifespan varies widely in people with PGM3-CDG; some do not survive past infancy while others live into late adulthood. ar Autosomal recessive PGM3 https://medlineplus.gov/genetics/gene/pgm3 AGM1 deficiency CID due to PGM3 deficiency Combined immunodeficiency due to PGM3 deficiency Deficiency of N-acetylglucosamine-phosphate mutase 1 Deficiency of phosphoglucomutase 3 Immunodeficiency 23 Immunodeficiency with hyper IgE and cognitive impairment Immunodeficiency-vasculitis-myoclonus syndrome PGM3 deficiency PGM3-CDG PGM3-related congenital disorder of glycosylation Phosphoglucomutase 3 deficiency Phosphoglucomutase deficiency type 3 GTR C4014371 MeSH D018981 OMIM 615816 2019-08 2020-08-18 PLCG2-associated antibody deficiency and immune dysregulation https://medlineplus.gov/genetics/condition/plcg2-associated-antibody-deficiency-and-immune-dysregulation descriptionPLCG2-associated antibody deficiency and immune dysregulation (PLAID) is an immune system disorder characterized by an allergic reaction to cold temperatures. Other immune system problems can also occur. The hallmark feature of PLAID is the development of a red, itchy rash (hives) when the skin is exposed to cool temperatures, which is known as cold urticaria. In PLAID, the hives typically develop in response to evaporative cooling, such as when a cool breeze or air conditioning blows on damp or sweaty skin. Being in a cold swimming pool can also trigger hives. In contrast, people with PLAID do not have a reaction when they touch a cold object, like an ice cube. (The ice cube test is a common test for a cold allergy; it triggers a reaction in people with other forms of cold urticaria, which usually begin later in life than PLAID.) However, some people with PLAID do experience a burning sensation in their throats when they eat cold foods, like ice cream. In PLAID, the hives go away once the skin warms up. Prolonged exposure to cold can lead to loss of consciousness or a serious allergic reaction known as anaphylaxis.Other skin problems can also occur in PLAID. A small number of affected individuals develop a blistering rash on the tip of their nose, ears, and fingers shortly after birth. The rash usually heals on its own in infancy, although in rare cases, it worsens over time. After the initial rash goes away, a different rash sometimes develops on the torso and limbs later in life. This rash, called a granuloma, can affect small patches of skin or be widespread. In people with PLAID, the granulomas do not occur in warm regions of the body, such as the armpits and other skin folds.In many people with PLAID, immune system function is reduced, leading to recurrent infections such as frequent colds, ear infections, or bouts of pneumonia. The infections are likely related to lower-than-normal levels of special proteins called antibodies or immunoglobulins, particularly immunoglobulin M (IgM) or immunoglobulin G (IgG). Antibodies attach to specific foreign particles and germs, marking them for destruction. The number of immune system cells called natural killer (NK) cells may also be reduced.Autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs, can also occur. Autoimmune disorders associated with PLAID include autoimmune thyroiditis and vitiligo. Autoimmune thyroiditis results from damage to the butterfly-shaped, hormone-producing gland in the lower neck (the thyroid). Vitiligo is caused by attacks on the pigment cells in the skin, resulting in a patchy loss of skin coloration. Most people with PLAID have abnormal antibodies called autoantibodies in their blood. One such antibody common in people with PLAID is known as antinuclear antibody (ANA). Autoantibodies attach to normal proteins and can trigger an immune attack against the body's own tissues. However, not everyone with these abnormal antibodies has an autoimmune disease. ad Autosomal dominant PLCG2 https://medlineplus.gov/genetics/gene/plcg2 Antibody deficiency and immune dysregulation, PLCG2-associated FACU Familial atypical cold urticaria Familial cold autoinflammatory syndrome 3 Familial cold urticaria with common variable immunodeficiency FCAS3 PLAID PLCG2 associated antibody deficiency and immune dysregulation GTR C3280914 MeSH D007154 MeSH D014581 OMIM 614468 2019-08 2026-03-04 PMM2-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/pmm2-congenital-disorder-of-glycosylation descriptionPMM2-congenital disorder of glycosylation (PMM2-CDG, also known as congenital disorder of glycosylation type Ia) is an inherited condition that affects many parts of the body. The type and severity of problems associated with PMM2-CDG vary widely among affected individuals, sometimes even among members of the same family.Individuals with PMM2-CDG typically develop signs and symptoms of the condition during infancy. Affected infants may have weak muscle tone (hypotonia), retracted (inverted) nipples, an abnormal distribution of fat, eyes that do not look in the same direction (strabismus), developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). Infants with PMM2-CDG also frequently have an underdeveloped cerebellum, which is the part of the brain that coordinates movement. Distinctive facial features are sometimes present in affected individuals, including a high forehead, a triangular face, large ears, and a thin upper lip. Children with PMM2-CDG may also have elevated liver function test results, seizures, fluid around the heart (pericardial effusion), and blood clotting disorders. About 20 percent of affected infants do not survive the first year of life due to multiple organ failure.The most severe cases of PMM2-CDG are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth.People with PMM2-CDG who survive infancy may have moderate intellectual disability, and some are unable to walk independently. Affected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. Recovery from these episodes usually occurs over a period of a few weeks to several months.During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and joint deformities (contractures). Some affected individuals have an eye disorder called retinitis pigmentosa that causes vision loss. Females with PMM2-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, females with PMM2-CDG do not go through puberty. Affected males experience normal puberty but often have small testes. ar Autosomal recessive PMM2 https://medlineplus.gov/genetics/gene/pmm2 Carbohydrate-deficient glycoprotein syndrome type Ia CDG Ia CDG1a CDGS1a Congenital disorder of glycosylation type Ia Jaeken syndrome Phosphomannomutase 2 deficiency PMM deficiency PMM2-CDG GTR C0349653 MeSH D018981 OMIM 212065 SNOMED CT 459063003 2010-07 2025-04-03 PPM-X syndrome https://medlineplus.gov/genetics/condition/ppm-x-syndrome descriptionPPM-X syndrome is a condition characterized by psychotic disorders (most commonly bipolar disorder), a pattern of movement abnormalities known as parkinsonism, and mild to severe intellectual disability with impaired language development. Other symptoms may include muscle stiffness (spasticity), exaggerated reflexes, and an abnormally small head (microcephaly). Affected males may have enlarged testes (macro-orchidism). Not all affected individuals have all these symptoms, but most have intellectual disability. Males with this condition are typically more severely affected than females, who usually have only mild intellectual disability or learning disabilities. x X-linked MECP2 https://medlineplus.gov/genetics/gene/mecp2 MRXS13 PPMX X-linked mental retardation, syndromic 13 GTR C0035372 MeSH D038901 OMIM 300055 SNOMED CT 702356009 2011-10 2020-08-18 PPP2R5D-related intellectual disability https://medlineplus.gov/genetics/condition/ppp2r5d-related-intellectual-disability descriptionPPP2R5D-related intellectual disability is a neurological disorder characterized by moderate to severe developmental delay and intellectual disability. Affected individuals have weak muscle tone (hypotonia); delayed development of motor skills, such as sitting, standing, and walking; and delayed speech development. Recurrent seizures (epilepsy) and autism spectrum disorder, which is characterized by impaired communications and social interaction, can also occur in affected individuals. Most people with PPP2R5D-related intellectual disability have an unusually large head size (macrocephaly), and some have other unusual facial features, including a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), and eyes that slant downward (downslanting palpebral fissures). ad Autosomal dominant PPP2R5D https://medlineplus.gov/genetics/gene/ppp2r5d Autosomal dominant mental retardation 35 GTR C4225345 MeSH D008607 OMIM 616355 2017-08 2021-02-01 PRICKLE1-related progressive myoclonus epilepsy with ataxia https://medlineplus.gov/genetics/condition/prickle1-related-progressive-myoclonus-epilepsy-with-ataxia descriptionPRICKLE1-related progressive myoclonus epilepsy with ataxia is a rare inherited condition characterized by recurrent seizures (epilepsy) and problems with movement. The signs and symptoms of this disorder usually begin between the ages of 5 and 10.Problems with balance and coordination (ataxia) are usually the first symptoms of PRICKLE1-related progressive myoclonus epilepsy with ataxia. Affected children often have trouble walking. Their gait is unbalanced and wide-based, and they may fall frequently. Later, children with this condition develop episodes of involuntary muscle jerking or twitching (myoclonus), which cause additional problems with movement. Myoclonus can also affect muscles in the face, leading to difficulty swallowing and slurred speech (dysarthria).Beginning later in childhood, some affected individuals develop tonic-clonic or grand mal seizures. These seizures involve a loss of consciousness, muscle rigidity, and convulsions. They often occur at night (nocturnally) while the person is sleeping.PRICKLE1-related progressive myoclonus epilepsy with ataxia does not seem to affect intellectual ability. Although a few affected individuals have died in childhood, many have lived into adulthood. ad Autosomal dominant ar Autosomal recessive PRICKLE1 https://medlineplus.gov/genetics/gene/prickle1 EPM1B PME with ataxia PRICKLE1-related progressive myoclonic epilepsy with ataxia Progressive myoclonic epilepsy 1B Progressive myoclonus epilepsy with ataxia GTR C2676254 MeSH D020191 OMIM 612437 SNOMED CT 702326000 2011-11 2020-08-18 PURA syndrome https://medlineplus.gov/genetics/condition/pura-syndrome descriptionPURA syndrome is a condition characterized by intellectual disability and delayed development of speech and motor skills, such as walking. Expressive language skills (vocabulary and the production of speech) are generally more severely affected than receptive language skills (the ability to understand speech), and most affected individuals are unable to speak. People with PURA syndrome may learn to walk later than their peers; many are never able to walk. In infancy, affected infants have very weak muscle tone (hypotonia) and feeding difficulties. Problems with swallowing (dysphagia) can last throughout life. In addition, affected infants can be excessively sleepy (hypersomnolent), have a low body temperature (hypothermia), and have short pauses in breathing (apnea) or episodes of abnormally slow breathing (hypoventilation). These breathing problems usually go away after age 1.Recurrent seizures (epilepsy) are also common in PURA syndrome. Seizures usually begin before age 5 with uncontrolled muscle jerks (myoclonus). Other types of seizures can develop, such as generalized tonic-clonic seizures, which involve loss of consciousness, muscle rigidity, and convulsions. In people with PURA syndrome, seizures are often difficult to control.Other features in people with PURA syndrome can include abnormalities of the heart, eyes, urogenital tract, gastrointestinal tract, and skeleton. Some affected individuals have symptoms of a hormonal problem, such as early sexual development (precocious puberty) or low levels of vitamin D (which is a hormone). ad Autosomal dominant PURA https://medlineplus.gov/genetics/gene/pura PURA-related neurodevelopmental disorder PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome GTR C4015357 MeSH D065886 OMIM 616158 2017-08 2024-10-02 Pachyonychia congenita https://medlineplus.gov/genetics/condition/pachyonychia-congenita descriptionPachyonychia congenita is a condition that primarily affects the skin and nails. The signs and symptoms of this condition usually become apparent within the first few years of life.Almost everyone with pachyonychia congenita develops very painful calluses on the soles of the feet. This condition is known as plantar keratoderma. Calluses usually begin to form on the feet in childhood when kids first start to walk. The calluses can make walking painful or impossible. In some affected individuals, blisters, bundles of blood vessels and nerves (neurovascular structures), or a deep itch may develop under or near the calluses, increasing pain and discomfort.Most people with pachyonychia congenita also show some signs of hypertrophic nail dystrophy, which causes the fingernails and toenails to become thick and abnormally shaped. The number of affected nails varies.Pachyonychia congenita can have several additional features. These features include thickened skin on the palms of the hands (palmar keratoderma), which can be painful; thick, white patches on the tongue and inside of the cheeks (oral leukokeratosis); bumps that develop around hair follicles (follicular keratoses) on the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; and excessive sweating on the palms and soles (palmoplantar hyperhidrosis).Some affected individuals also develop widespread cysts called steatocystomas, which are filled with an oily substance called sebum that normally lubricates the skin and hair. Some babies with pachyonychia congenita have prenatal or natal teeth, which are teeth that are present at birth or in early infancy. Some babies and children with pachyonychia congenita have pain in one or both ears when beginning to eat or drink. Pachyonychia congenita can also affect the voice box (larynx), causing hoarseness or breathing problems. Researchers used to classigy pachyonychia congenita as either PC-1 or PC-2 based on the genetic cause and pattern of signs and symptoms. However, as more affected individuals were identified, it became clear that the signs and symptoms of the types overlapped considerably. Pachyonychia congenita is now classified into five types based on the gene that is altered. ad Autosomal dominant KRT6A https://medlineplus.gov/genetics/gene/krt6a KRT6B https://medlineplus.gov/genetics/gene/krt6b KRT16 https://medlineplus.gov/genetics/gene/krt16 KRT17 https://medlineplus.gov/genetics/gene/krt17 KRT6C https://medlineplus.gov/genetics/gene/krt6c Congenital pachyonychia Jackson-Lawler syndrome (PC-2) Jadassohn-Lewandowski syndrome (PC-1) Pachyonychia congenita syndrome GTR C0265334 GTR C1706595 GTR C1721007 GTR C3714949 MeSH D053549 OMIM 167200 OMIM 167210 OMIM 615726 OMIM 615728 SNOMED CT 39427000 2023-04 2023-04-24 Paget disease of bone https://medlineplus.gov/genetics/condition/paget-disease-of-bone descriptionPaget disease of bone is a disorder that causes unusual growth in one or more bones. Affected bones may be weakened, misshapen, and easily broken (fractured).Paget disease of bone is typically diagnosed in middle age or later. The condition usually affects only one bone or just a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs.Approximately 70 percent of people with Paget disease of bone do not experience any signs or symptoms related to the bone abnormalities. In these individuals, the disease is often diagnosed unexpectedly by x-rays or laboratory tests that are done for other reasons. Pain is the most common symptom reported by people with Paget disease of bone. The affected bones may themselves be painful, or pain may be caused by arthritis in nearby joints. Arthritis occurs when the abnormal bones, particularly weight-bearing bones in the legs, cause extra wear and tear on the joints. Arthritis in the knees and hips is common.Other signs and symptoms of Paget disease of bone depend on the particular bones that are affected. If the disease affects the bones of the skull, affected individuals may have an enlarged head, hearing loss, headaches, and dizziness. When the condition affects bones in the spine(vertebrae), affected individuals may have an abnormal curvature of the spine or, less commonly, a narrowing of the spinal canal that can put pressure on the spinal cord (spinal stenosis). Spinal stenosis can lead to pain, tingling, and weakness in the legs. When the condition affects the leg bones, these bones may bow and fracture, which can interfere with the ability to walk. Some people with Paget disease of the bone have heart or kidney problems. Bone cancer (osteosarcoma) is a rare complication, affecting less than 1 percent of individuals with this condition.A form of Paget disease that typically develops in childhood, known as juvenile Paget disease, tends to affect multiple bones and has a different pattern of inheritance than Paget disease of bone.  ad Autosomal dominant TNFRSF11A https://medlineplus.gov/genetics/gene/tnfrsf11a SQSTM1 https://medlineplus.gov/genetics/gene/sqstm1 PFN1 https://www.ncbi.nlm.nih.gov/gene/5216 ZNF687 https://www.ncbi.nlm.nih.gov/gene/57592 Osteitis deformans Paget bone disease Paget's disease of bone PDB GTR C0029401 GTR C1853473 GTR C4085250 GTR C4085251 GTR C4085252 ICD-10-CM M88 ICD-10-CM M88.0 ICD-10-CM M88.1 ICD-10-CM M88.8 ICD-10-CM M88.81 ICD-10-CM M88.811 ICD-10-CM M88.812 ICD-10-CM M88.819 ICD-10-CM M88.82 ICD-10-CM M88.821 ICD-10-CM M88.822 ICD-10-CM M88.829 ICD-10-CM M88.83 ICD-10-CM M88.831 ICD-10-CM M88.832 ICD-10-CM M88.839 ICD-10-CM M88.84 ICD-10-CM M88.841 ICD-10-CM M88.842 ICD-10-CM M88.849 ICD-10-CM M88.85 ICD-10-CM M88.851 ICD-10-CM M88.852 ICD-10-CM M88.859 ICD-10-CM M88.86 ICD-10-CM M88.861 ICD-10-CM M88.862 ICD-10-CM M88.869 ICD-10-CM M88.87 ICD-10-CM M88.871 ICD-10-CM M88.872 ICD-10-CM M88.879 ICD-10-CM M88.88 ICD-10-CM M88.89 ICD-10-CM M88.9 MeSH D010001 OMIM 167250 OMIM 602080 OMIM 606263 OMIM 616833 SNOMED CT 2089002 2025-11 2025-11-20 Pallister-Hall syndrome https://medlineplus.gov/genetics/condition/pallister-hall-syndrome descriptionPallister-Hall syndrome is a disorder that affects the development of many parts of the body. Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder. In many cases, these growths do not cause any health problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister-Hall syndrome include a malformation of the airway called a bifid epiglottis, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications. ad Autosomal dominant GLI3 https://medlineplus.gov/genetics/gene/gli3 Hall-Pallister syndrome PHS GTR C0265220 MeSH D054975 OMIM 146510 SNOMED CT 56677004 2006-03 2020-08-18 Pallister-Killian mosaic syndrome https://medlineplus.gov/genetics/condition/pallister-killian-mosaic-syndrome descriptionPallister-Killian mosaic syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by extremely weak muscle tone (hypotonia) in infancy and early childhood, intellectual disability, distinctive facial features, sparse hair, areas of unusual skin coloring (pigmentation), and other birth defects.Most babies with Pallister-Killian mosaic syndrome are born with significant hypotonia, which can cause difficulty breathing and problems with feeding. Hypotonia also interferes with the normal development of motor skills such as sitting, standing, and walking. About 30 percent of affected individuals are ultimately able to walk without assistance. Additional developmental delays result from intellectual disability, which is usually severe to profound. Speech is often limited or absent in people with this condition.Pallister-Killian mosaic syndrome is associated with a distinctive facial appearance that is often described as "coarse." Characteristic facial features include a high, rounded forehead; a broad nasal bridge; a short nose; widely spaced eyes; low-set ears; rounded cheeks; and a wide mouth with a thin upper lip and a large tongue. Some affected children are born with an opening in the roof of the mouth (cleft palate) or a high arched palate.Most children with Pallister-Killian mosaic syndrome have sparse hair on their heads, particularly around the temples. These areas may fill in as affected children get older. Many affected individuals also have streaks or patches of skin that are darker or lighter than the surrounding skin. These skin changes can occur anywhere on the body, and they may be apparent at birth or occur later in life.Additional features of Pallister-Killian mosaic syndrome can include hearing loss, vision impairment, seizures, extra nipples, genital abnormalities, and heart defects. Affected individuals may also have skeletal abnormalities such as extra fingers and/or toes, large big toes (halluces), and unusually short arms and legs. About 40 percent of affected infants are born with a congenital diaphragmatic hernia, which is a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm). This potentially serious birth defect allows the stomach and intestines to move into the chest, where they can crowd the developing heart and lungs.The signs and symptoms of Pallister-Killian mosaic syndrome vary, although most people with this disorder have severe to profound intellectual disability and other serious health problems. The most severe cases involve birth defects that are life-threatening in early infancy. However, several affected people have had milder features, including mild intellectual disability and less noticeable physical abnormalities. n Not inherited 12 https://medlineplus.gov/genetics/chromosome/12 Isochromosome 12p syndrome Pallister-Killian syndrome PKS Teschler-Nicola/Killian syndrome Tetrasomy 12p, mosaic GTR C0265449 MeSH D025063 OMIM 601803 SNOMED CT 9527009 2009-06 2020-09-08 Palmoplantar keratoderma with deafness https://medlineplus.gov/genetics/condition/palmoplantar-keratoderma-with-deafness descriptionPalmoplantar keratoderma with deafness is a disorder characterized by skin abnormalities and hearing loss. Affected individuals develop unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma) beginning in childhood. Hearing loss ranges from mild to profound. It begins in early childhood and gets worse over time. Affected individuals have particular trouble hearing high-pitched sounds.The signs and symptoms of this disorder may vary even within the same family, with some individuals developing only skin abnormalities and others developing only hearing loss. m mitochondrial ad Autosomal dominant GJB2 https://medlineplus.gov/genetics/gene/gjb2 MT-TS1 https://medlineplus.gov/genetics/gene/mt-ts1 Palmoplantar hyperkeratosis-deafness syndrome Palmoplantar hyperkeratosis-hearing loss syndrome Palmoplantar keratoderma-deafness syndrome Palmoplantar keratoderma-hearing loss syndrome PPK with deafness PPK-deafness syndrome GTR C1835672 MeSH D007645 OMIM 148350 SNOMED CT 722203001 2012-11 2020-08-18 Pantothenate kinase-associated neurodegeneration https://medlineplus.gov/genetics/condition/pantothenate-kinase-associated-neurodegeneration descriptionPantothenate kinase-associated neurodegeneration (formerly called Hallervorden-Spatz syndrome) is a disorder of the nervous system. This condition is characterized by progressive difficulty with movement, typically beginning in childhood. Movement abnormalities include involuntary muscle spasms, rigidity, and trouble with walking that worsens over time. Many people with this condition also develop problems with speech (dysarthria), and some develop vision loss. Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, personality changes, and depression.Pantothenate kinase-associated neurodegeneration is characterized by an abnormal buildup of iron in certain areas of the brain. A particular change called the eye-of-the-tiger sign, which indicates an accumulation of iron, is typically seen on magnetic resonance imaging (MRI) scans of the brain in people with this disorder.Researchers have described classic and atypical forms of pantothenate kinase-associated neurodegeneration. The classic form usually appears in early childhood, causing severe problems with movement that worsen rapidly. Features of the atypical form appear later in childhood or adolescence and progress more slowly. Signs and symptoms vary, but the atypical form is more likely than the classic form to involve speech defects and psychiatric problems.A condition called HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration) syndrome, which was historically described as a separate syndrome, is now considered part of pantothenate kinase-associated neurodegeneration. ar Autosomal recessive PANK2 https://medlineplus.gov/genetics/gene/pank2 NBIA1 Neurodegeneration with brain iron accumulation type 1 PKAN GTR C0018523 ICD-10-CM G23.0 MeSH D006211 OMIM 234200 SNOMED CT 2992000 2006-10 2023-08-21 Paramyotonia congenita https://medlineplus.gov/genetics/condition/paramyotonia-congenita descriptionParamyotonia congenita is a disorder that affects muscles used for movement (skeletal muscles). Beginning in infancy or early childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness that typically appears after exercise and can be induced by muscle cooling. This stiffness chiefly affects muscles in the face, neck, arms, and hands, although it can also affect muscles used for breathing and muscles in the lower body. Unlike many other forms of myotonia, the muscle stiffness associated with paramyotonia congenita tends to worsen with repeated movements.Most people—even those without muscle disease—feel that their muscles do not work as well when they are cold. This effect is dramatic in people with paramyotonia congenita. Exposure to cold initially causes muscle stiffness in these individuals, and prolonged cold exposure leads to temporary episodes of mild to severe muscle weakness that may last for several hours at a time. Some older people with paramyotonia congenita develop permanent muscle weakness that can be disabling. ad Autosomal dominant SCN4A https://medlineplus.gov/genetics/gene/scn4a Eulenburg disease Paralysis periodica paramyotonia Paramyotonia congenita of von Eulenburg PMC Von Eulenberg's disease GTR C0221055 MeSH D020967 OMIM 168300 SNOMED CT 41574007 2007-04 2020-08-18 Parathyroid cancer https://medlineplus.gov/genetics/condition/parathyroid-cancer descriptionParathyroid cancer is a rare cancer that usually affects people in their forties or fifties and occurs in one of the four parathyroid glands. The parathyroid glands are located in the neck and secrete parathyroid hormone, which enhances the release of calcium into the blood.In about 90 percent of cases, the early signs of parathyroid cancer are high levels of parathyroid hormone (hyperparathyroidism) and calcium (hypercalcemia) in the blood. In these cases, the cancer is described as hormonally functional because the parathyroid glands are producing excess hormone.Many individuals with hormonally functional parathyroid cancer develop hypercalcemic crisis, in which calcium levels in the blood are very high. Neurological problems can develop, including changes in mood and depression. About 30 percent of individuals with hypercalcemia due to parathyroid cancer develop kidney and skeletal problems. These problems include increased urine production (polyuria), deposits of calcium in the kidneys (nephrocalcinosis) leading to the formation of kidney stones (nephrolithiasis), bone pain, bone loss, and increased bone fractures. Abdominal pain, inflammation of the pancreas (pancreatitis), sores (ulcers) in the lining of the digestive tract, nausea, vomiting, weight loss, and fatigue are also common.About 10 percent of cases of parathyroid cancer are described as hormonally nonfunctional. In these cases, levels of parathyroid hormone and calcium are normal. The signs and symptoms of hormonally nonfunctional parathyroid cancer are related to the tumor obstructing nearby structures in the neck. These problems include difficulty swallowing (dysphagia) and speaking (dysarthria), a hoarse voice, shortness of breath (dyspnea), or vocal cord paralysis.Up to 85 percent of individuals with parathyroid survive at least 5 years after they are diagnosed. The disease recurs in approximately half of individuals. If cancer does recur, it will commonly be within 3 years of the original diagnosis and up to 78 percent of people with recurrent cancer survive at least 5 years. Hormonally nonfunctional parathyroid cancer has a lower survival rate because it is often found at a later stage, as it does not have early signs such as increased calcium and parathyroid hormone levels.In hormonally functional parathyroid cancer, death is usually caused by organ failure (usually kidney failure) due to prolonged hypercalcemia and not directly due to the tumor. In hormonally nonfunctional parathyroid cancer, the cause of death is typically related to the tumor itself, such as its impact on the function of nearby structures or its spread to other tissues (metastasis). n Not inherited ad Autosomal dominant CDC73 https://medlineplus.gov/genetics/gene/cdc73 Cancer of the parathyroid Cancer of the parathyroid gland Carcinoma of parathyroid gland Malignant neoplasm of parathyroid Malignant neoplasm of parathyroid gland Malignant parathyroid gland neoplasm Malignant parathyroid gland tumor Malignant parathyroid neoplasm Malignant parathyroid tumor Malignant tumor of parathyroid Malignant tumor of parathyroid gland Parathyroid adenocarcinoma Parathyroid carcinoma Parathyroid gland cancer Parathyroid gland carcinoma Parathyroid neoplasms GTR C0687150 ICD-10-CM C75.0 MeSH D010282 OMIM 608266 SNOMED CT 363481002 2017-09 2020-08-18 Parkes Weber syndrome https://medlineplus.gov/genetics/condition/parkes-weber-syndrome descriptionParkes Weber syndrome is a disorder of the vascular system, which is the body's complex network of blood vessels. The vascular system consists of arteries, which carry oxygen-rich blood from the heart to the body's various organs and tissues; veins, which carry blood back to the heart; and capillaries, which are tiny blood vessels that connect arteries and veins.Parkes Weber syndrome is characterized by vascular abnormalities known as capillary malformations and arteriovenous fistulas (AVFs), which are present from birth. The capillary malformations increase blood flow near the surface of the skin. They usually look like large, flat, pink stains on the skin, and because of their color are sometimes called "port-wine stains." In people with Parkes Weber syndrome, capillary malformations occur together with multiple micro-AVFs, which are tiny abnormal connections between arteries and veins that affect blood circulation. These AVFs can be associated with life-threatening complications including abnormal bleeding and heart failure.Another characteristic feature of Parkes Weber syndrome is overgrowth of one limb, most commonly a leg. Abnormal growth occurs in bones and soft tissues, making one of the limbs longer and larger around than the corresponding one.Some vascular abnormalities seen in Parkes Weber syndrome are similar to those that occur in a condition called capillary malformation-arteriovenous malformation syndrome (CM-AVM). CM-AVM and some cases of Parkes Weber syndrome have the same genetic cause. ad Autosomal dominant RASA1 https://medlineplus.gov/genetics/gene/rasa1 Parkes-Weber syndrome PKWS GTR C5574870 MeSH D054079 OMIM 608354 SNOMED CT 234143003 2011-08 2023-08-21 Parkinson's disease https://medlineplus.gov/genetics/condition/parkinsons-disease descriptionParkinson's disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.Often the first symptom of Parkinson's disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson's disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.Parkinson's disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson's disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.Generally, Parkinson's disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson's disease. ad Autosomal dominant+1 affected parent ar Autosomal recessive u Pattern unknown GBA1 https://medlineplus.gov/genetics/gene/gba1 SNCA https://medlineplus.gov/genetics/gene/snca PRKN https://medlineplus.gov/genetics/gene/prkn UCHL1 https://medlineplus.gov/genetics/gene/uchl1 PINK1 https://medlineplus.gov/genetics/gene/pink1 PARK7 https://medlineplus.gov/genetics/gene/park7 LRRK2 https://medlineplus.gov/genetics/gene/lrrk2 ATP13A2 https://www.ncbi.nlm.nih.gov/gene/23400 VPS35 https://www.ncbi.nlm.nih.gov/gene/55737 Parkinson disease PD Primary parkinsonism GTR C1838867 GTR C1845165 GTR C1846862 GTR C1847360 GTR C1850100 GTR C1853202 GTR C1853445 GTR C1853833 GTR C1854182 GTR C1865581 GTR C1868595 GTR C1868675 GTR C2751012 GTR C2751842 GTR C3150899 GTR C3160718 GTR C3280133 GTR C3280271 GTR C4083045 ICD-10-CM G20 MeSH D010300 OMIM 168600 OMIM 168601 OMIM 260300 OMIM 300557 OMIM 556500 OMIM 600116 OMIM 602404 OMIM 605543 OMIM 605909 OMIM 606324 OMIM 606852 OMIM 607060 OMIM 607688 OMIM 610297 OMIM 612953 OMIM 613164 OMIM 613643 OMIM 614203 OMIM 614251 SNOMED CT 49049000 2012-05 2025-04-03 Paroxysmal extreme pain disorder https://medlineplus.gov/genetics/condition/paroxysmal-extreme-pain-disorder descriptionParoxysmal extreme pain disorder is a condition characterized by skin redness and warmth (flushing) and attacks of severe pain in various parts of the body. The area of flushing typically corresponds to the site of the pain. The pain attacks experienced by people with paroxysmal extreme pain disorder usually last seconds to minutes, but in some cases can last hours. These attacks can start as early as infancy. Early in life, the pain is typically concentrated in the lower part of the body, especially around the rectum, and is usually triggered by a bowel movement. Some children may develop constipation, which is thought to be due to fear of triggering a pain attack. Pain attacks in these young children may also be accompanied by seizures, slow heartbeat, or short pauses in breathing (apnea).As a person with paroxysmal extreme pain disorder ages, the location of pain changes. Pain attacks switch from affecting the lower body to affecting the head and face, especially the eyes and jaw. Triggers of these pain attacks include changes in temperature (such as a cold wind) and emotional distress as well as eating spicy foods and drinking cold drinks.Paroxysmal extreme pain disorder is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. ad Autosomal dominant SCN9A https://medlineplus.gov/genetics/gene/scn9a Familial rectal pain PEPD PEXPD Submandibular, ocular, and rectal pain with flushing GTR C1833661 MeSH D010148 OMIM 167400 SNOMED CT 699190008 2012-11 2020-08-18 Paroxysmal nocturnal hemoglobinuria https://medlineplus.gov/genetics/condition/paroxysmal-nocturnal-hemoglobinuria descriptionParoxysmal nocturnal hemoglobinuria (PNH) is an acquired (not inherited) disorder that leads to the premature death and impaired production of blood cells. The disorder affects red blood cells (erythrocytes), which carry oxygen; white blood cells (leukocytes), which protect the body from infections; and platelets (thrombocytes), which are involved in blood clotting. PNH can occur at any age, although it is most often diagnosed in young adulthood.People with PNH have sudden, recurring episodes of symptoms (paroxysmal symptoms), which may be triggered by stresses on the body, such as infections or physical exertion. During these episodes, red blood cells are broken down earlier than they should be (hemolysis). Affected individuals may pass dark-colored urine because of the presence of hemoglobin, the oxygen-carrying protein in blood. The abnormal presence of hemoglobin in the urine is called hemoglobinuria. In many, but not all cases, hemoglobinuria is most noticeable early in the morning, upon passing urine that has accumulated in the bladder during the night (nocturnal).The premature breakdown of red blood cells results in a shortage of these cells in the blood (hemolytic anemia), which can cause signs and symptoms such as fatigue, weakness, abnormally pale skin (pallor), shortness of breath, and an increased heart rate (tachycardia). People with PNH may also be prone to infections because of a shortage of white blood cells (leukopenia).Abnormal platelets associated with PNH can cause problems in the blood clotting process. As a result, people with this disorder may experience abnormal blood clotting (thrombosis), especially in large abdominal veins; or, less often, episodes of severe bleeding (hemorrhage).Individuals with PNH are at increased risk of developing cancer in blood-forming cells (leukemia). In some cases, people who have or have been treated for another blood disease called aplastic anemia may develop PNH. In a small number of affected individuals, the signs and symptoms of PNH disappear on their own.A very rare form of PNH involves abnormal inflammation in addition to the typical features described above. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). In people with this rare form of PNH, the immune response is turned on (activated) abnormally and can cause recurrent aseptic meningitis (which is inflammation of the membranes surrounding the brain and spinal cord that is not related to infection); a red, itchy rash (known as hives or urticaria); joint pain (arthralgia); or inflammatory bowel disease. The inflammatory disorders usually begin earlier than the blood cell problems. xd X-linked dominant ad Autosomal dominant+New variant PIGA https://medlineplus.gov/genetics/gene/piga PIGT https://medlineplus.gov/genetics/gene/pigt Hemoglobinuria, paroxysmal Marchiafava-Micheli syndrome PNH GTR C0024790 ICD-10-CM D59.5 MeSH D006457 OMIM 311770 SNOMED CT 1963002 2022-02 2022-04-05 Partington syndrome https://medlineplus.gov/genetics/condition/partington-syndrome descriptionPartington syndrome is a neurological disorder that causes intellectual disability along with a condition called focal dystonia that particularly affects movement of the hands. Partington syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe.The intellectual disability associated with Partington syndrome usually ranges from mild to moderate. Some affected individuals have characteristics of autism spectrum disorders that affect communication and social interaction. Recurrent seizures (epilepsy) may also occur in Partington syndrome.Focal dystonia of the hands is a feature that distinguishes Partington syndrome from other intellectual disability syndromes. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions; tremors; and other uncontrolled movements. The term "focal" refers to a type of dystonia that affects a single part of the body, in this case the hands. In Partington syndrome, focal dystonia of the hands, which is called the Partington sign, begins in early childhood and gradually gets worse. This condition typically causes difficulty with grasping movements or using a pen or pencil.People with Partington syndrome may also have dystonia affecting other parts of the body; dystonia affecting the muscles in the face and those involved in speech may cause impaired speech (dysarthria). People with this disorder may also have an awkward way of walking (gait). Signs and symptoms can vary widely, even within the same family. xr X-linked recessive ARX https://medlineplus.gov/genetics/gene/arx MRX36 Partington X-linked mental retardation syndrome Partington-Mulley syndrome PRTS X-linked intellectual deficit-dystonia-dysarthria X-linked mental retardation with dystonic movements, ataxia, and seizures GTR C0796250 MeSH D038901 OMIM 309510 SNOMED CT 702412005 2013-05 2020-08-18 Pearson syndrome https://medlineplus.gov/genetics/condition/pearson-syndrome descriptionPearson syndrome is a severe disorder that usually begins in infancy. It causes problems with the development of blood-forming (hematopoietic) cells in the bone marrow that have the potential to develop into different types of blood cells. For this reason, Pearson syndrome is considered a bone marrow failure disorder. Function of the pancreas and other organs can also be affected.Most affected individuals have a shortage of red blood cells (anemia), which can cause pale skin (pallor), weakness, and fatigue. Some of these individuals also have low numbers of white blood cells (neutropenia) and platelets (thrombocytopenia). Neutropenia can lead to frequent infections; thrombocytopenia sometimes causes easy bruising and bleeding. When visualized under the microscope, bone marrow cells from affected individuals may appear abnormal. Often, early blood cells (hematopoietic precursors) have multiple fluid-filled pockets called vacuoles. In addition, red blood cells in the bone marrow can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment with certain dyes. These abnormal cells are called ring sideroblasts.In people with Pearson syndrome, the pancreas does not work as well as usual. The pancreas produces and releases enzymes that aid in the digestion of fats and proteins. Reduced function of this organ can lead to high levels of fats in the liver (liver steatosis). The pancreas also releases insulin, which helps maintain correct levels of blood glucose, also called blood sugar. A small number of individuals with Pearson syndrome develop diabetes, a condition characterized by abnormally high blood glucose levels that can be caused by a shortage of insulin. In addition, affected individuals may have scarring (fibrosis) in the pancreas.People with Pearson syndrome have a reduced ability to absorb nutrients from the diet (malabsorption), and most affected infants have an inability to grow and gain weight at the expected rate (failure to thrive). Another common occurrence in people with this condition is buildup in the body of a chemical called lactic acid (lactic acidosis), which can be life-threatening. In addition, liver and kidney problems can develop in people with this condition. Some people with Pearson syndrome have droopy eyelids (ptosis), vision problems, hearing loss, seizures, or movement disorders.About half of children with this severe disorder die in infancy or early childhood due to severe lactic acidosis or liver failure. Many of those who survive develop signs and symptoms later in life of a related disorder called Kearns-Sayre syndrome. This condition causes weakness of muscles around the eyes and other problems. n Not inherited mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Pearson marrow-pancreas syndrome GTR C0342784 MeSH D028361 OMIM 557000 SNOMED CT 237985009 2013-05 2023-07-25 Peeling skin syndrome 2 https://medlineplus.gov/genetics/condition/peeling-skin-syndrome-2 descriptionPeeling skin syndrome 2 is a skin disorder characterized by painless peeling of the top layer of skin. In this form of peeling skin syndrome, the peeling is most apparent on the hands and feet. Occasionally, peeling also occurs on the arms and legs. The peeling usually starts soon after birth, although the condition can also begin in childhood or later in life. Skin peeling is made worse by exposure to heat, humidity and other forms of moisture, and friction. The underlying skin may be temporarily red and itchy, but it typically heals without scarring. Peeling skin syndrome 2 is not associated with any other health problems. ar Autosomal recessive TGM5 https://medlineplus.gov/genetics/gene/tgm5 Acral peeling skin syndrome APSS Peeling skin syndrome, acral type GTR C1853354 ICD-10-CM MeSH D003873 OMIM 609796 SNOMED CT 709416009 2023-09 2023-09-06 Pelizaeus-Merzbacher disease https://medlineplus.gov/genetics/condition/pelizaeus-merzbacher-disease descriptionPelizaeus-Merzbacher disease is an inherited condition involving the brain and spinal cord (central nervous system) that primarily affects males. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In particular, Pelizaeus-Merzbacher disease involves hypomyelination, which means that the nervous system has a reduced ability to form myelin. As a result, overall neurological function is reduced.Pelizaeus-Merzbacher disease is divided into classic and connatal (present from birth) types. Although these two types differ in severity, their features can overlap.Classic Pelizaeus-Merzbacher disease is the more common type. Within the first year of life, those affected with classic Pelizaeus-Merzbacher disease typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills, such as sitting or grasping objects. Some individuals are able to walk with assistance. Despite these neurological problems, intellectual and motor skills develop throughout childhood, but development usually stops around adolescence, and these skills are slowly lost (developmental regression). As the condition worsens, nystagmus usually goes away but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), head and neck tremors (titubation), involuntary tensing of the muscles (dystonia), and jerking (choreiform) movements.Connatal Pelizaeus-Merzbacher disease is the more severe of the two types. Symptoms can begin in infancy and include problems with feeding, poor weight gain and slow growth, high-pitched breathing caused by an obstructed airway (stridor), nystagmus, progressive speech difficulties (dysarthria), severe ataxia, hypotonia, and seizures. As the condition worsens, affected children develop spasticity leading to joint deformities (contractures) that restrict movement. Individuals with connatal Pelizaeus-Merzbacher disease are never able to walk, and many are not able to purposefully use their arms. They also have problems producing speech (expressive language) but can generally understand speech (receptive language). x X-linked PLP1 https://medlineplus.gov/genetics/gene/plp1 Cockayne-Pelizaeus-Merzbacher disease HLD1 Hypomyelinating leukodystrophy, 1 PMD Sudanophilic leukodystrophy GTR C0205711 MeSH D020371 OMIM 312080 SNOMED CT 64855000 2018-02 2020-08-18 Pelizaeus-Merzbacher-like disease type 1 https://medlineplus.gov/genetics/condition/pelizaeus-merzbacher-like-disease-type-1 descriptionPelizaeus-Merzbacher-like disease type 1 is an inherited condition involving the brain and spinal cord (central nervous system). This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In particular, Pelizaeus-Merzbacher-like disease type 1 involves hypomyelination, which means that the nervous system has a reduced ability to form myelin. The signs and symptoms of this condition are very similar to another leukodystrophy called Pelizaeus-Merzbacher disease, but the two disorders have different genetic causes.Beginning in the first few months of life, infants with Pelizaeus-Merzbacher-like disease type 1 typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of speech and motor skills, such as sitting or grasping objects. As children with Pelizaeus-Merzbacher-like disease type 1 get older, hypotonia changes to muscle stiffness (spasticity).During childhood, individuals with Pelizaeus-Merzbacher-like disease type 1 develop problems with movement and balance (ataxia), difficulty with movements that involve judging distance or scale (dysmetria), tremors that occur mainly during movement (intention tremors), and head and neck tremors (titubation). People with this condition have an inability to perform quick, alternating movements (dysdiadochokinesia), such as quickly tapping different fingers. Some develop involuntary tensing of the muscles (dystonia) and jerking (choreiform) movements. Many people with Pelizaeus-Merzbacher-like disease type 1 develop skeletal issues such as an abnormal curvature of the spine (scoliosis) and require wheelchair assistance from childhood.Muscle abnormalities can lead to difficulty swallowing and problems producing speech (expressive language), but affected individuals can understand speech (receptive language). Most individuals with Pelizaeus-Merzbacher-like disease type 1 have normal intelligence. Rarely, hearing loss, optic atrophy, and recurrent seizures (epilepsy) can occur. ar Autosomal recessive GJC2 https://medlineplus.gov/genetics/gene/gjc2 HLD2 Hypomyelinating leukodystrophy 2 Pelizaeus Merzbacher like disease Pelizaeus-Merzbacher-like disease PMLD - Pelizaeus Merzbacher like disease PMLD1 GTR C1837355 MeSH D020279 OMIM 608804 SNOMED CT 717042001 SNOMED CT 870287007 2018-04 2020-08-18 Pendred syndrome https://medlineplus.gov/genetics/condition/pendred-syndrome descriptionPendred syndrome is a disorder typically associated with hearing loss and a thyroid condition called a goiter. A goiter is an enlargement of the thyroid gland, which is a butterfly-shaped organ at the base of the neck that produces hormones. If a goiter develops in a person with Pendred syndrome, it usually forms between late childhood and early adulthood. In most cases, this enlargement does not cause the thyroid to malfunction.In most people with Pendred syndrome, severe to profound hearing loss caused by changes in the inner ear (sensorineural hearing loss) is evident at birth. Less commonly, hearing loss does not develop until later in infancy or early childhood. Some affected individuals also have problems with balance caused by dysfunction of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation.An inner ear abnormality called an enlarged vestibular aqueduct (EVA) is a characteristic feature of Pendred syndrome. The vestibular aqueduct is a bony canal that connects the inner ear with the inside of the skull. Some affected individuals also have an abnormally shaped cochlea, which is a snail-shaped structure in the inner ear that helps process sound. The combination of an enlarged vestibular aqueduct and an abnormally shaped cochlea is known as Mondini malformation.Pendred syndrome shares features with other hearing loss and thyroid conditions, and it is unclear whether they are best considered as separate disorders or as a spectrum of related signs and symptoms. These conditions include a form of nonsyndromic hearing loss (hearing loss that does not affect other parts of the body) called DFNB4, and, in a small number of people, a form of congenital hypothyroidism resulting from an abnormally small thyroid gland (thyroid hypoplasia). All of these conditions are caused by mutations in the same gene. ar Autosomal recessive SLC26A4 https://medlineplus.gov/genetics/gene/slc26a4 Autosomal recessive sensorineural hearing impairment, enlarged vestibular aqueduct, and goiter Deafness with goiter Goiter-deafness syndrome Pendred's syndrome GTR C0271829 ICD-10-CM E07.1 MeSH D006044 MeSH D006319 OMIM 274600 SNOMED CT 70348004 2016-03 2025-04-03 Periventricular heterotopia https://medlineplus.gov/genetics/condition/periventricular-heterotopia descriptionPeriventricular heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Heterotopia means "out of place." In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. The neurons then migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. In periventricular heterotopia, some neurons fail to migrate to their proper position and form clumps around the ventricles.Periventricular heterotopia usually becomes evident when seizures first appear, often during the teenage years. The nodules around the ventricles are then typically discovered when magnetic resonance imaging (MRI) studies are done. Affected individuals usually have normal intelligence, although some have mild intellectual disability. Difficulty with reading and spelling (dyslexia) and movement problems have been reported in some people with periventricular heterotopia.Less commonly, individuals with periventricular heterotopia may have other features including more severe brain malformations, small head size (microcephaly), developmental delays, recurrent infections, blood vessel abnormalities, stomach problems, or lung disease. Periventricular heterotopia may also occur in association with other conditions such as Ehlers-Danlos syndrome, which results in extremely flexible joints, skin that stretches easily, and fragile blood vessels. ar Autosomal recessive xd X-linked dominant FLNA https://medlineplus.gov/genetics/gene/flna ARFGEF2 https://medlineplus.gov/genetics/gene/arfgef2 NEDD4L https://www.ncbi.nlm.nih.gov/gene/23327 5 https://medlineplus.gov/genetics/chromosome/5 Familial nodular heterotopia Periventricular nodular heterotopia GTR C2678104 MeSH D054091 OMIM 300049 OMIM 608097 OMIM 608098 OMIM 617201 SNOMED CT 253150002 2007-11 2020-09-08 Permanent neonatal diabetes mellitus https://medlineplus.gov/genetics/condition/permanent-neonatal-diabetes-mellitus descriptionPermanent neonatal diabetes mellitus is a type of diabetes that typically appears within the first 6 months after birth (the neonatal period) and continues throughout life. Diabetes is characterized by high levels of glucose in the blood, also called blood sugar. In infants with permanent neonatal diabetes mellitus, diabetes results from a shortage or absence of the hormone insulin. Insulin is produced by the pancreas. It helps move glucose from the blood into cells, where glucose is converted into energy.The signs and symptoms of permanent neonatal diabetes mellitus can vary among affected individuals. Infants with this condition typically have abnormally high levels of glucose in the blood, glucose in the urine, severe fluid loss (dehydration), and a history of slow growth before birth (intrauterine growth retardation). After birth, affected infants may also have difficulty gaining weight and growing at the expected rate (failure to thrive).A small number of individuals with permanent neonatal diabetes mellitus have an underdeveloped pancreas. Because the pancreas produces digestive enzymes in addition to insulin, affected individuals may also experience digestive problems, such as fatty stools and an inability to absorb fat-soluble vitamins.The long-term complications of permanent neonatal diabetes mellitus can include kidney disease and retinopathy, which is damage to the small blood vessels in the specialized light-sensitive tissue that lines the back of the eye (retina). The risk of long-term complications is reduced with proper diabetes management. ad Autosomal dominant+New variant ar Autosomal recessive ABCC8 https://medlineplus.gov/genetics/gene/abcc8 KCNJ11 https://medlineplus.gov/genetics/gene/kcnj11 INS https://medlineplus.gov/genetics/gene/ins GCK https://medlineplus.gov/genetics/gene/gck PDX1 https://www.ncbi.nlm.nih.gov/gene/3651 Isolated permanent neonatal diabetes mellitus Isolated PNDM Monogenic diabetes of infancy PDMI permanent diabetes mellitus of infancy PNDM GTR C1833104 GTR C3891828 GTR C5393570 GTR C5394296 GTR C5394303 GTR C5394307 ICD-10-CM P70.2 MeSH D003920 OMIM 260370 OMIM 606176 OMIM 618856 OMIM 618857 OMIM 618858 SNOMED CT 609565001 2026-01 2026-01-13 Peroxisomal acyl-CoA oxidase deficiency https://medlineplus.gov/genetics/condition/peroxisomal-acyl-coa-oxidase-deficiency descriptionPeroxisomal acyl-CoA oxidase deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with peroxisomal acyl-CoA oxidase deficiency have weak muscle tone (hypotonia) and seizures. They may have unusual facial features, including widely spaced eyes (hypertelorism), a low nasal bridge, and low-set ears. Extra fingers or toes (polydactyly) or an enlarged liver (hepatomegaly) also occur in some affected individuals.Most babies with peroxisomal acyl-CoA oxidase deficiency learn to walk and begin speaking, but they experience a gradual loss of these skills (developmental regression), usually beginning between the ages of 1 and 3. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with peroxisomal acyl-CoA oxidase deficiency do not survive past early childhood. ar Autosomal recessive ACOX1 https://medlineplus.gov/genetics/gene/acox1 Acyl-coenzyme A oxidase deficiency Pseudo-NALD Pseudoadrenoleukodystrophy Pseudoneonatal adrenoleukodystrophy Straight-chain acyl-CoA oxidase deficiency GTR C1849678 MeSH D008052 MeSH D018901 OMIM 264470 SNOMED CT 238069004 2014-04 2020-08-18 Perrault syndrome https://medlineplus.gov/genetics/condition/perrault-syndrome descriptionPerrault syndrome is a rare condition that causes different patterns of signs and symptoms in affected males and females. A key feature of this condition is hearing loss, which occurs in both males and females. Affected females also have abnormalities of the ovaries. Neurological problems occur in some affected males and females.In Perrault syndrome, the problems with hearing are caused by changes in the inner ear, which is known as sensorineural hearing loss. The impairment usually affects both ears and can be present at birth or begin in early childhood. Unless hearing is completely impaired at birth, the hearing problems worsen over time.Females with Perrault syndrome have abnormal or missing ovaries (ovarian dysgenesis), although their external genitalia are normal. Severely affected girls do not begin menstruation by age 16 (primary amenorrhea), and most never have a menstrual period. Less severely affected women have an early loss of ovarian function (primary ovarian insufficiency); their menstrual periods begin in adolescence, but they become less frequent and eventually stop before age 40. Women with Perrault syndrome may have difficulty conceiving or be unable to have biological children (infertile).Neurological problems in individuals with Perrault syndrome can include intellectual disability, difficulty with balance and coordinating movements (ataxia), and loss of sensation and weakness in the limbs (peripheral neuropathy). However, not everyone with this condition has neurological problems. ar Autosomal recessive TWNK https://medlineplus.gov/genetics/gene/twnk HSD17B4 https://medlineplus.gov/genetics/gene/hsd17b4 CLPP https://medlineplus.gov/genetics/gene/clpp HARS2 https://medlineplus.gov/genetics/gene/hars2 LARS2 https://medlineplus.gov/genetics/gene/lars2 Gonadal dysgenesis with auditory dysfunction, autosomal recessive inheritance Gonadal dysgenesis with sensorineural deafness, autosomal recessive inheritance Gonadal dysgenesis, XX type, with deafness Ovarian dysgenesis with sensorineural deafness GTR C0685838 GTR C3554105 GTR C3809105 GTR C4015307 MeSH D006319 MeSH D023961 OMIM 233400 OMIM 614129 OMIM 614926 OMIM 615300 OMIM 616138 SNOMED CT 93466004 2014-12 2023-11-10 Perry syndrome https://medlineplus.gov/genetics/condition/perry-syndrome descriptionPerry syndrome is a progressive brain disease that is characterized by four major features: a pattern of movement abnormalities known as parkinsonism, psychiatric changes, weight loss, and abnormally slow breathing (hypoventilation). These signs and symptoms typically appear in a person's forties or fifties.Parkinsonism and psychiatric changes are usually the earliest features of Perry syndrome. Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. These movement abnormalities are often accompanied by changes in personality and behavior. The most frequent psychiatric changes that occur in people with Perry syndrome include depression, a general loss of interest and enthusiasm (apathy), withdrawal from friends and family, and suicidal thoughts. Many affected individuals also experience significant, unexplained weight loss early in the disease.Hypoventilation is a later feature of Perry syndrome. Abnormally slow breathing most often occurs at night, causing affected individuals to wake up frequently. As the disease worsens, hypoventilation can result in a life-threatening lack of oxygen and respiratory failure.People with Perry syndrome typically survive for about 5 years after signs and symptoms first appear. Most affected individuals ultimately die of respiratory failure or pneumonia. Suicide is another cause of death in this condition. ad Autosomal dominant DCTN1 https://medlineplus.gov/genetics/gene/dctn1 Parkinsonism with alveolar hypoventilation and mental depression GTR C1868594 MeSH D020734 OMIM 168605 SNOMED CT 699184009 2011-02 2020-08-18 Persistent Müllerian duct syndrome https://medlineplus.gov/genetics/condition/persistent-mullerian-duct-syndrome descriptionPersistent Müllerian duct syndrome is a disorder of sexual development that affects males. Males with this disorder have normal male reproductive organs, though they also have a uterus and fallopian tubes, which are female reproductive organs. The uterus and fallopian tubes are derived from a structure called the Müllerian duct during development of the fetus. The Müllerian duct usually breaks down during early development in males, but it is retained in those with persistent Müllerian duct syndrome. Affected individuals have the normal chromosomes of a male (46,XY) and normal external male genitalia.The first noted signs and symptoms in males with persistent Müllerian duct syndrome are usually undescended testes (cryptorchidism) or soft out-pouchings in the lower abdomen (inguinal hernias). The uterus and fallopian tubes are typically discovered when surgery is performed to treat these conditions.The testes and female reproductive organs can be located in unusual positions in persistent Müllerian duct syndrome. Occasionally, both testes are undescended (bilateral cryptorchidism) and the uterus is in the pelvis. More often, one testis has descended into the scrotum normally, and one has not. Sometimes, the descended testis pulls the fallopian tube and uterus into the track through which it has descended. This creates a condition called hernia uteri inguinalis, a form of inguinal hernia. In other cases, the undescended testis from the other side of the body is also pulled into the same track, forming an inguinal hernia. This condition, called transverse testicular ectopia, is common in people with persistent Müllerian duct syndrome.Other effects of persistent Müllerian duct syndrome may include the inability to father children (infertility) or blood in the semen (hematospermia). Also, the undescended testes may break down (degenerate) or develop cancer if left untreated. ar Autosomal recessive AMH https://medlineplus.gov/genetics/gene/amh AMHR2 https://medlineplus.gov/genetics/gene/amhr2 Persistent oviduct syndrome PMDS GTR C1849930 MeSH D058490 OMIM 261550 SNOMED CT 702358005 2011-03 2020-08-18 Peters anomaly https://medlineplus.gov/genetics/condition/peters-anomaly descriptionPeters anomaly is characterized by eye problems that occur in an area at the front part of the eye known as the anterior segment. The anterior segment consists of structures including the lens, the colored part (iris) of the eye, and the clear covering of the eye (cornea). During development of the eye, the elements of the anterior segment form separate structures. However, in Peters anomaly, development of the anterior segment is abnormal, leading to incomplete separation of the cornea from the iris or the lens. As a result, the cornea is cloudy (opaque), which causes blurred vision. The opaque area (opacity) of the cornea varies in size and intensity from a small, faint streak to a large, white cloudy area that covers the front surface of the eye. Additionally, the location of the opacity varies; the cloudiness may be at the center of the cornea or off-center. Large, centrally located opacities tend to cause poorer vision than smaller, off-center ones.Nearly half of the individuals affected with Peters anomaly have low vision early in life and about a quarter are legally blind. Due to a lack of visual stimulation, some individuals develop "lazy eye" (amblyopia). Peters anomaly is often associated with other eye problems, such as increased pressure within the eye (glaucoma), clouding of the lens (cataract), and unusually small eyeballs (microphthalmia). In most cases, Peters anomaly is bilateral, which means that it affects both eyes, although the level of vision impairment may be different in each eye. These individuals may have eyes that do not point in the same direction (strabismus). In some people with Peters anomaly, corneal clouding improves over time leading to improved vision.There are two types of Peters anomaly, which are distinguished by their signs and symptoms. Peters anomaly type I is characterized by an incomplete separation of the cornea and iris and mild to moderate corneal opacity. Type II is characterized by an incomplete separation of the cornea and lens and severe corneal opacity that may involve the entire cornea. ar Autosomal recessive ad Autosomal dominant CYP1B1 https://medlineplus.gov/genetics/gene/cyp1b1 SOX2 https://medlineplus.gov/genetics/gene/sox2 PAX6 https://medlineplus.gov/genetics/gene/pax6 FOXC1 https://medlineplus.gov/genetics/gene/foxc1 PITX2 https://medlineplus.gov/genetics/gene/pitx2 Irido-corneo-trabecular dysgenesis Peters congenital glaucoma GTR C0344559 GTR C1842031 GTR C4310623 GTR C5975707 ICD-10-CM Q13.4 MeSH D003318 OMIM 604229 SNOMED CT 204153003 2014-01 2025-07-02 Peters plus syndrome https://medlineplus.gov/genetics/condition/peters-plus-syndrome descriptionPeters plus syndrome is an inherited condition that is characterized by eye abnormalities, short stature, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), distinctive facial features, and intellectual disability.The eye problems in Peters plus syndrome occur in an area at the front part of the eye known as the anterior segment. The anterior segment consists of structures including the lens, the colored part of the eye (iris), and the clear covering of the eye (cornea). An eye problem called Peters anomaly is the most common anterior segment abnormality seen in Peters plus syndrome. Peters anomaly involves abnormal development of the anterior segment, which results in a cornea that is cloudy (opaque) and causes blurred vision. Peters anomaly may also be associated with clouding of the lenses of the eyes (cataracts) or other lens abnormalities. Peters anomaly is usually bilateral, which means that it affects both eyes. The severity of corneal clouding and other eye problems can vary between individuals with Peters plus syndrome, even among members of the same family. Many people with Peters plus syndrome experience vision loss that worsens over time.All people with Peters plus syndrome have short stature, which is evident before birth. The height of adult males with this condition ranges from 141 centimeters to 155 centimeters (4 feet, 7 inches to 5 feet, 1 inch), and the height of adult females ranges from 128 centimeters to 151 centimeters (4 feet, 2 inches to 4 feet, 11 inches). Individuals with Peters plus syndrome also have shortened upper limbs (rhizomelia) and shortened fingers and toes (brachydactyly).The characteristic facial features of Peters plus syndrome include a prominent forehead; small, malformed ears; narrow eyes; a long area between the nose and mouth (philtrum); and a pronounced double curve of the upper lip (Cupid's bow). The neck may also be broad and webbed. A cleft lip with or without a cleft palate is present in about half of the people with this condition.Developmental milestones, such as walking and speech, are delayed in most children with Peters plus syndrome. Most affected individuals also have intellectual disability that can range from mild to severe, although some have normal intelligence. The severity of physical features does not predict the level of intellectual disability.Less common signs and symptoms of Peters plus syndrome include heart defects, structural brain abnormalities, hearing loss, and kidney or genital abnormalities. ar Autosomal recessive B3GLCT https://medlineplus.gov/genetics/gene/b3glct Krause-Kivlin syndrome Krause-van Schooneveld-Kivlin syndrome Peters anomaly-short limb dwarfism syndrome Peters' plus syndrome Peters'-plus syndrome GTR C0796012 MeSH D015785 OMIM 261540 SNOMED CT 449817000 2013-09 2023-04-04 Peutz-Jeghers syndrome https://medlineplus.gov/genetics/condition/peutz-jeghers-syndrome descriptionPeutz-Jeghers syndrome is characterized by the development of noncancerous growths called hamartomatous polyps in the gastrointestinal tract (particularly the stomach and intestines) and a greatly increased risk of developing certain types of cancer.Children with Peutz-Jeghers syndrome often develop small, dark-colored spots on the lips, around and inside the mouth, near the eyes and nostrils, and around the anus. These spots may also occur on the hands and feet. They appear during childhood and often fade as the person gets older. In addition, most people with Peutz-Jeghers syndrome develop multiple polyps in the stomach and intestines during childhood or adolescence. Polyps can cause health problems such as recurrent bowel obstructions, chronic bleeding, and abdominal pain.People with Peutz-Jeghers syndrome have a high risk of developing cancer during their lifetimes. Cancers of the gastrointestinal tract, pancreas, cervix, ovary, and breast are among the most commonly reported tumors. ad Autosomal dominant STK11 https://medlineplus.gov/genetics/gene/stk11 Intestinal polyposis-cutaneous pigmentation syndrome Lentiginosis, perioral Periorificial lentiginosis syndrome Peutz-Jeghers polyposis PJS Polyposis, hamartomatous intestinal Polyposis, intestinal, II Polyps-and-spots syndrome GTR C0031269 ICD-10-CM Q85.8 MeSH D010580 OMIM 175200 SNOMED CT 54411001 2006-04 2020-08-18 Pfeiffer syndrome https://medlineplus.gov/genetics/condition/pfeiffer-syndrome descriptionPfeiffer syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. Pfeiffer syndrome also affects bones in the hands and feet.Many of the characteristic facial features of Pfeiffer syndrome result from premature fusion of the skull bones. Abnormal growth of these bones leads to bulging and wide-set eyes, a high forehead, an underdeveloped upper jaw, and a beaked nose. More than half of all children with Pfeiffer syndrome have hearing loss; dental problems are also common.In people with Pfeiffer syndrome, the thumbs and first (big) toes are wide and bend away from the other digits. Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly).Pfeiffer syndrome is divided into three subtypes. Type 1, also known as classic Pfeiffer syndrome, has symptoms as described above. Most individuals with type 1 Pfeiffer syndrome have normal intelligence and a normal life span. Types 2 and 3 are more severe forms of Pfeiffer syndrome that often involve problems with the nervous system. The premature fusion of skull bones can limit brain growth, leading to delayed development and other neurological problems. In addition, individuals with type 2 or 3 can have fusion of the bones (ankylosis) in the elbow or other joints, limiting mobility, and abnormalities of the face and airways, which can cause life-threatening breathing problems. Type 2 is distinguished from type 3 by the presence of a cloverleaf-shaped head, which is caused by more extensive fusion of bones in the skull. ad Autosomal dominant FGFR1 https://medlineplus.gov/genetics/gene/fgfr1 FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 Acrocephalosyndactyly, type V ACS V ACS5 Craniofacial-skeletal-dermatologic dysplasia Noack syndrome GTR C0220658 MeSH D000168 OMIM 101600 SNOMED CT 70410008 2008-02 2020-08-18 Phenylketonuria https://medlineplus.gov/genetics/condition/phenylketonuria descriptionPhenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a protein building block (an amino acid) that is obtained from eating certain foods (such as meat, eggs, nuts, and milk) and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems.The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent intellectual disability. Seizures, delayed development, behavioral problems, and psychiatric disorders are also common. Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema.Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia, have a smaller risk of brain damage. People with very mild cases may not require treatment.PKU can often be managed by following a diet that is low in phenylalanine. Since phenylalanine is found in all proteins, the PKU diet consists of avoiding meat, dairy, nuts, tofu, and other foods that are high in protein. Infants with PKU need to be fed with a low-protein formula. Affected individuals are often limited to certain fruits and vegetables and foods containing fats and sugars (such as butter, jelly, pasta, and potato chips). The artificial sweeter aspartame, which is found in diet soda and many other low-calorie items, should be avoided as it contains high amounts of phenylalanine. The amount of phenylalanine that is safe to consume is different for each person. Affected individuals should work with a health care professional to develop an individualized diet. Babies born to mothers who have PKU and are not following a low-phenylalanine diet have a significant risk of intellectual disability because they are exposed to very high levels of phenylalanine before birth. These infants may also have a low birth weight and grow more slowly than other children. They may also have heart defects or other heart problems, an abnormally small head size (microcephaly), and behavioral problems. Women with PKU who are not following a low-phenylalanine diet (and may have high levels of phenylalanine) also have higher risk of pregnancy loss. ar Autosomal recessive PAH https://medlineplus.gov/genetics/gene/pah Folling disease Folling's disease PAH deficiency Phenylalanine hydroxylase deficiency Phenylalanine hydroxylase deficiency disease PKU GTR C0751434 ICD-10-CM E70.0 MeSH D010661 OMIM 261600 SNOMED CT 297225000 SNOMED CT 60590005 SNOMED CT 7573000 2023-04 2025-04-03 Phosphoglycerate dehydrogenase deficiency https://medlineplus.gov/genetics/condition/phosphoglycerate-dehydrogenase-deficiency descriptionPhosphoglycerate dehydrogenase deficiency is a condition characterized by an unusually small head size (microcephaly); impaired development of physical reactions, movements, and speech (psychomotor retardation); and recurrent seizures (epilepsy). Different types of phosphoglycerate dehydrogenase deficiency have been described; they are distinguished by their severity and the age at which symptoms first begin. Most affected individuals have the infantile form, which is the most severe form, and are affected from infancy. Symptoms of the juvenile and adult types appear later in life; these types are very rare.In phosphoglycerate dehydrogenase deficiency there is a progressive loss of brain cells leading to a loss of brain tissue (brain atrophy), specifically affecting the fatty tissue known as myelin that surrounds nerve cells (hypomyelination). Frequently, the tissue that connects the two halves of the brain (corpus callosum) is small and thin, and the fluid-filled cavities (ventricles) near the center of the brain are enlarged. Because development of the brain is disrupted, the head does not grow at the same rate as the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Poor brain growth leads to an inability to achieve many developmental milestones such as sitting unsupported and speaking. Many affected infants also have difficulty feeding.The seizures in phosphoglycerate dehydrogenase deficiency can vary in type. Recurrent muscle contractions called infantile spasms are typical early in the disorder. Without early treatment, seizures may progress to tonic-clonic seizures, which involve a loss of consciousness, muscle rigidity, and convulsions; myoclonic seizures, which involve rapid, uncontrolled muscle jerks; or drop attacks, which are sudden episodes of weak muscle tone.Individuals with the infantile form of phosphoglycerate dehydrogenase deficiency develop many of the features described above. Individuals with the juvenile form typically have epilepsy as well as mild developmental delay and intellectual disability. Only one case of the adult form has been reported; signs and symptoms began in mid-adulthood and included mild intellectual disability; difficulty coordinating movements (ataxia); and numbness, tingling, and pain in the arms and legs (sensory neuropathy). ar Autosomal recessive PHGDH https://medlineplus.gov/genetics/gene/phgdh 3-PGDH deficiency 3-phosphoglycerate dehydrogenase deficiency PHGDH deficiency GTR C1866174 MeSH D000592 OMIM 601815 SNOMED CT 303098002 2014-05 2020-08-18 Phosphoglycerate kinase deficiency https://medlineplus.gov/genetics/condition/phosphoglycerate-kinase-deficiency descriptionPhosphoglycerate kinase deficiency is a genetic disorder that affects the body's ability to break down the simple sugar glucose, which is the primary energy source for most cells. Researchers have described two major forms of the condition. The most common form is sometimes called the hemolytic form. It is characterized by a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely. Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate. Some people with the hemolytic form also have symptoms related to abnormal brain function, including intellectual disability, seizures, and stroke.The other form of phosphoglycerate kinase deficiency is often called the myopathic form. It primarily affects muscles, causing progressive weakness, pain, and cramping, particularly with exercise. During exercise, muscle tissue can be broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can lead to kidney failure.Most people with phosphoglycerate kinase deficiency have either the hemolytic form or the myopathic form. However, other combinations of signs and symptoms (such as muscle weakness with neurologic symptoms) have also been reported. xr X-linked recessive PGK1 https://medlineplus.gov/genetics/gene/pgk1 PGK deficiency PGK1 deficiency Phosphoglycerate kinase 1 deficiency GTR C0684324 GTR C1970848 MeSH D008661 OMIM 300653 SNOMED CT 124335006 2011-12 2020-08-18 Phosphoglycerate mutase deficiency https://medlineplus.gov/genetics/condition/phosphoglycerate-mutase-deficiency descriptionPhosphoglycerate mutase deficiency is a disorder that primarily affects muscles used for movement (skeletal muscles). Beginning in childhood or adolescence, affected individuals experience muscle aches or cramping following strenuous physical activity. Some people with this condition also have recurrent episodes of myoglobinuria. Myoglobinuria occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin, which is processed by the kidneys and released in the urine. If untreated, myoglobinuria can lead to kidney failure.In some cases of phosphoglycerate mutase deficiency, microscopic tube-shaped structures called tubular aggregates are seen in muscle fibers. It is unclear how tubular aggregates are associated with the signs and symptoms of the disorder. ar Autosomal recessive PGAM2 https://medlineplus.gov/genetics/gene/pgam2 Deficiency mutase phosphoglycerate Glycogen storage disease X GSD X GSD10 GSDX Myopathy due to phosphoglycerate mutase deficiency PGAM deficiency PGAMM deficiency GTR C0268149 MeSH D008661 OMIM 261670 SNOMED CT 124675005 SNOMED CT 37666005 2011-12 2020-08-18 Phosphoribosylpyrophosphate synthetase superactivity https://medlineplus.gov/genetics/condition/phosphoribosylpyrophosphate-synthetase-superactivity descriptionPhosphoribosylpyrophosphate synthetase superactivity (PRS superactivity) is characterized by the overproduction and accumulation of uric acid (a waste product of normal chemical processes) in the blood and urine. The overproduction of uric acid can lead to gout, which is arthritis caused by an accumulation of uric acid crystals in the joints. Individuals with PRS superactivity also develop kidney or bladder stones that may result in episodes of acute kidney failure.There are two forms of PRS superactivity, a severe form that begins in infancy or early childhood, and a milder form that typically appears in late adolescence or early adulthood. In both forms, a kidney or bladder stone is often the first symptom. Gout and impairment of kidney function may develop if the condition is not adequately controlled with medication and dietary restrictions. People with the severe form may also have neurological problems, including hearing loss caused by changes in the inner ear (sensorineural hearing loss), weak muscle tone (hypotonia), impaired muscle coordination (ataxia), and developmental delay. xd X-linked dominant PRPS1 https://medlineplus.gov/genetics/gene/prps1 Gout, PRPS-related PRPP synthetase overactivity PRPP synthetase superactivity PRPS1 superactivity PRS overactivity PRS superactivity GTR C1970827 MeSH D033461 OMIM 300661 SNOMED CT 723454008 2009-09 2023-11-10 Piebaldism https://medlineplus.gov/genetics/condition/piebaldism descriptionPiebaldism is a condition characterized by the absence of cells called melanocytes in certain areas of the skin and hair. Melanocytes produce the pigment melanin, which contributes to hair, eye, and skin color. The absence of melanocytes leads to patches of skin and hair that are lighter than normal. Approximately 90 percent of affected individuals have a white section of hair near their front hairline (a white forelock). The eyelashes, the eyebrows, and the skin under the forelock may also be unpigmented.People with piebaldism usually have other unpigmented patches of skin, typically appearing symmetrically on both sides of the body. There may be spots or patches of pigmented skin within or around the borders of the unpigmented areas.In most cases, the unpigmented areas are present at birth and do not increase in size or number. The unpigmented patches are at increased risk of sunburn and skin cancer related to excessive sun exposure. Some people with piebaldism are self-conscious about the appearance of the unpigmented patches, which may be more noticeable in darker-skinned people. Aside from these potential issues, this condition has no effect on the health of the affected individual. ad Autosomal dominant SNAI2 https://medlineplus.gov/genetics/gene/snai2 KIT https://medlineplus.gov/genetics/gene/kit PBT Piebald trait GTR C0080024 MeSH D016116 OMIM 172800 SNOMED CT 718122005 2013-02 2023-03-21 Pilomatricoma https://medlineplus.gov/genetics/condition/pilomatricoma descriptionPilomatricoma, also known as pilomatrixoma, is a type of noncancerous (benign) skin tumor associated with hair follicles. Hair follicles are specialized structures in the skin where hair growth occurs. Pilomatricomas occur most often on the head or neck, although they can also be found on the arms, torso, or legs. A pilomatricoma feels like a small, hard lump under the skin. This type of tumor grows relatively slowly and usually does not cause pain or other symptoms. Most affected individuals have a single tumor, although rarely multiple pilomatricomas can occur. If a pilomatricoma is removed surgically, it tends not to grow back (recur).Most pilomatricomas occur in people under the age of 20. However, these tumors can also appear later in life. Almost all pilomatricomas are benign, but a very small percentage are cancerous (malignant). Unlike the benign form, the malignant version of this tumor (known as a pilomatrix carcinoma) occurs most often in middle age or late in life.Pilomatricoma usually occurs without other signs or symptoms (isolated), but this type of tumor has also rarely been reported with inherited conditions. Disorders that can be associated with pilomatricoma include Gardner syndrome, which is characterized by multiple growths (polyps) and cancers of the colon and rectum; myotonic dystrophy, which is a form of muscular dystrophy; and Rubinstein-Taybi syndrome, which is a condition that affects many parts of the body and is associated with an increased risk of both benign and malignant tumors. u Pattern unknown CTNNB1 https://medlineplus.gov/genetics/gene/ctnnb1 Benign pilomatricoma Benign pilomatrixoma Calcifying epithelioma of Malherbe Malherbe calcifying epithelioma Pilomatrixoma GTR C0206711 MeSH D018296 OMIM 132600 SNOMED CT 274901004 SNOMED CT 44155009 2012-06 2020-08-18 Pitt-Hopkins syndrome https://medlineplus.gov/genetics/condition/pitt-hopkins-syndrome descriptionPitt-Hopkins syndrome is a condition characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features.People with Pitt-Hopkins syndrome have moderate to severe intellectual disability. Most affected individuals have delayed development of mental and motor skills (psychomotor delay). They are delayed in learning to walk and developing fine motor skills such as picking up small items with their fingers. People with Pitt-Hopkins syndrome typically do not develop speech; some may learn to say a few words. Many affected individuals exhibit features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills.Breathing problems in individuals with Pitt-Hopkins syndrome are characterized by episodes of rapid breathing (hyperventilation) followed by periods in which breathing slows or stops (apnea). These episodes can cause a lack of oxygen in the blood, leading to a bluish appearance of the skin or lips (cyanosis). In some cases, the lack of oxygen can cause loss of consciousness. Some older individuals with Pitt-Hopkins syndrome develop widened and rounded tips of the fingers and toes (clubbing) because of recurrent episodes of decreased oxygen in the blood. The breathing problems occur only when the person is awake and typically first appear in mid-childhood, but they can begin as early as infancy. Episodes of hyperventilation and apnea can be triggered by emotions such as excitement or anxiety or by extreme tiredness (fatigue).Epilepsy occurs in most people with Pitt-Hopkins syndrome and usually begins during childhood, although it can be present from birth.Individuals with Pitt-Hopkins syndrome have distinctive facial features that include thin eyebrows, sunken eyes, a prominent nose with a high nasal bridge, a pronounced double curve of the upper lip (Cupid's bow), a wide mouth with full lips, and widely spaced teeth. The ears are usually thick and cup-shaped.Children with Pitt-Hopkins syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. However, they can also experience anxiety and behavioral problems.Other features of Pitt-Hopkins syndrome may include constipation and other gastrointestinal problems, an unusually small head (microcephaly), nearsightedness (myopia), eyes that do not look in the same direction (strabismus), short stature, and minor brain abnormalities. Affected individuals may also have small hands and feet, a single crease across the palms of the hands, flat feet (pes planus), or unusually fleshy pads at the tips of the fingers and toes. Males with Pitt-Hopkins syndrome may have undescended testes (cryptorchidism). ad Autosomal dominant TCF4 https://medlineplus.gov/genetics/gene/tcf4 PHS PTHS GTR C1970431 MeSH D008607 OMIM 610954 SNOMED CT 702344008 2011-05 2020-08-18 Platyspondylic dysplasia, Torrance type https://medlineplus.gov/genetics/condition/platyspondylic-dysplasia-torrance-type descriptionPlatyspondylic dysplasia, Torrance type is a severe disorder of bone growth. Infants with this condition have very short arms and legs, severely flattened bones of the spine (platyspondyly), and unusually short fingers and toes (brachydactyly). Affected individuals also tend to have a small chest with short ribs that can restrict the growth and expansion of the lungs.The serious health problems seen in infants with platyspondylic dysplasia, Torrance type often result in death before birth or shortly thereafter; respiratory failure is a common cause of death.  ad Autosomal dominant+New variant COL2A1 https://medlineplus.gov/genetics/gene/col2a1 Platyspondylic dysplasia, Torrance-Luton type Platyspondylic dysplasia, type Torrance, COL2A1-related Platyspondylic lethal skeletal dysplasia, Torrance type PLSD-T GTR C1835437 MeSH D003095 MeSH D010009 OMIM 151210 SNOMED CT 254047006 2024-12 2024-12-20 Poikiloderma with neutropenia https://medlineplus.gov/genetics/condition/poikiloderma-with-neutropenia descriptionPoikiloderma with neutropenia (PN) is a disorder that mainly affects the skin and the immune system. This condition begins with a bumpy rash that usually appears between the ages of 6 and 12 months, gradually spreading from the arms and legs to the torso and face. At about age 2, the rash fades, and the affected child is left with darker and lighter patches of skin coloring (hyperpigmentation and hypopigmentation) and small clusters of blood vessels just under the skin (telangiectases); this combination is known as poikiloderma. Other skin problems include unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma); calcium deposits that form small nodules (calcinosis cutis), especially on the knees, elbows, or ears; or sores (ulcers) that do not easily heal. Affected individuals also have fingernails and toenails that are thick and abnormally shaped (pachyonychia), fragile teeth, and low bone density.People with PN have chronic neutropenia, which is a persistent shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses. As a result, people with PN experience recurrent sinus infections and pneumonia, especially in the first few years of life. They often develop a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. The infections become less frequent after early childhood, but throughout life affected individuals usually have a chronic cough or a reactive airway disease. This term describes asthma and other conditions in which the airways abnormally constrict in response to stimuli such as smoke or a viral infection, leading to wheezing and shortness of breath.Researchers suggest that PN may increase the risk of cancer, although the level of risk is difficult to determine because only a small number of people have been diagnosed with PN. A type of skin cancer called squamous cell carcinoma, a precancerous blood disorder known as myelodysplastic syndrome (MDS), and a blood cancer called acute myelogenous leukemia that often follows MDS have occurred in a few people with PN.Some individuals with PN also develop unusual facial features as they grow. These features include a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), a flat or sunken appearance of the middle of the face (midface hypoplasia), a small nose with a depressed nasal bridge, and a chin that protrudes (prognathism). Short stature and hypogonadotropic hypogonadism (a condition affecting the production of hormones that direct sexual development) can also occur in this disorder. ar Autosomal recessive USB1 https://medlineplus.gov/genetics/gene/usb1 Clericuzio type poikiloderma with neutropenia Immune-deficient poikiloderma Poikiloderma with neutropenia, Clericuzio type GTR C1858723 MeSH D012873 OMIM 604173 2018-05 2020-08-18 Pol III-related leukodystrophy https://medlineplus.gov/genetics/condition/pol-iii-related-leukodystrophy descriptionPol III-related leukodystrophy is a disorder that affects the nervous system and other parts of the body. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter, which consists of nerve cells (neurons) covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses.Pol III-related leukodystrophy is a hypomyelinating disease, which means that the nervous system of affected individuals has a reduced ability to form myelin. Hypomyelination underlies most of the neurological problems associated with Pol III-related leukodystrophy. A small number of people with this disorder also have a loss of nerve cells in a part of the brain involved in coordinating movements (cerebellar atrophy) and underdevelopment (hypoplasia) of tissue that connects the left and right halves of the brain (the corpus callosum). These brain abnormalities likely contribute to the neurological problems in affected individuals.People with Pol III-related leukodystrophy usually have intellectual disability ranging from mild to severe, which gradually worsens over time. Some affected individuals have normal intelligence in early childhood but develop mild intellectual disability during the course of the disease.Difficulty coordinating movements (ataxia), which begins in childhood and slowly worsens over time, is a characteristic feature of Pol III-related leukodystrophy. Affected children typically have delayed development of motor skills such as walking. Their gait is unstable, and they usually walk with their feet wide apart for balance. Affected individuals may eventually need to use a walker or wheelchair. Involuntary rhythmic shaking (tremor) of the arms and hands may occur in this disorder. In some cases the tremor occurs mainly during movement (intention tremor); other affected individuals experience the tremor both during movement and at rest.Development of the teeth (dentition) is often abnormal in Pol III-related leukodystrophy, resulting in the absence of some teeth (known as hypodontia or oligodontia). Some affected infants are born with a few teeth (natal teeth), which fall out during the first weeks of life. The primary (deciduous) teeth appear later than usual, beginning at about age 2. In Pol III-related leukodystrophy, the teeth may not appear in the usual sequence, in which front teeth (incisors) appear before back teeth (molars). Instead, molars often appear first, with incisors appearing later or not at all. Permanent teeth are also delayed, and may not appear until adolescence. The teeth may also be unusually shaped.Some individuals with Pol III-related leukodystrophy have excessive salivation and difficulty chewing or swallowing (dysphagia), which can lead to choking. They may also have speech impairment (dysarthria). People with Pol III-related leukodystrophy often have abnormalities in eye movement, such as progressive vertical gaze palsy, which is restricted up-and-down eye movement that worsens over time. Nearsightedness is common in affected individuals, and clouding of the lens of the eyes (cataracts) has also been reported. Deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and seizures may also occur in this disorder.Hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development, may occur in Pol III-related leukodystrophy. Affected individuals have delayed development of the typical signs of puberty, such as the growth of body hair.People with Pol III-related leukodystrophy may have different combinations of its signs and symptoms. These varied combinations of clinical features were originally described as separate disorders. Affected individuals may be diagnosed with ataxia, delayed dentition, and hypomyelination (ADDH); hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); tremor-ataxia with central hypomyelination (TACH); leukodystrophy with oligodontia (LO); or hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). Because these disorders were later found to have the same genetic cause, researchers now group them as variations of the single condition Pol III-related leukodystrophy. ar Autosomal recessive POLR3A https://medlineplus.gov/genetics/gene/polr3a POLR3B https://medlineplus.gov/genetics/gene/polr3b 4H syndrome ADDH Ataxia, delayed dentition, and hypomyelination Dentoleukoencephalopathy HCAHC HLD7 HLD8 Hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum Hypomyelination, hypodontia, hypogonadotropic hypogonadism Leukodystrophy with oligodontia Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism Leukoencephalopathy-ataxia-hypodontia-hypomyelination LO Odontoleukodystrophy Pol III disorder Pol III-related hypomyelinating leukodystrophies Ribonucleic acid polymerase III-related leukodystrophy TACH Tremor-ataxia with central hypomyelination GTR C5679947 MeSH D020279 OMIM 607694 OMIM 614381 SNOMED CT 712637001 SNOMED CT 721846006 SNOMED CT 722064003 2013-06 2023-02-28 Poland syndrome https://medlineplus.gov/genetics/condition/poland-syndrome descriptionPoland syndrome is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals.People with Poland syndrome are typically missing part of one of the major chest muscles, called the pectoralis major. In most affected individuals, the missing part is the large section of the muscle that normally runs from the upper arm to the breastbone (sternum). The abnormal pectoralis major muscle may cause the chest to appear concave. In some cases, additional muscles on the affected side of the torso, including muscles in the chest wall, side, and shoulder, may be missing or underdeveloped. There may also be rib cage abnormalities, such as shortened ribs, and the ribs may be noticeable due to less fat under the skin (subcutaneous fat). Breast and nipple abnormalities may also occur, and underarm (axillary) hair is sometimes sparse or abnormally placed. In most cases, the abnormalities in the chest area do not cause health problems or affect movement.Many people with Poland syndrome have hand abnormalities on the affected side, commonly including an underdeveloped hand with abnormally short fingers (brachydactyly); small, underdeveloped (vestigial) fingers; and some fingers that are fused together (syndactyly). This combination of hand abnormalities is called symbrachydactyly. Some affected individuals have only one or two of these features, or have a mild hand abnormality that is hardly noticeable; more severe abnormalities can cause problems with use of the hand. The bones of the forearm (radius and ulna) are shortened in some people with Poland syndrome, but this shortening may also be difficult to detect unless measured.Mild cases of Poland syndrome without hand involvement may not be evident until puberty, when the differences (asymmetry) between the two sides of the chest become more apparent. By contrast, severely affected individuals have abnormalities of the chest, hand, or both that are apparent at birth. In rare cases, severely affected individuals have abnormalities of internal organs such as a lung or a kidney, or the heart is abnormally located in the right side of the chest (dextrocardia).Rarely, chest and hand abnormalities resembling those of Poland syndrome occur on both sides of the body, but researchers disagree as to whether this condition is a variant of Poland syndrome or a different disorder. u Pattern unknown Poland anomaly Poland sequence Poland syndactyly Poland's anomaly Poland's syndrome Unilateral defect of pectoralis major and syndactyly of the hand MeSH D011045 OMIM 173800 SNOMED CT 38371006 2013-03 2020-08-18 Polycystic kidney disease https://medlineplus.gov/genetics/condition/polycystic-kidney-disease descriptionPolycystic kidney disease is a disorder that affects the kidneys and other organs. Clusters of fluid-filled sacs, called cysts, develop in the kidneys and interfere with their ability to filter waste products from the blood. The growth of cysts causes the kidneys to become enlarged and can lead to kidney failure. Cysts may also develop in other organs, particularly the liver.Frequent complications of polycystic kidney disease include dangerously high blood pressure (hypertension), pain in the back or sides, blood in the urine (hematuria), recurrent urinary tract infections, kidney stones, and heart valve abnormalities. Additionally, people with polycystic kidney disease have an increased risk of an abnormal bulging (an aneurysm) in a large blood vessel called the aorta or in blood vessels at the base of the brain. Aneurysms can be life-threatening if they tear or rupture.The two major forms of polycystic kidney disease are distinguished by the usual age of onset and the pattern in which it is passed through families. The autosomal dominant form (sometimes called ADPKD) has signs and symptoms that typically begin in adulthood, although cysts in the kidney are often present from birth or childhood. Autosomal dominant polycystic kidney disease can be further divided into type 1 and type 2, depending on the genetic cause. The autosomal recessive form of polycystic kidney disease (sometimes called ARPKD) is much rarer and is often lethal early in life. The signs and symptoms of this condition are usually apparent at birth or in early infancy. ad Autosomal dominant ar Autosomal recessive PKD1 https://medlineplus.gov/genetics/gene/pkd1 PKD2 https://medlineplus.gov/genetics/gene/pkd2 PKHD1 https://medlineplus.gov/genetics/gene/pkhd1 PKD Polycystic renal disease GTR C0085413 GTR C0085548 GTR C2751306 GTR C3149841 GTR C3887964 ICD-10-CM Q61.1 ICD-10-CM Q61.11 ICD-10-CM Q61.19 ICD-10-CM Q61.2 ICD-10-CM Q61.3 ICD-10-CM Z82.71 MeSH D007690 OMIM 173900 OMIM 263200 OMIM 600666 OMIM 613095 SNOMED CT 28728008 SNOMED CT 28770003 2006-06 2024-12-16 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy https://medlineplus.gov/genetics/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy descriptionPolycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, commonly known as PLOSL, is a progressive disorder that affects the bones and brain.  "Polycystic lipomembranous osteodysplasia" refers to cyst-like bone changes that can be seen on x-rays.  "Sclerosing leukoencephalopathy" describes specific changes in the brain that are found in people with this disorder.The bone abnormalities associated with PLOSL usually become apparent in a person's twenties.  In most affected individuals, pain and tenderness in the ankles and feet are the first symptoms of the disease.  Several years later, broken bones (fractures) begin to occur frequently, particularly in the bones of the ankles, feet, wrists, and hands.  Bone pain and fractures are caused by thinning of the bones (osteoporosis) and cysts in the bones.  These abnormalities weaken bones and make them more likely to break.The brain abnormalities characteristic of PLOSL typically appear in a person's thirties. Personality changes are among the first noticeable problems, followed by a loss of judgment, feelings of intense happiness (euphoria), a loss of inhibition, and poor concentration. These neurologic changes cause significant problems in an affected person's social and family life.  As the disease progresses, it causes a severe decline in thinking and reasoning abilities (dementia). Affected people ultimately become unable to walk, speak, or care for themselves. People with this disease usually live only into their thirties or forties. ar Autosomal recessive TYROBP https://medlineplus.gov/genetics/gene/tyrobp TREM2 https://medlineplus.gov/genetics/gene/trem2 Nasu-Hakola disease NHD PLO-SL PLOSL Presenile dementia with bone cysts GTR C4721893 MeSH D019636 OMIM 221770 SNOMED CT 702347001 2023-10 2023-10-17 Polycystic ovary syndrome https://medlineplus.gov/genetics/condition/polycystic-ovary-syndrome descriptionPolycystic ovary syndrome is a condition that affects women in their child-bearing years and alters the levels of multiple hormones, resulting in problems affecting many body systems.Most women with polycystic ovary syndrome produce excess male sex hormones (androgens), a condition called hyperandrogenism. Having too much of these hormones typically leads to excessive body hair growth (hirsutism), acne, and male pattern baldness.Hyperandrogenism and abnormal levels of other sex hormones prevent normal release of egg cells from the ovaries (ovulation) and regular menstrual periods, leading to difficulty conceiving a child (subfertility) or a complete inability to conceive (infertility). For those who achieve pregnancy, there is an increased risk of complications and pregnancy loss. Due to irregular and infrequent menstruation and hormone abnormalities, affected women have an increased risk of cancer of the uterine lining (endometrial cancer).In polycystic ovary syndrome, one or both ovaries can contain multiple small, immature ovarian follicles that can appear as cysts on medical imaging. Normally, ovarian follicles contain egg cells, which are released during ovulation. In polycystic ovary syndrome, abnormal hormone levels prevent follicles from growing and maturing to release egg cells. Instead, these immature follicles accumulate in the ovaries. Affected women can have 12 or more of these follicles. The number of these follicles usually decreases with age.About half of all women with polycystic ovary syndrome are overweight or have obesity and are at increased risk of a fatty liver. Additionally, many women with polycystic ovary syndrome have elevated levels of insulin, which is a hormone that helps control levels of blood glucose, also called blood sugar. By age 40, about 10 percent of overweight women with polycystic ovary syndrome develop abnormally high blood glucose levels (type 2 diabetes), and up to 35 percent develop prediabetes (higher-than-normal blood glucose levels that do not reach the cutoff for diabetes). Obesity and increased insulin levels (hyperinsulinemia) further increase the production of androgens in polycystic ovary syndrome.Women with polycystic ovary syndrome are also at increased risk for developing metabolic syndrome, which is a group of conditions that include high blood pressure (hypertension), increased belly fat, high levels of unhealthy fats and low levels of healthy fats in the blood, and high blood glucose levels. About 20 percent of affected adults experience pauses in breathing during sleep (sleep apnea). Women with polycystic ovary syndrome are more likely than women in the general popluation to have mood disorders such as depression. u Pattern unknown AR https://medlineplus.gov/genetics/gene/ar LHCGR https://medlineplus.gov/genetics/gene/lhcgr INSR https://medlineplus.gov/genetics/gene/insr SUOX https://medlineplus.gov/genetics/gene/suox ERBB4 https://www.ncbi.nlm.nih.gov/gene/2066 FSHB https://www.ncbi.nlm.nih.gov/gene/2488 FSHR https://www.ncbi.nlm.nih.gov/gene/2492 GATA4 https://www.ncbi.nlm.nih.gov/gene/2626 RAB5B https://www.ncbi.nlm.nih.gov/gene/5869 HMGA2 https://www.ncbi.nlm.nih.gov/gene/8091 RAD50 https://www.ncbi.nlm.nih.gov/gene/10111 YAP1 https://www.ncbi.nlm.nih.gov/gene/10413 KRR1 https://www.ncbi.nlm.nih.gov/gene/11103 TOX3 https://www.ncbi.nlm.nih.gov/gene/27324 DENND1A https://www.ncbi.nlm.nih.gov/gene/57706 THADA https://www.ncbi.nlm.nih.gov/gene/63892 FTO https://www.ncbi.nlm.nih.gov/gene/79068 AOPEP https://www.ncbi.nlm.nih.gov/gene/84909 SUMO1P1 https://www.ncbi.nlm.nih.gov/gene/391257 Cystic disease of ovaries Cystic disease of ovary Multicystic ovaries PCO PCOD PCOS Polycystic ovarian disease Polycystic ovarian syndrome Sclerocystic ovarian degeneration Sclerocystic ovaries Sclerocystic ovary syndrome Stein-Leventhal syndrome GTR C0032460 ICD-10-CM E28.2 MeSH D011085 OMIM 184700 SNOMED CT 69878008 SNOMED CT 830047004 SNOMED CT 830048009 SNOMED CT 830049001 SNOMED CT 830052009 SNOMED CT 830053004 SNOMED CT 830054005 2018-02 2024-09-19 Polycythemia vera https://medlineplus.gov/genetics/condition/polycythemia-vera descriptionPolycythemia vera is a condition characterized by an increased number of red blood cells in the bloodstream. Affected individuals may also have excess white blood cells and blood clotting cells called platelets. These extra cells and platelets cause the blood to be thicker than normal. As a result, abnormal blood clots are more likely to form and block the flow of blood through arteries and veins. Individuals with polycythemia vera have an increased risk of deep vein thrombosis (DVT), a type of blood clot that occurs in the deep veins of the arms or legs. If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism (PE). Affected individuals also have an increased risk of heart attack and stroke caused by blood clots in the heart and brain.Polycythemia vera typically develops in adulthood, around age 60, although in rare cases it occurs in children and young adults. This condition may not cause any symptoms in its early stages. Some people with polycythemia vera experience headaches, dizziness, ringing in the ears (tinnitus), impaired vision, or itchy skin. Affected individuals frequently have reddened skin because of the extra red blood cells. Other complications of polycythemia vera include an enlarged spleen (splenomegaly), stomach ulcers, gout (a form of arthritis caused by a buildup of uric acid in the joints), heart disease, and cancer of blood-forming cells (leukemia). ad Autosomal dominant n Not inherited JAK2 https://medlineplus.gov/genetics/gene/jak2 TET2 https://medlineplus.gov/genetics/gene/tet2 Osler-Vaquez disease Polycythemia ruba vera Primary polycythemia PRV PV GTR C0032463 ICD-10-CM D45 MeSH D011087 OMIM 263300 SNOMED CT 109992005 SNOMED CT 127066000 SNOMED CT 128841001 SNOMED CT 414127000 SNOMED CT 871540009 2010-05 2020-08-18 Polymicrogyria https://medlineplus.gov/genetics/condition/polymicrogyria descriptionPolymicrogyria is a condition characterized by abnormal development of the brain before birth. The surface of the brain normally has many ridges or folds, called gyri. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small. The name of this condition literally means too many (poly-) small (micro-) folds (-gyria) in the surface of the brain.Polymicrogyria can affect part of the brain or the whole brain. When the condition affects one side of the brain, researchers describe it as unilateral. When it affects both sides of the brain, it is described as bilateral. The signs and symptoms associated with polymicrogyria depend on how much of the brain, and which particular brain regions, are affected.Researchers have identified multiple forms of polymicrogyria. The mildest form is known as unilateral focal polymicrogyria. This form of the condition affects a relatively small area on one side of the brain. It may cause minor neurological problems, such as mild seizures that can be easily controlled with medication. Some people with unilateral focal polymicrogyria do not have any problems associated with the condition.Bilateral forms of polymicrogyria tend to cause more severe neurological problems. Signs and symptoms of these conditions can include recurrent seizures (epilepsy), delayed development, crossed eyes, problems with speech and swallowing, and muscle weakness or paralysis. The most severe form of the disorder, bilateral generalized polymicrogyria, affects the entire brain. This condition causes severe intellectual disability, problems with movement, and seizures that are difficult or impossible to control with medication.Polymicrogyria most often occurs as an isolated feature, although it can occur with other brain abnormalities. It is also a feature of several genetic syndromes characterized by intellectual disability and multiple birth defects. These include 22q11.2 deletion syndrome, Adams-Oliver syndrome, Aicardi syndrome, Galloway-Mowat syndrome, Joubert syndrome, and Zellweger spectrum disorder. xd X-linked dominant ar Autosomal recessive ad Autosomal dominant xr X-linked recessive ADGRG1 https://medlineplus.gov/genetics/gene/adgrg1 TUBB2B https://medlineplus.gov/genetics/gene/tubb2b PMG GTR C1847352 GTR C3552236 GTR C4013648 MeSH D065706 OMIM 300388 OMIM 606854 OMIM 610031 OMIM 612691 SNOMED CT 438583008 SNOMED CT 4945003 SNOMED CT 715905006 SNOMED CT 722036008 2009-06 2023-11-08 Pompe disease https://medlineplus.gov/genetics/condition/pompe-disease descriptionPompe disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally.Researchers have described three types of Pompe disease, which differ in severity and the age at which they appear. These types are known as classic infantile-onset, non-classic infantile-onset, and late-onset.The classic form of infantile-onset Pompe disease begins within a few months of birth. Infants with this disorder typically experience muscle weakness (myopathy), poor muscle tone (hypotonia), an enlarged liver (hepatomegaly), and heart defects. Affected infants may also fail to gain weight and grow at the expected rate (failure to thrive) and have breathing problems. If untreated, this form of Pompe disease leads to death from heart failure in the first year of life.The non-classic form of infantile-onset Pompe disease usually appears by age 1. It is characterized by delayed motor skills (such as rolling over and sitting) and progressive muscle weakness. The heart may be abnormally large (cardiomegaly), but affected individuals usually do not experience heart failure. The muscle weakness in this disorder leads to serious breathing problems, and most children with non-classic infantile-onset Pompe disease live only into early childhood.The late-onset type of Pompe disease may not become apparent until later in childhood, adolescence, or adulthood. Late-onset Pompe disease is usually milder than the infantile-onset forms of this disorder and is less likely to involve the heart. Most individuals with late-onset Pompe disease experience progressive muscle weakness, especially in the legs and the trunk, including the muscles that control breathing. As the disorder progresses, breathing problems can lead to respiratory failure. ar Autosomal recessive GAA https://medlineplus.gov/genetics/gene/gaa Acid maltase deficiency Acid maltase deficiency disease Alpha-1,4-glucosidase deficiency AMD Deficiency of alpha-glucosidase GAA deficiency Glycogen storage disease type II Glycogenosis type II GSD II GSD2 Pompe's disease GTR C0017921 GTR C0751173 ICD-10-CM E74.02 MeSH D006009 OMIM 232300 SNOMED CT 124462004 SNOMED CT 274864009 2010-02 2021-05-20 Pontocerebellar hypoplasia https://medlineplus.gov/genetics/condition/pontocerebellar-hypoplasia descriptionPontocerebellar hypoplasia is a group of related conditions that affect the development of the brain. The term "pontocerebellar" refers to the pons and the cerebellum, which are the brain structures that are most severely affected in many forms of this disorder. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals between the cerebellum and the rest of the brain. The cerebellum, which is located at the back of the brain, normally coordinates movement. The term "hypoplasia" refers to the underdevelopment of these brain regions.Pontocerebellar hypoplasia also causes impaired growth of other parts of the brain, leading to an unusually small head size (microcephaly). This microcephaly is usually not apparent at birth but becomes noticeable as brain growth continues to be slow in infancy and early childhood.Researchers have described at least ten types of pontocerebellar hypoplasia. All forms of this condition are characterized by impaired brain development, delayed development overall, problems with movement, and intellectual disability. The brain abnormalities are usually present at birth, and in some cases they can be detected before birth. Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood.The two major forms of pontocerebellar hypoplasia are designated as type 1 (PCH1) and type 2 (PCH2). In addition to the brain abnormalities described above, PCH1 causes problems with muscle movement resulting from a loss of specialized nerve cells called motor neurons in the spinal cord, similar to another genetic disorder known as spinal muscular atrophy. Individuals with PCH1 also have very weak muscle tone (hypotonia), joint deformities called contractures, vision impairment, and breathing and feeding problems that are evident from early infancy.Common features of PCH2 include a lack of voluntary motor skills (such as grasping objects, sitting, or walking), problems with swallowing (dysphagia), and an absence of communication, including speech. Affected children typically develop temporary jitteriness (generalized clonus) in early infancy, abnormal patterns of movement described as chorea or dystonia, and stiffness (spasticity). Many also have impaired vision and seizures.The other forms of pontocerebellar hypoplasia, designated as type 3 (PCH3) through type 10 (PCH10), appear to be rare and have each been reported in only a small number of individuals. Because the different types have overlapping features, and some are caused by mutations in the same genes, researchers have proposed that the types be considered as a spectrum instead of distinct conditions. ar Autosomal recessive TSEN2 https://medlineplus.gov/genetics/gene/tsen2 TSEN34 https://medlineplus.gov/genetics/gene/tsen34 TSEN54 https://medlineplus.gov/genetics/gene/tsen54 RARS2 https://medlineplus.gov/genetics/gene/rars2 VRK1 https://medlineplus.gov/genetics/gene/vrk1 EXOSC3 https://medlineplus.gov/genetics/gene/exosc3 SEPSECS https://medlineplus.gov/genetics/gene/sepsecs AMPD2 https://www.ncbi.nlm.nih.gov/gene/271 CHMP1A https://www.ncbi.nlm.nih.gov/gene/5119 CLP1 https://www.ncbi.nlm.nih.gov/gene/10978 Congenital pontocerebellar hypoplasia OPCH PCH GTR C1261175 MeSH D002526 OMIM 225753 OMIM 277470 OMIM 607596 OMIM 608027 OMIM 610204 OMIM 611523 OMIM 612389 OMIM 612390 OMIM 613811 OMIM 614678 OMIM 614961 OMIM 614969 OMIM 615803 OMIM 615809 OMIM 615851 SNOMED CT 373666002 SNOMED CT 45163000 2014-11 2023-08-18 Popliteal pterygium syndrome https://medlineplus.gov/genetics/condition/popliteal-pterygium-syndrome descriptionPopliteal pterygium syndrome is a condition that affects the development of the face, skin, and genitals. Most people with this disorder are born with a cleft lip, a cleft palate (an opening in the roof of the mouth), or both. Affected individuals may have depressions (pits) near the center of the lower lip, which may appear moist due to the presence of salivary and mucous glands in the pits. Small mounds of tissue on the lower lip may also occur. In some cases, people with popliteal pterygium syndrome have missing teeth.Individuals with popliteal pterygium syndrome may be born with webs of skin on the backs of the legs across the knee joint, which may impair mobility unless surgically removed. Affected individuals may also have webbing or fusion of the fingers or toes (syndactyly), characteristic triangular folds of skin over the nails of the large toes, or tissue connecting the upper and lower eyelids or the upper and lower jaws. They may have abnormal genitals, including unusually small external genital folds (hypoplasia of the labia majora) in females. Affected males may have undescended testes (cryptorchidism) or a scrotum divided into two lobes (bifid scrotum).People with popliteal pterygium syndrome who have cleft lip and/or palate, like other individuals with these facial conditions, may have an increased risk of delayed language development, learning disabilities, or other mild cognitive problems. The average IQ of individuals with popliteal pterygium syndrome is not significantly different from that of the general population. ad Autosomal dominant IRF6 https://medlineplus.gov/genetics/gene/irf6 Facio-genito-popliteal syndrome PPS GTR C0265259 MeSH D000015 OMIM 119500 SNOMED CT 66783006 2022-07 2023-11-08 Porphyria https://medlineplus.gov/genetics/condition/porphyria descriptionPorphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. Heme is a vital molecule for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is a component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. Some types of porphyria, called cutaneous porphyrias, primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria, hepatoerythropoietic porphyria, and porphyria cutanea tarda.Other types of porphyria, called acute porphyrias, primarily affect the nervous system. These disorders are described as "acute" because their signs and symptoms appear quickly and usually last a short time. Episodes of acute porphyria can cause abdominal pain, vomiting, constipation, and diarrhea. During an episode, a person may also experience muscle weakness, seizures, fever, and mental changes such as anxiety and hallucinations. These signs and symptoms can be life-threatening, especially if the muscles that control breathing become paralyzed. Acute porphyrias include acute intermittent porphyria and ALAD deficiency porphyria. Two other forms of porphyria, hereditary coproporphyria and variegate porphyria, can have both acute and cutaneous symptoms.The porphyrias can also be split into erythropoietic and hepatic types, depending on where damaging compounds called porphyrins and porphyrin precursors first build up in the body. In erythropoietic porphyrias, these compounds originate in the bone marrow. Erythropoietic porphyrias include erythropoietic protoporphyria and congenital erythropoietic porphyria. Health problems associated with erythropoietic porphyrias include a low number of red blood cells (anemia) and enlargement of the spleen (splenomegaly). The other types of porphyrias are considered hepatic porphyrias. In these disorders, porphyrins and porphyrin precursors originate primarily in the liver, leading to abnormal liver function and an increased risk of developing liver cancer.Environmental factors can strongly influence the occurrence and severity of signs and symptoms of porphyria. Alcohol, smoking, certain drugs, hormones, other illnesses, stress, and dieting or periods without food (fasting) can all trigger the signs and symptoms of some forms of the disorder. Additionally, exposure to sunlight worsens the skin damage in people with cutaneous porphyrias. ar Autosomal recessive xd X-linked dominant ad Autosomal dominant HFE https://medlineplus.gov/genetics/gene/hfe ALAD https://medlineplus.gov/genetics/gene/alad HMBS https://medlineplus.gov/genetics/gene/hmbs UROS https://medlineplus.gov/genetics/gene/uros UROD https://medlineplus.gov/genetics/gene/urod CPOX https://medlineplus.gov/genetics/gene/cpox PPOX https://medlineplus.gov/genetics/gene/ppox FECH https://medlineplus.gov/genetics/gene/fech ALAS2 https://medlineplus.gov/genetics/gene/alas2 Hematoporphyria Porphyrin disorder GTR C0162531 GTR C0162532 GTR C0162565 GTR C0268323 GTR C2677889 GTR C4692546 GTR C5848305 GTR C5886774 ICD-10-CM E80.0 ICD-10-CM E80.1 ICD-10-CM E80.2 ICD-10-CM E80.20 ICD-10-CM E80.21 ICD-10-CM E80.29 MeSH D011164 OMIM 121300 OMIM 125270 OMIM 176000 OMIM 176100 OMIM 176200 OMIM 177000 OMIM 263700 OMIM 300752 SNOMED CT 22935002 SNOMED CT 234422006 SNOMED CT 238056003 SNOMED CT 276262000 SNOMED CT 276263005 SNOMED CT 276265003 SNOMED CT 418470004 SNOMED CT 44574006 SNOMED CT 51022005 SNOMED CT 58275005 SNOMED CT 7425008 SNOMED CT 84816006 2009-07 2020-08-18 Potassium-aggravated myotonia https://medlineplus.gov/genetics/condition/potassium-aggravated-myotonia descriptionPotassium-aggravated myotonia is a disorder that affects muscles used for movement (skeletal muscles). Beginning in childhood or adolescence, people with this condition experience episodes of sustained muscle tensing (myotonia) that prevent muscles from relaxing. Myotonia causes muscle stiffness that worsens after exercise. In this disorder, episodes of myotonia may also be triggered (aggravated) by eating foods that are high in the mineral potassium, such as bananas and potatoes. During these episodes, stiffness occurs in skeletal muscles throughout the body. Potassium-aggravated myotonia ranges in severity from mild episodes of muscle stiffness (myotonia fluctuans) to severe, disabling disease with frequent attacks (myotonia permanen). Unlike some other forms of myotonia, potassium-aggravated myotonia is not associated with episodes of muscle weakness. ad Autosomal dominant SCN4A https://medlineplus.gov/genetics/gene/scn4a PAM Sodium channel myotonia GTR C2931826 MeSH D020967 OMIM 608390 SNOMED CT 702355008 2007-04 2021-08-05 Potocki-Lupski syndrome https://medlineplus.gov/genetics/condition/potocki-lupski-syndrome descriptionPotocki-Lupski syndrome is a condition that results from having an extra copy (duplication) of a small piece of chromosome 17 in each cell. The duplication occurs on the short (p) arm of the chromosome at a position designated p11.2. This condition is also known as 17p11.2 duplication syndrome.Infants with Potocki-Lupski syndrome may have weak muscle tone (hypotonia) and swallowing difficulties (dysphagia) that lead to feeding problems. Some affected babies do not grow and gain weight at the expected rate (described as failure to thrive), and children with this condition tend to be shorter and weigh less than their peers. About 40 percent of babies with Potocki-Lupski syndrome are born with a heart defect, which in some cases is life-threatening.Babies and children with Potocki-Lupski syndrome have delayed development, including delayed speech and language skills and gross motor skills such sitting, standing, and walking. As they get older, affected individuals have intellectual disability, which is usually mild to moderate, and ongoing difficulties with speech. Potocki-Lupski syndrome is also associated with behavioral problems, which can include attention problems, hyperactivity, compulsive or impulsive behaviors, and anxiety. Many people with this condition have charateristics of autism spectrum disorder, which affects social interaction and communication.Other signs and symptoms of Potocki-Lupski syndrome can include vision and hearing problems, dental and skeletal abnormalities, and abnormal kidney development and function. Many affected individuals have problems with sleep, including short pauses in breathing during sleep (sleep apnea) and trouble falling asleep and staying asleep. The condition can also have subtle differences in facial features, including outside corners of the eyes that point downward (down-slanting palpebral fissures), a triangular face with a broad forehead and a small jaw (micrognathia), and widely spaced eyes (hypertelorism). ad Autosomal dominant RAI1 https://medlineplus.gov/genetics/gene/rai1 17 https://medlineplus.gov/genetics/chromosome/17 17p11.2 duplication syndrome 17p11.2 microduplication syndrome Chromosome 17p11.2 duplication syndrome Dup(17)(p11.2p11.2) Duplication 17p11.2 syndrome PLS PTLS GTR C2931246 MeSH D002658 MeSH D008607 MeSH D058674 OMIM 610883 SNOMED CT 734016004 2017-10 2023-07-13 Potocki-Shaffer syndrome https://medlineplus.gov/genetics/condition/potocki-shaffer-syndrome descriptionPotocki-Shaffer syndrome is a disorder that affects the development of the bones, brain, and other tissues. The signs and symptoms of Potocki-Shaffer syndrome vary widely among affected individuals.People with Potocki-Shaffer syndrome have enlarged openings (foramina) in the parietal bones, which are the two bones that form the top and sides of the skull. Openings in the parietal bones are normal during fetal development, but they usually close before birth. In people with this condition, the parietal foramina are larger than normal and may remain open after birth. Affected individuals often have a wide, short skull (brachycephaly). Their head size may be normal or unusually small.Most people with Potocki-Shaffer syndrome have multiple noncancerous (benign) bone tumors called osteochondromas. In rare instances, these tumors become cancerous.Other features of Potocki-Shaffer syndrome include intellectual disabilities, recurrent seizures (epilepsy), and delayed development of speech and motor skills (such as sitting and walking).Many people with Potocki-Shaffer syndrome have distinctive facial features, such as a broad and tall forehead, a prominent bridge of the nose, a narrow distance between the nose and upper lip (a short philtrum), a short nose with a wide tip, and a downturned mouth.Less commonly, Potocki-Shaffer syndrome causes vision problems; additional skeletal abnormalities; and defects in the heart, kidneys, and urinary tract. ad Autosomal dominant EXT2 https://medlineplus.gov/genetics/gene/ext2 ALX4 https://medlineplus.gov/genetics/gene/alx4 PHF21A https://medlineplus.gov/genetics/gene/phf21a 11 https://medlineplus.gov/genetics/chromosome/11 Chromosome 11p11.2 deletion syndrome P11pDS Proximal 11p deletion syndrome PSS GTR C1832588 MeSH D025063 OMIM 601224 SNOMED CT 702346005 2026-04 2026-04-07 Prader-Willi syndrome https://medlineplus.gov/genetics/condition/prader-willi-syndrome descriptionPrader-Willi syndrome is a complex genetic condition that affects many parts of the body. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, affected individuals develop an extreme hunger, which leads to chronic overeating (hyperphagia) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes (the most common form of diabetes).People with Prader-Willi syndrome typically have mild to moderate intellectual impairment and learning disabilities. Behavioral problems are common, including temper outbursts, stubbornness, and compulsive behavior such as picking at the skin. Sleep abnormalities can also occur. Additional features of this condition include distinctive facial features such as a narrow forehead, almond-shaped eyes, and a triangular mouth; short stature; and small hands and feet. Some people with Prader-Willi syndrome have unusually fair skin and light-colored hair. Both affected males and affected females have underdeveloped genitals. Puberty is delayed or incomplete, and most affected individuals are unable to have children (infertile). n Not inherited OCA2 https://medlineplus.gov/genetics/gene/oca2 15 https://medlineplus.gov/genetics/chromosome/15 Prader-Labhart-Willi syndrome PWS Willi-Prader syndrome GTR C0032897 MeSH D011218 OMIM 176270 SNOMED CT 89392001 2022-05 2022-05-13 Preeclampsia https://medlineplus.gov/genetics/condition/preeclampsia descriptionPreeclampsia is a complication of pregnancy in which affected women develop high blood pressure (hypertension); they can also have abnormally high levels of protein in their urine (proteinuria). This condition usually occurs in the last few months of pregnancy and often requires early delivery of the infant. However, this condition can also appear shortly after giving birth (postpartum preeclampsia).Many women with mild preeclampsia do not feel ill, and the condition is often first detected through blood pressure and urine testing in their doctor's office. In addition to hypertension and proteinuria, signs and symptoms of preeclampsia can include excessive swelling (edema) of the face or hands and a weight gain of more than 3 to 5 pounds in a week due to fluid retention. Affected women may also experience headaches, dizziness, irritability, shortness of breath, a decrease in urination, upper abdominal pain, and nausea or vomiting. Vision changes may develop, including flashing lights or spots, increased sensitivity to light (photophobia), blurry vision, or temporary blindness.In many cases, symptoms of preeclampsia go away within a few days after the baby is born. In severe cases, however, preeclampsia can damage the mother's organs, such as the heart, liver, and kidneys, and can lead to life-threatening complications. Extremely high blood pressure in the mother can cause bleeding in the brain (hemorrhagic stroke). The effects of high blood pressure on the brain (hypertensive encephalopathy) may also result in seizures. If seizures occur, the condition is considered to have worsened to eclampsia, which can result in coma. About 1 in 200 women with untreated preeclampsia develop eclampsia. Eclampsia can also develop without any obvious signs of preeclampsia.Between 10 and 20 percent of women with severe preeclampsia develop another potentially life-threatening complication called HELLP syndrome. HELLP stands for hemolysis (premature red blood cell breakdown), elevated liver enzyme levels, and low platelets (cells involved in blood clotting), which are the key features of this condition.Severe preeclampsia can also affect the fetus, with impairment of blood and oxygen flow leading to growth problems or stillbirth. Infants delivered early due to preeclampsia may have complications associated with prematurity, such as breathing problems caused by underdeveloped lungs.Women who have had preeclampsia have approximately twice the lifetime risk of heart disease and stroke than do women in the general population. Researchers suggest that preeclampsia, heart disease, and stroke may share common risk factors. Women who have diseases such as obesity, hypertension, heart disease, diabetes, or kidney disease before they become pregnant have an increased risk of developing preeclampsia. Preeclampsia is most likely to occur in a woman's first pregnancy, although it can occur in subsequent pregnancies, particularly in women with other health conditions. u Pattern unknown n Not inherited Gestational proteinuric hypertension Pre-eclampsia Pregnancy-induced hypertension Toxemia of pregnancy GTR C0032914 GTR C1836255 GTR C3281288 ICD-10-CM O11 ICD-10-CM O11.1 ICD-10-CM O11.2 ICD-10-CM O11.3 ICD-10-CM O11.9 ICD-10-CM O14.0 ICD-10-CM O14.00 ICD-10-CM O14.02 ICD-10-CM O14.03 ICD-10-CM O14.1 ICD-10-CM O14.10 ICD-10-CM O14.12 ICD-10-CM O14.13 ICD-10-CM O14.2 ICD-10-CM O14.20 ICD-10-CM O14.22 ICD-10-CM O14.23 ICD-10-CM O14.9 ICD-10-CM O14.90 ICD-10-CM O14.92 ICD-10-CM O14.93 MeSH D011225 OMIM 189800 OMIM 609402 OMIM 609403 OMIM 609404 OMIM 614595 SNOMED CT 48194001 2013-12 2025-01-22 Prekallikrein deficiency https://medlineplus.gov/genetics/condition/prekallikrein-deficiency descriptionPrekallikrein deficiency is a blood condition that usually causes no health problems. In people with this condition, blood tests show a prolonged activated partial thromboplastin time (PTT), a result that is typically associated with bleeding problems; however, bleeding problems generally do not occur in prekallikrein deficiency. The condition is usually discovered when blood tests are done for other reasons.A few people with prekallikrein deficiency have experienced health problems related to blood clotting such as heart attack, stroke, a clot in the deep veins of the arms or legs (deep vein thrombosis), nosebleeds, or excessive bleeding after surgery. However, these are common problems in the general population, and most affected individuals have other risk factors for developing them, so it is unclear whether their occurrence is related to prekallikrein deficiency. ar Autosomal recessive KLKB1 https://medlineplus.gov/genetics/gene/klkb1 Congenital prekallikrein deficiency Fletcher factor deficiency Fletcher trait PKK deficiency GTR C0272339 MeSH D001778 OMIM 612423 SNOMED CT 48976006 2014-07 2020-08-18 Primary carnitine deficiency https://medlineplus.gov/genetics/condition/primary-carnitine-deficiency descriptionPrimary carnitine deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Carnitine, a natural substance acquired mostly through food, is used by cells to process fats and produce energy.Signs and symptoms of primary carnitine deficiency typically appear during infancy or early childhood and can include severe brain dysfunction (encephalopathy), a weakened and enlarged heart (cardiomyopathy), vomiting, muscle weakness, and low blood glucose (hypoglycemia). The severity of this condition varies among affected individuals. Some people with primary carnitine deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. All individuals with this disorder are at risk for sudden death.Problems related to primary carnitine deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children who appear to be recovering from viral infections such as chickenpox or flu. ar Autosomal recessive SLC22A5 https://medlineplus.gov/genetics/gene/slc22a5 Carnitine transporter deficiency Carnitine uptake defect Carnitine uptake deficiency CUD Renal carnitine transport defect Systemic carnitine deficiency GTR C0342788 ICD-10-CM E71.41 MeSH D008052 OMIM 212140 SNOMED CT 21764004 2023-11 2023-11-27 Primary ciliary dyskinesia https://medlineplus.gov/genetics/condition/primary-ciliary-dyskinesia descriptionPrimary ciliary dyskinesia is a disorder that is characterized by chronic respiratory tract infections, abnormally positioned internal organs, and difficulties having biological children (decreased fertility). The signs and symptoms of this condition are caused by abnormal cilia and flagella. Cilia are microscopic, finger-like projections that stick out from the surface of cells. Cilia help cells move where they are needed; they also help move substances within the body. Flagella, which are similar to cilia, are tail-like structures that propel sperm cells forward. Without properly functioning cilia, people with primary ciliary dyskinesia often have problems removing fluid and particles from their airways. Most babies with primary ciliary dyskinesia experience breathing problems at birth (neonatal respiratory distress), which suggests that cilia also play an important role in clearing fetal fluid from the lungs. Children with primary ciliary dyskinesia typically have year-round nasal congestion and a chronic cough beginning in the first year of life. Because affected individuals also have trouble removing bacteria from the respiratory tract, they may experience frequent respiratory tract infections beginning in early childhood. Chronic respiratory tract infections can result in a condition called bronchiectasis, which damages the passages that lead from the windpipe to the lungs (bronchi). Bronchiectasis can cause life-threatening breathing problems.Another feature of primary ciliary dyskinesia is recurrent ear infections (otitis media), especially in young children. Otitis media can lead to permanent hearing loss if left untreated. These ear infections are likely related to abnormal cilia within the inner ear. About 40 percent of people with primary ciliary dyskinesia have a mirror-image reversal of their internal organs (situs inversus totalis). For example, the heart is on the right side of the body instead of the left in these individuals. These abnormalities arise early in embryonic development when the differences between the left and right sides of the body are established. Situs inversus totalis does not typically cause additional health problems. When someone with primary ciliary dyskinesia has situs inversus totalis, they are often said to have Kartagener syndrome.Heterotaxy syndrome (sometimes also called situs ambiguous) is another disorder of organ development that can be associated with primary ciliary dyskinesia. Approximately 9 to 12 percent of people with primary ciliary dyskinesia have heterotaxy syndrome, which is characterized by abnormalities of the heart, liver, intestines, or spleen. These organs may be structurally abnormal or improperly positioned. In addition, affected individuals may lack a spleen (asplenia) or have multiple spleens (polysplenia). Heterotaxy syndrome is also a result of problems establishing the left and right sides of the body during embryonic development. The severity of heterotaxy syndrome varies widely among affected individuals, and people with this condition may have heart abnormalities that can be life-threatening.Primary ciliary dyskinesia can also cause fertility problems. Vigorous movements of the flagella are necessary to propel the sperm cells forward to the egg cell. Because their sperm do not move properly, males with primary ciliary dyskinesia often have decreased fertility. Decreased fertility also occurs in some affected females and is likely due to abnormal cilia in the fallopian tubes, which impairs the movement of the egg cell from the ovary to the uterus.In rare cases, individuals with primary ciliary dyskinesia have an accumulation of fluid in the brain (hydrocephalus). Researchers do not fully understand why some people with primary ciliary dyskinesia develop hydrocephalus.  ad Autosomal dominant+New variant ar Autosomal recessive x X-linked OFD1 https://medlineplus.gov/genetics/gene/ofd1 DNAI1 https://medlineplus.gov/genetics/gene/dnai1 DNAH5 https://medlineplus.gov/genetics/gene/dnah5 RPGR https://medlineplus.gov/genetics/gene/rpgr DNAH11 https://medlineplus.gov/genetics/gene/dnah11 CCDC40 https://medlineplus.gov/genetics/gene/ccdc40 DNAH9 https://www.ncbi.nlm.nih.gov/gene/1770 FOXJ1 https://www.ncbi.nlm.nih.gov/gene/2302 DRC4 https://www.ncbi.nlm.nih.gov/gene/2622 SPAG1 https://www.ncbi.nlm.nih.gov/gene/6674 TP73 https://www.ncbi.nlm.nih.gov/gene/7161 NME5 https://www.ncbi.nlm.nih.gov/gene/8382 KIAA0586 https://www.ncbi.nlm.nih.gov/gene/9786 CCNO https://www.ncbi.nlm.nih.gov/gene/10309 TUBB4B https://www.ncbi.nlm.nih.gov/gene/10383 DNAAF11 https://www.ncbi.nlm.nih.gov/gene/23639 DNAH1 https://www.ncbi.nlm.nih.gov/gene/25981 STK36 https://www.ncbi.nlm.nih.gov/gene/27148 NME8 https://www.ncbi.nlm.nih.gov/gene/51314 ZMYND10 https://www.ncbi.nlm.nih.gov/gene/51364 HYDIN https://www.ncbi.nlm.nih.gov/gene/54768 DNAAF5 https://www.ncbi.nlm.nih.gov/gene/54919 TTC12 https://www.ncbi.nlm.nih.gov/gene/54970 ODAD2 https://www.ncbi.nlm.nih.gov/gene/55130 DNAAF2 https://www.ncbi.nlm.nih.gov/gene/55172 DNAH7 https://www.ncbi.nlm.nih.gov/gene/56171 CFAP298 https://www.ncbi.nlm.nih.gov/gene/56683 DNAI2 https://www.ncbi.nlm.nih.gov/gene/64446 CLXN https://www.ncbi.nlm.nih.gov/gene/79645 SPEF2 https://www.ncbi.nlm.nih.gov/gene/79925 IFT74 https://www.ncbi.nlm.nih.gov/gene/80173 ODAD4 https://www.ncbi.nlm.nih.gov/gene/83538 DNAL1 https://www.ncbi.nlm.nih.gov/gene/83544 RSPH3 https://www.ncbi.nlm.nih.gov/gene/83861 CFAP300 https://www.ncbi.nlm.nih.gov/gene/85016 CFAP74 https://www.ncbi.nlm.nih.gov/gene/85452 DRC2 https://www.ncbi.nlm.nih.gov/gene/85478 RSPH1 https://www.ncbi.nlm.nih.gov/gene/89765 DRC1 https://www.ncbi.nlm.nih.gov/gene/92749 ODAD1 https://www.ncbi.nlm.nih.gov/gene/93233 LRRC56 https://www.ncbi.nlm.nih.gov/gene/115399 ODAD3 https://www.ncbi.nlm.nih.gov/gene/115948 DNAAF1 https://www.ncbi.nlm.nih.gov/gene/123872 DNAAF6 https://www.ncbi.nlm.nih.gov/gene/139212 CFAP54 https://www.ncbi.nlm.nih.gov/gene/144535 CFAP57 https://www.ncbi.nlm.nih.gov/gene/149465 NEK10 https://www.ncbi.nlm.nih.gov/gene/152110 DNAAF4 https://www.ncbi.nlm.nih.gov/gene/161582 DAW1 https://www.ncbi.nlm.nih.gov/gene/164781 DNAH10 https://www.ncbi.nlm.nih.gov/gene/196385 CFAP221 https://www.ncbi.nlm.nih.gov/gene/200373 RSPH9 https://www.ncbi.nlm.nih.gov/gene/221421 GAS2L2 https://www.ncbi.nlm.nih.gov/gene/246176 CCDC39 https://www.ncbi.nlm.nih.gov/gene/339829 MCIDAS https://www.ncbi.nlm.nih.gov/gene/345643 RSPH4A https://www.ncbi.nlm.nih.gov/gene/345895 DNAAF3 https://www.ncbi.nlm.nih.gov/gene/352909 DNAJB13 https://www.ncbi.nlm.nih.gov/gene/374407 DNAAF19 https://www.ncbi.nlm.nih.gov/gene/388389 CILD Kartagener syndrome PCD GTR C0008780 MeSH D002925 OMIM 244400 OMIM 279000 OMIM 300991 OMIM 606763 OMIM 608644 OMIM 608646 OMIM 608647 OMIM 610852 OMIM 611884 OMIM 612274 OMIM 612444 OMIM 612518 OMIM 612649 OMIM 612650 OMIM 613193 OMIM 613807 OMIM 613808 OMIM 614017 OMIM 614679 OMIM 614874 OMIM 614935 OMIM 615067 OMIM 615294 OMIM 615444 OMIM 615451 OMIM 615481 OMIM 615482 OMIM 615500 OMIM 615504 OMIM 615505 OMIM 615872 OMIM 616037 OMIM 616481 OMIM 616726 OMIM 617091 OMIM 617092 OMIM 617577 OMIM 618063 OMIM 618254 OMIM 618300 OMIM 618449 OMIM 618695 OMIM 618699 OMIM 618781 OMIM 618801 OMIM 619436 OMIM 619466 OMIM 620032 OMIM 620197 OMIM 620356 OMIM 620438 OMIM 620570 OMIM 620642 OMIM 621125 SNOMED CT 42402006 SNOMED CT 86204009 2025-09 2025-12-10 Primary coenzyme Q10 deficiency https://medlineplus.gov/genetics/condition/primary-coenzyme-q10-deficiency descriptionPrimary coenzyme Q10 deficiency is a disorder that can affect many parts of the body, especially the brain, muscles, and kidneys. As its name suggests, the disorder involves a shortage (deficiency) of a substance called coenzyme Q10.The severity, combination of signs and symptoms, and age of onset of primary coenzyme Q10 deficiency vary widely. In the most severe cases, the condition becomes apparent in infancy and causes severe brain dysfunction combined with muscle weakness (encephalomyopathy) and the failure of other body systems. These problems can be life-threatening. The mildest cases of primary coenzyme Q10 deficiency can begin as late as a person's sixties and often cause cerebellar ataxia, which refers to problems with coordination and balance due to defects in the part of the brain that is involved in coordinating movement (cerebellum). Other neurological abnormalities that can occur in primary coenzyme Q10 deficiency include seizures, intellectual disability, poor muscle tone (hypotonia), involuntary muscle contractions (dystonia), progressive muscle stiffness (spasticity), abnormal eye movements (nystagmus), vision loss caused by degeneration (atrophy) of the optic nerves or breakdown of the light-sensing tissue at the back of the eyes (retinopathy), and sensorineural hearing loss (which is caused by abnormalities in the inner ear). The neurological problems gradually get worse unless treated with coenzyme Q10 supplementation.A type of kidney dysfunction called nephrotic syndrome is another common feature of primary coenzyme Q10 deficiency. It can occur with or without neurological abnormalities. Nephrotic syndrome occurs when damage to the kidneys impairs their function, which allows protein from the blood to pass into the urine (proteinuria). Other signs and symptoms of nephrotic syndrome include increased cholesterol in the blood (hypercholesterolemia), an abnormal buildup of fluid in the abdominal cavity (ascites), and swelling (edema). Affected individuals may also have blood in the urine (hematuria), which can lead to a reduced number of red blood cells in the body (anemia), abnormal blood clotting, or reduced amounts of certain white blood cells. Low white blood cell counts can lead to a weakened immune system and frequent infections in people with nephrotic syndrome. If not treated with coenzyme Q10 supplementation, affected individuals eventually develop irreversible kidney failure (end-stage renal disease).A type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy) can also occur in primary coenzyme Q10 deficiency. ar Autosomal recessive COQ2 https://medlineplus.gov/genetics/gene/coq2 COQ4 https://medlineplus.gov/genetics/gene/coq4 COQ8A https://medlineplus.gov/genetics/gene/coq8a COQ6 https://medlineplus.gov/genetics/gene/coq6 COQ8B https://medlineplus.gov/genetics/gene/coq8b COQ7 https://www.ncbi.nlm.nih.gov/gene/10229 PDSS1 https://www.ncbi.nlm.nih.gov/gene/23590 COQ9 https://www.ncbi.nlm.nih.gov/gene/57017 PDSS2 https://www.ncbi.nlm.nih.gov/gene/57107 Coenzyme Q deficiency CoQ deficiency Primary CoQ10 deficiency Ubiquinone deficiency MeSH D017237 OMIM 607426 OMIM 612016 OMIM 614650 OMIM 614651 OMIM 614652 OMIM 614654 OMIM 615573 OMIM 616276 OMIM 616733 SNOMED CT 724575009 SNOMED CT 725394006 2017-04 2020-08-18 Primary familial brain calcification https://medlineplus.gov/genetics/condition/primary-familial-brain-calcification descriptionPrimary familial brain calcification is a condition characterized by abnormal deposits of calcium (calcification) in blood vessels within the brain. These calcium deposits are visible only on medical imaging and typically occur in the basal ganglia, which are structures deep within the brain that help start and control movement of the body. Other brain regions may also be affected.The main signs and symptoms of primary familial brain calcification are movement disorders and psychiatric or behavioral problems. These difficulties usually begin in mid-adulthood, and worsen over time. Most affected individuals have a group of movement abnormalities called parkinsonism, which include unusually slow movement (bradykinesia), muscle rigidity, and tremors. Other movement problems common in people with primary familial brain calcification include involuntary tensing of various muscles (dystonia), uncontrollable movements of the limbs (choreoathetosis), and an unsteady walking style (gait).Psychiatric and behavioral problems occur in 20 to 30 percent of people with primary familial brain calcification. These problems can include difficulty concentrating, memory loss, changes in personality, a distorted view of reality (psychosis), and decline in intellectual function (dementia). Affected individuals may also have difficulty swallowing (dysphagia), impaired speech, headache, episodes of extreme dizziness (vertigo), seizures, or urinary problems.The severity of primary familial brain calcification varies among affected individuals; some people have no symptoms related to the condition, whereas others have significant movement and psychiatric problems. ar Autosomal recessive ad Autosomal dominant PDGFB https://medlineplus.gov/genetics/gene/pdgfb SLC20A2 https://medlineplus.gov/genetics/gene/slc20a2 PDGFRB https://medlineplus.gov/genetics/gene/pdgfrb XPR1 https://www.ncbi.nlm.nih.gov/gene/9213 MYORG https://www.ncbi.nlm.nih.gov/gene/57462 JAM2 https://www.ncbi.nlm.nih.gov/gene/58494 Bilateral striopallidodentate calcinosis Cerebrovascular ferrocalcinosis Familial idiopathic basal ganglia calcification FIBGC Striopallidodentate calcinosis GTR C3554321 GTR C3809645 GTR C4225335 GTR C4551624 MeSH D001480 OMIM 213600 OMIM 615007 OMIM 615483 OMIM 616413 OMIM 618317 SNOMED CT 110997000 2019-03 2020-08-18 Primary hyperoxaluria https://medlineplus.gov/genetics/condition/primary-hyperoxaluria descriptionPrimary hyperoxaluria is a rare condition characterized by recurrent kidney and bladder stones. The condition often results in end stage renal disease (ESRD), which is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.Primary hyperoxaluria results from the overproduction of a substance called oxalate. Oxalate is filtered through the kidneys and excreted as a waste product in urine, leading to abnormally high levels of this substance in urine (hyperoxaluria). During its excretion, oxalate can combine with calcium to form calcium oxalate, a hard compound that is the main component of kidney and bladder stones. Deposits of calcium oxalate can damage the kidneys and other organs and lead to blood in the urine (hematuria), urinary tract infections, kidney damage, ESRD, and injury to other organs. Over time, kidney function decreases such that the kidneys can no longer excrete as much oxalate as they receive. As a result oxalate levels in the blood rise, and the substance gets deposited in tissues throughout the body (systemic oxalosis), particularly in bones and the walls of blood vessels. Oxalosis in bones can cause fractures.There are three types of primary hyperoxaluria that differ in their severity and genetic cause. In primary hyperoxaluria type 1, kidney stones typically begin to appear anytime from childhood to early adulthood, and ESRD can develop at any age. Primary hyperoxaluria type 2 is similar to type 1, but ESRD develops later in life. In primary hyperoxaluria type 3, affected individuals often develop kidney stones in early childhood, but few cases of this type have been described so additional signs and symptoms of this type are unclear. ar Autosomal recessive AGXT https://medlineplus.gov/genetics/gene/agxt GRHPR https://medlineplus.gov/genetics/gene/grhpr HOGA1 https://medlineplus.gov/genetics/gene/hoga1 Congenital oxaluria D-glycerate dehydrogenase deficiency Glyceric aciduria Glycolic aciduria Hepatic AGT deficiency Hyperoxaluria, primary Oxalosis Oxaluria, primary Peroxisomal alanine:glyoxylate aminotransferase deficiency Primary oxalosis Primary oxaluria GTR C0020500 GTR C0020501 GTR C0268164 GTR C0268165 GTR C3150878 ICD-10-CM E72.53 MeSH D006960 OMIM 259900 OMIM 260000 OMIM 613616 SNOMED CT 17901006 SNOMED CT 373607009 SNOMED CT 40951006 SNOMED CT 65520001 2015-12 2025-04-03 Primary localized cutaneous amyloidosis https://medlineplus.gov/genetics/condition/primary-localized-cutaneous-amyloidosis descriptionPrimary localized cutaneous amyloidosis (PLCA) is a condition in which clumps of abnormal proteins called amyloids build up in the skin, specifically in the wave-like projections (dermal papillae) between the top two layers of skin (the dermis and the epidermis). The primary feature of PLCA is patches of skin with abnormal texture or color. The appearance of these patches defines three forms of the condition: lichen amyloidosis, macular amyloidosis, and nodular amyloidosis.Lichen amyloidosis is characterized by severely itchy patches of thickened skin with multiple small bumps. The patches are scaly and reddish brown in color. These patches usually occur on the shins but can also occur on the forearms, other parts of the legs, and elsewhere on the body.In macular amyloidosis, the patches are flat and dark brown. The coloring can have a lacy (reticulated) or rippled appearance, although it is often uniform. Macular amyloidosis patches are most commonly found on the upper back, but they can also occur on other parts of the torso or on the limbs. These patches are mildly itchy.Nodular amyloidosis is characterized by firm, raised bumps (nodules) that are pink, red, or brown. These nodules often occur on the face, torso, limbs, or genitals and are typically not itchy.In some affected individuals, the patches have characteristics of both lichen and macular amyloidosis. These cases are called biphasic amyloidosis.In all forms of PLCA, the abnormal patches of skin usually arise in mid-adulthood. They can remain for months to years and may recur after disappearing, either at the same location or elsewhere. Very rarely, nodular amyloidosis progresses to a life-threatening condition called systemic amyloidosis, in which amyloid deposits accumulate in tissues and organs throughout the body. ar Autosomal recessive n Not inherited ad Autosomal dominant IL31RA https://medlineplus.gov/genetics/gene/il31ra OSMR https://medlineplus.gov/genetics/gene/osmr Amyloidosis IX PLCA Primary cutaneous amyloidosis GTR C3151404 GTR C4551501 MeSH D000686 OMIM 105250 OMIM 613955 SNOMED CT 733729003 2017-02 2021-11-24 Primary macronodular adrenal hyperplasia https://medlineplus.gov/genetics/condition/primary-macronodular-adrenal-hyperplasia descriptionPrimary macronodular adrenal hyperplasia (PMAH) is a disorder characterized by multiple lumps (nodules) in the adrenal glands, which are small hormone-producing glands located on top of each kidney. These nodules, which usually are found in both adrenal glands (bilateral) and vary in size, cause adrenal gland enlargement (hyperplasia) and result in the production of higher-than-normal levels of the hormone cortisol. Cortisol is an important hormone that suppresses inflammation and protects the body from physical stress such as infection or trauma through several mechanisms including raising levels of blood glucose, also called blood sugar.PMAH typically becomes evident in a person's forties or fifties. It is considered a form of Cushing syndrome, which is characterized by increased levels of cortisol resulting from one of many possible causes. These increased cortisol levels lead to weight gain in the face and upper body, fragile skin, bone loss, fatigue, and other health problems. However, some people with PMAH do not experience these signs and symptoms and are said to have subclinical Cushing syndrome. n Not inherited ad Autosomal dominant APC https://medlineplus.gov/genetics/gene/apc MEN1 https://medlineplus.gov/genetics/gene/men1 FH https://medlineplus.gov/genetics/gene/fh GNAS https://medlineplus.gov/genetics/gene/gnas ARMC5 https://medlineplus.gov/genetics/gene/armc5 MC2R https://medlineplus.gov/genetics/gene/mc2r PDE11A https://www.ncbi.nlm.nih.gov/gene/50940 ACTH-independent macronodular adrenal hyperplasia ACTH-independent macronodular adrenocortical hyperplasia Adrenal Cushing syndrome due to AIMAH Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia AIMAH Corticotropin-independent macronodular adrenal hyperplasia PMAH Primary bilateral macronodular adrenal hyperplasia GTR C4014803 MeSH D003480 OMIM 219080 OMIM 615954 SNOMED CT 237778003 2015-05 2023-07-26 Primary myelofibrosis https://medlineplus.gov/genetics/condition/primary-myelofibrosis descriptionPrimary myelofibrosis is a condition characterized by the buildup of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. Because of the fibrosis, the bone marrow is unable to make enough normal blood cells. The shortage of blood cells causes many of the signs and symptoms of primary myelofibrosis.Initially, most people with primary myelofibrosis have no signs or symptoms. Eventually, fibrosis can lead to a reduction in the number of red blood cells, white blood cells, and platelets. A shortage of red blood cells (anemia) often causes extreme tiredness (fatigue) or shortness of breath. A loss of white blood cells can lead to an increased number of infections, and a reduction of platelets can cause easy bleeding or bruising.Because blood cell formation (hematopoiesis) in the bone marrow is disrupted, other organs such as the spleen or liver may begin to produce blood cells. This process, called extramedullary hematopoiesis, often leads to an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly). People with splenomegaly may feel pain or fullness in the abdomen, especially below the ribs on the left side. Other common signs and symptoms of primary myelofibrosis include fever, night sweats, and bone pain.Primary myelofibrosis is most commonly diagnosed in people aged 50 to 80 but can occur at any age. n Not inherited JAK2 https://medlineplus.gov/genetics/gene/jak2 TET2 https://medlineplus.gov/genetics/gene/tet2 MPL https://medlineplus.gov/genetics/gene/mpl IDH2 https://medlineplus.gov/genetics/gene/idh2 IDH1 https://medlineplus.gov/genetics/gene/idh1 CALR https://medlineplus.gov/genetics/gene/calr Agnogenic myeloid metaplasia Chronic idiopathic myelofibrosis Idiopathic myelofibrosis Myelofibrosis with myeloid metaplasia Myeloid metaplasia GTR C0001815 MeSH D055728 OMIM 254450 SNOMED CT 128843003 SNOMED CT 307651005 SNOMED CT 443230004 SNOMED CT 52967002 2014-09 2020-08-18 Primary sclerosing cholangitis https://medlineplus.gov/genetics/condition/primary-sclerosing-cholangitis descriptionPrimary sclerosing cholangitis is a condition that affects the bile ducts. These ducts carry bile (a fluid that helps to digest fats) from the liver, where bile is produced, to the gallbladder, where it is stored, and to the small intestine, where it aids in digestion. Primary sclerosing cholangitis occurs because of inflammation in the bile ducts (cholangitis) that leads to scarring (sclerosis) and narrowing of the ducts. As a result, bile cannot be released to the gallbladder and small intestine, and it builds up in the liver.Primary sclerosing cholangitis is usually diagnosed around age 40, and for unknown reasons, it affects men twice as often as women. Many people have no signs or symptoms of the condition when they are diagnosed, but routine blood tests reveal liver problems. When apparent, the earliest signs and symptoms of primary sclerosing cholangitis include extreme tiredness (fatigue), discomfort in the abdomen, and severe itchiness (pruritus). As the condition worsens, affected individuals may develop yellowing of the skin and whites of the eyes (jaundice) and an enlarged spleen (splenomegaly). Eventually, the buildup of bile damages the liver cells, causing chronic liver disease (cirrhosis) and liver failure. Without bile available to digest them, fats pass through the body. As a result, weight loss and shortages of vitamins that are absorbed with and stored in fats (fat-soluble vitamins) can occur. A fat-soluble vitamin called vitamin D helps absorb calcium and helps bones harden, and lack of this vitamin can cause thinning of the bones (osteoporosis) in people with primary sclerosing cholangitis.Primary sclerosing cholangitis is often associated with another condition called inflammatory bowel disease, which is characterized by inflammation of the intestines that causes open sores (ulcers) in the intestines and abdominal pain. However, the reason for this link is unclear. Approximately 70 percent of people with primary sclerosing cholangitis have inflammatory bowel disease, most commonly a form of the condition known as ulcerative colitis. In addition, people with primary sclerosing cholangitis are more likely to have an autoimmune disorder, such as type 1 diabetes, celiac disease, or thyroid disease, than people without the condition. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. People with primary sclerosing cholangitis also have an increased risk of developing cancer, particularly cancer of the bile ducts (cholangiocarcinoma). u Pattern unknown PSC Sclerosing cholangitis GTR C0566602 MeSH D015209 OMIM 613806 SNOMED CT 197441003 2012-05 2020-08-18 Primary spontaneous pneumothorax https://medlineplus.gov/genetics/condition/primary-spontaneous-pneumothorax descriptionPrimary spontaneous pneumothorax is an abnormal accumulation of air in the space between the lungs and the chest cavity (called the pleural space) that can result in the partial or complete collapse of a lung. This type of pneumothorax is described as primary because it occurs in the absence of lung disease such as emphysema. Spontaneous means the pneumothorax was not caused by an injury such as a rib fracture. Primary spontaneous pneumothorax is likely due to the formation of small sacs of air (blebs) in lung tissue that rupture, causing air to leak into the pleural space. Air in the pleural space creates pressure on the lung and can lead to its collapse. A person with this condition may feel chest pain on the side of the collapsed lung and shortness of breath.Blebs may be present on an individual's lung (or lungs) for a long time before they rupture. Many things can cause a bleb to rupture, such as changes in air pressure or a very sudden deep breath. Often, people who experience a primary spontaneous pneumothorax have no prior sign of illness; the blebs themselves typically do not cause any symptoms and are visible only on medical imaging. Affected individuals may have one bleb to more than thirty blebs. Once a bleb ruptures and causes a pneumothorax, there is an estimated 13 to 60 percent chance that the condition will recur. ad Autosomal dominant FLCN https://medlineplus.gov/genetics/gene/flcn Pneumothorax PSP Spontaneous pneumothorax GTR C1868193 ICD-10-CM J93.11 MeSH D011030 OMIM 173600 SNOMED CT 328561000119107 2012-11 2020-08-18 Prion disease https://medlineplus.gov/genetics/condition/prion-disease descriptionPrion disease represents a group of conditions that affect the nervous system in humans and animals. In people, these conditions impair brain function, causing changes in memory, personality, and behavior; a decline in intellectual function (dementia); and abnormal movements, particularly difficulty with coordinating movements (ataxia). The signs and symptoms of prion disease typically begin in adulthood and worsen with time, leading to death within a few months to several years. ad Autosomal dominant PRNP https://medlineplus.gov/genetics/gene/prnp Inherited human transmissible spongiform encephalopathies Prion protein diseases Prion-associated disorders Prion-induced disorders Transmissible dementias Transmissible spongiform encephalopathies TSEs GTR C0017495 GTR C0022336 GTR C0162534 GTR C0206042 GTR C1855588 ICD-10-CM A81.0 ICD-10-CM A81.00 ICD-10-CM A81.01 ICD-10-CM A81.09 ICD-10-CM A81.81 ICD-10-CM A81.82 ICD-10-CM A81.83 MeSH D017096 OMIM 123400 OMIM 137440 OMIM 245300 OMIM 600072 SNOMED CT 20484008 SNOMED CT 304603007 SNOMED CT 67155006 SNOMED CT 792004 SNOMED CT 840452004 2014-01 2020-08-18 Progressive external ophthalmoplegia https://medlineplus.gov/genetics/condition/progressive-external-ophthalmoplegia descriptionProgressive external ophthalmoplegia is a condition characterized by weakness of the eye muscles. The condition typically appears in adults between ages 18 and 40 and slowly worsens over time. The first sign of progressive external ophthalmoplegia is typically drooping eyelids (ptosis), which can affect one or both eyelids. As ptosis worsens, affected individuals may use the forehead muscles to try to lift the eyelids, or they may lift up their chin in order to see. Another characteristic feature of progressive external ophthalmoplegia is weakness or paralysis of the muscles that move the eye (ophthalmoplegia). Affected individuals have to turn their head to see in different directions, especially as the ophthalmoplegia worsens. People with progressive external ophthalmoplegia may also have general weakness of the muscles used for movement (myopathy), particularly those in the neck, arms, or legs. The weakness may be especially noticeable during exercise (exercise intolerance). Muscle weakness may also cause difficulty swallowing (dysphagia).When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells contain an excess of cell structures called mitochondria and are known as ragged-red fibers.Although muscle weakness is the primary symptom of progressive external ophthalmoplegia, this condition can be accompanied by other signs and symptoms. In these instances, the condition is referred to as progressive external ophthalmoplegia plus (PEO+). Additional signs and symptoms can include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), weakness and loss of sensation in the limbs due to nerve damage (neuropathy), impaired muscle coordination (ataxia), a pattern of movement abnormalities known as parkinsonism, and depression.Progressive external ophthalmoplegia is part of a spectrum of disorders with overlapping signs and symptoms. Similar disorders include ataxia neuropathy spectrum and Kearns-Sayre syndrome. Like progressive external ophthalmoplegia, the other conditions in this spectrum can involve weakness of the eye muscles. However, these conditions have many additional features not shared by most people with progressive external ophthalmoplegia. m mitochondrial ar Autosomal recessive ad Autosomal dominant MT-TL1 https://medlineplus.gov/genetics/gene/mt-tl1 SPG7 https://medlineplus.gov/genetics/gene/spg7 OPA1 https://medlineplus.gov/genetics/gene/opa1 TWNK https://medlineplus.gov/genetics/gene/twnk POLG https://medlineplus.gov/genetics/gene/polg SLC25A4 https://medlineplus.gov/genetics/gene/slc25a4 TK2 https://medlineplus.gov/genetics/gene/tk2 RRM2B https://medlineplus.gov/genetics/gene/rrm2b DNA2 https://www.ncbi.nlm.nih.gov/gene/1763 MT-TI https://www.ncbi.nlm.nih.gov/gene/4565 AFG3L2 https://www.ncbi.nlm.nih.gov/gene/10939 POLG2 https://www.ncbi.nlm.nih.gov/gene/11232 RNASEH1 https://www.ncbi.nlm.nih.gov/gene/246243 mitochondrial DNA https://medlineplus.gov/genetics/chromosome/mitochondrial-dna Chronic progressive external ophthalmoplegia CPEO PEO GTR C0162674 GTR C1834846 GTR C1836439 GTR C1836460 ICD-10-CM H49.4 ICD-10-CM H49.40 ICD-10-CM H49.41 ICD-10-CM H49.42 ICD-10-CM H49.43 MeSH D017246 OMIM 157640 OMIM 258450 OMIM 609283 OMIM 609286 SNOMED CT 46252003 2016-05 2020-09-08 Progressive familial heart block https://medlineplus.gov/genetics/condition/progressive-familial-heart-block descriptionProgressive familial heart block is a genetic condition that alters the normal beating of the heart. A normal heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. These signals begin in a specialized cluster of cells called the sinoatrial node (the heart's natural pacemaker) located in the heart's upper chambers (the atria). From there, a group of cells called the atrioventricular node carries the electrical signals to another cluster of cells called the bundle of His. This bundle separates into multiple thin spindles called bundle branches, which carry electrical signals into the heart's lower chambers (the ventricles). Electrical impulses move from the sinoatrial node down to the bundle branches, stimulating a normal heartbeat in which the ventricles contract slightly later than the atria.Heart block occurs when the electrical signaling is obstructed anywhere from the atria to the ventricles. In people with progressive familial heart block, the condition worsens over time: early in the disorder, the electrical signals are partially blocked, but the block eventually becomes complete, preventing any signals from passing through the heart. Partial heart block causes a slow or irregular heartbeat (bradycardia or arrhythmia, respectively), and can lead to the buildup of scar tissue (fibrosis) in the cells that carry electrical impulses. Fibrosis contributes to the development of complete heart block, resulting in uncoordinated electrical signaling between the atria and the ventricles and inefficient pumping of blood in the heart. Complete heart block can cause a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, fainting (syncope), or sudden cardiac arrest and death.Progressive familial heart block can be divided into type I and type II, with type I being further divided into types IA and IB. These types differ in where in the heart signaling is interrupted and the genetic cause. In types IA and IB, the heart block originates in the bundle branch, and in type II, the heart block originates in the atrioventricular node. The different types of progressive familial heart block have similar signs and symptoms.Most cases of heart block are not genetic and are not considered progressive familial heart block. The most common cause of heart block is fibrosis of the heart, which occurs as a normal process of aging. Other causes of heart block can include the use of certain medications or an infection of the heart tissue. ad Autosomal dominant SCN5A https://medlineplus.gov/genetics/gene/scn5a TRPM4 https://medlineplus.gov/genetics/gene/trpm4 GJA5 https://www.ncbi.nlm.nih.gov/gene/2702 SCN1B https://www.ncbi.nlm.nih.gov/gene/6324 Bundle branch block HBBD Hereditary bundle branch defect Hereditary bundle branch system defect Lenegre Lev disease Lev syndrome Lev's disease Lev-Lenègre disease PCCD Progressive cardiac conduction defect GTR C1879286 GTR C1970298 ICD-10-CM Q24.6 MeSH D006327 OMIM 113900 OMIM 140400 OMIM 604559 SNOMED CT 698249005 2015-04 2020-08-18 Progressive familial intrahepatic cholestasis https://medlineplus.gov/genetics/condition/progressive-familial-intrahepatic-cholestasis descriptionProgressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.Signs and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly).There are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause.In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood.The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma.Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3. ar Autosomal recessive ATP8B1 https://medlineplus.gov/genetics/gene/atp8b1 ABCB11 https://medlineplus.gov/genetics/gene/abcb11 ABCB4 https://medlineplus.gov/genetics/gene/abcb4 ABCB11-related intrahepatic cholestasis ABCB4-related intrahepatic cholestasis ATP8B1-related intrahepatic cholestasis BSEP deficiency Byler disease Byler syndrome FIC1 deficiency Low γ-GT familial intrahepatic cholestasis MDR3 deficiency GTR C0268312 GTR C1865643 GTR C3489789 MeSH D002780 OMIM 211600 OMIM 601847 OMIM 602347 SNOMED CT 74162007 2009-12 2020-08-18 Progressive myoclonic epilepsy type 1 https://medlineplus.gov/genetics/condition/progressive-myoclonic-epilepsy-type-1 descriptionProgressive myoclonic epilepsy type 1 (also called Unverricht-Lundborg disease or ULD) is a rare inherited form of epilepsy. Early development is normal in affected individuals. Signs and symptoms of the disorder typically begin between 6 and 15 years of age. People with progressive myoclonic epilepsy type 1 experience episodes of involuntary muscle jerking or twitching (myoclonus) that increase in frequency and severity over time. Episodes of myoclonus may be brought on by physical exertion, stress, light, or other stimuli. Within 5 to 10 years, the myoclonic episodes may become severe enough to interfere with walking and other everyday activities.Affected individuals also usually have seizures that involve loss of consciousness, muscle rigidity, and convulsions (tonic-clonic or grand mal seizures). Like the myoclonic episodes, these may increase in frequency over several years. However, the seizures may be controlled with treatment. After several years of progression, the frequency of seizures may stabilize or decrease.Eventually, people with progressive myoclonic epilepsy type 1 may develop problems with balance and coordination (ataxia) and speaking (dysarthria). They may also experience depression. Another feature of this condition is involuntary rhythmic shaking. This shaking is called intentional tremor because it worsens during intentional movements.People with progressive myoclonic epilepsy type 1 may live into adulthood. Life expectancy depends on the severity of the condition and a person's response to treatment. The severity of the condition can vary, even among members of the same family. ar Autosomal recessive CSTB https://medlineplus.gov/genetics/gene/cstb Baltic myoclonic epilepsy Baltic myoclonus Baltic myoclonus epilepsy EPM1 EPM1A Myoclonic epilepsy of Unverricht and Lundborg PME Progressive myoclonic epilepsy 1A Progressive myoclonus epilepsy type 1 ULD Unverricht-Lundborg syndrome GTR C0751785 ICD-10-CM MeSH D020194 OMIM 254800 SNOMED CT 230423006 2024-03 2024-04-02 Progressive osseous heteroplasia https://medlineplus.gov/genetics/condition/progressive-osseous-heteroplasia descriptionProgressive osseous heteroplasia is a disorder in which bone forms within skin and muscle tissue. Bone that forms outside the skeleton is called heterotopic or ectopic bone. In progressive osseous heteroplasia, ectopic bone formation begins in the deep layers of the skin (dermis and subcutaneous fat) and gradually moves into other tissues such as skeletal muscle and tendons. The bony lesions within the skin may be painful and may develop into open sores (ulcers). Over time, joints can become involved, resulting in impaired mobility.Signs and symptoms of progressive osseous heteroplasia usually become noticeable during infancy. In some affected individuals, however, the disorder may not become evident until later in childhood or in early adulthood. ad Autosomal dominant GNAS https://medlineplus.gov/genetics/gene/gnas Cutaneous ossification Ectopic ossification Heterotopic ossification Myositis ossificans progressiva Osteodermia Osteoma cutis Osteosis cutis POH GTR C0334041 ICD-10-CM M61.1 ICD-10-CM M61.10 ICD-10-CM M61.11 ICD-10-CM M61.111 ICD-10-CM M61.112 ICD-10-CM M61.119 ICD-10-CM M61.12 ICD-10-CM M61.121 ICD-10-CM M61.122 ICD-10-CM M61.129 ICD-10-CM M61.13 ICD-10-CM M61.131 ICD-10-CM M61.132 ICD-10-CM M61.139 ICD-10-CM M61.14 ICD-10-CM M61.141 ICD-10-CM M61.142 ICD-10-CM M61.143 ICD-10-CM M61.144 ICD-10-CM M61.145 ICD-10-CM M61.146 ICD-10-CM M61.15 ICD-10-CM M61.151 ICD-10-CM M61.152 ICD-10-CM M61.159 ICD-10-CM M61.16 ICD-10-CM M61.161 ICD-10-CM M61.162 ICD-10-CM M61.169 ICD-10-CM M61.17 ICD-10-CM M61.171 ICD-10-CM M61.172 ICD-10-CM M61.173 ICD-10-CM M61.174 ICD-10-CM M61.175 ICD-10-CM M61.176 ICD-10-CM M61.177 ICD-10-CM M61.178 ICD-10-CM M61.179 ICD-10-CM M61.18 ICD-10-CM M61.19 MeSH D009999 OMIM 166350 SNOMED CT 719271000 2009-01 2020-08-18 Progressive pseudorheumatoid dysplasia https://medlineplus.gov/genetics/condition/progressive-pseudorheumatoid-dysplasia descriptionProgressive pseudorheumatoid dysplasia (PPRD) is a joint disease that worsens over time. This condition is characterized by breakdown (degeneration) of the cartilage between bones (articular cartilage). This cartilage covers and protects the ends of bones, and its degeneration leads to pain and stiffness in the joints and other features of PPRD.PPRD usually begins in childhood, between ages 3 and 8. The first indications are usually an abnormal walking pattern, weakness and fatigue when active, and stiffness in the joints in the fingers and in the knees. Other signs and symptoms that develop over time include permanently bent fingers (camptodactyly), enlarged finger and knee joints (often mistaken as swelling), and a reduced amount of space between the bones at the hip and knee joints. Hip pain is a common problem by adolescence. Affected individuals have flattened bones in the spine (platyspondyly) that are abnormally shaped (beaked), which leads to an abnormal front-to-back curvature of the spine (kyphosis) and a short torso. At birth, people with PPRD are of normal length, but by adulthood, they are usually shorter than their peers. Affected adults also have abnormal deposits of calcium around the elbow, knee, and hip joints and limited movement in all joints, including those of the spine.PPRD is often mistaken for another joint disorder that affects young people called juvenile rheumatoid arthritis. However, the joint problems in juvenile rheumatoid arthritis are associated with inflammation, while those in PPRD are not. ar Autosomal recessive CCN6 https://medlineplus.gov/genetics/gene/ccn6 Progressive pseudorheumatoid arthropathy of childhood Spondyloepiphyseal dysplasia tarda with progressive arthropathy GTR C0432215 MeSH D010009 OMIM 208230 SNOMED CT 254065005 2013-04 2020-08-18 Progressive supranuclear palsy https://medlineplus.gov/genetics/condition/progressive-supranuclear-palsy descriptionProgressive supranuclear palsy is a brain disorder that affects movement, vision, speech, and thinking ability (cognition). The signs and symptoms of this disorder usually become apparent in mid- to late adulthood, most often in a person's 60s. Most people with progressive supranuclear palsy survive 5 to 9 years after the disease first appears, although a few affected individuals have lived for more than a decade.Loss of balance and frequent falls are the most common early signs of progressive supranuclear palsy. Affected individuals have problems with walking, including poor coordination and an unsteady, lurching gait. Other movement abnormalities develop as the disease progresses, including unusually slow movements (bradykinesia), clumsiness, and stiffness of the trunk muscles. These problems worsen with time, and most affected people ultimately require wheelchair assistance.Progressive supranuclear palsy is also characterized by abnormal eye movements, which typically develop several years after the other movement problems first appear. Restricted up-and-down eye movement (vertical gaze palsy) is a hallmark of this disease. Other eye movement problems include difficulty opening and closing the eyelids, infrequent blinking, and pulling back (retraction) of the eyelids. These abnormalities can lead to blurred vision, an increased sensitivity to light (photophobia), and a staring gaze.Additional features of progressive supranuclear palsy include slow and slurred speech (dysarthria) and trouble swallowing (dysphagia). Most affected individuals also experience changes in personality and behavior, such as a general loss of interest and enthusiasm (apathy). They develop problems with cognition, including difficulties with attention, planning, and problem solving. As the cognitive and behavioral problems worsen, affected individuals increasingly require help with personal care and other activities of daily living. u Pattern unknown ad Autosomal dominant MAPT https://medlineplus.gov/genetics/gene/mapt Progressive supranuclear ophthalmoplegia PSP Richardson's syndrome Steele-Richardson-Olszewski syndrome Supranuclear palsy, progressive GTR C4551863 ICD-10-CM G23.1 MeSH D013494 OMIM 601104 OMIM 609454 OMIM 610898 SNOMED CT 192976002 SNOMED CT 28978003 2011-03 2020-08-18 Prolidase deficiency https://medlineplus.gov/genetics/condition/prolidase-deficiency descriptionProlidase deficiency is a disorder that causes a wide variety of symptoms. The disorder typically becomes apparent during infancy. Affected individuals may have enlargement of the spleen (splenomegaly); in some cases, both the spleen and liver are enlarged (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency are susceptible to severe infections of the skin or ears, or potentially life-threatening respiratory tract infections. Some individuals with prolidase deficiency have chronic lung disease.Characteristic facial features in people with prolidase deficiency include prominent eyes that are widely spaced (hypertelorism), a high forehead, a flat bridge of the nose, and a very small lower jaw and chin (micrognathia). Affected children may experience delayed development, and about 75 percent of people with prolidase deficiency have intellectual disability that may range from mild to severe.People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. Skin ulcers, especially on the legs, may not heal completely, resulting in complications including infection and amputation.The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Some people with this disorder do not have any symptoms. In these individuals the condition can be detected by laboratory tests such as newborn screening tests or tests offered to relatives of affected individuals. ar Autosomal recessive PEPD https://medlineplus.gov/genetics/gene/pepd Hyperimidodipeptiduria Imidodipeptidase deficiency PD Peptidase deficiency GTR C0268532 MeSH D056732 OMIM 170100 SNOMED CT 360969006 SNOMED CT 360994007 SNOMED CT 410055005 2012-02 2020-08-18 Proopiomelanocortin deficiency https://medlineplus.gov/genetics/condition/proopiomelanocortin-deficiency descriptionProopiomelanocortin (POMC) deficiency causes severe obesity that begins at an early age. In addition to obesity, people with this condition have low levels of a hormone known as adrenocorticotropic hormone (ACTH) and tend to have red hair and pale skin.Affected infants are usually a normal weight at birth, but they are constantly hungry, which leads to excessive feeding (hyperphagia). The babies continuously gain weight and are severely obese by age 1. Affected individuals experience excessive hunger and remain obese for life. It is unclear if these individuals are prone to weight-related conditions like cardiovascular disease or type 2 diabetes.Low levels of ACTH lead to a condition called adrenal insufficiency, which occurs when the pair of small glands on top of the kidneys (the adrenal glands) do not produce enough hormones. Adrenal insufficiency often results in periods of severely low blood sugar (glucose), known as hypoglycemia. Adrenal insufficiency may also cause seizures, elevated levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia), and a reduced ability to produce and release a digestive fluid called bile (cholestasis). Without early treatment, adrenal insufficiency can be fatal.Pale skin that easily burns when exposed to the sun and red hair are common in POMC deficiency, although not everyone with the condition has these characteristics. ar Autosomal recessive POMC https://medlineplus.gov/genetics/gene/pomc Obesity, early-onset, adrenal insufficiency, and red hair POMC deficiency GTR C1857854 MeSH D009767 OMIM 609734 SNOMED CT 702949005 2014-02 2023-07-19 Propionic acidemia https://medlineplus.gov/genetics/condition/propionic-acidemia descriptionPropionic acidemia is an inherited disorder in which the body is unable to process certain parts of proteins and lipids (fats) properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.In most cases, the features of propionic acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including heart abnormalities, seizures, coma, and possibly death.Less commonly, the signs and symptoms of propionic acidemia appear during childhood and may come and go over time. Some affected children experience intellectual disability or delayed development. In children with this later-onset form of the condition, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), fever, or infections. ar Autosomal recessive PCCA https://medlineplus.gov/genetics/gene/pcca PCCB https://medlineplus.gov/genetics/gene/pccb Hyperglycinemia with ketoacidosis and leukopenia Ketotic glycinemia Ketotic hyperglycinemia PCC deficiency PROP Propionicacidemia Propionyl-CoA carboxylase deficiency ICD-10-CM E71.121 MeSH D056693 OMIM 606054 SNOMED CT 124718009 SNOMED CT 399087009 SNOMED CT 399149003 SNOMED CT 69080001 2007-07 2020-08-18 Prostate cancer https://medlineplus.gov/genetics/condition/prostate-cancer descriptionProstate cancer is a common disease that affects men, usually in middle age or later. In this disorder, certain cells in the prostate become abnormal, multiply without control or order, and form a tumor. The prostate is a gland that surrounds the male urethra and helps produce semen, the fluid that carries sperm.Early prostate cancer usually does not cause pain, and most affected men exhibit no noticeable symptoms. Men are often diagnosed as the result of health screenings, such as a blood test for a substance called prostate specific antigen (PSA) or a medical exam called a digital rectal exam (DRE). As the tumor grows larger, signs and symptoms can include difficulty starting or stopping the flow of urine, a feeling of not being able to empty the bladder completely, blood in the urine or semen, or pain with ejaculation. However, these changes can also occur with many other genitourinary conditions. Having one or more of these symptoms does not necessarily mean that a man has prostate cancer.The severity and outcome of prostate cancer varies widely. Early-stage prostate cancer can usually be treated successfully, and some older men have prostate tumors that grow so slowly that they may never cause health problems during their lifetime, even without treatment. In other men, however, the cancer is much more aggressive; in these cases, prostate cancer can be life-threatening.Some cancerous tumors can invade surrounding tissue and spread to other parts of the body. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers. The signs and symptoms of metastatic cancer depend on where the disease has spread. If prostate cancer spreads, cancerous cells most often appear in the lymph nodes, bones, lungs, liver, or brain. A small percentage of prostate cancers are hereditary and occur in families. These hereditary cancers are associated with inherited gene variants. Hereditary prostate cancers tend to develop earlier in life than non-inherited (sporadic) cases. ad Autosomal dominant n Not inherited u Pattern unknown FGFR2 https://medlineplus.gov/genetics/gene/fgfr2 FGFR4 https://medlineplus.gov/genetics/gene/fgfr4 BRCA1 https://medlineplus.gov/genetics/gene/brca1 BRCA2 https://medlineplus.gov/genetics/gene/brca2 PTEN https://medlineplus.gov/genetics/gene/pten AR https://medlineplus.gov/genetics/gene/ar WRN https://medlineplus.gov/genetics/gene/wrn EP300 https://medlineplus.gov/genetics/gene/ep300 GNMT https://medlineplus.gov/genetics/gene/gnmt NBN https://medlineplus.gov/genetics/gene/nbn CDH1 https://medlineplus.gov/genetics/gene/cdh1 STAT3 https://medlineplus.gov/genetics/gene/stat3 SRD5A2 https://medlineplus.gov/genetics/gene/srd5a2 IGF2 https://medlineplus.gov/genetics/gene/igf2 MED12 https://medlineplus.gov/genetics/gene/med12 WT1 https://medlineplus.gov/genetics/gene/wt1 LRP2 https://medlineplus.gov/genetics/gene/lrp2 ITGA6 https://medlineplus.gov/genetics/gene/itga6 PCNT https://medlineplus.gov/genetics/gene/pcnt TGFBR1 https://medlineplus.gov/genetics/gene/tgfbr1 EZH2 https://medlineplus.gov/genetics/gene/ezh2 HOXB13 https://medlineplus.gov/genetics/gene/hoxb13 HNF1B https://medlineplus.gov/genetics/gene/hnf1b ZFHX3 https://www.ncbi.nlm.nih.gov/gene/463 KLF6 https://www.ncbi.nlm.nih.gov/gene/1316 EPHB2 https://www.ncbi.nlm.nih.gov/gene/2048 CD82 https://www.ncbi.nlm.nih.gov/gene/3732 MSMB https://www.ncbi.nlm.nih.gov/gene/4477 MSR1 https://www.ncbi.nlm.nih.gov/gene/4481 MXI1 https://www.ncbi.nlm.nih.gov/gene/4601 PLXNB1 https://www.ncbi.nlm.nih.gov/gene/5364 RNASEL https://www.ncbi.nlm.nih.gov/gene/6041 MAD1L1 https://www.ncbi.nlm.nih.gov/gene/8379 CHEK2 https://www.ncbi.nlm.nih.gov/gene/11200 EHBP1 https://www.ncbi.nlm.nih.gov/gene/23301 ELAC2 https://www.ncbi.nlm.nih.gov/gene/60528 Cancer of the prostate Malignant neoplasm of the prostate Prostate carcinoma Prostate neoplasm Prostatic cancer Prostatic carcinoma Prostatic neoplasm GTR C1863600 GTR C1970250 GTR C2677821 GTR C2931456 GTR C3539120 GTR C4722327 ICD-10-CM C61 ICD-10-CM D07.5 MeSH D011471 OMIM 176807 OMIM 300147 OMIM 300704 OMIM 601518 OMIM 602759 OMIM 603688 OMIM 604845 OMIM 605097 OMIM 607592 OMIM 608656 OMIM 608658 OMIM 609299 OMIM 609558 OMIM 609717 OMIM 610321 OMIM 610997 OMIM 611100 OMIM 611868 OMIM 611928 OMIM 611955 OMIM 611958 OMIM 611959 OMIM 614731 OMIM 615452 SNOMED CT 399068003 2015-04 2021-08-05 Protein C deficiency https://medlineplus.gov/genetics/condition/protein-c-deficiency descriptionProtein C deficiency is a disorder that increases the risk of developing abnormal blood clots; the condition can be mild or severe.Individuals with mild protein C deficiency are at risk of a type of blood clot known as a deep vein thrombosis (DVT). These clots occur in the deep veins of the arms or legs, away from the surface of the skin. A DVT can travel through the bloodstream and lodge in the lungs, causing a life-threatening blockage of blood flow known as a pulmonary embolism (PE). While most people with mild protein C deficiency never develop abnormal blood clots, certain factors can add to the risk of their development. These factors include increased age, surgery, inactivity, or pregnancy. Having another inherited disorder of blood clotting in addition to protein C deficiency can also influence the risk of abnormal blood clotting.In severe cases of protein C deficiency, infants develop a life-threatening blood clotting disorder called purpura fulminans soon after birth. Purpura fulminans is characterized by the formation of blood clots in the small blood vessels throughout the body. These blood clots block normal blood flow and can lead to localized death of body tissue (necrosis). Widespread blood clotting uses up all available blood clotting proteins. As a result, abnormal bleeding occurs in various parts of the body, which can cause large, purple patches on the skin. Individuals who survive the newborn period may experience recurrent episodes of purpura fulminans. ad Autosomal dominant PROC https://medlineplus.gov/genetics/gene/proc Hereditary thrombophilia due to protein C deficiency PROC deficiency GTR C2674321 MeSH D020151 OMIM 176860 OMIM 612304 SNOMED CT 439274008 SNOMED CT 441101007 SNOMED CT 441188004 SNOMED CT 76407009 2009-10 2024-09-19 Protein S deficiency https://medlineplus.gov/genetics/condition/protein-s-deficiency descriptionProtein S deficiency is a disorder that increases the risk of developing blood clots. People with protein S deficiency are at risk of developing a type of clot called a deep vein thrombosis (DVT) that occurs in the deep veins of the arms or legs. A DVT can travel through the bloodstream and lodge in the lungs, causing a life-threatening clot called a pulmonary embolism (PE). Both DVTs and PEs are a type of venous thromboembolism, a general term for blood clots that form in a vein. Factors such as age, surgery, immobility, or pregnancy can increase the risk of clotting in people with protein S deficiency. In addition, people who have protein S deficiency and another inherited blood clotting disorder may have a higher risk of developing blood clots. Venous thromboembolism occurs in approximately fifty to sixty percent of people with protein S deficiency. In rare cases, individuals have a severe form of protein S deficiency with signs and symptoms that develop soon after birth. Affected infants typically develop a life-threatening blood clotting disorder called purpura fulminans. Purpura fulminans is characterized by the formation of blood clots within small blood vessels throughout the body. These blood clots disrupt normal blood flow and can lead to the death of tissues (necrosis). Widespread blood clotting uses up all available blood clotting proteins. As a result, the body can no longer create clots, and bleeding occurs in various parts of the body. This abnormal bleeding often appears as large, purple skin lesions. Affected individuals who survive the newborn period may experience recurrent episodes of purpura fulminans. ar Autosomal recessive ad Autosomal dominant PROS1 https://medlineplus.gov/genetics/gene/pros1 Hereditary thrombophilia due to protein S deficiency Thrombophilia due to protein S deficiency, autosomal dominant Thrombophilia due to protein S deficiency, autosomal recessive GTR C3278211 ICD-10-CM MeSH D018455 OMIM 612336 SNOMED CT 1563006 SNOMED CT 439702007 SNOMED CT 440988005 SNOMED CT 441189007 2024-04 2024-04-30 Proteus syndrome https://medlineplus.gov/genetics/condition/proteus-syndrome descriptionProteus syndrome is a rare condition characterized by overgrowth of the bones, skin, and other tissues. Organs and tissues affected by the disease grow out of proportion to the rest of the body. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the condition. Overgrowth becomes apparent between the ages of 6 and 18 months and gets more severe with age.In people with Proteus syndrome, the pattern of overgrowth varies greatly but can affect almost any part of the body. Bones in the limbs, skull, and spine are often affected. The condition can also cause a variety of skin growths, particularly a thick, raised, and deeply grooved lesion known as a cerebriform connective tissue nevus. This type of skin growth usually occurs on the soles of the feet and is hardly ever seen in conditions other than Proteus syndrome. Blood vessels (vascular tissue) and fat (adipose tissue) can also grow abnormally in Proteus syndrome.Some people with Proteus syndrome have neurological abnormalities, including intellectual disability, seizures, and vision loss. Affected individuals may also have distinctive facial features such as a long face, outside corners of the eyes that point downward (down-slanting palpebral fissures), a low nasal bridge with wide nostrils, and an open-mouth expression. For reasons that are unclear, affected people with neurological symptoms are more likely to have distinctive facial features than those without neurological symptoms. It is unclear how these signs and symptoms are related to abnormal growth.Other potential complications of Proteus syndrome include an increased risk of developing various types of noncancerous (benign) tumors and a type of blood clot called a deep venous thrombosis (DVT). DVTs occur most often in the deep veins of the legs or arms. If these clots travel through the bloodstream, they can lodge in the lungs and cause a life-threatening complication called a pulmonary embolism. Pulmonary embolism is a common cause of death in people with Proteus syndrome. u Pattern unknown AKT1 https://medlineplus.gov/genetics/gene/akt1 PS GTR C0085261 MeSH D016715 OMIM 176920 SNOMED CT 23150001 2012-06 2023-02-28 Prothrombin deficiency https://medlineplus.gov/genetics/condition/prothrombin-deficiency descriptionProthrombin deficiency is a bleeding disorder that slows the blood clotting process. People with this condition often experience prolonged bleeding following an injury, surgery, or having a tooth pulled. In severe cases of prothrombin deficiency, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Women with prothrombin deficiency can have prolonged and sometimes abnormally heavy menstrual bleeding. Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of prothrombin deficiency do not involve spontaneous bleeding, and the condition may only become apparent following surgery or a serious injury. ar Autosomal recessive F2 https://medlineplus.gov/genetics/gene/f2 Dysprothrombinemia Factor II deficiency Hypoprothrombinemia GTR C0272317 ICD-10-CM D68.2 MeSH D007020 OMIM 613679 SNOMED CT 73975000 2008-09 2023-08-22 Prothrombin thrombophilia https://medlineplus.gov/genetics/condition/prothrombin-thrombophilia descriptionProthrombin thrombophilia is a disorder that increases the risk of developing blood clots. Thrombophilia is the term used to describe an increased tendency to form blood clots. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss. People with thrombophilia can develop clots when they are not needed. These clots can block normal blood flow and cause harm.People who have prothrombin thrombophilia have a higher-than-average risk of developing a type of clot called a deep vein thrombosis, which typically occurs in the blood vessels of the arms or legs. People with prothrombin thrombophilia also have an increased risk of developing a pulmonary embolism, which is a clot that travels through the bloodstream and lodges in the lungs. Research suggests that pregnancy loss may be somewhat more likely in people with prothrombin thrombophilia than in those who do not have the condition. Some researchers have suggested that prothrombin thrombophilia may also increase the risk of other complications during pregnancy, though this remains controversial.While many people with prothrombin thrombophilia will never have clotting issues, several factors increase a person's risk of blood clots. Some risk factors that contribute to the development of harmful blood clots include surgery, injury or trauma, air travel, obesity, and a family history of blood clots. Additional risk factors include pregnancy, using contraceptives such as birth control pills or patches that contain estrogen, and receiving post-menopausal hormone replacement therapy. The combination of prothrombin thrombophilia and other clotting disorders may also increase a person's risk. ad Autosomal dominant F2 https://medlineplus.gov/genetics/gene/f2 Prothrombin G20210A thrombophilia Prothrombin-related thrombophilia Thrombophilia 1 due to thrombin defect GTR C3160733 ICD-10-CM D68.52 MeSH D019851 OMIM 188050 SNOMED CT 440989002 SNOMED CT 441420000 SNOMED CT 441421001 2025-01 2025-01-14 Proximal 18q deletion syndrome https://medlineplus.gov/genetics/condition/proximal-18q-deletion-syndrome descriptionProximal 18q deletion syndrome is a chromosomal condition that occurs when a piece of the long (q) arm of chromosome 18 is missing. The term "proximal" means that the missing piece occurs near the center of the chromosome. Individuals with proximal 18q deletion syndrome have a wide variety of signs and symptoms. Because only a small number of people are known to have this type of deletion, it can be difficult to determine which features should be considered characteristic of the disorder.Most people with proximal 18q deletion syndrome have delayed development of skills such as sitting, crawling, walking, and speaking, and intellectual disability that can range from mild to severe. In particular, vocabulary and the production of speech (expressive language skills) may be delayed. Recurrent seizures (epilepsy) and weak muscle tone (hypotonia) often occur in this disorder. Affected individuals also frequently have neurodevelopmental disorders such as hyperactivity, aggression, and autism spectrum disorder that affect communication and social interaction. ad Autosomal dominant 18 https://medlineplus.gov/genetics/chromosome/18 18q deletion syndrome 18q- syndrome Chromosome 18 deletion syndrome Chromosome 18 long arm deletion syndrome Chromosome 18q monosomy Chromosome 18q- syndrome Del(18q) syndrome Monosomy 18q GTR C0432443 MeSH D025063 OMIM 601808 2017-02 2023-08-02 Pseudoachondroplasia https://medlineplus.gov/genetics/condition/pseudoachondroplasia descriptionPseudoachondroplasia is an inherited disorder of bone growth. It was once thought to be related to another disorder of bone growth called achondroplasia, but without that disorder's characteristic facial features. More research has demonstrated that pseudoachondroplasia is a separate disorder.All people with pseudoachondroplasia have short stature. The average height of adult males with this condition is 120 centimeters (3 feet, 11 inches), and the average height of adult females is 116 centimeters (3 feet, 9 inches). Individuals with pseudoachondroplasia are not unusually short at birth; by the age of two, their growth rate falls below the standard growth curve.Other characteristic features of pseudoachondroplasia include short arms and legs; a waddling walk; joint pain in childhood that progresses to a joint disease known as osteoarthritis; an unusually large range of joint movement (hyperextensibility) in the hands, knees, and ankles; and a limited range of motion at the elbows and hips. Some people with pseudoachondroplasia have legs that turn outward or inward (valgus or varus deformity). Sometimes, one leg turns outward and the other inward, which is called windswept deformity. Some affected individuals have a spine that curves to the side (scoliosis) or an abnormally curved lower back (lordosis). People with pseudoachondroplasia have normal facial features, head size, and intelligence. ad Autosomal dominant COMP https://medlineplus.gov/genetics/gene/comp PSACH Pseudoachondroplastic dysplasia Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome GTR C0410538 MeSH D004392 OMIM 177170 SNOMED CT 22567005 2008-02 2020-08-18 Pseudocholinesterase deficiency https://medlineplus.gov/genetics/condition/pseudocholinesterase-deficiency descriptionPseudocholinesterase deficiency, also called butyrylcholinesterase deficiency, is a condition that is characterized by an increased sensitivity to certain substances, including the medications succinylcholine and mivacurium. These medications may be given during general anesthesia. General anesthesia is typically used during major surgeries and causes a brief period of unconsciousness. Succinylcholine and mivacurium relax the muscles used for movement (skeletal muscles), including the muscles involved in breathing. Succinylcholine and mivacurium are typically broken down (metabolized) by the body within a few minutes of being administered. However, people with pseudocholinesterase deficiency do not metabolize these medications as quickly, so they remain active longer than usual. As a result, people with pseudocholinesterase deficiency may not be able to move or breathe on their own for a few hours after succinylcholine and mivacurium are administered. Affected individuals must be supported with a machine to help them breathe (mechanical ventilation) until the medications are cleared from the body.People with pseudocholinesterase deficiency may also have an increased sensitivity to other substances, including cocaine and the local anesthetic procaine. Local anesthetics are used to numb a small area of the body. Affected individuals may also be more sensitive to specific agricultural pesticides. Because affected individuals typically have no other signs or symptoms, pseudocholinesterase deficiency is usually not discovered until a person has an abnormal reaction to one of these substances. ar Autosomal recessive n Not inherited BCHE https://medlineplus.gov/genetics/gene/bche Acholinesterasemia Butyrylcholinesterase deficiency Deficiency of butyrylcholine esterase Hereditary pseudocholinesterase deficiency GTR C1283400 MeSH D008661 OMIM 177400 SNOMED CT 191397007 SNOMED CT 360589003 SNOMED CT 360607009 SNOMED CT 418059000 2025-09 2025-09-25 Pseudohypoaldosteronism type 1 https://medlineplus.gov/genetics/condition/pseudohypoaldosteronism-type-1 descriptionPseudohypoaldosteronism type 1 (PHA1) is a condition characterized by problems regulating the amount of sodium in the body. Sodium regulation, which is important for blood pressure and fluid balance, primarily occurs in the kidneys. However, sodium can also be removed from the body through other tissues, such as the sweat glands and colon. Pseudohypoaldosteronism type 1 is named for its characteristic signs and symptoms, which mimic (pseudo) low levels (hypo) of a hormone called aldosterone that helps regulate sodium levels. However, people with PHA1 have high levels of aldosterone.There are two types of PHA1 distinguished by their severity, the genes involved, and how they are inherited. One type, called autosomal dominant PHA1 (also known as renal PHA1) is characterized by excessive sodium loss from the kidneys. This form of the condition is relatively mild and often improves in early childhood. The other type, called autosomal recessive PHA1 (also known as generalized or systemic PHA1) is characterized by sodium loss from the kidneys and other organs, including the sweat glands, salivary glands, and colon. This type of PHA1 is more severe and does not improve with age.The earliest signs of both types of PHA1 are usually the inability to gain weight and grow at the expected rate (failure to thrive) and dehydration, which are typically seen in infants. The characteristic features of both types of PHA1 are excessive amounts of sodium released in the urine (salt wasting), which leads to low levels of sodium in the blood (hyponatremia), and high levels of potassium in the blood (hyperkalemia). Infants with PHA1 can also have high levels of acid in the blood (metabolic acidosis). Hyponatremia, hyperkalemia, or metabolic acidosis can cause nonspecific symptoms such as nausea, vomiting, extreme tiredness (fatigue), and muscle weakness in infants with PHA1.Infants with autosomal recessive PHA1 can have additional signs and symptoms due to the involvement of multiple organs. Affected individuals may experience episodes of abnormal heartbeat (cardiac arrhythmia) or shock because of the imbalance of salts in the body. They may also have recurrent lung infections or lesions on the skin. Although adults with autosomal recessive PHA1 can have repeated episodes of salt wasting, they do not usually have other signs and symptoms of the condition. ad Autosomal dominant ar Autosomal recessive NR3C2 https://medlineplus.gov/genetics/gene/nr3c2 SCNN1A https://medlineplus.gov/genetics/gene/scnn1a SCNN1B https://medlineplus.gov/genetics/gene/scnn1b SCNN1G https://medlineplus.gov/genetics/gene/scnn1g PHA1 Pseudohypoaldosteronism type I GTR C1449842 GTR C5774176 MeSH D011546 OMIM 177735 OMIM 264350 SNOMED CT 43941006 2011-12 2023-08-21 Pseudohypoaldosteronism type 2 https://medlineplus.gov/genetics/condition/pseudohypoaldosteronism-type-2 descriptionPseudohypoaldosteronism type 2 (PHA2) is caused by problems that affect regulation of the amount of sodium and potassium in the body. Sodium and potassium are important in the control of blood pressure, and their regulation occurs primarily in the kidneys.People with PHA2 have high blood pressure (hypertension) and high levels of potassium in their blood (hyperkalemia) despite having normal kidney function. The age of onset of PHA2 is variable and difficult to pinpoint; some affected individuals are diagnosed in infancy or childhood, and others are diagnosed in adulthood. Hyperkalemia usually occurs first, and hypertension develops later in life. Affected individuals also have high levels of chloride (hyperchloremia) and acid (metabolic acidosis) in their blood (together, referred to as hyperchloremic metabolic acidosis). People with hyperkalemia, hyperchloremia, and metabolic acidosis can have nonspecific symptoms like nausea, vomiting, extreme tiredness (fatigue), and muscle weakness. People with PHA2 may also have high levels of calcium in their urine (hypercalciuria). ad Autosomal dominant ar Autosomal recessive WNK1 https://medlineplus.gov/genetics/gene/wnk1 WNK4 https://medlineplus.gov/genetics/gene/wnk4 CUL3 https://medlineplus.gov/genetics/gene/cul3 KLHL3 https://medlineplus.gov/genetics/gene/klhl3 Familial hyperkalemic hypertension Familial hyperpotassemia and hypertension Familial hypertensive hyperkalemia FHHt Gordon hyperkalemia-hypertension syndrome Gordon's syndrome PHAII Pseudohypoaldosteronism type II GTR C1840389 MeSH D011546 OMIM 145260 OMIM 614491 OMIM 614492 OMIM 614495 OMIM 614496 SNOMED CT 15689008 2016-03 2020-08-18 Pseudoxanthoma elasticum https://medlineplus.gov/genetics/condition/pseudoxanthoma-elasticum descriptionPseudoxanthoma elasticum (PXE) is a progressive disorder that is characterized by the accumulation of deposits of calcium and other minerals (mineralization) in elastic fibers. Elastic fibers are a component of connective tissue, which provides strength and flexibility to structures throughout the body.In PXE, mineralization can affect elastic fibers in the skin, eyes, and blood vessels, and less frequently in other areas such as the digestive tract. People with PXE may have yellowish bumps called papules on their necks, underarms, and other areas of skin that touch when a joint bends (flexor areas). They may also have abnormalities in the eyes, such as a change in the pigmented cells of the retina (the light-sensitive layer of cells at the back of the eye) known as peau d'orange. Another eye abnormality known as angioid streaks occurs when tiny breaks form in the layer of tissue under the retina called Bruch's membrane. Bleeding and scarring of the retina may also occur, which can cause vision loss.Mineralization of the blood vessels that carry blood from the heart to the rest of the body (arteries) may cause other signs and symptoms of PXE. For example, people with this condition can develop narrowing of the arteries (arteriosclerosis) or a condition called claudication that is characterized by cramping and pain during exercise due to decreased blood flow to the arms and legs. Rarely, bleeding from blood vessels in the digestive tract may also occur. ad Autosomal dominant ar Autosomal recessive ABCC6 https://medlineplus.gov/genetics/gene/abcc6 Groenblad-Strandberg syndrome Gronblad-Strandberg syndrome PXE GTR C0033847 MeSH D011561 OMIM 177850 OMIM 264800 SNOMED CT 252246005 SNOMED CT 72744008 2015-01 2020-08-18 Psoriatic arthritis https://medlineplus.gov/genetics/condition/psoriatic-arthritis descriptionPsoriatic arthritis is a condition involving joint inflammation (arthritis) that usually occurs in combination with a skin disorder called psoriasis. Psoriasis is a chronic inflammatory condition characterized by patches of red, irritated skin that are often covered by flaky white scales. People with psoriasis may also have changes in their fingernails and toenails, such as nails that become pitted or ridged, crumble, or separate from the nail beds.Signs and symptoms of psoriatic arthritis include stiff, painful joints with redness, heat, and swelling in the surrounding tissues. When the hands and feet are affected, swelling and redness may result in a "sausage-like" appearance of the fingers or toes (dactylitis).In most people with psoriatic arthritis, psoriasis appears before joint problems develop. Psoriasis typically begins during adolescence or young adulthood, and psoriatic arthritis usually occurs between the ages of 30 and 50. However, both conditions may occur at any age. In a small number of cases, psoriatic arthritis develops in the absence of noticeable skin changes.Psoriatic arthritis may be difficult to distinguish from other forms of arthritis, particularly when skin changes are minimal or absent. Nail changes and dactylitis are two features that are characteristic of psoriatic arthritis, although they do not occur in all cases.Psoriatic arthritis is categorized into five types: distal interphalangeal predominant, asymmetric oligoarticular, symmetric polyarthritis, spondylitis, and arthritis mutilans.The distal interphalangeal predominant type affects mainly the ends of the fingers and toes. The distal interphalangeal joints are those closest to the nails. Nail changes are especially frequent with this form of psoriatic arthritis.The asymmetric oligoarticular and symmetric polyarthritis types are the most common forms of psoriatic arthritis. The asymmetric oligoarticular type of psoriatic arthritis involves different joints on each side of the body, while the symmetric polyarthritis form affects the same joints on each side. Any joint in the body may be affected in these forms of the disorder, and symptoms range from mild to severe.Some individuals with psoriatic arthritis have joint involvement that primarily involves spondylitis, which is inflammation in the joints between the vertebrae in the spine. Symptoms of this form of the disorder involve pain and stiffness in the back or neck, and movement is often impaired. Joints in the arms, legs, hands, and feet may also be involved.The most severe and least common type of psoriatic arthritis is called arthritis mutilans. Fewer than 5 percent of individuals with psoriatic arthritis have this form of the disorder. Arthritis mutilans involves severe inflammation that damages the joints in the hands and feet, resulting in deformation and movement problems. Bone loss (osteolysis) at the joints may lead to shortening (telescoping) of the fingers and toes. Neck and back pain may also occur. u Pattern unknown HLA-B https://medlineplus.gov/genetics/gene/hla-b IL23R https://medlineplus.gov/genetics/gene/il23r HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 CARD14 https://medlineplus.gov/genetics/gene/card14 HLA-C https://www.ncbi.nlm.nih.gov/gene/3107 IL12B https://www.ncbi.nlm.nih.gov/gene/3593 IL13 https://www.ncbi.nlm.nih.gov/gene/3596 TRAF3IP2 https://www.ncbi.nlm.nih.gov/gene/10758 Arthropathic psoriasis Psoriatic arthropathy GTR C1835223 ICD-10-CM L40.5 ICD-10-CM L40.50 ICD-10-CM L40.51 ICD-10-CM L40.52 ICD-10-CM L40.53 ICD-10-CM L40.54 ICD-10-CM L40.59 MeSH D015535 OMIM 607507 SNOMED CT 33339001 2011-01 2020-08-18 Pulmonary alveolar microlithiasis https://medlineplus.gov/genetics/condition/pulmonary-alveolar-microlithiasis descriptionPulmonary alveolar microlithiasis is a disorder in which many tiny fragments (microliths) of a compound called calcium phosphate gradually accumulate in the small air sacs (alveoli) located throughout the lungs. These deposits eventually cause widespread damage to the alveoli and surrounding lung tissue (interstitial lung disease) that leads to breathing problems. People with this disorder can develop a persistent cough and difficulty breathing (dyspnea), especially during physical exertion. Affected individuals may also experience chest pain that worsens when coughing, sneezing, or taking deep breaths.Pulmonary alveolar microlithiasis is usually diagnosed before age 40. Often the disorder is discovered before symptoms develop, when medical imaging is done for other reasons. The condition typically worsens slowly over many years, although some affected individuals have signs and symptoms that remain stable for long periods of time.People with pulmonary alveolar microlithiasis can also develop calcium phosphate deposits in other organs and tissues of the body, including the kidneys, gallbladder, testes, and the valve that connects a large blood vessel called the aorta with the heart (the aortic valve). In rare cases, affected individuals have complications related to accumulation of these deposits, such as a narrowing (stenosis) of the aortic valve that can impede normal blood flow. ar Autosomal recessive SLC34A2 https://medlineplus.gov/genetics/gene/slc34a2 PAM GTR C0155912 ICD-10-CM J84.02 MeSH D017563 OMIM 265100 SNOMED CT 87153008 2014-12 2020-08-18 Pulmonary arterial hypertension https://medlineplus.gov/genetics/condition/pulmonary-arterial-hypertension descriptionPulmonary arterial hypertension is a progressive disorder characterized by abnormally high blood pressure (hypertension) in the pulmonary artery, the blood vessel that carries blood from the heart to the lungs. Pulmonary arterial hypertension is one form of a broader condition known as pulmonary hypertension. Pulmonary hypertension occurs when most of the very small arteries throughout the lungs narrow in diameter, which increases the resistance to blood flow through the lungs. To overcome the increased resistance, blood pressure increases in the pulmonary artery and in the right ventricle of the heart, which is the chamber that pumps blood into the pulmonary artery. Ultimately, the increased blood pressure can damage the right ventricle of the heart.Signs and symptoms of pulmonary arterial hypertension occur when increased blood pressure cannot fully overcome the elevated resistance. As a result, the flow of oxygenated blood from the lungs to the rest of the body is insufficient. Shortness of breath (dyspnea) during exertion and fainting spells are the most common symptoms of pulmonary arterial hypertension. People with this disorder may experience additional symptoms, particularly as the condition worsens. Other symptoms include dizziness, swelling (edema) of the ankles or legs, chest pain, and a rapid heart rate. ad Autosomal dominant BMPR2 https://medlineplus.gov/genetics/gene/bmpr2 ENG https://medlineplus.gov/genetics/gene/eng ACVRL1 https://medlineplus.gov/genetics/gene/acvrl1 EIF2AK4 https://medlineplus.gov/genetics/gene/eif2ak4 CAV1 https://medlineplus.gov/genetics/gene/cav1 BMPR1B https://www.ncbi.nlm.nih.gov/gene/658 CBLN2 https://www.ncbi.nlm.nih.gov/gene/870 KCNA5 https://www.ncbi.nlm.nih.gov/gene/3741 KCNK3 https://www.ncbi.nlm.nih.gov/gene/3777 SMAD9 https://www.ncbi.nlm.nih.gov/gene/4093 Ayerza syndrome Familial primary pulmonary hypertension FPPH Idiopathic pulmonary hypertension PAH PPH PPHT Primary pulmonary hypertension Sporadic primary pulmonary hypertension GTR C3809192 GTR C3809198 GTR C3888002 GTR C4552070 ICD-10-CM I27.0 ICD-10-CM I27.21 MeSH D065627 OMIM 178600 OMIM 615342 OMIM 615343 OMIM 615344 SNOMED CT 233943009 SNOMED CT 233944003 SNOMED CT 697897003 SNOMED CT 78862003 2016-01 2023-02-28 Pulmonary veno-occlusive disease https://medlineplus.gov/genetics/condition/pulmonary-veno-occlusive-disease descriptionPulmonary veno-occlusive disease (PVOD) is characterized by the blockage (occlusion) of the blood vessels that carry oxygen-rich (oxygenated) blood from the lungs to the heart (the pulmonary veins). The occlusion is caused by a buildup of abnormal fibrous tissue in the small veins in the lungs, which narrows the vessels and impairs blood flow. Because blood flow through the lungs is difficult, pressure rises in the vessels that carry blood that needs to be oxygenated to the lungs from the heart (the pulmonary arteries). Increased pressure in these vessels is known as pulmonary arterial hypertension.The problems with blood flow in PVOD also impair the delivery of oxygenated blood to the rest of the body, which leads to the signs and symptoms of the condition. Shortness of breath (dyspnea) and tiredness (fatigue) during exertion are the most common symptoms of this condition. Other common features include dizziness, a lack of energy (lethargy), difficulty breathing when lying down, and a cough that does not go away. As the condition worsens, affected individuals can develop a bluish tint to the skin (cyanosis), chest pains, fainting spells, and an accumulation of fluid in the lungs (pulmonary edema).Certain features commonly seen in people with PVOD can be identified using a test called a CT scan. One of these features, which is seen in the lungs of affected individuals, is an abnormality described as centrilobular ground-glass opacities. Affected individuals also have abnormal thickening of certain tissues in the lungs, which is described as septal lines. In addition, lymph nodes in the chest (mediastinal lymph nodes) are abnormally enlarged in people with PVOD.PVOD can begin at any age, and the blood flow problems worsen over time. Because of the increased blood pressure in the pulmonary arteries, the heart must work harder than normal to pump blood to the lungs, which can eventually lead to fatal heart failure. Most people with this severe disorder do not live more than 2 years after diagnosis. ad Autosomal dominant ar Autosomal recessive BMPR2 https://medlineplus.gov/genetics/gene/bmpr2 EIF2AK4 https://medlineplus.gov/genetics/gene/eif2ak4 Isolated pulmonary venous sclerosis Obstructive disease of the pulmonary veins Pulmonary venoocclusive disease PVOD Venous form of primary pulmonary hypertension GTR C3887658 MeSH D011668 OMIM 234810 OMIM 265450 SNOMED CT 89420002 2015-03 2023-03-01 Purine nucleoside phosphorylase deficiency https://medlineplus.gov/genetics/condition/purine-nucleoside-phosphorylase-deficiency descriptionPurine nucleoside phosphorylase deficiency is a disorder of the immune system called an immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses.People with purine nucleoside phosphorylase deficiency have low numbers of immune system cells called T cells, which normally recognize and attack foreign invaders to prevent infection. Some affected individuals also have low numbers of other immune system cells called B cells, which normally help fight infections by producing immune proteins called antibodies (or immunoglobulins). These proteins target foreign invaders and mark them for destruction. The most severely affected individuals, who lack T cells and B cells, have a serious condition called severe combined immunodeficiency (SCID).The shortage of immune system cells in people with purine nucleoside phosphorylase deficiency results in repeated and persistent infections typically beginning in infancy or early childhood. Infections most commonly affect the sinuses and lungs. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. The infections can be very serious or life-threatening, and without successful treatment to restore immune function, children with purine nucleoside phosphorylase deficiency usually do not survive past childhood.Infants with purine nucleoside phosphorylase deficiency typically grow more slowly than healthy babies. About two-thirds of individuals with this condition also have neurological problems, which may include developmental delay, intellectual disability, difficulty with balance and coordination (ataxia), and muscle stiffness (spasticity). People with purine nucleoside phosphorylase deficiency are also at increased risk of developing autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs. ar Autosomal recessive PNP https://medlineplus.gov/genetics/gene/pnp Nucleoside phosphorylase deficiency PNP deficiency GTR C0268125 ICD-10-CM D81.5 MeSH D016511 OMIM 613179 SNOMED CT 60743005 2019-04 2020-08-18 Pyle disease https://medlineplus.gov/genetics/condition/pyle-disease descriptionPyle disease is a disorder of the bones. Its hallmark feature is an abnormality of the long bones in the arms and legs in which the ends (metaphyses) of the bones are abnormally broad; the shape of the bones resembles a boat oar or paddle. The broad metaphyses are due to enlargement of the spongy inner layer of bone (trabecular bone). Although trabecular bone is expanded, the dense outermost layer of bone (cortical bone) is thinner than normal. As a result, the bones are fragile and fracture easily. The bone abnormalities in the legs commonly cause knock knees (genu valgum) in affected individuals.Other bone abnormalities can also occur in Pyle disease. Affected individuals may have widened collar bones (clavicles), ribs, or bones in the fingers and hands. Dental problems are common in Pyle disease, including delayed appearance (eruption) of permanent teeth and misalignment of the top and bottom teeth (malocclusion). ar Autosomal recessive SFRP4 https://medlineplus.gov/genetics/gene/sfrp4 Metaphyseal dysplasia, Pyle type Pyle metaphyseal dysplasia Pyle's disease Pyle's metaphyseal dysplasia syndrome GTR C0265294 ICD-10-CM Q78.5 MeSH D010009 OMIM 265900 SNOMED CT 27837003 2017-03 2020-08-18 Pyridoxal phosphate-responsive seizures https://medlineplus.gov/genetics/condition/pyridoxal-phosphate-responsive-seizures descriptionPyridoxal phosphate-responsive seizures (sometimes called pyridoxamine 5'-phosphate oxidase deficiency or PNPO deficiency) is a condition in which repeated seizures (epilepsy) typically begin within the first two weeks of life. In approximately 10 percent of individuals with PNPO deficiency, the seizures have a later onset, beginning after the first month of life. The seizures typically involve irregular involuntary muscle contractions (myoclonus), abnormal eye movements, or convulsions. In some cases, the seizures may last for several minutes or the seizures may occur too close together to allow for recovery between episodes (status epilepticus). Some babies with PNPO deficiency will experience seizures before birth, and some will experience a slow heart rate and a lack of oxygen before delivery (fetal distress). Anticonvulsant medications, which are usually given to control seizures, are not effective in people with PNPO deficiency. Instead, individuals with PNPO deficiency require lifelong treatment with one of the following forms of vitamin B6: pyridoxal 5'-phosphate (PLP) or pyridoxine. If untreated, people with this condition can develop severe brain dysfunction (encephalopathy), which can lead to death. Even though seizures can be controlled with PLP or pyridoxine, people with PNPO deficiency may still experience neurological problems such as developmental delays, learning disorders, and uncontrolled movements (dystonia).Other conditions present with signs and symptoms that are very similar to those seen in people with PNPO deficiency. These include pyridoxine-dependent epilepsy caused by changes in the ALDH7A1 gene and PLPBP deficiency caused by changes in the PLPBP gene. Individuals with these conditions are also typically treated with a form of vitamin B6. ar Autosomal recessive PNPO https://medlineplus.gov/genetics/gene/pnpo PNPO deficiency PNPO-related neonatal epileptic encephalopathy PNPOD Pyridoxal 5′-phosphate-dependent epilepsy Pyridoxal phosphate-dependent seizures Pyridoxamine 5'-oxidase deficiency Pyridoxamine 5'-phosphate oxidase deficiency Pyridoxamine 5-prime-phosphate oxidase deficiency Pyridoxine-resistant seizures, PLP-sensitive GTR C1864723 ICD-10-CM MeSH D004827 OMIM 610090 SNOMED CT 124174008 2024-03 2024-04-02 Pyridoxine-dependent epilepsy https://medlineplus.gov/genetics/condition/pyridoxine-dependent-epilepsy descriptionPyridoxine-dependent epilepsy is a condition that involves seizures beginning in infancy or, in some cases, before birth. Those affected typically experience prolonged seizures lasting several minutes (status epilepticus). These seizures involve muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures). Additional features of pyridoxine-dependent epilepsy include low body temperature (hypothermia), poor muscle tone (dystonia) soon after birth, and irritability before a seizure episode. In rare instances, children with this condition do not have seizures until they are 1 to 3 years old.Anticonvulsant drugs, which are usually given to control seizures, are ineffective in people with pyridoxine-dependent epilepsy. Instead, people with this type of seizure are medically treated with large daily doses of pyridoxine (a type of vitamin B6 found in food). If left untreated, people with this condition can develop severe brain dysfunction (encephalopathy). Even though seizures can be controlled with pyridoxine, neurological problems such as developmental delay and learning disorders may still occur. ar Autosomal recessive ALDH7A1 https://medlineplus.gov/genetics/gene/aldh7a1 AASA dehydrogenase deficiency EPD Epilepsy, pyridoxine-dependent PDE Pyridoxine dependency Pyridoxine dependency with seizures Pyridoxine-dependent seizures Vitamin B6-dependent seizures GTR C1849508 MeSH D012640 OMIM 266100 SNOMED CT 734434007 2008-06 2024-04-02 Pyruvate carboxylase deficiency https://medlineplus.gov/genetics/condition/pyruvate-carboxylase-deficiency descriptionPyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to accumulate in the blood. High levels of these substances can damage the body's organs and tissues, particularly in the nervous system.Researchers have identified at least three types of pyruvate carboxylase deficiency, which are distinguished by the severity of their signs and symptoms. Type A, which has been identified mostly in people from North America, has severe symptoms that begin in infancy. Characteristic features include developmental delay and a buildup of lactic acid in the blood (lactic acidosis). Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food (fasting). Children with pyruvate carboxylase deficiency type A typically survive only into infancy or early childhood.Pyruvate carboxylase deficiency type B has life-threatening signs and symptoms that become apparent shortly after birth. This form of the condition has been reported mostly in Europe, particularly France. Affected infants have severe lactic acidosis, a buildup of ammonia in the blood (hyperammonemia), and liver failure. They experience neurological problems including weak muscle tone (hypotonia), abnormal movements, seizures, and coma. Infants with this form of the condition usually survive for less than 3 months after birth.A milder form of pyruvate carboxylase deficiency, sometimes called type C, has also been described. This type is characterized by slightly increased levels of lactic acid in the blood and minimal signs and symptoms affecting the nervous system. ar Autosomal recessive PC https://medlineplus.gov/genetics/gene/pc Ataxia with lactic acidosis, type II Leigh necrotizing encephalopathy due to pyruvate carboxylase deficiency Leigh syndrome due to pyruvate carboxylase deficiency PC deficiency Pyruvate carboxylase deficiency disease Type II ataxia with lactic acidosis GTR C0034341 ICD-10-CM E74.4 MeSH D015324 OMIM 266150 SNOMED CT 87694001 2006-08 2020-08-18 Pyruvate dehydrogenase deficiency https://medlineplus.gov/genetics/condition/pyruvate-dehydrogenase-deficiency descriptionPyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood. ar Autosomal recessive x X-linked PDP1 https://medlineplus.gov/genetics/gene/pdp1 PDHA1 https://medlineplus.gov/genetics/gene/pdha1 PDHB https://medlineplus.gov/genetics/gene/pdhb PDHX https://medlineplus.gov/genetics/gene/pdhx DLAT https://medlineplus.gov/genetics/gene/dlat Ataxia with lactic acidosis Intermittent ataxia with pyruvate dehydrogenase deficiency PDH deficiency PDHC deficiency Pyruvate dehydrogenase complex deficiency GTR C0034345 GTR C1837429 GTR C1839413 GTR C1855553 GTR C1855565 GTR C3279841 MeSH D015325 OMIM 245348 OMIM 245349 OMIM 312170 OMIM 608782 OMIM 614111 SNOMED CT 46683007 2012-07 2021-06-24 Pyruvate kinase deficiency https://medlineplus.gov/genetics/condition/pyruvate-kinase-deficiency descriptionPyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Specifically, pyruvate kinase deficiency is a common cause of a type of inherited hemolytic anemia called hereditary nonspherocytic hemolytic anemia. In hereditary nonspherocytic hemolytic anemia, the red blood cells do not assume a spherical shape as they do in some other forms of hemolytic anemia.Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness (fatigue), shortness of breath (dyspnea), and a rapid heart rate (tachycardia). An enlarged spleen (splenomegaly), an excess of iron in the blood, and small pebble-like deposits in the gallbladder or bile ducts (gallstones) are also common in this disorder.In people with pyruvate kinase deficiency, hemolytic anemia and associated complications may range from mild to severe. Some affected individuals have few or no symptoms. Severe cases can be life-threatening in infancy, and such affected individuals may require regular blood transfusions to survive. The symptoms of this disorder may get worse during an infection or pregnancy. ar Autosomal recessive PKLR https://medlineplus.gov/genetics/gene/pklr PK deficiency PKD GTR C0340968 ICD-10-CM D55.2 MeSH D000745 OMIM 266200 SNOMED CT 124331002 2012-04 2020-08-18 RAB18 deficiency https://medlineplus.gov/genetics/condition/rab18-deficiency descriptionRAB18 deficiency causes two conditions with similar signs and symptoms that primarily affect the eyes, brain, and reproductive system. These two conditions, called Warburg micro syndrome and Martsolf syndrome, were once thought to be distinct disorders but are now considered to be part of the same disease spectrum because of their similar features and shared genetic cause.Warburg micro syndrome is the more severe condition. Individuals with this condition have several eye problems from birth, including clouding of the lenses of the eyes (cataracts), abnormally small eyes (microphthalmia), and small corneas (microcornea). The lens is a structure at the front of the eye that helps focus light, and the cornea is the outer covering of the eye. In addition, the pupils of the eyes may be abnormally small (constricted), and they may not enlarge (dilate) in low light. Individuals with Warburg micro syndrome also have degeneration of the nerves that carry visual information from the eyes to the brain (optic atrophy). The eye problems impair vision in affected individuals.People with Warburg micro syndrome have severe intellectual disability and other neurological features due to problems with growth and development of the brain. Affected individuals have delayed development and may never be able to sit, stand, walk, or speak. They usually have weak muscle tone (hypotonia) in infancy. By early childhood, they develop muscle stiffness (spasticity) and joint deformities (contractures) that restrict movement in the legs. The muscle problems worsen (progress) to include the arms and lead to paralysis of all four limbs (spastic quadriplegia). Eventually, breathing may be impaired. The brain abnormalities can contribute to vision problems (cortical visual impairment). Individuals with Warburg micro syndrome may also have recurrent seizures (epilepsy).Some people with Warburg micro syndrome have reduced production of the hormones that direct sexual development (hypogonadotropic hypogonadism). The shortage of these hormones impairs normal development of reproductive organs. Affected males may have a small penis (micropenis) or undescended testes (cryptorchidism). Affected females may have underdeveloped internal genital folds (labia minora) or a small clitoris or vaginal opening (introitus).Martsolf syndrome affects the same body systems as Warburg micro syndrome but is usually less severe. Individuals with Martsolf syndrome have cataracts, microphthalmia, and small pupils. They have milder optic atrophy and cortical visual impairment than people with Warburg micro syndrome. Intellectual disability is mild to moderate in people with Martsolf syndrome. While language and motor skills, such as sitting and walking, are delayed, affected individuals usually acquire them. Hypotonia is common in infants with Martsolf syndrome, although spasticity worsens more slowly than in individuals with Warburg micro syndrome, and it usually affects only the legs and feet. Hypogonadotropic hypogonadism can also occur in individuals with Martsolf syndrome.Neither Warburg micro syndrome nor Martsolf syndrome affect the life expectancy of affected individuals. ar Autosomal recessive RAB18 https://medlineplus.gov/genetics/gene/rab18 RAB3GAP1 https://medlineplus.gov/genetics/gene/rab3gap1 RAB3GAP2 https://medlineplus.gov/genetics/gene/rab3gap2 TBC1D20 https://medlineplus.gov/genetics/gene/tbc1d20 Martsolf syndrome Warburg micro syndrome GTR C0796037 GTR C5442005 ICD-10-CM MeSH D000015 OMIM 212720 OMIM 600118 OMIM 614222 OMIM 614225 OMIM 615663 SNOMED CT 722380003 2018-04 2023-08-22 RAPADILINO syndrome https://medlineplus.gov/genetics/condition/rapadilino-syndrome descriptionRAPADILINO syndrome is a rare condition that involves many parts of the body. Bone development is especially affected, causing many of the characteristic features of the condition.Most affected individuals have underdevelopment or absence of the bones in the forearms and the thumbs, which are known as radial ray malformations. The kneecaps (patellae) can also be underdeveloped or absent. Other features include an opening in the roof of the mouth (cleft palate) or a high arched palate; a long, slender nose; and dislocated joints.Many infants with RAPADILINO syndrome have difficulty feeding and experience diarrhea and vomiting. The combination of impaired bone development and feeding problems leads to slow growth and short stature in affected individuals.Some individuals with RAPADILINO syndrome have harmless light brown patches of skin that resemble a skin finding known as café-au-lait spots. In addition, people with RAPADILINO syndrome have a slightly increased risk of developing a type of bone cancer known as osteosarcoma or a blood-related cancer called lymphoma. In individuals with RAPADILINO syndrome, osteosarcoma most often develops during childhood or adolescence, and lymphoma typically develops in young adulthood.The condition name is an acronym for the characteristic features of the disorder: RA for radial ray malformations, PA for patella and palate abnormalities, DI for diarrhea and dislocated joints, LI for limb abnormalities and little size, and NO for slender nose and normal intelligence.The varied signs and symptoms of RAPADILINO syndrome overlap with features of other disorders, namely Baller-Gerold syndrome and Rothmund-Thomson syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Baller-Gerold syndrome, Rothmund-Thomson syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms. ar Autosomal recessive RECQL4 https://medlineplus.gov/genetics/gene/recql4 Absent thumbs, dislocated joints, long face with narrow palpebral fissures, long slender nose, arched palate Radial and patellar aplasia Radial and patellar hypoplasia GTR C1849453 MeSH D001848 OMIM 266280 SNOMED CT 702413000 2013-08 2023-03-01 REN-related kidney disease https://medlineplus.gov/genetics/condition/ren-related-kidney-disease descriptionREN-related kidney disease is an inherited condition that affects kidney function. This condition causes slowly progressive kidney disease that usually becomes apparent during childhood. As this condition progresses, the kidneys become less able to filter fluids and waste products from the body, resulting in kidney failure. Individuals with REN-related kidney disease typically require dialysis (to remove wastes from the blood) or a kidney transplant between ages 40 and 70.People with REN-related kidney disease sometimes have low blood pressure. They may also have mildly increased levels of potassium in their blood (hyperkalemia). In childhood, people with REN-related kidney disease develop a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue. In this disorder, anemia is usually mild and begins to improve during adolescence.Many individuals with this condition develop high blood levels of a waste product called uric acid. Normally, the kidneys remove uric acid from the blood and transfer it to urine so it can be excreted from the body. In REN-related kidney disease, the kidneys are unable to remove uric acid from the blood effectively. A buildup of uric acid can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints. Individuals with REN-related kidney disease may begin to experience the signs and symptoms of gout during their twenties. ad Autosomal dominant REN https://medlineplus.gov/genetics/gene/ren Familial juvenile hyperuricemic nephropathy 2 GTR C2751310 MeSH D007674 OMIM 613092 SNOMED CT 46785007 2010-01 2023-11-13 RNAse T2-deficient leukoencephalopathy https://medlineplus.gov/genetics/condition/rnase-t2-deficient-leukoencephalopathy descriptionRNAse T2-deficient leukoencephalopathy is a disorder that affects the brain. People with RNAse T2-deficient leukoencephalopathy have neurological problems that become apparent during infancy; the problems generally do not worsen over time (progress). Most affected individuals have severe intellectual disability; muscle stiffness (spasticity); and a delay in developing motor skills such as sitting, crawling, and walking. Some do not learn to walk, and most do not develop the ability to speak. Other neurological features that can occur in RNAse T2-deficient leukoencephalopathy include hearing loss caused by abnormalities in the inner ear (sensorineural deafness), seizures, involuntary writhing movements of the hands (athetosis), uncontrolled muscle tensing (dystonia), and involuntary eye movements (nystagmus). In addition to the neurological problems associated with this disorder, some affected individuals have unusual facial features sometimes described as a "doll-like face."The neurological problems in this disorder are caused by abnormalities in the brain. People with this condition have leukoencephalopathy, an abnormality of the brain's white matter that can be detected with medical imaging. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In people with RNAse T2-deficient leukoencephalopathy, myelin is not made in sufficient amounts during development, leading to patchy white matter abnormalities (lesions) in the brain. In addition, individuals with RNAse T2-deficient leukoencephalopathy may have cysts in regions of the brain called the temporal lobes and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. The white matter lesions are primarily concentrated around the cysts and the ventricles. An abnormally small head and brain size (microcephaly) often occurs in this disorder. ar Autosomal recessive RNASET2 https://medlineplus.gov/genetics/gene/rnaset2 Cystic leukoencephalopathy without megalencephaly LBATC Leukoencephalopathy with bilateral anterior temporal lobe cysts RNASET2-deficient cystic leukoencephalopathy GTR C2751843 MeSH D020279 OMIM 612951 SNOMED CT 720825005 2016-11 2022-10-26 RRM2B-related mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy https://medlineplus.gov/genetics/condition/rrm2b-related-mitochondrial-dna-depletion-syndrome-encephalomyopathic-form-with-renal-tubulopathy descriptionRRM2B-related mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy (RRM2B-MDS) is a severe condition that begins in infancy and affects multiple body systems. It is associated with brain dysfunction combined with muscle weakness (encephalomyopathy). Many affected individuals also have a kidney dysfunction known as renal tubulopathy.Infants with RRM2B-MDS have weak muscle tone (hypotonia) and a failure to grow or gain weight at the expected rate (failure to thrive). Many have a smaller-than-normal head size (microcephaly). Due to muscle weakness, affected infants typically have difficulty controlling head movement and may have delayed development of other motor skills, such as rolling over or sitting. Weakness of the muscles used for breathing leads to serious breathing difficulties and can result in life-threatening respiratory failure. Most affected infants have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can also be life-threatening.Some individuals with RRM2B-MDS have a digestion problem known as gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently. This disorder may lead to swallowing difficulties, vomiting, and diarrhea and can contribute to a failure to thrive. Less commonly, individuals with RRM2B-MDS develop seizures or hearing loss that is caused by nerve damage in the inner ear (sensorineural hearing loss).Because of the severity of the signs and symptoms, people with RRM2B-MDS usually live only into early childhood. ar Autosomal recessive RRM2B https://medlineplus.gov/genetics/gene/rrm2b Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MTDPS8A RRM2B-MDS MeSH D017237 OMIM 612075 2016-11 2023-11-13 Rabson-Mendenhall syndrome https://medlineplus.gov/genetics/condition/rabson-mendenhall-syndrome descriptionRabson-Mendenhall syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with Rabson-Mendenhall syndrome, insulin resistance impairs blood glucose regulation and ultimately leads to a condition called diabetes mellitus, in which blood glucose levels can become dangerously high.Severe insulin resistance in people with Rabson-Mendenhall syndrome affects the development of many parts of the body. Affected individuals are unusually small starting before birth, and infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features of the condition that become apparent early in life include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; dental abnormalities; excessive body hair growth (hirsutism); multiple cysts on the ovaries in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Rabson-Mendenhall syndrome include prominent, widely spaced eyes; a broad nose; and large, low-set ears.Rabson-Mendenhall syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Rabson-Mendenhall syndrome is intermediate in severity between Donohue syndrome (which is usually fatal before age 2) and type A insulin resistance syndrome (which is often not diagnosed until adolescence). People with Rabson-Mendenhall syndrome develop signs and symptoms early in life and live into their teens or twenties. Death usually results from complications related to diabetes mellitus, such as a toxic buildup of acids called ketones in the body (diabetic ketoacidosis). ar Autosomal recessive INSR https://medlineplus.gov/genetics/gene/insr Mendenhall syndrome Pineal hyperplasia and diabetes mellitus syndrome Pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities RMS GTR C0271695 MeSH D056731 OMIM 262190 SNOMED CT 33559001 2014-12 2023-07-19 Rapid-onset dystonia parkinsonism https://medlineplus.gov/genetics/condition/rapid-onset-dystonia-parkinsonism descriptionRapid-onset dystonia parkinsonism (sometimes referred to as RDP) is a rare movement disorder. "Rapid-onset" refers to the abrupt appearance of signs and symptoms over a period of hours to days. Dystonia  is a condition characterized by involuntary, sustained muscle contractions. Parkinsonism can include tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling walk that can cause falls.Rapid-onset dystonia parkinsonism causes movement abnormalities that can make it difficult to walk, talk, and carry out other activities of daily life. In people with this disorder, dystonia affects the arms and legs, causing muscle cramping and spasms. Facial muscles are often affected, resulting in problems with speech and swallowing. People with rapid-onset dystonia and parkinsonism may also have headaches; seizures; a distorted view of reality (psychosis); or difficulty processing, learning, and remembering information (cognitive impairment).The movement abnormalities associated with rapid-onset dystonia parkinsonism tend to begin near the top of the body and move downward. They affect the facial muscles first, then the arms, and finally the legs.The signs and symptoms of rapid-onset dystonia parkinsonism most commonly appear in adolescence or young adulthood. In some affected individuals, signs and symptoms can be triggered by an infection, physical stress (such as prolonged exercise), emotional stress, or alcohol consumption. The signs and symptoms tend to stabilize within about a month, but they typically do not improve much after that. In some people with this condition, the movement abnormalities abruptly worsen during a second episode several years later.Some people with rapid-onset dystonia parkinsonism have been diagnosed with anxiety, social phobias, depression, and seizures. It is unclear whether these disorders are related to the genetic changes that cause rapid-onset dystonia parkinsonism. ad Autosomal dominant+Inherited or new variant ATP1A3 https://medlineplus.gov/genetics/gene/atp1a3 Dystonia 12 DYT12 RDP RODP GTR C1868681 ICD-10-CM MeSH D020821 OMIM 128235 SNOMED CT 702323008 2024-04 2024-04-23 Raynaud phenomenon https://medlineplus.gov/genetics/condition/raynaud-phenomenon descriptionRaynaud phenomenon is a condition in which the body's normal response to cold or emotional stress is exaggerated, resulting in abnormal spasms (vasospasms) in small blood vessels called arterioles. The disorder mainly affects the fingers but can also involve the ears, nose, nipples, knees, or toes. The vasospasms reduce blood circulation, leading to discomfort and skin color changes.Raynaud phenomenon is episodic, meaning that it comes and goes. A typical episode lasts about 15 minutes after the cold exposure or stressor has ended and involves mild discomfort such as numbness or a feeling of "pins and needles." The affected areas usually turn white or blue when exposed to cold or when emotional stress occurs, and then turn red when re-warmed or when the stress eases.Raynaud phenomenon is categorized as primary when there is no underlying disorder that accounts for the exaggerated response of the blood vessels. It is called secondary when it is associated with another condition. Secondary Raynaud phenomenon is often associated with autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. Autoimmune disorders with which Raynaud phenomenon can be associated include systemic lupus erythematosus, scleroderma, rheumatoid arthritis, and Sjögren syndrome.Primary Raynaud phenomenon is much more common and usually less severe than secondary Raynaud phenomenon. In severe cases of secondary Raynaud phenomenon, sores on the pads of the fingers or tissue death (necrosis) can occur. Primary Raynaud phenomenon often begins between the ages of 15 and 25, while secondary Raynaud phenomenon usually starts after age 30. Some people with Raynaud phenomenon alone later go on to develop another associated condition; regardless of which comes first, these cases are classified as secondary Raynaud phenomenon. u Pattern unknown Raynaud disease Raynaud's Raynaud's disease Raynaud's phenomenon Raynaud's syndrome ICD-10-CM I73.0 ICD-10-CM I73.00 ICD-10-CM I73.01 MeSH D011928 OMIM 179600 SNOMED CT 195295006 SNOMED CT 266261006 SNOMED CT 286301000119102 2018-03 2025-12-22 Recombinant 8 syndrome https://medlineplus.gov/genetics/condition/recombinant-8-syndrome descriptionRecombinant 8 syndrome is a condition that involves complex congenital heart abnormalities, urinary tract abnormalities, moderate to severe intellectual disability, abnormal muscle tone, and a distinctive facial appearance. The most common heart abnormalities are known as tetrology of Fallot and conotruncal defects. The characteristic facial features include a wide, square face; a thin upper lip; a downturned mouth; a small chin (micrognathia); wide-set eyes (hypertelorism); and low-set or unusually shaped ears.  People with recombinant 8 syndrome may have overgrowth of the gums (gingival hyperplasia), abnormal tooth development, or an opening in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Males with this condition frequently have undescended testes (cryptorchidism). Some affected individuals have recurrent ear infections (otitis media), hearing loss, or hand and finger differences. In individuals with recombinant 8 syndrome, the heart abnormalities can be life-threatening. ad Autosomal dominant 8 https://medlineplus.gov/genetics/chromosome/8 Rec(8) syndrome Recombinant chromosome 8 syndrome San Luis Valley syndrome ICD-10-CM MeSH D025063 OMIM 179613 SNOMED CT 718189004 2009-04 2022-08-23 Recurrent hydatidiform mole https://medlineplus.gov/genetics/condition/recurrent-hydatidiform-mole descriptionRecurrent hydatidiform mole is a condition that affects women and is characterized by the occurrence of at least two abnormal pregnancies that result in the formation of hydatidiform moles. A hydatidiform mole is a mass that forms early in pregnancy and is made up of cells from an abnormally developed embryo and placenta. Normally, the embryo would develop into a fetus and the placenta would grow to provide nutrients to the growing fetus. When a hydatidiform mole occurs once, it is known as sporadic hydatidiform mole; if it happens again, the condition is known as recurrent hydatidiform mole.The first symptom of a hydatidiform mole is often vaginal bleeding in the first trimester of pregnancy. During an ultrasound examination, the abnormal placenta appears as numerous small sacs, often described as resembling a bunch of grapes.Hydatidiform moles are not naturally discharged from the body and must be surgically removed, typically by the end of the first trimester. After removal, there is up to a 20 percent risk that any tissue left behind will continue to grow and become a cancerous (malignant) tumor called a persistent mole. If the tumor invades the surrounding tissue of the uterus, it is called an invasive mole. In rare cases, this malignant tumor can transform into a different form of cancer called gestational choriocarcinoma that can spread (metastasize) to other tissues such as the liver, lungs, or brain. ar Autosomal recessive NLRP7 https://medlineplus.gov/genetics/gene/nlrp7 KHDC3L https://medlineplus.gov/genetics/gene/khdc3l TOP6BL https://www.ncbi.nlm.nih.gov/gene/79703 MEI1 https://www.ncbi.nlm.nih.gov/gene/150365 REC114 https://www.ncbi.nlm.nih.gov/gene/283677 Familial recurrent hydatidiform mole FRHM Recurrent androgenetic hydatidiform mole Recurrent biparental hydatidiform mole GTR C3280352 GTR C3463897 ICD-10-CM O01.0 MeSH D006828 OMIM 231090 OMIM 614293 SNOMED CT 237249000 2018-12 2020-08-18 Refsum disease https://medlineplus.gov/genetics/condition/refsum-disease descriptionRefsum disease is an inherited condition that causes vision loss, absence of the sense of smell (anosmia), and a variety of other signs and symptoms.The vision loss associated with Refsum disease is caused by an eye disorder called retinitis pigmentosa. This disorder affects the retina, the light-sensitive layer at the back of the eye. Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. The first sign of retinitis pigmentosa is usually a loss of night vision, which often becomes apparent in childhood. Over a period of years, the disease disrupts side (peripheral) vision and may eventually lead to blindness.Vision loss and anosmia are seen in almost everyone with Refsum disease, but other signs and symptoms vary. About one-third of affected individuals are born with bone abnormalities of the hands and feet. Features that appear later in life can include progressive muscle weakness and wasting; poor balance and coordination (ataxia); hearing loss; and dry, scaly skin (ichthyosis). Additionally, some people with Refsum disease develop an abnormal heart rhythm (arrhythmia) and related heart problems that can be life-threatening. ar Autosomal recessive PHYH https://medlineplus.gov/genetics/gene/phyh PEX7 https://medlineplus.gov/genetics/gene/pex7 Adult Refsum disease ARD Classic Refsum disease CRD Hereditary motor and sensory neuropathy type IV Heredopathia atactica polyneuritiformis HMSN IV HMSN type IV Phytanic acid storage disease Refsum syndrome Refsum's disease GTR C0034960 ICD-10-CM G60.1 MeSH D012035 OMIM 266500 SNOMED CT 25362006 2010-01 2023-04-04 Renal coloboma syndrome https://medlineplus.gov/genetics/condition/renal-coloboma-syndrome descriptionRenal coloboma syndrome (also known as papillorenal syndrome) is a condition that primarily affects kidney (renal) and eye development. People with this condition typically have kidneys that are small and underdeveloped (hypoplastic), which can lead to end-stage renal disease (ESRD). This serious disease occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. It has been estimated that approximately ten percent of children with hypoplastic kidneys may have renal coloboma syndrome. The kidney problems can affect one or both kidneys.Additionally, people with renal coloboma syndrome may have a malformation in the optic nerve, a structure that carries information from the eye to the brain. Optic nerve malformations are sometimes associated with a gap or hole (coloboma) in the light-sensitive tissue at the back of the eye (the retina). The vision problems caused by these abnormalities can vary depending on the size and location of the malformation. Some people have no visual problems, while others may have severely impaired vision.Less common features of renal coloboma syndrome include backflow of urine from the bladder (vesicoureteral reflux), multiple kidney cysts, loose joints, and mild hearing loss. ad Autosomal dominant PAX2 https://medlineplus.gov/genetics/gene/pax2 Coloboma of optic nerve with renal disease Coloboma-ureteral-renal syndrome ONCR Optic coloboma, vesicoureteral reflux, and renal anomalies Optic nerve coloboma renal syndrome Papillorenal syndrome RCS Renal-coloboma syndrome GTR C1852759 MeSH D003103 MeSH D007674 OMIM 120330 SNOMED CT 446449009 2022-08 2022-08-03 Renal hypouricemia https://medlineplus.gov/genetics/condition/renal-hypouricemia descriptionRenal hypouricemia is a kidney (renal) disorder that results in a reduced amount of urate in the blood. Urate is a byproduct of certain normal chemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. However, having too much urate in the body is toxic, so excess urate is removed from the body in urine.People with renal hypouricemia have little to no urate in their blood; they release an excessive amount of it in the urine. In many affected individuals, renal hypouricemia causes no signs or symptoms. However, some people with this condition develop kidney problems. After strenuous exercise, they can develop exercise-induced acute kidney injury, which causes pain in their sides and lower back as well as nausea and vomiting that can last several hours.Because an excessive amount of urate passes through the kidneys to be excreted in urine in people with renal hypouricemia, they have an increased risk of developing kidney stones (nephrolithiasis) formed from urate crystals. These urate stones can damage the kidneys and lead to episodes of blood in the urine (hematuria). Rarely, people with renal hypouricemia develop life-threatening kidney failure. ar Autosomal recessive SLC22A12 https://medlineplus.gov/genetics/gene/slc22a12 SLC2A9 https://medlineplus.gov/genetics/gene/slc2a9 Familial renal hypouricaemia Familial renal hypouricemia Hereditary renal hypouricemia RHUC GTR C0473219 GTR C2677549 MeSH D015499 OMIM 220150 OMIM 612076 SNOMED CT 236478009 2015-01 2023-03-01 Renal tubular acidosis with deafness https://medlineplus.gov/genetics/condition/renal-tubular-acidosis-with-deafness descriptionRenal tubular acidosis with deafness is a disorder characterized by kidney (renal) problems and hearing loss. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with this disorder, the kidneys do not remove enough acidic compounds from the body. Instead, the acids are absorbed back into the bloodstream, and the blood becomes too acidic. This chemical imbalance, called metabolic acidosis, can result in a range of signs and symptoms that vary in severity. Metabolic acidosis often causes nausea, vomiting, and dehydration; affected infants tend to have problems feeding and gaining weight (failure to thrive). Most children and adults with renal tubular acidosis with deafness have short stature, and many develop kidney stones.The metabolic acidosis that occurs in renal tubular acidosis with deafness may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. Rarely, people with renal tubular acidosis with deafness have episodes of hypokalemic paralysis, a condition that causes extreme muscle weakness associated with low levels of potassium in the blood (hypokalemia).In people with renal tubular acidosis with deafness, hearing loss caused by changes in the inner ear (sensorineural hearing loss) usually begins between childhood and young adulthood, and gradually gets worse. An inner ear abnormality affecting both ears occurs in most people with this disorder. This feature, which is called enlarged vestibular aqueduct, can be seen with medical imaging. The vestibular aqueduct is a bony canal that runs from the inner ear into the temporal bone of the skull and toward the brain. The relationship between enlarged vestibular aqueduct and hearing loss is unclear. In renal tubular acidosis with deafness, enlarged vestibular aqueduct typically occurs in individuals whose hearing loss begins in childhood. ar Autosomal recessive ATP6V1B1 https://medlineplus.gov/genetics/gene/atp6v1b1 ATP6V0A4 https://medlineplus.gov/genetics/gene/atp6v0a4 AR dRTA with deafness AR dRTA with hearing loss Autosomal recessive distal renal tubular acidosis with deafness Renal tubular acidosis type 1b Renal tubular acidosis with progressive nerve deafness Renal tubular acidosis, autosomal recessive, with progressive nerve deafness Renal tubular acidosis, distal, with progressive nerve deafness RTA with progressive nerve deafness GTR C0403554 MeSH D000141 OMIM 267300 SNOMED CT 236532003 2014-03 2020-08-18 Renal tubular dysgenesis https://medlineplus.gov/genetics/condition/renal-tubular-dysgenesis descriptionRenal tubular dysgenesis is a severe kidney disorder characterized by abnormal development of the kidneys before birth. In particular, kidney structures called proximal tubules are absent or underdeveloped. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete everything else into the urine. Without functional proximal tubules, the kidneys cannot produce urine (a condition called anuria).Fetal urine is the major component of the fluid that surrounds the fetus (amniotic fluid), and anuria leads to decreased amniotic fluid levels (oligohydramnios). Amniotic fluid helps cushion and protect the fetus and plays a role in the development of many organs, including the lungs. Oligohydramnios causes a set of abnormalities called the Potter sequence, which includes distinctive facial features such as a flattened nose and large, low-set ears; excess skin; inward- and upward-turning feet (clubfeet); and underdeveloped lungs.Renal tubular dysgenesis also causes severe low blood pressure (hypotension). In addition, bone development in the skull is abnormal in some affected individuals, causing a large space between the bones of the skull (fontanelles).As a result of the serious health problems caused by renal tubular dysgenesis, affected individuals usually die before birth, are stillborn, or die soon after birth from respiratory failure. Rarely, with treatment, affected individuals survive into childhood. Their blood pressure usually normalizes, but they quickly develop chronic kidney disease, which is characterized by reduced kidney function that worsens over time. ar Autosomal recessive REN https://medlineplus.gov/genetics/gene/ren ACE https://medlineplus.gov/genetics/gene/ace AGT https://medlineplus.gov/genetics/gene/agt AGTR1 https://medlineplus.gov/genetics/gene/agtr1 Allanson Pantzar McLeod syndrome Primitive renal tubule syndrome GTR C0266313 MeSH D007674 OMIM 267430 SNOMED CT 702397002 2013-05 2020-08-18 Renpenning syndrome https://medlineplus.gov/genetics/condition/renpenning-syndrome descriptionRenpenning syndrome is a disorder that almost exclusively affects males, causing developmental delay, moderate to severe intellectual disability, and distinctive physical features. Individuals with Renpenning syndrome typically have short stature and a small head size (microcephaly). Facial features characteristic of this disorder include a long, narrow face; outside corners of the eyes that point upward (upslanting palpebral fissures); a long, bulbous nose with a low-hanging separation between the nostrils (overhanging columella); a shortened space between the nose and mouth (philtrum); and cup-shaped ears. Males with Renpenning syndrome generally have small testes. Seizures and wasting away (atrophy) of muscles used for movement (skeletal muscles) may also occur in this disorder.About 20 percent of individuals with Renpenning syndrome also have other features, which may include a gap or split in structures that make up the eye (coloboma), an opening in the roof of the mouth (cleft palate), heart abnormalities, or malformations of the anus.Certain combinations of the features that often occur in Renpenning syndrome are sometimes called by other names, such as Golabi-Ito-Hall syndrome or Sutherland-Haan syndrome. However, all these syndromes, which have the same genetic cause, are now generally grouped under the term Renpenning syndrome. xr X-linked recessive PQBP1 https://medlineplus.gov/genetics/gene/pqbp1 Golabi-Ito-Hall syndrome Hamel cerebropalatocardiac syndrome Porteous syndrome Sutherland-Haan syndrome X-linked intellectual deficit due to PQBP1 mutations X-linked intellectual deficit, Renpenning type GTR C0796135 MeSH D038901 OMIM 309500 SNOMED CT 699669001 2012-06 2020-08-18 Restless legs syndrome https://medlineplus.gov/genetics/condition/restless-legs-syndrome descriptionRestless legs syndrome is a neurological condition that causes an irresistible urge to move the legs. The movement is triggered by strange or uncomfortable feelings, often described as crawling, pulling, or itching, deep within both legs. The feelings usually occur while the affected person is sitting or lying down and are worse at night. Movement, such as kicking, stretching, rubbing, or pacing, make the discomfort go away, at least temporarily. The unpleasant feelings and the resulting need to move the legs often make it difficult for an affected person to fall asleep or stay asleep.The signs and symptoms of restless legs syndrome range from mild to severe; people with mild cases may experience symptoms a few times a month, while those with more severe cases may have symptoms every night. In severe cases, the uncomfortable feelings can affect the arms or other parts of the body in addition to the legs.Many people with restless legs syndrome also experience uncontrollable, repetitive leg movements that occur while they are sleeping or while relaxed or drowsy. When these movements occur during sleep, they are called periodic limb movements of sleep (PLMS); when they occur while a person is awake, they are called periodic limb movements of wakefulness (PLMW). It is unclear whether PLMS and PLMW are features of restless legs syndrome itself or represent similar, but separate, conditions.Restless legs syndrome and PLMS can affect the quality and amount of sleep. As a result of these conditions, affected individuals may have difficulty concentrating during the day, and some develop mood swings, depression, or other health problems.Researchers have described early-onset and late-onset forms of restless legs syndrome. The early-onset form begins before age 45, and sometimes as early as childhood. The signs and symptoms of this form usually worsen slowly with time. The late-onset form begins after age 45, and its signs and symptoms tend to worsen more rapidly. u Pattern unknown ad Autosomal dominant MEIS1 https://www.ncbi.nlm.nih.gov/gene/4211 MAP2K5 https://www.ncbi.nlm.nih.gov/gene/5607 PTPRD https://www.ncbi.nlm.nih.gov/gene/5789 TOX3 https://www.ncbi.nlm.nih.gov/gene/27324 BTBD9 https://www.ncbi.nlm.nih.gov/gene/114781 SKOR1 https://www.ncbi.nlm.nih.gov/gene/390598 Ekbom syndrome Ekbom's syndrome Restless leg syndrome RLS WED Willis-Ekbom disease ICD-10-CM G25.81 MeSH D012148 OMIM 102300 OMIM 608831 OMIM 610438 OMIM 610439 OMIM 611185 OMIM 611242 OMIM 612853 OMIM 615197 SNOMED CT 32914008 2013-10 2024-09-19 Retinal arterial macroaneurysm with supravalvular pulmonic stenosis https://medlineplus.gov/genetics/condition/retinal-arterial-macroaneurysm-with-supravalvular-pulmonic-stenosis descriptionRetinal arterial macroaneurysm with supravalvular pulmonic stenosis (RAMSVPS) is a disorder that affects blood vessels in the eyes and heart. The condition generally becomes apparent in infancy or childhood.RAMSVPS damages the arteries in the light-sensitive tissue at the back of the eye (the retina). These arteries gradually develop multiple small bulges called beading. Eventually, larger bulges in the blood vessel walls (macroaneurysms) occur. These macroaneurysms can tear (rupture), leading to bleeding that can spread into other areas of the eye and cause vision loss.People with RAMSVPS also have a heart condition called supravalvular pulmonic stenosis. Pulmonic stenosis is a narrowing that affects the pulmonic valve between the heart and the lungs. The term "supravalvular" means that the narrowing occurs just above the valve, in a blood vessel called the pulmonary artery. Supravalvular pulmonic stenosis impairs blood flow into the lungs, where blood normally picks up oxygen for distribution to cells and tissues throughout the body. As a result, less oxygen is carried through the bloodstream, leading to signs and symptoms that include shortness of breath; a rapid heartbeat; fatigue; and swelling in the face, feet, or abdomen. ar Autosomal recessive IGFBP7 https://medlineplus.gov/genetics/gene/igfbp7 Familial retinal arterial macroaneurysm FRAM RAMSVPS GTR C3280205 ICD-10-CM H35.09 MeSH D015785 OMIM 614224 2015-08 2020-08-18 Retinitis pigmentosa https://medlineplus.gov/genetics/condition/retinitis-pigmentosa descriptionRetinitis pigmentosa is a group of related eye disorders that cause progressive vision loss. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with retinitis pigmentosa, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.The first sign of retinitis pigmentosa is usually a loss of night vision, which becomes apparent in childhood. Problems with night vision can make it difficult to navigate in low light. Later, the disease causes blind spots to develop in the side (peripheral) vision. Over time, these blind spots merge to produce tunnel vision. The disease progresses over years or decades to affect central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. In adulthood, many people with retinitis pigmentosa become legally blind.The signs and symptoms of retinitis pigmentosa are most often limited to vision loss. When the disorder occurs by itself, it is described as nonsyndromic. Researchers have identified several major types of nonsyndromic retinitis pigmentosa, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked.Less commonly, retinitis pigmentosa occurs as part of syndromes that affect other organs and tissues in the body. These forms of the disease are described as syndromic. The most common form of syndromic retinitis pigmentosa is Usher syndrome, which is characterized by the combination of vision loss and hearing loss beginning early in life. Retinitis pigmentosa is also a feature of several other genetic syndromes, including Bardet-Biedl syndrome; Refsum disease; and neuropathy, ataxia, and retinitis pigmentosa (NARP). ar Autosomal recessive ad Autosomal dominant xr X-linked recessive USH2A https://medlineplus.gov/genetics/gene/ush2a CLRN1 https://medlineplus.gov/genetics/gene/clrn1 PRPH2 https://medlineplus.gov/genetics/gene/prph2 BEST1 https://medlineplus.gov/genetics/gene/best1 CRB1 https://medlineplus.gov/genetics/gene/crb1 RPE65 https://medlineplus.gov/genetics/gene/rpe65 RHO https://medlineplus.gov/genetics/gene/rho RPGR https://medlineplus.gov/genetics/gene/rpgr RP2 https://medlineplus.gov/genetics/gene/rp2 ABCA4 https://medlineplus.gov/genetics/gene/abca4 PDE6B https://medlineplus.gov/genetics/gene/pde6b WDR19 https://medlineplus.gov/genetics/gene/wdr19 CRX https://medlineplus.gov/genetics/gene/crx CA4 https://www.ncbi.nlm.nih.gov/gene/762 CNGB1 https://www.ncbi.nlm.nih.gov/gene/1258 CNGA1 https://www.ncbi.nlm.nih.gov/gene/1259 GUCA1B https://www.ncbi.nlm.nih.gov/gene/2979 IDH3B https://www.ncbi.nlm.nih.gov/gene/3420 IMPDH1 https://www.ncbi.nlm.nih.gov/gene/3614 MT-TS2 https://www.ncbi.nlm.nih.gov/gene/4575 NRL https://www.ncbi.nlm.nih.gov/gene/4901 PDE6A https://www.ncbi.nlm.nih.gov/gene/5145 PDE6G https://www.ncbi.nlm.nih.gov/gene/5148 RBP3 https://www.ncbi.nlm.nih.gov/gene/5949 RGR https://www.ncbi.nlm.nih.gov/gene/5995 RLBP1 https://www.ncbi.nlm.nih.gov/gene/6017 ROM1 https://www.ncbi.nlm.nih.gov/gene/6094 RP9 https://www.ncbi.nlm.nih.gov/gene/6100 RP1 https://www.ncbi.nlm.nih.gov/gene/6101 SAG https://www.ncbi.nlm.nih.gov/gene/6295 TULP1 https://www.ncbi.nlm.nih.gov/gene/7287 PROM1 https://www.ncbi.nlm.nih.gov/gene/8842 PRPF3 https://www.ncbi.nlm.nih.gov/gene/9129 LRAT https://www.ncbi.nlm.nih.gov/gene/9227 NR2E3 https://www.ncbi.nlm.nih.gov/gene/10002 TOPORS https://www.ncbi.nlm.nih.gov/gene/10210 MERTK https://www.ncbi.nlm.nih.gov/gene/10461 SEMA4A https://www.ncbi.nlm.nih.gov/gene/10510 PRPF8 https://www.ncbi.nlm.nih.gov/gene/10594 SNRNP200 https://www.ncbi.nlm.nih.gov/gene/23020 FSCN2 https://www.ncbi.nlm.nih.gov/gene/25794 PRPF31 https://www.ncbi.nlm.nih.gov/gene/26121 IMPG2 https://www.ncbi.nlm.nih.gov/gene/50939 SPATA7 https://www.ncbi.nlm.nih.gov/gene/55812 KLHL7 https://www.ncbi.nlm.nih.gov/gene/55975 FAM161A https://www.ncbi.nlm.nih.gov/gene/84140 TTC8 https://www.ncbi.nlm.nih.gov/gene/123016 ZNF513 https://www.ncbi.nlm.nih.gov/gene/130557 RDH12 https://www.ncbi.nlm.nih.gov/gene/145226 EYS https://www.ncbi.nlm.nih.gov/gene/346007 CERKL https://www.ncbi.nlm.nih.gov/gene/375298 PCARE https://www.ncbi.nlm.nih.gov/gene/388939 PRCD https://www.ncbi.nlm.nih.gov/gene/768206 Pigmentary retinopathy Rod-cone dystrophy RP Tapetoretinal degeneration GTR C0035334 ICD-10-CM H35.52 MeSH D012174 OMIM 268000 SNOMED CT 28835009 SNOMED CT 80328002 2010-10 2023-03-01 Retinoblastoma https://medlineplus.gov/genetics/condition/retinoblastoma descriptionRetinoblastoma is a rare type of eye cancer that usually develops in early childhood, typically before the age of 5. This form of cancer develops in the retina, which is the specialized light-sensitive tissue at the back of the eye that detects light and color.In children with retinoblastoma, the disease often affects only one eye. However, one out of three children with retinoblastoma develops cancer in both eyes. The most common first sign of retinoblastoma is a visible whiteness in the pupil called "cat's eye reflex" or leukocoria. This unusual whiteness is particularly noticeable in dim light or in photographs taken with a flash. Other signs and symptoms of retinoblastoma include crossed eyes or eyes that do not point in the same direction (strabismus), which can cause squinting; a change in the color of the colored part of the eye (iris); redness, soreness, or swelling of the eyelids; and blindness or poor vision in the affected eye or eyes.Retinoblastoma is often curable when it is diagnosed early. However, if it is not treated promptly, this cancer can spread beyond the eye to other parts of the body. This advanced form of retinoblastoma can be life-threatening.When retinoblastoma is associated with a genetic change (mutation) that occurs in all of the body's cells, it is known as hereditary (or germinal) retinoblastoma. People with this form of retinoblastoma typically develop cancer in both eyes and also have an increased risk of developing several other cancers outside the eye. Specifically, they are more likely to develop a cancer of the pineal gland in the brain (pineoblastoma), a type of bone cancer known as osteosarcoma, cancers of soft tissues (such as muscle) called soft tissue sarcomas, and an aggressive form of skin cancer called melanoma. ad Autosomal dominant RB1 https://medlineplus.gov/genetics/gene/rb1 MYCN https://medlineplus.gov/genetics/gene/mycn 13 https://medlineplus.gov/genetics/chromosome/13 Glioma, retinal RB GTR C0035335 ICD-10-CM C69.2 ICD-10-CM C69.20 ICD-10-CM C69.21 ICD-10-CM C69.22 MeSH D012175 OMIM 180200 SNOMED CT 370967009 2009-04 2020-09-08 Retroperitoneal fibrosis https://medlineplus.gov/genetics/condition/retroperitoneal-fibrosis descriptionRetroperitoneal fibrosis is a disorder in which inflammation and extensive scar tissue (fibrosis) occur in the back of the abdominal cavity, behind (retro-) the membrane that surrounds the organs of the digestive system (the peritoneum). This area is known as the retroperitoneal space. Retroperitoneal fibrosis can occur at any age but appears most frequently between the ages of 40 and 60.The inflamed tissue characteristic of retroperitoneal fibrosis typically causes gradually increasing pain in the lower abdomen, back, or side. Other symptoms arise from blockage of blood flow to and from various parts of the lower body, due to the development of scar tissue around blood vessels. The fibrosis usually develops first around the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Additional blood vessels including the inferior vena cava, which returns blood from the lower part of the body to the heart, may also be involved. Obstruction of blood flow to and from the legs can result in pain, changes in color, and swelling in these limbs. Impairment of blood flow in the intestines may lead to death (necrosis) of intestinal tissue, severe pain, and excessive bleeding (hemorrhage). In men, reduced blood flow back toward the heart (venous flow) may cause swelling of the scrotum.Because the kidneys are located in the retroperitoneal space, retroperitoneal fibrosis may result in blockage of the ureters, which are tubes that carry urine from each kidney to the bladder. Such blockages can lead to decreased or absent urine flow and kidney failure. When the kidneys fail, toxic substances build up in the blood and tissues, leading to nausea, vomiting, weight loss, itching, a low number of red blood cells (anemia), and changes in brain function. u Pattern unknown n Not inherited Ormond disease Ormond's disease MeSH D012185 OMIM 228800 SNOMED CT 49120005 2013-07 2020-08-18 Rett syndrome https://medlineplus.gov/genetics/condition/rett-syndrome descriptionRett syndrome is a brain disorder that occurs almost exclusively in girls. The most common form of the condition is known as classic Rett syndrome. After birth, girls with classic Rett syndrome have 6 to 18 months of apparently normal development before developing severe problems with language and communication, learning, coordination, and other brain functions. Early in childhood, affected girls lose purposeful use of their hands and begin making repeated hand wringing, washing, or clapping motions. They tend to grow more slowly than other children and about three-quarters have a small head size (microcephaly). Other signs and symptoms that can develop include breathing abnormalities, spitting or drooling, unusual eye movements such as intense staring or excessive blinking, cold hands and feet, irritability, sleep disturbances, seizures, and an abnormal side-to-side curvature of the spine (scoliosis).Researchers have described several variant or atypical forms of Rett syndrome, which can be milder or more severe than the classic form.Rett syndrome is part of a spectrum of disorders with the same genetic cause. Other disorders on the spectrum include PPM-X syndrome, MECP2 duplication syndrome, and MECP2-related severe neonatal encephalopathy. These other conditions can affect males. xd X-linked dominant MECP2 https://medlineplus.gov/genetics/gene/mecp2 Autism-dementia-ataxia-loss of purposeful hand use syndrome Rett disorder Rett's disorder Rett's syndrome RTT GTR C0035372 ICD-10-CM F84.2 MeSH D015518 OMIM 312750 SNOMED CT 68618008 2013-12 2023-04-04 Rhabdoid tumor predisposition syndrome https://medlineplus.gov/genetics/condition/rhabdoid-tumor-predisposition-syndrome descriptionRhabdoid tumor predisposition syndrome (RTPS) is characterized by a high risk of developing cancerous (malignant) growths called rhabdoid tumors. These highly aggressive tumors are called rhabdoid because their cells resemble rhabdomyoblasts, which are cells that are normally found in embryos before birth and develop into muscles used for movement (skeletal muscles).Rhabdoid tumors are rare in the general population. They usually occur in the first year of life, and are much less likely to appear after age 4. In people with RTPS, the tumors occur at an average age of 4 to 7 months, and can even occur before birth. Affected individuals may have multifocal synchronous tumors, which means that multiple tumors that develop independently (primary tumors) occur at the same time. The rhabdoid tumors that occur in RTPS usually grow and spread more quickly than those in children without this predisposition, and affected individuals often do not survive past childhood.More than half of all malignant rhabdoid tumors (MRTs) develop in the cerebellum, which is the part of the brain that coordinates movement. Rhabdoid tumors in the brain and spinal cord (central nervous system) are called atypical teratoid/rhabdoid tumors (AT/RTs).Rhabdoid tumors also occur outside the central nervous system. These tumors include rhabdoid tumors of the kidneys (RTKs) and tumors that develop in other organs and tissues of the body (called extrarenal malignant rhabdoid tumors or eMRTs). The type of rhabdoid tumor can vary among individuals with RTPS, even within the same family.Tumors other than rhabdoid tumors can also occur in people with RTPS. Some affected children develop noncancerous (benign) tumors called schwannomas, which grow on nerve cells. Women with RTPS are at increased risk of developing a rare type of ovarian cancer called small cell cancer of the ovary hypercalcemic type (SCCOHT). ad Autosomal dominant SMARCA4 https://medlineplus.gov/genetics/gene/smarca4 SMARCB1 https://medlineplus.gov/genetics/gene/smarcb1 Familial posterior fossa brain tumor of infancy Familial posterior fossa brain tumor syndrome Familial rhabdoid tumor Hereditary SWI/SNF deficiency syndrome Rhabdoid predisposition syndrome RTPS GTR C1836327 GTR C2750074 MeSH D009386 OMIM 609322 OMIM 613325 2018-04 2020-08-18 Rheumatoid arthritis https://medlineplus.gov/genetics/condition/rheumatoid-arthritis descriptionRheumatoid arthritis is a disease that causes chronic inflammation that primarily affects the joints. The most common signs and symptoms are pain, swelling, and stiffness of the joints. This condition frequently affects the hands and feet, although the shoulders, hips, spine, and knees may become involved in the later stages of the disease. Joints are typically affected in a symmetrical pattern; for example, if joints in the hand are affected, both hands tend to be involved. People with rheumatoid arthritis may have trouble with tasks such as opening jars, turning doorknobs, or fastening buttons. Joint pain and stiffness tend to be worse after waking up in the morning or after a long rest. Rheumatoid arthritis can cause inflammation in other tissues and organs, including the eyes, skin, heart, and blood vessels. Affected individuals may also have inflammation in the lungs, which is known as interstitial lung disease. Additional signs and symptoms of rheumatoid arthritis can include a loss of energy, a low fever, weight loss, and a shortage of red blood cells (anemia). Some affected individuals develop rheumatoid nodules, which are firm lumps of noncancerous tissue that can grow under the skin and elsewhere in the body.Most people who have rheumatoid arthritis are 55 years old and older, although it can affect adults of any age. The signs and symptoms of rheumatoid arthritis usually appear in mid to late adulthood. Many affected people have recurrent episodes of symptoms (flares) followed by periods with no symptoms (remissions). In severe cases, affected individuals have continuous health problems related to the disease for many years. The abnormal inflammation can lead to severe joint damage, which limits movement and can cause significant disability. u Pattern unknown HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 Arthritis, rheumatoid RA GTR C0003873 ICD-10-CM M05 ICD-10-CM M05.0 ICD-10-CM M05.00 ICD-10-CM M05.01 ICD-10-CM M05.011 ICD-10-CM M05.012 ICD-10-CM M05.019 ICD-10-CM M05.02 ICD-10-CM M05.021 ICD-10-CM M05.022 ICD-10-CM M05.029 ICD-10-CM M05.03 ICD-10-CM M05.031 ICD-10-CM M05.032 ICD-10-CM M05.039 ICD-10-CM M05.04 ICD-10-CM M05.041 ICD-10-CM M05.042 ICD-10-CM M05.049 ICD-10-CM M05.05 ICD-10-CM M05.051 ICD-10-CM M05.052 ICD-10-CM M05.059 ICD-10-CM M05.06 ICD-10-CM M05.061 ICD-10-CM M05.062 ICD-10-CM M05.069 ICD-10-CM M05.07 ICD-10-CM M05.071 ICD-10-CM M05.072 ICD-10-CM M05.079 ICD-10-CM M05.09 ICD-10-CM M05.1 ICD-10-CM M05.10 ICD-10-CM M05.11 ICD-10-CM M05.111 ICD-10-CM M05.112 ICD-10-CM M05.119 ICD-10-CM M05.12 ICD-10-CM M05.121 ICD-10-CM M05.122 ICD-10-CM M05.129 ICD-10-CM M05.13 ICD-10-CM M05.131 ICD-10-CM M05.132 ICD-10-CM M05.139 ICD-10-CM M05.14 ICD-10-CM M05.141 ICD-10-CM M05.142 ICD-10-CM M05.149 ICD-10-CM M05.15 ICD-10-CM M05.151 ICD-10-CM M05.152 ICD-10-CM M05.159 ICD-10-CM M05.16 ICD-10-CM M05.161 ICD-10-CM M05.162 ICD-10-CM M05.169 ICD-10-CM M05.17 ICD-10-CM M05.171 ICD-10-CM M05.172 ICD-10-CM M05.179 ICD-10-CM M05.19 ICD-10-CM M05.2 ICD-10-CM M05.20 ICD-10-CM M05.21 ICD-10-CM M05.211 ICD-10-CM M05.212 ICD-10-CM M05.219 ICD-10-CM M05.22 ICD-10-CM M05.221 ICD-10-CM M05.222 ICD-10-CM M05.229 ICD-10-CM M05.23 ICD-10-CM M05.231 ICD-10-CM M05.232 ICD-10-CM M05.239 ICD-10-CM M05.24 ICD-10-CM M05.241 ICD-10-CM M05.242 ICD-10-CM M05.249 ICD-10-CM M05.25 ICD-10-CM M05.251 ICD-10-CM M05.252 ICD-10-CM M05.259 ICD-10-CM M05.26 ICD-10-CM M05.261 ICD-10-CM M05.262 ICD-10-CM M05.269 ICD-10-CM M05.27 ICD-10-CM M05.271 ICD-10-CM M05.272 ICD-10-CM M05.279 ICD-10-CM M05.29 ICD-10-CM M05.3 ICD-10-CM M05.30 ICD-10-CM M05.31 ICD-10-CM M05.311 ICD-10-CM M05.312 ICD-10-CM M05.319 ICD-10-CM M05.32 ICD-10-CM M05.321 ICD-10-CM M05.322 ICD-10-CM M05.329 ICD-10-CM M05.33 ICD-10-CM M05.331 ICD-10-CM M05.332 ICD-10-CM M05.339 ICD-10-CM M05.34 ICD-10-CM M05.341 ICD-10-CM M05.342 ICD-10-CM M05.349 ICD-10-CM M05.35 ICD-10-CM M05.351 ICD-10-CM M05.352 ICD-10-CM M05.359 ICD-10-CM M05.36 ICD-10-CM M05.361 ICD-10-CM M05.362 ICD-10-CM M05.369 ICD-10-CM M05.37 ICD-10-CM M05.371 ICD-10-CM M05.372 ICD-10-CM M05.379 ICD-10-CM M05.39 ICD-10-CM M05.4 ICD-10-CM M05.40 ICD-10-CM M05.41 ICD-10-CM M05.411 ICD-10-CM M05.412 ICD-10-CM M05.419 ICD-10-CM M05.42 ICD-10-CM M05.421 ICD-10-CM M05.422 ICD-10-CM M05.429 ICD-10-CM M05.43 ICD-10-CM M05.431 ICD-10-CM M05.432 ICD-10-CM M05.439 ICD-10-CM M05.44 ICD-10-CM M05.441 ICD-10-CM M05.442 ICD-10-CM M05.449 ICD-10-CM M05.45 ICD-10-CM M05.451 ICD-10-CM M05.452 ICD-10-CM M05.459 ICD-10-CM M05.46 ICD-10-CM M05.461 ICD-10-CM M05.462 ICD-10-CM M05.469 ICD-10-CM M05.47 ICD-10-CM M05.471 ICD-10-CM M05.472 ICD-10-CM M05.479 ICD-10-CM M05.49 ICD-10-CM M05.5 ICD-10-CM M05.50 ICD-10-CM M05.51 ICD-10-CM M05.511 ICD-10-CM M05.512 ICD-10-CM M05.519 ICD-10-CM M05.52 ICD-10-CM M05.521 ICD-10-CM M05.522 ICD-10-CM M05.529 ICD-10-CM M05.53 ICD-10-CM M05.531 ICD-10-CM M05.532 ICD-10-CM M05.539 ICD-10-CM M05.54 ICD-10-CM M05.541 ICD-10-CM M05.542 ICD-10-CM M05.549 ICD-10-CM M05.55 ICD-10-CM M05.551 ICD-10-CM M05.552 ICD-10-CM M05.559 ICD-10-CM M05.56 ICD-10-CM M05.561 ICD-10-CM M05.562 ICD-10-CM M05.569 ICD-10-CM M05.57 ICD-10-CM M05.571 ICD-10-CM M05.572 ICD-10-CM M05.579 ICD-10-CM M05.59 ICD-10-CM M05.6 ICD-10-CM M05.60 ICD-10-CM M05.61 ICD-10-CM M05.611 ICD-10-CM M05.612 ICD-10-CM M05.619 ICD-10-CM M05.62 ICD-10-CM M05.621 ICD-10-CM M05.622 ICD-10-CM M05.629 ICD-10-CM M05.63 ICD-10-CM M05.631 ICD-10-CM M05.632 ICD-10-CM M05.639 ICD-10-CM M05.64 ICD-10-CM M05.641 ICD-10-CM M05.642 ICD-10-CM M05.649 ICD-10-CM M05.65 ICD-10-CM M05.651 ICD-10-CM M05.652 ICD-10-CM M05.659 ICD-10-CM M05.66 ICD-10-CM M05.661 ICD-10-CM M05.662 ICD-10-CM M05.669 ICD-10-CM M05.67 ICD-10-CM M05.671 ICD-10-CM M05.672 ICD-10-CM M05.679 ICD-10-CM M05.69 ICD-10-CM M05.7 ICD-10-CM M05.70 ICD-10-CM M05.71 ICD-10-CM M05.711 ICD-10-CM M05.712 ICD-10-CM M05.719 ICD-10-CM M05.72 ICD-10-CM M05.721 ICD-10-CM M05.722 ICD-10-CM M05.729 ICD-10-CM M05.73 ICD-10-CM M05.731 ICD-10-CM M05.732 ICD-10-CM M05.739 ICD-10-CM M05.74 ICD-10-CM M05.741 ICD-10-CM M05.742 ICD-10-CM M05.749 ICD-10-CM M05.75 ICD-10-CM M05.751 ICD-10-CM M05.752 ICD-10-CM M05.759 ICD-10-CM M05.76 ICD-10-CM M05.761 ICD-10-CM M05.762 ICD-10-CM M05.769 ICD-10-CM M05.77 ICD-10-CM M05.771 ICD-10-CM M05.772 ICD-10-CM M05.779 ICD-10-CM M05.79 ICD-10-CM M05.8 ICD-10-CM M05.80 ICD-10-CM M05.81 ICD-10-CM M05.811 ICD-10-CM M05.812 ICD-10-CM M05.819 ICD-10-CM M05.82 ICD-10-CM M05.821 ICD-10-CM M05.822 ICD-10-CM M05.829 ICD-10-CM M05.83 ICD-10-CM M05.831 ICD-10-CM M05.832 ICD-10-CM M05.839 ICD-10-CM M05.84 ICD-10-CM M05.841 ICD-10-CM M05.842 ICD-10-CM M05.849 ICD-10-CM M05.85 ICD-10-CM M05.851 ICD-10-CM M05.852 ICD-10-CM M05.859 ICD-10-CM M05.86 ICD-10-CM M05.861 ICD-10-CM M05.862 ICD-10-CM M05.869 ICD-10-CM M05.87 ICD-10-CM M05.871 ICD-10-CM M05.872 ICD-10-CM M05.879 ICD-10-CM M05.89 ICD-10-CM M05.9 ICD-10-CM M06 ICD-10-CM M06.0 ICD-10-CM M06.00 ICD-10-CM M06.01 ICD-10-CM M06.011 ICD-10-CM M06.012 ICD-10-CM M06.019 ICD-10-CM M06.02 ICD-10-CM M06.021 ICD-10-CM M06.022 ICD-10-CM M06.029 ICD-10-CM M06.03 ICD-10-CM M06.031 ICD-10-CM M06.032 ICD-10-CM M06.039 ICD-10-CM M06.04 ICD-10-CM M06.041 ICD-10-CM M06.042 ICD-10-CM M06.049 ICD-10-CM M06.05 ICD-10-CM M06.051 ICD-10-CM M06.052 ICD-10-CM M06.059 ICD-10-CM M06.06 ICD-10-CM M06.061 ICD-10-CM M06.062 ICD-10-CM M06.069 ICD-10-CM M06.07 ICD-10-CM M06.071 ICD-10-CM M06.072 ICD-10-CM M06.079 ICD-10-CM M06.08 ICD-10-CM M06.09 ICD-10-CM M06.8 ICD-10-CM M06.80 ICD-10-CM M06.81 ICD-10-CM M06.811 ICD-10-CM M06.812 ICD-10-CM M06.819 ICD-10-CM M06.82 ICD-10-CM M06.821 ICD-10-CM M06.822 ICD-10-CM M06.829 ICD-10-CM M06.83 ICD-10-CM M06.831 ICD-10-CM M06.832 ICD-10-CM M06.839 ICD-10-CM M06.84 ICD-10-CM M06.841 ICD-10-CM M06.842 ICD-10-CM M06.849 ICD-10-CM M06.85 ICD-10-CM M06.851 ICD-10-CM M06.852 ICD-10-CM M06.859 ICD-10-CM M06.86 ICD-10-CM M06.861 ICD-10-CM M06.862 ICD-10-CM M06.869 ICD-10-CM M06.87 ICD-10-CM M06.871 ICD-10-CM M06.872 ICD-10-CM M06.879 ICD-10-CM M06.88 ICD-10-CM M06.89 ICD-10-CM M06.9 ICD-10-CM M08.0 ICD-10-CM M08.00 ICD-10-CM M08.01 ICD-10-CM M08.011 ICD-10-CM M08.012 ICD-10-CM M08.019 ICD-10-CM M08.02 ICD-10-CM M08.021 ICD-10-CM M08.022 ICD-10-CM M08.029 ICD-10-CM M08.03 ICD-10-CM M08.031 ICD-10-CM M08.032 ICD-10-CM M08.039 ICD-10-CM M08.04 ICD-10-CM M08.041 ICD-10-CM M08.042 ICD-10-CM M08.049 ICD-10-CM M08.05 ICD-10-CM M08.051 ICD-10-CM M08.052 ICD-10-CM M08.059 ICD-10-CM M08.06 ICD-10-CM M08.061 ICD-10-CM M08.062 ICD-10-CM M08.069 ICD-10-CM M08.07 ICD-10-CM M08.071 ICD-10-CM M08.072 ICD-10-CM M08.079 ICD-10-CM M08.08 ICD-10-CM M08.09 MeSH D001172 OMIM 180300 SNOMED CT 69896004 2025-09 2025-12-22 Rhizomelic chondrodysplasia punctata https://medlineplus.gov/genetics/condition/rhizomelic-chondrodysplasia-punctata descriptionRhizomelic chondrodysplasia punctata is a condition that impairs the normal development of many parts of the body. The major features of this disorder include skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory problems.Rhizomelic chondrodysplasia punctata is characterized by shortening of the bones in the upper arms and thighs (rhizomelia). Affected individuals also have a specific bone abnormality called chondrodysplasia punctata, which affects the growth of the long bones and can be seen on x-rays. People with rhizomelic chondrodysplasia punctata often develop joint deformities (contractures) that make the joints stiff and painful.Distinctive facial features are also seen with rhizomelic chondrodysplasia punctata. These include a prominent forehead, widely set eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), a small nose with upturned nostrils, and full cheeks. Additionally, almost all affected individuals have clouding of the lenses of the eyes (cataracts). The cataracts are apparent at birth (congenital) or develop in early infancy.Rhizomelic chondrodysplasia punctata is associated with significantly delayed development and severe intellectual disability. Most children with this condition do not achieve developmental milestones such as sitting without support, feeding themselves, or speaking in phrases. Affected infants grow much more slowly than other children their age, and many also have seizures. Recurrent respiratory infections and life-threatening breathing problems are common. Because of their severe health problems, most people with rhizomelic chondrodysplasia punctata survive only into childhood. It is rare for affected children to live past age 10. However, a few individuals with milder features of the condition have lived into early adulthood.Researchers have described three types of rhizomelic chondrodysplasia punctata: type 1 (RCDP1), type 2 (RCDP2), and type 3 (RCDP3). The types have similar features and are distinguished by their genetic cause. ar Autosomal recessive PEX7 https://medlineplus.gov/genetics/gene/pex7 AGPS https://medlineplus.gov/genetics/gene/agps GNPAT https://medlineplus.gov/genetics/gene/gnpat Chondrodysplasia punctata, rhizomelic RCDP RCP GTR C1838612 GTR C1857242 GTR C1859133 ICD-10-CM E71.540 MeSH D018902 OMIM 215100 OMIM 222765 OMIM 600121 SNOMED CT 56692003 2010-07 2025-04-03 Riboflavin transporter deficiency neuronopathy https://medlineplus.gov/genetics/condition/riboflavin-transporter-deficiency-neuronopathy descriptionRiboflavin transporter deficiency neuronopathy is a disorder that affects nerve cells (neurons). Affected individuals typically have hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and signs of damage to other nerves.In addition to nerves in the inner ear, riboflavin transporter deficiency neuronopathy involves nerves found in the part of the brain that is connected to the spinal cord (the brainstem), specifically in a region of the brainstem known as the pontobulbar region. Damage to these nerves causes paralysis of the muscles controlled by them, a condition called pontobulbar palsy. Nerves in the pontobulbar region help control several voluntary muscle activities, including breathing, speaking, and moving the limbs. As a result of pontobulbar palsy, people with riboflavin transporter deficiency neuronopathy can have breathing problems; slurred speech; and muscle weakness in the face, neck, shoulders, and limbs. Affected individuals can also have muscle stiffness (spasticity) and exaggerated reflexes.The age at which riboflavin transporter deficiency neuronopathy begins varies from infancy to young adulthood. When the condition begins in infancy, the first symptom is often breathing problems caused by nerve damage, which can be life-threatening. When the condition begins in children or young adults, sensorineural hearing loss usually occurs first, followed by signs of pontobulbar palsy.If not treated, the signs and symptoms of riboflavin transporter deficiency neuronopathy worsen over time. Severe breathing problems and respiratory infections are the usual cause of death in people with this condition. Without treatment, affected infants typically survive less than one year. However, those who develop the condition after age 4 often survive more than 10 years.Riboflavin transporter deficiency neuronopathy encompasses two conditions that were once considered distinct disorders: Brown-Vialetto-Van Laere syndrome (BVVLS) and Fazio-Londe disease. The two conditions have similar signs and symptoms, but Fazio-Londe disease does not include sensorineural hearing loss. Because these two conditions share a genetic cause and have overlapping features, researchers determined that they are forms of a single disorder. ar Autosomal recessive SLC52A3 https://medlineplus.gov/genetics/gene/slc52a3 SLC52A2 https://medlineplus.gov/genetics/gene/slc52a2 Brown-Vialetto-Van Laere syndrome BVVLS Fazio-Londe disease Fazio-Londe syndrome Pontobulbar palsy with deafness Progressive bulbar palsy with sensorineural deafness Riboflavin transporter deficiency GTR C0796274 MeSH D010244 OMIM 211530 SNOMED CT 699866005 2016-01 2020-08-18 Rigid spine muscular dystrophy https://medlineplus.gov/genetics/condition/rigid-spine-muscular-dystrophy descriptionRigid spine muscular dystrophy (RSMD) is a form of congenital muscular dystrophy. Disorders in this group cause muscle weakness and wasting (atrophy) beginning very early in life. In particular, RSMD involves weakness of the muscles of the torso and neck (axial muscles). Other characteristic features include spine stiffness and serious breathing problems.In RSMD, muscle weakness is often apparent at birth or within the first few months of life. Affected infants can have poor head control and weak muscle tone (hypotonia), which may delay the development of motor skills such as crawling or walking. Over time, muscles surrounding the spine atrophy, and the joints of the spine develop deformities called contractures that restrict movement. The neck and back become stiff and rigid, and affected children have limited ability to move their heads up and down or side to side. Affected children eventually develop an abnormal curvature of the spine (scoliosis). In some people with RSMD, muscles in the inner thighs also atrophy, although it does not impair the ability to walk.A characteristic feature of RSMD is breathing difficulty (respiratory insufficiency) due to restricted movement of the torso and weakness of the diaphragm, which is the muscle that separates the abdomen from the chest cavity. The breathing problems, which tend to occur only at night, can be life-threatening. Many affected individuals require a machine to help them breathe (mechanical ventilation) during sleep.The combination of features characteristic of RSMD, particularly axial muscle weakness, spine rigidity, and respiratory insufficiency, is sometimes referred to as rigid spine syndrome. While these features occur on their own in RSMD, they can also occur along with additional signs and symptoms in other muscle disorders. The features of rigid spine syndrome typically appear at a younger age in people with RSMD than in those with other muscle disorders. ar Autosomal recessive SELENON https://medlineplus.gov/genetics/gene/selenon Congenital muscular dystrophy with spine rigidity syndrome Muscular dystrophy, congenital, merosin-positive, with early spine rigidity Rigid spinal muscular dystrophy Rigid spine congenital muscular dystrophy RSMD GTR C0410180 MeSH D009136 OMIM 602771 2019-03 2024-05-22 Ring chromosome 14 syndrome https://medlineplus.gov/genetics/condition/ring-chromosome-14-syndrome descriptionRing chromosome 14 syndrome is a condition characterized by seizures and intellectual disability. Recurrent seizures (epilepsy) develop in infancy or early childhood. In many cases, the seizures are resistant to treatment with anti-epileptic drugs. Most people with ring chromosome 14 syndrome also have some degree of intellectual disability or learning problems. Development may be delayed, particularly the development of speech and of motor skills such as sitting, standing, and walking.Additional features of ring chromosome 14 syndrome can include slow growth and short stature, a small head (microcephaly), puffy hands and/or feet caused by a buildup of fluid (lymphedema), and subtle differences in facial features. Some affected individuals have problems with their immune system that lead to recurrent infections, especially involving the respiratory system. Abnormalities of the retina, the specialized tissue at the back of the eye that detects light and color, have also been reported in some people with this condition. These changes typically do not affect vision. Major birth defects are rarely seen with ring chromosome 14 syndrome. n Not inherited 14 https://medlineplus.gov/genetics/chromosome/14 Ring 14 Ring 14 syndrome Ring chromosome 14 GTR C2930916 MeSH D012303 OMIM 616606 SNOMED CT 702345009 2009-05 2020-09-08 Ring chromosome 20 syndrome https://medlineplus.gov/genetics/condition/ring-chromosome-20-syndrome descriptionRing chromosome 20 syndrome is a condition that affects the normal development and function of the brain. The most common feature of this condition is recurrent seizures (epilepsy) in childhood. The seizures may occur during the day or at night during sleep. They are described as partial seizures because they affect only one area of the brain, a region called the frontal lobe. In many cases, the seizures are complex and resistant to treatment with anti-epileptic drugs. Prolonged seizure episodes known as non-convulsive status epilepticus also appear to be characteristic of ring chromosome 20 syndrome. These episodes involve confusion and behavioral changes.Most people with ring chromosome 20 syndrome also have  intellectual disabilities and behavioral difficulties. Although these problems can appear either before or after the onset of epilepsy, they tend to worsen after seizures develop. Major birth defects and differences in facial features can occur in people with ring chromosome 20 syndrome, though these are rare. n Not inherited 20 https://medlineplus.gov/genetics/chromosome/20 R(20) syndrome Ring 20 syndrome Ring chromosome 20 Ring chromosome 20 epilepsy syndrome GTR C0265482 MeSH D012303 SNOMED CT 23686004 2024-01 2024-01-19 Rippling muscle disease https://medlineplus.gov/genetics/condition/rippling-muscle-disease descriptionRippling muscle disease is a condition in which the muscles are unusually sensitive to movement or pressure (irritable). The muscles near the center of the body (proximal muscles) are most affected, especially the thighs. In most people with this condition, stretching the muscle causes visible ripples to spread across the muscle, lasting 5 to 20 seconds. A bump or other sudden impact on the muscle causes it to bunch up (percussion-induced muscle mounding) or exhibit repetitive tensing (percussion-induced rapid contraction). The rapid contractions can continue for up to 30 seconds and may be painful.People with rippling muscle disease may have overgrowth (hypertrophy) of some muscles, especially in the calf. Some affected individuals have an abnormal pattern of walking (gait), such as walking on tiptoe. They may experience fatigue, cramps, or muscle stiffness, especially after exercise or in cold temperatures.The age of onset of rippling muscle disease varies widely, but it often begins in late childhood or adolescence. Rippling muscles may also occur as a feature of other muscle disorders such as limb-girdle muscular dystrophy. ad Autosomal dominant ar Autosomal recessive CAV3 https://medlineplus.gov/genetics/gene/cav3 Rippling muscle syndrome RMD GTR C1832560 MeSH D020967 OMIM 600332 OMIM 606072 SNOMED CT 709281006 2014-05 2023-03-01 Roberts syndrome https://medlineplus.gov/genetics/condition/roberts-syndrome descriptionRoberts syndrome is a genetic disorder characterized by limb and facial abnormalities. Affected individuals also grow slowly before and after birth. Mild to severe intellectual impairment occurs in about half of all people with Roberts syndrome.Children with Roberts syndrome are born with abnormalities of all four limbs. They have shortened arm and leg bones (hypomelia), particularly the bones in their forearms and lower legs. In severe cases, the limbs may be so short that the hands and feet are located very close to the body (phocomelia). People with Roberts syndrome may also have abnormal or missing fingers and toes, and joint deformities (contractures) commonly occur at the elbows and knees. The limb abnormalities are very similar on the right and left sides of the body, but arms are usually more severely affected than legs.Individuals with Roberts syndrome typically have numerous facial abnormalities, including an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (cleft palate), a small chin (micrognathia), ear abnormalities, wide-set eyes (hypertelorism), outer corners of the eyes that point downward (down-slanting palpebral fissures), small nostrils, and a beaked nose. They may have a small head size (microcephaly) or clouding of the clear front covering of the eyes (corneal opacities). In severe cases affected individuals have a sac-like protrusion of the brain (encephalocele) at the front of their head. In addition, people with Roberts syndrome may have heart, kidney, and genital abnormalities.Infants with a severe form of Roberts syndrome are often stillborn or die shortly after birth. Mildly affected individuals may live into adulthood. A condition called SC phocomelia syndrome was originally thought to be distinct from Roberts syndrome; however, it is now considered to be a mild variant. "SC" represents the first letters of the surnames of the two families first diagnosed with this disorder. ar Autosomal recessive ESCO2 https://medlineplus.gov/genetics/gene/esco2 Appelt-Gerken-Lenz syndrome Hypomelia hypotrichosis facial hemangioma syndrome Pseudothalidomide syndrome RBS Roberts-SC phocomelia syndrome SC phocomelia syndrome SC pseudothalidomide syndrome SC syndrome Tetraphocomelia-cleft palate syndrome GTR C0392475 MeSH D000015 OMIM 268300 SNOMED CT 48718006 2009-01 2020-08-18 Robinow syndrome https://medlineplus.gov/genetics/condition/robinow-syndrome descriptionRobinow syndrome is a rare disorder that affects the development of many parts of the body, particularly the skeleton. The types of Robinow syndrome can be distinguished by the severity of their signs and symptoms and by their pattern of inheritance: autosomal recessive or autosomal dominant.Autosomal recessive Robinow syndrome is characterized by skeletal abnormalities including shortening of the long bones in the arms and legs, particularly the forearms; abnormally short fingers and toes (brachydactyly); wedge-shaped spinal bones (hemivertebrae) leading to an abnormal curvature of the spine (kyphoscoliosis); fused or missing ribs; and short stature. Affected individuals also have distinctive facial features, such as a broad forehead, prominent and widely spaced eyes, a short nose with an upturned tip, a wide nasal bridge, and a broad and triangle-shaped mouth. Together, these facial features are sometimes described as "fetal facies" because they resemble the facial structure of a developing fetus. Other common features of autosomal recessive Robinow syndrome include underdeveloped genitalia in both males and females, and dental problems such as crowded teeth and overgrowth of the gums. Kidney and heart defects are also possible. Development is delayed in 10 to 15 percent of people with this condition, although intelligence is usually normal.Autosomal dominant Robinow syndrome has signs and symptoms that are similar to, but tend to be milder than, those of the autosomal recessive form. Abnormalities of the spine and ribs are rarely seen in the autosomal dominant form, and short stature is less pronounced. A variant form of autosomal dominant Robinow syndrome includes increased bone mineral density (osteosclerosis) affecting the bones of the skull in addition to the signs and symptoms listed above. This variant is called the osteosclerotic form of Robinow syndrome. ar Autosomal recessive ad Autosomal dominant ROR2 https://medlineplus.gov/genetics/gene/ror2 WNT5A https://medlineplus.gov/genetics/gene/wnt5a DVL1 https://medlineplus.gov/genetics/gene/dvl1 DVL3 https://medlineplus.gov/genetics/gene/dvl3 FZD2 https://medlineplus.gov/genetics/gene/fzd2 GPC4 https://www.ncbi.nlm.nih.gov/gene/2239 RAC3 https://www.ncbi.nlm.nih.gov/gene/5881 NXN https://www.ncbi.nlm.nih.gov/gene/64359 Acral dysostosis with facial and genital abnormalities Fetal face syndrome Mesomelic dwarfism-small genitalia syndrome Robinow dwarfism Robinow's syndrome Robinow-Silverman syndrome Robinow-Silverman-Smith syndrome GTR C4551475 GTR C5193143 GTR C5399974 MeSH D000015 OMIM 180700 OMIM 268310 OMIM 616331 OMIM 616894 SNOMED CT 76520005 2018-02 2023-08-21 Romano-Ward syndrome https://medlineplus.gov/genetics/condition/romano-ward-syndrome descriptionRomano-Ward syndrome is a condition that causes a disruption of the heart's normal rhythm (arrhythmia). This disorder is a form of long QT syndrome, which is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. The term "long QT" refers to a specific pattern of heart activity that is detected with an electrocardiogram (ECG or EKG), which is a test used to measure the electrical activity of the heart. In people with long QT syndrome, the part of the heartbeat known as the QT interval is abnormally long. Abnormalities in the time it takes to recharge the heart lead to abnormal heart rhythms.The arrhythmia associated with Romano-Ward syndrome can lead to fainting (syncope) or cardiac arrest and sudden death. However, some people with Romano-Ward syndrome never experience any health problems associated with the condition.Fifteen types of long QT syndrome have been defined based on their genetic cause. Some types of long QT syndrome involve other cardiac abnormalities or problems with additional body systems. Romano-Ward syndrome encompasses those types that involve only a long QT interval without other abnormalities. ad Autosomal dominant KCNQ1 https://medlineplus.gov/genetics/gene/kcnq1 KCNH2 https://medlineplus.gov/genetics/gene/kcnh2 SCN5A https://medlineplus.gov/genetics/gene/scn5a CAV3 https://medlineplus.gov/genetics/gene/cav3 KCNJ5 https://medlineplus.gov/genetics/gene/kcnj5 CALM1 https://www.ncbi.nlm.nih.gov/gene/801 CALM2 https://www.ncbi.nlm.nih.gov/gene/805 SCN4B https://www.ncbi.nlm.nih.gov/gene/6330 SNTA1 https://www.ncbi.nlm.nih.gov/gene/6640 AKAP9 https://www.ncbi.nlm.nih.gov/gene/10142 RWS Ward-Romano syndrome WRS GTR C0023976 ICD-10-CM I45.81 MeSH D029597 OMIM 192500 OMIM 603830 OMIM 613688 SNOMED CT 20852007 2017-05 2024-09-19 Rosacea https://medlineplus.gov/genetics/condition/rosacea descriptionRosacea is a long-lasting (chronic) skin disease that affects the face, primarily the forehead, nose, cheeks, and chin. The signs and symptoms of rosacea vary, and they may come and go or change over time.There are three main types of rosacea, categorized by their primary signs and symptoms. Erythematotelangiectatic rosacea causes skin redness and warmth (flushing) and visible clusters of blood vessels (telangiectasia). Papulopustular rosacea causes skin redness, swelling, and pus-filled bumps called pustules. Phymatous rosacea is characterized by thickened skin on the face and an enlarged, bulbous nose (rhinophyma). People with rosacea may feel itching, stinging, or burning sensations in affected areas. Often, the disorder affects the eyes, causing abnormal inflammation of the eyelids and eyes (ocular rosacea). This inflammation can cause dryness, redness, and irritation of the eyes and may affect vision. u Pattern unknown HLA-DQB1 https://medlineplus.gov/genetics/gene/hla-dqb1 HLA-DQA1 https://medlineplus.gov/genetics/gene/hla-dqa1 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 GSTM1 https://www.ncbi.nlm.nih.gov/gene/2944 GSTT1 https://www.ncbi.nlm.nih.gov/gene/2952 Erythematotelangiectatic rosacea Granulomatous rosacea Ocular rosacea Papulopustular rosacea Phymatous rosacea ICD-10-CM L71 ICD-10-CM L71.8 ICD-10-CM L71.9 MeSH D012393 SNOMED CT 398909004 2018-09 2024-09-19 Rothmund-Thomson syndrome https://medlineplus.gov/genetics/condition/rothmund-thomson-syndrome descriptionRothmund-Thomson syndrome is a rare condition that affects many parts of the body, especially the skin. People with this condition typically develop redness on the cheeks between ages 3 months and 6 months. Over time the rash spreads to the arms and legs, causing patchy changes in skin coloring, areas of thinning skin (atrophy), and small clusters of blood vessels just under the skin (telangiectases). These skin problems persist for life and are collectively known as poikiloderma.Rothmund-Thomson syndrome is also characterized by sparse hair, eyebrows, and eyelashes; slow growth and small stature; abnormalities of the teeth and nails; and gastrointestinal problems in infancy, such as chronic diarrhea and vomiting. Some affected children develop a clouding of the lens of the eye (cataract), which affects vision. Many people with this disorder have skeletal abnormalities including absent or malformed bones, fused bones, and low bone mineral density (osteopenia or osteoporosis). Some of these abnormalities affect the development of bones in the forearms and the thumbs, and are known as radial ray malformations.People with Rothmund-Thomson syndrome have an increased risk of developing cancer, particularly a form of bone cancer called osteosarcoma. These bone tumors most often develop during childhood or adolescence. Several types of skin cancer, including basal cell carcinoma and squamous cell carcinoma, are also more common in people with this disorder.The varied signs and symptoms of Rothmund-Thomson syndrome overlap with features of other disorders, namely Baller-Gerold syndrome and RAPADILINO syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Rothmund-Thomson syndrome, Baller-Gerold syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms. ar Autosomal recessive RECQL4 https://medlineplus.gov/genetics/gene/recql4 Congenital poikiloderma Poikiloderma atrophicans and cataract Poikiloderma congenitale Poikiloderma congenitale of Rothmund-Thomson RTS GTR C0032339 MeSH D011038 OMIM 268400 SNOMED CT 69093006 2013-08 2023-03-01 Rotor syndrome https://medlineplus.gov/genetics/condition/rotor-syndrome descriptionRotor syndrome is a relatively mild condition characterized by elevated levels of a substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. It has an orange-yellow tint, and buildup of this substance can cause yellowing of the skin or whites of the eyes (jaundice). In people with Rotor syndrome, jaundice is usually evident shortly after birth or in childhood and may come and go; yellowing of the whites of the eyes (also called conjunctival icterus) is often the only symptom.There are two forms of bilirubin in the body: a toxic form called unconjugated bilirubin and a nontoxic form called conjugated bilirubin. People with Rotor syndrome have a buildup of both unconjugated and conjugated bilirubin in their blood, but the majority is conjugated. ar Autosomal recessive SLCO1B1 https://medlineplus.gov/genetics/gene/slco1b1 SLCO1B3 https://medlineplus.gov/genetics/gene/slco1b3 Hyperbilirubinemia, Rotor type GTR C0220991 MeSH D006933 OMIM 237450 SNOMED CT 32891000 2013-02 2020-08-18 Rubinstein-Taybi syndrome https://medlineplus.gov/genetics/condition/rubinstein-taybi-syndrome descriptionRubinstein-Taybi syndrome is a condition characterized by short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes. Additional features of the disorder can include eye abnormalities, heart and kidney defects, dental problems, and obesity. These signs and symptoms vary among affected individuals. People with this condition have an increased risk of developing particular types of noncancerous brain and skin tumors. ad Autosomal dominant CREBBP https://medlineplus.gov/genetics/gene/crebbp EP300 https://medlineplus.gov/genetics/gene/ep300 16 https://medlineplus.gov/genetics/chromosome/16 Broad thumb-hallux syndrome RSTS RTS GTR C3150941 GTR C4551859 MeSH D012415 OMIM 180849 OMIM 613684 SNOMED CT 45582004 2020-01 2020-09-08 SADDAN https://medlineplus.gov/genetics/condition/saddan descriptionSADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities.All people with this condition have extremely short stature with particularly short arms and legs. Other features include unusual bowing of the leg bones; a small chest with short ribs and curved collar bones; short, broad fingers; and folds of extra skin on the arms and legs. Structural abnormalities of the brain cause seizures, profound developmental delay, and intellectual disability. Several affected individuals also have had episodes in which their breathing slows or stops for short periods (apnea). Acanthosis nigricans, a progressive skin disorder characterized by thick, dark, velvety skin, is another characteristic feature of SADDAN that develops in infancy or early childhood. ad Autosomal dominant FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 Achondroplasia, severe, with developmental delay and acanthosis nigricans SADDAN dysplasia Severe achondroplasia with developmental delay and acanthosis nigricans Skeleton-skin-brain syndrome SSB syndrome GTR C2674173 MeSH D000130 OMIM 616482 SNOMED CT 699870002 2006-06 2020-08-18 SATB2-associated syndrome https://medlineplus.gov/genetics/condition/satb2-associated-syndrome descriptionSATB2-associated syndrome is a condition that affects several body systems. It is characterized by intellectual disability, severe speech problems, dental abnormalities, abnormalities of the head and face (craniofacial anomalies), and behavioral problems. Some of the common features can be described using the acronym SATB2 (which is the name of the gene involved in the condition): severe speech anomalies, abnormalities of the palate, teeth anomalies, behavioral issues with or without bone or brain anomalies, and onset before age 2.Individuals with SATB2-associated syndrome typically have mild to severe intellectual disability, and their ability to speak is delayed or absent. Development of motor skills, such as rolling over, sitting, and walking, can also be delayed. Many affected individuals have behavioral problems, including hyperactivity and aggression. Some exhibit autistic behaviors, such as repetitive movements. A happy or overly friendly personality is also common among individuals with SATB2-associated syndrome. Less common neurological problems include feeding difficulties and weak muscle tone (hypotonia) in infancy. About half of affected individuals have abnormalities in the structure of the brain.The most common craniofacial anomalies in people with SATB2-associated syndrome are a high arch or an opening in the roof of the mouth (high-arched or cleft palate), a small lower jaw (micrognathia), and dental abnormalities, which can include abnormally sized or shaped teeth, extra (supernumerary) teeth, or missing teeth (oligodontia). Some people with SATB2-associated syndrome have other unusual facial features, such as a prominent forehead, low-set ears, or a large area between the nose and mouth (a long philtrum). People with this disorder may also have a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture.Less-commonly affected are the heart, genitals and urinary tract (genitourinary tract), skin, and hair. n Not inherited SATB2 https://medlineplus.gov/genetics/gene/satb2 2 https://medlineplus.gov/genetics/chromosome/2 2q32 deletion syndrome 2q33.1 microdeletion syndrome Chromosome 2q32-q33 deletion syndrome Glass syndrome SAS GTR C2676739 MeSH D008607 OMIM 612313 2017-02 2023-11-08 SCN8A-related epilepsy with encephalopathy https://medlineplus.gov/genetics/condition/scn8a-related-epilepsy-with-encephalopathy descriptionSCN8A-related epilepsy with encephalopathy is a condition characterized by recurrent seizures (epilepsy), abnormal brain function (encephalopathy), and intellectual disability. The signs and symptoms of this condition typically begin in infancy.The seizures in SCN8A-related epilepsy with encephalopathy include involuntary muscle contractions that occur before age 1 (infantile spasms), partial or complete loss of consciousness (absence seizures), involuntary muscle twitches (myoclonic seizures), or loss of consciousness with muscle rigidity and convulsions (tonic-clonic seizures). Most people with SCN8A-related epilepsy with encephalopathy have more than one type of seizure. The frequency of seizures in different individuals with this condition ranges from hundreds per day to fewer than one per month. In many individuals, the seizures are described as refractory because they do not respond to therapy with anti-epileptic medications.Other signs and symptoms of SCN8A-related epilepsy with encephalopathy include intellectual disability that may be mild to severe. Some affected infants have normal early development but begin to lose previously acquired skills (developmental regression) and have a gradual loss in thinking ability (cognitive decline) when epilepsy develops. Problems with movement are common, and about half of affected infants cannot perform intentional movements. Behavior disorders may also occur.In rare cases, individuals with this condition die unexpectedly for no known reason (sudden unexpected death in epilepsy or SUDEP). ad Autosomal dominant SCN8A https://medlineplus.gov/genetics/gene/scn8a Early infantile epileptic encephalopathy 13 EIEE13 SCN8A encephalopathy GTR C3281191 MeSH D001925 MeSH D004831 OMIM 614558 SNOMED CT 431071000124107 2017-07 2020-08-18 SETBP1 haploinsufficiency disorder https://medlineplus.gov/genetics/condition/setbp1-haploinsufficiency-disorder descriptionSETBP1 haploinsufficiency disorder is a condition that involves speech and language problems, intellectual disability, and distinctive facial features.In people with SETBP1 haploinsufficiency disorder, problems with vocabulary and the production of speech (expressive language skills) are generally more severely affected than the ability to understand speech (receptive language skills). About 80 percent of affected children have a condition called childhood apraxia of speech, in which they have difficulty with the mouth movements needed to speak. Speech development may be limited to a few words or no speech. Affected individuals often communicate using gestures or by mimicking the expressions of others.Individuals with SETBP1 haploinsufficiency disorder have intellectual disability that can range from mild to moderate. They may also have neurodevelopment problems, such as attention-deficit/hyperactivity disorder (ADHD) or autistic behaviors that affect communication and social interaction. Affected individuals may have weak muscle tone (hypotonia); delayed development of motor skills, such as sitting, standing, and walking; or recurrent seizures (epilepsy).Distinctive facial features in people with SETBP1 haploinsufficiency disorder can include a long face, a high forehead, eyebrows that grow together in the middle (synophrys), short eye openings (short palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), droopy eyelids (ptosis), puffiness of the skin around the eyes (periorbital fullness), small nostrils, a high nasal bridge, a broad tip of the nose, a thin upper lip, a high arch in the roof of the mouth (high-arched palate), and a small chin. ad Autosomal dominant SETBP1 https://medlineplus.gov/genetics/gene/setbp1 Mental retardation, autosomal dominant 29 MRD29 SETBP1 disorder SETBP1 LoF syndrome SETBP1 loss of function syndrome SETBP1 related developmental delay SETBP1-related disorder SETBP1-related intellectual disability GTR C4015141 ICD-10-CM MeSH D007805 MeSH D008607 OMIM 616078 SNOMED CT 2019-08 2023-08-07 SLC35A2-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/slc35a2-congenital-disorder-of-glycosylation descriptionSLC35A2-congenital disorder of glycosylation (SLC35A2-CDG, formerly known as congenital disorder of glycosylation type IIm) is an inherited condition that causes neurological problems and other abnormalities. This disorder's signs and symptoms and their severity vary among affected individuals.Individuals with SLC35A2-CDG typically develop signs and symptoms of the condition early in infancy. Seizures develop within the first months of life, usually involving uncontrollable muscle stiffening (infantile spasms) that can switch to shorter episodes of muscle jerks (epileptic spasms) later in childhood. In some individuals, the seizures do not improve with anti-epileptic medications. Individuals with SLC35A2-CDG often have abnormal brain function (encephalopathy), unusual facial features, skeletal abnormalities, and weak muscle tone (hypotonia) with poor head control. They also have severe intellectual disability and delayed development, often only being able to sit or crawl and never developing meaningful speech. Affected children may have feeding difficulties and fail to grow or gain weight at the expected rate. Some have vision or hearing problems.In SLC35A2-CDG, medical imaging shows loss of tissue (atrophy) in parts of the brain called the cerebrum and cerebellum. These brain regions are necessary for thinking ability, hearing, vision, emotion, and coordinated movement. There can also be thinning of the tissue that connects the left and right halves of the brain (the corpus callosum) or a fluid-filled sac (cyst) on the membrane that surrounds the brain (arachnoid pouch). xd X-linked dominant SLC35A2 https://medlineplus.gov/genetics/gene/slc35a2 CDG IIm CDG syndrome type IIm CDG-IIm CDG2M CDGIIm Congenital disorder of glycosylation, type IIm EIEE22 Epileptic encephalopathy, early infantile, 22 SLC35A2-CDG GTR C3806688 MeSH D018981 OMIM 300896 2018-08 2021-11-26 SLC4A1-associated distal renal tubular acidosis https://medlineplus.gov/genetics/condition/slc4a1-associated-distal-renal-tubular-acidosis descriptionSLC4A1-associated distal renal tubular acidosis is a kidney (renal) disorder that sometimes includes blood cell abnormalities. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with distal renal tubular acidosis, the kidneys are unable to remove enough acid from the body, and the blood becomes too acidic. This chemical imbalance is called metabolic acidosis. The inability to remove acids from the body often results in slowed growth and may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. In addition, most children and adults with SLC4A1-associated distal renal tubular acidosis have excess calcium in the urine (hypercalciuria), calcium deposits in the kidneys (nephrocalcinosis), and kidney stones (nephrolithiasis). In rare cases, these kidney abnormalities lead to life-threatening kidney failure. Affected individuals may also have low levels of potassium in the blood (hypokalemia).Individuals with the features described above have complete distal renal tubular acidosis, which usually becomes apparent in childhood. Some people do not develop metabolic acidosis even though their kidneys have trouble removing acids; these individuals are said to have incomplete distal renal tubular acidosis. Additionally, these individuals may have other features of distal renal tubular acidosis, such as bone problems and kidney stones. Often, people who initially have incomplete distal renal tubular acidosis develop metabolic acidosis later in life.Some people with SLC4A1-associated distal renal tubular acidosis also have blood cell abnormalities. These can vary in severity from no symptoms to a condition called hemolytic anemia, in which red blood cells prematurely break down (undergo hemolysis), causing a shortage of red blood cells (anemia). Hemolytic anemia can lead to unusually pale skin (pallor), extreme tiredness (fatigue), shortness of breath (dyspnea), and an enlarged spleen (splenomegaly).There are two forms of SLC4A1-associated distal renal tubular acidosis; they are distinguished by their inheritance pattern. The autosomal dominant form is more common and is usually less severe than the autosomal recessive form. The autosomal dominant form can be associated with incomplete or complete distal renal tubular acidosis and is rarely associated with blood cell abnormalities. The autosomal recessive form is always associated with complete distal renal tubular acidosis and is more commonly associated with blood cell abnormalities, although not everyone with this form has abnormal blood cells. ar Autosomal recessive ad Autosomal dominant SLC4A1 https://medlineplus.gov/genetics/gene/slc4a1 Classic distal renal tubular acidosis Renal tubular acidosis type I RTA, classic type GTR CN280572 MeSH D000141 OMIM 179800 OMIM 611590 SNOMED CT 236461000 2014-08 2024-10-02 SOST-related sclerosing bone dysplasia https://medlineplus.gov/genetics/condition/sost-related-sclerosing-bone-dysplasia descriptionSOST-related sclerosing bone dysplasia is a disorder of bone development characterized by excessive bone formation (hyperostosis). As a result of hyperostosis, bones throughout the body are denser and wider than normal, particularly the bones of the skull. Affected individuals typically have an enlarged jaw with misaligned teeth. People with this condition may also have a sunken appearance of the middle of the face (midface hypoplasia), bulging eyes with shallow eye sockets (ocular proptosis), and a prominent forehead. People with this condition often experience headaches because increased thickness of the skull bones increases pressure on the brain. The excessive bone formation seen in this condition seems to occur throughout a person's life, so the skeletal features become more pronounced over time. However, the excessive bone growth may only occur in certain areas.Abnormal bone growth can pinch (compress) the cranial nerves, which emerge from the brain and extend to various areas of the head and neck. Compression of the cranial nerves can lead to paralyzed facial muscles (facial nerve palsy), hearing loss, vision loss, and a sense of smell that is diminished (hyposmia) or completely absent (anosmia). Abnormal bone growth can cause life-threatening complications if it compresses the part of the brain that is connected to the spinal cord (the brainstem).There are two forms of SOST-related sclerosing bone dysplasia: sclerosteosis and van Buchem disease. The two forms are distinguished by the severity of their symptoms.Sclerosteosis is the more severe form of the disorder. People with sclerosteosis are often tall and have webbed or fused fingers (syndactyly), most often involving the second and third fingers. The syndactyly is present from birth, while the skeletal features typically appear in early childhood. People with sclerosteosis may also have absent or malformed nails.Van Buchem disease represents the milder form of the disorder. People with van Buchem disease are typically of average height and do not have syndactyly or nail abnormalities. Affected individuals tend to have less severe cranial nerve compression, resulting in milder neurological features. In people with van Buchem disease, the skeletal features typically appear in childhood or adolescence. ar Autosomal recessive SOST https://medlineplus.gov/genetics/gene/sost Hyperostosis corticalis generalisata Hyperotosis corticalis generalisata familiaris Hyperphosphatasemia tarda Sclerosteosis SOST sclerosing bone dysplasia Van Buchem disease GTR C0432272 MeSH D015576 OMIM 239100 OMIM 269500 SNOMED CT 17568006 SNOMED CT 59763006 2009-06 2020-08-18 STAC3 disorder https://medlineplus.gov/genetics/condition/stac3-disorder descriptionSTAC3 disorder (formerly known as Native American myopathy) is a condition that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with STAC3 disorder have muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body that typically begins at birth.Muscle weakness underlies many of the characteristic features of STAC3 disorder. Affected individuals may have feeding and swallowing difficulties in infancy. They usually have delayed development of motor skills such as sitting, crawling, standing, and walking. Many have facial features described as "myopathic facies", which include drooping eyelids (ptosis), sunken cheeks, and a mouth often held in an open position and with the corners turned downward. Other distinctive facial features in people with STAC3 disorder can include a small lower jaw (micrognathia), an opening in the roof of the mouth (cleft palate), low-set ears that slant backward, eye openings that are shorter than average or that point downward (short or downslanting palpebral fissures), or an increased distance between the inner corners of the eyes (ocular telecanthus).Individuals with STAC3 disorder may also be born with joint deformities that restrict movement (contractures) or develop an abnormal side-to-side or back-to-front curvature of the spine (scoliosis or kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family.People with STAC3 disorder also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic drugs, which are used to block the sensation of pain, either given alone or in combination with a particular type of muscle relaxant. If given these drugs, people at risk of malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever (hyperthermia), increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless the drugs are stopped and the symptoms are treated promptly. ar Autosomal recessive STAC3 https://medlineplus.gov/genetics/gene/stac3 Myopathy, congenital, Bailey-Bloch Myopathy, congenital, with myopathic facies, scoliosis, and malignant hyperthermia NAM Native American myopathy GTR C1850625 MeSH D009135 OMIM 255995 SNOMED CT 723439002 2020-04 2023-03-01 STING-associated vasculopathy with onset in infancy https://medlineplus.gov/genetics/condition/sting-associated-vasculopathy-with-onset-in-infancy descriptionSTING-associated vasculopathy with onset in infancy (SAVI) is a disorder involving abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs. Inflammation normally occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and help with tissue repair. Excessive inflammation damages the body's own cells and tissues. Disorders such as SAVI that result from abnormally increased inflammation are known as autoinflammatory diseases.The signs and symptoms of SAVI begin in the first few months of life, and most are related to problems with blood vessels (vasculopathy) and damage to the tissues that rely on these vessels for their blood supply. Affected infants develop areas of severely damaged skin (lesions), particularly on the face, ears, nose, fingers, and toes. These lesions begin as rashes and can progress to become wounds (ulcers) and dead tissue (necrosis). The skin problems, which worsen in cold weather, can lead to complications such as scarred ears, a hole in the tissue that separates the two nostrils (nasal septum perforation), or fingers or toes that require amputation. Individuals with SAVI also have a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin. Affected individuals may also experience episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities.In addition to problems affecting the skin, people with SAVI have recurrent low-grade fevers and swollen lymph nodes. They may also develop widespread lung damage (interstitial lung disease) that can lead to the formation of scar tissue in the lungs (pulmonary fibrosis) and difficulty breathing; these respiratory complications can become life-threatening. Rarely, muscle inflammation (myositis) and joint stiffness also occur. ad Autosomal dominant STING1 https://medlineplus.gov/genetics/gene/sting1 SAVI STING-associated vasculopathy, infantile onset GTR C4014722 MeSH D056660 OMIM 615934 SNOMED CT 711164003 2014-10 2026-03-04 STXBP1 encephalopathy https://medlineplus.gov/genetics/condition/stxbp1-encephalopathy descriptionSTXBP1 encephalopathy is a condition characterized by abnormal brain function (encephalopathy) and intellectual disability. Most affected individuals also have recurrent seizures (epilepsy). The signs and symptoms of this condition typically begin in infancy but can start later in childhood or early adulthood. In many affected individuals who have epilepsy, the seizures stop after a few years, and the other neurological problems continue throughout life. However, some people with STXBP1 encephalopathy have seizures that persist.In people with STXBP1 encephalopathy, intellectual disability is often severe to profound. In addition, speech and motor skills, such as sitting, crawling, and walking, can be delayed. Though they may acquire the skill late, many children with the condition can walk independently by age 5. Affected individuals usually learn their first words later than their peers, sometimes not until late childhood. Some can communicate verbally using simple sentences, while others never develop the skill.  About 85 percent of people with STXBP1 encephalopathy develop epilepsy. The most common seizures in this condition are infantile spasms, which occur before age 1 and consist of involuntary muscle contractions. Other seizure types that can occur in people with this condition include uncontrolled muscle twitches (myoclonic seizures), sudden episodes of weak muscle tone (atonic seizures), partial or complete loss of consciousness (absence seizures), or loss of consciousness with muscle rigidity and convulsions (tonic-clonic seizures). Most people who have STXBP1 encephalopathy have more than one type of seizure. In about one-quarter of affected individuals, the seizures are described as refractory because they do not respond to therapy with anti-epileptic medications.Other neurological problems that occur in people with STXBP1 encephalopathy include features of autism spectrum disorder; weak muscle tone (hypotonia); and movement problems, such as difficulty coordinating movements (ataxia), involuntary trembling (tremors), and muscle stiffness (spasticity). In some cases, areas of brain tissue loss (atrophy) have been found on medical imaging. ad Autosomal dominant STXBP1 https://medlineplus.gov/genetics/gene/stxbp1 DEE4 Developmental and epileptic encephalopathy 4 Developmental and epileptic encephalopathy, type 4 Early-infantile epileptic encephalopathy 4 EIEE4 STXBP1 encephalopathy with epilepsy STXBP1 epileptic encephalopathy STXBP1-related developmental and epileptic encephalopathy STXBP1-related early-onset encephalopathy STXBP1-related epileptic encephalopathy GTR C2677326 MeSH D001925 MeSH D004831 OMIM 612164 SNOMED CT 230429005 2017-07 2023-03-01 SUCLA2-related mitochondrial DNA depletion syndrome https://medlineplus.gov/genetics/condition/sucla2-related-mitochondrial-dna-depletion-syndrome descriptionSUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is an inherited disorder that affects the early development of the brain. Affected infants typically develop weak muscle tone (hypotonia) in the first few months of life. In these infants, hypotonia can delay the development of motor skills such as lifting the head and rolling over. Children with SUCLA2-related mtDNA depletion syndrome typically have difficulty eating and may require a feeding tube; as a result, they have difficulty growing and gaining weight as expected (failure to thrive). Additional features of SUCLA2-related mtDNA depletion syndrome can include uncontrolled movements (dystonia), hearing loss, muscle wasting (atrophy), and intellectual disabilities. In most affected children, a substance called methylmalonic acid builds up in the blood. People with SUCLA2-related mtDNA depletion syndrome typically have a shortened lifespan. Approximately 30 percent of individuals with SUCLA2-related mtDNA depletion syndrome do not survive past childhood. ar Autosomal recessive SUCLA2 https://medlineplus.gov/genetics/gene/sucla2 Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) Mitochondrial DNA depletion syndrome, encephalomyopathic form with or without methylmalonic aciduria, autosomal recessive, SUCLA2-related MTDPS5 Succinate-CoA ligase deficiency SUCLA2 deficiency SUCLA2-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria GTR C5980207 MeSH D028361 OMIM 612073 SNOMED CT 445275003 2024-07 2024-07-19 SUCLG1-related mitochondrial DNA depletion syndrome https://medlineplus.gov/genetics/condition/suclg1-related-mitochondrial-dna-depletion-syndrome descriptionSUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome is an inherited disorder that affects the early development of the brain. Signs and symptoms typically appear soon after birth. Most affected children develop severe brain dysfunction and muscle weakness (encephalomyopathy). Infants with SUCLG1-related mtDNA depletion syndrome often have weak muscle tone (hypotonia). They typically have difficulty eating and may require a feeding tube. Additional features may include liver abnormalities and thickening of the heart muscle (hypertrophic cardiomyopathy). In affected individuals, a substance called methylmalonic acid typically builds up in the blood and urine.  People with SUCLG1-related mtDNA depletion syndrome can have serious health complications, which result in a shortened lifespan. Individuals with SUCLG1-related mtDNA depletion syndrome typically do not survive past childhood. Some infants with SUCLG1-related mtDNA depletion syndrome develop a toxic buildup of acids in the body in the first few days of life. This form of the disorder is called fatal infantile lactic acidosis. Infants with fatal infantile lactic acidosis typically only survive for a few days after birth. ar Autosomal recessive SUCLG1 https://medlineplus.gov/genetics/gene/suclg1 Fatal infantile lactic acidosis with methylmalonic aciduria Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MTDPS9 Succinate-coenzyme A ligase deficiency SUCLG1 deficiency SUCLG1-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria SUCLG1-related succinyl-CoA ligase deficiency GTR C3151476 OMIM 245400 2024-07 2025-09-10 SYNGAP1-related intellectual disability https://medlineplus.gov/genetics/condition/syngap1-related-intellectual-disability descriptionSYNGAP1-related intellectual disability is a neurological disorder characterized by moderate to severe intellectual disability that is evident in early childhood. The earliest features are typically delayed development of speech and motor skills, such as sitting, standing, and walking. Many people with this condition have weak muscle tone (hypotonia), which contributes to the difficulty with motor skills. Some affected individuals lose skills they had already acquired (developmental regression). Other features of SYNGAP1-related intellectual disability include recurrent seizures (epilepsy), hyperactivity, and autism spectrum disorder, which is characterized by impaired communication and social interaction; almost everyone with SYNGAP1-related intellectual disability develops epilepsy, and about half have autism spectrum disorder. ad Autosomal dominant SYNGAP1 https://medlineplus.gov/genetics/gene/syngap1 Mental retardation, autosomal dominant 5 MRD5 GTR C2675473 MeSH D008607 OMIM 612621 2016-05 2023-03-01 Saethre-Chotzen syndrome https://medlineplus.gov/genetics/condition/saethre-chotzen-syndrome descriptionSaethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.Most people with Saethre-Chotzen syndrome have prematurely fused skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may be malformed as well. These changes can result in an abnormally shaped head, a high forehead, a low frontal hairline, droopy eyelids (ptosis), widely spaced eyes, and a broad nasal bridge. One side of the face may appear noticeably different from the other (facial asymmetry). Most people with Saethre-Chotzen syndrome also have small, rounded ears.The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. This condition can cause mild changes in the hands and feet, such as partial fusion of the skin between the second and third fingers on each hand and a broad or duplicated first (big) toe. Delayed development and learning difficulties have been reported, although most people with this condition are of normal intelligence. Less common signs and symptoms of Saethre-Chotzen syndrome include short stature, abnormalities of the bones of the spine (the vertebra), hearing loss, and heart defects.Robinow-Sorauf syndrome is a condition with features similar to those of Saethre-Chotzen syndrome, including craniosynostosis and broad or duplicated great toes. It was once considered a separate disorder, but was found to result from mutations in the same gene and is now thought to be a variant of Saethre-Chotzen syndrome. ad Autosomal dominant TWIST1 https://medlineplus.gov/genetics/gene/twist1 7 https://medlineplus.gov/genetics/chromosome/7 Acrocephalosyndactyly III Acrocephalosyndactyly, type III Acrocephaly, skull asymmetry, and mild syndactyly ACS III ACS3 Chotzen syndrome Dysostosis craniofacialis with hypertelorism SCS GTR C0175699 GTR C1867146 MeSH D000168 OMIM 101400 OMIM 180750 SNOMED CT 83015004 2020-04 2020-09-08 Sandhoff disease https://medlineplus.gov/genetics/condition/sandhoff-disease descriptionSandhoff disease is a rare inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord (central nervous system). This condition is classified into three major types based on the age at which signs and symptoms first appear: infantile, juvenile, and adult.The infantile form of Sandhoff disease is the most common and severe form and becomes apparent in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Sandhoff disease experience seizures, vision and hearing loss, and intellectual disability. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Some affected children also have distinctive facial features, enlarged organs (organomegaly), or bone abnormalities. Children with the infantile form of Sandhoff disease usually live only into early childhood.The juvenile and adult forms of Sandhoff disease are very rare. Signs and symptoms are usually milder than those seen with the infantile form, although they vary widely. The juvenile form can begin between ages 2 and 10.  Characteristic features include speech difficulties, loss of cognitive function (dementia), seizures, and  loss of muscle coordination (ataxia). Adult Sandhoff disease is characterized by problems with movement and psychiatric problems. ar Autosomal recessive HEXB https://medlineplus.gov/genetics/gene/hexb Beta-hexosaminidase-beta-subunit deficiency GM2 gangliosidosis, type 2 GM2 gangliosidosis, type II Hexosaminidase A and B deficiency disease Sandhoff-Jatzkewitz-Pilz disease Total hexosaminidase deficiency GTR C0036161 ICD-10-CM E75.01 MeSH D012497 OMIM 268800 SNOMED CT 23849003 2006-08 2023-11-08 Saul-Wilson syndrome https://medlineplus.gov/genetics/condition/saul-wilson-syndrome descriptionSaul-Wilson syndrome is characterized by short stature (dwarfism) and other skeletal abnormalities. The growth problems in Saul-Wilson syndrome are called primordial, which means they begin before birth; affected individuals show slow prenatal growth (intrauterine growth retardation). After birth, affected individuals continue to grow at a very slow rate, with the average adult height being 3 feet, 6 inches (107 centimeters).Individuals with Saul-Wilson syndrome have distinctive facial features that often include a prominent forehead, sparse scalp hair and eyebrows, prominent scalp veins, a narrow nasal bridge, a beaked nose, a wide area separating the nostrils (broad columella), a thin upper lip, and a small lower jaw (micrognathia). This combination of facial features can give affected individuals an appearance of premature aging, particularly in infancy, that is sometimes described as progeroid.Additional skeletal abnormalities in Saul-Wilson syndrome include abnormalities in the structure of the long bones, short fingers and toes, an inward- and downward-turning foot (clubfoot), an abnormality of the hip joint that causes a decreased angle between the head and shaft of the upper leg bones (coxa vara), or flattened bones of the spine (platyspondyly) and other spinal abnormalities. Some affected individuals have bones that are unusually fragile, resulting in bone fractures that occur with little or no trauma. Adults with Saul-Wilson syndrome may experience joint pain (osteoarthritis) due to breakdown (degeneration) of the joints.Children with Saul-Wilson syndrome often have hearing loss, clouding of the lenses of the eyes (cataracts), or a blue tint to the whites of the eyes (blue sclerae). They may also have retinitis pigmentosa, in which breakdown of the light-sensitive layer (retina) at the back of the eye can cause vision loss. Individuals with Saul-Wilson syndrome may have early delay of speech and motor development, but they usually have normal intelligence.In Saul-Wilson syndrome, levels of white blood cells can vary from normal to low (intermittent neutropenia). Neutropenia makes it more difficult for the body to fight off foreign invaders such as bacteria and viruses, and may contribute to recurrent respiratory infections that occur in childhood in some individuals with Saul-Wilson syndrome. ad Autosomal dominant COG4 https://medlineplus.gov/genetics/gene/cog4 Microcephalic osteodysplastic dysplasia Microcephalic osteodysplastic dysplasia Saul Wilson type GTR C4509877 MeSH D004392 OMIM 618150 SNOMED CT 723404002 2020-04 2020-08-18 Scalp-ear-nipple syndrome https://medlineplus.gov/genetics/condition/scalp-ear-nipple-syndrome descriptionScalp-ear-nipple syndrome, as its name suggests, is a condition characterized by abnormalities of the scalp, ears, and nipples. Less frequently, affected individuals have problems affecting other parts of the body. The features of this disorder can vary even within the same family.Babies with scalp-ear-nipple syndrome are born with a condition called aplasia cutis congenita, which involves patchy abnormal areas (lesions) on the scalp. These lesions are firm, raised, hairless nodules that resemble open wounds or ulcers at birth, but that heal during childhood.The external ears of people with scalp-ear-nipple syndrome may be small, cup-shaped, folded over, or otherwise mildly misshapen. Hearing is generally normal. Affected individuals also have nipples that are underdeveloped (hypothelia) or absent (athelia). In some cases the underlying breast tissue is absent as well (amastia).Other features that can occur in this disorder include malformed and brittle fingernails and toenails (nail dystrophy), dental abnormalities including widely-spaced or missing teeth, fusion of the skin between some of the fingers and toes (cutaneous syndactyly), and kidney defects such as underdevelopment (hypoplasia) of one or both kidneys. Unusual facial features, including narrowed openings of the eyes (narrowed palpebral fissures), an increased distance between the inner corners of the eyes (telecanthus), a flat bridge of the nose, and nostrils that open to the front rather than downward (anteverted nares), can also occur in this disorder. ad Autosomal dominant KCTD1 https://medlineplus.gov/genetics/gene/kctd1 Finlay-Marks syndrome Hereditary syndrome of lumpy scalp, odd ears, and rudimentary nipples SEN syndrome SENS GTR C1867020 MeSH D004476 OMIM 181270 SNOMED CT 721888002 2017-04 2020-08-18 Schimke immuno-osseous dysplasia https://medlineplus.gov/genetics/condition/schimke-immuno-osseous-dysplasia descriptionSchimke immuno-osseous dysplasia is a condition characterized by short stature, kidney disease, and a weakened immune system. People with this condition have flattened spinal bones (vertebrae) that shorten their neck and trunk. The adult height for people with this condition is typically between 3 and 5 feet. Additional skeletal problems in people with Schimke immuno-osseous dysplasia include abnormalities of the hip joints and the end of the leg bones where they meet the hip joint. These skeletal problems can cause the hip joints to break down (degenerate) over time, leading to joint pain and a limited range of movement. This combination of skeletal problems and spinal abnormalities is called spondyloepiphyseal dysplasia as it affects the bones of the spine (spondylo-) and the ends of long bones (epiphyses) in the legs. It affects most people with Schimke immuno-osseous dysplasia.People with Schimke immuno-osseous dysplasia often have kidney (renal) disease that may lead to life-threatening renal failure and end-stage renal disease (ESRD). Individuals with Schimke immuno-osseous dysplasia also have a shortage of immune system cells called T cells. T cells identify foreign substances and defend the body against infection. This shortage of T cells causes people with Schimke immuno-osseous dysplasia to have recurrent infections.Other features frequently seen in people with Schimke immuno-osseous dysplasia include an exaggerated curvature of the lower back (lordosis); darkened patches of skin (hyperpigmentation), typically on the chest and back; abnormalities of the teeth; and a broad nasal bridge with a rounded tip of the nose.Less common signs and symptoms of Schimke immuno-osseous dysplasia include an accumulation of fatty deposits in the lining of the arteries (atherosclerosis), reduced blood flow to the brain (ischemic stroke), migraine-like headaches, an underactive thyroid gland (hypothyroidism), a decrease in the number of blood cells (anemia), a lack of sperm (azoospermia), and irregular menstruation.In severe cases, individuals with Schimke immuno-osseous dysplasia do not survive past childhood. In mild cases, people with Schimke immuno-osseous dysplasia can survive into adulthood. ar Autosomal recessive SMARCAL1 https://medlineplus.gov/genetics/gene/smarcal1 Immunoosseous dysplasia, Schimke type Schimke immunoosseous dysplasia SIOD SMARCAL1-related immuno-osseous dysplasia (Schimke type) GTR C0877024 MeSH D007153 MeSH D010009 OMIM 242900 SNOMED CT 723995003 2024-07 2024-07-08 Schinzel-Giedion syndrome https://medlineplus.gov/genetics/condition/schinzel-giedion-syndrome descriptionSchinzel-Giedion syndrome is a severe condition that is apparent at birth and affects many body systems. Signs and symptoms of this condition include distinctive facial features, neurological problems, and organ and bone abnormalities. Because of their serious health problems, most affected individuals do not survive past childhood.Children with Schinzel-Giedion syndrome can have a variety of distinctive features. In most affected individuals, the middle of the face looks as though it has been drawn inward (midface retraction). Other facial features include a large or bulging forehead; wide-set eyes (ocular hypertelorism); a short, upturned nose; and a wide mouth with a large tongue (macroglossia). Affected individuals can have other distinctive features, including larger than normal gaps between the bones of the skull in infants (fontanelles), a short neck, low-set ears, and an inability to secrete tears (alacrima). Babies with Schinzel-Giedion syndrome often have excessive hairiness (hypertrichosis) that usually disappears in infancy.Children with Schinzel-Giedion syndrome have severe developmental delay. Other neurological problems can include severe feeding problems, seizures, or visual or hearing impairment. They may also experience short pauses in breathing during sleep (sleep apnea).Affected individuals can also have abnormalities of organs such as the heart, kidneys, or genitals. Heart defects include problems with the heart valves, which control blood flow in the heart; the chambers of the heart that pump blood to the body (ventricles); or the dividing wall between the sides of the heart (the septum). Most children with Schinzel-Giedion syndrome have an accumulation of urine in the kidneys (hydronephrosis), which can occur in one or both kidneys. Affected individuals can have genital abnormalities such as underdevelopment (hypoplasia) of the genitals. Affected boys may have the opening of the urethra on the underside of the penis (hypospadias).Bone abnormalities are common in people with Schinzel-Giedion syndrome. The bones at the base of the skull are often abnormally hard or thick (sclerotic), or the joint between the bones at the base of the skull (occipital synchondrosis) can be abnormally wide. In addition, affected individuals may have broad ribs, abnormal collarbones (clavicles), inward- and upward-turning feet (clubfeet), or shortened bones in the arms or legs or at the ends of the fingers (hypoplastic distal phalanges).Children with Schinzel-Giedion syndrome who survive past infancy have a higher than normal risk of developing certain types of brain tumors called neuroepithelial tumors. n Not inherited SETBP1 https://medlineplus.gov/genetics/gene/setbp1 Schinzel Giedion syndrome Schinzel-Giedion midface retraction syndrome GTR C0265227 MeSH D000015 OMIM 269150 SNOMED CT 18899000 2019-08 2020-08-18 Schizoaffective disorder https://medlineplus.gov/genetics/condition/schizoaffective-disorder descriptionSchizoaffective disorder is a mental health condition that includes features of both schizophrenia and a mood disorder such as bipolar disorder or depression. The prefix "schizo-" refers to the psychotic symptoms of schizophrenia that affect a person's thinking, sense of self, and perceptions. The term "-affective" refers to extreme shifts in mood, energy, and behavior.Schizoaffective disorder has a wide range of signs and symptoms that make it challenging to diagnose. Its features overlap significantly with those of schizophrenia and bipolar disorder, and there is debate about whether schizoaffective disorder should be considered a separate diagnosis or a subtype of one of these other conditions.Signs and symptoms of psychosis in people with schizoaffective disorder include false perceptions called hallucinations, such as hearing voices no one else can hear or experiencing visions, smells, or tactile (touch) sensations. Strongly held false beliefs (delusions) are also a characteristic feature. For example, affected individuals may be certain that they are a particular historical figure or that they are being plotted against or controlled by others.There are two major types of schizoaffective disorder, based on which mood disorder is involved: the bipolar type and the depressive type. The bipolar type includes both dramatic "highs," called manic episodes, and "lows," called depressive episodes. The depressive type includes only depressive episodes. Manic episodes are characterized by increased energy and activity, irritability, restlessness, an inability to sleep, and reckless behavior. Depressive episodes are marked by low energy and activity, a feeling of hopelessness, and an inability to perform everyday tasks.The psychosis and mood problems associated with schizoaffective disorder usually become evident in adolescence or young adulthood. People with this condition often have difficulty functioning at school, at work, and in social settings. Disordered thinking and concentration, inappropriate emotional responses, erratic speech and behavior, and difficulty with personal hygiene and everyday tasks are also common. People with schizoaffective disorder have a higher risk of substance abuse problems and dying by suicide than the general population. u Pattern unknown GABRA4 https://www.ncbi.nlm.nih.gov/gene/2557 GABRA5 https://www.ncbi.nlm.nih.gov/gene/2558 GABRB1 https://www.ncbi.nlm.nih.gov/gene/2560 GABRB3 https://www.ncbi.nlm.nih.gov/gene/2562 GABRR1 https://www.ncbi.nlm.nih.gov/gene/2569 GABRR3 https://www.ncbi.nlm.nih.gov/gene/200959 Schizo-affective psychosis Schizo-affective type schizophrenia Schizoaffective psychosis Schizoaffective schizophrenia Schizophrenia, schizo-affective type Schizophreniform psychosis, affective type ICD-10-CM F25.0 ICD-10-CM F25.1 ICD-10-CM F25.8 ICD-10-CM F25.9 MeSH D011618 OMIM 181500 SNOMED CT 68890003 2018-02 2023-03-01 Schizophrenia https://medlineplus.gov/genetics/condition/schizophrenia descriptionSchizophrenia is a disorder of the brain that affects a person's thoughts, perceptions, and behavior. Affected individuals may have difficulty distinguishing between what is real and what is not (psychosis).Schizophrenia is typically diagnosed during late adolescence or early adulthood in men. The condition tends to be diagnosed slightly later in women. In a very small number of people, it can be diagnosed at a much younger age. The signs and symptoms of schizophrenia include hallucinations, which involve experiencing things that are not there. Hearing voices (auditory hallucination) is the most common type of hallucination that people with schizophrenia experience, but hallucinations may also involve sight, smell, or touch. Strongly held false beliefs (delusions) are also characteristic of schizophrenia. For example, affected individuals may be certain that they are a particular historical figure or that they are being plotted against or controlled by others.Certain features of schizophrenia can make it difficult for affected individuals to function at school, at work, and in social settings. These features include odd and bizarre thinking and behavior (disorganization), unpredictable or inappropriate emotional responses, jumbled speech that cannot be understood, and neglect of personal hygiene. Affected individuals often have difficulty expressing emotions through facial expressions or body movements (flat affect). Cognitive impairment, which can include problems with memory, concentration, and problem-solving, may also make it difficult for people with schizophrenia to live or work independently. Substance abuse and suicidal thoughts and actions are more common in people with schizophrenia than in the general population.Abnormal movements, such as tremors, facial tics, rigidity, and unusually slow movement (bradykinesia), are often seen in people with schizophrenia. In many cases these abnormal movements are the side effects of the medicines that are prescribed to help control the disorder. However, some affected individuals exhibit movement abnormalities before starting medications, suggesting that the abnormal movements may be part of the disorder itself.Some people with schizophrenia also have a mood disorder or severe mood symptoms, such as depression or periods of extreme excitement (mania). Mood disorders primarily affect a person's emotional state. u Pattern unknown SCZD GTR C0036341 ICD-10-CM F20 MeSH D012559 OMIM 181500 SNOMED CT 58214004 2026-03 2026-03-24 Schwannomatosis https://medlineplus.gov/genetics/condition/schwannomatosis descriptionSchwannomatosis is a disorder characterized by multiple noncancerous (benign) tumors called schwannomas, which are a type of tumor that grows on nerves. Schwannomas develop when Schwann cells, which are specialized cells that normally form an insulating layer around the nerve, grow uncontrollably to form a tumor.The signs and symptoms of schwannomatosis usually appear in early adulthood. The most common symptom is long-lasting (chronic) pain, which can affect any part of the body. In some cases, the pain is felt in areas where there are no known tumors. The pain associated with this condition ranges from mild to severe and can be difficult to manage. Other signs and symptoms that can occur with schwannomatosis depend on the location of the tumors and which nerves are affected. These problems include numbness, weakness, tingling, and headaches. The life expectancy of people with schwannomatosis is normal.Schwannomatosis is usually considered to be a form of neurofibromatosis, which is a group of disorders characterized by the growth of tumors in the nervous system. The other two recognized forms of neurofibromatosis are neurofibromatosis type 1 and neurofibromatosis type 2. The features of schwannomatosis can be very similar to those of neurofibromatosis type 2. However, schwannomatosis almost never includes inner ear tumors called vestibular schwannomas, which are a hallmark of neurofibromatosis type 2. Additional features of the other forms of neurofibromatosis, including the development of other types of tumors, are much less common in schwannomatosis. u Pattern unknown ad Autosomal dominant NF2 https://medlineplus.gov/genetics/gene/nf2 SMARCB1 https://medlineplus.gov/genetics/gene/smarcb1 LZTR1 https://medlineplus.gov/genetics/gene/lztr1 Multiple neurilemmomas Multiple schwannomas Neurilemmomatosis Neurilemmomatosis, congenital cutaneous Neurinomatosis Neurofibromatosis type 3 GTR C1335929 GTR C3810283 ICD-10-CM Q85.03 MeSH D009442 MeSH D012878 MeSH D017253 OMIM 162091 OMIM 615670 SNOMED CT 142071000119101 SNOMED CT 254240003 2017-01 2023-03-01 Schwartz-Jampel syndrome https://medlineplus.gov/genetics/condition/schwartz-jampel-syndrome descriptionSchwartz-Jampel syndrome is a rare condition characterized by permanent muscle stiffness (myotonia) and bone abnormalities known as chondrodysplasia. The signs and symptoms of this condition become apparent sometime after birth, usually in early childhood. Either muscle stiffness or chondrodysplasia can appear first. The muscle and bone abnormalities worsen in childhood, although most affected individuals have a normal lifespan. The specific features of Schwartz-Jampel syndrome vary widely.Myotonia involves continuous tensing (contraction) of muscles used for movement (skeletal muscles) throughout the body. This sustained muscle contraction causes stiffness that interferes with eating, sitting, walking, and other movements. Sustained contraction of muscles in the face leads to a fixed, "mask-like" facial expression with narrow eye openings (blepharophimosis) and pursed lips. This facial appearance is very specific to Schwartz-Jampel syndrome. Affected individuals may also be nearsighted and experience abnormal blinking or spasms of the eyelids (blepharospasm).Chondrodysplasia affects the development of the skeleton, particularly the long bones in the arms and legs and the bones of the hips. These bones are shortened and unusually wide at the ends, so affected individuals have short stature. The long bones may also be abnormally curved (bowed). Other bone abnormalities associated with Schwartz-Jampel syndrome include a protruding chest (pectus carinatum), abnormal curvature of the spine, flattened bones of the spine (platyspondyly), and joint abnormalities called contractures that further restrict movement.Researchers originally described two types of Schwartz-Jampel syndrome. Type 1 has the signs and symptoms described above, while type 2 has more severe bone abnormalities and other health problems and is usually life-threatening in early infancy. Researchers have since discovered that the condition they thought was Schwartz-Jampel syndrome type 2 is actually part of another disorder, Stüve-Wiedemann syndrome, which is caused by mutations in a different gene. They have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used. ar Autosomal recessive HSPG2 https://medlineplus.gov/genetics/gene/hspg2 Chondrodystrophic myotonia Myotonic myopathy, dwarfism, chondrodystrophy, and ocular and facial abnormalities Schwartz-Jampel syndrome, type 1 Schwartz-Jampel-Aberfeld syndrome SJA syndrome SJS SJS1 GTR C4551479 ICD-10-CM G71.13 MeSH D010009 OMIM 255800 SNOMED CT 29145002 2016-04 2020-08-18 Seasonal affective disorder https://medlineplus.gov/genetics/condition/seasonal-affective-disorder descriptionSeasonal affective disorder is a mental health condition that is triggered by the changing of the seasons. This condition is a subtype of major depressive disorder and bipolar disorder. Major depressive disorder is characterized by prolonged sadness and a general lack of interest, while bipolar disorder is characterized by similar depressive episodes alternating with periods of abnormally high energy and activity (hypomania or mania). People with seasonal affective disorder have signs and symptoms of either major depressive disorder or bipolar disorder only during certain months of the year. Major depressive disorder is more common than bipolar disorder among people with seasonal affective disorder. This condition usually begins in a person's twenties or thirties.The signs and symptoms that occur during depressive episodes in people with seasonal affective disorder are similar to those of major depressive disorder, including a loss of interest or enjoyment in activities, a decrease in energy, a depressed mood, and low self-esteem. In most people with seasonal affective disorder, depression and other features appear in the fall and winter months and subside in the spring and summer months. In these individuals, additional symptoms often include weight gain due to increased cravings for carbohydrates and an increase in sleep (hypersomnia). Affected individuals with underlying bipolar disorder typically have alternating episodes of depression in the fall and winter months and mania during the spring and summer months.In about 10 percent of people with seasonal affective disorder, the condition has the opposite seasonal pattern, occurring in the spring and summer months and stopping during the fall and winter months. These individuals usually have a loss of appetite and sleep, unlike those with symptoms in the fall and winter.For those affected, it is estimated that symptoms of seasonal affective disorder are present during 40 percent of the year. In some individuals, seasonal affective disorder does not recur every year. Thirty to 50 percent of affected individuals do not show symptoms of the disorder in consecutive winters. In about 40 percent of individuals with seasonal affective disorder, depressive episodes continue after winter and do not alleviate in the summer months, leading to a change in diagnosis to either major depressive disorder or bipolar disorder.Individuals with seasonal affective disorder tend to have another psychological condition, such as attention-deficit/hyperactivity disorder (ADHD), an eating disorder, anxiety disorder, or panic disorder. u Pattern unknown BMAL1 https://www.ncbi.nlm.nih.gov/gene/406 CRY2 https://www.ncbi.nlm.nih.gov/gene/1408 HTR2A https://www.ncbi.nlm.nih.gov/gene/3356 NPAS2 https://www.ncbi.nlm.nih.gov/gene/4862 PER2 https://www.ncbi.nlm.nih.gov/gene/8864 CLOCK https://www.ncbi.nlm.nih.gov/gene/9575 OPN4 https://www.ncbi.nlm.nih.gov/gene/94233 Affective disorder, seasonal Depression in a seasonal pattern Depression; seasonal Major depressive disorder with a seasonal pattern SAD Seasonal depression Seasonal mood disorder MeSH D016574 OMIM 608516 SNOMED CT 247803002 2017-12 2023-03-01 Senior-Løken syndrome https://medlineplus.gov/genetics/condition/senior-loken-syndrome descriptionSenior-Løken syndrome is a rare disorder characterized by the combination of two specific features: a kidney condition called nephronophthisis and an eye condition known as Leber congenital amaurosis.Nephronophthisis causes fluid-filled cysts to develop in the kidneys beginning in childhood. These cysts impair kidney function, initially causing increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). Nephronophthisis leads to end-stage renal disease (ESRD) later in childhood or in adolescence. ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.Leber congenital amaurosis primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. This condition causes vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). Some people with Senior-Løken syndrome develop the signs of Leber congenital amaurosis within the first few years of life, while others do not develop vision problems until later in childhood. ar Autosomal recessive CEP290 https://medlineplus.gov/genetics/gene/cep290 WDR19 https://medlineplus.gov/genetics/gene/wdr19 NPHP1 https://medlineplus.gov/genetics/gene/nphp1 IQCB1 https://www.ncbi.nlm.nih.gov/gene/9657 SDCCAG8 https://www.ncbi.nlm.nih.gov/gene/10806 NPHP4 https://www.ncbi.nlm.nih.gov/gene/261734 Loken-Senior syndrome Renal dysplasia and retinal aplasia Renal-retinal syndrome Senior-Loken syndrome GTR C1836517 GTR C1846979 GTR C1846980 GTR C1857779 GTR C3150877 GTR C4551559 MeSH D052177 MeSH D057130 OMIM 266900 OMIM 606995 OMIM 606996 OMIM 609254 OMIM 610189 OMIM 613615 SNOMED CT 236531005 2012-06 2023-03-01 Sepiapterin reductase deficiency https://medlineplus.gov/genetics/condition/sepiapterin-reductase-deficiency descriptionSepiapterin reductase deficiency is a condition characterized by movement problems, most often a pattern of involuntary, sustained muscle contractions known as dystonia. Other movement problems can include muscle stiffness (spasticity), tremors, problems with coordination and balance (ataxia), and involuntary jerking movements (chorea). People with sepiapterin reductase deficiency can experience episodes called oculogyric crises. These episodes involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck. Movement abnormalities are often worse late in the day. Most affected individuals have delayed development of motor skills such as sitting and crawling, and they typically are not able to walk unassisted. The problems with movement tend to worsen over time.People with sepiapterin reductase deficiency may have additional signs and symptoms including an unusually small head size (microcephaly), intellectual disability, seizures, excessive sleeping, and mood swings. ar Autosomal recessive SPR https://medlineplus.gov/genetics/gene/spr Dopa-responsive dystonia due to sepiapterin reductase deficiency SPR deficiency GTR C0268468 MeSH D004421 OMIM 612716 SNOMED CT 45116002 2011-06 2020-08-18 Septo-optic dysplasia https://medlineplus.gov/genetics/condition/septo-optic-dysplasia descriptionSepto-optic dysplasia is a disorder that affects early brain development. This condition is typically defined as a combination of at least two of the following three features: underdevelopment (hypoplasia) of the nerves that carry visual information from the eye to the brain (optic nerves); abnormal development of the structures that separate the right and left halves (the midline) of the brain; and hypoplasia of the hormone-producing gland (pituitary gland) at the base of the brain. The signs and symptoms of septo-optic dysplasia can vary widely among affected individuals. Less than half of people with septo-optic dysplasia have all three of the main features. In individuals with optic nerve hypoplasia, the optic nerves are often abnormally small and make fewer connections than usual between the eyes and the brain. As a result, affected individuals have impaired vision in one or both eyes. People with optic nerve hypoplasia can also have other eye abnormalities, including rapid, involuntary eye movements (nystagmus) and eyes that do not point in the same direction (strabismus).Abnormal development of the structures along the midline of the brain occurs in many people with septo-optic dysplasia. These structures include the corpus callosum, which is a band of tissue that connects the two halves of the brain, and the septum pellucidum, which separates the fluid-filled spaces in the brain. In affected individuals, these structures may form abnormally or fail to develop at all. Additional brain abnormalities, such as slits or clefts in one or both halves of the brain (schizencephaly), may also be present in people with septo-optic dysplasia. Depending on which structures are affected, abnormal brain development can lead to intellectual disabilities and other behavioral and neurological problems, including recurrent seizures (epilepsy); developmental delays; and autism spectrum disorder, which is characterized by impaired social skills and communication problems.Many people who have septo-optic dysplasia have an underdeveloped pituitary gland. Pituitary hypoplasia can lead to a shortage (deficiency) of essential hormones. These hormones help control growth, reproduction, and other critical body functions. In most cases, pituitary hypoplasia causes growth hormone (GH) deficiency, which results in slow growth and short stature. Less commonly, individuals who have septo-optic dysplasia have panhypopituitarism, a condition in which the production of multiple hormones is impaired. Panhypopituitarism can be associated with slow growth, low levels of glucose in the blood (hypoglycemia), genital abnormalities, and problems with sexual development.Because the signs and symptoms of septo-optic dysplasia can vary significantly, researchers have suggested that this condition may actually represent a spectrum of related conditions rather than a single disorder. Researchers have suggested various names for this spectrum, including "septo-optic-pituitary dysplasia,"  "septo-optic pituitary dysplasia complex," and "hypothalamo-pituitary-optic dysplasia." Researchers are working to better understand this condition. ad Autosomal dominant ar Autosomal recessive SOX2 https://medlineplus.gov/genetics/gene/sox2 HESX1 https://medlineplus.gov/genetics/gene/hesx1 OTX2 https://medlineplus.gov/genetics/gene/otx2 SOX3 https://www.ncbi.nlm.nih.gov/gene/6658 Combined pituitary hormone deficiency 5 CPHD5 De Morsier syndrome Septo-optic dysplasia complex Septo-optic-pituitary dysplasia complex Septooptic dysplasia SOD GTR C0338503 ICD-10-CM Q04.4 MeSH D025962 OMIM 182230 SNOMED CT 7611002 2025-05 2025-07-08 Severe congenital neutropenia https://medlineplus.gov/genetics/condition/severe-congenital-neutropenia descriptionSevere congenital neutropenia is a condition that increases the risk of repeated infections in affected individuals. People with this condition have an abnormally low level (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The shortage of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to frequent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and likely to fracture. In people with severe congenital neutropenia, bone disorders can begin at any time from infancy through adulthood.Approximately 20 percent of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence.Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities. ar Autosomal recessive ad Autosomal dominant xr X-linked recessive WAS https://medlineplus.gov/genetics/gene/was ELANE https://medlineplus.gov/genetics/gene/elane HAX1 https://medlineplus.gov/genetics/gene/hax1 TCIRG1 https://medlineplus.gov/genetics/gene/tcirg1 CSF3R https://www.ncbi.nlm.nih.gov/gene/1441 GFI1 https://www.ncbi.nlm.nih.gov/gene/2672 VPS45 https://www.ncbi.nlm.nih.gov/gene/11311 JAGN1 https://www.ncbi.nlm.nih.gov/gene/84522 G6PC3 https://www.ncbi.nlm.nih.gov/gene/92579 Congenital agranulocytosis Congenital neutropenia Infantile genetic agranulocytosis Kostmann disease Kostmann's agranulocytosis Kostmann's syndrome Severe infantile genetic neutropenia GTR C1853118 ICD-10-CM D70.0 MeSH D009503 OMIM 202700 OMIM 300299 OMIM 610738 OMIM 612541 OMIM 613107 OMIM 615285 OMIM 616022 OMIM 617014 SNOMED CT 718882006 SNOMED CT 89655007 2010-04 2023-11-10 Sheldon-Hall syndrome https://medlineplus.gov/genetics/condition/sheldon-hall-syndrome descriptionSheldon-Hall syndrome, also known as distal arthrogryposis type 2B, is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The term "arthrogryposis" comes from the Greek words for joint (arthro-) and crooked or hooked (gryposis). "Distal" refers to areas of the body away from the center. The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity called ulnar deviation in which all of the fingers are angled outward toward the fifth (pinky) finger. Inward- and upward-turning feet (a condition called clubfoot) is also commonly seen in Sheldon-Hall syndrome. The specific hand and foot abnormalities vary among affected individuals; the abnormalities are present at birth and generally do not get worse over time.People with Sheldon-Hall syndrome also usually have distinctive facial features, which include a triangular face; outside corners of the eyes that point downward (down-slanting palpebral fissures); deep folds in the skin between the nose and lips (nasolabial folds); and a small mouth with a high, arched roof of the mouth (palate). Other features that may occur in Sheldon-Hall syndrome include extra folds of skin on the neck (webbed neck) and short stature.Sheldon-Hall syndrome does not usually affect other parts of the body, and intelligence and life expectancy are normal in this disorder. ad Autosomal dominant MYH3 https://medlineplus.gov/genetics/gene/myh3 TPM2 https://medlineplus.gov/genetics/gene/tpm2 TNNI2 https://medlineplus.gov/genetics/gene/tnni2 TNNT3 https://medlineplus.gov/genetics/gene/tnnt3 Arthrogryposis multiplex congenita, distal, type 2B DA2B Distal arthrogryposis type 2B SHS ICD-10-CM Q74.3 MeSH D001176 OMIM 601680 SNOMED CT 715216008 2015-06 2023-11-08 Shingles https://medlineplus.gov/genetics/condition/shingles descriptionShingles (also known as herpes zoster) results from infection by the varicella zoster virus. This common virus causes chickenpox (also known as varicella), which is characterized by itchy spots on the skin that cover the whole body and usually occurs in childhood or adolescence. After the body fights the initial infection, the varicella zoster virus remains in nerve cells for the rest of a person's life. Because the virus is controlled by immune system cells called T cells, it is generally inactive (latent) and typically causes no health problems. However, in some people, the virus becomes active again (reactivates) and causes shingles. Shingles can occur at any age, although it is rare in childhood and becomes more common after age 50.Shingles is characterized by a severely painful, itchy, or tingling rash, most commonly on one side of the torso, although it can occur anywhere on the body. Reactivation of the virus usually occurs in a single nerve, leading to the symptoms of shingles in just the region of skin connected to that nerve. When the nerve connected to the eye and the skin surrounding it is affected, the condition is called herpes zoster ophthalmicus. This form of shingles, which accounts for about 20 percent of cases, can cause permanent vision impairment.Some individuals with shingles feel throbbing or tingling in the affected region shortly before the rash appears. Blisters form in the rash area, break open, and scab over in a few days. Healing usually takes 2 to 4 weeks. Most people have only one episode of shingles, although it can recur in rare cases.In 5 to 20 percent of people with shingles, severe pain continues in the affected region after healing of the rash, which is known as postherpetic neuralgia (PHN). PHN is the most common complication of shingles. It can also involve severe itchiness or an overactive pain response to things that do not usually cause pain (allodynia), such as a light touch. PHN can last weeks, months, or even years. The likelihood of developing PHN after shingles and its severity increase with age. The pain caused by shingles and PHN can disrupt day-to-day activities and reduce a person's quality of life. u Pattern unknown HLA-B https://medlineplus.gov/genetics/gene/hla-b STAT3 https://medlineplus.gov/genetics/gene/stat3 POLR3A https://medlineplus.gov/genetics/gene/polr3a STAT1 https://medlineplus.gov/genetics/gene/stat1 HLA-A https://www.ncbi.nlm.nih.gov/gene/3105 IL10 https://www.ncbi.nlm.nih.gov/gene/3586 POLR3C https://www.ncbi.nlm.nih.gov/gene/10623 Herpes zoster Zoster ICD-10-CM B02 ICD-10-CM B02.0 ICD-10-CM B02.1 ICD-10-CM B02.2 ICD-10-CM B02.21 ICD-10-CM B02.22 ICD-10-CM B02.23 ICD-10-CM B02.24 ICD-10-CM B02.29 ICD-10-CM B02.3 ICD-10-CM B02.30 ICD-10-CM B02.31 ICD-10-CM B02.32 ICD-10-CM B02.33 ICD-10-CM B02.34 ICD-10-CM B02.39 ICD-10-CM B02.7 ICD-10-CM B02.8 ICD-10-CM B02.9 MeSH D006562 SNOMED CT 4740000 2018-01 2020-08-18 Short QT syndrome https://medlineplus.gov/genetics/condition/short-qt-syndrome descriptionShort QT syndrome is a condition that can cause a disruption of the heart's normal rhythm (arrhythmia). In people with this condition, the heart (cardiac) muscle takes less time than usual to recharge between beats. The term "short QT" refers to a specific pattern of heart activity that is detected with an electrocardiogram (EKG), which is a test used to measure the electrical activity of the heart. In people with this condition, the part of the heartbeat known as the QT interval is abnormally short.If untreated, the arrhythmia associated with short QT syndrome can lead to a variety of signs and symptoms, from dizziness and fainting (syncope) to cardiac arrest and sudden death. These signs and symptoms can occur any time from early infancy to old age. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of unexplained death in babies younger than 1 year. However, some people with short QT syndrome never experience any health problems associated with the condition. ad Autosomal dominant KCNQ1 https://medlineplus.gov/genetics/gene/kcnq1 KCNH2 https://medlineplus.gov/genetics/gene/kcnh2 KCNJ2 https://medlineplus.gov/genetics/gene/kcnj2 CACNA1C https://medlineplus.gov/genetics/gene/cacna1c SQTS GTR C1865018 GTR C1865019 GTR C1865020 MeSH D001145 OMIM 609620 OMIM 609621 OMIM 609622 SNOMED CT 698272007 2013-06 2020-08-18 Short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay https://medlineplus.gov/genetics/condition/short-stature-hyperextensibility-hernia-ocular-depression-rieger-anomaly-and-teething-delay descriptionShort stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay, commonly known by the acronym SHORT syndrome, is a rare disorder that affects many parts of the body.Most people with SHORT syndrome are small at birth and gain weight slowly in childhood. Affected adults tend to have short stature compared with others in their family. Many have a lack of fatty tissue under the skin (lipoatrophy), primarily in the face, arms, and chest. This lack of fat, together with thin, wrinkled skin and veins visible beneath the skin, makes affected individuals look older than their biological age. This appearance of premature aging is sometimes described as progeroid.Most people with SHORT syndrome have distinctive facial features. These include a triangular face shape with a prominent forehead and deep-set eyes (ocular depression), thin nostrils, a downturned mouth, and a small chin. Eye abnormalities are common in affected individuals, particularly Rieger anomaly, which affects structures at the front of the eye. Rieger anomaly can be associated with increased pressure in the eye (glaucoma) and vision loss. Some people with SHORT syndrome also have dental abnormalities such as delayed appearance (eruption) of teeth in early childhood, small teeth, fewer teeth than normal (hypodontia), and a lack of protective covering (enamel) on the surface of the teeth.Other signs and symptoms that have been reported in people with SHORT syndrome include immune system abnormalities, a kidney disorder known as nephrocalcinosis, hearing loss, loose (hyperextensible) joints, and a soft out-pouching in the lower abdomen called an inguinal hernia. A few affected individuals have developed problems with blood sugar (glucose) regulation including insulin resistance and diabetes. Most people with SHORT syndrome have normal intelligence, although a few have been reported with mild cognitive impairment or delayed development of speech in childhood. ad Autosomal dominant PIK3R1 https://medlineplus.gov/genetics/gene/pik3r1 Growth retardation-Rieger anomaly Lipodystrophy, partial, with Rieger anomaly and short stature Short stature-hyperextensibility-Rieger anomaly-teething delay SHORT syndrome GTR C0878684 MeSH D006130 OMIM 269880 SNOMED CT 237608006 2013-12 2023-07-25 Short-chain acyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/short-chain-acyl-coa-dehydrogenase-deficiency descriptionShort-chain acyl-CoA dehydrogenase (SCAD) deficiency is a condition that prevents the body from converting certain fats into energy, especially during periods without food (fasting).Signs and symptoms of SCAD deficiency may appear during infancy or early childhood and can include vomiting, low blood glucose (hypoglycemia), a lack of energy (lethargy), poor feeding, and failure to gain weight and grow at the expected rate (failure to thrive). Other features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delay, and a small head size (microcephaly).The symptoms of SCAD deficiency may be triggered by fasting or illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe condition that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.In some people with SCAD deficiency, signs and symptoms do not appear until adulthood. These individuals are more likely to have problems related to muscle weakness and wasting.The severity of this condition varies widely, even among members of the same family. Some individuals are diagnosed with SCAD deficiency based on laboratory testing but never develop any symptoms of the condition. ar Autosomal recessive ACADS https://medlineplus.gov/genetics/gene/acads ACADS deficiency Deficiency of butyryl-CoA dehydrogenase Lipid-storage myopathy secondary to short-chain acyl-coa dehydrogenase deficiency SCAD deficiency SCADH deficiency Short-chain acyl-coenzyme A dehydrogenase deficiency GTR C0342783 ICD-10-CM E71.312 MeSH D008052 OMIM 201470 SNOMED CT 124166007 SNOMED CT 237998000 2009-11 2023-07-26 Short/branched chain acyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/short-branched-chain-acyl-coa-dehydrogenase-deficiency descriptionShort/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency (also known as 2-methylbutyryl-CoA dehydrogenase deficiency) is a rare disorder in which the body is unable to process proteins properly. Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for the body. People with SBCAD deficiency cannot process a particular amino acid called isoleucine.Most cases of SBCAD deficiency are detected shortly after birth by newborn screening, which identifies abnormal levels of certain compounds in the blood. In individuals with this condition, a compound called 2-methylbutyryl carnitine is elevated in the blood and another called 2-methylbutyrylglycine is elevated in the urine (2-methylbutyrylglycinuria).Most people with SBCAD deficiency have no health problems related to the disorder. A small percentage of affected individuals develop signs and symptoms of the condition, which can begin soon after birth or later in childhood. The initial symptoms often include poor feeding, lack of energy (lethargy), vomiting, and irritability. These symptoms sometimes progress to serious health problems such as difficulty breathing, seizures, and coma. Additional problems can include poor growth, vision impairment, learning disabilities, muscle weakness, and delays in motor skills such as standing and walking.It is unclear why some people with SBCAD deficiency develop health problems and others do not. Doctors suggest that in some cases, signs and symptoms may be triggered by infections, prolonged periods without food (fasting), or an increased amount of protein-rich foods in the diet. ar Autosomal recessive ACADSB https://medlineplus.gov/genetics/gene/acadsb 2-MBADD 2-MBCD deficiency 2-MBG 2-methylbutyryl glycinuria 2-methylbutyryl-CoA dehydrogenase deficiency 2-methylbutyryl-coenzyme A dehydrogenase deficiency SBCADD Short/branched-chain acyl-CoA dehydrogenase deficiency GTR C1864912 MeSH D000592 OMIM 610006 SNOMED CT 444838008 2007-04 2020-08-18 Shprintzen-Goldberg syndrome https://medlineplus.gov/genetics/condition/shprintzen-goldberg-syndrome descriptionShprintzen-Goldberg syndrome is a disorder that affects many parts of the body. Affected individuals have a combination of distinctive facial features and skeletal and neurological abnormalities.A common feature in people with Shprintzen-Goldberg syndrome is craniosynostosis, which is the premature fusion of certain skull bones. This early fusion prevents the skull from growing normally. Affected individuals can also have distinctive facial features, including a long, narrow head; widely spaced eyes (hypertelorism); protruding eyes (exophthalmos); outside corners of the eyes that point downward (downslanting palpebral fissures); a high, narrow palate; a small lower jaw (micrognathia); and low-set ears that are rotated backward.People with Shprintzen-Goldberg syndrome are often said to have a marfanoid habitus, because their bodies resemble those of people with a genetic condition called Marfan syndrome. For example, they may have long, slender fingers (arachnodactyly), unusually long limbs, a sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and an abnormal side-to-side curvature of the spine (scoliosis). People with Shprintzen-Goldberg syndrome can have other skeletal abnormalities, such as one or more fingers that are permanently bent (camptodactyly) and an unusually large range of joint movement (hypermobility).People with Shprintzen-Goldberg syndrome often have delayed development and mild to moderate intellectual disability.Other common features of Shprintzen-Goldberg syndrome include heart or brain abnormalities, weak muscle tone (hypotonia) in infancy, and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia).Shprintzen-Goldberg syndrome has signs and symptoms similar to those of Marfan syndrome and another genetic condition called Loeys-Dietz syndrome. However, intellectual disability is more likely to occur in Shprintzen-Goldberg syndrome than in the other two conditions. In addition, heart abnormalities are more common and usually more severe in Marfan syndrome and Loeys-Dietz syndrome. ad Autosomal dominant SKI https://medlineplus.gov/genetics/gene/ski Marfanoid-craniosynostosis syndrome Shprintzen-Goldberg craniosynostosis syndrome GTR C1321551 MeSH D003398 OMIM 182212 SNOMED CT 719069008 2013-02 2026-02-25 Shwachman-Diamond syndrome https://medlineplus.gov/genetics/condition/shwachman-diamond-syndrome descriptionShwachman-Diamond syndrome is an inherited condition that affects many parts of the body, particularly the bone marrow, pancreas, and bones.The major function of bone marrow is to produce new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infection; and platelets, which are blood cells that are necessary for normal blood clotting. In Shwachman-Diamond syndrome, the bone marrow malfunctions and does not make some or all types of white blood cells. A shortage of neutrophils, the most common type of white blood cell, causes a condition called neutropenia. Most people with Shwachman-Diamond syndrome have at least occasional episodes of neutropenia, which makes them more vulnerable to infections, often involving the lungs (pneumonia), ears (otitis media), or skin. Less commonly, bone marrow abnormalities lead to a shortage of red blood cells (anemia), which causes fatigue and weakness, or a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding.People with Shwachman-Diamond syndrome have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS) and aplastic anemia, which are disorders caused by abnormal blood stem cells, and a cancer of blood-forming tissue known as acute myeloid leukemia (AML).Shwachman-Diamond syndrome also affects the pancreas, which is an organ that plays an essential role in digestion. One of this organ's main functions is to produce enzymes that help break down and use nutrients from food. In most infants with Shwachman-Diamond syndrome, the pancreas does not produce enough of these enzymes. This condition is known as pancreatic insufficiency. Infants with pancreatic insufficiency have trouble digesting food and absorbing nutrients and vitamins that are needed for growth. As a result, they often have fatty, foul-smelling stools (steatorrhea); are slow to grow and gain weight (failure to thrive); and experience malnutrition. Pancreatic insufficiency often improves with age in people with Shwachman-Diamond syndrome.Skeletal abnormalities are another common feature of Shwachman-Diamond syndrome. Many affected individuals have problems with bone formation and growth, most often affecting the hips and knees. Low bone density is also frequently associated with this condition. Some affected infants are born with a narrow rib cage and short ribs, which can cause life-threatening problems with breathing. The combination of skeletal abnormalities and slow growth results in short stature in most people with this disorder.The complications of Shwachman-Diamond syndrome can affect several other parts of the body, including the liver, heart, endocrine system (which produces hormones), eyes, teeth, and skin. Additionally, studies suggest that Shwachman-Diamond syndrome may be associated with delayed speech and the delayed development of motor skills such as sitting, standing, and walking. ar Autosomal recessive ad Autosomal dominant SBDS https://medlineplus.gov/genetics/gene/sbds SRP54 https://www.ncbi.nlm.nih.gov/gene/6729 EFL1 https://www.ncbi.nlm.nih.gov/gene/79631 DNAJC21 https://www.ncbi.nlm.nih.gov/gene/134218 Congenital lipomatosis of pancreas Metaphyseal chondrodysplasia, Shwachman type SDS Shwachman syndrome Shwachman-Bodian syndrome Shwachman-Bodian-Diamond syndrome Shwachman-Diamond-Oski Syndrome GTR C4692625 MeSH D001855 MeSH D010188 OMIM 260400 SNOMED CT 89454001 2020-03 2020-08-18 Sialidosis https://medlineplus.gov/genetics/condition/sialidosis descriptionSialidosis is a severe inherited disorder that affects many organs and tissues, including the nervous system. This disorder is divided into two types, which are distinguished by the age at which symptoms appear and the severity of features.Sialidosis type I, also referred to as cherry-red spot myoclonus syndrome, is the less severe form of this condition. People with type I develop signs and symptoms of sialidosis in their teens or twenties. Initially, affected individuals experience problems walking (gait disturbance) and/or a loss of sharp vision (reduced visual acuity). Individuals with sialidosis type I also experience muscle twitches (myoclonus), difficulty coordinating movements (ataxia), leg tremors, and seizures. The myoclonus worsens over time, causing difficulty sitting, standing, or walking. People with sialidosis type I eventually require wheelchair assistance. Affected individuals have progressive vision problems, including impaired color vision or night blindness. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Sialidosis type I does not affect intelligence or life expectancy.Sialidosis type II, the more severe type of the disorder, is further divided into congenital, infantile, and juvenile forms. The features of congenital sialidosis type II can develop before birth. This form of sialidosis is associated with an abnormal buildup of fluid in the abdominal cavity (ascites) or widespread swelling before birth caused by fluid accumulation (hydrops fetalis). Affected infants may also have an enlarged liver and spleen (hepatosplenomegaly), abnormal bone development (dysostosis multiplex), and distinctive facial features that are often described as "coarse." As a result of these serious health problems, individuals with congenital sialidosis type II usually are stillborn or die soon after birth.Infantile sialidosis type II shares some features with the congenital form, although the signs and symptoms are slightly less severe and begin within the first year of life. Features of the infantile form include hepatosplenomegaly, dysostosis multiplex, "coarse" facial features, short stature, and intellectual disability. As children with infantile sialidosis type II get older, they may develop myoclonus and cherry-red spots. Other signs and symptoms include hearing loss, overgrowth of the gums (gingival hyperplasia), and widely spaced teeth. Affected individuals may survive into childhood or adolescence.The juvenile form has the least severe signs and symptoms of the different forms of sialidosis type II. Features of this condition usually appear in late childhood and may include mildly "coarse" facial features, mild bone abnormalities, cherry-red spots, myoclonus, intellectual disability, and dark red spots on the skin (angiokeratomas). The life expectancy of individuals with juvenile sialidosis type II varies depending on the severity of symptoms. ar Autosomal recessive NEU1 https://medlineplus.gov/genetics/gene/neu1 Cherry red spot myoclonus syndrome Mucolipidosis I Mucolipidosis type I Myoclonus cherry red spot syndrome GTR C0023806 GTR C4282398 MeSH D009081 OMIM 256550 SNOMED CT 124461006 SNOMED CT 38795005 2010-05 2020-08-18 Sialuria https://medlineplus.gov/genetics/condition/sialuria descriptionSialuria is a rare disorder that affects development. Infants with sialuria are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice), an enlarged liver and spleen (hepatosplenomegaly), and unusually small red blood cells (microcytic anemia). They may develop a somewhat flat face and distinctive-looking facial features that are described as "coarse." Temporarily delayed development and weak muscle tone (hypotonia) have also been reported.Young children with sialuria tend to have frequent upper respiratory infections and episodes of dehydration and stomach upset (gastroenteritis). Older children may have seizures and learning difficulties. In some affected children, intellectual development is nearly normal.The features of sialuria vary widely among affected people. Many of the problems associated with this disorder appear to improve with age, although little is known about the long-term effects of the disease. It is likely that some adults with sialuria never come to medical attention because they have very mild signs and symptoms or no health problems related to the condition. ad Autosomal dominant+New variant GNE https://medlineplus.gov/genetics/gene/gne French type sialuria Sialuria, French type GTR C0342853 MeSH D008661 OMIM 269921 SNOMED CT 238051008 2024-03 2024-04-01 Sick sinus syndrome https://medlineplus.gov/genetics/condition/sick-sinus-syndrome descriptionSick sinus syndrome (also known as sinus node dysfunction) is a group of related heart conditions that can affect how the heart beats. "Sick sinus" refers to the sino-atrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally. In some cases, it does not produce the right signals to trigger a regular heartbeat. In others, abnormalities disrupt the electrical impulses and prevent them from reaching the rest of the heart.Sick sinus syndrome tends to cause the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia). In some cases, the heartbeat rapidly switches from being too fast to being too slow, a condition known as tachycardia-bradycardia syndrome. Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue). Once symptoms of sick sinus syndrome appear, they usually worsen with time. However, some people with the condition never experience any related health problems.Sick sinus syndrome occurs most commonly in older adults, although it can be diagnosed in people of any age. The condition increases the risk of several life-threatening problems involving the heart and blood vessels. These include a heart rhythm abnormality called atrial fibrillation, heart failure, cardiac arrest, and stroke. ar Autosomal recessive ad Autosomal dominant SCN5A https://medlineplus.gov/genetics/gene/scn5a HCN4 https://medlineplus.gov/genetics/gene/hcn4 MYH6 https://medlineplus.gov/genetics/gene/myh6 Sinus node disease Sinus node dysfunction SND SSS GTR C1834144 GTR C1837845 GTR C3279791 ICD-10-CM I49.5 MeSH D012804 OMIM 163800 OMIM 608567 OMIM 614090 SNOMED CT 233913007 SNOMED CT 36083008 SNOMED CT 60423000 2013-08 2020-08-18 Sickle cell disease https://medlineplus.gov/genetics/condition/sickle-cell-disease descriptionSickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disease have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle or crescent shape.Signs and symptoms of sickle cell disease usually begin in early childhood. Characteristic features of this disorder include a low number of red blood cells (anemia), repeated infections, and periodic episodes of pain. The severity of signs and symptoms varies from person to person. Some people have mild health issues, while others are frequently hospitalized for more serious complications. The signs and symptoms of sickle cell disease are caused by the sickling of red blood cells. When red blood cells sickle, they break down prematurely, which can lead to anemia. Anemia can cause shortness of breath, fatigue, and delayed growth and development in children. The rapid breakdown of red blood cells may also cause yellowing of the skin and whites of the eyes (jaundice). Painful episodes can occur when sickled red blood cells, which are stiff and inflexible, get stuck in small blood vessels. These episodes deprive tissues and organs, such as the lungs, kidneys, spleen, and brain, of oxygen-rich blood and can lead to organ damage. A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension), which can lead to heart failure. Pulmonary hypertension occurs in about 10 percent of adults with sickle cell disease.There are currently a range of treatment options for people with sickle cell disease. Some treatments address the symptoms of the condition, while others address the genetic cause of sickle cell disease and effectively cure the condition.  Without treatment, individuals with sickle cell disease often have lifelong health problems. ar Autosomal recessive HBB https://medlineplus.gov/genetics/gene/hbb HbS disease Hemoglobin S disease SCD Sickle cell disorders Sickling disorder due to hemoglobin S GTR C0002895 ICD-10-CM D57 ICD-10-CM D57.0 ICD-10-CM D57.00 ICD-10-CM D57.01 ICD-10-CM D57.02 ICD-10-CM D57.1 ICD-10-CM D57.2 ICD-10-CM D57.20 ICD-10-CM D57.21 ICD-10-CM D57.211 ICD-10-CM D57.212 ICD-10-CM D57.219 ICD-10-CM D57.3 ICD-10-CM D57.4 ICD-10-CM D57.40 ICD-10-CM D57.41 ICD-10-CM D57.411 ICD-10-CM D57.412 ICD-10-CM D57.419 ICD-10-CM D57.8 ICD-10-CM D57.80 ICD-10-CM D57.81 ICD-10-CM D57.811 ICD-10-CM D57.812 ICD-10-CM D57.819 MeSH D000755 OMIM 603903 SNOMED CT 127041004 SNOMED CT 127045008 SNOMED CT 416180004 SNOMED CT 417357006 SNOMED CT 417425009 2024-03 2025-04-03 Silver syndrome https://medlineplus.gov/genetics/condition/silver-syndrome descriptionSilver syndrome belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and, frequently, development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. Both types involve the lower limbs; the complex types may also involve the upper limbs, although to a lesser degree. In addition, the complex types may affect the brain and parts of the nervous system involved in muscle movement and sensations. Silver syndrome is a complex hereditary spastic paraplegia.The first sign of Silver syndrome is usually weakness in the muscles of the hands. These muscles waste away (amyotrophy), resulting in abnormal positioning of the thumbs and difficulty using the fingers and hands for tasks such as handwriting. People with Silver syndrome often have high-arched feet (pes cavus) and spasticity in the legs. The signs and symptoms of Silver syndrome typically begin in late childhood but can start anytime from early childhood to late adulthood. The muscle problems associated with Silver syndrome slowly worsen with age, but affected individuals can remain active throughout life. ad Autosomal dominant BSCL2 https://medlineplus.gov/genetics/gene/bscl2 Silver spastic paraplegia syndrome Spastic paraplegia 17 Spastic paraplegia with amyotrophy of hands and feet SPG17 GTR C0037773 GTR C2931276 ICD-10-CM G11.4 MeSH D015419 OMIM 270685 SNOMED CT 230261006 SNOMED CT 39912006 2012-02 2021-04-27 Silver-Russell syndrome https://medlineplus.gov/genetics/condition/silver-russell-syndrome descriptionSilver-Russell syndrome is a rare disorder that is characterized by slow growth before and after birth. Babies with this condition typically have a low birth weight and often do not grow and gain weight at the expected rate (failure to thrive). Head growth is normal, however, so the head may appear large compared to the rest of the body. In some affected individuals, one side of the body may be bigger than the other.Affected children often have difficulty feeding. Some children develop recurrent episodes of low blood glucose (hypoglycemia). Gastrointestinal problems, such as vomiting and a backflow of stomach acid into the esophagus (called gastroesophageal reflux or GERD), are also common.Adults with Silver-Russell syndrome are typically shorter than average and may have an increased risk of developing metabolic problems such as type 2 diabetes (the most common form of diabetes). Affected individuals often have asymmetric or uneven growth of certain parts of the body, such as the arms and legs. Additional skeletal features may include an unusual curving of the fifth finger (clinodactyly), short fingers (brachydactyly), and abnormal curvature of the spine (scoliosis). Many people with Silver-Russell syndrome have a small, triangular face with distinctive features, including a prominent forehead, a narrow chin, a small jaw, and downturned corners of the mouth. Other features can include the delayed development of motor skills, speech and language problems, and learning disabilities. ad Autosomal dominant+New variant IGF2 https://medlineplus.gov/genetics/gene/igf2 CDKN1C https://medlineplus.gov/genetics/gene/cdkn1c H19 https://medlineplus.gov/genetics/gene/h19 PLAG1 https://www.ncbi.nlm.nih.gov/gene/5324 HMGA2 https://www.ncbi.nlm.nih.gov/gene/8091 7 https://medlineplus.gov/genetics/chromosome/7 11 https://medlineplus.gov/genetics/chromosome/11 RSS Russell-Silver syndrome Silver-Russell dwarfism SRS GTR C4225307 GTR C5393125 GTR C5394446 GTR C5394450 GTR C5394456 GTR C5679840 GTR C5679841 GTR C5680247 GTR C5680916 GTR C5680917 GTR C5681157 MeSH D056730 OMIM 180860 OMIM 616489 OMIM 618905 OMIM 618907 OMIM 618908 SNOMED CT 15069006 2025-03 2025-03-17 Simpson-Golabi-Behmel syndrome https://medlineplus.gov/genetics/condition/simpson-golabi-behmel-syndrome descriptionSimpson-Golabi-Behmel syndrome is a condition that affects many parts of the body and occurs primarily in males. This condition is classified as an overgrowth syndrome, which means that affected infants are considerably larger than normal at birth (macrosomia) and continue to grow and gain weight at an unusual rate. The other signs and symptoms of Simpson-Golabi-Behmel syndrome vary widely. People with mild cases often live into adulthood.People with Simpson-Golabi-Behmel syndrome have distinctive facial features including widely spaced eyes (ocular hypertelorism), an unusually large mouth (macrostomia), a large tongue (macroglossia) that may have a deep groove or furrow down the middle, a broad nose with an upturned tip, and abnormalities affecting the roof of the mouth (the palate). The facial features are often described as "coarse" in older children and adults with this condition.Other features of Simpson-Golabi-Behmel syndrome involve the chest and abdomen. Affected infants may be born with one or more extra nipples, an abnormal opening in the muscle covering the abdomen (diastasis recti), a soft out-pouching around the belly-button (an umbilical hernia), or a hole in the diaphragm (a diaphragmatic hernia) that allows the stomach and intestines to move into the chest and crowd the developing heart and lungs.Simpson-Golabi-Behmel syndrome can also cause heart defects, malformed or abnormally large kidneys, an enlarged liver and spleen (hepatosplenomegaly), and skeletal abnormalities. Additionally, the syndrome can affect the development of the gastrointestinal system, urinary system, and genitalia. Some people with this condition have mild to severe intellectual disability, while others have normal intelligence.About 10 percent of people with Simpson-Golabi-Behmel syndrome develop cancerous or noncancerous tumors in early childhood. The most common tumors are a rare form of kidney cancer called Wilms tumor and a cancerous tumor called a neuroblastoma that arises from developing nerve cells. x X-linked PIGA https://medlineplus.gov/genetics/gene/piga GPC3 https://medlineplus.gov/genetics/gene/gpc3 OFD1 https://medlineplus.gov/genetics/gene/ofd1 GPC4 https://www.ncbi.nlm.nih.gov/gene/2239 DGSX Mental retardation-overgrowth syndrome SDYS SGBS SGBS1 Simpson dysplasia syndrome Simpson syndrome Simpson-Golabi-Behmel syndrome type 1 GTR C0796154 GTR C1846175 MeSH D000015 MeSH D005877 OMIM 300209 OMIM 312870 SNOMED CT 439143004 2017-07 2020-08-18 Sitosterolemia https://medlineplus.gov/genetics/condition/sitosterolemia descriptionSitosterolemia is a condition in which fatty substances (lipids) from vegetable oils, nuts, and other plant-based foods accumulate in the blood and tissues. These lipids are called plant sterols (or phytosterols). Sitosterol is one of several plant sterols that accumulate in this disorder, with a blood level 30 to 100 times greater than normal. Cholesterol, a similar fatty substance found in animal products, is mildly to moderately elevated in many people with sitosterolemia. Cholesterol levels are particularly high in some affected children. However, some people with sitosterolemia have normal cholesterol levels.Plant sterols are not produced by the body; they are taken in as components of foods. Signs and symptoms of sitosterolemia may begin to appear early in life after foods containing plant sterols are introduced into the diet, although some affected individuals have no obvious symptoms.In people with sitosterolemia, accumulation of fatty deposits in arteries (atherosclerosis) can occur as early as childhood. These deposits narrow the arteries and can eventually block blood flow, increasing the chance of a heart attack, stroke, or sudden death.Some people with sitosterolemia develop small yellowish growths called xanthomas beginning in childhood. Xanthomas consist of accumulated lipids and may be located anywhere on or just under the skin, typically on the heels, knees, elbows, and buttocks. They may also occur in the bands that connect muscles to bones (tendons), including tendons of the hand and the tendon that connects the heel of the foot to the calf muscles (the Achilles tendon). Large xanthomas can cause pain, difficulty with movement, and cosmetic problems.Joint stiffness and pain resulting from plant sterol deposits may also occur in individuals with sitosterolemia. Less often, affected individuals have blood abnormalities. Occasionally the blood abnormalities are the only signs of the disorder. The red blood cells may be broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). This type of anemia is called hemolytic anemia. Affected individuals sometimes have abnormally shaped red blood cells called stomatocytes. In addition, the blood cells involved in clotting, called platelets or thrombocytes, may be abnormally large (macrothrombocytopenia). ar Autosomal recessive ABCG5 https://medlineplus.gov/genetics/gene/abcg5 ABCG8 https://medlineplus.gov/genetics/gene/abcg8 Beta-sitosterolemia Phytosterolaemia Phytosterolemia Plant sterol storage disease Sitosterolaemia GTR C0342907 MeSH D008052 OMIM 210250 SNOMED CT 238104009 SNOMED CT 65419005 2013-05 2020-08-18 Sjögren syndrome https://medlineplus.gov/genetics/condition/sjogren-syndrome descriptionSjögren syndrome is a disorder whose main features are dry eyes and a dry mouth. The condition typically develops gradually beginning in middle adulthood but can occur at any age.Sjögren syndrome is classified as an autoimmune disorder, one of a large group of conditions that occur when the immune system attacks the body's own tissues and organs. In Sjögren syndrome, the immune system primarily attacks the glands that produce tears (the lacrimal glands) and saliva (the salivary glands), impairing the glands' ability to secrete these fluids.Dry eyes may lead to itching, burning, a feeling of sand in the eyes, blurry vision, or intolerance of bright or fluorescent lighting. A dry mouth can feel chalky or full of cotton, and affected individuals may have difficulty speaking, tasting food, or swallowing. Because saliva helps protect the teeth and the tissues of the oral cavity, people with Sjögren syndrome are at increased risk of tooth decay and infections in the mouth.In most people with Sjögren syndrome, dry eyes and dry mouth are the primary features of the disorder, and general health and life expectancy are largely unaffected. However, in some cases the immune system also attacks and damages other organs and tissues. This complication is known as extraglandular involvement. Affected individuals may develop inflammation in connective tissues, which provide strength and flexibility to structures throughout the body. Disorders involving connective tissue inflammation are sometimes called rheumatic conditions. In Sjögren syndrome, extraglandular involvement may result in painful inflammation of the joints and muscles; dry, itchy skin and skin rashes; chronic cough; a hoarse voice; kidney and liver problems; numbness or tingling in the hands and feet; and, in women, vaginal dryness. Prolonged and extreme tiredness (fatigue) severe enough to affect activities of daily living may also occur in this disorder. A small number of people with Sjögren syndrome develop lymphoma, a blood-related cancer that causes tumor formation in the lymph nodes but can spread to other organs.Some individuals who are first diagnosed with another rheumatic disorder, such as rheumatoid arthritis or systemic lupus erythematosus, later develop the dry eyes and dry mouth characteristic of Sjögren syndrome. Other autoimmune disorders can also develop after the onset of Sjögren syndrome. In all, about half of all individuals with Sjögren syndrome also have another autoimmune disorder. u Pattern unknown Dacryosialoadenopathia atrophicans Gougerot-Houwer-Sjogren syndrome Gougerot-Sjogren syndrome Keratoconjunctivitis sicca Keratoconjunctivitis sicca-xerostomia Secreto-inhibitor-xerodermostenosis Sicca syndrome Sjogren's syndrome Sjogren-Gougerot syndrome ICD-10-CM M35.0 ICD-10-CM M35.00 ICD-10-CM M35.01 ICD-10-CM M35.02 ICD-10-CM M35.03 ICD-10-CM M35.04 ICD-10-CM M35.09 MeSH D012859 OMIM 270150 SNOMED CT 302896008 SNOMED CT 83901003 2022-02 2025-12-22 Sjögren-Larsson syndrome https://medlineplus.gov/genetics/condition/sjogren-larsson-syndrome descriptionSjögren-Larsson syndrome is a condition that affects the skin and eyes as well as the brain and spinal cord (central nervous system). Infants with Sjögren-Larsson syndrome tend to be born prematurely. At birth, the skin may be thicker than normal (hyperkeratosis) and red (erythema), but it typically becomes dry and scaly (ichthyosis). Mild to severe itchiness (pruritus) is also common. The skin abnormalities generally affect the neck, torso, arms, and legs. The face is usually not affected.Tiny crystals in the light-sensitive tissue at the back of the eye (retina) can be seen during an eye exam in most affected individuals who are older than 3 to 4 years of age. This feature is unique to people with Sjögren-Larsson syndrome and can be used to diagnose the condition. These retinal crystals are often called “glistening white dots.” People with Sjögren-Larsson syndrome may also have nearsightedness (myopia) or an increased sensitivity to light (photophobia).People with Sjögren-Larsson syndrome may have neurological signs and symptoms. Affected individuals often have leukoencephalopathy, which is a change in a type of brain tissue called white matter. White matter consists of nerve fibers that are covered by a substance (myelin) that insulates and protects the nerves. Leukoencephalopathy is thought to contribute to many of the neurological signs and symptoms seen in people with Sjögren-Larsson syndrome.Most people with Sjögren-Larsson syndrome have intellectual disabilities, which can vary from mild to severe. Speech difficulties (dysarthria) are common, and speech development is often delayed. Affected individuals typically have more trouble speaking than understanding language. Approximately 35 to 40 percent of people with Sjögren-Larsson syndrome have seizures.Children with Sjögren-Larsson syndrome typically experience abnormal muscle stiffness (spasticity) in their legs and, less commonly, in their arms. The spasticity may cause a delay in the development of motor skills such as sitting, crawling, and walking. Joint deformities (contractures) are also common. Approximately 50 percent of people with Sjögren-Larsson syndrome will require wheelchair assistance. ar Autosomal recessive ALDH3A2 https://medlineplus.gov/genetics/gene/aldh3a2 FALDH deficiency Fatty acid alcohol oxidoreductase deficiency Fatty alcohol-nicotinamide adenine dinucleotide oxidoreductase deficiency Fatty aldehyde dehydrogenase deficiency Ichthyosis oligophrenia syndrome Ichthyosis, spastic neurologic disorder, and oligophrenia Sjogren-Larsson syndrome SLS GTR C0037231 MeSH D016111 OMIM 270200 SNOMED CT 111303009 2025-12 2025-12-19 Small fiber neuropathy https://medlineplus.gov/genetics/condition/small-fiber-neuropathy descriptionSmall fiber neuropathy is a condition characterized by severe pain attacks that typically begin in the feet or hands. As a person ages, the pain attacks can affect other regions. Some people initially experience a more generalized, whole-body pain. The attacks usually consist of pain described as stabbing or burning, or abnormal skin sensations such as tingling or itchiness. In some individuals, the pain is more severe during times of rest or at night. The signs and symptoms of small fiber neuropathy usually begin in adolescence to mid-adulthood.Individuals with small fiber neuropathy cannot feel pain that is concentrated in a very small area, such as the prick of a pin. However, they have an increased sensitivity to pain in general (hyperalgesia) and experience pain from stimulation that typically does not cause pain (allodynia). People affected with this condition may also have a reduced ability to differentiate between hot and cold. However, in some individuals, the pain attacks are provoked by cold or warm triggers.Some affected individuals have urinary or bowel problems, episodes of rapid heartbeat (palpitations), dry eyes or mouth, or abnormal sweating. They can also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting.Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. ad Autosomal dominant SCN9A https://medlineplus.gov/genetics/gene/scn9a SCN10A https://medlineplus.gov/genetics/gene/scn10a SFN SFNP Small nerve fiber neuropathy GTR C3276706 MeSH D000071075 OMIM 133020 SNOMED CT 709489006 2012-11 2020-08-18 Smith-Kingsmore syndrome https://medlineplus.gov/genetics/condition/smith-kingsmore-syndrome descriptionSmith-Kingsmore syndrome is a neurological disorder characterized by a head that is larger than normal (macrocephaly), intellectual disability, and seizures. In some people with this condition, the ability to speak is delayed or never develops. Some children with Smith-Kingsmore syndrome have neurodevelopmental conditions known as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder, which is characterized by impaired communication and social interaction. Structural brain abnormalities may also be present in affected individuals. For example, one or both sides of the brain may be enlarged (hemimegalencephaly or megalencephaly) or have too many ridges on the surface (polymicrogyria), or the fluid-filled spaces near the center of the brain (ventricles) may be bigger than normal (ventriculomegaly).Many people with Smith-Kingsmore syndrome have unusual facial features, such as a triangular face with a pointed chin, a protruding forehead (frontal bossing), widely spaced eyes (hypertelorism) with outside corners that point downward (downslanting palpebral fissures), a flat nasal bridge, or a long space between the nose and upper lip (long philtrum). However, not everyone with Smith-Kingsmore syndrome has distinctive facial features. ad Autosomal dominant MTOR https://medlineplus.gov/genetics/gene/mtor Macrocephaly, seizures, intellectual disability, umbilical hernia, and facial dysmorphism Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome MINDS syndrome SKS GTR C4225259 MeSH D008607 OMIM 616638 2019-01 2023-08-02 Smith-Lemli-Opitz syndrome https://medlineplus.gov/genetics/condition/smith-lemli-opitz-syndrome descriptionSmith-Lemli-Opitz syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by distinctive facial features, small head size (microcephaly), intellectual disability or learning problems, and behavioral problems. Many affected children have the characteristic features of autism, a developmental condition that affects communication and social interaction. Malformations of the heart, lungs, kidneys, gastrointestinal tract, and genitalia are also common. Infants with Smith-Lemli-Opitz syndrome have weak muscle tone (hypotonia), experience feeding difficulties, and tend to grow more slowly than other infants. Most affected individuals have fused second and third toes (syndactyly), and some have extra fingers or toes (polydactyly).The signs and symptoms of Smith-Lemli-Opitz syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve profound intellectual disability and major physical abnormalities. ar Autosomal recessive DHCR7 https://medlineplus.gov/genetics/gene/dhcr7 7-dehydrocholesterol reductase deficiency RSH Syndrome SLO syndrome SLOS GTR C0175694 ICD-10-CM E78.72 MeSH D019082 OMIM 270400 SNOMED CT 43929004 2007-07 2020-08-18 Smith-Magenis syndrome https://medlineplus.gov/genetics/condition/smith-magenis-syndrome descriptionSmith-Magenis syndrome is a developmental disorder that affects behavior, emotions, and learning processes. The major features of this condition include distinctive facial features, sleep disturbances, behavioral problems, mild to moderate intellectual disability, and delayed speech and language skills.Most people with Smith-Magenis syndrome have a broad, square-shaped face with deep-set eyes, full cheeks, and a prominent lower jaw. The middle of the face and the bridge of the nose often appear flattened. The mouth tends to turn downward with a full, outward-curving upper lip. These facial differences can be subtle in early childhood, but they usually become more distinctive in later childhood and adulthood. Dental abnormalities are also common in affected individuals.Disrupted sleep patterns are characteristic of Smith-Magenis syndrome, and they typically begin early in life. Affected people may have trouble falling asleep at night and awaken several times during the night and early morning. They may be very sleepy during the day.People with Smith-Magenis syndrome typically have affectionate, engaging personalities, but most also have behavioral problems. These include frequent temper tantrums and outbursts, aggression, anxiety, impulsiveness, and difficulty paying attention. Self-injury, including biting, hitting, head banging, and skin picking, is very common. People with Smith-Magenis syndrome may have other behaviors, such as repetitive self-hugging or compulsively licking their fingers and flipping pages of books and magazines (a behavior known as "lick and flip").Other signs and symptoms of Smith-Magenis syndrome include short stature, abnormal curvature of the spine (scoliosis), obesity, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia) and other vision problems. Although less common, heart and kidney defects also have been reported in people with Smith-Magenis syndrome. n Not inherited RAI1 https://medlineplus.gov/genetics/gene/rai1 17 https://medlineplus.gov/genetics/chromosome/17 17p- syndrome 17p11.2 monosomy Chromosome 17p deletion syndrome Deletion 17p syndrome Partial monosomy 17p SMS GTR C0795864 MeSH D058496 OMIM 182290 SNOMED CT 401315004 2017-10 2023-05-04 Snijders Blok-Campeau syndrome https://medlineplus.gov/genetics/condition/snijders-blok-campeau-syndrome descriptionSnijders Blok-Campeau syndrome is characterized by intellectual disability, speech problems, and distinctive facial features.Intellectual disability in individuals with Snijders Blok-Campeau syndrome ranges from mild to severe. Some people with this condition also have low muscle tone (hypotonia), seizures, or autistic behaviors that affect communication and social interaction.While some people with Snijders Blok-Campeau syndrome develop limited language, others acquire only a few words or never speak. If speech occurs, it usually develops after age 2. Affected individuals can experience stuttering, problems coordinating movements of the mouth and tongue (oromotor dysfunction), or difficulty producing the sequences of sounds and syllables needed to form words (apraxia). In general, people with this condition have a very social personality.Individuals with Snijders Blok-Campeau syndrome have distinctive facial features. The eyes are frequently affected, and features often include widely spaced eyes (ocular hypertelorism), deep-set eyes, narrowed openings of the eyes (narrowed palpebral fissures), an increased distance between the inner corners of the eyes (telecanthus), and sparse eyebrows. Additional facial features can include full cheeks, a pointed chin, a prominent forehead (frontal bossing), a sunken appearance of the middle of the face (midface hypoplasia), a broad nasal bridge, low-set ears that may be rotated backward, and a thin upper lip. Affected individuals often have an abnormally sized head; most have an unusually large head (macrocephaly), though some have an unusually small head (microcephaly). Some people with Snijders Blok-Campeau syndrome have premature closure of certain bones of the skull (craniosynostosis), which can contribute to an abnormal head shape.Most individuals with Snijders Blok-Campeau syndrome have vision problems, including farsightedness (hyperopia) or eyes that do not look in the same direction (strabismus).About half of people with Snijders Blok-Campeau syndrome have brain abnormalities, such as enlarged spaces in the brain where cerebrospinal fluid (CSF) accumulates. Less commonly, affected individuals are born with a hole between the two upper chambers of the heart (atrial septal defect) or another problem with the heart's structure or function (congenital heart disease). ad Autosomal dominant CHD3 https://medlineplus.gov/genetics/gene/chd3 IDDMSF Intellectual developmental disorder with macrocephaly, speech delay, and dysmorphic facies SNIBCPS MeSH D001072 MeSH D008607 OMIM 618205 2020-06 2020-08-18 Snyder-Robinson syndrome https://medlineplus.gov/genetics/condition/snyder-robinson-syndrome descriptionSnyder-Robinson syndrome is a condition characterized by intellectual disability, muscle and bone abnormalities, and other problems with development. It occurs exclusively in males.Males with Snyder-Robinson syndrome have delayed development and intellectual disability beginning in early childhood. The intellectual disability can range from mild to profound. Speech often develops late, and speech difficulties are common. Some affected individuals never develop any speech.Most affected males are thin and have low muscle mass, a body type described as an asthenic habitus. Weakness or "floppiness" (hypotonia) typically becomes apparent in infancy, and the loss of muscle tissue continues with age. People with this condition often have difficulty walking; most have an unsteady gait.Snyder-Robinson syndrome causes skeletal problems, particularly thinning of the bones (osteoporosis) that starts in early childhood. Osteoporosis causes the bones to be brittle and to break easily, often during normal activities. In people with Snyder-Robinson syndrome, broken bones occur most often in the arms and legs. Most affected individuals also develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family.Snyder-Robinson syndrome is associated with distinctive facial features, including a prominent lower lip; a high, narrow roof of the mouth or an opening in the roof of the mouth (a cleft palate); and differences in the size and shape of the right and left sides of the face (facial asymmetry). Other signs and symptoms that have been reported include seizures that begin in childhood and abnormalities of the genitalia and kidneys. xr X-linked recessive SMS https://medlineplus.gov/genetics/gene/sms Mental retardation, X-linked, syndromic, Snyder-Robinson type Snyder-Robinson X-linked mental retardation syndrome Spermine synthase deficiency SRS GTR C0796160 MeSH D002658 MeSH D038901 OMIM 309583 SNOMED CT 702416008 2013-08 2020-08-18 Sotos syndrome https://medlineplus.gov/genetics/condition/sotos-syndrome descriptionSotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin.  In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.People with Sotos syndrome often have intellectual disability, and most also have neurodevelopmental disorders. Conditions that commonly occur in people with Sotos syndrome include autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common.  Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population. ad Autosomal dominant NSD1 https://medlineplus.gov/genetics/gene/nsd1 Cerebral gigantism Sotos sequence Sotos' syndrome GTR C0175695 ICD-10-CM E22.0 MeSH D058495 OMIM 117550 SNOMED CT 75968004 2015-02 2023-11-07 Spastic paraplegia type 11 https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-11 descriptionSpastic paraplegia type 11 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can affect the upper limbs to a lesser degree. Complex spastic paraplegias also affect the structure or functioning of the brain and the peripheral nervous system, which consists of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Spastic paraplegia type 11 is a complex hereditary spastic paraplegia.Like all hereditary spastic paraplegias, spastic paraplegia type 11 involves spasticity of the leg muscles and muscle weakness. In almost all individuals with this type of spastic paraplegia, the tissue connecting the left and right halves of the brain (corpus callosum) is abnormally thin. People with this form of spastic paraplegia can also experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); disturbance in the nerves used for muscle movement (motor neuropathy); intellectual disability; exaggerated reflexes (hyperreflexia) of the lower limbs; speech difficulties (dysarthria); reduced bladder control; and muscle wasting (amyotrophy). Less common features include difficulty swallowing (dysphagia), high-arched feet (pes cavus), an abnormal curvature of the spine (scoliosis), and involuntary movements of the eyes (nystagmus). The onset of symptoms varies greatly; however, abnormalities in muscle tone and difficulty walking usually become noticeable in adolescence.Many features of spastic paraplegia type 11 are progressive. Most people experience a decline in intellectual ability and an increase in muscle weakness and nerve abnormalities over time. As the condition progresses, some people require wheelchair assistance. ar Autosomal recessive SPG11 https://medlineplus.gov/genetics/gene/spg11 Autosomal recessive spastic paraplegia complicated with thin corpus callosum Autosomal recessive spastic paraplegia with mental impairment and thin corpus callosum HSP-TCC SPG11-related hereditary spastic paraplegia with thin corpus callosum GTR C0037773 GTR C1858479 ICD-10-CM G11.4 MeSH D010264 MeSH D015419 OMIM 604360 SNOMED CT 715491000 2009-04 2021-04-27 Spastic paraplegia type 15 https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-15 descriptionSpastic paraplegia type 15 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Spastic paraplegia type 15 is classified as a complex hereditary spastic paraplegia because it involves all four limbs as well as additional features, including abnormalities of the brain. In addition to the muscles and brain, spastic paraplegia type 15 affects the peripheral nervous system, which consists of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound.Spastic paraplegia type 15 usually becomes apparent in childhood or adolescence with the development of weak muscle tone (hypotonia), difficulty walking, or intellectual disability. In almost all affected individuals, the tissue connecting the left and right halves of the brain (corpus callosum) is abnormally thin and becomes thinner over time. Additionally, there is often a loss (atrophy) of nerve cells in several parts of the brain, including the cerebral cortex, which controls thinking and emotions, and the cerebellum, which coordinates movement.People with this form of spastic paraplegia can have numbness, tingling, or pain in the arms and legs (sensory neuropathy); impairment of the nerves used for muscle movement (motor neuropathy); exaggerated reflexes (hyperreflexia) of the lower limbs; muscle wasting (amyotrophy); or reduced bladder control. Rarely, spastic paraplegia type 15 is associated with a group of movement abnormalities called parkinsonism, which includes tremors, rigidity, and unusually slow movement (bradykinesia). People with spastic paraplegia type 15 may have an eye condition called pigmentary maculopathy that often impairs vision. This condition results from the breakdown (degeneration) of tissue at the back of the eye called the macula, which is responsible for sharp central vision.Most people with spastic paraplegia type 15 experience a decline in intellectual ability and an increase in muscle weakness and nerve abnormalities over time. As the condition progresses, many people require walking aids or wheelchair assistance in adulthood. ar Autosomal recessive ZFYVE26 https://medlineplus.gov/genetics/gene/zfyve26 Autosomal recessive spastic paraplegia 15 Kjellin syndrome Spastic paraplegia and retinal degeneration SPG15 GTR C0037773 GTR C1849128 ICD-10-CM G11.4 MeSH D015419 OMIM 270700 SNOMED CT 709417000 2014-04 2021-06-15 Spastic paraplegia type 2 https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-2 descriptionSpastic paraplegia type 2 belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by muscle stiffness (spasticity) and weakness that worsens over time and paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure (also called uncomplicated) types only involve the legs. The complex (also called complicated) types involve the lower limbs and can also affect the upper limbs to a lesser degree. The complex type can also affect the structure or function of the brain. It can also affect the network of nerves (the peripheral nervous system) that connects the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Spastic paraplegia type 2 can be classified as either pure or complex, depending on the signs and symptoms. The pure type of this condition is more common. The complex type of spastic paraplegia type 2 is sometimes called hypomyelination of early myelinating structures (HEMS).People with the pure type of spastic paraplegia type 2 experience spasticity in the leg muscles. Over time, affected individuals may lose the ability to walk. Some affected individuals may also have poor bladder control. The signs and symptoms of spastic paraplegia type 2 usually appear between the ages of 1 and 5 years, but it can develop later in life. Individuals with spastic paraplegia type 2 typically have a normal lifespan.In addition to leg spasticity and poor bladder control, people with HEMS can also experience problems with movement and balance (ataxia); involuntary movements of the eyes (nystagmus); and involuntary, rhythmic shaking (tremor). They may also have mild intellectual disabilities and degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. The signs and symptoms of HEMS also typically appear between the ages of 1 and 5 years. Individuals with HEMS usually survive into mid to late adulthood. x X-linked PLP1 https://medlineplus.gov/genetics/gene/plp1 Hereditary spastic paraplegia type 2 PLP1 hereditary spastic paraplegia Spastic paraparesis type 2 Spastic paraplegia 2 SPG2 X-linked spastic paraplegia 2 X-linked spastic paraplegia type 2 GTR C0751604 ICD-10-CM G11.4 MeSH D010264 MeSH D015419 OMIM 312920 SNOMED CT 723622007 2025-09 2025-09-04 Spastic paraplegia type 31 https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-31 descriptionSpastic paraplegia type 31 is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia) caused by degeneration of nerve cells that trigger muscle movement (motor neurons). Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only the lower limbs, while the complicated types also involve the upper limbs and other areas of the body, including the brain. Spastic paraplegia type 31 is usually a pure hereditary spastic paraplegia, although a few complicated cases have been reported.The first signs and symptoms of spastic paraplegia type 31 usually appear before age 20 or after age 30. An early feature is difficulty walking due to spasticity and weakness, which typically affect both legs equally. People with spastic paraplegia type 31 can also experience progressive muscle wasting (amyotrophy) in the lower limbs, exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, reduced bladder control, and high-arched feet (pes cavus). As the condition progresses, some individuals require walking support. ad Autosomal dominant REEP1 https://medlineplus.gov/genetics/gene/reep1 Autosomal dominant spastic paraplegia 31 Spastic paraplegia 31 SPG31 GTR C0037773 GTR C1853247 ICD-10-CM G11.4 MeSH D015419 OMIM 610250 SNOMED CT 230260007 2015-04 2021-04-27 Spastic paraplegia type 3A https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-3a descriptionSpastic paraplegia type 3A is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by muscle stiffness (spasticity) and weakness in the lower limbs (paraplegia). Hereditary spastic paraplegias are often divided into two types: pure and complex. The pure types involve only the lower limbs, while the complex types also involve other areas of the body; additional features can include changes in vision, changes in intellectual functioning, difficulty walking, and disturbances in nerve function (neuropathy). Spastic paraplegia type 3A is usually a pure hereditary spastic paraplegia, although a few complex cases have been reported.In addition to spasticity and weakness, which typically affect both legs equally, people with spastic paraplegia type 3A can also experience progressive muscle wasting (amyotrophy) in the lower limbs, reduced bladder control, an abnormal curvature of the spine (scoliosis), loss of sensation in the feet (peripheral neuropathy), or high arches of the feet (pes cavus). The signs and symptoms of spastic paraplegia type 3A usually appear before the age of 10; the average age of onset is 4 years. In some affected individuals the condition slowly worsens over time, sometimes leading to a need for walking support. ad Autosomal dominant ATL1 https://medlineplus.gov/genetics/gene/atl1 Spastic paraplegia 3 Spastic paraplegia 3A SPG3A GTR C0037773 GTR C2931355 ICD-10-CM G11.4 MeSH D015419 OMIM 182600 SNOMED CT 39912006 2015-03 2021-04-27 Spastic paraplegia type 4 https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-4 descriptionSpastic paraplegia type 4 (also known as SPG4) is the most common of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) in the legs and difficulty walking. Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types generally involve only spasticity of the lower limbs and walking difficulties. The complex types involve more widespread problems with the nervous system; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). In complex forms, there can also be features outside of the nervous system. Spastic paraplegia type 4 is usually a pure hereditary spastic paraplegia, although a few complex cases have been reported.Like all hereditary spastic paraplegias, spastic paraplegia type 4 involves spasticity of the leg muscles and muscle weakness. People with this condition can also experience exaggerated reflexes (hyperreflexia), ankle spasms, high-arched feet (pes cavus), and reduced bladder control. Spastic paraplegia type 4 generally affects nerve and muscle function in the lower half of the body only. ad Autosomal dominant SPAST https://medlineplus.gov/genetics/gene/spast Spastic paraplegia 4 SPG4 GTR C0037773 GTR C1866855 ICD-10-CM G11.4 MeSH D010264 MeSH D015419 OMIM 182601 SNOMED CT 230260007 2020-07 2021-04-27 Spastic paraplegia type 49 https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-49 descriptionSpastic paraplegia type 49 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the lower limbs, whereas the complex types also involve the upper limbs (to a lesser degree) and other problems with the nervous system. Spastic paraplegia type 49 is a complex hereditary spastic paraplegia.Spastic paraplegia type 49 often begins with weak muscle tone (hypotonia) that starts in infancy. During childhood, spasticity and paraplegia develop and gradually worsen, causing difficulty walking and frequent falls. In addition, affected individuals have moderate to severe intellectual disability and distinctive physical features, including short stature; chubbiness; an unusually small head size (microcephaly); a wide, short skull (brachycephaly); a short, broad neck; and facial features described as coarse. Some people with spastic paraplegia type 49 develop seizures.Problems with autonomic nerve cells (autonomic neurons), which control involuntary body functions such as heart rate, digestion, and breathing, result in several features of spastic paraplegia type 49. Affected individuals have difficulty feeding beginning in infancy. They experience a backflow of stomach acids into the esophagus (called gastroesophageal reflux or GERD), causing vomiting. GERD can also lead to recurrent bacterial lung infections called aspiration pneumonia, which can be life-threatening. In addition, people with spastic paraplegia type 49 have problems regulating their breathing, resulting in pauses in breathing (apnea), initially while sleeping but eventually also while awake. Their blood pressure, pulse rate, and body temperature are also irregular.People with spastic paraplegia type 49 can develop recurrent episodes of severe weakness, hypotonia, and abnormal breathing, which can be life threatening. By early adulthood, some affected individuals need a machine to help them breathe (mechanical ventilation).Other signs and symptoms of spastic paraplegia type 49 reflect problems with sensory neurons, which transmit information about sensations such as pain, temperature, and touch to the brain. Many affected individuals are less able to feel pain or temperature sensations than individuals in the general population. Affected individuals also have abnormal or absent reflexes (areflexia).Because of the nervous system abnormalities that occur in spastic paraplegia type 49, it has been suggested that the condition also be classified as a hereditary sensory and autonomic neuropathy, which is a group of conditions that affect sensory and autonomic neurons. ar Autosomal recessive TECPR2 https://medlineplus.gov/genetics/gene/tecpr2 Autosomal recessive spastic paraplegia type 49 Spastic paraplegia 49, autosomal recessive SPG49 GTR C0037773 GTR C3542549 MeSH D009477 MeSH D015419 OMIM 615031 2018-06 2021-04-27 Spastic paraplegia type 5A https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-5a descriptionSpastic paraplegia type 5A belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by muscle stiffness (spasticity) and severe weakness in the lower limbs (paraplegia). Hereditary spastic paraplegias are often divided into two types: pure and complex. The pure types involve spasticity and weakness only in the lower limbs, while the complex types involve additional problems with other areas of the body. Additional features can include changes in vision, changes in intellectual functioning, brain abnormalities, and disturbances in nerve function (neuropathy). Spastic paraplegia type 5A is usually classified as a pure hereditary spastic paraplegia, although complex-type features have been reported in some individuals.The signs and symptoms of spastic paraplegia type 5A usually appear in adolescence, but they can begin at any time between infancy and mid-adulthood. In addition to spasticity and weakness, people with spastic paraplegia type 5A can lose the ability to sense the position of their limbs or detect vibrations with their lower limbs. They may also have muscle wasting (amyotrophy), reduced bladder control, or high arches of the feet (pes cavus). Some affected individuals have low bone density (osteopenia) or vitamin D deficiency. Affected individuals eventually require walking support, usually around 20 years after symptoms begin, or wheelchair assistance, around 30 years after symptoms begin. ar Autosomal recessive CYP7B1 https://medlineplus.gov/genetics/gene/cyp7b1 Autosomal recessive spastic paraplegia 5A Spastic paraplegia 5 Spastic paraplegia 5A SPG5 SPG5A GTR C0037773 GTR C1849115 ICD-10-CM G11.4 MeSH D015419 OMIM 270800 SNOMED CT 39912006 2026-03 2026-03-19 Spastic paraplegia type 7 https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-7 descriptionSpastic paraplegia type 7 (also called SPG7) is one of more than 80 genetic disorders known as hereditary spastic paraplegias. These disorders primarily affect the brain and spinal cord (central nervous system),specifically nerve cells (neurons) that extend down the spinal cord. These neurons are used for muscle movement and sensation.Signs and symptoms of hereditary spastic paraplegias are characterized by progressive muscle stiffness (spasticity) in the legs and difficulty walking. Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types generally involve only spasticity of the lower limbs and walking difficulties. The complex types involve more widespread problems with the nervous system; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). In complex forms, there can also be features outside of the nervous system. Spastic paraplegia type 7 can occur in either the pure or complex form.Like all hereditary spastic paraplegias, spastic paraplegia type 7 involves spasticity of the leg muscles and some muscle weakness. People with this form of spastic paraplegia can also have ataxia; a pattern of movement abnormalities known as parkinsonism; exaggerated reflexes (hyperreflexia) in the arms; speech difficulties (dysarthria); difficulty swallowing (dysphagia); involuntary movements of the eyes (nystagmus); mild hearing loss; abnormal curvature of the spine (scoliosis); high-arched feet (pes cavus); numbness, tingling, or pain in the arms and legs (sensory neuropathy); disturbance in the nerves used for muscle movement (motor neuropathy); and muscle wasting (amyotrophy). The onset of symptoms varies greatly among those with spastic paraplegia type 7; however, abnormalities in muscle tone and other features usually become noticeable in adulthood. ar Autosomal recessive SPG7 https://medlineplus.gov/genetics/gene/spg7 Hereditary spastic paraplegia, paraplegin type Spastic paraplegia 7 GTR C0037773 GTR C1846564 ICD-10-CM G11.4 MeSH D010264 MeSH D015419 OMIM 607259 SNOMED CT 715776003 2020-07 2021-06-25 Spastic paraplegia type 8 https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-8 descriptionSpastic paraplegia type 8 belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and weakness. Hereditary spastic paraplegias are divided into two types: pure and complex. The pure (also called uncomplicated) types involve only the nerves and muscles that control the legs and bladder, whereas the complex (also called complicated) types also involve the nervous system in other parts of the body. Spastic paraplegia type 8 is a pure hereditary spastic paraplegia.People with spastic paraplegia type 8 have spasticity and weakness of the leg muscles. Affected individuals may also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, and reduced bladder control. The signs and symptoms of spastic paraplegia type 8 can begin in childhood, although they typically appear in early to mid-adulthood. People with spastic paraplegia type 8 tend to be more severely affected than those with other types of hereditary spastic paraplegias; affected individuals typically require wheelchair assistance in adulthood. However, the signs and symptoms of spastic paraplegia type 8 can vary, even among members of the same family. ad Autosomal dominant+Inherited or new variant WASHC5 https://medlineplus.gov/genetics/gene/washc5 Autosomal dominant spastic paraplegia 8 Hereditary spastic paraplegia 8 Spastic paraplegia 8 SPG8 GTR C0037773 GTR C1863704 ICD-10-CM G11.4 MeSH D010264 MeSH D015419 OMIM 603563 SNOMED CT 230260007 2024-07 2024-07-30 Spina bifida https://medlineplus.gov/genetics/condition/spina-bifida descriptionSpina bifida is a condition in which the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. As a result, when the spine forms, the bones of the spinal column do not close completely around the developing nerves of the spinal cord. Part of the spinal cord may stick out through an opening in the spine, leading to permanent nerve damage. Because spina bifida is caused by abnormalities of the neural tube, it is classified as a neural tube defect.Children born with spina bifida often have a fluid-filled sac on their back that is covered by skin, called a meningocele. If the sac contains part of the spinal cord and its protective covering, it is known as a myelomeningocele. The signs and symptoms of these abnormalities range from mild to severe, depending on where the opening in the spinal column is located and how much of the spinal cord is contained in the sac. Related problems can include a loss of feeling below the level of the opening, weakness or paralysis of the feet or legs, and problems with bladder and bowel control. Some affected individuals have additional complications, including a buildup of excess fluid around the brain (hydrocephalus) and learning problems. With surgery and other forms of treatment, many people with spina bifida live into adulthood.In a milder form of the condition, called spina bifida occulta, the bones of the spinal column are abnormally formed, but the nerves of the spinal cord usually develop normally. Unlike in the more severe form of spina bifida, the spinal cord does not stick out through an opening in the spine. Spina bifida occulta most often causes no health problems, although rarely it can cause back pain or changes in bladder function. u Pattern unknown MTHFR https://medlineplus.gov/genetics/gene/mthfr Cleft spine Open spine Rachischisis Spinal dysraphism GTR C0027794 GTR C1866558 ICD-10-CM Q05 ICD-10-CM Q05.0 ICD-10-CM Q05.1 ICD-10-CM Q05.2 ICD-10-CM Q05.3 ICD-10-CM Q05.4 ICD-10-CM Q05.5 ICD-10-CM Q05.6 ICD-10-CM Q05.7 ICD-10-CM Q05.8 ICD-10-CM Q05.9 ICD-10-CM Q07.01 ICD-10-CM Q07.03 ICD-10-CM Q76.0 MeSH D016135 OMIM 182940 OMIM 601634 SNOMED CT 61819007 SNOMED CT 67531005 2014-11 2024-12-16 Spinal and bulbar muscular atrophy https://medlineplus.gov/genetics/condition/spinal-and-bulbar-muscular-atrophy descriptionSpinal and bulbar muscular atrophy, also known as Kennedy disease, is a disorder of specialized nerve cells that control muscle movement (motor neurons). These nerve cells originate in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem).Spinal and bulbar muscular atrophy mainly affects males and is characterized by muscle weakness and wasting (atrophy) that usually begins in adulthood and worsens slowly over time. Muscle wasting in the arms and legs results in cramping; leg muscle weakness can also lead to difficulty walking and a tendency to fall. Certain muscles in the face and throat (bulbar muscles) are also affected, which causes progressive problems with swallowing and speech. Additionally, muscle twitches (fasciculations) are common. Some males with the disorder experience unusual breast development (gynecomastia) and may be unable to father a child (infertile). xr X-linked recessive AR https://medlineplus.gov/genetics/gene/ar Bulbospinal muscular atrophy, X-linked KD Kennedy disease Kennedy spinal and bulbar muscular atrophy Kennedy's disease SBMA X-linked spinal and bulbar muscular atrophy GTR C1839259 MeSH D055534 OMIM 313200 SNOMED CT 230253001 2006-05 2020-08-18 Spinal muscular atrophy https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy descriptionSpinal muscular atrophy is a genetic disorder characterized by weakness and wasting (atrophy) in muscles used for movement (skeletal muscles). It is caused by a loss of specialized nerve cells, called motor neurons that control muscle movement. The weakness tends to be more severe in the muscles that are close to the center of the body (proximal) compared to muscles away from the body's center (distal). The muscle weakness usually worsens with age. There are many types of spinal muscular atrophy that are caused by changes in the same genes. The types differ in age of onset and severity of muscle weakness; however, there is overlap between the types. Other forms of spinal muscular atrophy and related motor neuron diseases, such as spinal muscular atrophy with progressive myoclonic epilepsy, spinal muscular atrophy with lower extremity predominance, X-linked infantile spinal muscular atrophy, and spinal muscular atrophy with respiratory distress type 1 are caused by mutations in other genes.Spinal muscular atrophy type 0 is evident before birth and is the rarest and most severe form of the condition. Affected infants move less in the womb, and as a result they are often born with joint deformities (contractures). They have extremely weak muscle tone (hypotonia) at birth. Their respiratory muscles are very weak and they often do not survive past infancy due to respiratory failure. Some infants with spinal muscular atrophy type 0 also have heart defects that are present from birth (congenital).Spinal muscular atrophy type I (also called Werdnig-Hoffmann disease) is the most common form of the condition. It is a severe form of the disorder with muscle weakness evident at birth or within the first few months of life. Most affected children cannot control their head movements or sit unassisted. Children with this type may have swallowing problems that can lead to difficulty feeding and poor growth. They can also have breathing problems due to weakness of respiratory muscles and an abnormally bell-shaped chest that prevents the lungs from fully expanding. Most children with spinal muscular atrophy type I do not survive past early childhood due to respiratory failure.Spinal muscular atrophy type II (also called Dubowitz disease) is characterized by muscle weakness that develops in children between ages 6 and 12 months. Children with this type can sit without support, although they may need help getting to a seated position. However, as the muscle weakness worsens later in childhood, affected individuals may need support to sit. Individuals with spinal muscular atrophy type II cannot stand or walk unaided. They often have involuntary trembling (tremors) in their fingers, a spine that curves side-to-side (scoliosis), and respiratory muscle weakness that can be life-threatening. The life span of individuals with spinal muscular atrophy type II varies, but many people with this condition live into their twenties or thirties.Spinal muscular atrophy type III (also called Kugelberg-Welander disease) typically causes muscle weakness after early childhood. Individuals with this condition can stand and walk unaided, but over time, walking and climbing stairs may become increasingly difficult. Many affected individuals require wheelchair assistance later in life. People with spinal muscular atrophy type III typically have a normal life expectancy.Spinal muscular atrophy type IV is rare and often begins in early adulthood. Affected individuals usually experience mild to moderate muscle weakness, tremors, and mild breathing problems. People with spinal muscular atrophy type IV have a normal life expectancy. ar Autosomal recessive SMN1 https://medlineplus.gov/genetics/gene/smn1 SMN2 https://medlineplus.gov/genetics/gene/smn2 5q SMA Proximal SMA SMA SMA-associated SMA Spinal amyotrophies Spinal amyotrophy Spinal muscle degeneration Spinal muscle wasting GTR C0152109 GTR C0393538 GTR C1838230 GTR C5848259 ICD-10-CM G12.0 ICD-10-CM G12.1 MeSH D009134 OMIM 253300 OMIM 253400 OMIM 253550 OMIM 271150 SNOMED CT 128212001 SNOMED CT 5262007 SNOMED CT 54280009 SNOMED CT 64383006 SNOMED CT 85505000 2018-07 2023-11-07 Spinal muscular atrophy with lower extremity predominance https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy-with-lower-extremity-predominance descriptionSpinal muscular atrophy with lower extremity predominance (SMA-LED) is characterized by muscle weakness and wasting (atrophy) in the lower limbs, most severely affecting the thigh muscles (quadriceps). (In SMA-LED, the "D" stands for dominant, which refers to the inheritance pattern of this condition.) The loss of nerve cells that control muscle movement (motor neurons) leads to atrophy of the muscles in the lower limbs. Affected individuals often have a waddling or unsteady walk and walk on the balls of their feet. They may have difficulty rising from a seated position and climbing stairs. Some people with SMA-LED also have weakness in upper limb muscles.Joint deformities (contractures) in the hips, knees, feet, and ankles can occur in SMA-LED, and in severe cases are present from birth and can impair walking. Some individuals with this disorder have rigidity of joints (arthrogryposis) in their shoulders, elbows, and hands.In most people with SMA-LED, the muscle problems are apparent in infancy or early childhood; however, about one-quarter of affected individuals do not develop muscle weakness until adulthood. The muscle weakness and related health problems typically do not worsen over time. ad Autosomal dominant DYNC1H1 https://medlineplus.gov/genetics/gene/dync1h1 BICD2 https://medlineplus.gov/genetics/gene/bicd2 Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Kugelberg-Welander syndrome, autosomal dominant Lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures SMA-LED Spinal muscular atrophy, childhood, proximal, autosomal dominant Spinal muscular atrophy, juvenile, proximal, autosomal dominant Spinal muscular atrophy, lower extremity, autosomal dominant Spinal muscular atrophy, lower extremity, dominant GTR C1834690 MeSH D014897 OMIM 158600 OMIM 615290 SNOMED CT 5262007 2018-05 2020-08-18 Spinal muscular atrophy with progressive myoclonic epilepsy https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy descriptionSpinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that begins in childhood. SMA-PME causes muscle weakness and wasting (atrophy) and a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy).In individuals with SMA-PME, spinal muscular atrophy results from a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). After a few years of normal development, affected children begin experiencing muscle weakness and atrophy in the lower limbs, causing difficulty walking and frequent falls. The muscles in the upper limbs are later affected, and soon the muscle weakness and atrophy spreads throughout the body. Once weakness reaches the muscles used for breathing and swallowing, affected individuals develop life-threatening breathing problems and increased susceptibility to pneumonia.A few years after the muscle weakness begins, affected individuals start to experience recurrent seizures (epilepsy). Most people with SMA-PME have a variety of seizure types. In addition to myoclonic epilepsy, they may have  generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Affected individuals can also have absence seizures, which cause loss of consciousness for a short period that may or may not be accompanied by muscle jerks. In SMA-PME, seizures often increase in frequency over time and are usually not well-controlled with medication. Individuals with SMA-PME may also have episodes of rhythmic shaking (tremors), usually in the hands; these tremors are not thought to be related to epilepsy. Some people with SMA-PME develop hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss).Individuals with SMA-PME have a shortened lifespan; they generally live into late childhood or early adulthood. Near the end of their lives, affected individuals often have limited mobility, difficulty swallowing, and decline in cognitive functioning. The cause of death is often respiratory failure or pneumonia. ar Autosomal recessive ASAH1 https://medlineplus.gov/genetics/gene/asah1 Hereditary myoclonus with progressive distal muscular atrophy Jankovic-Rivera syndrome SMA-PME SMAPME GTR C1834569 MeSH D009134 MeSH D020191 OMIM 159950 SNOMED CT 703524005 2013-12 2022-05-23 Spinal muscular atrophy with respiratory distress type 1 https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy-with-respiratory-distress-type-1 descriptionSpinal muscular atrophy with respiratory distress type 1 (SMARD1) is an inherited condition that causes muscle weakness and respiratory failure typically beginning in infancy. Early features of this condition are difficult and noisy breathing, especially when inhaling; a weak cry; problems feeding; and recurrent episodes of pneumonia. Typically between the ages of 6 weeks and 6 months, infants with this condition will experience a sudden inability to breathe due to paralysis of the muscle that separates the abdomen from the chest cavity (the diaphragm). Normally, the diaphragm contracts and moves downward during inhalation to allow the lungs to expand. With diaphragm paralysis, affected individuals require life-long support with a machine to help them breathe (mechanical ventilation). Rarely, children with SMARD1 develop signs or symptoms of the disorder later in childhood.Soon after respiratory failure occurs, individuals with SMARD1 develop muscle weakness in their distal muscles. These are the muscles farther from the center of the body, such as muscles in the hands and feet. The weakness soon spreads to all muscles; however, within 2 years, the muscle weakness typically stops getting worse. Some individuals may retain a low level of muscle function, while others lose all ability to move their muscles. Muscle weakness severely impairs motor development, such as sitting, standing, and walking. Some affected children develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). After approximately the first year of life, individuals with SMARD1 may lose their deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.Other features of SMARD1 can include reduced pain sensitivity, excessive sweating (hyperhidrosis), loss of bladder and bowel control, and an irregular heartbeat (arrhythmia). ar Autosomal recessive IGHMBP2 https://medlineplus.gov/genetics/gene/ighmbp2 Autosomal recessive distal spinal muscular atrophy 1 DHMN6 Diaphragmatic spinal muscular atrophy Distal hereditary motor neuronopathy type VI Distal spinal muscular atrophy type 1 DSMA1 HMN6 HMNVI Severe infantile axonal neuropathy with respiratory failure SIANRF SMARD1 Spinal muscular atrophy with respiratory distress GTR C1858517 MeSH D014897 OMIM 604320 SNOMED CT 711483003 2013-01 2020-08-18 Spinocerebellar ataxia type 1 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-1 descriptionSpinocerebellar ataxia type 1 (SCA1) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other signs and symptoms of SCA1 include speech and swallowing difficulties, muscle stiffness (spasticity), and weakness in the muscles that control eye movement (ophthalmoplegia). Eye muscle weakness leads to rapid, involuntary eye movements (nystagmus). Individuals with SCA1 may have difficulty processing, learning, and remembering information (cognitive impairment).Over time, individuals with SCA1 may develop numbness, tingling, or pain in the arms and legs (sensory neuropathy); uncontrolled muscle tensing (dystonia); muscle wasting (atrophy); and muscle twitches (fasciculations). Rarely, rigidity, tremors, and involuntary jerking movements (chorea) have been reported in people who have been affected for many years.Signs and symptoms of the disorder typically begin in early adulthood but can appear anytime from childhood to late adulthood. People with SCA1 typically survive 10 to 20 years after symptoms first appear. ad Autosomal dominant ATXN1 https://medlineplus.gov/genetics/gene/atxn1 Olivopontocerebellar atrophy I SCA1 Spinocerebellar atrophy I Type 1 spinocerebellar ataxia GTR C0752120 MeSH D020754 OMIM 164400 SNOMED CT 715748006 2011-02 2020-08-18 Spinocerebellar ataxia type 2 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-2 descriptionSpinocerebellar ataxia type 2 (SCA2) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA2 include additional movement problems, speech and swallowing difficulties, and weakness in the muscles that control eye movement (ophthalmoplegia). Eye muscle weakness leads to involuntary back-and-forth eye movements (nystagmus) and a decreased ability to make rapid eye movements (saccadic slowing).Over time, individuals with SCA2 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle wasting (atrophy), uncontrolled muscle tensing (dystonia), and involuntary jerking movements (chorea). Some people with SCA2 develop a group of movement abnormalities known as parkinsonism, which includes unusually slow movement (bradykinesia), involuntary trembling (tremor), and muscle stiffness (rigidity). Individuals with SCA2 may have problems with short term memory, planning, and problem solving, or experience an overall decline in intellectual function (dementia).Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA2 usually survive 10 to 20 years after symptoms first appear. ad Autosomal dominant ATXN2 https://medlineplus.gov/genetics/gene/atxn2 SCA2 GTR C0752121 MeSH D020754 OMIM 183090 SNOMED CT 715751004 2011-02 2020-08-18 Spinocerebellar ataxia type 3 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-3 descriptionSpinocerebellar ataxia type 3 (SCA3) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA3 include speech difficulties, uncontrolled muscle tensing (dystonia), muscle stiffness (spasticity), rigidity, tremors, bulging eyes, and double vision. People with this condition may experience sleep disorders such as restless leg syndrome or REM sleep behavior disorder. Restless leg syndrome is a condition characterized by numbness or tingling in the legs accompanied by an urge to move the legs to stop the sensations. REM sleep behavior disorder is a condition in which the muscles are active during the dream (REM) stage of sleep, so an affected person often acts out his or her dreams. These sleep disorders tend to leave affected individuals feeling tired during the day.Over time, individuals with SCA3 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle cramps, muscle twitches (fasciculations), and swallowing difficulties. Individuals with SCA3 may have problems with memory, planning, and problem solving.Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA3 eventually require wheelchair assistance. They usually survive 10 to 20 years after symptoms first appear. ad Autosomal dominant ATXN3 https://medlineplus.gov/genetics/gene/atxn3 Azorean ataxia Azorean disease Machado-Joseph disease MJD SCA3 GTR C0024408 MeSH D017827 OMIM 109150 SNOMED CT 91952008 2011-02 2020-09-29 Spinocerebellar ataxia type 36 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-36 descriptionSpinocerebellar ataxia type 36 (SCA36) is a condition characterized by progressive problems with movement that typically begin in mid-adulthood. People with this condition initially experience problems with coordination and balance (ataxia). Affected individuals often have exaggerated reflexes (hyperreflexia) and problems with speech (dysarthria). They also usually develop muscle twitches (fasciculations) of the tongue and over time, the muscles in the tongue waste away (atrophy). These tongue problems can cause difficulties swallowing liquids. As the condition progresses, individuals with SCA36 develop muscle atrophy in the legs, forearms, and hands. Another common feature of SCA36 is the atrophy of specialized nerve cells that control muscle movement (motor neurons), which can contribute to the tongue and limb muscle atrophy in affected individuals.Some people with SCA36 have abnormalities of the eye muscles, which can lead to involuntary eye movements (nystagmus), rapid eye movements (saccades), trouble moving the eyes side-to-side (oculomotor apraxia), and droopy eyelids (ptosis). Sensorineural hearing loss, which is hearing loss caused by changes in the inner ear, may also occur in people with SCA36.Brain imaging of people with SCA36 shows progressive atrophy of various parts of the brain, particularly within the cerebellum, which is the area of the brain involved in coordinating movements. Over time, the loss of cells in the cerebellum causes the movement problems characteristic of SCA36. In older affected individuals, the frontal lobes of the brain may show atrophy resulting in loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies.Signs and symptoms of SCA36 typically begin in a person's forties or fifties but can appear anytime during adulthood. People with SCA36 have a normal lifespan and are usually mobile for 15 to 20 years after they are diagnosed. ad Autosomal dominant NOP56 https://medlineplus.gov/genetics/gene/nop56 Asidan ataxia Costa de Morte ataxia SCA36 Spinocerebellar ataxia 36 GTR C3472711 MeSH D020754 OMIM 614153 SNOMED CT 711158005 2014-12 2020-08-18 Spinocerebellar ataxia type 6 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-6 descriptionSpinocerebellar ataxia type 6 (SCA6) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA6 include speech difficulties, involuntary eye movements (nystagmus), and double vision. Over time, individuals with SCA6 may develop loss of coordination in their arms, tremors, and uncontrolled muscle tensing (dystonia).Signs and symptoms of SCA6 typically begin in a person's forties or fifties but can appear anytime from childhood to late adulthood. People with this disorder may require walking or mobility assistance later in life. ad Autosomal dominant CACNA1A https://medlineplus.gov/genetics/gene/cacna1a SCA6 Type 6 spinocerebellar ataxia GTR C0752124 MeSH D020754 OMIM 183086 SNOMED CT 715752006 2011-02 2022-07-29 Spondylocarpotarsal synostosis syndrome https://medlineplus.gov/genetics/condition/spondylocarpotarsal-synostosis-syndrome descriptionSpondylocarpotarsal synostosis syndrome is a disorder that affects the development of bones throughout the body. Newborns with this disorder are of approximately normal length, but impaired growth of the torso results in short stature over time. The bones of the spine (vertebrae) are misshapen and abnormally joined together (fused). The vertebral abnormalities may result in an abnormally curved lower back (lordosis) and a spine that curves to the side (scoliosis).People with spondylocarpotarsal synostosis syndrome have abnormalities and fusion of the bones of the wrist (carpal bones) and ankle (tarsal bones). They may also have inward- and upward-turning feet (clubfeet). Characteristic facial features include a round face, a large forehead (frontal bossing), and nostrils that open to the front rather than downward (anteverted nares).Some people with spondylocarpotarsal synostosis syndrome have an opening in the roof of the mouth (a cleft palate), hearing loss, thin tooth enamel, flat feet, or an unusually large range of joint movement (hypermobility). Individuals with this disorder can survive into adulthood. Intelligence is generally unaffected, although mild developmental delay has been reported in some affected individuals. ar Autosomal recessive ad Autosomal dominant MYH3 https://medlineplus.gov/genetics/gene/myh3 FLNB https://medlineplus.gov/genetics/gene/flnb Congenital scoliosis with unilateral unsegmented bar Congenital synspondylism SCT SCT syndrome Spondylocarpotarsal syndrome Vertebral fusion with carpal coalition GTR C1848934 MeSH D010009 OMIM 272460 SNOMED CT 702351004 2011-09 2020-08-18 Spondylocostal dysostosis https://medlineplus.gov/genetics/condition/spondylocostal-dysostosis descriptionSpondylocostal dysostosis is a group of conditions characterized by abnormal development of bones in the spine and ribs. The bones of the spine (vertebrae) are misshapen and abnormally joined together (fused). Many people with this condition have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae. In addition to spinal abnormalities, some of the rib bones may be fused together or missing. Affected individuals have short, rigid necks and short torsos because of the bone malformations. As a result, people with spondylocostal dysostosis have short bodies but normal-length arms and legs, called short-trunk dwarfism.The spine and rib abnormalities, which are present from birth, cause other signs and symptoms of spondylocostal dysostosis. Infants with this condition have small chests that cannot expand adequately, often leading to life-threatening breathing problems. As the lungs expand in the narrow chest, the muscle that separates the abdomen from the chest cavity (the diaphragm) is forced down and the abdomen is pushed out. The increased pressure in the abdomen can cause a soft out-pouching around the lower abdomen (inguinal hernia), particularly in males with spondylocostal dysostosis.Some people with spondylocostal dysostosis also have a type of birth defect known as a neural tube defect. Neural tube defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Examples of neural tube defects that occur in people with spondylocostal dysostosis include a spinal cord abnormality known as spina bifida and a brain abnormality called a Chiari malformation.Although breathing problems can be fatal early in life, many affected individuals live into adulthood.Spondylocostal dysostosis has often been grouped with a similar condition called spondylothoracic dysostosis, and both are sometimes called Jarcho-Levin syndrome; however, they are now considered distinct conditions. ar Autosomal recessive ad Autosomal dominant MESP2 https://medlineplus.gov/genetics/gene/mesp2 DLL3 https://medlineplus.gov/genetics/gene/dll3 LFNG https://www.ncbi.nlm.nih.gov/gene/3955 TBX6 https://www.ncbi.nlm.nih.gov/gene/6911 HES7 https://www.ncbi.nlm.nih.gov/gene/84667 RIPPLY2 https://www.ncbi.nlm.nih.gov/gene/134701 Jarcho-Levin syndrome SCDO GTR C0265343 GTR C1837549 GTR C1853296 GTR C3150942 GTR C4083048 GTR C4225279 GTR CN032975 MeSH D004413 OMIM 122600 OMIM 277300 OMIM 608681 OMIM 609813 OMIM 613686 OMIM 616566 SNOMED CT 61367005 2016-06 2020-08-18 Spondyloenchondrodysplasia with immune dysregulation https://medlineplus.gov/genetics/condition/spondyloenchondrodysplasia-with-immune-dysregulation descriptionSpondyloenchondrodysplasia with immune dysregulation (SPENCDI) is an inherited condition that primarily affects bone growth and immune system function. The signs and symptoms of SPENCDI can become apparent anytime from infancy to adolescence.Bone abnormalities in individuals with SPENCDI include flattened spinal bones (platyspondyly), abnormalities at the ends of long bones in the limbs (metaphyseal dysplasia), and areas of damage (lesions) on the long bones and spinal bones that can be seen on x-rays. Additional skeletal problems occur because of abnormalities of the tough, flexible tissue called cartilage that makes up much of the skeleton during early development. Individuals with SPENCDI often have areas where cartilage did not convert to bone. They may also have noncancerous growths of cartilage (enchondromas). The bone and cartilage problems contribute to short stature in people with SPENCDI.Individuals with SPENCDI have a combination of immune system problems. Many affected individuals have malfunctioning immune systems that attack the body's own tissues and organs, which is known as an autoimmune reaction. The malfunctioning immune system can lead to a variety of disorders, such as a decrease in blood cells called platelets (thrombocytopenia), premature destruction of red blood cells (hemolytic anemia), an underactive thyroid gland (hypothyroidism), or chronic inflammatory disorders such as systemic lupus erythematosus or rheumatoid arthritis. In addition, affected individuals often have abnormal immune cells that cannot grow and divide in response to harmful invaders such as bacteria and viruses. As a result of this immune deficiency, these individuals have frequent fevers and recurrent respiratory infections.Some people with SPENCDI have neurological problems such as abnormal muscle stiffness (spasticity), difficulty with coordinating movements (ataxia), and intellectual disability. They may also have abnormal deposits of calcium (calcification) in the brain.Due to the range of immune system problems, people with SPENCDI typically have a shortened life expectancy, but figures vary widely. ar Autosomal recessive ACP5 https://medlineplus.gov/genetics/gene/acp5 Combined immunodeficiency with autoimmunity and spondylometaphyseal dysplasia Roifman-Melamed syndrome Roifman–Costa syndrome SPENCDI GTR C1842763 MeSH D007153 MeSH D010009 OMIM 607944 SNOMED CT 703523004 2013-12 2020-12-21 Spondyloepiphyseal dysplasia congenita https://medlineplus.gov/genetics/condition/spondyloepiphyseal-dysplasia-congenita descriptionSpondyloepiphyseal dysplasia (SED) congenita is a disorder of bone development that causes short stature with a particularly short torso and short arms and legs. The parts of the body are not proportional to one another (disproportionate short stature) in people with this condition. Affected individuals typically have hands and feet that are of average size. SED congenita affects the bones of the spine (spondylo-) and the ends (epiphyses) of the long bones in the arms and legs. People with this condition also have problems with vision and hearing. The word "congenita" indicates that the condition is often noticeable at birth. The signs and symptoms of SED congenita can vary among affected individuals.People with SED congenita have an adult height that ranges from 3 feet to almost 5 feet. Affected individuals may develop abnormal curvature of the spine (scoliosis or kyphosis), which can worsen during childhood. Instability of the spinal bones (vertebrae) in the neck can cause these bones to shift, which increases the risk of damage to the spinal cord. Other skeletal issues in individuals with SED congenita can include flattened vertebrae (platyspondyly), an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara), and inward- and upward-turning feet (clubfoot). Arthritis and decreased joint mobility often develop early in life. An abnormally short, broad, and barrel-shaped chest can cause problems with breathing. People with SED congenita may also have breathing problems due to weakness of the windpipe. SED congenita often causes mild differences in facial features such as underdeveloped cheek bones (malar hypoplasia). Some affected individuals have a particular group of physical features called Pierre Robin sequence, which includes an opening in the roof of the mouth (cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). Severe nearsightedness (high myopia) is common in SED congenita, as are other eye problems that can impair vision such as a tearing of the light-sensitive tissue at the back of the eye (retinal detachment). Some people with SED congenita have hearing loss.Some disorders, such as spondyloepiphyseal dysplasia with premature-onset arthrosis and Namaqualand type hip dysplasia, are similar to SED congenita but have milder signs and symptoms. These milder conditions were once thought to be separate disorders, but they are now considered to be part of SED congenita. People with these disorders typically have joint pain and stiffness, which can restrict movement. Symptoms can begin in childhood and often worsen over time. ad Autosomal dominant+New variant ar Autosomal recessive COL2A1 https://medlineplus.gov/genetics/gene/col2a1 SED congenita SED, congenital type SEDC SEDc Spondyloepiphyseal dysplasia congenita (SEDC), COL2A1-related Spondyloepiphyseal dysplasia, congenital type GTR C2745959 ICD-10-CM Q77.7 MeSH D010009 OMIM 183900 SNOMED CT 278713008 2024-12 2024-12-19 Spondyloepiphyseal dysplasia with marked metaphyseal changes https://medlineplus.gov/genetics/condition/spondyloepiphyseal-dysplasia-with-marked-metaphyseal-changes descriptionSpondyloepiphyseal dysplasia (SED) with marked metaphyseal changes is a group of rare skeletal disorders. People with SED with marked metaphyseal changes have abnormalities of the spine (spondylo-) and the regions near the ends (metaphyses) and at the ends (epiphyses) of the long bones in the arms and legs. The severity of the signs and symptoms can vary from person to person.People with SED with marked metaphyseal changes may have a short torso, shortened arms and legs, and flattened bones of the spine (platyspondyly), which all lead to short stature. People with SED with marked metaphyseal changes may develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). This abnormal spinal curvature may be severe and can cause problems with breathing. Instability of the spinal bones (vertebrae) in the neck can cause these bones to shift, which increases the risk of damage to the spinal cord. Other features of SED with marked metaphyseal changes may include legs that curve outward or inward (valgus or varus deformity) and irregular bone formation (ossification) in the long bones. Changes in the position of the thigh bone where it meets the hip joint can cause difficulty walking.  Affected individuals may also have joint pain, swollen joints, and joint deformities (contractures). Arthritis may develop early in life.The conditions that make up SED with marked metaphyseal changes were once thought to be distinct disorders, but they are now considered to be part of the same disease spectrum. These conditions include spondyloepimetaphyseal dysplasia, Strudwick type (SEMD-S); spondylometaphyseal dysplasia, Algerian type (SMD-A); spondyloepiphyseal dysplasia, Stanescu type (SED-S); some cases of spondylometaphyseal dysplasia, corner fracture type (SMDCF); and dysspondyloenchondromatosis (DSC). ad Autosomal dominant+New variant COL2A1 https://medlineplus.gov/genetics/gene/col2a1 SED with marked metaphyseal changes Spondyloepimetaphyseal dysplasia, COL2A1-related GTR C0700635 MeSH D003095 MeSH D010009 OMIM 184250 OMIM 184253 OMIM 184255 OMIM 616583 SNOMED CT 702350003 2024-12 2024-12-20 Spondyloepiphyseal dysplasia with metatarsal shortening https://medlineplus.gov/genetics/condition/spondyloepiphyseal-dysplasia-with-metatarsal-shortening descriptionSpondyloepiphyseal dysplasia (SED) with metatarsal shortening (formerly called Czech dysplasia) is an inherited condition that affects joint function and bone development. People with this condition have joint pain that begins in late childhood or adolescence. The cartilage in their hips, knees, shoulders, and spine usually degenerates over time (osteoarthritis), which may impair their mobility. Due to these severe joint problems, people with SED with metatarsal shortening may require joint replacement in early adulthood.People with SED with metatarsal shortening often have shortened bones in their third and fourth toes, which make their first two toes appear unusually long. Affected individuals may also have abnormalities in the bones of the spine (vertebrae), including flattened vertebrae (platyspondyly), a reduction in the space between the vertebrae, or an abnormal curvature of the spine. Some people with SED with metatarsal shortening have progressive hearing loss. ad Autosomal dominant ad Autosomal dominant+1 affected parent COL2A1 https://medlineplus.gov/genetics/gene/col2a1 Czech dysplasia, metatarsal type Progressive pseudorheumatoid dysplasia with hypoplastic toes SED with metatarsal shortening SED with metatarsal shortening, COL2A1-related Spondyloepiphyseal dysplasia with precocious osteoarthritis GTR C1836683 MeSH D010009 OMIM 609162 SNOMED CT 389159004 2024-04 2024-12-19 Spondyloperipheral dysplasia https://medlineplus.gov/genetics/condition/spondyloperipheral-dysplasia descriptionSpondyloperipheral dysplasia is a disorder that impairs bone growth. The signs and symptoms of this condition can vary among affected individuals. People with spondyloperipheral dysplasia typically have short stature, with a short torso, short arms and legs, and short fingers and toes (brachydactyly). These parts of the body are not proportional to one another (disproportionate short stature) in people with this condition. Affected individuals also tend to have flattened bones of the spine (platyspondyly) and inward- and upward-turning feet (clubfoot). Some people with spondyloperipheral dysplasia may also experience nearsightedness (myopia) or hearing loss.   ad Autosomal dominant COL2A1 https://medlineplus.gov/genetics/gene/col2a1 Spondyloperipheral dysplasia, COL2A1-related GTR C0796173 MeSH D003095 MeSH D010009 OMIM 271700 SNOMED CT 702339001 2024-12 2024-12-20 Spondylothoracic dysostosis https://medlineplus.gov/genetics/condition/spondylothoracic-dysostosis descriptionSpondylothoracic dysostosis is a condition characterized by malformation of the bones of the spine and ribs. The bones of the spine (vertebrae) do not develop properly, which causes them to be misshapen and abnormally joined together (fused). The ribs are also fused at the part nearest the spine (posteriorly), which gives the rib cage its characteristic fan-like or "crab" appearance in x-rays. Affected individuals have short, rigid necks and short torsos because of the bone malformations. As a result, people with spondylothoracic dysostosis have short bodies but normal-length arms and legs, called short-trunk dwarfism.The spine and rib abnormalities, which are present from birth, cause other signs and symptoms of spondylothoracic dysostosis. Infants with this condition have small chests that cannot expand adequately, often leading to life-threatening breathing problems. As the lungs expand in the narrow chest, the muscle that separates the abdomen from the chest cavity (the diaphragm) is forced down and the abdomen is pushed out. The increased pressure in the abdomen can cause a soft out-pouching around the lower abdomen (inguinal hernia) or belly-button (umbilical hernia).Breathing problems can be fatal early in life; however, some affected individuals live into adulthood.Spondylothoracic dysostosis is sometimes called spondylocostal dysostosis, a similar condition with abnormalities of the spine and ribs. The two conditions have been grouped in the past, and both are sometimes referred to as Jarcho-Levin syndrome; however, they are now considered distinct conditions. ar Autosomal recessive MESP2 https://medlineplus.gov/genetics/gene/mesp2 Jarcho-Levin syndrome STD GTR C0265343 MeSH D004413 OMIM 277300 OMIM 608681 SNOMED CT 61367005 2016-06 2020-08-18 Sporadic hemiplegic migraine https://medlineplus.gov/genetics/condition/sporadic-hemiplegic-migraine descriptionSporadic hemiplegic migraine is a rare form of migraine headache. Migraines typically cause intense, throbbing pain in one area of the head. Some people with migraines also experience nausea, vomiting, and sensitivity to light and sound. These recurrent headaches typically begin in childhood or adolescence and can be triggered by certain foods, emotional stress, and minor head trauma. Each headache may last from a few hours to a few days.In sporadic hemiplegic migraine and some other types of migraine, a pattern of neurological symptoms called an aura occurs before onset of the headache. An aura commonly includes temporary visual changes such as blind spots (scotomas), flashing lights, zig-zagging lines, and double vision. In people with sporadic hemiplegic migraine, auras are also characterized by temporary numbness or weakness, often affecting one side of the body (hemiparesis). Additional features of an aura can include difficulty with speech, confusion, and drowsiness. An aura typically develops gradually over a few minutes and lasts about an hour.Some people with sporadic hemiplegic migraine experience unusually severe migraine episodes. These episodes can include fever, prolonged weakness, seizures, and coma. Although most people with sporadic hemiplegic migraine recover completely between episodes, neurological symptoms such as memory loss and problems with attention can last for weeks or months. Some affected individuals develop mild but permanent difficulty coordinating movements (ataxia), which may worsen with time, and rapid, involuntary eye movements called nystagmus. Mild to severe intellectual disability has been reported in some people with sporadic hemiplegic migraine. ad Autosomal dominant n Not inherited CACNA1A https://medlineplus.gov/genetics/gene/cacna1a ATP1A2 https://medlineplus.gov/genetics/gene/atp1a2 Non-familial hemiplegic migraine SHM ICD-10-CM G43.4 ICD-10-CM G43.40 ICD-10-CM G43.401 ICD-10-CM G43.409 ICD-10-CM G43.41 ICD-10-CM G43.411 ICD-10-CM G43.419 MeSH D020325 OMIM 602481 SNOMED CT 230464001 2014-02 2023-03-01 Stargardt macular degeneration https://medlineplus.gov/genetics/condition/stargardt-macular-degeneration descriptionStargardt macular degeneration is a genetic eye disorder that causes progressive vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, Stargardt macular degeneration affects a small area near the center of the retina called the macula. The macula is responsible for the type of vision needed for detailed tasks such as reading, driving, and recognizing faces. In most people with Stargardt macular degeneration, a fatty yellow pigment called lipofuscin builds up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear vision. People with Stargardt macular degeneration have problems with night vision that can make it difficult to navigate in low light. Some affected individuals also have impaired color vision. The signs and symptoms of Stargardt macular degeneration typically appear in late childhood to early adulthood and worsen over time. ar Autosomal recessive ad Autosomal dominant ABCA4 https://medlineplus.gov/genetics/gene/abca4 ELOVL4 https://medlineplus.gov/genetics/gene/elovl4 Juvenile macular degeneration Macular dystrophy with flecks, type 1 Stargardt disease STGD GTR C1838644 GTR C1855465 ICD-10-CM H35.53 MeSH D008268 OMIM 248200 OMIM 600110 SNOMED CT 47673003 SNOMED CT 70099003 2023-10 2023-10-27 Steatocystoma multiplex https://medlineplus.gov/genetics/condition/steatocystoma-multiplex descriptionSteatocystoma multiplex is a skin disorder characterized by the development of multiple noncancerous (benign) cysts known as steatocystomas. These growths begin in the skin's sebaceous glands, which normally produce an oily substance called sebum that lubricates the skin and hair. Steatocystomas are filled with sebum.In affected individuals, steatocystomas typically first appear during adolescence and are found most often on the torso, neck, upper arms, and upper legs. These cysts are usually the only sign of the condition. However, some affected individuals also have mild abnormalities involving the teeth or the fingernails and toenails. ad Autosomal dominant KRT17 https://medlineplus.gov/genetics/gene/krt17 Multiple sebaceous cysts Multiplex steatocystoma Sebocystomatosis GTR C0259771 ICD-10-CM L72.2 MeSH D062685 OMIM 184500 SNOMED CT 109433009 2012-08 2023-03-01 Stevens-Johnson syndrome/toxic epidermal necrolysis https://medlineplus.gov/genetics/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis descriptionStevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe skin reaction most often triggered by particular medications. Although Stevens-Johnson syndrome and toxic epidermal necrolysis were once thought to be separate conditions, they are now considered part of a continuum. Stevens-Johnson syndrome represents the less severe end of the disease spectrum, and toxic epidermal necrolysis represents the more severe end.SJS/TEN often begins with a fever and flu-like symptoms. Within a few days, the skin begins to blister and peel, forming very painful raw areas called erosions that resemble a severe hot-water burn. The skin erosions usually start on the face and chest before spreading to other parts of the body. In most affected individuals, the condition also damages the mucous membranes, including the lining of the mouth and the airways, which can cause trouble with swallowing and breathing. The painful blistering can also affect the urinary tract and genitals. SJS/TEN often affects the eyes as well, causing irritation and redness of the conjunctiva, which are the mucous membranes that protect the white part of the eye and line the eyelids, and damage to the clear front covering of the eye (the cornea).Severe damage to the skin and mucous membranes makes SJS/TEN a life-threatening disease. Because the skin normally acts as a protective barrier, extensive skin damage can lead to a dangerous loss of fluids and allow infections to develop. Serious complications can include pneumonia, overwhelming bacterial infections (sepsis), shock, multiple organ failure, and death. About 10 percent of people with Stevens-Johnson syndrome die from the disease, while the condition is fatal in up to 50 percent of those with toxic epidermal necrolysis.Among people who survive, long-term effects of SJS/TEN can include changes in skin coloring (pigmentation), dryness of the skin and mucous membranes (xerosis), excess sweating (hyperhidrosis), hair loss (alopecia), and abnormal growth or loss of the fingernails and toenails. Other long-term problems can include impaired taste, difficulty urinating, and genital abnormalities. A small percentage of affected individuals develop chronic dryness or inflammation of the eyes, which can lead to increased sensitivity to light (photophobia) and vision impairment. n Not inherited HLA-B https://medlineplus.gov/genetics/gene/hla-b Drug-induced Stevens Johnson syndrome Lyell's syndrome Mycoplasma-induced Stevens Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome toxic epidermal necrolysis spectrum Toxic epidermal necrolysis ICD-10-CM L51.1 ICD-10-CM L51.3 MeSH D013262 OMIM 608579 SNOMED CT 124911000119100 SNOMED CT 73442001 2015-07 2020-08-18 Stickler syndrome https://medlineplus.gov/genetics/condition/stickler-syndrome descriptionStickler syndrome is a group of hereditary conditions that are characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals, even among members of the same family.A characteristic feature of Stickler syndrome is a flattened facial appearance that results from underdeveloped bones in the middle of the face. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing after birth.Many individuals with Stickler syndrome have severe nearsightedness (high myopia), which means they have trouble seeing things that are far away. In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common in people with Stickler syndrome, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the light-sensitive tissue at the back of the eye (retinal detachment). These eye abnormalities can impair vision and may lead to blindness.Hearing loss is also common in people with Stickler syndrome. In affected individuals, the degree of hearing loss can vary and may worsen over time. People with Stickler syndrome typically have sensorineural hearing loss (caused by changes in the inner ear) with or without conductive hearing loss (caused by changes in the middle ear).Most people with Stickler syndrome have joint abnormalities. Arthritis often develops early in life and may cause joint pain or stiffness. People with severe joint disease may need surgery to replace damaged joints in their 20s or 30s. Affected individuals may also have abnormal curvature of the spine (scoliosis or kyphosis) that causes back pain.Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes, features, and patterns of inheritance. In particular, the eye abnormalities and severity of hearing loss vary among the different types. Some types of Stickler syndrome are very rare and have been diagnosed in only a few individuals. ad Autosomal dominant+New variant ar Autosomal recessive COL11A2 https://medlineplus.gov/genetics/gene/col11a2 COL11A1 https://medlineplus.gov/genetics/gene/col11a1 COL2A1 https://medlineplus.gov/genetics/gene/col2a1 COL9A1 https://medlineplus.gov/genetics/gene/col9a1 COL9A2 https://medlineplus.gov/genetics/gene/col9a2 COL9A3 https://medlineplus.gov/genetics/gene/col9a3 Arthroophthalmopathy Hereditary arthro-ophthalmo-dystrophy Hereditary arthro-ophthalmopathy Stickler dysplasia GTR C0265235 GTR C0265253 GTR C1848488 GTR C1858084 GTR C2020284 GTR C3279941 GTR C3280342 MeSH D003095 OMIM 108300 OMIM 184840 OMIM 604841 OMIM 609508 OMIM 614134 OMIM 614284 SNOMED CT 33410002 SNOMED CT 78675000 2024-12 2024-12-19 Stormorken syndrome https://medlineplus.gov/genetics/condition/stormorken-syndrome descriptionStormorken syndrome is a rare condition that affects many body systems. Affected individuals usually have thrombocytopenia, in which there are abnormally low numbers of blood cells called platelets. Platelets are involved in normal blood clotting; a shortage of platelets typically results in easy bruising and abnormal bleeding. In addition, affected individuals often have a muscle disorder, called tubular aggregate myopathy, that leads to muscle weakness. Another feature of Stormorken syndrome is permanent constriction of the pupils of the eyes (miosis), which may be caused by abnormalities in the muscles that control the size of the pupils. Other features include lack of a functioning spleen (asplenia), scaly skin (ichthyosis), headaches, and difficulty with reading and spelling (dyslexia). ad Autosomal dominant STIM1 https://medlineplus.gov/genetics/gene/stim1 Stormorken-Sjaastad-Langslet syndrome Thrombocytopathy, asplenia, and miosis GTR C1861451 MeSH D000015 MeSH D013921 OMIM 185070 SNOMED CT 711407000 2014-08 2020-08-18 Sturge-Weber syndrome https://medlineplus.gov/genetics/condition/sturge-weber-syndrome descriptionSturge-Weber syndrome is a condition that affects the development of certain blood vessels, causing abnormalities in the brain, skin, and eyes from birth. Sturge-Weber syndrome has three major features: a red or pink birthmark called a port-wine birthmark, a brain abnormality called a leptomeningeal angioma, and increased pressure in the eye (glaucoma). These features can vary in severity and not all individuals with Sturge-Weber syndrome have all three features.Most people with Sturge-Weber syndrome are born with a port-wine birthmark. This type of birthmark is caused by enlargement (dilatation) of small blood vessels (capillaries) near the surface of the skin. Port-wine birthmarks are typically initially flat and can vary in color from pale pink to deep purple. In people with Sturge-Weber syndrome, the port-wine birthmark is most often on the face, typically on the forehead, temple, or eyelid. The port-wine birthmark is usually only on one side of the face but can be on both sides. Over time, the skin within the port-wine birthmark can darken and thicken.In Sturge-Weber syndrome, there is usually abnormal formation and growth of blood vessels within the two thin layers of tissue that cover the brain and spinal cord. This abnormality, which is called leptomeningeal angioma, can affect one or both sides of the brain and impair blood flow in the brain and lead to loss of brain tissue (atrophy) and deposits of calcium (calcification) in the brain below the angioma. The decrease in blood flow caused by leptomeningeal angiomas can cause stroke-like episodes in people with Sturge-Weber syndrome. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), vision abnormalities, seizures, and migraine headaches. In affected individuals, these episodes usually begin by age 2. The seizures usually involve only one side of the brain (focal seizures), during which the port-wine birthmark may darken and individuals may lose consciousness. People with Sturge-Weber syndrome have varying levels of cognitive function, from normal intelligence to intellectual disability. Some individuals have learning disabilities with problems focusing similar to attention-deficit/hyperactivity disorder (ADHD).In individuals with Sturge-Weber syndrome, glaucoma typically develops either in infancy or early adulthood and can cause vision impairment. In some affected infants, the pressure can become so great that the eyeballs appear enlarged and bulging (buphthalmos). Individuals with Sturge-Weber syndrome can have tangles of abnormal blood vessels (hemangiomas) in various parts of the eye. When these abnormal blood vessels develop in the network of blood vessels at the back of the eye (choroid), it is called a diffuse choroidal hemangioma and occurs in about one-third of individuals with Sturge-Weber syndrome. A diffuse choroidal hemangioma can cause vision loss. When present, the eye abnormalities typically occur on the same side of the head as the port-wine birthmark. n Not inherited GNAQ https://medlineplus.gov/genetics/gene/gnaq Angiomatosis aculoorbital-thalamic syndrome Encephalofacial hemangiomatosis Encephalofacial hemangiomatosis syndrome Meningo-oculo-facial angiomatosis Meningofacial angiomatosis-cerebral calcification syndrome Neuroretinoangiomatosis Phakomatosis, Sturge-Weber Sturge-Weber-Dimitri syndrome Sturge-Weber-Krabbe syndrome SWS GTR C0038505 ICD-10-CM Q85.8 MeSH D013341 OMIM 185300 SNOMED CT 19886006 2017-02 2020-08-18 Stüve-Wiedemann syndrome https://medlineplus.gov/genetics/condition/stuve-wiedemann-syndrome descriptionStüve-Wiedemann syndrome is a severe condition characterized by bone abnormalities and dysfunction of the autonomic nervous system, which controls involuntary body processes such as the regulation of breathing rate and body temperature. The condition is apparent from birth, and its key features include abnormal curvature (bowing) of the long bones in the legs, difficulty feeding and swallowing, and episodes of dangerously high body temperature (hyperthermia).In addition to bowed legs, affected infants can have bowed arms, permanently bent fingers and toes (camptodactyly), and joint deformities (contractures) in the elbows and knees that restrict their movement. Other features include abnormalities of the pelvic bones (the ilia) and reduced bone mineral density (osteopenia).In infants with Stüve-Wiedemann syndrome, dysfunction of the autonomic nervous system typically leads to difficulty feeding and swallowing, breathing problems, and episodes of hyperthermia. Affected infants may also sweat excessively, even when the body temperature is not elevated, or have a reduced ability to feel pain. Many babies with this condition do not survive past infancy because of the problems regulating breathing and body temperature; however, some people with Stüve-Wiedemann syndrome live into adolescence or later.Problems with breathing and swallowing usually improve in affected children who survive infancy; however, they still have difficulty regulating body temperature. In addition, the leg bowing worsens, and children with Stüve-Wiedemann syndrome may develop prominent joints, an abnormal curvature of the spine (scoliosis), and spontaneous bone fractures. Some affected individuals have a smooth tongue that lacks the bumps that house taste buds (fungiform papillae). Affected children may also lose certain reflexes, particularly the reflex to blink when something touches the eye (corneal reflex) and the knee-jerk reflex (patellar reflex).Another condition once known as Schwartz-Jampel syndrome type 2 is now considered to be part of Stüve-Wiedemann syndrome. Researchers have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used. ar Autosomal recessive LIFR https://medlineplus.gov/genetics/gene/lifr Neonatal Schwartz-Jampel syndrome Schwartz-Jampel type 2 syndrome SJS2 Stuve-Wiedemann dysplasia Stuve-Wiedemann syndrome Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome STWS SWS GTR C0796176 MeSH D010009 OMIM 601559 SNOMED CT 254097005 2016-04 2023-04-04 Subcortical band heterotopia https://medlineplus.gov/genetics/condition/subcortical-band-heterotopia descriptionSubcortical band heterotopia is a condition in which nerve cells (neurons) do not move (migrate) to their proper locations in the fetal brain during early development. (Heterotopia means "out of place.") Normally, the neurons that make up the outer surface of the brain (cerebral cortex) are distributed in a well-organized and multi-layered way. In people with subcortical band heterotopia, some neurons that should be part of the cerebral cortex do not reach it. These neurons stop their migration process in areas of the brain where they are not supposed to be and form band-like clusters of tissue. Since these bands are located beneath the cerebral cortex, they are said to be subcortical. In most cases, the bands are symmetric, which means they occur in the same places on the right and left sides of the brain.The abnormal brain development causes neurological problems in people with subcortical band heterotopia. The signs and symptoms of the condition depend on the size of the bands and the lack of development of the cerebral cortex. The signs and symptoms can vary from severe intellectual disability and seizures that begin early in life and affect both sides of the brain (generalized seizures) to normal intelligence with seizures occurring later in life and affecting only one side of the brain (focal seizures). Some affected individuals also have weak muscle tone (hypotonia), loss of fine motor skills such as using utensils, or behavioral problems. Subcortical band heterotopia is typically found when brain imaging is done following the onset of seizures, usually in adolescence or early adulthood. n Not inherited x X-linked DCX https://medlineplus.gov/genetics/gene/dcx PAFAH1B1 https://medlineplus.gov/genetics/gene/pafah1b1 DC syndrome Double cortex syndrome Heterotopia, subcortical band SBH SCLH Subcortical laminar heterotopia GTR C1848201 MeSH D054221 OMIM 300067 OMIM 607432 2018-08 2020-08-18 Succinic semialdehyde dehydrogenase deficiency https://medlineplus.gov/genetics/condition/succinic-semialdehyde-dehydrogenase-deficiency descriptionSuccinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delays, especially in speech development; intellectual disabilities; and decreased muscle tone (hypotonia) soon after birth. Communication problems may improve over time in people with this disorder.About half of people with succinic semialdehyde dehydrogenase deficiency experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems.  The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Other behavioral and psychiatric features, including aggression and obsessive-compulsive disorder (OCD), tend to develop in adolescence and early adulthood.  ar Autosomal recessive ALDH5A1 https://medlineplus.gov/genetics/gene/aldh5a1 4-hydroxybutyric aciduria Gamma-hydroxybutyric acidemia Gamma-hydroxybutyric aciduria SSADH deficiency GTR C0268631 ICD-10-CM MeSH D020739 OMIM 271980 SNOMED CT 49748000 2024-03 2024-03-06 Succinyl-CoA:3-ketoacid CoA transferase deficiency https://medlineplus.gov/genetics/condition/succinyl-coa3-ketoacid-coa-transferase-deficiency descriptionSuccinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is an inherited disorder that impairs the body's ability to break down ketones, which are molecules produced in the liver during the breakdown of fats.The signs and symptoms of SCOT deficiency typically appear within the first few years of life. Affected individuals experience episodes of extreme tiredness (lethargy), appetite loss, vomiting, rapid breathing, and, occasionally, seizures. These episodes, which are called ketoacidotic attacks, sometimes lead to coma. About half of affected individuals have a ketoacidotic attack within the first 4 days of life. Affected individuals have no symptoms of the disorder between ketoacidotic attacks.People with SCOT deficiency usually have a permanently elevated level of ketones in their blood (persistent ketosis). If the level of ketones gets too high, which can be brought on by infections, fevers, or periods without food (fasting), a ketoacidotic attack can occur. The frequency of ketoacidotic attacks varies among affected individuals. ar Autosomal recessive OXCT1 https://medlineplus.gov/genetics/gene/oxct1 3-oxoacid CoA transferase deficiency Ketoacidosis due to SCOT deficiency SCOT deficiency Succinyl-CoA 3-oxoacid transferase deficiency Succinyl-CoA:3-oxoacid CoA transferase deficiency Succinyl-CoA:acetoacetate transferase deficiency GTR C0342792 MeSH D007662 OMIM 245050 SNOMED CT 124366000 SNOMED CT 238004006 2011-12 2021-04-19 Sudden infant death with dysgenesis of the testes syndrome https://medlineplus.gov/genetics/condition/sudden-infant-death-with-dysgenesis-of-the-testes-syndrome descriptionSudden infant death with dysgenesis of the testes syndrome (SIDDT) is a rare condition that is fatal in the first year of life; its major features include abnormalities of the reproductive system in males, feeding difficulties, and breathing problems.Infants with SIDDT who are genetically male, with one X chromosome and one Y chromosome in each cell, have underdeveloped or abnormal testes. They may also have external genitalia that appear female-typical or that do not look clearly male or clearly female. In affected infants who are genetically female, with two X chromosomes in each cell, development of the internal and external reproductive organs is normal.SIDDT is associated with abnormal development of the brain, particularly the brainstem, which is the part of the brain that is connected to the spinal cord. The brainstem regulates many basic body functions, including heart rate, breathing, eating, and sleeping. It also relays information about movement and the senses between the brain and the rest of the body. Many features of SIDDT appear to be related to brainstem malfunction, including a slow or uneven heart rate, abnormal breathing patterns, difficulty controlling body temperature, unusual tongue and eye movements, an exaggerated startle reflex to sudden lights or loud noises, and feeding difficulties. Affected infants also have an unusual cry that has been described as similar to the bleating of a goat, which is probably a result of abnormal nerve connections between the brain and the voicebox (larynx).The brainstem abnormalities lead to death in the first year of life, when affected infants suddenly stop breathing or their heart stops beating (cardiorespiratory arrest). ar Autosomal recessive TSPYL1 https://medlineplus.gov/genetics/gene/tspyl1 SIDDT GTR C1837371 ICD-10-CM MeSH D006061 MeSH D013398 OMIM 608800 SNOMED CT 711157000 2014-12 2023-10-27 Supravalvular aortic stenosis https://medlineplus.gov/genetics/condition/supravalvular-aortic-stenosis descriptionSupravalvular aortic stenosis (SVAS) is a heart defect that develops before birth. This defect is a narrowing (stenosis) of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). The condition is described as supravalvular because the section of the aorta that is narrowed is located just above the valve that connects the aorta with the heart (the aortic valve). Some people with SVAS also have defects in other blood vessels, most commonly stenosis of the artery from the heart to the lungs (the pulmonary artery). An abnormal heart sound during a heartbeat (heart murmur) can often be heard during a chest exam. If SVAS is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and ultimately heart failure.The severity of SVAS varies considerably, even among family members. Some affected individuals die in infancy, while others never experience symptoms of the disorder. ad Autosomal dominant ELN https://medlineplus.gov/genetics/gene/eln Aortic stenosis, supravalvular Stenosis, aortic supravalvular Stenosis, supravalvular aortic Supravalvar aortic stenosis Supravalvular stenosis, aortic SVAS GTR C0003499 ICD-10-CM Q25.3 MeSH D021921 OMIM 185500 SNOMED CT 268185002 2012-05 2022-02-24 Surfactant dysfunction https://medlineplus.gov/genetics/condition/surfactant-dysfunction descriptionSurfactant dysfunction is a lung disorder that causes breathing problems. This condition results from abnormalities in the composition or function of surfactant, a mixture of certain fats (called phospholipids) and proteins that lines the lung tissue and makes breathing easy. Without normal surfactant, the tissue surrounding the air sacs in the lungs (the alveoli) sticks together (because of a force called surface tension) after exhalation, causing the alveoli to collapse. As a result, filling the lungs with air on each breath becomes very difficult, and the delivery of oxygen to the body is impaired.The signs and symptoms of surfactant dysfunction can vary in severity. The most severe form of this condition causes respiratory distress syndrome in newborns. Affected babies have extreme difficulty breathing and are unable to get enough oxygen. The lack of oxygen can damage the baby's brain and other organs. This syndrome leads to respiratory failure, and most babies with this form of the condition do not survive more than a few months.Less severe forms of surfactant dysfunction cause gradual onset of breathing problems in children or adults. Signs and symptoms of these milder forms are abnormally rapid breathing (tachypnea); low concentrations of oxygen in the blood (hypoxemia); and an inability to grow or gain weight at the expected rate (failure to thrive).There are several types of surfactant dysfunction, which are identified by the genetic cause of the condition. One type, called SP-B deficiency, causes respiratory distress syndrome in newborns. Other types, known as SP-C dysfunction and ABCA3 deficiency, have signs and symptoms that range from mild to severe. ar Autosomal recessive ad Autosomal dominant SFTPB https://medlineplus.gov/genetics/gene/sftpb SFTPC https://medlineplus.gov/genetics/gene/sftpc ABCA3 https://medlineplus.gov/genetics/gene/abca3 CSF2RA https://www.ncbi.nlm.nih.gov/gene/1438 CSF2RB https://www.ncbi.nlm.nih.gov/gene/1439 Interstitial lung disease due to surfactant deficiency Pulmonary surfactant metabolism dysfunction Surfactant metabolism deficiency GTR C1968602 GTR C1970470 GTR C2677877 GTR C3280574 ICD-10-CM J84.83 MeSH D017563 OMIM 265120 OMIM 300770 OMIM 610913 OMIM 614370 SNOMED CT 328641000119109 2012-07 2020-08-18 Swyer syndrome https://medlineplus.gov/genetics/condition/swyer-syndrome descriptionSwyer syndrome is a condition that affects sex development. Sex development usually follows a particular path based on an individual's chromosomes; however, in Swyer syndrome, sex development is not typical for the affected individual's chromosomal pattern.Chromosomes contain the genetic instructions for how the body develops and functions. People usually have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female reproductive structures. Girls and women typically have two X chromosomes (46,XX karyotype), while boys and men typically have one X chromosome and one Y chromosome (46,XY karyotype). In Swyer syndrome, individuals have one X chromosome and one Y chromosome in each cell, which is the pattern typically found in boys and men; however, they have female reproductive structures.People with Swyer syndrome have female external genitalia and some female internal reproductive structures. These individuals usually have a uterus and fallopian tubes, but their gonads (ovaries or testes) are not functional. Instead, the gonads are small and underdeveloped and contain little gonadal tissue. These structures are called  streak gonads. The streak gonadal tissue is at risk of developing cancer that is often hard-to-detect, so it is usually removed surgically. Swyer syndrome is also called 46,XY complete gonadal dysgenesis; the medical term “dysgenesis” means "abnormal development."Swyer syndrome may be identified before birth, at birth, or later when a child does not go through puberty as usual. Because they do not have functional ovaries that produce hormones, affected individuals often begin hormone replacement therapy during early adolescence to start puberty, causing the breasts and uterus to grow, and eventually leading to menstruation. Hormone replacement therapy is also important for bone health and helps reduce the risk of low bone density (osteopenia) and fragile bones (osteoporosis). Women with Swyer syndrome do not produce eggs (ova), but if they have a uterus, they may be able to become pregnant with a donated egg or embryo. ad Autosomal dominant y Y-linked ar Autosomal recessive n Not inherited NR0B1 https://medlineplus.gov/genetics/gene/nr0b1 SRY https://medlineplus.gov/genetics/gene/sry DHH https://medlineplus.gov/genetics/gene/dhh NR5A1 https://medlineplus.gov/genetics/gene/nr5a1 SOX9 https://medlineplus.gov/genetics/gene/sox9 MAP3K1 https://medlineplus.gov/genetics/gene/map3k1 CBX2 https://www.ncbi.nlm.nih.gov/gene/876 DMRT1 https://www.ncbi.nlm.nih.gov/gene/1761 ZFPM2 https://www.ncbi.nlm.nih.gov/gene/23414 FTHL17 https://www.ncbi.nlm.nih.gov/gene/53940 DHX37 https://www.ncbi.nlm.nih.gov/gene/57647 46,XY CGD 46,XY complete gonadal dysgenesis 46,XY sex reversal Gonadal dysgenesis, 46,XY Pure gonadal dysgenesis 46,XY XY pure gonadal dysgenesis GTR C2936694 GTR CN043561 ICD-10-CM Q97.3 MeSH D006061 OMIM 154230 OMIM 233420 OMIM 300018 OMIM 400044 OMIM 612965 OMIM 613080 OMIM 613762 OMIM 616067 SNOMED CT 95218005 2015-03 2025-01-31 Systemic lupus erythematosus https://medlineplus.gov/genetics/condition/systemic-lupus-erythematosus descriptionSystemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. The signs and symptoms of SLE vary among affected individuals, and can involve many organs and systems, including the skin, joints, kidneys, lungs, central nervous system, and blood-forming (hematopoietic) system. SLE is one of a large group of conditions called autoimmune disorders that occur when the immune system attacks the body's own tissues and organs.SLE may first appear as extreme tiredness (fatigue), a vague feeling of discomfort or illness (malaise), fever, loss of appetite, and weight loss. Most affected individuals also have joint pain, typically affecting the same joints on both sides of the body, and muscle pain and weakness. Skin problems are common in SLE. A characteristic feature is a flat red rash across the cheeks and bridge of the nose, called a "butterfly rash" because of its shape. The rash, which generally does not hurt or itch, often appears or becomes more pronounced when exposed to sunlight. Other skin problems that may occur in SLE include calcium deposits under the skin (calcinosis), damaged blood vessels (vasculitis) in the skin, and tiny red spots called petechiae. Petechiae are caused by a shortage of cells involved in clotting (platelets), which leads to bleeding under the skin. Affected individuals may also have hair loss (alopecia) and open sores (ulcerations) in the moist lining (mucosae) of the mouth, nose, or, less commonly, the genitals.About a third of people with SLE develop kidney disease (nephritis). Heart problems may also occur in SLE, including inflammation of the sac-like membrane around the heart (pericarditis) and abnormalities of the heart valves, which control blood flow in the heart. Heart disease caused by fatty buildup in the blood vessels (atherosclerosis), which is very common in the general population, is even more common in people with SLE. The inflammation characteristic of SLE can also damage the nervous system, and may result in abnormal sensation and weakness in the limbs (peripheral neuropathy); seizures; stroke; and difficulty processing, learning, and remembering information (cognitive impairment). Anxiety and depression are also common in SLE.People with SLE have episodes in which the condition gets worse (exacerbations) and other times when it gets better (remissions). Overall, SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening. n Not inherited ar Autosomal recessive TREX1 https://medlineplus.gov/genetics/gene/trex1 PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 IRF5 https://medlineplus.gov/genetics/gene/irf5 STAT4 https://medlineplus.gov/genetics/gene/stat4 NCF2 https://medlineplus.gov/genetics/gene/ncf2 C4A https://www.ncbi.nlm.nih.gov/gene/720 C4B https://www.ncbi.nlm.nih.gov/gene/721 CR2 https://www.ncbi.nlm.nih.gov/gene/1380 CRP https://www.ncbi.nlm.nih.gov/gene/1401 CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 DNASE1 https://www.ncbi.nlm.nih.gov/gene/1773 DNASE1L3 https://www.ncbi.nlm.nih.gov/gene/1776 FCGR2B https://www.ncbi.nlm.nih.gov/gene/2213 ITGAM https://www.ncbi.nlm.nih.gov/gene/3684 LTK https://www.ncbi.nlm.nih.gov/gene/4058 PDCD1 https://www.ncbi.nlm.nih.gov/gene/5133 TLR5 https://www.ncbi.nlm.nih.gov/gene/7100 TNFAIP3 https://www.ncbi.nlm.nih.gov/gene/7128 TNFSF4 https://www.ncbi.nlm.nih.gov/gene/7292 RIPK1 https://www.ncbi.nlm.nih.gov/gene/8737 RASGRP1 https://www.ncbi.nlm.nih.gov/gene/10125 BANK1 https://www.ncbi.nlm.nih.gov/gene/55024 Disseminated lupus erythematosus LE syndrome Libman-Sacks disease Lupus SLE GTR C1835919 GTR C1854577 GTR C1866373 GTR C1970455 GTR C2677097 GTR C3280742 ICD-10-CM M32 MeSH D008180 OMIM 152700 OMIM 300809 OMIM 601744 OMIM 605218 OMIM 605480 OMIM 607279 OMIM 607965 OMIM 607966 OMIM 607967 OMIM 608437 OMIM 609903 OMIM 609939 OMIM 610065 OMIM 610066 OMIM 610927 OMIM 612251 OMIM 612253 OMIM 612254 OMIM 612378 OMIM 613145 OMIM 614420 SNOMED CT 55464009 2014-06 2025-12-22 Systemic mastocytosis https://medlineplus.gov/genetics/condition/systemic-mastocytosis descriptionSystemic mastocytosis is a blood disorder that can affect many different body systems. Individuals with the condition can develop signs and symptoms at any age, but it usually appears after adolescence.Signs and symptoms of systemic mastocytosis often include extreme tiredness (fatigue), skin redness and warmth (flushing), nausea, abdominal pain, bloating, diarrhea, the backflow of stomach acids into the esophagus (gastroesophageal reflux), nasal congestion, shortness of breath, low blood pressure (hypotension), lightheadedness, and headache. Some affected individuals have attention or memory problems, anxiety, or depression. Many individuals with systemic mastocytosis develop a skin condition called urticaria pigmentosa, which is characterized by raised patches of brownish skin that sting or itch with contact or changes in temperature. Nearly half of individuals with systemic mastocytosis will experience severe allergic reactions (anaphylaxis).There are five subtypes of systemic mastocytosis, which are differentiated by their severity and the signs and symptoms. The mildest forms of systemic mastocytosis are the indolent and smoldering types. Individuals with these types tend to have only the general signs and symptoms of systemic mastocytosis described above. Individuals with smoldering mastocytosis may have more organs affected and more severe features than those with indolent mastocytosis. The indolent type is the most common type of systemic mastocytosis.The severe types include aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. These types are associated with a reduced life span, which varies among the types and affected individuals. In addition to the general signs and symptoms of systemic mastocytosis, these types typically involve impaired function of an organ, such as the liver, spleen, or lymph nodes. The organ dysfunction can result in an abnormal buildup of fluid in the abdominal cavity (ascites). Aggressive systemic mastocytosis is associated with a loss of bone tissue (osteoporosis and osteopenia) and multiple bone fractures. Systemic mastocytosis with an associated hematologic neoplasm and mast cell leukemia both involve blood cell disorders or blood cell cancer (leukemia). Mast cell leukemia is the rarest and most severe type of systemic mastocytosis.Individuals with the milder forms of the condition generally have a normal or near normal life expectancy, while those with the more severe forms typically survive months or a few years after diagnosis. n Not inherited TET2 https://medlineplus.gov/genetics/gene/tet2 KIT https://medlineplus.gov/genetics/gene/kit RUNX1 https://medlineplus.gov/genetics/gene/runx1 DNMT3A https://medlineplus.gov/genetics/gene/dnmt3a ASXL1 https://medlineplus.gov/genetics/gene/asxl1 SRSF2 https://www.ncbi.nlm.nih.gov/gene/6427 Mast cell disease, systemic Mastocytosis, systemic Systemic mast cell disease Systemic mast-cell disease Systemic mastocytoses Systemic tissue mast cell disease GTR C0221013 ICD-10-CM D47.02 MeSH D034721 OMIM 154800 SNOMED CT 397016004 2018-10 2020-08-18 Systemic scleroderma https://medlineplus.gov/genetics/condition/systemic-scleroderma descriptionSystemic scleroderma is an autoimmune disorder that affects the skin and internal organs. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. The word "scleroderma" means hard skin in Greek, and the condition is characterized by the buildup of scar tissue (fibrosis) in the skin and other organs. The condition is also called systemic sclerosis because the fibrosis can affect organs other than the skin. Fibrosis is due to the excess production of a tough protein called collagen, which normally strengthens and supports connective tissues throughout the body.The signs and symptoms of systemic scleroderma usually begin with episodes of Raynaud phenomenon, which can occur weeks to years before fibrosis. In Raynaud phenomenon, the fingers and toes of affected individuals turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities. Another early sign of systemic scleroderma is puffy or swollen hands before thickening and hardening of the skin due to fibrosis. Skin thickening usually occurs first in the fingers (called sclerodactyly) and may also involve the hands and face. In addition, people with systemic scleroderma often have open sores (ulcers) on their fingers, painful bumps under the skin (calcinosis), or small clusters of enlarged blood vessels just under the skin (telangiectasia).Fibrosis can also affect internal organs and can lead to impairment or failure of the affected organs. The most commonly affected organs are the esophagus, heart, lungs, and kidneys. Internal organ involvement may be signaled by heartburn, difficulty swallowing (dysphagia), high blood pressure (hypertension), kidney problems, shortness of breath, diarrhea, or impairment of the muscle contractions that move food through the digestive tract (intestinal pseudo-obstruction).There are three types of systemic scleroderma, defined by the tissues affected in the disorder. In one type of systemic scleroderma, known as limited cutaneous systemic scleroderma, fibrosis usually affects only the hands, arms, and face. Limited cutaneous systemic scleroderma used to be known as CREST syndrome, which is named for the common features of the condition: calcinosis, Raynaud phenomenon, esophageal motility dysfunction, sclerodactyly, and telangiectasia. In another type of systemic scleroderma, known as diffuse cutaneous systemic scleroderma, the fibrosis affects large areas of skin, including the torso and the upper arms and legs, and often involves internal organs. In diffuse cutaneous systemic scleroderma, the condition worsens quickly and organ damage occurs earlier than in other types of the condition. In the third type of systemic scleroderma, called systemic sclerosis sine scleroderma ("sine" means without in Latin), fibrosis affects one or more internal organs but not the skin.Approximately 15 percent to 25 percent of people with features of systemic scleroderma also have signs and symptoms of another condition that affects connective tissue, such as polymyositis, dermatomyositis, rheumatoid arthritis, Sjögren syndrome, or systemic lupus erythematosus. The combination of systemic scleroderma with other connective tissue abnormalities is known as scleroderma overlap syndrome. n Not inherited u Pattern unknown PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 IRF5 https://medlineplus.gov/genetics/gene/irf5 STAT4 https://medlineplus.gov/genetics/gene/stat4 BLK https://www.ncbi.nlm.nih.gov/gene/640 TNFSF4 https://www.ncbi.nlm.nih.gov/gene/7292 BANK1 https://www.ncbi.nlm.nih.gov/gene/55024 Familial progressive scleroderma Progressive scleroderma Systemic sclerosis ICD-10-CM M34 ICD-10-CM M34.0 ICD-10-CM M34.1 ICD-10-CM M34.8 ICD-10-CM M34.81 ICD-10-CM M34.82 ICD-10-CM M34.83 ICD-10-CM M34.89 ICD-10-CM M34.9 MeSH D012595 OMIM 181750 SNOMED CT 89155008 2011-09 2025-12-22 Sézary syndrome https://medlineplus.gov/genetics/condition/sezary-syndrome descriptionSézary syndrome is an aggressive form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions. In Sézary syndrome, the cancerous T cells, called Sézary cells, are present in the blood, skin, and lymph nodes. A characteristic of Sézary cells is an abnormally shaped nucleus, described as cerebriform.People with Sézary syndrome develop a red, severely itchy rash (erythroderma) that covers large portions of their body. Sézary cells are found in the rash. However, the skin cells themselves are not cancerous; the skin problems result when Sézary cells move from the blood into the skin. People with Sézary syndrome also have enlarged lymph nodes (lymphadenopathy). Other common signs and symptoms of this condition include hair loss (alopecia), skin swelling (edema), thickened skin on the palms of the hands and soles of the feet (palmoplantar keratoderma), abnormalities of the fingernails and toenails, and lower eyelids that turn outward (ectropion). Some people with Sézary syndrome are less able to control their body temperature than people without the condition.The cancerous T cells can spread to other organs in the body, including the lymph nodes, liver, spleen, and bone marrow. In addition, affected individuals have an increased risk of developing another lymphoma or other type of cancer.Sézary syndrome most often occurs in adults over age 60 and usually progresses rapidly; historically, affected individuals survived an average of 2 to 4 years after development of the condition, although survival has improved with newer treatments.Although Sézary syndrome is sometimes referred to as a variant of another cutaneous T-cell lymphoma called mycosis fungoides, these two cancers are generally considered separate conditions. u Pattern unknown Sezary erythroderma Sezary syndrome Sezary's lymphoma GTR C0036920 ICD-10-CM C84.1 ICD-10-CM C84.10 ICD-10-CM C84.11 ICD-10-CM C84.12 ICD-10-CM C84.13 ICD-10-CM C84.14 ICD-10-CM C84.15 ICD-10-CM C84.16 ICD-10-CM C84.17 ICD-10-CM C84.18 ICD-10-CM C84.19 MeSH D012751 OMIM 254400 SNOMED CT 4950009 2013-02 2023-03-01 T-cell immunodeficiency, congenital alopecia, and nail dystrophy https://medlineplus.gov/genetics/condition/t-cell-immunodeficiency-congenital-alopecia-and-nail-dystrophy descriptionT-cell immunodeficiency, congenital alopecia, and nail dystrophy is a type of severe combined immunodeficiency (SCID), which is a group of disorders characterized by an almost total lack of immune protection from foreign invaders such as bacteria and viruses. People with this form of SCID are missing functional immune cells called T cells, which normally recognize and attack foreign invaders to prevent infection. Without functional T cells, affected individuals develop repeated and persistent infections starting early in life. The infections result in slow growth and can be life-threatening; without effective treatment, most affected individuals live only into infancy or early childhood.T-cell immunodeficiency, congenital alopecia, and nail dystrophy also affects growth of the hair and nails. Congenital alopecia refers to an absence of hair that is apparent from birth. Affected individuals have no scalp hair, eyebrows, or eyelashes. Nail dystrophy is a general term that describes malformed fingernails and toenails; in this condition, the nails are often ridged, pitted, or abnormally curved.Researchers have described abnormalities of the brain and spinal cord (central nervous system) in at least two cases of this condition. However, it is not yet known whether central nervous system abnormalities are a common feature of T-cell immunodeficiency, congenital alopecia, and nail dystrophy. ar Autosomal recessive FOXN1 https://medlineplus.gov/genetics/gene/foxn1 Alymphoid cystic thymic dysgenesis Congenital alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency Pignata Guarino syndrome Winged helix deficiency GTR C1866426 MeSH D016511 OMIM 601705 SNOMED CT 720345008 2014-08 2020-08-18 TK2-related mitochondrial DNA depletion syndrome, myopathic form https://medlineplus.gov/genetics/condition/tk2-related-mitochondrial-dna-depletion-syndrome-myopathic-form descriptionTK2-related mitochondrial DNA depletion syndrome, myopathic form (TK2-MDS) is an inherited condition that causes progressive muscle weakness (myopathy).The signs and symptoms of TK2-MDS typically begin in early childhood. Development is usually normal early in life, but as muscle weakness progresses, people with TK2-MDS lose motor skills such as standing, walking, eating, and talking. Some affected individuals have increasing weakness in the muscles that control eye movement, leading to droopy eyelids (progressive external ophthalmoplegia).Most often in TK2-MDS, the muscles are the only affected tissues; however, the liver may be enlarged (hepatomegaly), seizures can occur, and hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) may be present. Intelligence is usually not affected.As the disorder worsens, the muscles that control breathing become weakened and affected individuals frequently have to rely on mechanical ventilation. Respiratory failure is the most common cause of death in people with TK2-MDS, often occurring in childhood. Rarely, the disorder progresses slowly and affected individuals survive into adolescence or adulthood. ar Autosomal recessive TK2 https://medlineplus.gov/genetics/gene/tk2 Mitochondrial DNA depletion syndrome 2 (myopathic type) MTDPS2 TK2-related mitochondrial DNA depletion myopathy GTR C3149750 MeSH D017240 OMIM 609560 SNOMED CT 703527003 2013-09 2020-08-18 TRNT1 deficiency https://medlineplus.gov/genetics/condition/trnt1-deficiency descriptionTRNT1 deficiency is a condition that affects many body systems. Its signs and symptoms can involve blood cells, the immune system, the eyes, and the nervous system. The severity of the signs and symptoms vary widely.A common feature of TRNT1 deficiency is a blood condition called sideroblastic anemia, which is characterized by a shortage of red blood cells (anemia). In TRNT1 deficiency, the red blood cells that are present are unusually small (erythrocytic microcytosis). In addition, developing red blood cells in the bone marrow (erythroblasts) can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment in the lab with certain dyes. These abnormal cells are called ring sideroblasts.Many people with TRNT1 deficiency have an immune system disorder (immunodeficiency) that can lead to recurrent bacterial infections. Repeated infections can cause life-threatening damage to internal organs. The immunodeficiency is characterized by low numbers of immune system cells called B cells, which normally help fight infections by producing immune proteins called antibodies (or immunoglobulins). These proteins target foreign invaders such as bacteria and viruses and mark them for destruction. In many individuals with TRNT1 deficiency, the amount of immunoglobulins is also low (hypogammaglobulinemia).In addition, many individuals with TRNT1 deficiency have recurrent fevers that are not caused by an infection. These fever episodes are often one of the earliest recognized symptoms of TRNT1 deficiency, usually beginning in infancy. The fever episodes are typically accompanied by poor feeding, vomiting, and diarrhea, and can lead to hospitalization. In many affected individuals, the episodes occur regularly, arising approximately every 2 to 4 weeks and lasting 5 to 7 days, although the frequency can decrease with age.Eye abnormalities, often involving the light-sensing tissue at the back of the eye (the retina), can occur in people with TRNT1 deficiency. Some of these individuals have a condition called retinitis pigmentosa, in which the light-sensing cells of the retina gradually deteriorate. Eye problems in TRNT1 deficiency can lead to vision loss.Neurological problems are also frequent in TRNT1 deficiency. Many affected individuals have delayed development of speech and motor skills, such as sitting, standing, and walking, and some have low muscle tone (hypotonia).Features that occur less commonly in people with TRNT1 deficiency include hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss), recurrent seizures (epilepsy), and problems with the kidneys or heart.TRNT1 deficiency encompasses what was first thought to be two separate disorders, a severe disorder called sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) and a milder disorder called retinitis pigmentosa with erythrocytic microcytosis (RPEM), each named for its most common features. SIFD begins in infancy, and affected individuals usually do not survive past childhood. RPEM, on the other hand, is recognized in early adulthood, and the microcytosis usually does not cause any health problems. However, it has since been recognized that some individuals have a combination of features that fall between these two ends of the severity spectrum. All of these cases are now considered part of TRNT1 deficiency. ar Autosomal recessive TRNT1 https://medlineplus.gov/genetics/gene/trnt1 Retinitis pigmentosa with erythrocytic microcytosis RPEM Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay SIFD TRNT1 enzyme deficiency TRNT1-related immunodeficiency TRNT1-related immunodeficiency+ GTR C4015172 GTR C4310776 MeSH D000756 MeSH D012174 OMIM 616084 OMIM 616959 2017-11 2023-11-07 TUBB4A-related leukodystrophy https://medlineplus.gov/genetics/condition/tubb4a-related-leukodystrophy descriptionTUBB4A-related leukodystrophy is a disorder that affects the nervous system. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In particular, TUBB4A-related leukodystrophy involves hypomyelination, which means that the nervous system has a reduced ability to form myelin. In some affected individuals, myelin may also break down, which is known as demyelination.People with TUBB4A-related leukodystrophy have different combinations of signs and symptoms. Some of these combinations are described as separate disorders. However, the features in some affected individuals do not fit into these defined disorders. Researchers now group all of these cases of leukodystrophy, which have the same genetic cause, as TUBB4A-related leukodystrophy.At the most severe end of the TUBB4A-related leukodystrophy spectrum is a condition called hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). This disorder begins in infancy or early childhood. Most affected individuals have delayed development of motor skills, such as sitting and walking, and some are never able to walk on their own. In other cases, motor skills develop normally and then are lost in early childhood (developmental regression). In addition, individuals with H-ABC have other movement abnormalities, such as involuntary muscle contractions (dystonia), uncontrolled movements of the limbs (choreoathetosis), muscle stiffness (rigidity), and difficulty coordinating movements (ataxia). These individuals also often have impaired speech (dysarthria), a weak voice (dysphonia), and swallowing problems (dysphagia). Some develop seizures. Learning difficulty is common in individuals with H-ABC.H-ABC is characterized by particular brain abnormalities, including hypomyelination. In addition, tissue in certain regions of the brain breaks down (atrophies), most prominently in a region called the putamen, which is part of a group of structures that help control movement (the basal ganglia). Atrophy of brain tissue in another region involved in movement called the cerebellum is common, and atrophy of the cerebrum, which controls most voluntary activity, language, sensory perception, learning, and memory, can also occur.At the mildest end of the TUBB4A-related leukodystrophy spectrum is a condition called isolated hypomyelination, which begins at any time from late childhood to adulthood. Individuals at this end of the spectrum have mild hypomyelination and sometimes mild atrophy of the cerebellum, but no problems with the basal ganglia. These individuals can have movement problems, dysarthria, and learning difficulty, although these features are typically milder than in H-ABC.The features in other individuals with TUBB4A-related leukodystrophy fall in between these two extremes. Affected individuals can have varying degrees of hypomyelination and atrophy or impairment of the basal ganglia or other brain regions. Movement problems can also occur. A small group of affected individuals develop muscle stiffness and paralysis of the lower limbs (spastic paraplegia) that slowly worsen. In addition, these individuals may have mild hypomyelination and ataxia without the other movement or learning problems common in H-ABC. ad Autosomal dominant TUBB4A https://medlineplus.gov/genetics/gene/tubb4a TUBB4A-associated hypomyelinating leukoencephalopathies TUBB4A-related hypomyelinating leukodystrophy GTR C2676244 MeSH D020279 OMIM 612438 2017-08 2020-08-18 Tangier disease https://medlineplus.gov/genetics/condition/tangier-disease descriptionTangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood. HDL transports cholesterol and certain fats called phospholipids from the body's tissues to the liver, where they are removed from the blood. HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. Because people with Tangier disease have very low levels of HDL, they have a moderately increased risk of cardiovascular disease.Additional signs and symptoms of Tangier disease include a slightly elevated amount of fat in the blood (mild hypertriglyceridemia); disturbances in nerve function (neuropathy); and enlarged, orange-colored tonsils. Affected individuals often develop atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. Other features of this condition may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of the outermost layer of the eye (corneal clouding), and type 2 diabetes. ar Autosomal recessive ABCA1 https://medlineplus.gov/genetics/gene/abca1 A-alphalipoprotein neuropathy Alpha high density lipoprotein deficiency disease Analphalipoproteinemia Cholesterol thesaurismosis Familial high density lipoprotein deficiency disease Familial hypoalphalipoproteinemia HDL lipoprotein deficiency disease Lipoprotein deficiency disease, HDL, familial Tangier disease neuropathy Tangier hereditary neuropathy GTR C0039292 MeSH D013631 OMIM 205400 SNOMED CT 15346004 SNOMED CT 723579009 SNOMED CT 838348004 2023-10 2023-10-30 Tarsal-carpal coalition syndrome https://medlineplus.gov/genetics/condition/tarsal-carpal-coalition-syndrome descriptionTarsal-carpal coalition syndrome is a rare, inherited bone disorder that affects primarily the hands and feet. Several individual bones make up each wrist (carpal bones) and ankle (tarsal bones). In tarsal-carpal coalition syndrome, the carpal bones fuse together, as do the tarsal bones, which causes stiffness and immobility of the hands and feet. Symptoms of the condition can become apparent in infancy, and they worsen with age. The severity of the symptoms can vary, even among members of the same family.In this condition, fusion at the joints between the bones that make up each finger and toe (symphalangism) can also occur. Consequently, the fingers and toes become stiff and difficult to bend. Stiffness of the pinky fingers and toes (fifth digits) is usually noticeable first. The joints at the base of the pinky fingers and toes fuse first, and slowly, the other joints along the length of these digits may also be affected. Progressively, the bones in the fourth, third, and second digits (the ring finger, middle finger, and forefinger, and the corresponding toes) become fused. The thumb and big toe are usually not involved. Affected individuals have increasing trouble forming a fist, and walking often becomes painful and difficult. Occasionally, there is also fusion of bones in the upper and lower arm at the elbow joint (humeroradial fusion). Less common features of tarsal-carpal coalition syndrome include short stature or the development of hearing loss. ad Autosomal dominant NOG https://medlineplus.gov/genetics/gene/nog NOG-related-symphalangism spectrum disorder TCC GTR C1861305 MeSH D013580 OMIM 186570 SNOMED CT 702312009 2012-04 2020-08-18 Task-specific focal dystonia https://medlineplus.gov/genetics/condition/task-specific-focal-dystonia descriptionTask-specific focal dystonia is a movement disorder that interferes with the performance of particular tasks, such as writing, playing a musical instrument, or participating in a sport. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions, tremors, and other uncontrolled movements. The term "focal" refers to a type of dystonia that affects a single part of the body, such as the hand or jaw.Researchers have described several forms of task-specific focal dystonia. The most common is writer's cramp, in which muscle cramps or spasms in the hand, wrist, or forearm interfere with holding a pen or pencil. Writer's cramp begins in the hand used for writing (the dominant hand) and is usually limited to that task, but with time it can spread to the other hand and affect other fine-motor activities such as shaving or typing.Musician's dystonia is a form of task-specific focal dystonia characterized by muscle cramps and spasms that occur while playing a musical instrument. This condition can affect amateur or professional musicians, and the location of the dystonia depends on the instrument. Some musicians (such as piano, guitar, and violin players) develop focal hand dystonia, which causes loss of fine-motor control in the hand and wrist muscles. This condition reduces finger coordination, speed, and endurance while playing. Musicians who play woodwind or brass instruments can develop what is known as embouchure dystonia. This condition causes muscle cramps or spasms involving the lips, tongue, or jaw, which prevents normal positioning of the mouth around the instrument's mouthpiece. Musician's dystonia often occurs only when playing a particular instrument. However, over time focal hand dystonia may impair other activities, and embouchure dystonia can worsen to affect eating and speech.Task-specific focal dystonia can affect people who play sports and engage in other occupations involving repetitive, highly practiced movements. For example, some golfers experience involuntary jerking of the wrists during putting, a condition known informally as "the yips." Cramps and spasms of the hand and arm muscles can also affect tennis players, billiards players, dart throwers, and other athletes. Additionally, task-specific dystonia has been reported in tailors, shoemakers, hair stylists, and people who frequently type or use a computer mouse.The abnormal movements associated with task-specific focal dystonia are usually painless, although they can cause anxiety when they interfere with musical performance and other activities. Severe cases can cause professional disability. ad Autosomal dominant Focal hand dystonia Focal task-specific dystonia FTSD Occupational cramp Occupational dystonia Task-specific dystonia MeSH D020821 OMIM 611284 SNOMED CT 230330004 2012-12 2020-08-18 Tay-Sachs disease https://medlineplus.gov/genetics/condition/tay-sachs-disease descriptionTay-Sachs disease is a rare, inherited disorder that is characterized by neurological problems caused by  the death of nerve cells (neurons) in the brain and spinal cord (central nervous system).The most common form of Tay-Sachs disease, known as infantile Tay-Sachs disease, becomes apparent early in life. Infants with this disorder typically develop normally until they are 3 to 6 months old. During this time, their development slows and muscles used for movement weaken. Affected infants stop achieving normal developmental milestones and begin to lose previously acquired skills such as turning over, sitting, and crawling. Infants with this condition develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Tay-Sachs disease experience involuntary muscle twitches(myoclonic jerks), seizures, difficulty swallowing (dysphagia),vision and hearing loss, and intellectual disability. An eye abnormality called a cherry-red spot, which is identified by eye examination, is characteristic of this disorder. Children with infantile  Tay-Sachs disease usually live only into early childhood.Two other forms of Tay-Sachs disease, known as juvenile and late-onset, are rare. Signs and symptoms of the juvenile form can appear between the ages of 5 years and late adolescence. Features of late-onset Tay-Sachs disease typically appear in adulthood. People with either of these forms of the condition usually have milder and more variable signs and symptoms than those with the infantile form. Characteristic features of juvenile or late-onset Tay-Saches disease include muscle weakness, loss of muscle coordination (ataxia), speech problems, and psychiatric symptoms. These signs and symptoms vary widely among people with late-onset forms of Tay-Sachs disease. ar Autosomal recessive HEXA https://medlineplus.gov/genetics/gene/hexa B variant GM2 gangliosidosis GM2 gangliosidosis, type 1 HexA deficiency Hexosaminidase A deficiency Hexosaminidase alpha-subunit deficiency (variant B) Sphingolipidosis, Tay-Sachs TSD GTR C0039373 ICD-10-CM E75.02 MeSH D013661 OMIM 272800 SNOMED CT 111385000 2006-08 2021-09-30 Tetra-amelia syndrome https://medlineplus.gov/genetics/condition/tetra-amelia-syndrome descriptionTetra-amelia syndrome (sometimes known as TETAMS) is a very rare disorder characterized by the absence of all four limbs. ("Tetra" is the Greek word for "four," and "amelia" refers to the failure of an arm or leg to develop before birth.)  This syndrome can also cause severe malformations of other parts of the body, including the nervous system, face, head, heart, skeleton, gastrointestinal system, urinary tract, and genitalia. The lungs are underdeveloped in many cases, which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems, most are stillborn or die shortly after birth. There are two forms of tetra-amelia syndrome that have been described, and while the features overlap, they are distinguished by their signs and symptoms and genetic cause. Tetra-amelia syndrome type 1 is typically characterized by severe gastrointestinal problems. These problems include an opening in the abdomen through which various abdominal organs can protrude(abdominal wall defect), abnormalities in the muscle (diaphragm) that separates the organs in the abdomen from those in the chest, and lack of an anal opening (imperforate anus). People with type 1 also tend to have frequent urinary tract problems, such as a lack of kidney development (renal agenesis). Tetra-amelia syndrome type 2 is usually characterized by complete absence of both lungs. Affected individuals often have heart abnormalities, such as defects in the walls between the chambers of the heart (septal defects) or absence of the mitral valve, which connects the two left chambers of the heart. People with type 2 can also have facial abnormalities that include partial or complete fusion of the upper and lower eyelids, the bottom of the tongue attached to the floor of the mouth, or a small lower jaw (micrognathia). ar Autosomal recessive WNT3 https://medlineplus.gov/genetics/gene/wnt3 RSPO2 https://medlineplus.gov/genetics/gene/rspo2 TETAMS Tetra-amelia Tetra-amelia, autosomal recessive GTR C4012268 GTR C4747923 ICD-10-CM Q73.0 MeSH D000015 MeSH D004480 OMIM 273395 OMIM 618021 SNOMED CT 702313004 2023-02 2024-05-22 Tetrahydrobiopterin deficiency https://medlineplus.gov/genetics/condition/tetrahydrobiopterin-deficiency descriptionTetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency. This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain.Infants with tetrahydrobiopterin deficiency appear normal at birth, but medical problems ranging from mild to severe become apparent over time. Signs and symptoms of this condition can include intellectual disability, progressive problems with development, movement disorders, difficulty swallowing, seizures, behavioral problems, and an inability to control body temperature. ar Autosomal recessive QDPR https://medlineplus.gov/genetics/gene/qdpr PCBD1 https://medlineplus.gov/genetics/gene/pcbd1 GCH1 https://medlineplus.gov/genetics/gene/gch1 PTS https://medlineplus.gov/genetics/gene/pts BH4 deficiency Hyperphenylalaninemia caused by a defect in biopterin metabolism Hyperphenylalaninemia, non-phenylketonuric Non-phenylketonuric hyperphenylalaninemia GTR C0268465 GTR C0268467 GTR C0878676 GTR C1849700 ICD-10-CM E70.1 MeSH D010661 OMIM 233910 OMIM 261630 OMIM 261640 OMIM 264070 SNOMED CT 23447005 SNOMED CT 237914002 SNOMED CT 276261007 SNOMED CT 45116002 SNOMED CT 58256000 SNOMED CT 68724006 2011-05 2020-08-18 Tetrasomy 18p https://medlineplus.gov/genetics/condition/tetrasomy-18p descriptionTetrasomy 18p is a chromosomal condition that affects many parts of the body. This condition usually causes feeding difficulties in infancy, delayed development, intellectual disability that is often mild to moderate but can be severe, changes in muscle tone, distinctive facial features, and other birth defects. However, the signs and symptoms vary among affected individuals.Babies with tetrasomy 18p often have trouble feeding and may vomit frequently, which makes it difficult for them to gain weight. Some affected infants also have breathing problems and jaundice, which is a yellowing of the skin and the whites of the eyes.Changes in muscle tone are commonly seen with tetrasomy 18p. Some affected children have weak muscle tone (hypotonia), while others have increased muscle tone (hypertonia) and stiffness (spasticity). These changes contribute to delayed development of motor skills, including sitting, crawling, and walking.Tetrasomy 18p is associated with a distinctive facial appearance that can include unusually shaped and low-set ears, a small mouth, a flat area between the upper lip and the nose (philtrum), and a thin upper lip. Many affected individuals also have a high, arched roof of the mouth (palate), and a few have had a split in the roof of the mouth (cleft palate).Additional features of tetrasomy 18p can include seizures, vision problems, recurrent ear infections, mild to moderate hearing loss, constipation and other gastrointestinal problems, abnormal curvature of the spine (scoliosis or kyphosis), a shortage of growth hormone, and birth defects affecting the heart and other organs. Males with tetrasomy 18p may be born with undescended testes (cryptorchidism) or the opening of the urethra on the underside of the penis (hypospadias). Psychiatric conditions, such as attention-deficit/hyperactivity disorder (ADHD) and anxiety, as well as social and behavioral challenges have also been reported in some people with tetrasomy 18p. n Not inherited 18 https://medlineplus.gov/genetics/chromosome/18 18p isochromosome 18p tetrasomy GTR C0795868 MeSH D025063 OMIM 614290 SNOMED CT 698849002 2011-03 2020-09-08 Thanatophoric dysplasia https://medlineplus.gov/genetics/condition/thanatophoric-dysplasia descriptionThanatophoric dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra (redundant) skin on the arms and legs. Other features of this condition include a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes.Researchers have described two major forms of thanatophoric dysplasia, type I and type II. Type I thanatophoric dysplasia is distinguished by the presence of curved thigh bones and flattened bones of the spine (platyspondyly). Type II thanatophoric dysplasia is characterized by straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull.The term thanatophoric is Greek for "death bearing." Infants with thanatophoric dysplasia are usually stillborn or die shortly after birth from respiratory failure; however, a few affected individuals have survived into childhood with extensive medical help. ad Autosomal dominant FGFR3 https://medlineplus.gov/genetics/gene/fgfr3 Dwarf, thanatophoric Thanatophoric dwarfism Thanatophoric short stature GTR C1300257 GTR C1868678 ICD-10-CM Q77.1 MeSH D013796 OMIM 187600 OMIM 187601 SNOMED CT 29352008 SNOMED CT 389158007 2006-06 2020-08-18 Thiamine-responsive megaloblastic anemia syndrome https://medlineplus.gov/genetics/condition/thiamine-responsive-megaloblastic-anemia-syndrome descriptionThiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare condition that is characterized by hearing loss, diabetes, and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the red blood cells that are present are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, diarrhea, and tingling or numbness in the hands and feet. Individuals with TRMA typically develop megaloblastic anemia between infancy and adolescence. TRMA is called "thiamine-responsive" because the anemia can be treated with daily doses of vitamin B1 (thiamine).In people with TRMA, hearing loss typically develops during early childhood and is caused by abnormalities of the inner ear (sensorineural hearing loss). The hearing loss usually worsens over time. It remains unclear whether treatment with thiamine can improve hearing or delay hearing loss in people with TRMA.People with TRMA often develop diabetes mellitus, a condition in which glucose levels can become dangerously high, at an early age. Although some individuals with TRMA develop diabetes during childhood, they do not have the autoimmune form of diabetes that typically develops in children, called type 1 diabetes. People with TRMA usually require insulin to treat their diabetes. In some cases, treatment with thiamine may delay the onset of diabetes or reduce the amount of insulin a person needs.Some individuals with TRMA have abnormalities of the eye, including optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Additional features of this condition may include heart and blood vessel (cardiovascular) problems, intellectual disabilities, behavioral changes, and seizures.  ar Autosomal recessive SLC19A2 https://medlineplus.gov/genetics/gene/slc19a2 Rogers syndrome Thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural hearing loss TRMA GTR C0342287 MeSH D000749 OMIM 249270 SNOMED CT 237617006 2024-12 2024-12-09 Thiopurine S-methyltransferase deficiency https://medlineplus.gov/genetics/condition/thiopurine-s-methyltransferase-deficiency descriptionThiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body's immune system. Thiopurine drugs are used to treat some autoimmune disorders, including Crohn's disease and rheumatoid arthritis, which occur when the immune system malfunctions. These drugs are also used to treat several forms of cancer, particularly cancers of blood-forming tissue (leukemias) and cancers of immune system cells (lymphomas). Additionally, thiopurine drugs are used in organ transplant recipients to help prevent the immune system from attacking the transplanted organ.A potential complication of treatment with thiopurine drugs is damage to the bone marrow (hematopoietic toxicity). Although this complication can occur in anyone who takes these drugs, people with TPMT deficiency are at highest risk. Bone marrow normally makes several types of blood cells, including red blood cells, which carry oxygen; white blood cells, which help protect the body from infection; and platelets, which are involved in blood clotting. Damage to the bone marrow results in myelosuppression, a condition in which the bone marrow is unable to make enough of these cells. A shortage of red blood cells (anemia) can cause pale skin (pallor), weakness, shortness of breath, and extreme tiredness (fatigue). Low numbers of white blood cells (neutropenia) can lead to frequent and potentially life-threatening infections. A shortage of platelets (thrombocytopenia) can cause easy bruising and bleeding.Many healthcare providers recommend that patients' TPMT activity levels be tested before thiopurine drugs are prescribed. In people who are found to have reduced enzyme activity, the drugs may be given at a significantly lower dose or different medications can be used to reduce the risk of hematopoietic toxicity.TPMT deficiency does not appear to cause any health problems other than those associated with thiopurine drug treatment. ac Autosomal codominant TPMT https://medlineplus.gov/genetics/gene/tpmt Poor metabolism of thiopurines Thiopurine methyltransferase deficiency TPMT deficiency GTR C0342801 MeSH D004342 MeSH D011686 OMIM 610460 2015-04 2023-07-17 Thrombocytopenia-absent radius syndrome https://medlineplus.gov/genetics/condition/thrombocytopenia-absent-radius-syndrome descriptionThrombocytopenia-absent radius (TAR) syndrome is characterized by the absence of a bone called the radius in each forearm and a shortage (deficiency) of blood cells involved in clotting (platelets). This platelet deficiency (thrombocytopenia) usually appears during infancy and becomes less severe over time; in some cases the platelet levels become normal.Thrombocytopenia prevents normal blood clotting, resulting in easy bruising and frequent nosebleeds. Potentially life-threatening episodes of severe bleeding (hemorrhages) may occur in the brain and other organs, especially during the first year of life. Hemorrhages can damage the brain and lead to intellectual disability. Affected children who survive this period and do not have damaging hemorrhages in the brain usually have a normal life expectancy and normal intellectual development.The severity of skeletal problems in TAR syndrome varies among affected individuals. The radius, which is the bone on the thumb side of the forearm, is almost always missing in both arms. The other bone in the forearm, which is called the ulna, is sometimes underdeveloped or absent in one or both arms. TAR syndrome is unusual among similar malformations in that affected individuals have thumbs, while people with other conditions involving an absent radius typically do not. However, there may be other abnormalities of the hands, such as webbed or fused fingers (syndactyly) or curved pinky fingers (fifth finger clinodactyly). Some people with TAR syndrome also have skeletal abnormalities affecting the upper arms, legs, or hip sockets.Other features that can occur in TAR syndrome include malformations of the heart or kidneys. Some people with this disorder have unusual facial features including a small lower jaw (micrognathia), a prominent forehead, and low-set ears. About half of affected individuals have allergic reactions to cow's milk that may worsen the thrombocytopenia associated with this disorder. ar Autosomal recessive RBM8A https://medlineplus.gov/genetics/gene/rbm8a 1 https://medlineplus.gov/genetics/chromosome/1 Chromosome 1q21.1 deletion syndrome, 200-KB Radial aplasia-amegakaryocytic thrombocytopenia Radial aplasia-thrombocytopenia syndrome TAR syndrome Thrombocytopenia absent radii GTR C0175703 MeSH D038062 OMIM 274000 SNOMED CT 85589009 2012-10 2023-03-01 Thrombotic thrombocytopenic purpura https://medlineplus.gov/genetics/condition/thrombotic-thrombocytopenic-purpura descriptionThrombotic thrombocytopenic purpura is a rare disorder that causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart. Complications resulting from these clots can include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems.Blood clots normally form to stop blood loss at the sites of blood vessel injury. In people with thrombotic thrombocytopenic purpura, clots develop even in the absence of apparent injury. Blood clots are formed from clumps of cells called platelets that circulate in the blood and assist with clotting. Because a large number of platelets are used to make clots in people with thrombotic thrombocytopenic purpura, fewer platelets are available in the bloodstream. A reduced level of circulating platelets is known as thrombocytopenia. Thrombocytopenia can lead to small areas of bleeding just under the surface of the skin, resulting in purplish spots called purpura.This disorder also causes red blood cells to break down (undergo hemolysis) prematurely. As blood squeezes past clots within blood vessels, red blood cells can break apart. A condition called hemolytic anemia occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.There are two major forms of thrombotic thrombocytopenic purpura, an acquired (noninherited) form and a familial (inherited) form. The acquired form usually appears in late childhood or adulthood. Affected individuals may have a single episode of signs and symptoms, or, more commonly, they may experience multiple recurrences over time. The familial form of this disorder is much rarer and typically appears in infancy or early childhood, although it can appear later in life. In people with the familial form, signs and symptoms often recur on a regular basis and may return during times of stress, such as during illness or pregnancy. ar Autosomal recessive ADAMTS13 https://medlineplus.gov/genetics/gene/adamts13 Chronic relapsing thrombotic thrombocytopenic purpura Familial thrombotic thrombocytopenia purpura Moschkowitz disease Purpura, thrombotic thrombocytopenic TTP GTR C1268935 ICD-10-CM D69.42 MeSH D011697 OMIM 274150 SNOMED CT 373420004 SNOMED CT 78129009 2020-05 2020-08-18 Tibial muscular dystrophy https://medlineplus.gov/genetics/condition/tibial-muscular-dystrophy descriptionTibial muscular dystrophy is a condition that affects the muscles at the front of the lower leg. The signs and symptoms of this condition typically appear after age 35. The first sign is usually weakness and wasting (atrophy) of a muscle in the lower leg called the tibialis anterior. This muscle helps control up-and-down movement of the foot. Weakness in the tibialis anterior muscle makes it difficult or impossible to walk on the heels, but it usually does not interfere significantly with regular walking.Muscle weakness worsens very slowly in people with tibial muscular dystrophy. Ten to 20 years after the onset of symptoms, weakness may develop in muscles that help extend the toes (long-toe extensors). Weakness in these muscles makes it difficult to lift the toes while walking, a condition known as foot drop. Later in life, about one third of people with tibial muscular dystrophy experience mild to moderate difficulty with walking because of weakness in other leg muscles. However, most affected individuals remain able to walk throughout their lives.A small percentage of people with tibial muscular dystrophy have a somewhat different pattern of signs and symptoms than those described above. Starting in childhood, these individuals may have generalized muscle weakness, weakness and atrophy of the thigh muscles (quadriceps) or other muscles in the legs, and weakness affecting muscles in the arms. ad Autosomal dominant TTN https://medlineplus.gov/genetics/gene/ttn Tardive tibial muscular dystrophy TMD Udd distal myopathy Udd myopathy Udd-Markesbery muscular dystrophy GTR C1838244 MeSH D049310 OMIM 600334 SNOMED CT 698846009 2012-02 2020-08-18 Tietz syndrome https://medlineplus.gov/genetics/condition/tietz-syndrome descriptionTietz syndrome is a disorder characterized by profound hearing loss from birth, fair skin, and light-colored hair. The hearing loss in affected individuals is caused by abnormalities of the inner ear (sensorineural hearing loss) and is present from birth. Although people with Tietz syndrome are born with white hair and very pale skin, their hair color often darkens over time to blond or red. The skin of affected individuals, which sunburns very easily, may tan slightly or develop reddish freckles with limited sun exposure; however, their skin and hair color remain lighter than those of other members of their family.Tietz syndrome also affects the eyes. The colored part of the eye (the iris) in affected individuals is blue, and specialized cells in the eye called retinal pigment epithelial cells lack their normal pigment. The retinal pigment epithelium nourishes the retina, the part of the eye that detects light and color. The changes to the retinal pigment epithelium are generally detectable only by an eye examination; it is unclear whether the changes affect vision. ad Autosomal dominant MITF https://medlineplus.gov/genetics/gene/mitf Albinism and complete nerve deafness Albinism-deafness of Tietz Hypopigmentation-deafness syndrome Hypopigmentation/deafness of Tietz Tietz albinism-deafness syndrome Tietz's syndrome GTR C0391816 MeSH D017496 OMIM 103500 SNOMED CT 403805009 2015-12 2020-08-18 Timothy syndrome https://medlineplus.gov/genetics/condition/timothy-syndrome descriptionTimothy syndrome is a rare disorder that primarily affects the heart but can affect many other areas of the body. The severity of this condition varies among affected individuals, although it is often life-threatening.Timothy syndrome is characterized by a heart condition called long QT syndrome, which causes the heart (cardiac) muscle to take longer than usual to recharge between beats. This abnormality in the heart's electrical system can cause severe abnormalities of the heart rhythm (arrhythmias), which can lead to sudden death. Some people with Timothy syndrome are also born with structural heart defects (cardiomyopathy) that affect the heart's ability to pump blood effectively. As a result of these serious heart problems, some people with Timothy syndrome live only into childhood. In about 80 percent of cases of Timothy syndrome, the cause of death is a severe form of arrhythmia called ventricular tachycardia, in which the lower chambers of the heart (the ventricles) beat abnormally fast, often leading to cardiac arrest (the heart suddenly stops beating) and sudden death.Timothy syndrome is also characterized by webbing or fusion of the skin between some fingers or toes (cutaneous syndactyly). About half of affected people have distinctive facial features such as a flattened nasal bridge, low-set ears, a small upper jaw, and a thin upper lip. Children with this condition have small, misplaced teeth and frequent cavities (dental caries). Additional signs and symptoms of Timothy syndrome can include baldness at birth, low muscle tone (hypotonia), frequent infections, episodes of low blood glucose (hypoglycemia), and an abnormally low body temperature (hypothermia). The respiratory system and gastrointestinal tract can also be affected.Neuropsychiatric features are also common in individuals with Timothy syndrome. Researchers have found that many children with Timothy syndrome have the characteristic features of autism spectrum disorders. Affected children tend to have impaired communication and socialization skills, as well as delayed development of speech and language. Poor coordination is also frequent in affected individuals. Other nervous system disorders that can occur in Timothy syndrome include attention-deficit/hyperactivity disorder, intellectual disability and recurrent seizures (epilepsy); some affected individuals have photosensitive epilepsy, in which seizures are triggered by flashing lights. ad Autosomal dominant CACNA1C https://medlineplus.gov/genetics/gene/cacna1c Long QT syndrome with syndactyly LQT8 TS GTR C1832916 MeSH D000015 MeSH D008133 MeSH D013576 OMIM 601005 SNOMED CT 699256006 SNOMED CT 719907006 2023-01 2023-07-26 Tourette syndrome https://medlineplus.gov/genetics/condition/tourette-syndrome descriptionTourette syndrome is a complex disorder characterized by repetitive, sudden, and involuntary movements or noises called tics. Tics usually appear in childhood, and their severity varies over time. In most cases, tics become milder and less frequent in late adolescence and adulthood.Tourette syndrome involves both motor tics, which are uncontrolled body movements, and vocal or phonic tics, which are outbursts of sound. Some motor tics are simple and involve only one muscle group. Simple motor tics, such as rapid eye blinking, shoulder shrugging, or nose twitching, are usually the first signs of Tourette syndrome. Motor tics also can be complex (involving multiple muscle groups), such as jumping, kicking, hopping, or spinning.Vocal tics, which generally appear later than motor tics, also can be simple or complex. Simple vocal tics include grunting, sniffing, and throat-clearing. More complex vocalizations include repeating the words of others (echolalia) or repeating one's own words (palilalia). The involuntary use of inappropriate or obscene language (coprolalia) is possible, but uncommon, among people with Tourette syndrome.In addition to frequent tics, people with Tourette syndrome are at risk for associated problems including attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and problems with sleep. u Pattern unknown SLITRK1 https://medlineplus.gov/genetics/gene/slitrk1 Chronic motor and vocal tic disorder Gilles de la Tourette syndrome Gilles de la Tourette's syndrome GTS TD Tourette disorder Tourette's disease TS GTR C0040517 ICD-10-CM F95.2 MeSH D005879 OMIM 137580 SNOMED CT 5158005 2008-05 2024-09-19 Townes-Brocks Syndrome https://medlineplus.gov/genetics/condition/townes-brocks-syndrome descriptionTownes-Brocks syndrome is a genetic condition that affects several parts of the body. The most common features of this condition are a malformation of the anal opening (imperforate anus), abnormally shaped ears, and hand malformations that most often affect the thumbs. People with this condition often have at least two of these three major features.Other signs and symptoms of Townes-Brocks syndrome can include kidney abnormalities, mild to profound hearing loss, eye abnormalities, heart defects, foot abnormalities, and genital malformations. These features vary among affected individuals, even within the same family. Mild intellectual disability or learning problems have been reported in about 10 percent of people with Townes-Brocks syndrome. ad Autosomal dominant SALL1 https://medlineplus.gov/genetics/gene/sall1 Anal-ear-renal-radial malformation syndrome Deafness-imperforate anus-hypoplastic thumbs syndrome Imperforate anus-hand and foot anomalies syndrome Renal-ear-anal-radial syndrome (REAR) Sensorineural deafness-imperforate anus-hypoplastic thumbs syndrome Townes syndrome GTR C4551481 MeSH D000015 MeSH D001006 OMIM 107480 OMIM 617466 SNOMED CT 24750000 2020-06 2020-08-18 Transcobalamin deficiency https://medlineplus.gov/genetics/condition/transcobalamin-deficiency descriptionTranscobalamin deficiency is a disorder that impairs the transport of cobalamin (also known as vitamin B12) within the body. Cobalamin is obtained from the diet; this vitamin is found in animal products such as meat, eggs, and shellfish. An inability to transport cobalamin within the body results in cells that lack cobalamin, which they need for many functions including cell growth and division (proliferation) and DNA production. The absence of cobalamin leads to impaired growth, a shortage of blood cells, and many other signs and symptoms that usually become apparent within the first weeks or months of life.The first signs of transcobalamin deficiency are typically a failure to gain weight and grow at the expected rate (failure to thrive), vomiting, diarrhea, and open sores (ulcers) on the mucous membranes such as the lining inside the mouth. Neurological function is impaired in affected individuals, and they can experience progressive stiffness and weakness in their legs (paraparesis), muscle twitches (myoclonus), or intellectual disability.People with transcobalamin deficiency often develop a blood disorder called megaloblastic anemia. Megaloblastic anemia results in a shortage of red blood cells, and the remaining red blood cells are abnormally large. Individuals with transcobalamin deficiency may also have a shortage of white blood cells (neutropenia), which can lead to reduced immune system function. Decreased cellular cobalamin can lead to a buildup of certain compounds in the body, resulting in metabolic conditions known as methylmalonic aciduria or homocystinuria. ar Autosomal recessive TCN2 https://medlineplus.gov/genetics/gene/tcn2 TC deficiency TC II deficiency TCN2 deficiency Transcobalamin II deficiency GTR C0342701 ICD-10-CM D51.2 MeSH D008661 OMIM 275350 SNOMED CT 237934001 2014-10 2024-10-02 Transthyretin amyloidosis https://medlineplus.gov/genetics/condition/transthyretin-amyloidosis descriptionTransthyretin amyloidosis is a progressive condition characterized by the buildup of abnormal protein deposits called amyloids (amyloidosis) in the body's organs and tissues. These protein deposits most frequently occur in the peripheral nervous system, which is made up of nerves that connect the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Protein deposits in these nerves result in a loss of sensation or in muscle weakness in the extremities (peripheral neuropathy). The autonomic nervous system, which controls involuntary body functions such as blood pressure, heart rate, and digestion, may also be affected by amyloidosis. In some cases, the brain and spinal cord (central nervous system) are affected. Other areas of amyloidosis include the heart, kidneys, eyes, and gastrointestinal tract. The age at which symptoms begin to develop varies widely among individuals with this condition, typically ranging from age 20 to 70.There are two major forms of transthyretin amyloidosis, which are distinguished by their symptoms and the body systems they affect.The neuropathic form of transthyretin amyloidosis primarily affects the peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. Impairments to bodily functions can include sexual impotence, diarrhea, constipation, problems with urination, and a sharp drop in blood pressure upon standing (orthostatic hypotension). Some people experience heart and kidney problems as well. Various eye problems may occur, such as cloudiness of the clear gel that fills the eyeball (vitreous opacity), dry eyes, increased pressure in the eyes (glaucoma), or pupils with an irregular or "scalloped" appearance. Some people with this form of transthyretin amyloidosis develop carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers.The cardiac form of transthyretin amyloidosis affects the heart. People with cardiac amyloidosis may have an abnormal heartbeat (arrhythmia), an enlarged heart (cardiomegaly), or orthostatic hypertension. These abnormalities can lead to progressive heart failure and death. Occasionally, people with the cardiac form of transthyretin amyloidosis have mild peripheral neuropathy.A less common form of transthyretin amyloidosis, called the leptomeningeal form, primarily affects the central nervous system. In people with this form, amyloidosis occurs in the leptomeninges, which are two thin layers of tissue that cover the brain and spinal cord. A buildup of proteins in this tissue can cause stroke and bleeding in the brain, an accumulation of fluid in the brain (hydrocephalus), difficulty coordinating movements (ataxia), muscle stiffness and weakness (spastic paralysis), seizures, and loss of intellectual function (dementia). Eye problems similar to those seen in the neuropathic form of transthyretin amyloidosis may also occur; people with leptomeningeal transthyretin amyloidosis who have these eye problems are said to have the oculoleptomeningeal form. ad Autosomal dominant+Inherited or new variant TTR https://medlineplus.gov/genetics/gene/ttr ATTR hATTR Portuguese polyneuritic amyloidosis Portuguese type familial amyloid neuropathy Swiss type amyloid polyneuropathy Type I familial amyloid polyneuropathy Type II familial amyloid polyneuropathy GTR C2751492 ICD-10-CM E85.82 MeSH D028227 OMIM 105210 SNOMED CT 398229007 SNOMED CT 4463009 2023-11 2025-04-03 Treacher Collins syndrome https://medlineplus.gov/genetics/condition/treacher-collins-syndrome descriptionTreacher Collins syndrome is a condition that affects the development of bones and other tissues of the face. The signs and symptoms of this disorder vary greatly, ranging from almost unnoticeable to severe. Most affected individuals have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Some people with this condition are also born with an opening in the roof of the mouth called a cleft palate. In severe cases, underdevelopment of the facial bones may restrict an affected infant's airway, causing potentially life-threatening respiratory problems.People with Treacher Collins syndrome often have eyes that slant downward, sparse eyelashes, and a notch in the lower eyelids called an eyelid coloboma. Some affected individuals have additional eye abnormalities that can lead to vision loss. This condition is also characterized by absent, small, or unusually formed ears. Hearing loss occurs in about half of all affected individuals; hearing loss is caused by defects of the three small bones in the middle ear, which transmit sound, or by underdevelopment of the ear canal. People with Treacher Collins syndrome usually have normal intelligence. ad Autosomal dominant TCOF1 https://medlineplus.gov/genetics/gene/tcof1 POLR1C https://medlineplus.gov/genetics/gene/polr1c POLR1D https://medlineplus.gov/genetics/gene/polr1d Franceschetti-Zwahlen-Klein syndrome Mandibulofacial dysostosis (MFD1) Treacher Collins-Franceschetti syndrome Zygoauromandibular dysplasia GTR C0242387 ICD-10-CM Q75.4 MeSH D008342 OMIM 154500 OMIM 248390 OMIM 613717 SNOMED CT 82203000 2012-06 2023-08-18 Trichohepatoenteric syndrome https://medlineplus.gov/genetics/condition/trichohepatoenteric-syndrome descriptionTrichohepatoenteric syndrome is a condition that affects the hair (tricho-), liver (hepato-), and intestines (enteric), as well as other tissues and organs in the body. This condition is also known as syndromic diarrhea because chronic, difficult-to-treat diarrhea is one of its major features. Within the first few weeks of life, affected infants develop watery diarrhea that occurs multiple times per day. Even with nutritional support through intravenous feedings (parenteral nutrition), many of these children experience failure to thrive, which means they do not gain weight or grow at the expected rate. Most children with trichohepatoenteric syndrome are small at birth, and they remain shorter than their peers throughout life.Abnormal hair is another feature of trichohepatoenteric syndrome. Hair in affected individuals is described as wooly, brittle, patchy, and easily pulled out. Under a microscope, some strands of hair can be seen to vary in diameter, with thicker and thinner spots. This feature is known as trichorrhexis nodosa.Other signs and symptoms of trichohepatoenteric syndrome can include liver disease; skin abnormalities; and distinctive facial features, including a wide forehead, a broad base of the nose, and widely spaced eyes. Overall, the facial features are described as "coarse." Most affected individuals also experience immune system abnormalities that can make them prone to developing infections. Less commonly, trichohepatoenteric syndrome is associated with heart (cardiac) abnormalities. Mild intellectual disability has been reported in at least half of all children with the condition.Trichohepatoenteric syndrome is often life-threatening in childhood, particularly in children who develop liver disease or severe infections. ar Autosomal recessive SKIC2 https://medlineplus.gov/genetics/gene/skic2 SKIC3 https://medlineplus.gov/genetics/gene/skic3 Diarrhea, fatal infantile, with trichorrhexis nodosa Diarrhea, syndromic Intractable diarrhea with phenotypic anomalies Phenotypic diarrhea of infancy SD/THE Syndromic diarrhea THE syndrome THES Tricho-hepato-enteric syndrome GTR C1857276 GTR C3281289 MeSH D003968 OMIM 222470 OMIM 614602 SNOMED CT 703406006 2014-03 2024-07-18 Trichorhinophalangeal syndrome type I https://medlineplus.gov/genetics/condition/trichorhinophalangeal-syndrome-type-i descriptionTrichorhinophalangeal syndrome type I (TRPS I) is a condition that causes bone and joint malformations; distinctive facial features; and abnormalities of the skin, hair, teeth, sweat glands, and nails. The name of the condition describes some of the areas of the body that are commonly affected: hair (tricho-), nose (rhino-), and fingers and toes (phalangeal).In people with TRPS I, the ends (epiphyses) of one or more bones in the fingers or toes are abnormally cone-shaped. Additionally, the fingernails and toenails are typically thin and abnormally formed. Affected individuals often have short feet.Individuals with TRPS I may have a misalignment of the hip joints (hip dysplasia), which often develops in early adulthood but can occur in infancy or childhood. Children with TRPS I often have an unusually large range of movement (hypermobility) in many of their joints. Over time, however, the joints may break down (degenerate), leading to joint pain and a limited range of joint movement.The characteristic appearance of individuals with TRPS I involves thick eyebrows; a broad nose with a rounded tip; large ears, a long, smooth area between the nose and the upper lip (philtrum); a thin upper lip; and small teeth that are either decreased (oligodontia) or increased (supernumerary) in number. Almost all affected individuals have sparse scalp hair. Males are particularly affected by hair loss with many being nearly or completely bald soon after puberty. Some children with this condition have loose skin, but the skin becomes tighter over time. Individuals with TRPS I may experience excessive sweating (hyperhidrosis). ad Autosomal dominant TRPS1 https://medlineplus.gov/genetics/gene/trps1 Trichorhinophalangeal dysplasia type I TRP syndrome TRPS I TRPS1 GTR C0432233 MeSH D015826 OMIM 190350 SNOMED CT 254091006 2017-06 2020-08-18 Trichorhinophalangeal syndrome type II https://medlineplus.gov/genetics/condition/trichorhinophalangeal-syndrome-type-ii descriptionTrichorhinophalangeal syndrome type II (TRPS II) is a condition that causes bone and joint malformations; distinctive facial features; intellectual disability; and abnormalities of the skin, hair, teeth, sweat glands, and nails. The name of the condition describes some of the areas of the body that are commonly affected: hair (tricho-), nose (rhino-), and fingers and toes (phalangeal).People with this condition have multiple noncancerous (benign) bone tumors called osteochondromas. Affected individuals may develop a few to several hundred osteochondromas. These bone growths typically begin in infancy to early childhood and stop forming around adolescence. Depending on the location of the osteochondromas, they can cause pain, limited range of joint movement, or damage to blood vessels or the spinal cord. Individuals with TRPS II may have reduced bone mineral density (osteopenia). Affected individuals often have slow growth before and after birth resulting in short stature. In TRPS II, the ends (epiphyses) of one or more bones in the fingers or toes are abnormally cone-shaped. Additionally, the fingernails and toenails are typically thin and abnormally formed.Children with TRPS II often have an unusually large range of joint movement (hypermobility). However, as osteochondromas begin to develop, typically starting between infancy and mid-childhood, the joints begin to stiffen, leading to decreased mobility. Individuals with TRPS II may also have a misalignment of the hip joints (hip dysplasia), which often develops in early adulthood but can occur in infancy or childhood.The characteristic appearance of individuals with TRPS II involves thick eyebrows; a broad nose with a rounded tip; a long, smooth area between the nose and the upper lip (philtrum); a thin upper lip; and small teeth that are either decreased (oligodontia) or increased (supernumerary) in number. Almost all affected individuals have sparse scalp hair. Males are particularly affected by hair loss, with many being nearly or completely bald soon after puberty. Some children with this condition have loose skin, but the skin becomes tighter over time. Individuals with TRPS II may experience excessive sweating (hyperhidrosis).Most individuals with TRPS II have mild intellectual disability. ad Autosomal dominant EXT1 https://medlineplus.gov/genetics/gene/ext1 TRPS1 https://medlineplus.gov/genetics/gene/trps1 RAD21 https://medlineplus.gov/genetics/gene/rad21 8 https://medlineplus.gov/genetics/chromosome/8 Chromosome 8q24.1 deletion syndrome Giedion-Langer syndrome Langer-Giedion syndrome LGS Tricho-rhino-phalangeal syndrome type II Trichorhinophalangeal syndrome with exostosis TRPS II TRPS2 GTR C0023003 MeSH D015826 OMIM 150230 SNOMED CT 41069008 2017-06 2020-09-08 Trichothiodystrophy https://medlineplus.gov/genetics/condition/trichothiodystrophy descriptionTrichothiodystrophy, commonly called TTD, is a rare inherited condition that affects many parts of the body. The hallmark of this condition is hair that is sparse and easily broken. In people with trichothiodystrophy, tests show that the hair is lacking sulfur-containing proteins that normally gives hair its strength. A cross section of a cut hair shows alternating light and dark banding that has been described as a "tiger tail."The signs and symptoms of trichothiodystrophy vary widely. Mild cases may involve only the hair. More severe cases also cause delayed development, significant intellectual disability, and recurrent infections; severely affected individuals may survive only into infancy or early childhood.Mothers of children with trichothiodystrophy may experience problems during pregnancy including pregnancy-induced high blood pressure (preeclampsia) and a related condition called HELLP syndrome that can damage the liver. Babies with trichothiodystrophy are at increased risk of premature birth, low birth weight, and slow growth. Most children with trichothiodystrophy have short stature compared to others their age. Intellectual disability and delayed development are common in people with trichothiodystrophy, although most affected individuals are highly social with an outgoing and engaging personality. Some people with trichothiodystrophy have brain abnormalities that can be seen with imaging tests. A common neurological feature of this disorder is impaired myelin production (dysmyelination). Myelin is a fatty substance that insulates nerve cells and promotes the rapid transmission of nerve impulses.Trichothiodystrophy is also associated with recurrent infections, particularly respiratory infections, which can be life-threatening. People with trichothiodystrophy may have abnormal red blood cells, including red blood cells that are smaller than normal. They may also have elevated levels of a type of hemoglobin called A2, which is a protein found in red blood cells. Other features of trichothiodystrophy can include dry, scaly skin (ichthyosis); abnormalities of the fingernails and toenails; clouding of the lens in both eyes from birth (congenital cataracts); poor coordination; and skeletal abnormalities including degeneration of both hips at an early age.About half of all people with trichothiodystrophy have a photosensitive form of the disorder, which causes them to be extremely sensitive to ultraviolet (UV) rays from sunlight. They develop a severe sunburn after spending just a few minutes in the sun. However, for reasons that are unclear, they do not develop other sun-related problems such as excessive freckling of the skin or an increased risk of skin cancer. Many people with trichothiodystrophy report that they do not sweat. ar Autosomal recessive ERCC2 https://medlineplus.gov/genetics/gene/ercc2 ERCC3 https://medlineplus.gov/genetics/gene/ercc3 GTF2H5 https://medlineplus.gov/genetics/gene/gtf2h5 MPLKIP https://medlineplus.gov/genetics/gene/mplkip AARS1 https://www.ncbi.nlm.nih.gov/gene/16 CARS1 https://www.ncbi.nlm.nih.gov/gene/833 GTF2E2 https://www.ncbi.nlm.nih.gov/gene/2961 MARS1 https://www.ncbi.nlm.nih.gov/gene/4141 TARS1 https://www.ncbi.nlm.nih.gov/gene/6897 RNF113A https://www.ncbi.nlm.nih.gov/gene/7737 Amish brittle hair syndrome BIDS syndrome Brittle hair-intellectual impairment-decreased fertility-short stature syndrome IBIDS PIBIDS TTD GTR C1313961 GTR C1866504 GTR C4017171 GTR C4225344 GTR C4225420 GTR C4310785 GTR C5231403 GTR C5562057 GTR C5562058 MeSH D054463 OMIM 234050 OMIM 601675 SNOMED CT 403796005 SNOMED CT 723551003 2023-04 2023-08-18 Trimethylaminuria https://medlineplus.gov/genetics/condition/trimethylaminuria descriptionTrimethylaminuria is a disorder in which the body is unable to break down trimethylamine, a chemical compound that has a pungent odor. Trimethylamine has been described as smelling like rotten or decaying fish. As this compound builds up in the body, it causes affected people to give off a strong fishy odor in their sweat, urine, and breath. The intensity of the odor may vary over time. The odor can interfere with many aspects of daily life, affecting a person's relationships, social life, and career. Some people with trimethylaminuria experience depression and social isolation as a result of this condition. ad Autosomal dominant FMO3 https://medlineplus.gov/genetics/gene/fmo3 Fish malodor syndrome Fish odor syndrome Stale fish syndrome TMAU TMAuria GTR C0342739 ICD-10-CM E72.52 MeSH D008661 OMIM 602079 SNOMED CT 237959005 2007-04 2022-11-14 Triosephosphate isomerase deficiency https://medlineplus.gov/genetics/condition/triosephosphate-isomerase-deficiency descriptionTriosephosphate isomerase deficiency is a disorder characterized by a shortage of red blood cells (anemia), movement problems, increased susceptibility to infection, and muscle weakness that can affect breathing and heart function.The anemia in this condition begins in infancy. Since the anemia results from the premature breakdown of red blood cells (hemolysis), it is known as hemolytic anemia. A shortage of red blood cells to carry oxygen throughout the body leads to extreme tiredness (fatigue), pale skin (pallor), and shortness of breath. When the red cells are broken down, iron and a molecule called bilirubin are released; individuals with triosephosphate isomerase deficiency have an excess of these substances circulating in the blood. Excess bilirubin in the blood causes jaundice, which is a yellowing of the skin and the whites of the eyes.Movement problems typically become apparent by age 2 in people with triosephosphate isomerase deficiency. The movement problems are caused by impairment of motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. This impairment leads to muscle weakness and wasting (atrophy) and causes the movement problems typical of triosephosphate isomerase deficiency, including involuntary muscle tensing (dystonia), tremors, and weak muscle tone (hypotonia). Affected individuals may also develop seizures.Weakness of other muscles, such as the heart (a condition known as cardiomyopathy) and the muscle that separates the abdomen from the chest cavity (the diaphragm) can also occur in triosephosphate isomerase deficiency. Diaphragm weakness can cause breathing problems and ultimately leads to respiratory failure.Individuals with triosephosphate isomerase deficiency are at increased risk of developing infections because they have poorly functioning white blood cells. These immune system cells normally recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The most common infections in people with triosephosphate isomerase deficiency are bacterial infections of the respiratory tract.People with triosephosphate isomerase deficiency often do not survive past childhood due to respiratory failure. In a few rare cases, affected individuals without severe nerve damage or muscle weakness have lived into adulthood. ar Autosomal recessive TPI1 https://medlineplus.gov/genetics/gene/tpi1 Deficiency of phosphotriose isomerase Hereditary nonspherocytic hemolytic anemia due to triosephosphate isomerase deficiency TPI deficiency TPID Triose phosphate isomerase deficiency GTR C1860808 ICD-10-CM D55.2 MeSH D002239 OMIM 615512 SNOMED CT 44641000 2014-08 2024-05-22 Triple A syndrome https://medlineplus.gov/genetics/condition/triple-a-syndrome descriptionTriple A syndrome, also called Allgrove syndrome, is an inherited condition that gets its name from three specific features: achalasia, adrenal insufficiency, and alacrima. Most people with triple A syndrome have all three of these features, although some have only two. Achalasia is a disorder that affects the ability to move food through the esophagus, the tube that connects the throat to the stomach. Achalasia can lead to severe feeding difficulties, vomiting, and weight loss. Signs and symptoms of achalasia can appear at any time between the ages of 6 months and late adolescence.Adrenal insufficiency occurs when the small hormone-producing glands on top of each kidney (adrenal glands) do not produce enough hormones. Features of adrenal insufficiency can include fatigue, loss of appetite, weight loss, low blood pressure, low blood glucose (hypoglycemia), and seizures.The third major feature of triple A syndrome is alacrima. Tear secretion is reduced or completely absent in people with alacrima. This feature is often the first noticeable sign of triple A syndrome in affected infants.Approximately one-third of all people with triple A syndrome also have dysfunction of the autonomic nervous system (dysautonomia). The autonomic nervous system regulates involuntary bodily processes, including digestion, blood pressure, and body temperature. People with triple A syndrome may experience abnormal sweating, changes in the production of saliva, difficulty regulating blood pressure and heart rate, unequal pupil size (anisocoria), and other problems.Additional features of triple A syndrome can include cognitive abilities that decline over time. Affected individuals may also have muscle weakness, difficulty coordinating movements (ataxia), speech problems (dysarthria), short stature, and a small head size (microcephaly). Adults with triple A syndrome often have brittle bones that are prone to fracture (osteoporosis). Optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain, has also been found in affected individuals.People with triple A syndrome may develop skin abnormalities, such as darkening of the skin and thickening of the outer layer of the skin (hyperkeratosis) on the palms of the hands and the soles of the feet. The symptoms of triple A syndrome typically develop gradually over a period of several years and can vary widely, even among members of the same family. ar Autosomal recessive AAAS https://medlineplus.gov/genetics/gene/aaas GMPPA https://www.ncbi.nlm.nih.gov/gene/29926 TRAPPC11 https://www.ncbi.nlm.nih.gov/gene/60684 2A syndrome 3A syndrome 4A syndrome AAA AAA syndrome Achalasia-addisonianism-alacrima syndrome Achalasia-alacrima syndrome Adrenal insufficiency-achalasia-alacrima syndrome Allgrove syndrome Double A syndrome Quarternary A syndrome GTR C0271742 MeSH D000309 MeSH D004931 MeSH D007766 OMIM 231550 SNOMED CT 45414006 2025-08 2025-08-22 Trisomy 13 https://medlineplus.gov/genetics/condition/trisomy-13 descriptionTrisomy 13, also called Patau syndrome, is a chromosomal condition associated with severe intellectual disability and physical abnormalities in many parts of the body. Individuals with trisomy 13 often have heart defects, brain or spinal cord abnormalities, very small or poorly developed eyes (microphthalmia), extra fingers or toes, an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (a cleft palate), and weak muscle tone (hypotonia). Due to the presence of several life-threatening medical problems, many infants with trisomy 13 die within their first days or weeks of life. Only five percent to 10 percent of children with this condition live past their first year. n Not inherited 13 https://medlineplus.gov/genetics/chromosome/13 Bartholin-Patau syndrome Complete trisomy 13 syndrome Patau syndrome Patau's syndrome Trisomy 13 syndrome GTR C0152095 ICD-10-CM Q91.4 ICD-10-CM Q91.5 ICD-10-CM Q91.6 ICD-10-CM Q91.7 MeSH D000073839 SNOMED CT 21111006 SNOMED CT 254268004 SNOMED CT 737540008 2009-01 2021-09-09 Trisomy 18 https://medlineplus.gov/genetics/condition/trisomy-18 descriptionTrisomy 18, also called Edwards syndrome, is a chromosomal condition associated with abnormalities in many parts of the body. Individuals with trisomy 18 often have slow growth before birth (intrauterine growth retardation) and a low birth weight. Affected individuals may have heart defects and abnormalities of other organs that develop before birth. Other features of trisomy 18 include a small, abnormally shaped head; a small jaw and mouth; and clenched fists with overlapping fingers. Due to the presence of several life-threatening medical problems, many individuals with trisomy 18 die before birth or within their first month. Five to 10 percent of children with this condition live past their first year, and these children often have severe intellectual disability. n Not inherited 18 https://medlineplus.gov/genetics/chromosome/18 Complete trisomy 18 syndrome Edwards syndrome Trisomy 18 syndrome Trisomy E syndrome GTR C0152096 ICD-10-CM Q91 ICD-10-CM Q91.0 ICD-10-CM Q91.1 ICD-10-CM Q91.2 ICD-10-CM Q91.3 ICD-10-CM Q91.4 ICD-10-CM Q91.5 ICD-10-CM Q91.6 ICD-10-CM Q91.7 MeSH D000073842 SNOMED CT 254266000 SNOMED CT 51500006 SNOMED CT 737541007 2012-03 2021-02-16 Trisomy X https://medlineplus.gov/genetics/condition/trisomy-x descriptionTrisomy X, also called triple X syndrome or 47,XXX, is characterized by the presence of an additional X chromosome in each of a female's cells. Although females with this condition may be taller than average, this chromosomal change typically causes no unusual physical features. Most females with trisomy X have normal sexual development and are able to conceive children.Trisomy X is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills (such as sitting and walking), weak muscle tone (hypotonia), and behavioral and emotional difficulties are also possible, but these characteristics vary widely. Seizures or kidney abnormalities occur in about 10 percent of affected females. n Not inherited X https://medlineplus.gov/genetics/chromosome/x 47,XXX 47,XXX syndrome Triple X syndrome Triplo X syndrome Trisomy X XXX syndrome GTR C0221033 ICD-10-CM Q97.0 MeSH D025064 SNOMED CT 35111009 2022-02 2022-03-01 Troyer syndrome https://medlineplus.gov/genetics/condition/troyer-syndrome descriptionTroyer syndrome is a type of hereditary spastic paraplegia, also called hereditary spastic paraparesis. Hereditary spastic paraplegias are a group of genetic disorders characterized by progressive stiffness (spasticity) and weakness of the leg muscles. The degree of leg weakness in people with hereditary spastic paraplegia can vary. Paraparesis is the term used to describe leg weakness, while paraplegia refers to severe weakness of the leg muscles. Hereditary spastic paraplegias are divided into two types: pure and complex (sometimes called uncomplicated and complicated). The pure types of hereditary spastic paraplegia involve the legs and the bladder. Complex hereditary spastic paraplegias may include additional signs and symptoms such as intellectual disabilities, problems with coordination and balance (ataxia), and damage to the nerves that connect the brain and spinal cord to the rest of the body (peripheral neuropathy). Troyer syndrome is a complex hereditary spastic paraplegia. People with Troyer syndrome can experience a variety of signs and symptoms. These health problems typically begin in early childhood and slowly worsen over time. Common features of Troyer syndrome include delays in learning to walk and talk, progressive weakness and spasticity of the leg muscles, muscle wasting in the hands and feet (distal amyotrophy), and short stature. Affected individuals may also have speech difficulties (dysarthria), skeletal (bone) abnormalities, and mood swings. Troyer syndrome causes the breakdown (degeneration) and death of muscle cells and motor neurons (specialized nerve cells that control muscle movement) throughout a person's lifetime, leading to a slow decline in muscle and nerve function. Most affected individuals require wheelchair assistance by the time they are in their 50s or 60s. Troyer syndrome generally does not affect a person's life expectancy. ar Autosomal recessive SPART https://medlineplus.gov/genetics/gene/spart Autosomal recessive spastic paraplegia type 20 Spastic paraparesis, childhood-onset, with distal muscle wasting Spastic paraplegia 20, autosomal recessive Spastic paraplegia, autosomal recessive, Troyer type SPG20 GTR C0037773 GTR C0393559 ICD-10-CM G11.4 MeSH D010264 MeSH D015419 OMIM 275900 SNOMED CT 230264003 2024-09 2024-09-09 Tuberous sclerosis complex https://medlineplus.gov/genetics/condition/tuberous-sclerosis-complex descriptionTuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body. These tumors can occur in the brain, kidneys, heart, skin, and other organs, in some cases leading to significant health problems. Tuberous sclerosis complex also causes developmental problems, and the signs and symptoms of the condition vary from person to person.Tuberous sclerosis complex often affects the brain, with some affected individuals having benign growths in the outer surface of the brain (cerebral cortex) known as cortical tubers. Individuals with tuberous sclerosis complex often develop a pattern of behaviors called TSC-associated neuropsychiatric disorders (TAND). These disorders include hyperactivity, aggression, psychiatric conditions, intellectual disability, and problems with communication and social interaction (autism spectrum disorder). Additionally, individuals with tuberous sclerosis complex may have attention-deficit/hyperactivity disorder (ADHD) or seizures.Kidney tumors are common in people with tuberous sclerosis complex; these growths can cause severe problems with kidney function and may be life-threatening in some cases. Additionally, tumors can develop in the heart (cardiac rhabdomyoma) and the light-sensitive tissue at the back of the eye (the retina). Some women with tuberous sclerosis complex develop lymphangioleiomyomatosis (LAM), which is a lung disease characterized by the abnormal overgrowth of smooth muscle-like tissue in the lungs that causes coughing, shortness of breath, chest pain, and lung collapse.Virtually all affected people have skin abnormalities, including patches of unusually light-colored skin, areas of raised and thickened skin, and growths under the nails. Tumors on the face called facial angiofibromas are also common beginning in childhood. Sometimes, affected individuals have areas of bone or dental damage. ad Autosomal dominant TSC1 https://medlineplus.gov/genetics/gene/tsc1 TSC2 https://medlineplus.gov/genetics/gene/tsc2 Bourneville disease Bourneville phakomatosis Cerebral sclerosis Sclerosis tuberosa Tuberose sclerosis GTR C1854465 GTR C1860707 ICD-10-CM Q85.1 MeSH D014402 OMIM 191100 OMIM 613254 SNOMED CT 36025004 SNOMED CT 7199000 2009-06 2022-05-16 Tubular aggregate myopathy https://medlineplus.gov/genetics/condition/tubular-aggregate-myopathy descriptionTubular aggregate myopathy is a disorder that primarily affects the skeletal muscles, which are muscles the body uses for movement. This disorder causes muscle pain, cramping, or weakness that begins in childhood and worsens over time. The muscles of the lower limbs are most often affected, although the upper limbs can also be involved. Affected individuals can have difficulty running, climbing stairs, or getting up from a squatting position. The weakness may also lead to an unusual walking style (gait). Some people with this condition develop joint deformities (contractures) in the arms and legs.Skeletal muscles are normally made up of two types of fibers, called type I and type II fibers, in approximately equal quantities. Type I fibers, also called slow twitch fibers, are used for long, sustained activity, such as walking long distances. Type II fibers, also known as fast twitch fibers, are used for short bursts of strength, which are needed for activities such as running up stairs or sprinting. In people with tubular aggregate myopathy, type II fibers waste away (atrophy), so affected individuals have mostly type I fibers. In addition, proteins build up abnormally in both type I and type II fibers, forming clumps of tube-like structures called tubular aggregates. Tubular aggregates can occur in other muscle disorders, but they are the primary muscle cell abnormality in tubular aggregate myopathy. ar Autosomal recessive ad Autosomal dominant STIM1 https://medlineplus.gov/genetics/gene/stim1 ORAI1 https://www.ncbi.nlm.nih.gov/gene/84876 Myopathy with tubular aggregates TAM GTR C4011726 MeSH D020914 OMIM 160565 SNOMED CT 240087000 2014-09 2020-08-18 Tumor necrosis factor receptor-associated periodic syndrome https://medlineplus.gov/genetics/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome descriptionTumor necrosis factor receptor-associated periodic syndrome (commonly known as TRAPS) is a condition characterized by recurrent episodes of fever. These fevers typically last about 3 weeks but can last from a few days to a few months. The frequency of the episodes varies greatly among affected individuals; fevers can occur anywhere between every 6 weeks to every few years. Some individuals can go many years without having a fever episode. Fever episodes usually occur spontaneously, but sometimes they can be brought on by a variety of triggers, such as minor injury, infection, stress, exercise, or hormonal changes.During episodes of fever, people with TRAPS can have additional signs and symptoms. These include abdominal and muscle pain and a spreading skin rash, typically found on the limbs. Affected individuals may also experience puffiness or swelling in the skin around the eyes (periorbital edema); joint pain; and inflammation in various areas of the body including the eyes, heart muscle, certain joints, throat, or mucous membranes such as the moist lining of the mouth and digestive tract. Occasionally, people with TRAPS develop amyloidosis, an abnormal buildup of a protein called amyloid in the kidneys that can lead to kidney failure. It is estimated that 15 to 20 percent of people with TRAPS develop amyloidosis, typically in mid-adulthood.The fever episodes characteristic of TRAPS can begin at any age, from infancy to late adulthood, but most people have their first episode in childhood. ad Autosomal dominant TNFRSF1A https://medlineplus.gov/genetics/gene/tnfrsf1a Autosomal dominant familial periodic fever Familial Hibernian fever FPF TNF receptor-associated periodic fever syndrome TRAPS GTR C1275126 MeSH D056660 OMIM 142680 SNOMED CT 403833009 2011-08 2026-03-04 Turner syndrome https://medlineplus.gov/genetics/condition/turner-syndrome descriptionTurner syndrome is a chromosomal condition that affects development. Females typically have two X chromosomes, but in individuals with Turner syndrome, one copy of the X chromosome is missing or altered.The most common feature of Turner syndrome is short stature, which becomes evident by about age 5. Reduced functioning of the ovaries, the female reproductive organs that produce egg cells (oocytes) and female sex hormones, is also very common. The ovaries develop normally at first, but egg cells usually die prematurely and most ovarian tissue breaks down before birth. Many females with Turner syndrome do not undergo puberty unless they receive hormone therapy, and most are unable to become pregnant naturally. A small percentage of people with Turner syndrome retain normal ovarian function through young adulthood.About 30 percent of individuals with Turner syndrome have extra folds of skin on the neck (webbed neck), a low hairline at the back of the neck, puffiness or swelling (lymphedema) of the hands and feet, skeletal abnormalities, or kidney problems. One-third to one-half of individuals with Turner syndrome are born with a heart defect, such as a narrowing of the large artery that leaves the heart (coarctation of the aorta) or abnormalities of the valve that connects the aorta to the heart (the aortic valve). Complications associated with these heart defects can be life-threatening.Most people with Turner syndrome have normal intelligence. Developmental delays, nonverbal learning disabilities, and behavioral problems are possible, although these characteristics vary among affected individuals. n Not inherited SHOX https://medlineplus.gov/genetics/gene/shox X https://medlineplus.gov/genetics/chromosome/x 45,X Monosomy X TS Turner's syndrome Ullrich-Turner syndrome GTR C0041408 ICD-10-CM Q96 ICD-10-CM Q96.0 ICD-10-CM Q96.1 ICD-10-CM Q96.2 ICD-10-CM Q96.3 ICD-10-CM Q96.4 ICD-10-CM Q96.8 ICD-10-CM Q96.9 MeSH D014424 SNOMED CT 38804009 2023-04 2025-03-06 Type 1 diabetes https://medlineplus.gov/genetics/condition/type-1-diabetes descriptionType 1 diabetes is a disorder characterized by abnormally high levels of blood glucose, also called blood sugar. In this form of diabetes, specialized cells in the pancreas called beta cells stop producing insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Lack of insulin results in the inability to use glucose for energy or to control the amount of glucose in the blood.Type 1 diabetes can occur at any age, from early childhood to late adulthood. The first signs and symptoms of the disorder are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet, and weight loss. These symptoms may recur during the course of the disorder if blood glucose is not well controlled by insulin replacement therapy. Improper control can also cause blood glucose levels to become too low (hypoglycemia). This may occur when the body's needs change, such as during exercise or if eating is delayed. Hypoglycemia can cause headache, dizziness, hunger, shaking, sweating, weakness, and agitation.Uncontrolled type 1 diabetes can lead to a life-threatening complication called diabetic ketoacidosis. Without insulin, cells cannot take in glucose. A lack of glucose in cells prompts the liver to try to compensate by releasing more glucose into the blood, and blood glucose can become extremely high. The cells, unable to use the glucose in the blood for energy, respond by using fats instead. Breaking down fats to obtain energy produces waste products called ketones, which can build up to toxic levels in people with type 1 diabetes, resulting in diabetic ketoacidosis. Affected individuals may begin breathing rapidly; develop a fruity odor in the breath; and experience nausea, vomiting, facial flushing, stomach pain, and dryness of the mouth (xerostomia). In severe cases, diabetic ketoacidosis can lead to coma and death.Over many years, the chronic high blood glucose associated with diabetes may cause damage to blood vessels and nerves, leading to complications affecting many organs and tissues. The retina, which is the light-sensitive tissue at the back of the eye, can be damaged (diabetic retinopathy), leading to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) may also occur and can lead to kidney failure and end-stage renal disease (ESRD). Pain, tingling, and loss of normal sensation (diabetic neuropathy) often occur, especially in the feet. Impaired circulation and absence of the normal sensations that prompt reaction to injury can result in permanent damage to the feet; in severe cases, the damage can lead to amputation. People with type 1 diabetes are also at increased risk of heart attacks, strokes, and problems with urinary and sexual function. u Pattern unknown FOXP3 https://medlineplus.gov/genetics/gene/foxp3 PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 HLA-DQB1 https://medlineplus.gov/genetics/gene/hla-dqb1 INS https://medlineplus.gov/genetics/gene/ins HLA-DQA1 https://medlineplus.gov/genetics/gene/hla-dqa1 HLA-DRB1 https://medlineplus.gov/genetics/gene/hla-drb1 HNF1A https://medlineplus.gov/genetics/gene/hnf1a CCR5 https://www.ncbi.nlm.nih.gov/gene/1234 CTLA4 https://www.ncbi.nlm.nih.gov/gene/1493 IL2RA https://www.ncbi.nlm.nih.gov/gene/3559 IL6 https://www.ncbi.nlm.nih.gov/gene/3569 ITPR3 https://www.ncbi.nlm.nih.gov/gene/3710 OAS1 https://www.ncbi.nlm.nih.gov/gene/4938 SUMO4 https://www.ncbi.nlm.nih.gov/gene/387082 Autoimmune diabetes Diabetes mellitus type 1 Diabetes mellitus, insulin-dependent Diabetes mellitus, type 1 IDDM Insulin-dependent diabetes mellitus JOD Juvenile diabetes Juvenile-onset diabetes Juvenile-onset diabetes mellitus T1D Type 1 diabetes mellitus GTR C0011854 GTR C1832392 GTR C1838260 GTR C1852092 GTR C1866040 GTR C2675864 ICD-10-CM E10 ICD-10-CM E10.1 ICD-10-CM E10.10 ICD-10-CM E10.11 ICD-10-CM E10.2 ICD-10-CM E10.21 ICD-10-CM E10.22 ICD-10-CM E10.29 ICD-10-CM E10.3 ICD-10-CM E10.31 ICD-10-CM E10.311 ICD-10-CM E10.319 ICD-10-CM E10.32 ICD-10-CM E10.321 ICD-10-CM E10.329 ICD-10-CM E10.33 ICD-10-CM E10.331 ICD-10-CM E10.339 ICD-10-CM E10.34 ICD-10-CM E10.341 ICD-10-CM E10.349 ICD-10-CM E10.35 ICD-10-CM E10.351 ICD-10-CM E10.359 ICD-10-CM E10.36 ICD-10-CM E10.39 ICD-10-CM E10.4 ICD-10-CM E10.40 ICD-10-CM E10.41 ICD-10-CM E10.42 ICD-10-CM E10.43 ICD-10-CM E10.44 ICD-10-CM E10.49 ICD-10-CM E10.5 ICD-10-CM E10.51 ICD-10-CM E10.52 ICD-10-CM E10.59 ICD-10-CM E10.6 ICD-10-CM E10.61 ICD-10-CM E10.610 ICD-10-CM E10.618 ICD-10-CM E10.62 ICD-10-CM E10.620 ICD-10-CM E10.621 ICD-10-CM E10.622 ICD-10-CM E10.628 ICD-10-CM E10.63 ICD-10-CM E10.630 ICD-10-CM E10.638 ICD-10-CM E10.64 ICD-10-CM E10.641 ICD-10-CM E10.649 ICD-10-CM E10.65 ICD-10-CM E10.69 ICD-10-CM E10.8 ICD-10-CM E10.9 ICD-10-CM O24.01 ICD-10-CM O24.011 ICD-10-CM O24.012 ICD-10-CM O24.013 ICD-10-CM O24.019 MeSH D003922 OMIM 125852 OMIM 222100 OMIM 300136 OMIM 600318 OMIM 600319 OMIM 600320 OMIM 600321 OMIM 600883 OMIM 601208 OMIM 601318 OMIM 601388 OMIM 601666 OMIM 601941 OMIM 601942 OMIM 603266 OMIM 605598 OMIM 610155 OMIM 612520 OMIM 612521 OMIM 612522 OMIM 612622 OMIM 613006 SNOMED CT 46635009 SNOMED CT 870528001 2013-03 2025-12-22 Type 2 diabetes https://medlineplus.gov/genetics/condition/type-2-diabetes descriptionType 2 diabetes is a disorder characterized by abnormally high levels of blood glucose, also called blood sugar. In this form of diabetes, the body stops using and making insulin properly. Insulin is a hormone produced in the pancreas that helps regulate blood glucose levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source. When blood glucose levels are high (such as after a meal), the pancreas releases insulin to move the excess glucose into cells, which reduces the amount of glucose in the blood.Most people who develop type 2 diabetes first have insulin resistance, a condition in which the body's cells use insulin less efficiently than normal. As insulin resistance develops, more and more insulin is needed to keep blood glucose levels in the normal range. To keep up with the increasing need, insulin-producing cells in the pancreas (called beta cells) make larger amounts of insulin. Over time, the beta cells become less able to respond to blood glucose changes, leading to an insulin shortage that prevents the body from reducing blood glucose levels effectively. Most people have some insulin resistance as they age, but inadequate exercise and excessive weight gain make it worse, greatly increasing the likelihood of developing type 2 diabetes.Type 2 diabetes can occur at any age, but it most commonly begins in middle age or later. Signs and symptoms develop slowly over years. They include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet (diabetic neuropathy), sores that do not heal well, and weight loss. If blood glucose levels are not controlled through medication or diet, type 2 diabetes can cause long-lasting (chronic) health problems including heart disease and stroke; nerve damage; and damage to the kidneys, eyes, and other parts of the body. u Pattern unknown Adult-onset diabetes Adult-onset diabetes mellitus AODM Diabetes mellitus, adult-onset Diabetes mellitus, non-insulin-dependent Diabetes mellitus, type 2 Diabetes mellitus, type II Maturity-onset diabetes Maturity-onset diabetes mellitus NIDDM Noninsulin-dependent diabetes mellitus T2D Type 2 diabetes mellitus GTR C0011860 ICD-10-CM E11 ICD-10-CM E11.0 ICD-10-CM E11.00 ICD-10-CM E11.01 ICD-10-CM E11.2 ICD-10-CM E11.21 ICD-10-CM E11.22 ICD-10-CM E11.29 ICD-10-CM E11.3 ICD-10-CM E11.31 ICD-10-CM E11.311 ICD-10-CM E11.319 ICD-10-CM E11.32 ICD-10-CM E11.321 ICD-10-CM E11.329 ICD-10-CM E11.33 ICD-10-CM E11.331 ICD-10-CM E11.339 ICD-10-CM E11.34 ICD-10-CM E11.341 ICD-10-CM E11.349 ICD-10-CM E11.35 ICD-10-CM E11.351 ICD-10-CM E11.352 ICD-10-CM E11.353 ICD-10-CM E11.354 ICD-10-CM E11.355 ICD-10-CM E11.359 ICD-10-CM E11.36 ICD-10-CM E11.37 ICD-10-CM E11.39 ICD-10-CM E11.4 ICD-10-CM E11.40 ICD-10-CM E11.41 ICD-10-CM E11.42 ICD-10-CM E11.43 ICD-10-CM E11.44 ICD-10-CM E11.49 ICD-10-CM E11.5 ICD-10-CM E11.51 ICD-10-CM E11.52 ICD-10-CM E11.59 ICD-10-CM E11.6 ICD-10-CM E11.61 ICD-10-CM E11.610 ICD-10-CM E11.618 ICD-10-CM E11.62 ICD-10-CM E11.620 ICD-10-CM E11.621 ICD-10-CM E11.622 ICD-10-CM E11.628 ICD-10-CM E11.63 ICD-10-CM E11.630 ICD-10-CM E11.638 ICD-10-CM E11.64 ICD-10-CM E11.641 ICD-10-CM E11.649 ICD-10-CM E11.65 ICD-10-CM E11.69 ICD-10-CM E11.8 ICD-10-CM E11.9 MeSH D003924 OMIM 125853 SNOMED CT 44054006 2017-11 2025-04-03 Type A insulin resistance syndrome https://medlineplus.gov/genetics/condition/type-a-insulin-resistance-syndrome descriptionType A insulin resistance syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with type A insulin resistance syndrome, insulin resistance impairs blood glucose regulation and ultimately leads to a condition called diabetes mellitus, in which blood glucose levels can become dangerously high.Severe insulin resistance also underlies the other signs and symptoms of type A insulin resistance syndrome. In affected females, the major features of the condition become apparent in adolescence. Many affected females do not begin menstruation by age 16 (primary amenorrhea) or their periods may be light and irregular (oligomenorrhea). They develop cysts on the ovaries and excessive body hair growth (hirsutism). Most affected females also develop a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Unlike most people with insulin resistance, females with type A insulin resistance syndrome are usually not overweight.The features of type A insulin resistance syndrome are more subtle in affected males. Some males have low blood glucose (hypoglycemia) as the only sign; others may also have acanthosis nigricans. In many cases, males with this condition come to medical attention only when they develop diabetes mellitus in adulthood.Type A insulin resistance syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and Rabson-Mendenhall syndrome, are considered part of a spectrum. Type A insulin resistance syndrome represents the mildest end of the spectrum: its features often do not become apparent until puberty or later, and it is generally not life-threatening. ad Autosomal dominant ar Autosomal recessive INSR https://medlineplus.gov/genetics/gene/insr Diabetes mellitus, insulin-resistant, with acanthosis nigricans Extreme insulin resistance with acanthosis nigricans, hirsutism and abnormal insulin receptors Insulin resistance - type A Insulin resistance syndrome, type A Insulin-resistance syndrome type A Insulin-resistant diabetes mellitus and acanthosis nigricans Type A insulin resistance GTR C0342278 MeSH D000052 MeSH D007333 OMIM 610549 SNOMED CT 237651005 SNOMED CT 24203005 2014-12 2023-07-19 Tyrosine hydroxylase deficiency https://medlineplus.gov/genetics/condition/tyrosine-hydroxylase-deficiency descriptionTyrosine hydroxylase (TH) deficiency is a disorder that primarily affects movement. There are three forms of tyrosine hydroxylase deficiency, and they are categorized based on the severity of their symptoms and their response to treatment. The three forms range in severity from mild to severe.For those with the mild form of tyrosine hydroxylase deficiency (also called TH-deficient dopa-responsive dystonia), symptoms usually appear during childhood. Affected individuals may have difficulties walking and running, which can sometimes lead to falls. Some people with the disorder may walk on their toes because of stiffness in the leg muscles. Additional signs and symptoms may include involuntary muscle contractions (dystonia) that lead to abnormal repetitive movements in the legs, tremor when holding a position (postural tremor), or involuntary upward-rolling movements of the eyes. Symptoms tend to worsen later in the day for some people with TH-deficient dopa-responsive dystonia. Affected individuals may experience more pronounced movement difficulties as they age, but these symptoms almost always get better with medical treatment.The more severe forms of tyrosine hydroxylase deficiency are often called TH-deficient infantile parkinsonism or TH-deficient progressive infantile encephalopathy. These forms of the disorder appear soon after birth and are more difficult to treat.Signs and symptoms of TH-deficient infantile parkinsonism typically begin in the first year of life. Affected infants often have delayed development of motor skills such as sitting unsupported or reaching for a toy. Some signs and symptoms may resemble those seen in people with Parkinson disease: stiffness of the muscles in the arms and legs, slow or diminished movements (hypokinesia), and tremors. Additional signs and symptoms may include droopy eyelids (ptosis), involuntary upward-rolling eye movements, and intellectual disabilities. People with TH-deficient infantile parkinsonism may respond to treatment, though treatment may not work right away and may not resolve all of the symptoms of the condition.The most severe form of tyrosine hydroxylase deficiency (also called TH-deficient progressive infantile encephalopathy) is characterized by brain dysfunction that leads to profound physical and intellectual disabilities. Signs and symptoms typically begin in the first six months of life. Babies with this form of tyrosine hydroxylase deficiency often have feeding difficulties and delayed growth. Additional features include hypokinesia and abnormal eye movements. This form of tyrosine hydroxylase deficiency is difficult to treat, as affected infants tend to be more likely to experience harmful side effects from the medicine. ar Autosomal recessive TH https://medlineplus.gov/genetics/gene/th Autosomal recessive dopa-responsive dystonia Autosomal recessive infantile parkinsonism Autosomal recessive Segawa syndrome DYT5b TH deficiency TH-deficient DRD Tyrosine hydroxylase-deficient dopa-responsive dystonia GTR C2673535 GTR C5700309 ICD-10-CM MeSH D020734 OMIM 605407 SNOMED CT 715827001 2024-05 2024-04-29 Tyrosinemia https://medlineplus.gov/genetics/condition/tyrosinemia descriptionTyrosinemia is a genetic disorder characterized by problems breaking down the amino acid tyrosine, which is a building block of most proteins. If the condition is untreated, tyrosine and its byproducts build up in tissues and organs, which can lead to serious health problems.There are three types of tyrosinemia, distinguished by their symptoms and genetic cause. Tyrosinemia type I is the most severe form of this disorder and usually begins in the first few months of life. Affected infants do not gain weight and grow at the expected rate (failure to thrive) because eating high-protein foods leads to diarrhea and vomiting. Affected infants may also have yellowing of the skin and whites of the eyes (jaundice), a cabbage-like odor, and an increased tendency to bleed (particularly nosebleeds). In addition, tyrosinemia type I can lead to liver and kidney failure, softening and weakening of the bones (rickets), and an increased risk of liver cancer (hepatocellular carcinoma). Some affected children have repeated neurologic crises that consist of changes in their mental state, reduced sensation in the arms and legs (peripheral neuropathy), abdominal pain, and serious breathing problems (respiratory failure). These crises can last from 1 to 7 days. Without treatment, children with tyrosinemia type I often do not survive past the age of 10. With early diagnosis and treatment, though, affected individuals can live into adulthood.Tyrosinemia type II often begins in early childhood and affects the eyes, skin, and mental development. Signs and symptoms include eye pain and redness, excessive tearing, abnormal sensitivity to light (photophobia), and thick, painful skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). About half of individuals with tyrosinemia type II have some degree of intellectual disability.Tyrosinemia type III is the rarest of the three types. The characteristic features of this type include intellectual disabilities, seizures, and periodic loss of balance and coordination (intermittent ataxia). Liver problems do not occur in types II and III.About 1 in 10 of all newborns have temporarily elevated levels of tyrosine (transient tyrosinemia). These cases are not genetic. The most likely causes are vitamin C deficiency or an immature liver due to premature birth. ar Autosomal recessive FAH https://medlineplus.gov/genetics/gene/fah TAT https://medlineplus.gov/genetics/gene/tat HPD https://medlineplus.gov/genetics/gene/hpd Hereditary tyrosinemia Hypertyrosinaemia Hypertyrosinemia Tyrosinaemia GTR C0268487 GTR C0268490 GTR C0268623 ICD-10-CM E70.21 MeSH D020176 OMIM 276600 OMIM 276700 OMIM 276710 SNOMED CT 124287008 SNOMED CT 124536006 SNOMED CT 190694001 SNOMED CT 271847005 SNOMED CT 27373000 SNOMED CT 410056006 SNOMED CT 413356003 SNOMED CT 415764005 SNOMED CT 4887000 SNOMED CT 52452006 SNOMED CT 56595005 SNOMED CT 75387001 2023-06 2025-04-03 UNC80 deficiency https://medlineplus.gov/genetics/condition/unc80-deficiency descriptionUNC80 deficiency is a severe disorder characterized by nervous system and developmental problems that are apparent from birth or early infancy. The disorder does not typically get worse over time; development of intellectual function and motor skills, such as rolling over and sitting, is slow and limited, but once skills are learned, they are usually retained.People with UNC80 deficiency have profound intellectual disability. Muscle tone is generally weak (hypotonia), but affected individuals may have increased muscle tone (hypertonia) in the arms and legs. Most people with this disorder never learn to walk. Some affected individuals have feeding difficulties because hypotonia leads to problems controlling movements of the mouth. Speech is also generally absent, although in some cases individuals have limited communication using body language, gestures, and signs. Seizures, involuntary side-to-side movements of the eyes (nystagmus), eyes that do not point in the same direction (strabismus), and a high-pitched cry can also occur in this disorder.People with UNC80 deficiency are of normal size at birth but grow slowly during infancy and childhood. Unusual facial features typically occur in this disorder, and vary among affected individuals. These features can include a wide, short skull (brachycephaly); a triangular face shape with a prominent forehead (frontal bossing); droopy eyelids (ptosis); folds of skin covering the inner corners of the eyes (epicanthal folds); outside corners of the eyes that point downward (downslanting palpebral fissures); a nose with a prominent bridge and a bulbous or upturned tip; a short, smooth space between the upper lip and nose (philtrum); a mouth that remains open; and low-set ears. Other physical differences that can occur in people with UNC80 deficiency include a short neck, abnormal curvature of the spine (scoliosis), permanently bent joints (contractures), and inward- and upward-turning feet (clubfeet). ar Autosomal recessive UNC80 https://medlineplus.gov/genetics/gene/unc80 IHPRF2 Infantile hypotonia with psychomotor retardation and characteristic facies-2 GTR C4225203 MeSH D001927 MeSH D053447 OMIM 616801 2017-12 2020-08-18 UV-sensitive syndrome https://medlineplus.gov/genetics/condition/uv-sensitive-syndrome descriptionUV-sensitive syndrome is a condition that is characterized by sensitivity to the ultraviolet (UV) rays in sunlight. Even a small amount of sun exposure can cause a sunburn in affected individuals. In addition, these individuals can have freckles, dryness, or changes in coloring (pigmentation) on sun-exposed areas of skin after repeated exposure. Some people with UV-sensitive syndrome have small clusters of enlarged blood vessels just under the skin (telangiectasia), usually on the cheeks and nose. Although UV exposure can cause skin cancers, people with UV-sensitive syndrome do not have an increased risk of developing these forms of cancer compared with the general population. ar Autosomal recessive ERCC6 https://medlineplus.gov/genetics/gene/ercc6 ERCC8 https://medlineplus.gov/genetics/gene/ercc8 UVSSA https://medlineplus.gov/genetics/gene/uvssa Ultraviolet sensitive syndrome UVSS GTR C3551173 GTR C3553298 GTR C3553328 MeSH D010787 OMIM 600630 OMIM 614621 OMIM 614640 SNOMED CT 698253007 2012-07 2020-08-18 Ulcerative colitis https://medlineplus.gov/genetics/condition/ulcerative-colitis descriptionUlcerative colitis is a chronic disorder that affects the digestive system. This condition is characterized by abnormal inflammation of the inner surface (epithelium) of the rectum and colon. The rectum and colon make up most of the length of the large intestine. The inflammation usually causes open sores (ulcers) to develop in the large intestine. Ulcerative colitis usually appears between the age of 15 and 30, although it can develop at any age. The inflammation tends to flare up multiple times throughout a person's life, which causes recurring signs and symptoms.The most common symptoms of ulcerative colitis are cramping abdominal pain and frequent diarrhea, often with blood, pus, or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, bowel urgency, fatigue, and fevers. Chronic bleeding from the inflamed and ulcerated intestinal tissue can cause a shortage of red blood cells (anemia) in some affected individuals. People with this disorder have difficulty absorbing enough fluids and nutrients from their diet and often experience weight loss. Affected children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys, or liver, which are most likely due to abnormal inflammation.Toxic megacolon is a rare complication of ulcerative colitis that can be life-threatening. Toxic megacolon involves a widening (dilation) of the colon and an overwhelming inflammatory response. Ulcerative colitis also increases the risk of developing colon cancer, especially in people whose entire colon is inflamed and in those who have had ulcerative colitis for 8 years or more.Ulcerative colitis is one common form of inflammatory bowel disease (IBD). Another type of IBD, Crohn's disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn's disease can cause inflammation in any part of the digestive system, and the inflammation extends deeper into the intestinal tissue. u Pattern unknown IL23R https://medlineplus.gov/genetics/gene/il23r IRF5 https://medlineplus.gov/genetics/gene/irf5 IL10RA https://www.ncbi.nlm.nih.gov/gene/3587 IL10RB https://www.ncbi.nlm.nih.gov/gene/3588 ABCB1 https://www.ncbi.nlm.nih.gov/gene/5243 PTPN2 https://www.ncbi.nlm.nih.gov/gene/5771 Colitis gravis Idiopathic proctocolitis Inflammatory bowel disease, ulcerative colitis type UC GTR C0009319 ICD-10-CM K51 ICD-10-CM K51.0 ICD-10-CM K51.00 ICD-10-CM K51.01 ICD-10-CM K51.011 ICD-10-CM K51.012 ICD-10-CM K51.013 ICD-10-CM K51.014 ICD-10-CM K51.018 ICD-10-CM K51.019 ICD-10-CM K51.2 ICD-10-CM K51.20 ICD-10-CM K51.21 ICD-10-CM K51.211 ICD-10-CM K51.212 ICD-10-CM K51.213 ICD-10-CM K51.214 ICD-10-CM K51.218 ICD-10-CM K51.219 ICD-10-CM K51.3 ICD-10-CM K51.30 ICD-10-CM K51.31 ICD-10-CM K51.311 ICD-10-CM K51.312 ICD-10-CM K51.313 ICD-10-CM K51.314 ICD-10-CM K51.318 ICD-10-CM K51.319 ICD-10-CM K51.5 ICD-10-CM K51.50 ICD-10-CM K51.51 ICD-10-CM K51.511 ICD-10-CM K51.512 ICD-10-CM K51.513 ICD-10-CM K51.514 ICD-10-CM K51.518 ICD-10-CM K51.519 ICD-10-CM K51.8 ICD-10-CM K51.80 ICD-10-CM K51.81 ICD-10-CM K51.811 ICD-10-CM K51.812 ICD-10-CM K51.813 ICD-10-CM K51.814 ICD-10-CM K51.818 ICD-10-CM K51.819 ICD-10-CM K51.9 ICD-10-CM K51.90 ICD-10-CM K51.91 ICD-10-CM K51.911 ICD-10-CM K51.912 ICD-10-CM K51.913 ICD-10-CM K51.914 ICD-10-CM K51.918 ICD-10-CM K51.919 MeSH D003093 OMIM 266600 SNOMED CT 64766004 2023-08 2023-08-28 Uncombable hair syndrome https://medlineplus.gov/genetics/condition/uncombable-hair-syndrome descriptionUncombable hair syndrome is a condition that is characterized by dry, frizzy hair that cannot be combed flat. This condition develops in childhood, often between infancy and age 3, but can appear as late as age 12. Affected children have light-colored hair, described as blond or silvery with a glistening sheen. The hair does not grow downward but out from the scalp in multiple directions. Despite its appearance, the hair is not fragile or brittle, and it grows at a normal or slightly slower rate. Only scalp hair is affected in uncombable hair syndrome.For unknown reasons, this condition usually improves over time. By adolescence individuals with uncombable hair syndrome have hair that lies flat and has normal or nearly normal texture. ad Autosomal dominant ar Autosomal recessive PADI3 https://medlineplus.gov/genetics/gene/padi3 TCHH https://medlineplus.gov/genetics/gene/tchh TGM3 https://medlineplus.gov/genetics/gene/tgm3 Cheveux incoiffables Pili trianguli et canaliculi Spun glass hair UHS Unmanageable hair syndrome MeSH D006201 OMIM 191480 OMIM 617251 OMIM 617252 SNOMED CT 254230001 2017-05 2020-08-18 Usher syndrome https://medlineplus.gov/genetics/condition/usher-syndrome descriptionUsher syndrome is a condition characterized by partial or total hearing loss and vision loss that worsens over time. The hearing loss is classified as sensorineural, which means that it is caused by abnormalities of the inner ear. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually break down. Loss of night vision begins first, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. In some cases, vision is further impaired by clouding of the lens of the eye (cataracts). However, many people with retinitis pigmentosa retain some central vision throughout their lives.Researchers have identified three major types of Usher syndrome, designated as types I, II, and III. These types are distinguished by the severity of hearing loss, the presence or absence of balance problems, and the age at which signs and symptoms appear. The types are further divided into subtypes based on their genetic cause.Most individuals with Usher syndrome type I are born with severe to profound hearing loss. Worsening vision loss caused by retinitis pigmentosa becomes apparent in childhood. This type of Usher syndrome also causes abnormalities of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation in space. As a result of the vestibular abnormalities, children with the condition have trouble with balance. They begin sitting independently and walking later than usual, and they may have difficulty riding a bicycle and playing certain sports.Usher syndrome type II is characterized by hearing loss from birth and progressive vision loss that begins in adolescence or adulthood. The hearing loss associated with this form of Usher syndrome ranges from mild to severe and mainly affects the ability to hear high-frequency sounds. For example, it is difficult for affected individuals to hear high, soft speech sounds, such as those of the letters d and t. The degree of hearing loss varies within and among families with this condition, and it may become more severe over time. Unlike the other forms of Usher syndrome, type II is not associated with vestibular abnormalities that cause difficulties with balance.People with Usher syndrome type III experience hearing loss and vision loss beginning somewhat later in life. Unlike the other forms of Usher syndrome, type III is usually associated with normal hearing at birth. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and becomes more severe over time. By middle age, most affected individuals have profound hearing loss. Vision loss caused by retinitis pigmentosa also develops in late childhood or adolescence. Some people with Usher syndrome type III develop vestibular abnormalities that cause problems with balance. ar Autosomal recessive MYO7A https://medlineplus.gov/genetics/gene/myo7a USH2A https://medlineplus.gov/genetics/gene/ush2a CLRN1 https://medlineplus.gov/genetics/gene/clrn1 CDH23 https://medlineplus.gov/genetics/gene/cdh23 HARS1 https://www.ncbi.nlm.nih.gov/gene/3035 USH1C https://www.ncbi.nlm.nih.gov/gene/7394 CIB2 https://www.ncbi.nlm.nih.gov/gene/10518 WHRN https://www.ncbi.nlm.nih.gov/gene/25861 PCDH15 https://www.ncbi.nlm.nih.gov/gene/65217 ADGRV1 https://www.ncbi.nlm.nih.gov/gene/84059 USH1G https://www.ncbi.nlm.nih.gov/gene/124590 Deafness-retinitis pigmentosa syndrome Graefe-Usher syndrome Hallgren syndrome Retinitis pigmentosa-deafness syndrome Usher's syndrome GTR C0339534 GTR C1568247 GTR C1568248 GTR C1568249 GTR C1832845 GTR C1847089 GTR C1848604 GTR C1848634 GTR C1865865 GTR C1865885 GTR C2675458 GTR C2931206 GTR C2931213 GTR C3148929 GTR C3281066 GTR C3539124 GTR C3553944 GTR CN121478 GTR CN469326 MeSH D052245 OMIM 276900 OMIM 276901 OMIM 276902 OMIM 276904 OMIM 601067 OMIM 602083 OMIM 602097 OMIM 605472 OMIM 606943 OMIM 609439 OMIM 611383 OMIM 612632 OMIM 614504 OMIM 614990 SNOMED CT 232057003 SNOMED CT 57838006 SNOMED CT 73119000 2016-05 2025-12-16 VACTERL association https://medlineplus.gov/genetics/condition/vacterl-association descriptionVACTERL association is a disorder that affects many body systems. VACTERL stands for vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. People diagnosed with VACTERL association typically have at least three of these characteristic features. Affected individuals may have additional abnormalities that are not among the characteristic features of VACTERL association.Defects in the bones of the spine (vertebrae) are present in 60 to 80 percent of people with VACTERL association. These defects may include misshapen vertebrae, fused vertebrae, and missing or extra vertebrae. In some people, spinal problems require surgery or cause health problems, such as back pain of varying severity, throughout life. Sixty to 90 percent of individuals with VACTERL association have narrowing or blockage of the anus (anal atresia). Anal atresia may be accompanied by abnormalities of the genitalia and urinary tract (genitourinary anomalies). Heart (cardiac) defects occur in 40 to 80 percent of individuals with VACTERL association. Cardiac defects can range in severity from a life-threatening problem to a subtle defect that does not cause health problems. Fifty to 80 percent of people with VACTERL association have a tracheo-esophageal fistula, which is an abnormal connection (fistula) between the esophagus and the windpipe (trachea). Tracheo-esophageal fistula can cause problems with breathing and feeding early in life and typically requires surgical correction in infancy. Kidney (renal) anomalies occur in 50 to 80 percent of individuals with VACTERL association. Affected individuals may be missing one or both kidneys or have abnormally developed or misshapen kidneys, which can affect kidney function. Limb abnormalities are seen in 40 to 50 percent of people with VACTERL association. These abnormalities most commonly include poorly developed or missing thumbs or underdeveloped forearms and hands.Some of the features of VACTERL association can be subtle and are not identified until late in childhood or adulthood, making diagnosis of this condition difficult. u Pattern unknown VATER association GTR C1848599 GTR C2931228 MeSH D000015 OMIM 192350 SNOMED CT 27742002 SNOMED CT 431395004 2011-12 2025-05-29 VEXAS syndrome https://medlineplus.gov/genetics/condition/vexas-syndrome descriptionVEXAS syndrome is a disorder involving episodes of fever and abnormal inflammation. VEXAS is an acronym that stands for the technical terms of key descriptors of the condition. Normally, inflammation is an immune system response to injury or foreign invaders (such as bacteria). In people with VEXAS syndrome, part of the immune system called the innate immune response is turned on (activated) abnormally, when there is no injury or foreign invader, which causes fevers and inflammation-related damage to tissues and organs. Based on this process, VEXAS syndrome is classified as an autoinflammatory disease.VEXAS syndrome typically affects older adults, primarily males, with signs and symptoms of the condition developing in a person's fifties, sixties, or seventies. People with VEXAS syndrome often have inflammation of the joints (arthritis), skin (dermatitis), cartilage in the ear and nose (chondritis), or blood vessels (vasculitis). Inflammation can also develop in other tissues, including in the lungs and eyes. Affected individuals may also have enlarged lymph nodes.Blood cell abnormalities are common in VEXAS syndrome. Most affected individuals develop a shortage of red blood cells (a condition called anemia), and the red blood cells that are present are abnormally large (macrocytic). People with VEXAS syndrome can also have a shortage of blood cells called platelets (a disorder known as thrombocytopenia); platelets  are needed for normal blood clotting.  Some affected individuals develop myelodyspastic syndrome, a condition in which immature blood cells fail to develop normally; this condition may progress to a form of blood cancer calledleukemia. n Not inherited UBA1 https://medlineplus.gov/genetics/gene/uba1 vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome VEXAS ICD-10-CM MeSH OMIM 301054 SNOMED CT 2022-06 2026-03-04 Van der Woude syndrome https://medlineplus.gov/genetics/condition/van-der-woude-syndrome descriptionVan der Woude syndrome is a condition that affects the development of the face. Many people with this disorder are born with either a cleft lip or a cleft palate (an opening in the upper lip or roof of the mouth), or both. Affected individuals usually have depressions (pits) near the center of the lower lip, which may appear moist due to the presence of salivary and mucous glands in the pits. Small mounds of tissue on the lower lip may also occur. In some cases, people with van der Woude syndrome have missing teeth.People with van der Woude syndrome who have cleft lip and/or palate, like other individuals with these facial conditions, have an increased risk of delayed language development, learning disabilities, or other mild cognitive problems. The average IQ of individuals with van der Woude syndrome is not significantly different from that of the general population. ad Autosomal dominant IRF6 https://medlineplus.gov/genetics/gene/irf6 GRHL3 https://www.ncbi.nlm.nih.gov/gene/57822 Cleft lip and/or palate with mucous cysts of lower lip Lip-pit syndrome VDWS VWS GTR C4551864 MeSH D019465 OMIM 119300 SNOMED CT 79261008 2022-07 2022-07-07 Very long-chain acyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency descriptionVery long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a condition that prevents the body from converting certain fats into energy, particularly during periods without food (fasting).There are three forms of VLCAD deficiency, and they are defined by when the signs and symptoms of the condition begin. The early-onset form is the most severe and begins in infancy. Signs and symptoms can include lack of energy (lethargy) and muscle weakness. People with VCLAD deficiency can have low blood sugar (glucose), known as hypoglycemia. Affected individuals are also at risk for serious complications such, as liver abnormalities and life-threatening heart problems. Individuals with childhood-onset VLCAD deficiency typically experience an enlarged liver (hepatomegaly) and low blood glucose. This form is sometimes referred to as the hepatic or hypoketotic hypoglycemic form because of these signs. Additional signs and symptoms include other liver problems or muscle weakness.The adult-onset form, which begins in adolescence or adulthood, usually involves muscle pain and the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a large amount of a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobinuria causes the urine to be red or brown.In both children and adults, problems related to VLCAD deficiency can be triggered by periods of fasting, illness, exercise, and exposure to hot or cold temperatures. In children, this disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome occur in children who take aspirin during these viral infections. ar Autosomal recessive ACADVL https://medlineplus.gov/genetics/gene/acadvl ACADVL Acyl-CoA dehydrogenase very long chain deficiency Very long-chain acyl coenzyme A dehydrogenase deficiency Very long-chain acyl-coenzyme A dehydrogenase deficiency VLCAD deficiency VLCAD-C VLCAD-H GTR C3887523 ICD-10-CM E71.310 MeSH D008052 OMIM 201475 SNOMED CT 237997005 2023-06 2023-07-19 Vibratory urticaria https://medlineplus.gov/genetics/condition/vibratory-urticaria descriptionVibratory urticaria is a condition in which exposing the skin to vibration, repetitive stretching, or friction results in allergy symptoms such as hives (urticaria), swelling (angioedema), redness (erythema), and itching (pruritus) in the affected area. The reaction can be brought on by towel drying, hand clapping, running, a bumpy ride in a vehicle, or other repetitive stimulation. Headaches, fatigue, faintness, blurry vision, a metallic taste in the mouth, facial flushing, and more widespread swelling (especially of the face) can also occur during these episodes, especially if the stimulation is extreme or prolonged. The reaction occurs within a few minutes of the stimulation and generally lasts up to an hour. Affected individuals can have several episodes per day. ad Autosomal dominant ADGRE2 https://medlineplus.gov/genetics/gene/adgre2 DDU Dermodistortive urticaria VBU Vibratory angioedema ICD-10-CM L50.4 MeSH D000799 MeSH D014581 OMIM 125630 SNOMED CT 51247001 2016-07 2020-08-18 Vici syndrome https://medlineplus.gov/genetics/condition/vici-syndrome descriptionVici syndrome is a severe disorder that begins early in life and affects many body systems. It is characterized by abnormalities of the brain, immune system, heart, skin, and eyes. Other organs and tissues are less commonly affected.A characteristic feature of Vici syndrome is a brain abnormality called agenesis of the corpus callosum, in which the tissue that connects the left and right halves of the brain (the corpus callosum) fails to form normally during the early stages of development before birth. A region of the brain known as  the pons (pontine hypoplasia) may be underdeveloped in people with Vici syndrome. Affected individuals may also have lower levels of myelin, which is a fatty substance that covers and protects nerve cells. In addition to problems with brain development, breakdown (degeneration) of brain tissue may occur over time, resulting in an unusually small head size (microcephaly).These brain problems contribute to profound developmental delays in individuals with Vici syndrome. Affected infants have weak muscle tone (hypotonia).  Generally, children with Vici syndrome are not able to roll or sit, and those that can may lose this skill when they get older. In addition, affected children cannot walk or speak.Another characteristic feature of Vici syndrome is impaired immune function (immune deficiency), which leads to recurrent infections that can be life-threatening. Respiratory infections are the most common type of infection, though gastrointestinal and urinary tract infections also frequently occur.A potentially life-threatening heart condition called cardiomyopathy is common in children with Vici syndrome. This condition, which worsens over time, makes it difficult for the heart to pump blood efficiently. Some affected children also have heart defects that are present from birth (congenital)..cf0{font-style:italic;font-family:Segoe UI;font-size:9pt;}People with Vici syndrome may have skin and hair that are lighter in color than that of family members and other people with the same ethnic background (hypopigmentation). They may also experience clouding of the lenses of the eyes (cataracts) or other eye abnormalities, which may reduce their ability to see.Other, less common signs and symptoms of Vici syndrome include seizures; hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss); an opening in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate) or other unusual facial features; and abnormal function of the thyroid, liver, or kidneys. Many affected infants grow and gain weight more slowly than expected.Most people with Vici syndrome do not survive beyond childhood, though this can vary widely. ar Autosomal recessive EPG5 https://medlineplus.gov/genetics/gene/epg5 Absent corpus callosum cataract immunodeficiency Corpus callosum agenesis-cataract-immunodeficiency syndrome Dionisi Vici Sabetta Gambarara syndrome Dionisi-Vici-Sabetta-Gambarara syndrome Immunodeficiency with cleft lip/palate, cataract, hypopigmentation and absent corpus callosum GTR C1855772 MeSH D000015 MeSH D007153 OMIM 242840 SNOMED CT 719824001 2023-08 2023-08-28 Vitamin D-dependent rickets https://medlineplus.gov/genetics/condition/vitamin-d-dependent-rickets descriptionVitamin D-dependent rickets is a group of disorders that are characterized by soft, weak bones (rickets). In people with these conditions, the process by which minerals are deposited into developing bones (mineralization) is disrupted. The long bones in the arms and legs are particularly affected. People with vitamin D-dependent rickets have problems using vitamin D, which helps maintain the proper levels of calcium and phosphate in the blood. These minerals are needed for the normal development of strong bones and teeth.There are several forms of vitamin D-dependent rickets: type 1A (VDDR1A), type 1B (VDDR1B), type 2A (VDDR2A), type 2B (VDDR2B), and type 3 (VDDR3). The types are distinguished by their genetic cause.The signs and symptoms of vitamin D-dependent rickets often begin in infancy. Infants with vitamin D-dependent rickets may have weak muscle tone (hypotonia) and fail to grow or gain weight at the expected rate (failure to thrive). When affected children begin to walk, they may develop abnormally curved (bowed) legs because the bones are too weak to bear weight. The weakened bones are often painful and are prone to fractures. Bone growth is often delayed, and affected individuals may be shorter than their peers. Additional skeletal features include enlargement of the skull, the wrists, and the ends of the ribs.Affected individuals may also have dental abnormalities, such as delayed tooth formation and thin tooth enamel. Some people with vitamin D-dependent rickets who have very low levels of calcium in the blood can have muscle cramps, tingling sensations (paresthesias), or seizures. Hair loss (alopecia) has been reported in some individuals with VDDR2A.With early treatment, affected individuals may have less-severe skeletal signs and symptoms and fewer long-term health issues. Unlike with some other forms of rickets, vitamin D-dependent rickets cannot be treated with standard doses of vitamin D. ad Autosomal dominant ar Autosomal recessive VDR https://medlineplus.gov/genetics/gene/vdr CYP27B1 https://medlineplus.gov/genetics/gene/cyp27b1 CYP2R1 https://medlineplus.gov/genetics/gene/cyp2r1 CYP3A4 https://www.ncbi.nlm.nih.gov/gene/1576 HNRNPC https://www.ncbi.nlm.nih.gov/gene/3183 Hereditary vitamin D-resistant ricket HVDRR VDDR GTR C0221468 GTR C0268689 GTR C0342646 GTR C2748783 GTR C3536983 GTR C5436733 GTR CN283242 ICD-10-CM E83.32 MeSH D012279 OMIM 264700 OMIM 277440 OMIM 600081 OMIM 600785 OMIM 619073 SNOMED CT 68295002 2026-03 2026-03-20 Vitelliform macular dystrophy https://medlineplus.gov/genetics/condition/vitelliform-macular-dystrophy descriptionVitelliform macular dystrophy is a genetic eye disorder that can cause worsening (progressive) vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, vitelliform macular dystrophy disrupts cells in a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces.Vitelliform macular dystrophy causes a fatty yellow pigment (called lipofuscin) to build up in cells underlying the macula. Over time, large amounts of this substance can damage cells that are critical for clear central vision. As a result, people with this disorder often lose their central vision, and their eyesight may become blurry or distorted. Vitelliform macular dystrophy typically does not affect side (peripheral) vision or the ability to see at night.Researchers have described two forms of vitelliform macular dystrophy with similar features. The early-onset form (known as Best disease) usually appears in childhood; the age at which symptoms begin and the severity of vision loss vary widely. The adult-onset form begins later, usually in mid-adulthood, and tends to cause vision loss that worsens slowly over time. The two forms of vitelliform macular dystrophy each have characteristic changes in the macula that can be detected during an eye examination. ad Autosomal dominant PRPH2 https://medlineplus.gov/genetics/gene/prph2 BEST1 https://medlineplus.gov/genetics/gene/best1 Vitelliform dystrophy GTR C0339510 GTR C1842914 MeSH D057826 OMIM 153700 OMIM 608161 SNOMED CT 90036004 2008-10 2022-02-14 Vitiligo https://medlineplus.gov/genetics/condition/vitiligo descriptionVitiligo is a condition that causes patchy loss of skin coloring (pigmentation). In addition, hair on these regions of skin can also lose pigment and appear white. The average age of onset of vitiligo is in the mid-twenties, but it can appear at any age. The size and number of patches varies from person to person. The condition tends to progress over time, with larger areas of the skin losing pigment. However, the patches can remain stable or even improve in some affected individuals.  Researchers have identified several forms of vitiligo. Generalized vitiligo (also called nonsegmental vitiligo), which is the most common form, involves loss of pigment (depigmentation) in patches of skin all over the body. Depigmentation typically occurs on the face, neck, and scalp, and around body openings such as the mouth and genitals. Sometimes pigment is lost in mucous membranes, such as the lips. Loss of pigmentation is also frequently seen in areas that tend to experience rubbing, impact, or other trauma, such as the hands, arms, and places where bones are close to the skin surface (bony prominences). Another form of the condition, called segmental vitiligo, is associated with smaller patches of depigmented skin that appear on one side of the body in a limited area. This form occurs in about 10 percent of affected individuals.Vitiligo is generally considered to be an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs. In people with vitiligo the immune system appears to attack the pigment cells (melanocytes) in the skin. About 15 to 25 percent of people with vitiligo are also affected by at least one other autoimmune disorder, particularly autoimmune thyroid disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, Addison disease, systemic lupus erythematosus, celiac disease, Crohn's disease, or ulcerative colitis.In the absence of other autoimmune conditions, vitiligo does not affect general health or physical functioning. However, concerns about appearance and ethnic identity are significant issues for many affected individuals. u Pattern unknown NLRP1 https://medlineplus.gov/genetics/gene/nlrp1 PTPN22 https://medlineplus.gov/genetics/gene/ptpn22 ICD-10-CM H02.73 ICD-10-CM H02.731 ICD-10-CM H02.732 ICD-10-CM H02.733 ICD-10-CM H02.734 ICD-10-CM H02.735 ICD-10-CM H02.736 ICD-10-CM H02.739 ICD-10-CM L80 MeSH D014820 OMIM 193200 OMIM 606579 SNOMED CT 56727007 2015-01 2024-09-19 Vohwinkel syndrome https://medlineplus.gov/genetics/condition/vohwinkel-syndrome descriptionVohwinkel syndrome is a disorder with classic and variant forms, both of which affect the skin.In the classic form of Vohwinkel syndrome, affected individuals have thick, honeycomb-like calluses on the palms of the hands and soles of the feet (palmoplantar keratoses) beginning in infancy or early childhood. Affected children also typically have distinctive starfish-shaped patches of thickened skin on the tops of the fingers and toes or on the knees. Within a few years they develop tight bands of abnormal fibrous tissue around their fingers and toes (pseudoainhum); the bands may cut off the circulation to the digits and result in spontaneous amputation. People with the classic form of the disorder also have hearing loss.The variant form of Vohwinkel syndrome does not involve hearing loss, and the skin features also include widespread dry, scaly skin (ichthyosis), especially on the limbs. The ichthyosis is usually mild, and there may also be mild reddening of the skin (erythroderma). Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. ad Autosomal dominant GJB2 https://medlineplus.gov/genetics/gene/gjb2 LORICRIN https://medlineplus.gov/genetics/gene/loricrin Congenital deafness with keratopachydermia and constrictions of fingers and toes Keratoderma hereditarium mutilans KHM Mutilating keratoderma Palmoplantar keratoderma mutilans Palmoplantar keratoderma mutilans Vohwinkel PPK mutilans Vohwinkel GTR C0265964 GTR C1858805 MeSH D007645 OMIM 124500 OMIM 604117 SNOMED CT 24559001 2012-11 2020-08-18 Von Hippel-Lindau syndrome https://medlineplus.gov/genetics/condition/von-hippel-lindau-syndrome descriptionVon Hippel-Lindau syndrome is an inherited disorder characterized by the formation of tumors and fluid-filled sacs (cysts) in many different parts of the body. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood; however, the signs and symptoms of von Hippel-Lindau syndrome can occur throughout life.Tumors called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels. Although they are typically noncancerous, they can cause serious or life-threatening complications. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination (ataxia). Hemangioblastomas can also occur in the light-sensitive tissue that lines the back of the eye (the retina). These tumors, which are also called retinal angiomas, may cause vision loss.People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys, pancreas, and genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor.Von Hippel-Lindau syndrome is associated with a type of tumor called a pheochromocytoma, which most commonly occurs in the adrenal glands (small hormone-producing glands located on top of each kidney). Pheochromocytomas are usually noncancerous. They may cause no symptoms, but in some cases they are associated with headaches, panic attacks, excess sweating, or dangerously high blood pressure that may not respond to medication. Pheochromocytomas are particularly dangerous in times of stress or trauma, such as when undergoing surgery or in an accident, or during pregnancy.About 10 percent of people with von Hippel-Lindau syndrome develop endolymphatic sac tumors, which are noncancerous tumors in the inner ear. These growths can cause hearing loss in one or both ears, as well as ringing in the ears (tinnitus) and problems with balance. Without treatment, these tumors can cause sudden profound deafness.Noncancerous tumors may also develop in the liver and lungs in people with von Hippel-Lindau syndrome. These tumors do not appear to cause any signs or symptoms. ad Autosomal dominant VHL https://medlineplus.gov/genetics/gene/vhl Angiomatosis retinae Cerebelloretinal angiomatosis, familial Hippel-Lindau disease VHL syndrome Von Hippel-Lindau disease GTR C0019562 ICD-10-CM Q85.8 MeSH D006623 OMIM 193300 SNOMED CT 46659004 2008-07 2020-08-18 Von Willebrand disease https://medlineplus.gov/genetics/condition/von-willebrand-disease descriptionVon Willebrand disease is a bleeding disorder that slows the blood clotting process, causing prolonged bleeding after an injury. People with this condition often experience easy bruising, long-lasting nosebleeds, and excessive bleeding or oozing following an injury, surgery, or dental work. Mild forms of von Willebrand disease may become apparent only when abnormal bleeding occurs following surgery or a serious injury. People with this condition who have menstrual periods typically have heavy or prolonged bleeding during menstruation (menorrhagia), and some may also experience reproductive tract bleeding during pregnancy and childbirth. In severe cases of von Willebrand disease, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Symptoms of von Willebrand disease may change over time. Increased age, pregnancy, exercise, and stress may cause bleeding symptoms to become less frequent.Von Willebrand disease is divided into three types. Type 1 has one subtype (1C), and type 2 is divided into four subtypes (2A, 2B, 2M, and 2N). Type 1 is the most common of the three types, accounting for 75 percent of affected individuals. Type 1 is typically mild, but some people are severely affected. Type 2 accounts for about 15 percent of cases. This type is usually of intermediate severity. Type 3 is the rarest form of the condition, accounting for about 5 percent of affected individuals, and is usually the most severe. Another form of the disorder, acquired von Willebrand syndrome, is not caused by inherited gene variants (also called mutations).  Acquired von Willebrand syndrome is typically seen in people with other disorders, such as diseases that affect bone marrow or immune cell function. This rare form of the condition is characterized by abnormal bleeding into the skin and other soft tissues, usually beginning in adulthood. ar Autosomal recessive ad Autosomal dominant VWF https://medlineplus.gov/genetics/gene/vwf Angiohemophilia Vascular pseudohemophilia Von Willebrand disorder Von Willebrand's factor deficiency GTR C0042974 ICD-10-CM D68.0 MeSH D014842 OMIM 193400 OMIM 277480 OMIM 613554 SNOMED CT 12501008 SNOMED CT 128105004 SNOMED CT 128106003 SNOMED CT 128107007 SNOMED CT 128108002 SNOMED CT 128113003 SNOMED CT 128114009 SNOMED CT 1908008 SNOMED CT 19520006 SNOMED CT 234446004 SNOMED CT 234447008 SNOMED CT 234448003 SNOMED CT 234450006 SNOMED CT 24663001 SNOMED CT 35066007 SNOMED CT 359700009 SNOMED CT 359704000 SNOMED CT 359709005 SNOMED CT 359711001 SNOMED CT 359714009 SNOMED CT 359717002 SNOMED CT 359721009 SNOMED CT 359725000 SNOMED CT 359729006 SNOMED CT 359732009 SNOMED CT 52137009 SNOMED CT 71723006 SNOMED CT 860725002 SNOMED CT 87397002 2023-08 2023-08-08 WAGR syndrome https://medlineplus.gov/genetics/condition/wagr-syndrome descriptionWAGR syndrome is a disorder that affects many body systems and is named for its main features: Wilms tumor, aniridia, genitourinary anomalies, and a range of developmental delays.People with WAGR syndrome have a 45 to 60 percent chance of developing Wilms tumor, a rare form of kidney cancer. This type of cancer is most often diagnosed in children but is sometimes seen in adults. Some people with WAGR syndrome develop nephrogenic rests, which are abnormal clumps of cells in the kidneys. These can lead to Wilms tumor, but some people with nephrogenic rests never develop Wilms tumor.Most people with WAGR syndrome have aniridia, an absence of the colored part of the eye (the iris). This can reduce the sharpness of a person's vision (visual acuity) and increase sensitivity to light (photophobia). Aniridia is typically the first noticeable sign of WAGR syndrome. Other eye problems may also develop, such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), and involuntary eye movements (nystagmus).Abnormalities of the genitalia and urinary tract (genitourinary anomalies) are seen more frequently in males with WAGR syndrome than in affected females. The most common genitourinary abnormality in affected males is undescended testes (cryptorchidism). Affected females may not have functional ovaries and may instead have undeveloped clumps of tissue called streak gonads. Females with WAGR syndrome may also have a heart-shaped (bicornate) uterus, which makes it difficult to carry a pregnancy to term.Intellectual disability and other developmental delays are also common in people with WAGR syndrome. Affected individuals often have difficulty processing, learning, and properly responding to information. Many affected individuals have difficulty speaking or understanding language. Some individuals with WAGR syndrome also have psychiatric or behavioral problems such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or a developmental disorder called autism spectrum disorder that affects communication and social interaction.Other signs and symptoms of WAGR syndrome can include ongoing constipation, inflammation of the pancreas (pancreatitis), kidney failure, breathing problems, and allergies. Some affected children have obesity. When WAGR syndrome includes childhood-onset obesity, it is often referred to as WAGRO syndrome. n Not inherited WT1 https://medlineplus.gov/genetics/gene/wt1 PAX6 https://medlineplus.gov/genetics/gene/pax6 BDNF https://medlineplus.gov/genetics/gene/bdnf 11 https://medlineplus.gov/genetics/chromosome/11 11p deletion syndrome 11p partial monosomy syndrome WAGR complex WAGR contiguous gene syndrome WAGR spectrum disorder Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome Wilms tumor-aniridia-genital anomalies-retardation syndrome Wilms tumor-aniridia-genitourinary anomalies-MR syndrome GTR C0206115 GTR C2675904 ICD-10-CM MeSH D017624 OMIM 194072 OMIM 612469 SNOMED CT 4135001 2023-06 2023-06-28 Waardenburg syndrome https://medlineplus.gov/genetics/condition/waardenburg-syndrome descriptionWaardenburg syndrome is a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes. Although most people with Waardenburg syndrome have normal hearing, moderate to profound hearing loss can occur in one or both ears. The hearing loss is present from birth (congenital). People with this condition often have very pale blue eyes or different colored eyes, such as one blue eye and one brown eye. Sometimes one eye has segments of two different colors. Distinctive hair coloring (such as a patch of white hair or hair that prematurely turns gray) is another common sign of the condition. The features of Waardenburg syndrome vary among affected individuals, even among people in the same family.There are four recognized types of Waardenburg syndrome, which are distinguished by their physical characteristics and sometimes by their genetic cause. Types I and II have very similar features, although people with type I almost always have eyes that appear widely spaced and people with type II do not. In addition, hearing loss occurs more often in people with type II than in those with type I. Type III (sometimes called Klein-Waardenburg syndrome) includes abnormalities of the arms and hands in addition to hearing loss and changes in pigmentation. Type IV (also known as Waardenburg-Hirschsprung disease or Waardenburg-Shah syndrome) has signs and symptoms of both Waardenburg syndrome and Hirschsprung disease, an intestinal disorder that causes severe constipation or blockage of the intestine. ad Autosomal dominant PAX3 https://medlineplus.gov/genetics/gene/pax3 MITF https://medlineplus.gov/genetics/gene/mitf SOX10 https://medlineplus.gov/genetics/gene/sox10 EDNRB https://medlineplus.gov/genetics/gene/ednrb EDN3 https://medlineplus.gov/genetics/gene/edn3 SNAI2 https://medlineplus.gov/genetics/gene/snai2 Waardenburg's syndrome GTR C1837203 GTR C1838447 GTR C1847722 GTR C1847800 GTR C1848519 GTR C1860339 GTR C2700405 GTR C2750452 GTR C2750457 MeSH D014849 OMIM 148820 OMIM 193500 OMIM 193510 OMIM 277580 OMIM 600193 OMIM 606662 OMIM 611584 OMIM 613265 OMIM 613266 SNOMED CT 47434006 2022-08 2023-04-04 Wagner syndrome https://medlineplus.gov/genetics/condition/wagner-syndrome descriptionWagner syndrome is a hereditary disorder that causes progressive vision loss. The eye problems that lead to vision loss typically begin in childhood, although the vision impairment might not be immediately apparent.In people with Wagner syndrome, the light-sensitive tissue that lines the back of the eye (the retina) becomes thin and may separate from the back of the eye (retinal detachment). The blood vessels within the retina (known as the choroid) may also be abnormal. The retina and the choroid progressively break down (degenerate). Some people with Wagner syndrome have blurred vision because of ectopic fovea, an abnormality in which the part of the retina responsible for sharp central vision is out of place. Additionally, the thick, clear gel that fills the eyeball (the vitreous) becomes watery and thin. People with Wagner syndrome develop a clouding of the lens of the eye (cataract). Affected individuals may also experience nearsightedness (myopia), progressive night blindness, or a narrowing of their field of vision.Vision impairment in people with Wagner syndrome can vary from near normal vision to complete loss of vision in both eyes. ad Autosomal dominant VCAN https://medlineplus.gov/genetics/gene/vcan Hyaloideoretinal degeneration of Wagner VCAN-related vitreoretinopathy Wagner disease Wagner vitreoretinal degeneration Wagner vitreoretinopathy GTR C1840452 MeSH D012162 OMIM 143200 SNOMED CT 232064001 2010-01 2023-08-22 Waldenström macroglobulinemia https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia descriptionWaldenström macroglobulinemia is a rare blood cell cancer characterized by an excess of abnormal white blood cells in the bone marrow.  These abnormal cells have characteristics of both white blood cells (lymphocytes) called B cells and more mature cells derived from B cells known as plasma cells. These abnormal cells with both lymphocyte and plasma characteristics are known as lymphoplasmacytic cells. Due to these cells, Waldenström macroglobulinemia is classified as a lymphoplasmacytic lymphoma. In Waldenström macroglobulinemia, these abnormal cells produce excess amounts of IgM, the largest of a type of protein known as an immunoglobulin; the overproduction of this large protein contributes to the condition's name (macroglobulinemia). Waldenström macroglobulinemia usually begins in a person's sixties and is a slow-growing (indolent) cancer. Some affected individuals have elevated levels of IgM and lymphoplasmacytic cells but no symptoms of the condition; in these cases, the disease is usually found incidentally by a blood test taken for another reason. These individuals are diagnosed with smoldering (or asymptomatic) Waldenström macroglobulinemia. It can be many years before a person with the condition develops noticable signs and symptoms.The most common signs and symptoms to first appear in people with Waldenström macroglobulinemia are weakness and extreme tiredness (fatigue) caused by a shortage of red blood cells (anemia). Affected individuals can also experience general symptoms such as fever, night sweats, and weight loss. Some people with Waldenström macroglobulinemia develop a loss of sensation and weakness in the limbs (peripheral neuropathy). Doctors are unsure why this feature occurs, although they speculate that the IgM protein attaches to the protective covering of nerve cells (myelin) and breaks it down. The damaged nerves cannot carry signals normally, leading to neuropathy.Other features of Waldenström macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues. For example, accumulation of these cells can lead to an enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy). In the bone marrow, the lymphoplasmacytic cells interfere with normal blood cell development, causing a shortage of healthy blood cells (pancytopenia). Several other signs and symptoms of Waldenström macroglobulinemia are related to the excess amounts of IgM. Increased IgM can thicken blood and impair circulation, causing a condition known as hyperviscosity syndrome. Features related to hyperviscosity syndrome include bleeding in the nose or mouth, blurring or loss of vision, headache, dizziness, and confusion. In some affected individuals, IgM and other immunoglobulins react to cold temperatures to form gel-like clumps that block blood flow in areas exposed to the cold, such as the hands and feet. These clumped proteins are referred to as cryoglobulins, and their clumping causes a condition known as cryoglobulinemia. Cryoglobulinemia can lead to pain in the hands and feet or episodes of Raynaud phenomenon, in which the fingers and toes turn white or blue in response to cold temperatures. The IgM protein, along with another protein called amyloid, can build up in organs and interfere with their normal function. This buildup causes a condition called amyloidosis. Organs that are typically affected by amyloidosis include the heart, kidneys, liver or spleen. Affected individuals can experience weakness, fatigue, shortness of breath, irregular heartbeat, or joint pain.  n Not inherited MYD88 https://medlineplus.gov/genetics/gene/myd88 CXCR4 https://medlineplus.gov/genetics/gene/cxcr4 Macroglobulinemia of Waldenstrom Waldenstrom macroglobulinemia Waldenstrom's macroglobulinemia WM GTR C1835192 ICD-10-CM C88.0 MeSH D008258 OMIM 153600 SNOMED CT 190818004 2015-03 2021-09-24 Walker-Warburg syndrome https://medlineplus.gov/genetics/condition/walker-warburg-syndrome descriptionWalker-Warburg syndrome is an inherited disorder that affects development of the muscles, brain, and eyes. It is the most severe of a group of genetic conditions known as congenital muscular dystrophies, which cause muscle weakness and wasting (atrophy) beginning very early in life. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past childhood.Walker-Warburg syndrome affects the skeletal muscles, which are muscles the body uses for movement. Affected babies have weak muscle tone (hypotonia) and are sometimes described as "floppy." The muscle weakness worsens over time.Walker-Warburg syndrome also affects the brain; individuals with this condition typically have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead develops a bumpy, irregular appearance (like that of cobblestones). These individuals may also have a buildup of fluid in the brain (hydrocephalus) or abnormalities of certain parts of the brain, including a region called the cerebellum and the part of the brain that connects to the spinal cord (the brainstem). These changes in the structure of the brain lead to significantly delayed development and intellectual disability. Some individuals with Walker-Warburg syndrome experience seizures.Eye abnormalities are also characteristic of Walker-Warburg syndrome. These can include unusually small eyeballs (microphthalmia), enlarged eyeballs caused by increased pressure in the eyes (buphthalmos), clouding of the lenses of the eyes (cataracts), and problems with the nerve that relays visual information from the eyes to the brain (the optic nerve). These eye problems lead to vision impairment in affected individuals. ar Autosomal recessive FKTN https://medlineplus.gov/genetics/gene/fktn POMT1 https://medlineplus.gov/genetics/gene/pomt1 POMT2 https://medlineplus.gov/genetics/gene/pomt2 FKRP https://medlineplus.gov/genetics/gene/fkrp CRPPA https://medlineplus.gov/genetics/gene/crppa LARGE1 https://medlineplus.gov/genetics/gene/large1 DAG1 https://www.ncbi.nlm.nih.gov/gene/1605 RXYLT1 https://www.ncbi.nlm.nih.gov/gene/10329 B4GAT1 https://www.ncbi.nlm.nih.gov/gene/11041 POMGNT1 https://www.ncbi.nlm.nih.gov/gene/55624 POMK https://www.ncbi.nlm.nih.gov/gene/84197 POMGNT2 https://www.ncbi.nlm.nih.gov/gene/84892 B3GALNT2 https://www.ncbi.nlm.nih.gov/gene/148789 Cerebroocular dysplasia-muscular dystrophy syndrome Chemke syndrome COD-MD syndrome HARD syndrome Hydrocephalus, agyria, and retinal dysplasia MDDGA Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A Muscular dystrophy-dystroglycanopathy [with brain and eye anomalies], type A Walker-Warburg congenital muscular dystrophy GTR C0265221 MeSH D058494 OMIM 236670 OMIM 253800 OMIM 613150 OMIM 613153 OMIM 613154 OMIM 614643 OMIM 614830 OMIM 615041 OMIM 615181 OMIM 615249 OMIM 615287 OMIM 616538 SNOMED CT 111504002 2017-01 2023-08-11 Warfarin resistance https://medlineplus.gov/genetics/condition/warfarin-resistance descriptionWarfarin resistance is a condition in which individuals have a high tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming. Warfarin is often prescribed to prevent blood clots in people with heart valve disease who have replacement heart valves, people with an irregular heart beat (atrial fibrillation), or those with a history of heart attack, stroke, or a prior blood clot in the deep veins of the arms or legs (deep vein thrombosis).There are two types of warfarin resistance: incomplete and complete. Those with incomplete warfarin resistance can achieve the benefits of warfarin treatment with a high dose of warfarin. Individuals with complete warfarin resistance do not respond to warfarin treatment, no matter how high the dose. If people with warfarin resistance require anticoagulant therapy and take the average warfarin dose, they will remain at risk of developing a potentially harmful blood clot.Both types of warfarin resistance are related to how the body processes warfarin. In some people with warfarin resistance, their blood-clotting process does not react effectively to the drug. Others rapidly break down (metabolize) warfarin, so the medication is quickly processed by their bodies; these individuals are classified as "fast metabolizers" or "rapid metabolizers" of warfarin. The severity of these abnormal processes determines whether the warfarin resistance is complete or incomplete.Warfarin resistance does not appear to cause any health problems other than those associated with warfarin drug treatment. ad Autosomal dominant UGT1A1 https://medlineplus.gov/genetics/gene/ugt1a1 VKORC1 https://medlineplus.gov/genetics/gene/vkorc1 CALU https://www.ncbi.nlm.nih.gov/gene/813 CYP2A6 https://www.ncbi.nlm.nih.gov/gene/1548 NQO1 https://www.ncbi.nlm.nih.gov/gene/1728 ABCB1 https://www.ncbi.nlm.nih.gov/gene/5243 CYP4F2 https://www.ncbi.nlm.nih.gov/gene/8529 Coumarin resistance Poor metabolism of coumarin GTR C0750384 MeSH D004305 OMIM 122700 SNOMED CT 293344008 SNOMED CT 871777003 2015-07 2024-09-19 Warfarin sensitivity https://medlineplus.gov/genetics/condition/warfarin-sensitivity descriptionWarfarin sensitivity is a condition in which individuals have a low tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming. Warfarin is often prescribed to prevent blood clots in people with heart valve disease who have replacement heart valves, people with an irregular heart beat (atrial fibrillation), or those with a history of heart attack, stroke, or a prior blood clot in the deep veins of the arms or legs (deep vein thrombosis).Many people with warfarin sensitivity take longer than normal to break down (metabolize) warfarin. The medication remains active in their body longer than usual, so they require lower doses. These individuals are classified as "slow metabolizers" of warfarin. Other people with warfarin sensitivity do not need as much drug to prevent clots because their clot-forming process is naturally slower than average and can be stopped by low warfarin doses. If people with warfarin sensitivity take the average dose (or more) of warfarin, they are at risk of an overdose, which can cause abnormal bleeding in the brain, gastrointestinal tract, or other tissues, and may lead to serious health problems or death.Warfarin sensitivity does not appear to cause any health problems other than those associated with warfarin drug treatment. ad Autosomal dominant F9 https://medlineplus.gov/genetics/gene/f9 CYP2C9 https://medlineplus.gov/genetics/gene/cyp2c9 VKORC1 https://medlineplus.gov/genetics/gene/vkorc1 GGCX https://www.ncbi.nlm.nih.gov/gene/2677 CYP4F2 https://www.ncbi.nlm.nih.gov/gene/8529 Coumadin sensitivity Warfarin response GTR C0750384 MeSH D004305 OMIM 122700 SNOMED CT 726543008 SNOMED CT 871777003 2015-06 2024-09-19 Warsaw breakage syndrome https://medlineplus.gov/genetics/condition/warsaw-breakage-syndrome descriptionWarsaw breakage syndrome is a condition that can cause multiple abnormalities. People with Warsaw breakage syndrome have intellectual disability that varies from mild to severe. They also have impaired growth from birth leading to short stature and a small head size (microcephaly). Affected individuals have distinctive facial features that may include a small forehead, a short nose, a small lower jaw, a flat area between the nose and mouth (philtrum), and prominent cheeks. Other common features include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and heart malformations. ar Autosomal recessive DDX11 https://medlineplus.gov/genetics/gene/ddx11 WABS GTR C3150658 MeSH D049914 OMIM 613398 SNOMED CT 702829000 2014-02 2020-08-18 Weaver syndrome https://medlineplus.gov/genetics/condition/weaver-syndrome descriptionWeaver syndrome is a condition that involves tall stature with or without a large head size (macrocephaly), a variable degree of intellectual disability (usually mild), and characteristic facial features. These features can include a broad forehead; widely spaced eyes (hypertelorism); large, low-set ears; a dimpled chin, and a small lower jaw (micrognathia).People with Weaver syndrome can also have joint deformities called contractures that restrict the movement of affected joints. The contractures may particularly affect the fingers and toes, resulting in permanently bent digits (camptodactyly). Other features of this disorder can include abnormal curvature of the spine (kyphoscoliosis); muscle tone that is either reduced (hypotonia) or increased (hypertonia); loose, saggy skin; and a soft-outpouching around the belly-button (umbilical hernia). Some affected individuals have abnormalities in the folds (gyri) of the brain, which can be seen by medical imaging; the relationship between these brain abnormalities and the intellectual disability associated with Weaver syndrome is unclear.Researchers suggest that people with Weaver syndrome may have an increased risk of developing cancer, in particular a slightly increased risk of developing a tumor called neuroblastoma in early childhood, but the small number of affected individuals makes it difficult to determine the exact risk. ad Autosomal dominant EZH2 https://medlineplus.gov/genetics/gene/ezh2 Camptodactyly-overgrowth-unusual facies Weaver-Smith syndrome WSS GTR C0265210 MeSH D000015 OMIM 277590 SNOMED CT 63119004 2016-02 2020-08-18 Weill-Marchesani syndrome https://medlineplus.gov/genetics/condition/weill-marchesani-syndrome descriptionWeill-Marchesani syndrome is a disorder of connective tissue. Connective tissue forms the body's supportive framework, providing structure and strength to the muscles, joints, organs, and skin.The major signs and symptoms of Weill-Marchesani syndrome include short stature, eye abnormalities, unusually short fingers and toes (brachydactyly), and joint stiffness. Adult height for men with Weill-Marchesani syndrome ranges from 4 feet, 8 inches to 5 feet, 6 inches. Adult height for women with this condition ranges from 4 feet, 3 inches to 5 feet, 2 inches.An eye abnormality called microspherophakia is characteristic of Weill-Marchesani syndrome. This term refers to a small, sphere-shaped lens, which is associated with nearsightedness (myopia) that worsens over time. The lens also may be positioned abnormally within the eye (ectopia lentis). Many people with Weill-Marchesani syndrome develop glaucoma, an eye disease that increases the pressure in the eye and can lead to blindness.Occasionally, heart defects or an abnormal heart rhythm can occur in people with Weill-Marchesani syndrome. ar Autosomal recessive ad Autosomal dominant FBN1 https://medlineplus.gov/genetics/gene/fbn1 ADAMTS10 https://medlineplus.gov/genetics/gene/adamts10 Brachydactyly-spherophakia syndrome Brachymorphy with spherophakia syndrome Congenital mesodermal dysmorphodystrophy Marchesani syndrome Marchesani-Weill Syndrome Spherophakia-brachymorphia syndrome WMS GTR C0265313 GTR C1869115 GTR C4552002 MeSH D056846 OMIM 277600 OMIM 608328 SNOMED CT 2884008 2008-10 2020-08-18 Weissenbacher-Zweymüller syndrome https://medlineplus.gov/genetics/condition/weissenbacher-zweymuller-syndrome descriptionWeissenbacher-Zweymüller syndrome is a condition that affects bone growth. It is characterized by skeletal abnormalities, hearing loss, and distinctive facial features. The features of this condition significantly overlap those of two similar conditions, otospondylomegaepiphyseal dysplasia (OSMED) and Stickler syndrome type III. All of these conditions are caused by mutations in the same gene, and in some cases, it can be difficult to tell them apart. Some researchers believe they represent a single disorder with a range of signs and symptoms.Infants born with Weissenbacher-Zweymüller syndrome are smaller than average because the bones in their arms and legs are unusually short. The thigh and upper arm bones are wider than usual at the ends (described as dumbbell-shaped), and the bones of the spine (vertebrae) may also be abnormally shaped. High-frequency hearing loss occurs in some cases. Distinctive facial features include wide-set protruding eyes, a small and upturned nose with a flat bridge, and a small lower jaw. Some affected infants are born with an opening in the roof of the mouth (a cleft palate).Most people with Weissenbacher-Zweymüller syndrome experience significant "catch-up" growth in the bones of the arms and legs during childhood. As a result, adults with this condition are not unusually short. However, affected adults still have other signs and symptoms of Weissenbacher-Zweymüller syndrome, including distinctive facial features and hearing loss. ad Autosomal dominant COL11A2 https://medlineplus.gov/genetics/gene/col11a2 Heterozygous OSMED Heterozygous otospondylomegaepiphyseal dysplasia Otospondylomegaepiphyseal dysplasia, autosomal dominant Pierre Robin syndrome with fetal chondrodysplasia WZS GTR C1848488 MeSH D003095 OMIM 184840 SNOMED CT 699313003 2016-05 2024-09-19 Werner syndrome https://medlineplus.gov/genetics/condition/werner-syndrome descriptionWerner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature. The characteristic aged appearance of individuals with Werner syndrome typically begins to develop when they are in their twenties and includes graying and loss of hair; a hoarse voice; and thin, hardened skin. They may also have a facial appearance described as "bird-like." Many people with Werner syndrome have thin arms and legs and a thick trunk due to abnormal fat deposition.As Werner syndrome progresses, affected individuals may develop disorders of aging early in life, such as cloudy lenses (cataracts) in both eyes, skin ulcers, type 2 diabetes, diminished fertility, severe hardening of the arteries (atherosclerosis), thinning of the bones (osteoporosis), and some types of cancer. It is not uncommon for affected individuals to develop multiple, rare cancers during their lifetime. People with Werner syndrome usually live into their late forties or early fifties. The most common causes of death are cancer and atherosclerosis. ar Autosomal recessive WRN https://medlineplus.gov/genetics/gene/wrn Adult premature aging syndrome Adult progeria Werner's syndrome Werners syndrome WS GTR C0043119 MeSH D014898 OMIM 277700 SNOMED CT 51626007 2008-08 2022-02-24 Weyers acrofacial dysostosis https://medlineplus.gov/genetics/condition/weyers-acrofacial-dysostosis descriptionWeyers acrofacial dysostosis is a disorder that affects the development of the teeth, nails, and bones. Dental abnormalities can include small, peg-shaped teeth; fewer teeth than normal (hypodontia); and one front tooth instead of two (a single central incisor). Additionally, the lower jaw (mandible) may be abnormally shaped. People with Weyers acrofacial dysostosis have abnormally small or malformed fingernails and toenails. Most people with the condition are relatively short, and they may have extra fingers or toes (polydactyly).The features of Weyers acrofacial dysostosis overlap with those of another, more severe condition called Ellis-van Creveld syndrome. In addition to tooth and nail abnormalities, people with Ellis-van Creveld syndrome have very short stature and are often born with heart defects. The two conditions are caused by mutations in the same genes. ad Autosomal dominant EVC https://medlineplus.gov/genetics/gene/evc EVC2 https://medlineplus.gov/genetics/gene/evc2 Acrodental dysostosis of Weyers Curry-Hall syndrome Weyers acrodental dysostosis GTR C0457013 MeSH D004413 OMIM 193530 SNOMED CT 277807007 2012-12 2023-03-01 White sponge nevus https://medlineplus.gov/genetics/condition/white-sponge-nevus descriptionWhite sponge nevus is a condition characterized by the formation of white patches of tissue called nevi (singular: nevus) that appear as thickened, velvety, sponge-like tissue. The nevi are most commonly found on the moist lining of the mouth (oral mucosa), especially on the inside of the cheeks (buccal mucosa). Affected individuals usually develop multiple nevi. Rarely, white sponge nevi also occur on the mucosae (singular: mucosa) of the nose, esophagus, genitals, or anus. The nevi are caused by a noncancerous (benign) overgrowth of cells.White sponge nevus can be present from birth but usually first appears during early childhood. The size and location of the nevi can change over time. In the oral mucosa, both sides of the mouth are usually affected. The nevi are generally painless, but the folds of extra tissue can promote bacterial growth, which can lead to infection that may cause discomfort. The altered texture and appearance of the affected tissue, especially the oral mucosa, can be bothersome for some affected individuals. ad Autosomal dominant KRT4 https://medlineplus.gov/genetics/gene/krt4 KRT13 https://medlineplus.gov/genetics/gene/krt13 Cannon's disease Familial white folded mucosal dysplasia Hereditary leukokeratosis Hereditary mucosal leukokeratosis Hereditary oral keratosis Leukokeratosis of oral mucosa Leukokeratosis, hereditary mucosal Nevus of Cannon White folded gingivostomatosis White gingivostomatitis White sponge naevus White sponge nevus of Cannon White sponge nevus of mucosa WSN GTR C4011926 GTR C4014321 MeSH D053529 OMIM 193900 OMIM 615785 SNOMED CT 389203001 2014-02 2020-08-18 White-Sutton syndrome https://medlineplus.gov/genetics/condition/white-sutton-syndrome descriptionWhite-Sutton syndrome is a disorder that causes intellectual disability, specific facial features, and other signs and symptoms affecting various parts of the body. Most affected individuals have features of autism spectrum disorder (ASD), a varied condition characterized by impaired social skills, communication problems, and repetitive behaviors. However, in White-Sutton syndrome these features can occur along with other characteristics that are unusual in people with ASD, such as an overly friendly demeanor.People with White-Sutton syndrome have delayed development, with speech and language usually being more delayed than motor skills such as walking. Intellectual disability can range from borderline normal to severe.Most people with White-Sutton syndrome have mild abnormalities of the head and face, which can include an unusually small head (microcephaly); a wide, short skull (brachycephaly); wide-set eyes (hypertelorism); a flat or sunken appearance of the middle of the face (midface hypoplasia); and a small mouth with a thin upper lip.A wide variety of additional signs and symptoms can occur with White-Sutton syndrome. Among the more common are hyperactivity; sleeping difficulties; vision defects, especially farsightedness; gastrointestinal problems; obesity; and short stature. Some individuals with White-Sutton syndrome are born with a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia. ad Autosomal dominant POGZ https://medlineplus.gov/genetics/gene/pogz Mental retardation, autosomal dominant 37 MRD37 WHSUS GTR C4225351 MeSH D008607 OMIM 616364 2018-06 2023-03-01 Wiedemann-Rautenstrauch syndrome https://medlineplus.gov/genetics/condition/wiedemann-rautenstrauch-syndrome descriptionWiedemann-Rautenstrauch syndrome is a type of progeria. People with progeria have certain features that make them look older than they are. The signs and symptoms of Wiedemann-Rautenstrauch syndrome begin before birth as affected individuals do not grow and gain weight at the expected rate (intrauterine growth restriction).People with Wiedemann-Rautenstrauch syndrome have distinctive facial features that give the appearance of old age. They often have a triangular face with a prominent forehead and pointed chin, a small mouth with a thin upper lip, a small jaw, low-set ears, and abnormal lower eyelids. In most affected individuals, the middle of the face looks as though it is drawn inward (midface retraction). On the head, hair is sparse, and the veins are prominent.In people with Wiedemann-Rautenstrauch syndrome, the spaces (fontanelles) between the skull bones (that are noticeable as "soft spots" on the heads of infants) are larger than normal. The fontanelles normally close in early childhood, but they may remain open in people with this condition. Individuals with Wiedemann-Rautenstrauch syndrome may appear to have an abnormally large head, but their head size is typically normal for their age (pseudohydrocephalus).Some individuals with Wiedemann-Rautenstrauch syndrome have intellectual disabilities. Affected children may also have developmental disabilities.Many affected infants are born with teeth (natal teeth); these teeth fall out a few weeks after birth. Some or all of their permanent (adult) teeth may never develop (hypodontia).A lack of fatty tissue under the skin (lipodystrophy), particularly in the face, arms, and legs, can make people with Wiedemann-Rautenstrauch syndrome look older than they are. In addition, the skin is thin and translucent.Some individuals with Wiedemann-Rautenstrauch syndrome develop joint abnormalities called contractures that can limit movement. Additionally, movement problems such as difficulty with coordination and balance (ataxia) or involuntary rhythmic shaking (tremor), can appear during childhood and worsen over time. Some people with Wiedemann-Rautenstrauch syndrome have vision or hearing problems.While many people with Wiedemann-Rautenstrauch syndrome do not survive past infancy or early childhood, others live into their teens or twenties. ar Autosomal recessive POLR3A https://medlineplus.gov/genetics/gene/polr3a Congenital pseudohydrocephalic progeroid syndrome Neonatal progeroid syndrome Neonatal pseudo-hydrocephalic progeroid syndrome Neonatal pseudohydrocephalic progeroid syndrome WRS GTR C0406586 MeSH D011371 OMIM 264090 SNOMED CT 238874008 2024-11 2024-11-12 Williams syndrome https://medlineplus.gov/genetics/condition/williams-syndrome descriptionWilliams syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate intellectual disability or learning problems, unique personality characteristics, distinctive facial features, and heart and blood vessel (cardiovascular) problems.People with Williams syndrome typically have difficulty with visual-spatial tasks such as drawing and assembling puzzles, but they tend to do well on tasks that involve spoken language, music, and learning by repetition (rote memorization). Affected individuals have outgoing, engaging personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common among people with this disorder.Young children with Williams syndrome have distinctive facial features including a broad forehead, puffiness around the eyes, a flat bridge of the nose, full cheeks, and a small chin. Many affected people have dental problems such as teeth that are small, widely spaced, crooked, or missing. Older children and adults typically have a longer face with a wide mouth and full lips. A form of cardiovascular disease called supravalvular aortic stenosis (SVAS) occurs frequently in people with Williams syndrome. Supravalvular aortic stenosis is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). If this condition is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and heart failure. Narrowing of other vessels, including the artery from the heart to the lungs (pulmonary stenosis) and the arteries that supply blood to the heart (coronary artery stenosis) can also occur. Other problems with the heart and blood vessels, including high blood pressure (hypertension) and stiff blood vessels, have also been reported in people with Williams syndrome. Individuals with Williams syndrome have an increased risk of complications with the use of anesthesia.Additional signs and symptoms of Williams syndrome include abnormalities of connective tissue (tissue that supports the body's joints and organs) such as joint problems and soft, loose skin. Affected people may also have increased calcium levels in the blood (hypercalcemia) in infancy, developmental delays, problems with coordination, and short stature. Medical problems involving vision or hearing, including sensitivity to sound (hyperacusis), are frequently associated with Williams syndrome. In addition, problems with the digestive tract and the urinary system are also possible. Obesity or diabetes can develop in adulthood. ad Autosomal dominant ELN https://medlineplus.gov/genetics/gene/eln LIMK1 https://medlineplus.gov/genetics/gene/limk1 GTF2IRD1 https://medlineplus.gov/genetics/gene/gtf2ird1 GTF2I https://medlineplus.gov/genetics/gene/gtf2i NCF1 https://medlineplus.gov/genetics/gene/ncf1 CLDN4 https://www.ncbi.nlm.nih.gov/gene/1364 CLDN3 https://www.ncbi.nlm.nih.gov/gene/1365 RFC2 https://www.ncbi.nlm.nih.gov/gene/5982 STX1A https://www.ncbi.nlm.nih.gov/gene/6804 EIF4H https://www.ncbi.nlm.nih.gov/gene/7458 CLIP2 https://www.ncbi.nlm.nih.gov/gene/7461 LAT2 https://www.ncbi.nlm.nih.gov/gene/7462 FZD9 https://www.ncbi.nlm.nih.gov/gene/8326 FKBP6 https://www.ncbi.nlm.nih.gov/gene/8468 BAZ1B https://www.ncbi.nlm.nih.gov/gene/9031 BCL7B https://www.ncbi.nlm.nih.gov/gene/9275 TBL2 https://www.ncbi.nlm.nih.gov/gene/26608 MLXIPL https://www.ncbi.nlm.nih.gov/gene/51085 NSUN5 https://www.ncbi.nlm.nih.gov/gene/55695 ABHD11 https://www.ncbi.nlm.nih.gov/gene/83451 GTF2IRD2 https://www.ncbi.nlm.nih.gov/gene/84163 DNAJC30 https://www.ncbi.nlm.nih.gov/gene/84277 BUD23 https://www.ncbi.nlm.nih.gov/gene/114049 TMEM270 https://www.ncbi.nlm.nih.gov/gene/135886 TRIM50 https://www.ncbi.nlm.nih.gov/gene/135892 METTL27 https://www.ncbi.nlm.nih.gov/gene/155368 VPS37D https://www.ncbi.nlm.nih.gov/gene/155382 BICDL3P https://www.ncbi.nlm.nih.gov/gene/171022 MIR590 https://www.ncbi.nlm.nih.gov/gene/693175 ELN-AS1 https://www.ncbi.nlm.nih.gov/gene/107986809 7 https://medlineplus.gov/genetics/chromosome/7 Beuren syndrome Elfin facies syndrome Elfin facies with hypercalcemia Hypercalcemia-supravalvar aortic stenosis WBS Williams-Beuren syndrome WS GTR C0175702 MeSH D018980 OMIM 194050 SNOMED CT 63247009 2022-03 2023-03-01 Wilms tumor https://medlineplus.gov/genetics/condition/wilms-tumor descriptionWilms tumor is a form of kidney cancer that primarily develops in children. Nearly all cases of Wilms tumor are diagnosed before the age of 10, with two-thirds being found before age 5.Wilms tumor is often first noticed because of abdominal swelling or a mass in the kidney that can be felt upon physical examination. Some affected children have abdominal pain, fever, a low number of red blood cells (anemia), blood in the urine (hematuria), or high blood pressure (hypertension). Additional signs of Wilms tumor can include loss of appetite, weight loss, nausea, vomiting, and tiredness (lethargy).Wilms tumor can develop in one or both kidneys. About 5 to 10 percent of affected individuals develop multiple tumors in one or both kidneys. Wilms tumor may spread from the kidneys to other parts of the body (metastasize). In rare cases, Wilms tumor does not involve the kidneys and occurs instead in the genital tract, bladder, abdomen, chest, or lower back. It is unclear how Wilms tumor develops in these tissues.With proper treatment, children with Wilms tumor have a 90 percent survival rate. However, the risk that the cancer will come back (recur) is between 15 and 50 percent, depending on traits of the original tumor. Tumors usually recur in the first 2 years following treatment and develop in the kidneys or other tissues, such as the lungs. Individuals who have had Wilms tumor may experience related health problems or late effects of their treatment in adulthood, such as decreased kidney function, heart disease, and development of additional cancers. ad Autosomal dominant xd X-linked dominant n Not inherited TP53 https://medlineplus.gov/genetics/gene/tp53 IGF2 https://medlineplus.gov/genetics/gene/igf2 H19 https://medlineplus.gov/genetics/gene/h19 WT1 https://medlineplus.gov/genetics/gene/wt1 CTNNB1 https://medlineplus.gov/genetics/gene/ctnnb1 AMER1 https://medlineplus.gov/genetics/gene/amer1 REST https://www.ncbi.nlm.nih.gov/gene/5978 POU6F2 https://www.ncbi.nlm.nih.gov/gene/11281 DROSHA https://www.ncbi.nlm.nih.gov/gene/29102 DGCR8 https://www.ncbi.nlm.nih.gov/gene/54487 Embryonal adenosarcoma Embryonal nephroma Kidney Wilms tumor Kidney, adenomyosarcoma, embryonal Kidney, carcinosarcoma, embryonal Kidney, embryoma Kidney, embryonal mixed tumor Nephroblastoma Nephroma Renal adenosarcoma Renal cancer, Wilms Renal Wilms tumor Tumor, Wilms Wilms' tumor GTR C1832099 GTR C1832426 GTR C3887743 GTR C3891301 GTR CN033288 ICD-10-CM Z85.528 MeSH D009396 OMIM 194070 OMIM 194071 OMIM 194090 OMIM 601363 OMIM 601583 OMIM 616806 SNOMED CT 25081006 SNOMED CT 302849000 2018-09 2025-03-06 Wilson disease https://medlineplus.gov/genetics/condition/wilson-disease descriptionWilson disease is an inherited disorder in which excessive amounts of copper accumulate in the body, particularly in the liver, brain, and eyes. The signs and symptoms of Wilson disease usually first appear between the ages of 6 and 45, but they most often begin during the teenage years. The features of this condition include a combination of liver disease and neurological and psychiatric problems.Liver disease is typically the initial feature of Wilson disease in affected children and young adults; individuals diagnosed at an older age usually do not have symptoms of liver problems, although they may have very mild liver disease. The signs and symptoms of liver disease include yellowing of the skin or whites of the eyes (jaundice), fatigue, loss of appetite, and abdominal swelling.Nervous system or psychiatric problems are often the initial features in individuals diagnosed in adulthood and commonly occur in young adults with Wilson disease. Signs and symptoms of these problems can include clumsiness, tremors, difficulty walking, speech problems, impaired thinking ability, depression, anxiety, and mood swings.In many individuals with Wilson disease, copper deposits in the front surface of the eye (the cornea) form a green-to-brownish ring, called the Kayser-Fleischer ring, that surrounds the colored part of the eye. Abnormalities in eye movements, such as a restricted ability to gaze upwards, may also occur. ar Autosomal recessive ATP7B https://medlineplus.gov/genetics/gene/atp7b PRNP https://medlineplus.gov/genetics/gene/prnp Copper storage disease Hepatolenticular degeneration syndrome WD Wilson's disease GTR C0019202 ICD-10-CM E83.01 MeSH D006527 OMIM 277900 SNOMED CT 88518009 2007-02 2022-07-11 Winchester syndrome https://medlineplus.gov/genetics/condition/winchester-syndrome descriptionWinchester syndrome is a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. Winchester syndrome used to be considered part of a related condition now called multicentric osteolysis, nodulosis, and arthropathy (MONA). However, because Winchester syndrome and MONA are caused by mutations in different genes, they are now thought to be separate disorders.In most cases of Winchester syndrome, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities later spread to other parts of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with Winchester syndrome develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature.Some people with Winchester syndrome have skin abnormalities including patches of dark, thick, and leathery skin. Other features of the condition can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as "coarse." ar Autosomal recessive MMP14 https://medlineplus.gov/genetics/gene/mmp14 Winchester disease WNCHRS GTR C0432289 MeSH D010014 OMIM 277950 SNOMED CT 254151006 2013-12 2020-08-18 Wiskott-Aldrich syndrome https://medlineplus.gov/genetics/condition/wiskott-aldrich-syndrome descriptionWiskott-Aldrich syndrome is characterized by abnormal immune system function (immune deficiency), eczema (an inflammatory skin disorder characterized by abnormal patches of red, irritated skin), and a reduced ability to form blood clots. This condition primarily affects males.Individuals with Wiskott-Aldrich syndrome have microthrombocytopenia, which is a decrease in the number and size of blood cells involved in clotting (platelets). This platelet abnormality, which is typically present from birth, can lead to easy bruising, bloody diarrhea, or episodes of prolonged bleeding following nose bleeds or minor trauma. Microthrombocytopenia can also lead to small areas of bleeding just under the surface of the skin, resulting in purplish spots called purpura, or variably sized rashes made up of tiny red spots called petechiae. In some cases, particularly if a bleeding episode occurs within the brain, prolonged bleeding can be life-threatening.Wiskott-Aldrich syndrome is also characterized by abnormal or nonfunctional immune system cells known as white blood cells. Changes in white blood cells lead to an increased risk of several immune and inflammatory disorders in people with Wiskott-Aldrich syndrome. These immune problems vary in severity and include an increased susceptibility to infection from bacteria, viruses, and fungi. People with Wiskott-Aldrich syndrome are at greater risk of developing autoimmune disorders, such as rheumatoid arthritis, vasculitis, or hemolytic anemia. These disorder occur when the immune system malfunctions and attacks the body's own tissues and organs. The chance of developing certain types of cancer, such as cancer of the immune system cells (lymphoma), is also increased in people with Wiskott-Aldrich syndrome.Wiskott-Aldrich syndrome is often considered to be part of a disease spectrum with two other disorders: X-linked thrombocytopenia and severe congenital neutropenia. These conditions have overlapping signs and symptoms and the same genetic cause. x X-linked WAS https://medlineplus.gov/genetics/gene/was Eczema-thrombocytopenia-immunodeficiency syndrome IMD2 Immunodeficiency 2 Wiskott syndrome GTR C0043194 ICD-10-CM D82.0 MeSH D014923 OMIM 301000 SNOMED CT 36070007 2013-02 2023-04-04 Wolf-Hirschhorn syndrome https://medlineplus.gov/genetics/condition/wolf-hirschhorn-syndrome descriptionWolf-Hirschhorn syndrome is a condition that affects many parts of the body. The major features of this disorder include a characteristic facial features, delayed growth and development, intellectual disability, and seizures.Almost everyone with this disorder has distinctive facial features, including a broad nasal bridge, large and protruding eyes, and a high forehead.  This combination is described as a "Greek warrior helmet" appearance. Other characteristic facial features include a shortened distance between the nose and upper lip (a short philtrum), a downturned mouth, a small chin (micrognathia), and poorly formed ears with small holes (pits) or flaps of skin (tags). Additionally, affected individuals may have asymmetrical facial features and an unusually small head (microcephaly).People with Wolf-Hirschhorn syndrome experience delayed growth and development. Slow growth begins before birth, and affected infants tend to have problems feeding and gaining weight (failure to thrive). They also have weak muscle tone (hypotonia) and underdeveloped muscles. Motor skills such as sitting, standing, and walking are significantly delayed. Most children and adults with this disorder also have short stature.Intellectual disability ranges from mild to severe in people with Wolf-Hirschhorn syndrome. Compared to people with other forms of intellectual disability, their socialization skills are strong, but verbal communication and language skills tend to be weaker. Most affected children also have seizures, which may be resistant to treatment. Seizures tend to disappear with age.Additional features of Wolf-Hirschhorn syndrome include skin changes, such as mottled or dry skin; skeletal abnormalities, such as abnormal curvature of the spine (scoliosis and kyphosis); dental problems including, missing teeth; and an opening in the roof of the mouth (cleft palate) and/or a split in the upper lip (cleft lip). Wolf-Hirschhorn syndrome can also cause abnormalities of the eyes, heart, and genitourinary tract.A condition called Pitt-Rogers-Danks syndrome has features that overlap with those of Wolf-Hirschhorn syndrome. Researchers now recognize that these two conditions are actually part of a single syndrome with variable signs and symptoms. n Not inherited NSD2 https://medlineplus.gov/genetics/gene/nsd2 LETM1 https://medlineplus.gov/genetics/gene/letm1 MSX1 https://medlineplus.gov/genetics/gene/msx1 CPLX1 https://www.ncbi.nlm.nih.gov/gene/10815 4 https://medlineplus.gov/genetics/chromosome/4 4p deletion syndrome 4p- syndrome Chromosome 4p deletion syndrome Chromosome 4p monosomy Del(4p) syndrome Monosomy 4p Partial monosomy 4p WHS GTR C1956097 ICD-10-CM Q93.3 MeSH D054877 OMIM 194190 SNOMED CT 17122004 2023-05 2023-05-22 Wolff-Parkinson-White syndrome https://medlineplus.gov/genetics/condition/wolff-parkinson-white-syndrome descriptionWolff-Parkinson-White syndrome is a condition characterized by abnormal electrical pathways in the heart that cause a disruption of the heart's normal rhythm (arrhythmia).The heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. A specialized cluster of cells called the atrioventricular node conducts electrical impulses from the heart's upper chambers (the atria) to the lower chambers (the ventricles). Impulses move through the atrioventricular node during each heartbeat, stimulating the ventricles to contract slightly later than the atria.People with Wolff-Parkinson-White syndrome are born with an extra connection in the heart, called an accessory pathway, that allows electrical signals to bypass the atrioventricular node and move from the atria to the ventricles faster than usual. The accessory pathway may also transmit electrical impulses abnormally from the ventricles back to the atria. This extra connection can disrupt the coordinated movement of electrical signals through the heart, leading to an abnormally fast heartbeat (tachycardia) and other changes in heart rhythm. Resulting symptoms include dizziness, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, and fainting (syncope). In rare cases, arrhythmias associated with Wolff-Parkinson-White syndrome can lead to cardiac arrest and sudden death. The most common arrhythmia associated with Wolff-Parkinson-White syndrome is called paroxysmal supraventricular tachycardia.Complications of Wolff-Parkinson-White syndrome can occur at any age, although some individuals born with an accessory pathway in the heart never experience any health problems associated with the condition.Wolff-Parkinson-White syndrome often occurs with other structural abnormalities of the heart or underlying heart disease. The most common heart defect associated with the condition is Ebstein anomaly, which affects the valve that allows blood to flow from the right atrium to the right ventricle (the tricuspid valve). Additionally, the heart rhythm problems associated with Wolff-Parkinson-White syndrome can be a component of several other genetic syndromes, including hypokalemic periodic paralysis (a condition that causes episodes of extreme muscle weakness), Pompe disease (a disorder characterized by the storage of excess glycogen), Danon disease (a condition that weakens the heart and skeletal muscles and causes intellectual disability), and tuberous sclerosis complex (a condition that results in the growth of noncancerous tumors in many parts of the body). ad Autosomal dominant PRKAG2 https://medlineplus.gov/genetics/gene/prkag2 Ventricular pre-excitation with arrhythmia WPW Syndrome GTR C0043202 ICD-10-CM I45.6 MeSH D014927 OMIM 194200 SNOMED CT 74390002 2007-02 2024-09-19 Wolfram syndrome https://medlineplus.gov/genetics/condition/wolfram-syndrome descriptionWolfram syndrome is a condition that affects many of the body's systems. The hallmark features of Wolfram syndrome are high blood sugar (glucose) levels resulting from a shortage of the hormone insulin (a condition called diabetes mellitus) and progressive vision loss due to degeneration of the nerves that carry information from the eyes to the brain (a condition called optic atrophy). People with Wolfram syndrome often also have pituitary gland dysfunction that results in excess urine production (a condition called diabetes insipidus), hearing loss caused by changes in the inner ear (sensorineural deafness), urinary tract problems, reduced amounts of the sex hormone testosterone in males (hypogonadism), or neurological or psychiatric disorders.Diabetes mellitus is typically the first symptom of Wolfram syndrome, usually diagnosed around age 6. Nearly everyone with Wolfram syndrome who develops diabetes mellitus requires insulin replacement therapy. Optic atrophy is often the next symptom to appear, usually around age 11. The first signs of optic atrophy are loss of color vision and side (peripheral) vision. Over time, the vision problems get worse, and people with optic atrophy are usually blind within approximately 8 years after signs of optic atrophy first begin.In diabetes insipidus, the pituitary gland, which is located at the base of the brain, does not function normally. This abnormality disrupts the release of a hormone called vasopressin, which helps control the body's water balance and urine production. Approximately 70 percent of people with Wolfram syndrome have diabetes insipidus. Pituitary gland dysfunction can also cause hypogonadism in males. The lack of testosterone that occurs with hypogonadism affects growth and sexual development. About 65 percent of people with Wolfram syndrome have sensorineural deafness that can range in severity from deafness beginning at birth to mild hearing loss beginning in adolescence that worsens over time. Sixty to 90 percent of people with Wolfram syndrome have a urinary tract problem. Urinary tract problems include obstruction of the ducts between the kidneys and bladder (ureters), a large bladder that cannot empty normally (high-capacity atonal bladder), disrupted urination (bladder sphincter dyssynergia), and difficulty controlling the flow of urine (incontinence).About 60 percent of people with Wolfram syndrome develop a neurological or psychiatric disorder, most commonly problems with balance and coordination (ataxia), typically beginning in early adulthood. Other neurological problems experienced by people with Wolfram syndrome include irregular breathing caused by the brain's inability to control breathing (central apnea), loss of the sense of smell (anosmia), loss of the gag reflex, muscle spasms (myoclonus), seizures, reduced sensation in the lower extremities (peripheral neuropathy), and intellectual impairment. Psychiatric disorders associated with Wolfram syndrome include psychosis, episodes of severe depression, and impulsive and aggressive behavior.There are two types of Wolfram syndrome with many overlapping features. The two types are differentiated by their genetic cause. In addition to the usual features of Wolfram syndrome type 1 (described above), individuals with Wolfram syndrome type 2 have stomach or intestinal ulcers and excessive bleeding after an injury. The tendency to bleed excessively combined with the ulcers typically leads to abnormal bleeding in the gastrointestinal system. People with Wolfram syndrome type 2 do not develop diabetes insipidus.Historically, Wolfram syndrome was fatal by mid-adulthood due to complications from the many features of the condition, such as health problems related to diabetes mellitus or neurological problems. However, with better diagnosis and management, life expectancy has risen. ar Autosomal recessive WFS1 https://medlineplus.gov/genetics/gene/wfs1 CISD2 https://medlineplus.gov/genetics/gene/cisd2 Diabetes insipidus and mellitus with optic atrophy and deafness Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness DIDMOAD DIDMOAD syndrome DIDMOADUD GTR C0043207 GTR C1858028 MeSH D014929 OMIM 222300 OMIM 604928 SNOMED CT 70694009 2012-04 2023-07-19 Woodhouse-Sakati syndrome https://medlineplus.gov/genetics/condition/woodhouse-sakati-syndrome descriptionWoodhouse-Sakati syndrome is a disorder that primarily affects the body's network of hormone-producing glands (the endocrine system) and the nervous system. The signs and symptoms of this condition vary widely among affected individuals, even within the same family.People with Woodhouse-Sakati syndrome produce abnormally low amounts of hormones that direct sexual development (hypogonadism), which typically becomes apparent during adolescence. Without hormone replacement therapy, affected individuals do not develop secondary sexual characteristics such as pubic hair, breast growth in women, or a deepening voice in men. Women with Woodhouse-Sakati syndrome do not have functional ovaries and may instead have undeveloped tissues called streak gonads. The uterus may also be small or absent. Men with this disorder have testes that produce little to no sperm. As a result, people with Woodhouse-Sakati syndrome have difficulty having biological children (a condition called infertility).Some affected individuals have certain characteristic facial features, including a long, triangular face; widely spaced eyes (hypertelorism); and a prominent bridge of the nose. People with Woodhouse-Sakati syndrome also experience hair loss (alopecia) that begins in childhood and worsens over time. Eyelashes and eyebrows are sparse or absent, and affected men have little or no facial hair. By their mid-twenties, almost all affected individuals develop diabetes mellitus, and they may also have reduced production of thyroid hormones (hypothyroidism). Individuals with Woodhouse-Sakati syndrome may have neurological problems. A group of movement abnormalities called dystonias are common in affected individuals, and they generally begin in adolescence or young adulthood. These movement abnormalities can include involuntary tensing of the muscles (muscle contractions) or twisting of specific body parts such as an arm or a leg. Other neurological features can include difficulty with speech (dysarthria) or swallowing (dysphagia), and mild intellectual disabilities. Changes in the inner ears can lead to hearing loss (sensorineural hearing loss) in people with Woodhouse-Sakati syndrome. The hearing loss can range from mild to total. This loss usually occurs in adolescence.In some affected individuals, abnormal deposits of iron in the brain have been detected with medical imaging. For this reason, Woodhouse-Sakati syndrome is sometimes classified as part of a group of disorders called neurodegeneration with brain iron accumulation (NBIA).Some researchers classify Woodhouse-Sakati syndrome into two types, depending on the signs and symptoms. People with Woodhouse-Sakati syndrome type 1 tend to have more severe neurological problems, and those with type 2 have milder or no neurological problems.  ar Autosomal recessive DCAF17 https://medlineplus.gov/genetics/gene/dcaf17 Diabetes-hypogonadism-deafness-intellectual disability syndrome WSS GTR C0342286 ICD-10-CM MeSH D001480 MeSH D007006 OMIM 241080 SNOMED CT 237616002 2023-07 2023-08-14 X-linked acrogigantism https://medlineplus.gov/genetics/condition/x-linked-acrogigantism descriptionX-linked acrogigantism (X-LAG) is a condition that causes abnormally fast growth beginning early in life. Babies with this condition are a normal size at birth but begin to grow rapidly in infancy or early childhood, and affected children are taller than their peers.This rapid growth is caused by an abnormality of the pituitary gland. The pituitary gland, which is found at the base of the brain, produces hormones that control many important body functions, including growth. Individuals with X-LAG may have the condition as a result of enlargement (hyperplasia) of the gland or development of a noncancerous tumor in the gland (called a pituitary neuroendocrine tumor or PitNET). Rarely, an affected individual has both pituitary hyperplasia and a pituitary neuroendocrine tumor. The abnormal gland releases excess amounts of growth hormone, a hormone that normally helps direct growth of the body's bones and tissues. The abnormal gland can also release excess amounts of another hormone called prolactin, which helps control the function of the internal reproductive organs (gonads). Some people with X-LAG have additional signs and symptoms such as facial features that are described as coarse; disproportionately large hands or feet (acral enlargement); an increased appetite; and a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. ad Autosomal dominant GPR101 https://medlineplus.gov/genetics/gene/gpr101 X https://medlineplus.gov/genetics/chromosome/x Chromosome Xq26 microduplication syndrome Chromosome Xq26.3 duplication syndrome X-LAG X-linked acrogigantism syndrome XLAG GTR C3891556 MeSH D005877 OMIM 300942 2017-10 2023-05-15 X-linked adrenal hypoplasia congenita https://medlineplus.gov/genetics/condition/x-linked-adrenal-hypoplasia-congenita descriptionX-linked adrenal hypoplasia congenita is a disorder that is noticeable from birth (congenital) and affects the development of the adrenal glands, which are hormone-producing (endocrine) organs (glands) located on top of each kidney. These glands produce a variety of hormones that regulate many essential functions in the body, such as response to stress.One of the main signs of this disorder is adrenal insufficiency, which occurs when the adrenal glands do not produce enough hormones. Adrenal insufficiency typically begins in infancy or childhood and can cause vomiting, difficulty with feeding, dehydration, extremely low blood glucose (hypoglycemia), and shock. If untreated, these complications are often life-threatening.Individuals with X-linked adrenal hypoplasia congenita may also have a shortage of male sex hormones, which leads to underdeveloped reproductive tissues, undescended testicles (cryptorchidism), delayed puberty, and an inability to father children (infertility). Together, these characteristics are known as hypogonadotropic hypogonadism.The onset and severity of these signs and symptoms can vary, even among affected members of the same family. xr X-linked recessive NR0B1 https://medlineplus.gov/genetics/gene/nr0b1 Adrenal hypoplasia congenita X-linked AHC GTR C0342482 MeSH D000307 OMIM 300200 SNOMED CT 237764004 2022-05 2023-07-26 X-linked adrenoleukodystrophy https://medlineplus.gov/genetics/condition/x-linked-adrenoleukodystrophy descriptionX-linked adrenoleukodystrophy is a genetic disorder that mainly affects the nervous system and the adrenal glands, which are located on top of each kidney. In this disorder, the fatty covering (myelin) that insulates nerves in the brain and spinal cord tends to deteriorate (a condition called demyelination). The loss of myelin reduces the ability of the nerves to relay information to the brain. In addition, damage to the outer layer of the adrenal glands (adrenal cortex) causes a shortage of certain hormones (adrenocortical insufficiency). Adrenocortical insufficiency may cause weakness, weight loss, skin changes, vomiting, and coma.There are four distinct types of X-linked adrenoleukodystrophy: a childhood cerebral form, an adrenomyeloneuropathy type, an adrenal insufficiency only form, and a type called asymptomatic.The childhood cerebral form of X-linked adrenoleukodystrophy typically occurs in boys. Girls are rarely affected with this type. If not treated, affected boys experience learning and behavioral problems that usually begin between the ages of 4 and 10. Over time the symptoms can worsen, and children may have difficulty reading, writing, understanding speech, and comprehending written material. Additional signs and symptoms of the cerebral form include aggressive behavior, vision problems, difficulty swallowing, poor coordination, and impaired adrenal gland function. The rate at which this disorder progresses is variable but can be extremely rapid, often leading to total disability within a few years. The life expectancy of individuals with this type depends on whether early diagnosis and treatment are available. Without treatment, individuals with the cerebral form of X-linked adrenoleukodystrophy usually survive only a few years after symptoms begin.Signs and symptoms of the adrenomyeloneuropathy type appear between early adulthood and middle age. Affected individuals develop progressive stiffness and weakness in their legs (paraparesis), experience urinary and genital tract disorders, and often show changes in behavior and intellectual function. Most people with the adrenomyeloneuropathy type also have adrenocortical insufficiency. Some severely affected individuals develop cerebral X-linked adrenoleukodystrophy. People with X-linked adrenoleukodystrophy whose only symptom is adrenocortical insufficiency are said to have the adrenal insufficiency only form. In these individuals, adrenocortical insufficiency can begin anytime between the first year of life and adulthood. However, most affected individuals develop the additional features of cerebral X-linked adrenoleukodystrophy in childhood or the adrenomyeloneuropathy type by the time they reach middle age. The life expectancy of individuals with the adrenal insufficiency form depends on the severity of the signs and symptoms, but typically this is the mildest of the three types.Children with the asymptomatic form do not appear to have any symptoms of X-linked adrenoleukodystrophy, but medical testing may show brain or biochemical abnormalities. Some individuals with the asymptomatic form may develop features of other types of X-linked adrenoleukodystrophy later in life.Rarely, individuals with X-linked adrenoleukodystrophy develop multiple features of the disorder in adolescence or early adulthood. In addition to adrenocortical insufficiency, these individuals usually have psychiatric disorders and a loss of intellectual function (dementia). It is unclear whether these individuals have a distinct form of the condition or a variation of one of the previously described types.For reasons that are unclear, different forms of X-linked adrenoleukodystrophy can be seen in affected individuals within the same family. x X-linked ABCD1 https://medlineplus.gov/genetics/gene/abcd1 X-ALD GTR C0162309 ICD-10-CM E71.52 ICD-10-CM E71.520 ICD-10-CM E71.521 ICD-10-CM E71.522 ICD-10-CM E71.528 ICD-10-CM E71.529 MeSH D000326 OMIM 300100 SNOMED CT 366951000119109 SNOMED CT 367041000119108 SNOMED CT 65389002 2013-07 2022-10-26 X-linked agammaglobulinemia https://medlineplus.gov/genetics/condition/x-linked-agammaglobulinemia descriptionX-linked agammaglobulinemia (XLA) is a condition that affects the immune system and occurs almost exclusively in males. It is part of a group of disorders called primary immunodeficiencies (or inborn errors of immunity), in which part of the immune system does not function as it should. People with XLA have very few B cells, which are specialized white blood cells that help protect the body against infection. B cells can mature into the cells that produce special proteins called antibodies or immunoglobulins. Antibodies attach to specific foreign particles and germs, marking them for destruction. Individuals with XLA are more susceptible to infections because their body makes very few antibodies.Children with XLA are usually healthy for the first 1 or 2 months of life because they are protected by antibodies acquired before birth from their mother. After this time, the maternal antibodies are cleared from the body, and the affected child begins to develop recurrent infections. .cf0{font-style:italic;font-family:Segoe UI;font-size:9pt;}Children with XLA generally take longer to recover from infections, and infections often occur again, even in children who are taking antibiotic medications.The most common bacterial infections that occur in people with XLA are lung infections (pneumonia and bronchitis), ear infections (otitis), pink eye (conjunctivitis), and sinus infections (sinusitis). Infections that cause chronic diarrhea are also common. Recurrent infections can lead to organ damage. .cf0{font-style:italic;font-family:Segoe UI;font-size:9pt;}Treatments that replace antibodies can help prevent infections, improving the quality of life for people with XLA. xr X-linked recessive BTK https://medlineplus.gov/genetics/gene/btk Agammaglobulinemia Bruton's agammaglobulinemia Congenital agammaglobulinemia Hypogammaglobulinemia GTR C0221026 ICD-10-CM D80.0 MeSH D000361 OMIM 300755 SNOMED CT 65880007 2023-03 2023-03-17 X-linked cardiac valvular dysplasia https://medlineplus.gov/genetics/condition/x-linked-cardiac-valvular-dysplasia descriptionX-linked cardiac valvular dysplasia is a condition characterized by the abnormal development (dysplasia) of heart (cardiac) valves. The normal heart has four valves, two on the left side of the heart and two on the right side, that allow blood to move through the heart and prevent blood from flowing backward. In X-linked cardiac valvular dysplasia, one or more of the four heart valves is thickened and cannot open and close completely when the heart beats and pumps blood. These malformed valves can cause abnormal blood flow and an irregular heart sound during a heartbeat (heart murmur).The signs and symptoms of X-linked cardiac valvular dysplasia vary greatly among affected individuals. Some people have no health problems, while in others blood can leak through the thickened and partially closed valves. This valve leakage (regurgitation) typically affects the mitral valve, which connects the two left chambers of the heart, or the aortic valve, which regulates blood flow from the heart into the large artery called the aorta. Valve regurgitation forces the heart to pump harder to move blood through the heart. As a result, affected individuals may develop chest pains, shortness of breath, or lightheadedness.In X-linked cardiac valvular dysplasia, the mitral or aortic valve can also be prolapsed, which means that the valve is weak or floppy. Valve prolapse further prevents the thickened valve from closing properly and can lead to valve regurgitation. Other rare complications of X-linked cardiac valvular dysplasia include inflammation of the inner lining of the heart (endocarditis), abnormal blood clots, or sudden death.X-linked cardiac valvular dysplasia can be diagnosed anytime from birth (in some cases prenatally) to late adulthood but is typically diagnosed in early to mid-adulthood because valve malformation is often a slow process. This condition affects males more often and more severely than females. x X-linked FLNA https://medlineplus.gov/genetics/gene/flna Congenital valvular heart disease CVD1 Filamin-A-associated myxomatous mitral valve disease Filamin-A-related myxomatous mitral valve dystrophy X-linked myxomatous valvular dystrophy XMVD MeSH D016127 OMIM 314400 SNOMED CT 5203004 2016-08 2020-08-18 X-linked chondrodysplasia punctata 1 https://medlineplus.gov/genetics/condition/x-linked-chondrodysplasia-punctata-1 descriptionX-linked chondrodysplasia punctata 1 is a disorder of cartilage and bone development that occurs almost exclusively in males. Chondrodysplasia punctata is an abnormality that appears on x-rays as spots (stippling) near the ends of bones and in cartilage. In most infants with X-linked chondrodysplasia punctata 1, this stippling is seen in bones of the ankles, toes, and fingers; however, it can also appear in other bones. The stippling generally disappears in early childhood.Other characteristic features of X-linked chondrodysplasia punctata 1 include short stature and unusually short fingertips and ends of the toes. This condition is also associated with distinctive facial features, particularly a flattened-appearing nose with crescent-shaped nostrils and a flat nasal bridge.People with X-linked chondrodysplasia punctata 1 typically have normal intelligence and a normal life expectancy. However, some affected individuals have had serious or life-threatening complications including abnormal thickening (stenosis) of the cartilage that makes up the airways, which restricts breathing. Also, abnormalities of spinal bones in the neck can lead to pinching (compression) of the spinal cord, which can cause pain, numbness, and weakness. Other, less common features of X-linked chondrodysplasia punctata 1 include delayed development, hearing loss, vision abnormalities, and heart defects. xr X-linked recessive ARSL https://medlineplus.gov/genetics/gene/arsl Arylsulfatase E deficiency CDPX1 Chondrodysplasia punctata 1, X-linked X-linked recessive chondrodysplasia punctata 1 GTR C1844853 ICD-10-CM Q77.3 MeSH D002806 OMIM 302950 SNOMED CT 254082007 2011-11 2022-07-01 X-linked chondrodysplasia punctata 2 https://medlineplus.gov/genetics/condition/x-linked-chondrodysplasia-punctata-2 descriptionX-linked chondrodysplasia punctata 2 is a disorder characterized by bone, skin, and eye abnormalities. It occurs almost exclusively in females.Although the signs and symptoms of this condition vary widely, almost all affected individuals have chondrodysplasia punctata, an abnormality that appears on x-rays as spots (stippling) near the ends of bones and in cartilage. In this form of chondrodysplasia punctata, the stippling typically affects the long bones in the arms and legs, the ribs, the spinal bones (vertebrae), and the cartilage that makes up the windpipe (trachea). The stippling is apparent in infancy but disappears in early childhood. Other skeletal abnormalities seen in people with X-linked chondrodysplasia punctata 2 include shortening of the bones in the upper arms and thighs (rhizomelia) that is often different on the right and left sides, and progressive abnormal curvature of the spine (kyphoscoliosis). As a result of these abnormalities, people with this condition tend to have short stature.Infants with X-linked chondrodysplasia punctata 2 are born with dry, scaly patches of skin (ichthyosis) in a linear or spiral (whorled) pattern. The scaly patches fade over time, leaving abnormally colored blotches of skin without hair (follicular atrophoderma). Most affected individuals also have sparse, coarse hair on their scalps.Most people with X-linked chondrodysplasia punctata 2 have clouding of the lens of the eye (cataracts) from birth or early childhood. Other eye abnormalities that have been associated with this disorder include unusually small eyes (microphthalmia) and small corneas (microcornea). The cornea is the clear front surface of the eye. These eye abnormalities can impair vision.In affected females, X-linked chondrodysplasia punctata 2 is typically associated with normal intelligence and a normal lifespan. However, a much more severe form of the condition has been reported in a small number of males. Affected males have some of the same features as affected females, as well as weak muscle tone (hypotonia), changes in the structure of the brain, moderately to profoundly delayed development, seizures, distinctive facial features, and other birth defects. The health problems associated with X-linked chondrodysplasia punctata 2 are often life-threatening in males. xd X-linked dominant EBP https://medlineplus.gov/genetics/gene/ebp CDPX2 Chondrodysplasia punctata 2, X-linked Conradi-Hünermann syndrome Conradi-Hünermann-Happle syndrome Happle syndrome X-linked dominant chondrodysplasia punctata GTR C0282102 ICD-10-CM Q77.3 MeSH D002806 OMIM 302960 SNOMED CT 398719004 2011-11 2021-04-07 X-linked congenital stationary night blindness https://medlineplus.gov/genetics/condition/x-linked-congenital-stationary-night-blindness descriptionX-linked congenital stationary night blindness is a disorder of the retina, which is a specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing in low light (night blindness). They also have other vision problems, including increased sensitivity to light (photophobia), loss of sharpness (reduced visual acuity), severe nearsightedness (high myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus). Color vision is typically not affected in people with X-linked congenital stationary night blindness.The vision problems associated with X-linked congenital stationary night blindness are congenital, which means they are present from birth. The vision problems also tend to remain stable (stationary) over time.Researchers have identified two major types of X-linked congenital stationary night blindness: the complete form and the incomplete form. The types have very similar signs and symptoms. However, everyone with the complete form has night blindness, while not all people with the incomplete form have night blindness. The types are distinguished by their genetic causes and by the results of a test called an electroretinogram, which measures the function of the retina. xr X-linked recessive NYX https://medlineplus.gov/genetics/gene/nyx CACNA1F https://medlineplus.gov/genetics/gene/cacna1f X-linked CSNB XLCSNB GTR C0339535 GTR C1848172 GTR C3495587 ICD-10-CM H53.63 MeSH D009755 OMIM 300071 OMIM 310500 SNOMED CT 232061009 2024-06 2025-03-10 X-linked creatine deficiency https://medlineplus.gov/genetics/condition/x-linked-creatine-deficiency descriptionX-linked creatine deficiency is an inherited disorder that primarily affects the brain. People with this disorder have intellectual disability, which can range from mild to severe, and delayed speech development. Some affected individuals develop behavioral disorders such as attention-deficit/hyperactivity disorder (ADHD) or autistic behaviors that affect communication and social interaction. They may also experience seizures. Children with X-linked creatine deficiency may grow slower and develop motor skills, such as sitting and walking, later than their peers. Affected individuals tend to tire easily.A small number of people with X-linked creatine deficiency have additional signs and symptoms including abnormal heart rhythms, an unusually small head (microcephaly), or distinctive facial features such as a broad forehead and a flat or sunken appearance of the middle of the face (midface hypoplasia). x X-linked SLC6A8 https://medlineplus.gov/genetics/gene/slc6a8 Creatine transporter defect Creatine transporter deficiency SLC6A8 deficiency SLC6A8-related creatine transporter deficiency X-linked creatine deficiency syndrome GTR C1845862 MeSH D020739 OMIM 300352 SNOMED CT 698290008 2011-06 2023-02-06 X-linked dilated cardiomyopathy https://medlineplus.gov/genetics/condition/x-linked-dilated-cardiomyopathy descriptionX-linked dilated cardiomyopathy is a form of heart disease. Dilated cardiomyopathy enlarges and weakens the heart (cardiac) muscle, preventing the heart from pumping blood efficiently. Signs and symptoms of this condition can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. In males with X-linked dilated cardiomyopathy, heart problems usually develop early in life and worsen quickly, leading to heart failure in adolescence or early adulthood. In affected females, the condition appears later in life and worsens more slowly.X-linked dilated cardiomyopathy is part of a spectrum of related conditions caused by mutations in the DMD gene. The other conditions in the spectrum, Duchenne and Becker muscular dystrophy, are characterized by progressive weakness and wasting of muscles used for movement (skeletal muscles) in addition to heart disease. People with X-linked dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing. Based on these skeletal muscle changes, X-linked dilated cardiomyopathy is sometimes classified as subclinical Becker muscular dystrophy. xd X-linked dominant DMD https://medlineplus.gov/genetics/gene/dmd CMD3B Dilated cardiomyopathy 3B DMD-associated dilated cardiomyopathy DMD-related dilated cardiomyopathy XLCM XLDC GTR C3668940 ICD-10-CM I42.0 MeSH D002311 OMIM 302045 SNOMED CT 702424003 2012-02 2020-08-18 X-linked dystonia-parkinsonism https://medlineplus.gov/genetics/condition/x-linked-dystonia-parkinsonism descriptionX-linked dystonia-parkinsonism is a movement disorder that has been found only in people of Filipino descent. This condition affects men much more often than women.Parkinsonism is usually the first sign of X-linked dystonia-parkinsonism. Parkinsonism is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling gait that can cause recurrent falls.Later in life, many affected individuals also develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia associated with X-linked dystonia-parkinsonism typically starts in one area, most often the eyes, jaw, or neck, and later spreads to other parts of the body. The continuous muscle cramping and spasms can be disabling. Depending on which muscles are affected, widespread (generalized) dystonia can cause difficulty with speaking, swallowing, coordination, and walking.The signs and symptoms of X-linked dystonia-parkinsonism vary widely. In the mildest cases, affected individuals have slowly progressive parkinsonism with little or no dystonia. More severe cases involve dystonia that rapidly becomes generalized. These individuals become dependent on others for care within a few years after signs and symptoms appear, and they may die prematurely from breathing difficulties, infections (such as aspiration pneumonia), or other complications. xr X-linked recessive TAF1 https://medlineplus.gov/genetics/gene/taf1 Dystonia 3, torsion, X-linked Dystonia musculorum deformans Dystonia-parkinsonism, X-linked DYT3 Lubag Torsion dystonia-parkinsonism, Filipino type X-linked dystonia-parkinsonism syndrome X-linked torsion dystonia-parkinsonism syndrome XDP GTR C1839130 MeSH D020734 OMIM 314250 SNOMED CT 698279003 2022-11 2022-11-07 X-linked hyper IgM syndrome https://medlineplus.gov/genetics/condition/x-linked-hyper-igm-syndrome descriptionX-linked hyper IgM syndrome is a condition that affects the immune system and occurs almost exclusively in males. People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. There are several classes of antibodies, and each one has a different function in the immune system. Although the name of this condition implies that affected individuals always have high levels of immunoglobulin M (IgM), some people have normal levels of this antibody. People with X-linked hyper IgM syndrome have low levels of three other classes of antibodies: immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). The lack of certain antibody classes makes it difficult for people with this disorder to fight off infections.Individuals with X-linked hyper IgM syndrome begin to develop frequent infections in infancy and early childhood. Common infections include pneumonia, sinus infections (sinusitis), and ear infections (otitis). Infections often cause these children to have chronic diarrhea and they fail to gain weight and grow at the expected rate (failure to thrive). Some people with X-linked hyper IgM syndrome have low levels of white blood cells called neutrophils (neutropenia). Affected individuals may develop autoimmune disorders, neurologic complications from brain and spinal cord (central nervous system) infections, liver disease, and gastrointestinal tumors. They also have an increased risk of lymphoma, which is a cancer of immune system cells.The severity of X-linked hyper IgM syndrome varies among affected individuals, even among members of the same family. Without treatment, this condition can result in death during childhood or adolescence. xr X-linked recessive CD40LG https://medlineplus.gov/genetics/gene/cd40lg HIGM1 Hyper-IgM syndrome 1 Immunodeficiency with Hyper-IgM, type 1 GTR C0398689 ICD-10-CM D80.5 MeSH D053307 OMIM 308230 SNOMED CT 403835002 2008-10 2023-02-06 X-linked hypophosphatemia https://medlineplus.gov/genetics/condition/x-linked-hypophosphatemia descriptionX-linked hypophosphatemia is characterized by low levels of phosphate in the blood (hypophosphatemia), which can lead to skeletal abnormalities. Phosphate is a mineral that is essential for the normal development of bones and teeth. Without adequate amounts of phosphate, the bones can weaken or soften, leading to a condition called rickets in growing children or a similar condition called osteomalacia in adults.The features of X-linked hypophosphatemia vary widely, even among members of the same family. Mildly affected individuals may have hypophosphatemia without other signs and symptoms. More severely affected individuals typically experience slow growth beginning in early childhood, and they may be shorter than their peers. They often develop bone abnormalities that can impair movement and cause pain, such as legs that are abnormally curved (bowed) because the bones are too weak to bear weight. These abnormalities tend to worsen over time.In adults with X-linked hypophosphatemia, osteomalacia can make the bones more prone to a type of fracture called a stress fracture, which can be painful. Affected adults may also have abnormal calcium deposits that occur near the joints where the ligaments and tendons attach (enthesopathy) and a painful joint disorder called osteoarthritis.Other signs and symptoms of X-linked hypophosphatemia can include premature fusion of the skull bones (craniosynostosis) and hearing loss. Affected individuals may also have dental abnormalities, which can include pus caused by a bacterial infection (abscess). In rare cases, people with X-linked hypophosphatemia have abnormalities of the spine, which can include a narrowing of the spinal canal that can pinch the upper part of the spinal cord (spinal stenosis) and the formation of fluid-filled cysts (syrinx) within the spinal cord.With early treatment, people with X-linked hypophosphatemia may have less-severe skeletal signs and symptoms and fewer long-term health issues. x X-linked PHEX https://medlineplus.gov/genetics/gene/phex Hypophosphatemic rickets, PHEX-Related X-Linked Hypophosphatemic Rickets X-Linked Vitamin D-Resistant Rickets XLHR GTR C0733682 ICD-10-CM E83.31 MeSH D053098 OMIM 307800 SNOMED CT 237889002 SNOMED CT 237891005 SNOMED CT 4996001 SNOMED CT 82236004 SNOMED CT 90505000 2026-02 2026-02-13 X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia https://medlineplus.gov/genetics/condition/x-linked-immunodeficiency-with-magnesium-defect-epstein-barr-virus-infection-and-neoplasia descriptionX-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym XMEN) is a disorder that affects the immune system in males. In XMEN, certain types of immune system cells called T cells are reduced in number or do not function properly. Normally these cells recognize foreign invaders, such as viruses, bacteria, and fungi, and are then turned on (activated) to attack these invaders in order to prevent infection and illness. Because males with XMEN do not have enough functional T cells, they have frequent infections, such as ear infections, sinus infections, and pneumonia.In particular, affected individuals are vulnerable to the Epstein-Barr virus (EBV). EBV is a very common virus that infects more than 90 percent of the general population and in most cases goes unnoticed. Normally, after initial infection, EBV remains in the body for the rest of a person's life. However, the virus is generally inactive (latent) because it is controlled by T cells. In males with XMEN, however, the T cells cannot control the virus, and EBV infection can lead to cancers of immune system cells (lymphomas). The word "neoplasia" in the condition name refers to these lymphomas; neoplasia is a general term meaning abnormal growths of tissue. The EBV infection itself usually does not cause any other symptoms in males with XMEN, and affected individuals may not come to medical attention until they develop lymphoma. xr X-linked recessive MAGT1 https://medlineplus.gov/genetics/gene/magt1 Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection, and neoplasia XMEN GTR C3275445 MeSH D008231 OMIM 300853 SNOMED CT 711481001 2014-06 2020-08-18 X-linked infantile nystagmus https://medlineplus.gov/genetics/condition/x-linked-infantile-nystagmus descriptionX-linked infantile nystagmus is a condition characterized by abnormal eye movements. Nystagmus is a term that refers to involuntary side-to-side, up-and-down, or circular movements of the eyes. In people with X-linked infantile nystagmus, the movements are typically side-to-side. In individuals with this condition, nystagmus is present at birth or develops within the first six months of life. The abnormal eye movements may worsen when an affected person is feeling anxious or tries to stare directly at an object. Some affected individuals will experience involuntary changes in the direction of their eye movements (periodic alternating nystagmus). The severity of nystagmus varies, even among affected individuals within the same family. Sometimes, affected individuals will turn or tilt their head to compensate for the irregular eye movements. Individuals with X-linked infantile nystagmus may have other eye abnormalities. For example, the region at the back of the eye responsible for sharp central vision may be underdeveloped (foveal hypoplasia). x X-linked FRMD7 https://medlineplus.gov/genetics/gene/frmd7 Congenital motor nystagmus FRMD7-related infantile nystagmus Idiopathic infantile nystagmus NYS1 X-linked congenital nystagmus X-linked idiopathic infantile nystagmus GTR C1839580 ICD-10-CM H55.01 MeSH D020417 OMIM 310700 SNOMED CT 307671001 SNOMED CT 64635004 2023-09 2025-03-06 X-linked infantile spinal muscular atrophy https://medlineplus.gov/genetics/condition/x-linked-infantile-spinal-muscular-atrophy descriptionX-linked infantile spinal muscular atrophy is a condition that affects only boys and is characterized by severe muscle weakness and absent reflexes (areflexia). Affected children often have multiple joint deformities (contractures) from birth that cause joint stiffness (arthrogryposis) and impair movement. In severe cases, affected infants are born with broken bones. The muscle weakness worsens over time; affected children reach some early motor developmental milestones, such as sitting unassisted, but these skills are often lost (developmental regression).Additional features of X-linked infantile spinal muscular atrophy include an unusually small chin (micrognathia), abnormal curvature of the spine (scoliosis or kyphosis), and undescended testes (cryptorchidism).Weakness of the chest muscles used for breathing often leads to life-threatening breathing problems. Children with X-linked infantile spinal muscular atrophy usually do not survive past early childhood due to respiratory failure, although, in rare cases, affected individuals can survive into adolescence. xr X-linked recessive UBA1 https://medlineplus.gov/genetics/gene/uba1 AMCX1 Arthrogryposis multiplex congenita, distal, X-linked Arthrogryposis, X-lined, type I Distal X-linked AMC Infantile X-linked SMA SMAX2 Spinal muscular atrophy, infantile X-linked Spinal muscular atrophy, X-linked 2 Spinal muscular atrophy, X-linked lethal infantile X-linked arthrogryposis multiplex congenita X-linked arthrogryposis type I X-linked lethal infantile SMA XL-SMA XLSMA GTR C1844934 MeSH D014897 OMIM 301830 SNOMED CT 719836007 2018-07 2020-08-18 X-linked intellectual disability, Siderius type https://medlineplus.gov/genetics/condition/x-linked-intellectual-disability-siderius-type descriptionX-linked intellectual disability, Siderius type is a condition characterized by mild to moderate intellectual disability that affects only males. Affected boys often have delayed development of motor skills such as walking, and their speech may be delayed.Individuals with X-linked intellectual disability, Siderius type frequently also have an opening in the lip (cleft lip) with an opening in the roof of the mouth (cleft palate). A cleft can occur on one or both sides of the upper lip.Some boys and men with this condition have distinctive facial features, including a long face, a sloping forehead, a broad nasal bridge, a prominent bone in the lower forehead (supraorbital ridge), and outside corners of the eyes that point upward (upslanting palpebral fissures). Affected individuals may also have low-set ears and large hands. xr X-linked recessive PHF8 https://medlineplus.gov/genetics/gene/phf8 MRXSSD Siderius X-linked mental retardation syndrome Siderius-Hamel syndrome Syndromic X-linked mental retardation, Siderius type X-linked mental retardation Hamel type X-linked mental retardation Siderius type GTR C1846055 MeSH D038901 OMIM 300263 SNOMED CT 718908009 2015-06 2020-08-18 X-linked juvenile retinoschisis https://medlineplus.gov/genetics/condition/x-linked-juvenile-retinoschisis descriptionX-linked juvenile retinoschisis is a condition characterized by impaired vision that begins in childhood and occurs almost exclusively in males. This disorder affects the retina, which is a specialized light-sensitive tissue that lines the back of the eye. Damage to the retina impairs the sharpness of vision (visual acuity) in both eyes. Typically, X-linked juvenile retinoschisis affects cells in the central area of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. X-linked juvenile retinoschisis is one type of a broader disorder called macular degeneration, which disrupts the normal functioning of the macula. Occasionally, side (peripheral) vision is affected in people with X-linked juvenile retinoschisis.X-linked juvenile retinoschisis is usually diagnosed when affected boys start school and poor vision and difficulty with reading become apparent. In more severe cases, eye squinting and involuntary movement of the eyes (nystagmus) begin in infancy. Other early features of X-linked juvenile retinoschisis include eyes that do not look in the same direction (strabismus) and farsightedness (hyperopia). Visual acuity often declines in childhood and adolescence but then stabilizes throughout adulthood until a significant decline in visual acuity typically occurs in a man's fifties or sixties. Sometimes, severe complications develop, such as separation of the retinal layers (retinal detachment) or leakage of blood vessels in the retina (vitreous hemorrhage). These eye abnormalities can further impair vision or cause blindness. xr X-linked recessive RS1 https://medlineplus.gov/genetics/gene/rs1 Congenital X-linked retinoschisis Degenerative retinoschisis Juvenile retinoschisis X-linked retinoschisis XJR GTR C3714753 MeSH D041441 OMIM 312700 SNOMED CT 232013002 SNOMED CT 232014008 SNOMED CT 86923008 SNOMED CT 95493003 2008-08 2020-08-18 X-linked lissencephaly with abnormal genitalia https://medlineplus.gov/genetics/condition/x-linked-lissencephaly-with-abnormal-genitalia descriptionX-linked lissencephaly with abnormal genitalia (XLAG) is a condition that affects the development of the brain and genitalia. It occurs most often in males.XLAG is characterized by abnormal brain development that results in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. Individuals without any folds in the brain (agyria) typically have more severe symptoms than people with reduced folds and grooves (pachygyria). Individuals with XLAG may also have a lack of development (agenesis) of the tissue connecting the left and right halves of the brain (corpus callosum). In XLAG, the brain abnormalities can cause severe intellectual disability and developmental delay, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. Starting soon after birth, babies with XLAG have frequent and recurrent seizures (epilepsy). Most children with XLAG do not survive past early childhood.Another key feature of XLAG in males is abnormal genitalia that can include an unusually small penis (micropenis), undescended testes (cryptorchidism), or external genitalia that do not look clearly male or clearly female.Additional signs and symptoms of XLAG include chronic diarrhea, periods of increased blood glucose (transient hyperglycemia), and problems with body temperature regulation. xd X-linked dominant ARX https://medlineplus.gov/genetics/gene/arx LISX2 X-linked lissencephaly 2 X-linked lissencephaly with ambiguous genitalia XLAG XLISG GTR C1846171 ICD-10-CM Q04.3 MeSH D054221 OMIM 300215 SNOMED CT 717632002 2013-08 2023-10-26 X-linked lymphoproliferative disease https://medlineplus.gov/genetics/condition/x-linked-lymphoproliferative-disease descriptionX-linked lymphoproliferative disease (XLP) is a disorder of the immune system and blood-forming cells that is found almost exclusively in males. More than half of individuals with this disorder experience an exaggerated immune response to the Epstein-Barr virus (EBV). EBV is a very common virus that eventually infects most humans. In some people it causes infectious mononucleosis (commonly known as "mono"). Normally, after initial infection, EBV remains in certain immune system cells (lymphocytes) called B cells. However, the virus is generally inactive (latent) because it is controlled by other lymphocytes called T cells that specifically target EBV-infected B cells.People with XLP may respond to EBV infection by producing abnormally large numbers of T cells, B cells, and other lymphocytes called macrophages. This proliferation of immune cells often causes a life-threatening reaction called hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis causes fever, destroys blood-producing cells in the bone marrow, and damages the liver. The spleen, heart, kidneys, and other organs and tissues may also be affected. In some individuals with XLP, hemophagocytic lymphohistiocytosis or related symptoms may occur without EBV infection.About one-third of people with XLP experience dysgammaglobulinemia, which means they have abnormal levels of some types of antibodies. Antibodies (also known as immunoglobulins) are proteins that attach to specific foreign particles and germs, marking them for destruction. Individuals with dysgammaglobulinemia are prone to recurrent infections.Cancers of immune system cells (lymphomas) occur in about one-third of people with XLP.Without treatment, most people with XLP survive only into childhood. Death usually results from hemophagocytic lymphohistiocytosis.XLP can be divided into two types based on its genetic cause and pattern of signs and symptoms: XLP1 (also known as classic XLP) and XLP2. People with XLP2 have not been known to develop lymphoma, are more likely to develop hemophagocytic lymphohistiocytosis without EBV infection, usually have an enlarged spleen (splenomegaly), and may also have inflammation of the large intestine (colitis). Some researchers believe that these individuals should actually be considered to have a similar but separate disorder rather than a type of XLP. xr X-linked recessive XIAP https://medlineplus.gov/genetics/gene/xiap SH2D1A https://medlineplus.gov/genetics/gene/sh2d1a Duncan disease Epstein-Barr virus-induced lymphoproliferative disease in males Familial fatal Epstein-Barr infection Purtilo syndrome Severe susceptibility to EBV infection Severe susceptibility to infectious mononucleosis X-linked lymphoproliferative syndrome XLP GTR C0549463 GTR C1845076 GTR C5399825 ICD-10-CM D82.3 MeSH D008232 OMIM 300635 OMIM 308240 SNOMED CT 77121009 2010-08 2023-08-22 X-linked myotubular myopathy https://medlineplus.gov/genetics/condition/x-linked-myotubular-myopathy descriptionX-linked myotubular myopathy is a condition that primarily affects muscles used for movement (skeletal muscles) and occurs almost exclusively in males. People with this condition have muscle weakness (myopathy) and decreased muscle tone (hypotonia) that are usually evident at birth. When viewed under a microscope, the muscle fibers of affected individuals are typically small and underdeveloped.The muscle problems in X-linked myotubular myopathy impair the development of motor skills such as sitting, standing, and walking. Affected infants may also have difficulties with feeding due to muscle weakness. Individuals with this condition often do not have the muscle strength to breathe regularly on their own and must be supported with a machine to help them get enough oxygen (mechanical ventilation). Some affected individuals need breathing assistance only periodically, typically during sleep, while others require it continuously. People with X-linked myotubular myopathy may also have weakness in the muscles that control eye movement (ophthalmoplegia), weakness in other muscles of the face, and absent reflexes (areflexia).In X-linked myotubular myopathy, muscle weakness often disrupts normal bone development and can lead to fragile bones, an abnormal curvature of the spine (scoliosis), and joint deformities (contractures) of the hips and knees. People with X-linked myotubular myopathy may have a large head with a narrow and elongated face and a high, arched roof of the mouth (palate). They may also have recurrent ear and respiratory infections, seizures, or liver disease. Some affected individuals develop a serious liver condition called peliosis hepatitis, which can cause life-threatening bleeding (hemorrhage).Because of their severe breathing problems, individuals with X-linked myotubular myopathy usually survive only into early childhood; however, some people with this condition have lived into adulthood.X-linked myotubular myopathy is the most severe condition in a group of disorders called centronuclear myopathy. In centronuclear myopathy, the nucleus is found at the center of many rod-shaped muscle cells instead of at either end, where it is normally located. xr X-linked recessive MTM1 https://medlineplus.gov/genetics/gene/mtm1 CNM MTMX X-linked centronuclear myopathy XLMTM XMTM GTR C0410203 ICD-10-CM G71.2 MeSH D020914 OMIM 310400 SNOMED CT 46804001 2008-09 2023-04-04 X-linked severe combined immunodeficiency https://medlineplus.gov/genetics/condition/x-linked-severe-combined-immunodeficiency descriptionX-linked severe combined immunodeficiency (SCID) is an inherited disorder of the immune system that occurs almost exclusively in males. Children with X-linked SCID are prone to recurrent and persistent infections because they lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. If untreated, infants with X-linked SCID can develop poor growth, chronic diarrhea, a fungal infection called thrush, skin rashes, and life-threatening infections. X-linked SCID can be detected shortly after birth by newborn screening, which allows for prompt treatment. xr X-linked recessive IL2RG https://medlineplus.gov/genetics/gene/il2rg IL2RG SCID, T- B+ NK- SCIDX1 X-linked SCID X-SCID XSCID GTR C1279481 MeSH D053632 OMIM 300400 SNOMED CT 203592006 2022-03 2022-03-18 X-linked sideroblastic anemia https://medlineplus.gov/genetics/condition/x-linked-sideroblastic-anemia descriptionX-linked sideroblastic anemia belongs to a group of disorders that are characterized by a shortage of healthy red blood cells (anemia). X-linked sideroblastic anemia prevents developing red blood cells from making enough hemoglobin, which is the protein that carries oxygen in the blood. People with X-linked sideroblastic anemia have red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. This disorder also leads to an abnormal accumulation of iron in red blood cells. The iron-loaded red blood cells, which are present in bone marrow, are called ring sideroblasts.The signs and symptoms of X-linked sideroblastic anemia are caused by a combination of too little hemoglobin and too much iron. Common signs and symptoms include extreme tiredness (fatigue), dizziness, a rapid heartbeat, pale skin, and an enlarged liver and spleen (hepatosplenomegaly). Over time, severe health problems such as heart disease and liver damage (cirrhosis), can result from the buildup of iron in these organs.Males with X-linked sideroblastic anemia typically have the classic signs and symptoms of the condition, while females tend to be less severely affected. Females with X-linked sideroblastic anemia usually develop features of the condition in mid to late adulthood, while affected males often first experience symptoms in adolescence to early adulthood. x X-linked ALAS2 https://medlineplus.gov/genetics/gene/alas2 ANH1 X-linked pyridoxine-responsive sideroblastic anemia XLSA GTR C4551511 ICD-10-CM D64.0 MeSH D000756 OMIM 300751 SNOMED CT 62677000 2025-09 2025-09-19 X-linked sideroblastic anemia and ataxia https://medlineplus.gov/genetics/condition/x-linked-sideroblastic-anemia-and-ataxia descriptionX-linked sideroblastic anemia and ataxia is a rare condition that is characterized by a blood disorder called sideroblastic anemia and movement problems known as ataxia. This condition primarily occurs in males.Anemia is defined by a shortage of healthy red blood cells. Sideroblastic anemia occurs when developing red blood cells called erythroblasts do not make enough hemoglobin, which is the protein that carries oxygen in the blood. People with X-linked sideroblastic anemia and ataxia have red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. The anemia seen in people with this condition is typically mild.X-linked sideroblastic anemia and ataxia leads to an abnormal accumulation of iron in red blood cells. The iron-loaded red blood cells, which are present in bone marrow, are called ring sideroblasts.X-linked sideroblastic anemia and ataxia causes problems with balance and coordination that appear early in life. Ataxia can make it difficult to sit, stand, and walk unassisted. People with this condition may find it difficult to make rapid, alternating movements (dysdiadochokinesia), such as tapping their foot. In addition to ataxia, people with this condition often have trouble coordinating movements that involve judging distance or scale (dysmetria), such as reaching out to grab an object. Affected individuals can also experience involuntary rhythmic shaking that worsens during movement (intention tremor). Mild speech difficulties (dysarthria) and abnormal eye movements have also been reported in some individuals with X-linked sideroblastic anemia and ataxia. x X-linked ABCB7 https://medlineplus.gov/genetics/gene/abcb7 SCAX6 X-linked sideroblastic anaemia with ataxia X-linked spinocerebellar ataxia-6 with or without sideroblastic anemia XLSA/A GTR C1845028 ICD-10-CM D64.0 MeSH D000756 OMIM 301310 SNOMED CT 62677000 2025-11 2025-11-18 X-linked spondyloepiphyseal dysplasia tarda https://medlineplus.gov/genetics/condition/x-linked-spondyloepiphyseal-dysplasia-tarda descriptionX-linked spondyloepiphyseal dysplasia tarda is a condition that impairs bone growth and occurs almost exclusively in males. The name of the condition indicates that it affects the bones of the spine (spondylo-) and the ends of long bones (epiphyses) in the arms and legs. "Tarda" indicates that signs and symptoms of this condition are not present at birth, but appear later in childhood, typically between ages 6 and 10.Males with X-linked spondyloepiphyseal dysplasia tarda have skeletal abnormalities and short stature. Affected boys grow steadily until late childhood, when their growth slows. Their adult height ranges from 4 feet 6 inches (137 cm) to 5 feet 4 inches (163 cm). Impaired growth of the spinal bones (vertebrae) primarily causes the short stature. Spinal abnormalities include flattened vertebrae (platyspondyly) with hump-shaped bulges, progressive thinning of the discs between vertebrae, and an abnormal curvature of the spine (scoliosis or kyphosis). These spinal problems also cause back pain in people with this condition. Individuals with X-linked spondyloepiphyseal dysplasia tarda have a short torso and neck, and their arms are disproportionately long compared to their height.Other skeletal features of X-linked spondyloepiphyseal dysplasia tarda include an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara); multiple abnormalities of the epiphyses, including a short upper end of the thigh bone (femoral neck); and a broad, barrel-shaped chest. A painful joint condition called osteoarthritis that typically occurs in older adults often develops in early adulthood in people with X-linked spondyloepiphyseal dysplasia tarda and worsens over time, most often affecting the hips, knees, and shoulders. xr X-linked recessive TRAPPC2 https://medlineplus.gov/genetics/gene/trappc2 Late onset spondyloepiphyseal dysplasia SED tarda X-linked SED X-linked SEDT GTR C3541456 ICD-10-CM Q77.7 MeSH D010009 OMIM 313400 SNOMED CT 51952004 2018-01 2023-03-01 X-linked thrombocytopenia https://medlineplus.gov/genetics/condition/x-linked-thrombocytopenia descriptionX-linked thrombocytopenia is a bleeding disorder that primarily affects males. This condition is characterized by a blood cell abnormality called thrombocytopenia, which is a shortage in the number of blood cells involved in clotting (platelets). Affected individuals often have abnormally small platelets as well, a condition called microthrombocytopenia. X-linked thrombocytopenia can cause individuals to bruise easily or have episodes of prolonged bleeding following minor trauma or even in the absence of injury (spontaneous bleeding). Some people with this condition experience spontaneous bleeding in the brain (cerebral hemorrhage), which can cause brain damage that can be life-threatening.Some people with X-linked thrombocytopenia also have patches of red, irritated skin (eczema) or an increased susceptibility to infections. In severe cases, additional features can develop, such as cancer or autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. It is unclear, however, if people with these features have X-linked thrombocytopenia or a more severe disorder with similar signs and symptoms called Wiskott-Aldrich syndrome.Some people have a mild form of the disorder called intermittent thrombocytopenia. These individuals have normal platelet production at times with episodes of thrombocytopenia. xr X-linked recessive WAS https://medlineplus.gov/genetics/gene/was Thrombocytopenia 1 XLT GTR C1839163 ICD-10-CM D69.42 MeSH D013921 OMIM 313900 SNOMED CT 37492005 2013-02 2020-08-18 Xeroderma pigmentosum https://medlineplus.gov/genetics/condition/xeroderma-pigmentosum descriptionXeroderma pigmentosum, commonly known as XP, is an inherited condition characterized by an extreme sensitivity to ultraviolet radiation (UVR), which is present in sunlight and may also be found in some types of artificial lighting. This condition mostly affects the eyes and areas of skin exposed to the sun. Xeroderma pigmentosum is associated with an increased risk of UVR-induced cancers. People with this condition often experience premature aging. Some affected individuals also have problems involving the nervous system.The signs of xeroderma pigmentosum usually appear in infancy or early childhood. About half of affected children develop a severe sunburn after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. However, some children with xeroderma pigmentosum can tan normally. By age 2, almost all children with xeroderma pigmentosum develop freckling of the skin in sun-exposed areas (such as the face, arms, and lips); this type of freckling rarely occurs in young children without the disorder. In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name.People with xeroderma pigmentosum are 10,000 times more likely to develop non-melanoma skin cancer and up to 2,000 times more likely to  develop melanoma skin cancer compared to individuals without this condition. The types of skin cancer that can develop include basal cell carcinoma, squamous cell carcinoma, and melanoma. Most commonly, the first skin cancer appears in affected individuals before age 10. Without protection from the sun and other sources of UVR, most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on  portions of the body that are exposed to the sun, including the face, the lips, the eyelids, the surface of the eyes, the scalp, and the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of some internal cancers, including brain tumors, thyroid cancer, and blood cancers. Additionally, affected individuals who smoke cigarettes have a significantly increased risk of lung cancer.The eyes of people with xeroderma pigmentosum may be painfully sensitive to UVR (photophobia). If the eyes are not protected from UVR, they may become bloodshot and irritated, and the clear front covering of the eyes (the cornea) may become cloudy. In some people, the eyelashes fall out and the eyelids may be thin and turn abnormally inward or outward. In addition to an increased risk of cancer on the surface of the eye, xeroderma pigmentosum is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.About 30 percent of people with xeroderma pigmentosum develop progressive neurological abnormalities in addition to problems involving the skin and eyes. These abnormalities can include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. When these neurological problems occur, they tend to worsen with time.Individuals with xeroderma pigmentosum may experience early menopause.Researchers have identified at least eight genetic forms of xeroderma pigmentosum: complementation group A (XP-A) through complementation group G (XP-G), plus a variant type (XP-V). The types are distinguished by their genetic cause. All of the types increase the risk of skin cancer, although some are more likely than others to be associated with neurological abnormalities. ar Autosomal recessive XPA https://medlineplus.gov/genetics/gene/xpa XPC https://medlineplus.gov/genetics/gene/xpc ERCC2 https://medlineplus.gov/genetics/gene/ercc2 ERCC3 https://medlineplus.gov/genetics/gene/ercc3 POLH https://medlineplus.gov/genetics/gene/polh DDB2 https://www.ncbi.nlm.nih.gov/gene/1643 ERCC1 https://www.ncbi.nlm.nih.gov/gene/2067 ERCC4 https://www.ncbi.nlm.nih.gov/gene/2072 ERCC5 https://www.ncbi.nlm.nih.gov/gene/2073 DeSanctis-Cacchione syndrome XP GTR C0043346 GTR C0268135 GTR C0268136 GTR C0268138 GTR C0268140 GTR C0268141 GTR C1848410 GTR C1848411 GTR C2752147 GTR CN381176 ICD-10-CM Q82.1 MeSH D014983 OMIM 278700 OMIM 278720 OMIM 278730 OMIM 278740 OMIM 278750 OMIM 278760 OMIM 278780 OMIM 610651 SNOMED CT 1073003 SNOMED CT 25784009 SNOMED CT 36454001 SNOMED CT 414673004 SNOMED CT 42530008 SNOMED CT 44600005 SNOMED CT 68637004 2023-06 2023-06-27 Xia-Gibbs syndrome https://medlineplus.gov/genetics/condition/xia-gibbs-syndrome descriptionXia-Gibbs syndrome is a neurological disorder characterized by weak muscle tone (hypotonia), mild to severe intellectual disability and delayed development. Expressive language skills (vocabulary and the production of speech) are particularly affected; children with this condition usually do not speak their first word, a milestone typically achieved within the first year, until age two or later, and some never learn to talk. Development of motor skills, such as crawling and walking, can also be delayed.Other signs and symptoms of Xia-Gibbs syndrome vary among affected individuals. Additional neurological features include poor coordination and balance (ataxia) and seizures. Feeding problems and sleep abnormalities can also occur in people with the condition, and many affected individuals experience short pauses in breathing while they sleep (obstructive sleep apnea). In some people with Xia-Gibbs syndrome, imaging tests of the brain show abnormalities in the brain's structure. For example, the tissue connecting the left and right halves of the brain (the corpus callosum) can be abnormally thin.Xia-Gibbs syndrome can also affect physical development. Growth is usually impaired, and many affected individuals are shorter than their peers. Side-to-side curvature of the spine (scoliosis) is also a common feature. Some people with Xia-Gibbs syndrome have unusual facial features, such as a broad forehead, low-set ears or ears that stick out, widely spaced eyes (hypertelorism), eye openings that slant up or down (upslanting palpebral fissures or downslanting palpebral fissures), a flat bridge of the nose, or a thin upper lip. Other, less-common abnormalities involving the bones and skin include premature fusion of certain skull bones (craniosynostosis), unusually loose (lax) joints, and loose skin.Neurodevelopmental disorders can also occur in Xia-Gibbs syndrome. Some affected individuals have autism spectrum disorder, which is characterized by impaired communication and social interactions, or attention-deficit/hyperactivity disorder (ADHD). Other problems can include aggression, anxiety, poor impulse control, and self-injury. ad Autosomal dominant AHDC1 https://medlineplus.gov/genetics/gene/ahdc1 AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome Autosomal dominant intellectual disability 25 XGS GTR C4014419 MeSH D008607 OMIM 615829 2019-02 2023-07-13 Y chromosome infertility https://medlineplus.gov/genetics/condition/y-chromosome-infertility descriptionY chromosome infertility is a condition that affects the production of sperm and causes male infertility, which means it is difficult or impossible for affected men to father children. An affected man's body may produce no mature sperm cells (azoospermia), fewer than the usual number of sperm cells (oligospermia), or sperm cells that are abnormally shaped or that do not move properly. Men with Y chromosome infertility do not have any other signs or symptoms related to the condition.Some men with Y chromosome infertility who have mild to moderate oligospermia may eventually father a child naturally. Men with oligospermia may also be helped with assisted reproductive technologies; most men with Y chromosome infertility have some sperm cells in the testes that can be extracted for this purpose. y Y-linked n Not inherited Y https://medlineplus.gov/genetics/chromosome/y DAZ1 https://www.ncbi.nlm.nih.gov/gene/1617 RBMY1A1 https://www.ncbi.nlm.nih.gov/gene/5940 TSPY1 https://www.ncbi.nlm.nih.gov/gene/7258 KDM5D https://www.ncbi.nlm.nih.gov/gene/8284 USP9Y https://www.ncbi.nlm.nih.gov/gene/8287 DDX3Y https://www.ncbi.nlm.nih.gov/gene/8653 PRY https://www.ncbi.nlm.nih.gov/gene/9081 VCY https://www.ncbi.nlm.nih.gov/gene/9084 CDY1 https://www.ncbi.nlm.nih.gov/gene/9085 DAZ3 https://www.ncbi.nlm.nih.gov/gene/57054 DAZ2 https://www.ncbi.nlm.nih.gov/gene/57055 DAZ4 https://www.ncbi.nlm.nih.gov/gene/57135 HSFY1 https://www.ncbi.nlm.nih.gov/gene/86614 RPS4Y2 https://www.ncbi.nlm.nih.gov/gene/140032 HSFY2 https://www.ncbi.nlm.nih.gov/gene/159119 Spermatogenic failure, Y-linked Y chromosome-related azoospermia GTR C1839071 GTR C4551960 MeSH D007248 OMIM 400042 OMIM 415000 SNOMED CT 236791009 2018-12 2024-09-19 Yao syndrome https://medlineplus.gov/genetics/condition/yao-syndrome descriptionYao syndrome (formerly called NOD2-associated autoinflammatory disease) is a disorder involving episodes of fever and abnormal inflammation affecting many parts of the body, particularly the skin, joints, and gastrointestinal system. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). In people with Yao syndrome, part of the immune system called the innate immune response is turned on (activated) abnormally, which causes fevers and inflammation-related damage to tissues and organs. Based on this process, Yao syndrome is classified as an autoinflammatory disease. Autoinflammatory diseases are distinct from autoimmune diseases; these two groups of diseases involve abnormalities in different parts of the immune system.The episodes of fever and inflammation associated with Yao syndrome can last for several days and occur weeks to months apart. During these episodes, most affected individuals develop reddened, inflamed areas on the skin called erythematous patches or plaques. This reddening occurs most commonly on the face, chest, and back but can also affect the arms and legs. Episodes of joint pain and inflammation similar to arthritis are common, particularly in the legs, as is swelling of the ankles and feet. Inflammation also affects the gastrointestinal system, causing attacks of abdominal pain, bloating, and cramping with diarrhea in more than half of affected individuals. Dry eyes and dry mouth (described as "sicca-like" symptoms, which refers to dryness) are reported in about half of people with this disease. Other potential signs and symptoms of Yao syndrome include mouth sores, chest pain, and enlargement of various glands.Yao syndrome is usually diagnosed in adulthood. It is a long-lasting (chronic) disease, and episodes can recur for many years. u Pattern unknown NOD2 https://medlineplus.gov/genetics/gene/nod2 NAID NOD2-associated AID NOD2-associated autoinflammatory disease YAOS GTR C4310620 MeSH D056660 OMIM 617321 2017-12 2026-03-04 Yuan-Harel-Lupski syndrome https://medlineplus.gov/genetics/condition/yuan-harel-lupski-syndrome descriptionYuan-Harel-Lupski (YUHAL) syndrome is a rare neurological condition that has a combination of features of two other disorders, Potocki-Lupski syndrome and type 1A Charcot-Marie-Tooth disease.The first signs and symptoms of YUHAL syndrome begin in infancy. Infants with YUHAL syndrome usually have weak muscle tone (hypotonia), which may lead to feeding problems. They typically do not grow and gain weight at the expected rate. Babies and children with YUHAL syndrome have delayed development, including delayed speech and language skills and motor skills such as walking. YUHAL syndrome is also associated with behavioral difficulties. Many affected individuals have sleep problems, including pauses in breathing during sleep (sleep apnea) or trouble falling asleep and staying asleep. Some people with YUHAL syndrome have subtle differences in facial features, including outside corners of the eyes that point downward (down-slanting palpebral fissures), a triangular face, and eyes that do not look in the same direction (strabismus). These signs and symptoms are similar to those of Potocki-Lupski syndrome.Other signs and symptoms of YUHAL syndrome begin in childhood and result from damage to peripheral nerves, which connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat. Damage to peripheral nerves can lead to loss of sensation and wasting (atrophy) of muscles in the legs. Children with YUHAL syndrome often develop muscle weakness, particularly in the lower legs, which may lead to an unusual walking style (gait). Some affected individuals have foot abnormalities such as flat feet (pes planus), high arches (pes cavus), or an inward- and upward-turning foot (clubfoot). They may also experience reduced reflexes and a decreased sensitivity to touch, heat, and cold in the feet and lower legs. Similar features are seen in individuals with type 1A Charcot-Marie-Tooth disease, although they may appear earlier in people with YUHAL syndrome, often before age 5.Abnormal development of other tissues and organs, such as the heart or kidneys, can occur in YUHAL syndrome. ad Autosomal dominant PMP22 https://medlineplus.gov/genetics/gene/pmp22 RAI1 https://medlineplus.gov/genetics/gene/rai1 17 https://medlineplus.gov/genetics/chromosome/17 PMP22-RAI1 contiguous gene duplication syndrome YUHAL syndrome MeSH D002658 MeSH D015417 MeSH D058674 OMIM 616652 2018-09 2023-03-01 ZAP70-related severe combined immunodeficiency https://medlineplus.gov/genetics/condition/zap70-related-severe-combined-immunodeficiency descriptionZAP70-related severe combined immunodeficiency (SCID) is an inherited disorder that damages the immune system. ZAP70-related SCID is one of several forms of severe combined immunodeficiency, a group of disorders with several genetic causes. Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people. Infants with SCID typically experience pneumonia, chronic diarrhea, and widespread skin rashes. They also grow much more slowly than healthy children. If not treated in a way that restores immune function, children with SCID usually live only a year or two.Most individuals with ZAP70-related SCID are diagnosed in the first 6 months of life. At least one individual first showed signs of the condition later in childhood and had less severe symptoms, primarily recurrent respiratory and skin infections. ar Autosomal recessive ZAP70 https://medlineplus.gov/genetics/gene/zap70 Selective T-cell defect ZAP70-related SCID Zeta-associated protein 70 deficiency GTR C2931299 MeSH D016511 OMIM 176947 SNOMED CT 190993005 2009-11 2025-05-29 Zellweger spectrum disorder https://medlineplus.gov/genetics/condition/zellweger-spectrum-disorder descriptionZellweger spectrum disorder is a condition that affects many parts of the body. Cases of Zellweger spectrum disorder are often categorizes as severe, intermediate, or mild.Individuals with severe Zellweger spectrum disorder usually have signs and symptoms at birth, which worsen over time. These infants experience weak muscle tone (hypotonia), feeding problems, hearing and vision loss, and seizures. These problems are caused by reduced myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. The part of the brain and spinal cord that contains myelin is called white matter. Reduced myelin (demyelination) leads to loss of white matter (leukodystrophy). Children with severe Zellweger spectrum disorder also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys, and their liver or spleen may be enlarged. They may have skeletal abnormalities, including a large space between the bones of the skull (fontanelles) and characteristic bone spots known as chondrodysplasia punctata that can be seen on x-ray. Affected individuals can have eye abnormalities, including clouding of the lenses of the eyes (cataracts) or involuntary, side-to-side movements of the eyes (nystagmus). Severe Zellweger spectrum disorder involves distinctive facial features, including a flattened face, broad nasal bridge, high forehead, and widely spaced eyes (hypertelorism). Children with severe Zellweger spectrum disorder typically do not survive beyond the first year of life.People with intermediate or mild Zellweger spectrum disorder have more variable features that progress more slowly than those with the severe form. Affected children usually do not develop signs and symptoms of the disease until late infancy or early childhood. Children with these intermediate and mild forms often have hypotonia, vision problems, hearing loss, liver dysfunction, developmental delay, and some degree of intellectual disability. Most people with the intermediate form survive into childhood, and those with the mild form may reach adulthood. In rare cases, individuals at the mildest end of the condition spectrum have developmental delay in childhood and hearing loss or vision problems beginning in adulthood and do not develop the other features of this disorder.The severe, intermediate, and mild forms of Zellweger spectrum disorder were once thought to be distinct disorders. The severe form was known as Zellweger syndrome, the intermediate form was neonatal adrenoleukodystrophy (NALD), and the mild form was infantile Refsum disease. These conditions were renamed as a single condition when they were found to be part of the same condition spectrum.  ar Autosomal recessive PEX1 https://medlineplus.gov/genetics/gene/pex1 PEX6 https://www.ncbi.nlm.nih.gov/gene/5190 PEX10 https://www.ncbi.nlm.nih.gov/gene/5192 PEX12 https://www.ncbi.nlm.nih.gov/gene/5193 PEX13 https://www.ncbi.nlm.nih.gov/gene/5194 PEX14 https://www.ncbi.nlm.nih.gov/gene/5195 PEX19 https://www.ncbi.nlm.nih.gov/gene/5824 PEX2 https://www.ncbi.nlm.nih.gov/gene/5828 PEX5 https://www.ncbi.nlm.nih.gov/gene/5830 PEX3 https://www.ncbi.nlm.nih.gov/gene/8504 PEX11B https://www.ncbi.nlm.nih.gov/gene/8799 PEX16 https://www.ncbi.nlm.nih.gov/gene/9409 PEX26 https://www.ncbi.nlm.nih.gov/gene/55670 Cerebrohepatorenal syndrome PBD, ZSS PBD-ZSD Peroxisome biogenesis disorders, Zellweger syndrome spectrum Zellweger spectrum Zellweger syndrome spectrum ZSD GTR C0282527 GTR C1832200 GTR C3550234 GTR C4721541 ICD-10-CM E71.510 ICD-10-CM E71.511 ICD-10-CM G60.1 MeSH D015211 OMIM 202370 OMIM 214100 OMIM 214110 OMIM 266510 OMIM 601539 OMIM 614859 OMIM 614862 OMIM 614866 OMIM 614870 OMIM 614872 OMIM 614876 OMIM 614882 OMIM 614883 OMIM 614886 OMIM 614887 OMIM 614920 SNOMED CT 238061001 SNOMED CT 238062008 SNOMED CT 88469006 2015-06 2026-02-12 AAAS aladin WD repeat nucleoporin https://medlineplus.gov/genetics/gene/aaas functionThe AAAS gene provides instructions for making a protein called ALADIN. ALADIN belongs to a family of proteins called nucleoporins that help transport molecules between the nucleus and the fluid surrounding the nucleus (cytoplasm).ALADIN is abundant in the adrenal glands, the brain, and the digestive system. Within cells, ALADIN is found in the nuclear envelope, the structure that surrounds the nucleus and separates it from the rest of the cell. ALADIN acts as a gatekeeper that controls which molecules can enter or exit the nucleus, helping to ensure that the proteins that cells need to function reach the proper locations within the nucleus at the appropriate times. ALADIN is also believed to help protect cells in the adrenal glands from the damage caused by unstable oxygen-containing molecules. Triple A syndrome https://medlineplus.gov/genetics/condition/triple-a-syndrome AAA AAASb achalasia, adrenocortical insufficiency, alacrimia achalasia, adrenocortical insufficiency, alacrimia (Allgrove, triple-A) ADRACALA ADRACALIN ALADIN GL003 NCBI Gene 8086 OMIM 605378 2025-08 2025-08-25 AASS aminoadipate-semialdehyde synthase https://medlineplus.gov/genetics/gene/aass functionThe AASS gene provides instructions for making an enzyme called alpha-aminoadipic semialdehyde synthase. This enzyme is found in many tissues, including the liver.  Alpha-aminoadipic semialdehyde synthase is involved in the breakdown of lysine, which is a building block (amino acid) of many different proteins. Amino acids are broken down when they are no longer needed. Alpha-aminoadipic semialdehyde synthase is called a bifunctional enzyme because it performs two functions during the breakdown of lysine. First, it converts lysine to a molecule called saccharopine, and then it converts saccharopine to a molecule called alpha-aminoadipic semialdehyde. Hyperlysinemia https://medlineplus.gov/genetics/condition/hyperlysinemia alpha-aminoadipate semialdehyde synthase LKR/SDH LKRSDH LORSDH lysine-ketoglutarate reductase /saccharopine dehydrogenase saccharopine dehydrogenase (NAD(+), L-glutamate-forming) saccharopine dehydrogenase (NADP(+), L-lysine-forming) NCBI Gene 10157 OMIM 605113 2025-06 2025-06-11 ABAT 4-aminobutyrate aminotransferase https://medlineplus.gov/genetics/gene/abat functionThe ABAT gene provides instructions for making the GABA-transaminase enzyme. This enzyme helps break down a brain chemical (neurotransmitter) called GABA when it is not needed. GABA normally helps slow down (inhibit) brain cell activity when necessary, to prevent the brain from being overloaded with too many signals. For this reason GABA is called an inhibitory neurotransmitter. GABA-transaminase deficiency https://medlineplus.gov/genetics/condition/gaba-transaminase-deficiency (S)-3-amino-2-methylpropionate transaminase 4-aminobutyrate aminotransferase, mitochondrial precursor 4-aminobutyrate transaminase GABA aminotransferase GABA transaminase GABA transferase GABA-AT GABAT gamma-amino-N-butyrate transaminase NPD009 NCBI Gene 18 OMIM 137150 2018-04 2020-08-18 ABCA1 ATP binding cassette subfamily A member 1 https://medlineplus.gov/genetics/gene/abca1 functionThe ABCA1 gene belongs to a group of genes called the ATP-binding cassette family. These genes provide instructions for making proteins that transport molecules across cell membranes. The ABCA1 protein is produced in many tissues, but high levels of this protein are found in the liver and in immune cells called macrophages. The ABCA1 protein helps move cholesterol and certain fats called phospholipids across the cell membrane to the outside of the cell. These substances are then picked up by a protein called apolipoprotein A-I (apoA-I), which is produced from the APOA1 gene. ApoA-I, cholesterol, and phospholipids combine to make high-density lipoprotein (HDL), often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. HDL carries cholesterol and phospholipids through the bloodstream from the body's tissues to the liver. Once in the liver, cholesterol and phospholipids are redistributed to other tissues or removed from the body. The process of removing excess cholesterol from cells is extremely important for balancing cholesterol levels and maintaining cardiovascular health. Tangier disease https://medlineplus.gov/genetics/condition/tangier-disease Familial HDL deficiency https://medlineplus.gov/genetics/condition/familial-hdl-deficiency ABC1 ABCA1_HUMAN ATP binding cassette transporter 1 ATP-binding cassette 1 ATP-binding cassette, sub-family A (ABC1), member 1 CERP cholesterol efflux regulatory protein FLJ14958 HDLDT1 high density lipoprotein deficiency, Tangier type, 1 TGD NCBI Gene 19 OMIM 600046 2023-10 2023-10-30 ABCA12 ATP binding cassette subfamily A member 12 https://medlineplus.gov/genetics/gene/abca12 functionThe ABCA12 gene provides instructions for making a protein known as an ATP-binding cassette (ABC) transporter.  ABC transporter proteins carry many types of molecules across cell membranes.  In particular, the ABCA12 protein plays a major role in transporting fats (lipids) and enzymes in cells that make up the outermost layer of skin (the epidermis). This transport of molecules is needed to maintain the layers of lipids within the epidermis that are necessary to prevent water loss (dehydration) and for normal development of the skin.  Harlequin ichthyosis https://medlineplus.gov/genetics/condition/harlequin-ichthyosis Lamellar ichthyosis https://medlineplus.gov/genetics/condition/lamellar-ichthyosis Nonbullous congenital ichthyosiform erythroderma https://medlineplus.gov/genetics/condition/nonbullous-congenital-ichthyosiform-erythroderma ABCAC_HUMAN ATP-binding cassette 12 ATP-binding cassette transporter 12 ATP-binding cassette, sub-family A (ABC1), member 12 ATP-binding cassette, sub-family A, member 12 ICR2B NCBI Gene 26154 OMIM 607800 2017-07 2023-03-03 ABCA3 ATP binding cassette subfamily A member 3 https://medlineplus.gov/genetics/gene/abca3 functionThe ABCA3 gene provides instructions for making a protein involved in surfactant production. Surfactant is a mixture of certain fats (called phospholipids) and proteins that lines the lung tissue and makes breathing easy. Without normal surfactant, the tissue surrounding the air sacs in the lungs (the alveoli) sticks together after exhalation (because of a force called surface tension), causing the alveoli to collapse. As a result, filling the lungs with air on each breath becomes very difficult, and delivery of oxygen to the body is impaired.The ABCA3 protein is found in the membrane that surrounds lamellar bodies, which are the cellular structures in which the phospholipids and proteins that make up surfactant are packaged. The ABCA3 protein transports phospholipids into the lamellar bodies where they interact with surfactant proteins to form surfactant. The ABCA3 protein also appears to be involved in the formation of normal lamellar bodies. In addition to packaging, lamellar bodies are important for the correct processing of surfactant proteins, which is necessary for the proteins to mature and become functional. Idiopathic pulmonary fibrosis https://medlineplus.gov/genetics/condition/idiopathic-pulmonary-fibrosis Surfactant dysfunction https://medlineplus.gov/genetics/condition/surfactant-dysfunction ABC transporter 3 ABC-C ABC-C transporter ABC3 ABCA3_HUMAN ATP-binding cassette sub-family A member 3 ATP-binding cassette transporter 3 ATP-binding cassette, sub-family A (ABC1), member 3 SMDP3 NCBI Gene 21 OMIM 601615 2012-07 2020-08-18 ABCA4 ATP binding cassette subfamily A member 4 https://medlineplus.gov/genetics/gene/abca4 functionThe ABCA4 gene provides instructions for making a protein that is found in the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, the ABCA4 protein is produced in the retina's light-sensing cells (photoreceptors). The ABCA4 protein transports potentially toxic substances that can damage photoreceptors. These substances form after phototransduction, the process by which light entering the eye is converted into electrical signals that are transmitted to the brain. The ABCA4 protein removes one of these substances, called N-retinylidene-PE, from photoreceptors. Retinitis pigmentosa https://medlineplus.gov/genetics/condition/retinitis-pigmentosa Stargardt macular degeneration https://medlineplus.gov/genetics/condition/stargardt-macular-degeneration Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration Cone-rod dystrophy https://medlineplus.gov/genetics/condition/cone-rod-dystrophy ABCA4_HUMAN ABCR ATP-binding cassette sub-family A member 4 ATP-binding cassette transporter, retinal-specific ATP-binding cassette, sub-family A (ABC1), member 4 photoreceptor rim protein retina-specific ABC transporter retinal-specific ATP-binding cassette transporter RIM ABC transporter RIM protein RMP NCBI Gene 24 OMIM 601691 2023-10 2023-10-27 ABCB11 ATP binding cassette subfamily B member 11 https://medlineplus.gov/genetics/gene/abcb11 functionThe ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP), which is found in the liver. Bile salts are a component of bile that help the body digest fats. Bile salts are produced by liver cells and then transported out of the cell by the BSEP to make bile. The release of bile salts from liver cells is critical for the normal secretion of bile. Progressive familial intrahepatic cholestasis https://medlineplus.gov/genetics/condition/progressive-familial-intrahepatic-cholestasis Benign recurrent intrahepatic cholestasis https://medlineplus.gov/genetics/condition/benign-recurrent-intrahepatic-cholestasis ABC16 ATP-binding cassette, sub-family B (MDR/TAP), member 11 bile salt export pump BRIC2 BSEP PFIC2 PGY4 progressive familial intrahepatic cholestasis 2 sister of p-glycoprotein SPGP ICD-10-CM MeSH NCBI Gene 8647 OMIM 603201 SNOMED CT 2024-05 2024-04-25 ABCB4 ATP binding cassette subfamily B member 4 https://medlineplus.gov/genetics/gene/abcb4 functionThe ABCB4 gene (also known as MDR3) provides instructions for making a protein that helps move certain fats called phospholipids across the membranes of liver cells. The protein essentially flips the phospholipids from the inside to the outside of the cells. The protein then releases the phospholipids into a digestive fluid called bile. Outside the liver cells, in the bile duct, phospholipids attach (bind) to bile acids, which are the component of bile that digests fats. Large amounts of bile acids are potentially harmful to cells. When bile acids are bound to phospholipids, they are less toxic. Progressive familial intrahepatic cholestasis https://medlineplus.gov/genetics/condition/progressive-familial-intrahepatic-cholestasis Intrahepatic cholestasis of pregnancy https://medlineplus.gov/genetics/condition/intrahepatic-cholestasis-of-pregnancy ABC21 ATP-binding cassette, sub-family B (MDR/TAP), member 4 ATP-binding cassette, subfamily B, member 4 GBD1 ICP3 MDR3 multidrug resistance 3 P-glycoprotein 3 PFIC-3 PGY3 ICD-10-CM MeSH NCBI Gene 5244 OMIM 171060 OMIM 600803 SNOMED CT 2024-05 2025-01-31 ABCB7 ATP binding cassette subfamily B member 7 https://medlineplus.gov/genetics/gene/abcb7 functionThe ABCB7 gene provides instructions for making a protein known as an ATP-binding cassette (ABC) transporter. ABC transporter proteins carry many types of molecules across cell membranes.The ABCB7 protein is located in the inner membrane of cell structures called mitochondria. Mitochondria are the energy-producing centers of cells, but they are also involved in a variety of cellular activities, including chemical signaling and the regulation of cell growth and division. In the mitochondria of developing red blood cells (erythroblasts), the ABCB7 protein plays a critical role in the production of heme. Heme contains iron and is required for cell processes such as energy production and molecule transport. Most importantly, heme is a component of hemoglobin, the protein that carries oxygen in the blood.The ABCB7 protein is also involved in the formation of clusters of iron and sulfur atoms (Fe-S clusters). The ABCB7 protein transports a sulfur-containing compound from mitochondria to the surrounding cellular fluid (cytosol), where Fe-S clusters are formed. These clusters are then incorporated into proteins. Proteins that contain Fe-S clusters are necessary for many functions, including the maintenance of cells and genes. The ABCB7 protein appears to play a key role in maintaining an appropriate balance of iron (iron homeostasis) in erythroblasts. X-linked sideroblastic anemia and ataxia https://medlineplus.gov/genetics/condition/x-linked-sideroblastic-anemia-and-ataxia ABCB7_HUMAN ATP-binding cassette 7 NCBI Gene 22 OMIM 300135 2025-11 2025-11-18 ABCC2 ATP binding cassette subfamily C member 2 https://medlineplus.gov/genetics/gene/abcc2 functionThe ABCC2 gene provides instructions for producing a protein called multidrug resistance protein 2 (MRP2). This protein is one of a family of multidrug resistance proteins involved in the transport of substances out of cells. For example, MRP2 clears certain drugs from organs and tissues, playing a part in drug metabolism. Drug metabolism involves the breakdown of drugs into different chemical components allowing the drugs to have their intended effects and eventually be eliminated from the body. MRP2 also transports a substance called bilirubin out of liver cells and into bile (a digestive fluid produced by the liver). Bilirubin is produced during the breakdown of old red blood cells and has an orange-yellow tint.MRP2 is primarily found within the outer membrane that surrounds cells in the liver, with smaller amounts in the kidneys, intestine, and placenta. Dubin-Johnson syndrome https://medlineplus.gov/genetics/condition/dubin-johnson-syndrome ATP-binding cassette, sub-family C (CFTR/MRP), member 2 canalicular multispecific organic anion transporter CMOAT cMRP MRP2 MRP2_HUMAN NCBI Gene 1244 OMIM 601107 2009-03 2020-08-18 ABCC6 ATP binding cassette subfamily C member 6 https://medlineplus.gov/genetics/gene/abcc6 functionThe ABCC6 gene provides instructions for making a protein called multidrug resistance-associated protein 6 (MRP6, also known as the ABCC6 protein). This protein is found primarily in the liver and kidneys, with small amounts in other tissues such as the skin, stomach, blood vessels, and eyes. The MRP6 protein belongs to a group of proteins that transport molecules across cell membranes; however, little is known about the substances transported by MRP6.Some studies suggest that MRP6 stimulates the release of a molecule called adenosine triphosphate (ATP) from cells through an unknown mechanism. This ATP is quickly broken down into other molecules called adenosine monophosphate (AMP) and pyrophosphate. Pyrophosphate helps control deposition of calcium (calcification) and other minerals (mineralization) in the body.Other studies suggest that MRP6 transports a substance that is involved in the breakdown of ATP. This unidentified substance is thought to help prevent mineralization of tissues. Pseudoxanthoma elasticum https://medlineplus.gov/genetics/condition/pseudoxanthoma-elasticum Generalized arterial calcification of infancy https://medlineplus.gov/genetics/condition/generalized-arterial-calcification-of-infancy ABC34 anthracycline resistance-associated protein ARA ATP-binding cassette, sub-family C (CFTR/MRP), member 6 EST349056 MLP1 MOAT-E MRP6 MRP6_HUMAN multidrug resistance-associated protein 6 multispecific organic anion transporter-E NCBI Gene 368 OMIM 603234 2015-01 2023-03-03 ABCC8 ATP binding cassette subfamily C member 8 https://medlineplus.gov/genetics/gene/abcc8 functionThe ABCC8 gene provides instructions for making one part (subunit) of the ATP-sensitive potassium (KATP) channels that are found in specialized pancreas cells called beta cells. These KATP channels consist of eight subunits: four of these subunits are produced from the ABCC8 gene and four are produced from another gene called KCNJ11.These KATP channels span the cell membranes of the beta cells. Beta cells secrete the hormone insulin, which helps control the levels of glucose in the blood, also called blood sugar. Glucose is a simple sugar and the primary energy source for most cells in the body. When blood glucose levels are high, the KATP channels close, which triggers the beta cells to release insulin into the bloodstream. In this way, KATP channels help regulate insulin secretion and control blood glucose levels. Congenital hyperinsulinism https://medlineplus.gov/genetics/condition/congenital-hyperinsulinism Permanent neonatal diabetes mellitus https://medlineplus.gov/genetics/condition/permanent-neonatal-diabetes-mellitus Maturity-onset diabetes of the young https://medlineplus.gov/genetics/condition/maturity-onset-diabetes-of-the-young ABC36 ATP-binding cassette, sub-family C (CFTR/MRP), member 8 ATP-binding cassette, sub-family C, member 8 MRP8 sulfonylurea receptor sulfonylurea receptor, beta cell high affinity SUR1 TNDM2 NCBI Gene 6833 OMIM 600509 2026-01 2026-01-16 ABCC9 ATP binding cassette subfamily C member 9 https://medlineplus.gov/genetics/gene/abcc9 functionThe ABCC9 gene provides instructions for making the sulfonylurea receptor 2 (SUR2) protein. This protein forms one part (subunit) of a channel that transports charged atoms of potassium (potassium ions) across cell membranes. Each of these channels consists of eight subunits: four SUR2 proteins and four proteins produced from either the KCNJ8 or KCNJ11 gene. The SUR2 subunits regulate the activity of the channel, determining whether it is open or closed.Channels made with the SUR2 protein are known as ATP-sensitive potassium (K-ATP) channels. The channels open and close in response to the amount of ATP, the cell's main energy source, inside the cell. The resulting transport of potassium ions is part of a complex network of signals that relay chemical messages into and out of cells.Although K-ATP channels are present in cells and tissues throughout the body, the highest levels of SUR2-containing channels are found in skeletal and heart (cardiac) muscle. These channels indirectly help regulate the concentration of calcium ions in cells. This regulation is essential for normal heart function. The function of these channels in other tissues is unclear. Familial atrial fibrillation https://medlineplus.gov/genetics/condition/familial-atrial-fibrillation Cantú syndrome https://medlineplus.gov/genetics/condition/cantu-syndrome ABC37 ABCC9_HUMAN ATFB12 ATP-binding cassette sub-family C member 9 ATP-binding cassette sub-family C member 9 isoform SUR2A ATP-binding cassette sub-family C member 9 isoform SUR2B ATP-binding cassette transporter sub-family C member 9 ATP-binding cassette, sub-family C (CFTR/MRP), member 9 CANTU CMD1O sulfonylurea receptor 2 SUR2 NCBI Gene 10060 OMIM 601439 OMIM 608569 2013-01 2025-11-19 ABCD1 ATP binding cassette subfamily D member 1 https://medlineplus.gov/genetics/gene/abcd1 functionThe ABCD1 gene provides instructions for producing the adrenoleukodystrophy protein (ALDP). ALDP is located in the membranes of cell structures called peroxisomes. Peroxisomes are small sacs within cells that process many types of molecules. ALDP brings a group of fats called very long-chain fatty acids (VLCFAs) into peroxisomes, where they are broken down. X-linked adrenoleukodystrophy https://medlineplus.gov/genetics/condition/x-linked-adrenoleukodystrophy ABCD1_HUMAN ALD ALDP AMN ATP-binding cassette, sub-family D (ALD), member 1 NCBI Gene 215 OMIM 300371 2013-07 2020-08-18 ABCD4 ATP binding cassette subfamily D member 4 https://medlineplus.gov/genetics/gene/abcd4 functionThe ABCD4 gene provides instructions for making a protein that is involved in the conversion of vitamin B12 (also known as cobalamin) into one of two molecules, adenosylcobalamin (AdoCbl) or methylcobalamin (MeCbl). AdoCbl is required for the normal function of an enzyme known as methylmalonyl CoA mutase. This enzyme helps break down certain protein building blocks (amino acids), fat building blocks (fatty acids), and cholesterol. AdoCbl is called a cofactor because it helps methylmalonyl CoA mutase carry out its function. MeCbl is also a cofactor, but for an enzyme known as methionine synthase. This enzyme converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.The ABCD4 protein is found in the membrane that surrounds cell structures called lysosomes. Lysosomes are compartments within cells in which enzymes digest and recycle materials. In the lysosomal membrane, the ABCD4 protein interacts with another protein called LMBD1 (produced from the LMBRD1 gene). Together, these two proteins transport vitamin B12 out of lysosomes, making it available for further processing into AdoCbl and MeCbl. Methylmalonic acidemia with homocystinuria https://medlineplus.gov/genetics/condition/methylmalonic-acidemia-with-homocystinuria 69 kDa peroxisomal ABC-transporter ABC41 ATP-binding cassette sub-family D member 4 ATP-binding cassette, sub-family D (ALD), member 4 EST352188 MAHCJ P70R P79R peroxisomal membrane protein 69 PMP69 PMP70-related protein PXMP1-L PXMP1L NCBI Gene 5826 OMIM 603214 2022-08 2022-08-02 ABCG2 ATP binding cassette subfamily G member 2 (JR blood group) https://medlineplus.gov/genetics/gene/abcg2 functionThe ABCG2 gene belongs to a group of genes called the ATP-binding cassette family; genes in this family provide instructions for making proteins that transport molecules across cell membranes. In the intestines, the ABCG2 protein helps release (secrete) a substance called urate into the urine. Urate is a byproduct of certain normal biochemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. Urate levels are regulated by the kidneys and, to a lesser extent, by the intestines.The ABCG2 protein also transports certain drugs out of cells. For example, this protein clears some chemotherapy drugs from organs and tissues. Transport of these drugs allows them to have their intended effects and be eliminated from the body. Gout https://medlineplus.gov/genetics/condition/gout ABC15 ABCP ATP-binding cassette transporter G2 ATP-binding cassette, sub-family G (WHITE), member 2 (Junior blood group) BCRP BCRP1 BMDP breast cancer resistance protein CD338 CDw338 EST157481 mitoxantrone resistance-associated protein MRX multi drug resistance efflux transport ATP-binding cassette sub-family G (WHITE) member 2 MXR MXR-1 MXR1 placenta specific MDR protein placenta-specific ATP-binding cassette transporter UAQTL1 NCBI Gene 9429 OMIM 603756 2018-08 2024-05-01 ABCG5 ATP binding cassette subfamily G member 5 https://medlineplus.gov/genetics/gene/abcg5 functionThe ABCG5 gene provides instructions for making sterolin-1, which makes up half of a protein called sterolin. The other half of the sterolin protein, sterolin-2, is produced from a gene called ABCG8. Sterolin is involved in eliminating plant sterols, which are fatty components of plant-based foods that cannot be used by human cells.Sterolin is a transporter protein, which is a type of protein that moves substances across cell membranes. It is found mostly in cells of the intestines and liver and transports plant sterols. After plant sterols are absorbed from food into intestinal cells, the sterolin transporters in these cells pump them back into the intestinal tract. Sterolin transporters in liver cells pump the plant sterols into a fluid called bile that is released into the intestine. From the intestine, the plant sterols are eliminated with the feces. This process removes most of the dietary plant sterols, and allows only about 5 percent of these substances to get into the bloodstream. Sterolin also helps regulate levels of cholesterol, another fatty substance found in animal products, in a similar fashion; normally about 50 percent of cholesterol in the diet is absorbed by the body. Sitosterolemia https://medlineplus.gov/genetics/condition/sitosterolemia ABCG5_HUMAN ATP-binding cassette sub-family G member 5 ATP-binding cassette, sub-family G (WHITE), member 5 ATP-binding cassette, subfamily G, member 5 sterolin 1 sterolin-1 STSL NCBI Gene 64240 OMIM 605459 2013-05 2020-08-18 ABCG8 ATP binding cassette subfamily G member 8 https://medlineplus.gov/genetics/gene/abcg8 functionThe ABCG8 gene provides instructions for making sterolin-2, which makes up half of a protein called sterolin. The other half of the sterolin protein, sterolin-1, is produced from a gene called ABCG5. Sterolin is involved in eliminating plant sterols, which are fatty components of plant-based foods that cannot be used by human cells.Sterolin is a transporter protein, which is a type of protein that moves substances across cell membranes. It is found mostly in cells of the intestines and liver and transports plant sterols. After plant sterols are absorbed from food into intestinal cells, the sterolin transporters in these cells pump them back into the intestinal tract. Sterolin transporters in liver cells pump the plant sterols into a fluid called bile that is released into the intestine. From the intestine, the plant sterols are eliminated with the feces. This process removes most of the dietary plant sterols, and allows only about 5 percent of these substances to get into the bloodstream. Sterolin also helps regulate levels of cholesterol, another fatty substance found in animal products, in a similar fashion; normally about 50 percent of cholesterol in the diet is absorbed by the body. Sitosterolemia https://medlineplus.gov/genetics/condition/sitosterolemia ABCG8_HUMAN ATP-binding cassette sub-family G member 8 ATP-binding cassette, sub-family G (WHITE), member 8 ATP-binding cassette, subfamily G, member 8 GBD4 sterolin 2 sterolin-2 STSL NCBI Gene 64241 OMIM 605460 2013-05 2020-08-18 ABHD5 abhydrolase domain containing 5, lysophosphatidic acid acyltransferase https://medlineplus.gov/genetics/gene/abhd5 functionThe ABHD5 gene provides instructions for making a protein that turns on (activates) an enzyme called adipose triglyceride lipase (ATGL). The ATGL enzyme plays a role in breaking down fats called triglycerides, which are a major source of stored energy in cells. Cells primarily store triglycerides in structures called lipid droplets (also called adiposomes). The ABHD5 protein and the ATGL enzyme are found on the surface of lipid droplets. Once activated, the ATGL enzyme breaks down triglycerides in these structures to provide energy for the body. Chanarin-Dorfman syndrome https://medlineplus.gov/genetics/condition/chanarin-dorfman-syndrome CGI58 comparative gene identification 58 IECN2 NCIE2 ICD-10-CM MeSH NCBI Gene 51099 OMIM 604780 SNOMED CT 2024-05 2024-05-07 ABL1 ABL proto-oncogene 1, non-receptor tyrosine kinase https://medlineplus.gov/genetics/gene/abl1 functionThe ABL1 gene provides instructions for making a protein involved in many processes in cells throughout the body. The ABL1 protein functions as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. The ABL1 kinase is normally turned off (inactive) and must be turned on (activated) to perform its functions.The ABL1 kinase can be turned on by a number of different triggers and can add a phosphate group to many different proteins (also called substrates). This diversity allows ABL1 to be involved in a wide variety of cellular processes, including cell growth and division (proliferation), maturation (differentiation), and movement (migration). It can either aid in cell survival or trigger controlled cell death (apoptosis), depending on cellular conditions. The ABL1 kinase interacts with several proteins involved in the network of fibers called the actin cytoskeleton, which makes up the structural framework inside cells. These interactions help control cell migration and the attachment of cells to one another (adhesion), among many other processes. ABL1 can also help regulate the activity of other genes.The ABL1 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. Chronic myeloid leukemia https://medlineplus.gov/genetics/condition/chronic-myeloid-leukemia Abelson tyrosine-protein kinase 1 ABL bcr/abl bcr/c-abl oncogene protein c-ABL c-abl oncogene 1, receptor tyrosine kinase c-ABL1 JTK7 p150 proto-oncogene c-Abl proto-oncogene tyrosine-protein kinase ABL1 tyrosine-protein kinase ABL1 isoform a tyrosine-protein kinase ABL1 isoform b v-abl v-abl Abelson murine leukemia viral oncogene homolog 1 NCBI Gene 25 OMIM 189980 OMIM 613065 2016-09 2023-03-03 ACAD8 acyl-CoA dehydrogenase family member 8 https://medlineplus.gov/genetics/gene/acad8 functionThe ACAD8 gene provides instructions for making an enzyme called isobutyryl-CoA dehydrogenase (IBD). This enzyme is found in mitochondria, the energy-producing centers inside cells. The IBD enzyme is involved in breaking down proteins from food. Specifically, this enzyme is responsible for the third step in the breakdown of a protein building block (amino acid) called valine. The IBD enzyme converts a molecule called isobutyryl-CoA into a molecule called methacrylyl-CoA. Other enzymes further break down methacrylyl-CoA into molecules that cells can use for energy. Isobutyryl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/isobutyryl-coa-dehydrogenase-deficiency ACAD-8 ACAD8_HUMAN Activator-recruited cofactor 42 kDa component acyl-CoA dehydrogenase family, member 8 acyl-coenzyme A dehydrogenase 8 ARC42 FLJ22590 NCBI Gene 27034 OMIM 604773 2025-03 2025-03-31 ACAD9 acyl-CoA dehydrogenase family member 9 https://medlineplus.gov/genetics/gene/acad9 functionThe ACAD9 gene provides instructions for making an enzyme that is found in mitochondria, the energy-producing structures inside cells. The ACAD9 enzyme is critical in helping assemble a group of proteins known as complex I. Complex I is one of several complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy.The ACAD9 enzyme also plays a role in fatty acid oxidation, a multistep process that occurs within mitochondria to break down (metabolize) fats and convert them into energy. The ACAD9 enzyme helps metabolize two fats called palmitate and oleate, which belong to a certain group of fats called long-chain fatty acids. Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues. ACAD9 deficiency https://medlineplus.gov/genetics/condition/acad9-deficiency Mitochondrial complex I deficiency https://medlineplus.gov/genetics/condition/mitochondrial-complex-i-deficiency acyl-CoA dehydrogenase family member 9, mitochondrial acyl-Coenzyme A dehydrogenase family, member 9 MGC14452 NPD002 NCBI Gene 28976 OMIM 611103 2017-04 2020-08-18 ACADM acyl-CoA dehydrogenase medium chain https://medlineplus.gov/genetics/gene/acadm functionThe ACADM gene provides instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase (MCAD). This enzyme functions within mitochondria, the energy-producing centers in cells. MCAD is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them to energy.MCAD is required to metabolize a group of fats called medium-chain fatty acids. These fatty acids are found in foods and body fat and are produced when larger fatty acids are metabolized. Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues. Medium-chain acyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/medium-chain-acyl-coa-dehydrogenase-deficiency ACAD1 ACADM_HUMAN acyl-CoA dehydrogenase, C-4 to C-12 straight chain MCAD MCADH NCBI Gene 34 OMIM 607008 2009-11 2025-04-03 ACADS acyl-CoA dehydrogenase short chain https://medlineplus.gov/genetics/gene/acads functionThe ACADS gene provides instructions for making an enzyme called short-chain acyl-CoA dehydrogenase (SCAD). This enzyme functions within mitochondria, the energy-producing centers within cells. SCAD is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them to energy.SCAD is required to metabolize a group of fats called short-chain fatty acids. These fatty acids are found in some foods and are also produced when larger fatty acids are metabolized. Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues. Short-chain acyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/short-chain-acyl-coa-dehydrogenase-deficiency ACAD3 ACADS_HUMAN acyl-CoA dehydrogenase, C-2 to C-3 short chain acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain precursor Butyryl dehydrogenase Butyryl-CoA dehydrogenase SCAD Unsaturated acyl-CoA reductase NCBI Gene 35 OMIM 606885 2009-11 2023-07-26 ACADSB acyl-CoA dehydrogenase short/branched chain https://medlineplus.gov/genetics/gene/acadsb functionThe ACADSB gene provides instructions for making an enzyme called short/branched chain acyl-CoA dehydrogenase (SBCAD, also known as 2-methylbutyryl-CoA dehydrogenase), which plays an important role in processing proteins. Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for the body. In cells throughout the body, SBCAD is found within specialized structures called mitochondria. Mitochondria convert energy from food into a form that cells can use.The SBCAD enzyme helps break down a particular amino acid called isoleucine. Specifically, this enzyme helps with the third step of the process, performing a chemical reaction that converts a molecule called 2-methylbutyryl-CoA to another molecule, tiglyl-CoA. Additional chemical reactions convert tiglyl-CoA into molecules that are used for energy. Through similar chemical reactions, the SBCAD enzyme also aids in the breakdown of other amino acids. Short/branched chain acyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/short-branched-chain-acyl-coa-dehydrogenase-deficiency 2-MEBCAD 2-methyl branched chain acyl-CoA dehydrogenase 2-methylbutyryl-CoA dehydrogenase ACAD7 ACDSB_HUMAN acyl-CoA dehydrogenase, short/branched chain SBCAD short/branched chain acyl-CoA dehydrogenase NCBI Gene 36 OMIM 600301 2007-04 2020-08-18 ACADVL acyl-CoA dehydrogenase very long chain https://medlineplus.gov/genetics/gene/acadvl functionThe ACADVL gene provides instructions for making an enzyme called very long-chain acyl-CoA dehydrogenase (VLCAD). This enzyme functions within mitochondria, the energy-producing centers in cells. Very long-chain acyl-CoA dehydrogenase is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them to energy.Very long-chain acyl-CoA dehydrogenase is required to break down a group of fats called very long-chain fatty acids. These fatty acids are found in food and body fat. Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues. Very long-chain acyl-CoA dehydrogenase deficiency https://medlineplus.gov/genetics/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency ACAD6 ACADV_HUMAN acyl-CoA dehydrogenase, very long chain acyl-coenzyme A dehydrogenase, very long chain LCACD VLCAD NCBI Gene 37 OMIM 609575 2009-11 2023-07-26 ACAN aggrecan https://medlineplus.gov/genetics/gene/acan functionThe ACAN gene provides instructions for making the aggrecan protein. Aggrecan is a type of protein known as a proteoglycan, which means it has several sugar molecules attached to it. It is the most abundant proteoglycan in cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways, and external ears.Aggrecan attaches to the other components of cartilage, organizing the network of molecules that gives cartilage its strength. These interactions occur at a specific region of the aggrecan protein called the C-type lectin domain (CLD). Because of the attached sugars, aggrecan attracts water molecules and gives cartilage its gel-like structure. This feature enables the cartilage to resist compression, protecting bones and joints. Although its role is unclear, aggrecan affects bone development. Familial osteochondritis dissecans https://medlineplus.gov/genetics/condition/familial-osteochondritis-dissecans Intervertebral disc disease https://medlineplus.gov/genetics/condition/intervertebral-disc-disease AGC1 AGCAN aggrecan core protein cartilage-specific proteoglycan core protein chondroitin sulfate proteoglycan core protein 1 CSPG1 CSPGCP large aggregating proteoglycan MSK16 SEDK NCBI Gene 176 OMIM 155760 OMIM 608361 OMIM 612813 2012-10 2023-03-03 ACAT1 acetyl-CoA acetyltransferase 1 https://medlineplus.gov/genetics/gene/acat1 functionThe ACAT1 gene provides instructions for making an enzyme that is found in the energy-producing centers within cells (mitochondria). This enzyme plays an essential role in breaking down proteins and fats from the diet. Specifically, it helps process isoleucine, an amino acid that is a building block of many proteins. This enzyme is also involved in processing ketones, which are molecules that are produced when fats are broken down in the body.During the breakdown of proteins, the ACAT1 enzyme is responsible for a step in processing isoleucine. It converts a molecule called 2-methyl-acetoacetyl-CoA into two smaller molecules, propionyl-CoA and acetyl-CoA, that can be used to produce energy.The ACAT1 enzyme carries out the last step in ketone breakdown (ketolysis) during the processing of fats. The enzyme converts a molecule called acetoacetyl-CoA into two molecules of acetyl-CoA, which can be used to produce energy. In the liver, the enzyme also carries out this chemical reaction in reverse, which is a step in building new ketones (ketogenesis). Beta-ketothiolase deficiency https://medlineplus.gov/genetics/condition/beta-ketothiolase-deficiency ACAT acetoacetyl Coenzyme A thiolase acetyl-Coenzyme A acetyltransferase 1 acetyl-Coenzyme A acetyltransferase 1 (acetoacetyl Coenzyme A thiolase) MAT methylacetoacetyl-Coenzyme A thiolase T2 THIL THIL_HUMAN NCBI Gene 38 OMIM 607809 2020-06 2020-08-18 ACE angiotensin I converting enzyme https://medlineplus.gov/genetics/gene/ace functionThe ACE gene provides instructions for making the angiotensin-converting enzyme. This enzyme is able to cut (cleave) proteins. It is part of the renin-angiotensin system, which regulates blood pressure and the balance of fluids and salts in the body. By cutting a protein called angiotensin I at a particular location, the angiotensin-converting enzyme converts this protein to angiotensin II. Angiotensin II causes blood vessels to narrow (constrict), which results in increased blood pressure. This protein also stimulates production of the hormone aldosterone, which triggers the absorption of salt and water by the kidneys. The increased amount of fluid in the body also increases blood pressure. Proper blood pressure during fetal growth, which delivers oxygen to the developing tissues, is required for normal development of the kidneys, particularly of structures called the proximal tubules, and other tissues. In addition, angiotensin II may play a more direct role in kidney development, perhaps by affecting growth factors involved in the development of kidney structures.The angiotensin-converting enzyme can cleave other proteins, including bradykinin. Bradykinin causes blood vessels to widen (dilate), which decreases blood pressure. Cleavage by the angiotensin-converting enzyme inactivates bradykinin, helping to increase blood pressure. Renal tubular dysgenesis https://medlineplus.gov/genetics/condition/renal-tubular-dysgenesis ACE1 ACE_HUMAN angiotensin converting enzyme, somatic isoform angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 angiotensin I converting enzyme peptidyl-dipeptidase A 1 transcript angiotensin-converting enzyme CD143 CD143 antigen DCP DCP1 dipeptidyl carboxypeptidase 1 dipeptidyl carboxypeptidase I EC 3.4.15.1 ICH kininase II MVCD3 NCBI Gene 1636 OMIM 106180 OMIM 612624 OMIM 614519 2013-05 2023-03-03 ACOX1 acyl-CoA oxidase 1 https://medlineplus.gov/genetics/gene/acox1 functionThe ACOX1 gene provides instructions for making an enzyme called peroxisomal straight-chain acyl-CoA oxidase. This enzyme is found in sac-like cell structures (organelles) called peroxisomes, which contain a variety of enzymes that break down many different substances. The peroxisomal straight-chain acyl-CoA oxidase enzyme plays a role in the breakdown of certain fat molecules called very long-chain fatty acids (VLCFAs). Specifically, it is involved in the first step of a process called the peroxisomal fatty acid beta-oxidation pathway. This process shortens the VLCFA molecules by two carbon atoms at a time until the VLCFAs are converted to a molecule called acetyl-CoA, which is transported out of the peroxisomes for reuse by the cell. Peroxisomal acyl-CoA oxidase deficiency https://medlineplus.gov/genetics/condition/peroxisomal-acyl-coa-oxidase-deficiency ACOX acyl-CoA oxidase 1, palmitoyl acyl-CoA oxidase, straight-chain acyl-Coenzyme A oxidase 1, palmitoyl AOX PALMCOX palmitoyl-CoA oxidase peroxisomal acyl-coenzyme A oxidase 1 peroxisomal fatty acyl-CoA oxidase SCOX straight-chain acyl-CoA oxidase NCBI Gene 51 OMIM 609751 2014-04 2020-08-18 ACP5 acid phosphatase 5, tartrate resistant https://medlineplus.gov/genetics/gene/acp5 functionThe ACP5 gene provides instructions for making an enzyme called tartrate-resistant acid phosphatase type 5 (TRAP). The TRAP enzyme primarily regulates the activity of a protein called osteopontin, which is produced in bone cells called osteoclasts and in immune cells. Osteopontin performs a variety of functions in these cells. Two versions (isoforms) of the TRAP enzyme are produced: TRAP5a is found primarily in immune cells and TRAP5b is found primarily in bone cells called osteoclasts.Osteoclasts are specialized cells that break down and remove (resorb) bone tissue that is no longer needed. These cells are involved in bone remodeling, which is a normal process that replaces old bone tissue with new bone. During bone remodeling, osteopontin is turned on (activated), allowing osteoclasts to attach (bind) to bones. When the breakdown of bone is complete, TRAP5b turns off (inactivates) osteopontin, causing the osteoclasts to release themselves from bone.In the immune system, osteopontin is found primarily in cells called macrophages and dendritic cells. The protein helps fight infection by promoting inflammation, regulating immune cell activity, and turning on various immune system cells that are necessary to fight off foreign invaders such as bacteria and viruses. Like TRAP5b in bone cells, the TRAP5a enzyme inactivates osteopontin in macrophages and dendritic cells when it is no longer needed. Spondyloenchondrodysplasia with immune dysregulation https://medlineplus.gov/genetics/condition/spondyloenchondrodysplasia-with-immune-dysregulation PPA5_HUMAN tartrate-resistant acid ATPase tartrate-resistant acid phosphatase type 5 TRAP TrATPase NCBI Gene 54 OMIM 171640 2013-12 2020-08-18 ACSF3 acyl-CoA synthetase family member 3 https://medlineplus.gov/genetics/gene/acsf3 functionThe ACSF3 gene provides instructions for making an enzyme involved in the formation (synthesis) of fatty acids, which are building blocks used to make fats (lipids). The ACSF3 enzyme performs a chemical reaction that converts malonic acid to malonyl-CoA, which is the first step of fatty acid synthesis. Based on this activity, the enzyme is classified as a malonyl-CoA synthetase. The ACSF3 enzyme also converts methylmalonic acid to methylmalonyl-CoA, making it a methylmalonyl-CoA synthetase as well.Fatty acid synthesis occurs through two pathways, one of which takes place in cellular structures called mitochondria. Mitochondria convert the energy from food into a form that cells can use, and fatty acid synthesis in these structures is thought to be important for their proper functioning. The ACSF3 enzyme is found only in mitochondria and is involved in mitochondrial fatty acid synthesis. Combined malonic and methylmalonic aciduria https://medlineplus.gov/genetics/condition/combined-malonic-and-methylmalonic-aciduria ACSF3_HUMAN acyl-CoA synthetase family member 3, mitochondrial acyl-CoA synthetase family member 3, mitochondrial precursor NCBI Gene 197322 OMIM 614245 2013-01 2020-08-18 ACTA1 actin alpha 1, skeletal muscle https://medlineplus.gov/genetics/gene/acta1 functionThe ACTA1 gene provides instructions for making a protein called skeletal alpha (α)-actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing of muscle fibers (muscle contraction). These proteins also help maintain the cytoskeleton, which is the structural framework that determines cell shape and organizes cell contents.Skeletal α-actin plays an important role in skeletal muscles, which are muscles that the body uses for movement. Within skeletal muscle cells, skeletal α-actin is an essential component of structures called sarcomeres. Sarcomeres are composed of thin filaments made up of actin and thick filaments made up of another protein called myosin. Attachment (binding) and release of the overlapping thick and thin filaments allows them to move relative to each other so that the muscles can contract. Congenital fiber-type disproportion https://medlineplus.gov/genetics/condition/congenital-fiber-type-disproportion Nemaline myopathy https://medlineplus.gov/genetics/condition/nemaline-myopathy Intranuclear rod myopathy https://medlineplus.gov/genetics/condition/intranuclear-rod-myopathy Actin-accumulation myopathy https://medlineplus.gov/genetics/condition/actin-accumulation-myopathy Cap myopathy https://medlineplus.gov/genetics/condition/cap-myopathy ACTA ACTS_HUMAN alpha skeletal muscle actin ASMA NCBI Gene 58 OMIM 102610 2012-04 2023-03-03 ACTA2 actin alpha 2, smooth muscle https://medlineplus.gov/genetics/gene/acta2 functionThe ACTA2 gene provides instructions for making a protein called smooth muscle alpha (α)-2 actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing (contraction) of muscles.Smooth muscle α-2 actin is found in smooth muscle cells. Smooth muscles line the internal organs, including the blood vessels, stomach, and intestines. Within smooth muscle cells, smooth muscle α-2 actin forms the core of structures called sarcomeres, which are necessary for muscles to contract. Smooth muscles contract and relax as part of their normal function without being consciously controlled.Layers of smooth muscle cells are found in the walls of the arteries, which are blood vessels that carry blood from the heart to the rest of the body. Smooth muscle α-2 actin contributes to the ability of these muscles to contract, which allows the arteries to maintain their shape instead of stretching out as blood is pumped through them. Familial thoracic aortic aneurysm and dissection https://medlineplus.gov/genetics/condition/familial-thoracic-aortic-aneurysm-and-dissection AAT6 ACTA_HUMAN actin, aortic smooth muscle ACTSA alpha 2 actin alpha-actin-2 cell growth-inhibiting gene 46 protein growth-inhibiting gene 46 NCBI Gene 59 OMIM 102620 OMIM 613834 2015-01 2022-07-01 ACTB actin beta https://medlineplus.gov/genetics/gene/actb functionThe ACTB gene provides instructions for making a protein called beta (β)-actin, which is part of the actin protein family. Proteins in this family are organized into a network of fibers called the actin cytoskeleton, which makes up the structural framework inside cells. There are six types of actin; four are present only in muscle cells, where they are involved in the tensing of muscle fibers (muscle contraction). The other two actin proteins, β-actin and gamma (γ)-actin (produced from the ACTG1 gene), are found in cells throughout the body. These proteins play important roles in determining cell shape and controlling cell movement (motility). Studies suggest that β-actin may also be involved in relaying chemical signals within cells. Coloboma https://medlineplus.gov/genetics/condition/coloboma Baraitser-Winter syndrome https://medlineplus.gov/genetics/condition/baraitser-winter-syndrome ACTB_HUMAN actin, beta actin, cytoplasmic 1 beta cytoskeletal actin BRWS1 PS1TP5-binding protein 1 PS1TP5BP1 NCBI Gene 60 OMIM 102630 2013-04 2020-08-18 ACTG1 actin gamma 1 https://medlineplus.gov/genetics/gene/actg1 functionThe ACTG1 gene provides instructions for making a protein called gamma (γ)-actin, which is part of the actin protein family. Proteins in this family are organized into a network of fibers called the actin cytoskeleton, which makes up the structural framework inside cells. There are six types of actin; four are present only in muscle cells, where they are involved in the tensing of muscle fibers (muscle contraction). The other two actin proteins, γ-actin and beta (β)-actin (produced from the ACTB gene), are found in cells throughout the body. These proteins play important roles in determining cell shape and controlling cell movement (motility).γ-actin is particularly abundant in certain cells in the intestines and the inner ear. Within the inner ear, this protein is found in specialized cells called hair cells, which are essential for normal hearing. Nonsyndromic hearing loss https://medlineplus.gov/genetics/condition/nonsyndromic-hearing-loss Coloboma https://medlineplus.gov/genetics/condition/coloboma Baraitser-Winter syndrome https://medlineplus.gov/genetics/condition/baraitser-winter-syndrome ACT ACTG ACTG_HUMAN actin, cytoplasmic 2 actin, gamma 1 actin-like protein cytoskeletal gamma-actin deafness, autosomal dominant 20 deafness, autosomal dominant 26 DFNA20 DFNA26 gamma-actin NCBI Gene 71 OMIM 102560 2013-04 2020-08-18 ACTG2 actin gamma 2, smooth muscle https://medlineplus.gov/genetics/gene/actg2 functionThe ACTG2 gene provides instructions for making a protein called gamma (γ)-2 actin, which is part of the actin protein family. Actin proteins are organized into filaments, which are important for the tensing of muscle fibers (muscle contraction) and cell movement. These filaments also help maintain the cytoskeleton, which is the structural framework that determines cell shape and organizes cell contents.The γ-2 actin protein is found in smooth muscle cells of the urinary and intestinal tracts. Smooth muscles line the internal organs; they contract and relax without being consciously controlled. The γ-2 actin protein is necessary for contraction of the smooth muscles in the bladder and intestines. These contractions empty urine from the bladder and move food through the intestines as part of the digestive process. Intestinal pseudo-obstruction https://medlineplus.gov/genetics/condition/intestinal-pseudo-obstruction Megacystis-microcolon-intestinal hypoperistalsis syndrome https://medlineplus.gov/genetics/condition/megacystis-microcolon-intestinal-hypoperistalsis-syndrome ACT ACTA3 ACTE actin, gamma-enteric smooth muscle isoform 1 precursor actin, gamma-enteric smooth muscle isoform 2 precursor actin-like protein ACTL3 ACTSG alpha-actin-3 VSCM NCBI Gene 72 OMIM 102545 2017-12 2022-07-05 ACVR1 activin A receptor type 1 https://medlineplus.gov/genetics/gene/acvr1 functionThe ACVR1 gene provides instructions for making the activin receptor type-1 (ACVR1) protein, which is a member of a protein family called bone morphogenetic protein (BMP) type I receptors. BMP receptors span the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This arrangement allows receptors to receive signals from outside the cell and transmit them inside to affect cell development and function.The ACVR1 protein is found in many tissues of the body including skeletal muscle and cartilage. It helps to control the growth and development of the bones and muscles, including the gradual replacement of cartilage by bone (ossification). This process occurs in normal skeletal maturation from birth to young adulthood.The ACVR1 protein is normally turned on (activated) at appropriate times by molecules called ligands. Activation may occur when these ligands, such as BMPs or a protein called activin A, attach (bind) to the receptor or to other proteins with which it forms a complex. Another protein called FKBP12 can turn off (inhibit) ACVR1 by binding to the receptor and preventing inappropriate (leaky) activation in the absence of ligands. Fibrodysplasia ossificans progressiva https://medlineplus.gov/genetics/condition/fibrodysplasia-ossificans-progressiva activin A receptor type I activin A receptor, type I activin A receptor, type II-like kinase 2 activin A type I receptor activin A type I receptor precursor ActR-IA protein, human ACTRI ACVR1_HUMAN ACVR1A ACVRLK2 ALK2 hydroxyalkyl-protein kinase SKR1 NCBI Gene 90 OMIM 102576 2007-08 2022-07-15 ACVRL1 activin A receptor like type 1 https://medlineplus.gov/genetics/gene/acvrl1 functionThe ACVRL1 gene provides instructions for making a protein called activin receptor-like kinase 1. This protein is found on the surface of cells, especially in the lining of developing arteries.The ACVRL1 protein is a receptor. It acts as a "lock" waiting for a specific protein, called its ligand, to serve as the "key." In the case of the ACVRL1 protein, the ligand is called transforming growth factor beta. The interaction between these proteins plays a role in the development of blood vessels. In particular, this protein interaction is involved in the specialization of new blood vessels into arteries or veins. Pulmonary arterial hypertension https://medlineplus.gov/genetics/condition/pulmonary-arterial-hypertension Hereditary hemorrhagic telangiectasia https://medlineplus.gov/genetics/condition/hereditary-hemorrhagic-telangiectasia activin A receptor type II-like 1 activin A receptor type IL Activin A receptor, type II-like kinase 1 ACVL1_HUMAN ACVRLK1 ALK-1 ALK1 EC 2.7.1.37 HHT HHT2 ORW2 Serine/threonine-protein kinase Receptor R3 Precursor SKR3 TGF-B Superfamily Receptor Type I ICD-10-CM MeSH NCBI Gene 94 OMIM 108010 OMIM 601284 SNOMED CT 2007-02 2021-05-20 ACY1 aminoacylase 1 https://medlineplus.gov/genetics/gene/acy1 functionThe ACY1 gene provides instructions for making an enzyme called aminoacylase 1, which is found in many tissues and organs, including the kidneys and the brain. This enzyme is involved in the breakdown of proteinswhen they are no longer needed. Many proteins in the body have a chemical group called an acetyl group attached to one end. This modification, called N-acetylation, helps protect and stabilize the protein. Aminoacylase 1 performs the final step in the breakdown of these proteins by removing the acetyl group from certain protein building blocks (amino acids). The amino acids can then be recycled and used to build other proteins. Aminoacylase 1 deficiency https://medlineplus.gov/genetics/condition/aminoacylase-1-deficiency ACY-1 ACY1D acylase 1 aminoacylase-1 N-acyl-L-amino-acid amidohydrolase NCBI Gene 95 OMIM 104620 2014-05 2020-08-18 ADA adenosine deaminase https://medlineplus.gov/genetics/gene/ada functionThe ADA gene provides instructions for producing the enzyme adenosine deaminase. This enzyme is produced in all cells, but the highest levels of adenosine deaminase are found in immune system cells called lymphocytes. These cells defend the body against foreign invaders, such as viruses or bacteria. Lymphocytes are produced in specialized lymphoid tissues throughout the body, including in a gland located behind the breastbone called the thymus and in the lymph nodes.The function of the adenosine deaminase enzyme is to get rid of a molecule called deoxyadenosine, which is generated when DNA is broken down. A buildup of deoxyadenosine in cells can lead to early cell death. Adenosine deaminase converts deoxyadenosine to another molecule called deoxyinosine, which is not harmful. Adenosine deaminase deficiency https://medlineplus.gov/genetics/condition/adenosine-deaminase-deficiency ADA_HUMAN adenosine aminohydrolase NCBI Gene 100 OMIM 608958 2024-05 2024-05-21 ADA2 adenosine deaminase 2 https://medlineplus.gov/genetics/gene/ada2 functionThe ADA2 gene provides instructions for making an enzyme called adenosine deaminase 2. This enzyme breaks down molecules called adenosine and 2'-deoxyadenosine. Because this enzyme functions in the spaces between cells, it is described as extracellular. Another form of the enzyme, adenosine deaminase 1, breaks down the same molecules inside cells. This other version of the enzyme is produced from the ADA gene.Researchers are still working to determine the functions of adenosine deaminase 2. Studies suggest that it acts as a growth factor, which means that it stimulates cell growth and division. In particular, the enzyme appears to be involved in the growth and development of certain immune system cells, including macrophages, which are a type of white blood cell that plays a critical role in inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). Some macrophages are pro-inflammatory, meaning they promote inflammation, while others are anti-inflammatory, meaning they reduce inflammation. Adenosine deaminase 2 deficiency https://medlineplus.gov/genetics/condition/adenosine-deaminase-2-deficiency adenosine deaminase CECR1 ADGF cat eye syndrome chromosome region, candidate 1 cat eye syndrome critical region protein 1 CECR1 IDGFL SNEDS NCBI Gene 51816 OMIM 607575 2018-08 2020-08-18 ADAMTS10 ADAM metallopeptidase with thrombospondin type 1 motif 10 https://medlineplus.gov/genetics/gene/adamts10 functionThe ADAMTS10 gene provides instructions for making an enzyme that is found in many of the body's cells and tissues. This enzyme is part of a family of metalloproteases, which are zinc-containing enzymes that cut apart other proteins. Although the function of the ADAMTS10 enzyme is unknown, it is critical for growth before and after birth. Researchers believe that it may be involved in the development of structures including the skin, eyes, heart, and skeleton. Weill-Marchesani syndrome https://medlineplus.gov/genetics/condition/weill-marchesani-syndrome a disintegrin and metalloproteinase with thrombospondin motifs 10 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 10 a disintegrin-like and metalloprotease domain with thrombospondin type I repeats 10 ADAM metallopeptidase with thrombospondin type 1 motif, 10 ADAM-TS10 ADAMTS-10 ATS10_HUMAN NCBI Gene 81794 OMIM 608990 2008-10 2020-08-18 ADAMTS13 ADAM metallopeptidase with thrombospondin type 1 motif 13 https://medlineplus.gov/genetics/gene/adamts13 functionThe ADAMTS13 gene provides instructions for making an enzyme that is involved in regulating blood clotting. After an injury, clots normally protect the body by sealing off damaged blood vessels and preventing further blood loss.The ADAMTS13 enzyme processes a large protein called von Willebrand factor. This protein is involved in the first step of blood clotting at the site of injury, which is to help cells called platelets stick together and attach to the walls of blood vessels, forming temporary clots. The ADAMTS13 enzyme cuts von Willebrand factor into smaller pieces to regulate its interaction with platelets. By processing von Willebrand factor in this way, the enzyme prevents it from triggering the formation of blood clots in normal circulation. Thrombotic thrombocytopenic purpura https://medlineplus.gov/genetics/condition/thrombotic-thrombocytopenic-purpura ADAM metallopeptidase with thrombospondin type 1 motif, 13 ADAMTS-13 ATS13_HUMAN C9orf8 von Willebrand factor-cleaving protease vWF-cleaving protease vWF-CP VWFCP NCBI Gene 11093 OMIM 604134 2020-05 2020-08-18 ADAMTS2 ADAM metallopeptidase with thrombospondin type 1 motif 2 https://medlineplus.gov/genetics/gene/adamts2 functionThe ADAMTS2 gene provides instructions for making an enzyme that processes several types of procollagen molecules. Procollagens are the precursors of collagens, which are complex molecules found in the spaces between cells that add strength, support, and stretchiness (elasticity) to many body tissues. The ADAMTS2 enzyme cuts a short chain of protein building blocks (amino acids) off one end of procollagens. This clipping step is necessary for the resulting collagen molecules to assemble into strong, slender fibrils. Ehlers-Danlos syndrome https://medlineplus.gov/genetics/condition/ehlers-danlos-syndrome a disintegrin and metalloproteinase with thrombospondin motifs 2 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 2 ADAM metallopeptidase with thrombospondin type 1 motif, 2 ADAM-TS2 ATS2_HUMAN hPCPNI NPI PCINP PCPNI pNPI procollagen I N-proteinase procollagen I/II amino-propeptide processing enzyme procollagen N-endopeptidase NCBI Gene 9509 OMIM 604539 2015-11 2020-08-18 ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif 3 https://medlineplus.gov/genetics/gene/adamts3 functionThe ADAMTS3 gene provides instructions for making an enzyme that is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. The ADAMTS3 protein is part of a family of proteins that help process procollagen molecules. Procollagens are the precursors of collagens, which are complex molecules that add strength, support, and stretchiness (elasticity) to many body tissues.Within the extracellular matrix, the ADAMTS3 enzyme works with another protein that is produced from the CCBE1 gene to help regulate the activity of a protein called vascular endothelial growth factor receptor 3 (VEGFR3). VEGFR3 plays a key role in the development and maintenance of the lymphatic system, which is a network of vessels that transport white blood cells (lymphocytes), nutrients, and proteins in a fluid called lymph.  Hennekam syndrome https://medlineplus.gov/genetics/condition/hennekam-syndrome ADAMTS-4 KIAA0366 NCBI Gene 9508 OMIM 605011 2026-03 2026-03-20 ADAMTSL2 ADAMTS like 2 https://medlineplus.gov/genetics/gene/adamtsl2 functionThe ADAMTSL2 gene provides instructions for making a protein whose exact function is unknown. The ADAMTSL2 protein is active in many different tissues and is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells.Studies suggest that the ADAMTSL2 protein interacts with a protein called latent transforming growth factor beta-binding protein 1 (LTBP1). The LTBP1 protein is involved in the storage of another protein called transforming growth factor beta (TGF-β). TGF-β helps regulate important cell processes, including the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis).The interaction between the ADAMTSL2 and LTBP1 proteins suggests that ADAMTSL2 may play a role in the microfibrillar network. This organized arrangement of thread-like filaments (microfibrils) within the extracellular matrix provides strength and flexibility to tissues throughout the body.Researchers also suspect that the ADAMTSL2 protein may help regulate the availability of TGF-β, which is stored in the microfibrillar network. Once released from the microfibrillar network, TGF-β activates important signaling pathways, including the signaling pathways involved in bone formation.  Geleophysic dysplasia https://medlineplus.gov/genetics/condition/geleophysic-dysplasia KIAA0605 NCBI Gene 9719 OMIM 612277 2026-02 2026-02-25 ADAMTSL4 ADAMTS like 4 https://medlineplus.gov/genetics/gene/adamtsl4 functionThe ADAMTSL4 gene provides instructions for making a protein that is found throughout the body. The ADAMTSL4 protein is released from cells into the extracellular matrix, which is an intricate lattice of proteins and other molecules that forms in the spaces between cells. The ADAMTSL4 protein binds to other proteins within the extracellular matrix. One of these proteins is called fibrillin-1. Fibrillin-1 proteins bind to each other and to other proteins to form threadlike filaments called microfibrils. Research suggests that ADAMTSL4 binds to fibrillin-1 to promote microfibril assembly in many tissues. Within the eyes, microfibrils form small bundles called zonular fibers that hold the lenses of the eyes in their central position. The lens is a clear structure at the front of the eye that helps focus light. Isolated ectopia lentis https://medlineplus.gov/genetics/condition/isolated-ectopia-lentis DKFZP434K1772 NCBI Gene 54507 OMIM 225200 OMIM 610113 2026-04 2026-04-01 ADAR adenosine deaminase RNA specific https://medlineplus.gov/genetics/gene/adar functionThe ADAR gene provides instructions for making a protein called RNA-specific adenosine deaminase 1 (ADAR1). This protein is involved in making changes to (editing) RNA, a chemical cousin of DNA. Specifically, it attaches (binds) to RNA and changes an RNA building block (nucleotide) called adenosine to another nucleotide called inosine.The ADAR1 protein is involved in the control of the innate immune response, which is the immune system's early response to foreign invaders (pathogens). The immune system sometimes fails to recognize the body’s own RNA and may act as though it belongs to a pathogen that should be attacked. By changing adenosine to inosine, ADAR1 may prevent the immune system from targeting the body's own tissues.The ADAR1 protein is also thought to inhibit the replication and spread of certain viruses, such as human immunodeficiency virus (HIV) and hepatitis C, by modifying their RNA. In addition, the ADAR1 protein controls the function of certain chemical messengers called neurotransmitters at particular sites in the body by modifying the RNA blueprint for the receptor proteins that interact with the neurotransmitters. Studies suggest that the ADAR1 protein may have other functions that are not well understood. Aicardi-Goutières syndrome https://medlineplus.gov/genetics/condition/aicardi-goutieres-syndrome ADAR1 adenosine deaminase acting on RNA 1-A DRADA DSH DSRAD dsRNA adenosine deaminase dsRNA adeonosine deaminase IFI-4 IFI4 interferon-induced protein 4 interferon-inducible protein 4 NCBI Gene 103 OMIM 127400 OMIM 146920 2024-09 2024-09-26 ADCY5 adenylate cyclase 5 https://medlineplus.gov/genetics/gene/adcy5 functionThe ADCY5 gene provides instructions for making an enzyme called adenylate cyclase 5. This enzyme helps convert a molecule called adenosine triphosphate (ATP) to another molecule called cyclic adenosine monophosphate (cAMP). ATP is a molecule that supplies energy for cells' activities, including muscle contraction, and cAMP is involved in signaling for many cellular functions. ADCY5-related dyskinesia https://medlineplus.gov/genetics/condition/adcy5-related-dyskinesia AC5 adenylate cyclase type 5 adenylate cyclase type 5 isoform 1 adenylate cyclase type 5 isoform 2 adenylate cyclase type V adenylyl cyclase 5 ATP pyrophosphate-lyase 5 FDFM NCBI Gene 111 OMIM 600293 2015-07 2023-07-25 ADGRE2 adhesion G protein-coupled receptor E2 https://medlineplus.gov/genetics/gene/adgre2 functionThe ADGRE2 gene provides instructions for making a protein found in several types of immune system cells, including mast cells. Mast cells, which are found in many body tissues including the skin, are important for the normal protective functions of the immune system. They also play a role in allergic reactions, which occur when the immune system overreacts to stimuli that are not harmful. The specific role of the ADGRE2 protein in mast cells is not well understood.The ADGRE2 protein consists of two parts (subunits) that interact with each other: an alpha subunit that lies on the outside surface of the cell and a beta subunit that crosses the cell membrane and extends into the cell. Vibratory urticaria https://medlineplus.gov/genetics/condition/vibratory-urticaria CD312 EGF-like module-containing mucin-like hormone receptor-like 2 EMR2 NCBI Gene 30817 OMIM 606100 2016-07 2020-08-18 ADGRG1 adhesion G protein-coupled receptor G1 https://medlineplus.gov/genetics/gene/adgrg1 functionThe ADGRG1 gene, formerly known as GPR56, provides instructions for making a protein that is critical for normal brain development. Before birth, the ADGRG1 protein appears to be essential for the normal growth and movement (migration) of nerve cells (neurons) in a part of the brain called the cerebral cortex. This outer layer of the brain carries out many important functions, such as sensation, voluntary muscle movement, thought, planning, and memory.Although the ADGRG1 protein has been studied most extensively in the brain, it is active in many of the body's tissues. This protein interacts with other proteins on the cell surface to trigger a series of chemical signals within the cell. Studies suggest that ADGRG1 signaling may play an important role in attaching cells to one another (cell adhesion). Polymicrogyria https://medlineplus.gov/genetics/condition/polymicrogyria 7-transmembrane protein with no EGF-like N-terminal domains-1 DKFZp781L1398 EGF-TM7-like G protein-coupled receptor 56 GPR56 GPR56_HUMAN TM7LN4 TM7XN1 NCBI Gene 9289 OMIM 604110 2009-06 2020-08-18 ADNP activity dependent neuroprotector homeobox https://medlineplus.gov/genetics/gene/adnp functionThe ADNP gene provides instructions for making a protein that helps control the activity (expression) of other genes through a process called chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed. As part of the remodeling process, the ADNP protein attaches to DNA and interacts with groups of proteins called SWI/SNF complexes, which direct changes in the structure of chromatin.By regulating gene expression, the ADNP protein is involved in many aspects of development. It is particularly important for regulation of genes involved in normal brain development, and it likely controls the activity of genes that direct the development and function of other body systems. ADNP syndrome https://medlineplus.gov/genetics/condition/adnp-syndrome Autism spectrum disorder https://medlineplus.gov/genetics/condition/autism-spectrum-disorder activity-dependent neuroprotective protein activity-dependent neuroprotector activity-dependent neuroprotector homeobox protein ADNP homeobox 1 ADNP1 HVDAS KIAA0784 MRD28 NCBI Gene 23394 OMIM 611386 2017-03 2020-08-18 ADSL adenylosuccinate lyase https://medlineplus.gov/genetics/gene/adsl functionThe ADSL gene provides instructions for making an enzyme called adenylosuccinate lyase. This enzyme performs two steps in the process that produces (synthesizes) purine nucleotides. These nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP that serve as energy sources in the cell. Adenylosuccinate lyase and other enzymes involved in purine synthesis form a group of proteins (a protein complex) called the purinosome. This complex comes together when there is a shortage of purines or when a large amount of purines is needed, such as during cell division. As part of this complex, adenylosuccinate lyase converts a molecule called succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and converts succinyladenosine monophosphate (SAMP) to adenosine monophosphate (AMP). Adenylosuccinate lyase deficiency https://medlineplus.gov/genetics/condition/adenylosuccinate-lyase-deficiency adenylosuccinase adenylosuccinate lyase isoform a adenylosuccinate lyase isoform b AMPS ASASE ASL NCBI Gene 158 OMIM 608222 2014-12 2020-08-18 AFF2 ALF transcription elongation factor 2 https://medlineplus.gov/genetics/gene/aff2 functionThe AFF2 gene provides instructions for making a protein that is found in the nucleus of cells but whose function is not well understood. Some studies suggest that it acts as a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of other genes, although the identity of these genes is unknown. Other studies show that the protein can attach to specific regions of messenger RNA (mRNA), which is a chemical cousin of DNA that serves as the genetic blueprint for protein production. It is thought that the AFF2 protein helps control the process by which the mRNA blueprint is cut and rearranged to produce different versions of proteins (alternative splicing).One region of the AFF2 gene contains a particular DNA segment known as a CCG trinucleotide repeat, so called because this segment of three DNA building blocks (nucleotides) is repeated multiple times within the gene. In most people, the number of CCG repeats ranges from 6 to about 30. Fragile XE syndrome https://medlineplus.gov/genetics/condition/fragile-xe-syndrome AFF2_HUMAN FMR2 FMR2P FRAXE MRX2 NCBI Gene 2334 OMIM 300806 2014-01 2024-07-17 AFF4 ALF transcription elongation factor 4 https://medlineplus.gov/genetics/gene/aff4 functionThe AFF4 gene provides instructions for making part of a protein complex called the super elongation complex (SEC). During embryonic development, the SEC is involved in an activity called transcription, which is the first step in the production of proteins from genes. By re-starting the transcription of certain genes after pauses that normally occur during the process, the SEC helps ensure that development proceeds appropriately before birth. CHOPS syndrome https://medlineplus.gov/genetics/condition/chops-syndrome AF4/FMR2 family, member 4 AF5Q31 ALL1-fused gene from chromosome 5q31 protein major CDK9 elongation factor-associated protein MCEF NCBI Gene 27125 OMIM 604417 2015-10 2022-07-01 AGA aspartylglucosaminidase https://medlineplus.gov/genetics/gene/aga functionThe AGA gene provides instructions for producing an enzyme called aspartylglucosaminidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Within lysosomes, the enzyme helps break down complex chains of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). Specifically, this enzyme cuts (cleaves) glycoproteins between a protein building block (amino acid) called asparagine and a sugar molecule called N-acetylglucosamine. This cut is one of the last steps in breaking down a glycoprotein in the lysosome. Aspartylglucosaminuria https://medlineplus.gov/genetics/condition/aspartylglucosaminuria ASRG glycosylasparaginase N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase NCBI Gene 175 OMIM 613228 2008-12 2022-01-19 AGL amylo-alpha-1,6-glucosidase and 4-alpha-glucanotransferase https://medlineplus.gov/genetics/gene/agl functionThe AGL gene provides instructions for making the glycogen debranching enzyme. This enzyme is involved in the breakdown of a complex sugar called glycogen, which is a major source of stored energy in the body. Glycogen is made up of several molecules of a simple sugar called glucose. Some glucose molecules are linked together in a straight line, while others branch off and form side chains. The glycogen debranching enzyme is involved in the breakdown of these side chains. The branched structure of glycogen makes it more compact for storage and allows it to break down more easily when it is needed for fuel.The AGL gene provides instructions for making several different versions (isoforms) of the glycogen debranching enzyme. These isoforms vary by size and are active (expressed) in different tissues. Glycogen storage disease type III https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-iii amylo-1, 6-glucosidase, 4-alpha-glucanotransferase GDE GDE_HUMAN glycogen debrancher glycogen debranching enzyme NCBI Gene 178 OMIM 610860 2010-09 2024-11-01 AGPAT2 1-acylglycerol-3-phosphate O-acyltransferase 2 https://medlineplus.gov/genetics/gene/agpat2 functionThe AGPAT2 gene provides instructions for making an enzyme that is found in many of the body's cells and tissues. It plays a critical role in the growth and development of adipocytes, which are cells that store fats for energy. Adipocytes are the major component of the body's fatty (adipose) tissue.The AGPAT2 enzyme is part of a chemical pathway in many cells that produces two important types of fats (lipids): glycerophospholipids and triacylglycerols. Glycerophospholipids are the major component of cell membranes and are involved in chemical signaling within cells. Triacylglycerols (also known as triglycerides) are fat molecules that are stored in adipocytes for later conversion to energy.The AGPAT2 enzyme is responsible for a particular chemical reaction in the production of these two types of lipids. Specifically, the enzyme helps convert a molecule called lysophosphatidic acid (LPA) to another molecule, phosphatidic acid (PA). Additional reactions convert phosphatidic acid to glycerophospholipids and triacylglycerols. Congenital generalized lipodystrophy https://medlineplus.gov/genetics/condition/congenital-generalized-lipodystrophy 1-acyl-sn-glycerol-3-phosphate acyltransferase beta 1-acylglycerol-3-phosphate O-acyltransferase 2 (lysophosphatidic acid acyltransferase, beta) 1-AGP acyltransferase 2 1-AGPAT2 BSCL1 LPAAB LPAAT-beta lysophosphatidic acid acyltransferase-beta PLCB_HUMAN NCBI Gene 10555 OMIM 603100 2015-12 2020-08-18 AGPS alkylglycerone phosphate synthase https://medlineplus.gov/genetics/gene/agps functionThe AGPS gene provides instructions for making an enzyme known as alkylglycerone phosphate synthase. This enzyme is found in structures called peroxisomes, which are sac-like compartments within cells that contain enzymes needed to break down many different substances. Peroxisomes are also important for the production of fats (lipids) used in digestion and in the nervous system.Within peroxisomes, alkylglycerone phosphate synthase is responsible for a critical step in the production of lipid molecules called plasmalogens. These molecules are found in cell membranes throughout the body. They are also abundant in myelin, which is the protective substance that covers nerve cells. However, little is known about the functions of plasmalogens. Researchers suspect that these molecules may help protect cells from oxidative stress, which occurs when unstable molecules called free radicals accumulate to levels that damage or kill cells. Plasmalogens may also play important roles in interactions between lipids and proteins, the transmission of chemical signals in cells, and the fusion of cell membranes. Rhizomelic chondrodysplasia punctata https://medlineplus.gov/genetics/condition/rhizomelic-chondrodysplasia-punctata ADAP-S ADAS_HUMAN ADHAPS alkyl-DHAP synthase alkyl-dihydroxyacetone phosphate synthase alkyldihydroxyacetone phosphate synthetase alkyldihydroxyacetonephosphate synthase, peroxisomal alkylglycerone-phosphate synthase NCBI Gene 8540 OMIM 603051 2010-07 2020-08-18 AGT angiotensinogen https://medlineplus.gov/genetics/gene/agt functionThe AGT gene provides instructions for making a protein called angiotensinogen. This protein is part of the renin-angiotensin system, which regulates blood pressure and the balance of fluids and salts in the body. In the first step of this process, angiotensinogen is converted to angiotensin I. Through an additional step, angiotensin I is converted to angiotensin II. Angiotensin II causes blood vessels to narrow (constrict), which results in increased blood pressure. This molecule also stimulates production of the hormone aldosterone, which triggers the absorption of salt and water by the kidneys. The increased amount of fluid in the body also increases blood pressure. Proper blood pressure during fetal growth, which delivers oxygen to the developing tissues, is required for normal development of the kidneys, particularly of structures called the proximal tubules, and other tissues. In addition, angiotensin II may play a more direct role in kidney development, perhaps by affecting growth factors involved in the development of kidney structures. Renal tubular dysgenesis https://medlineplus.gov/genetics/condition/renal-tubular-dysgenesis Hypertension https://medlineplus.gov/genetics/condition/hypertension angiotensinogen (serpin peptidase inhibitor, clade A, member 8) angiotensinogen preproprotein ANGT_HUMAN ANHU pre-angiotensinogen serpin A8 SERPINA8 NCBI Gene 183 OMIM 106150 OMIM 145500 2013-05 2020-08-18 AGTR1 angiotensin II receptor type 1 https://medlineplus.gov/genetics/gene/agtr1 functionThe AGTR1 gene provides instructions for making a protein called the angiotensin II receptor type 1 (AT1 receptor). This protein is part of the renin-angiotensin system, which regulates blood pressure and the balance of fluids and salts in the body. Through a series of steps, the renin-angiotensin system produces a molecule called angiotensin II, which attaches (binds) to the AT1 receptor, stimulating chemical signaling. This signaling causes blood vessels to narrow (constrict), which results in increased blood pressure. Binding of angiotensin II to the AT1 receptor also stimulates production of the hormone aldosterone, which triggers the absorption of water and salt by the kidneys. The increased amount of fluid in the body also increases blood pressure. Proper blood pressure during fetal growth, which delivers oxygen to the developing tissues, is required for normal development of the kidneys, particularly of structures called the proximal tubules, and other tissues. In addition, angiotensin II may play a more direct role in kidney development, perhaps by affecting growth factors involved in the development of kidney structures. Renal tubular dysgenesis https://medlineplus.gov/genetics/condition/renal-tubular-dysgenesis Hypertension https://medlineplus.gov/genetics/condition/hypertension AG2S AGTR1_HUMAN AGTR1A AGTR1B angiotensin II receptor, type 1 AT1 AT1AR AT1B AT1BR AT1R AT2R1 AT2R1A AT2R1B HAT1R type-1 angiotensin II receptor type-1B angiotensin II receptor NCBI Gene 185 OMIM 106165 OMIM 145500 2013-05 2020-08-18 AGXT alanine--glyoxylate aminotransferase https://medlineplus.gov/genetics/gene/agxt functionThe AGXT gene provides instructions for making an enzyme called alanine-glyoxylate aminotransferase. This enzyme is found in liver cells, specifically within cell structures called peroxisomes. These structures are important for several cellular activities, such as ridding the cell of toxic substances and helping to break down certain fats. In the peroxisome, alanine-glyoxylate aminotransferase converts a compound called glyoxylate to the protein building block (amino acid) glycine. Primary hyperoxaluria https://medlineplus.gov/genetics/condition/primary-hyperoxaluria AGT AGT1 AGXT1 alanine glyoxylate aminotransferase alanine-glyoxylate aminotransferase alanine-glyoxylate aminotransferase (oxalosis I; hyperoxaluria I; glycolicaciduria; serine-pyruvate aminotransferase) alanine-glyoxylate transaminase L-alanine: glyoxylate aminotransferase 1 pyruvate (glyoxylate) aminotransferase serine-pyruvate aminotransferase serine:pyruvate aminotransferase SPAT SPT NCBI Gene 189 OMIM 604285 2015-12 2022-09-01 AHCY adenosylhomocysteinase https://medlineplus.gov/genetics/gene/ahcy functionThe AHCY gene provides instructions for producing the enzyme S-adenosylhomocysteine hydrolase. This enzyme is involved in a multistep process that breaks down the protein building block (amino acid) methionine. Specifically, S-adenosylhomocysteine hydrolase controls the step that converts the compound S-adenosylhomocysteine to the compounds adenosine and homocysteine. This reaction also plays an important role in regulating the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to other compounds (methylation). Methylation is important in many cellular processes. These include determining whether the instructions in a particular segment of DNA are carried out, regulating reactions involving proteins and lipids, and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters). Hypermethioninemia https://medlineplus.gov/genetics/condition/hypermethioninemia SAHH SAHH_HUMAN NCBI Gene 191 OMIM 180960 2007-04 2021-08-06 AHDC1 AT-hook DNA binding motif containing 1 https://medlineplus.gov/genetics/gene/ahdc1 functionThe AHDC1 gene provides instructions for making a protein whose function is not known. The AHDC1 protein is found in the nucleus of cells, and a region of the protein is thought to allow it to attach (bind) to DNA. Based on its location and possible DNA-binding ability, researchers suspect the protein may help control the activity of other genes. Xia-Gibbs syndrome https://medlineplus.gov/genetics/condition/xia-gibbs-syndrome AT-HOOK DNA-BINDING MOTIF-CONTAINING PROTEIN 1 NCBI Gene 27245 OMIM 615790 2019-02 2020-08-18 AIP AHR interacting HSP90 co-chaperone https://medlineplus.gov/genetics/gene/aip functionThe AIP gene provides instructions for making a protein called AH receptor-interacting protein (AIP). Although AIP's function is not well understood, it is known to interact with numerous other proteins, including one called the aryl hydrocarbon receptor. Through these interactions, AIP likely helps regulate certain cell processes, such as the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), and cell survival. This protein is thought to act as a tumor suppressor, which means it normally helps prevent cells from proliferating in an uncontrolled way. Familial isolated pituitary adenoma https://medlineplus.gov/genetics/condition/familial-isolated-pituitary-adenoma AH receptor-interacting protein AIP_HUMAN ARA9 aryl hydrocarbon receptor interacting protein FKBP16 FKBP37 HBV X-associated protein 2 immunophilin homolog ARA9 SMTPHN XAP-2 XAP2 NCBI Gene 9049 OMIM 605555 2013-08 2025-04-01 AIRE autoimmune regulator https://medlineplus.gov/genetics/gene/aire functionThe AIRE gene provides instructions for making a protein called the autoimmune regulator. This protein is active primarily in the thymus, which is an organ located behind the breastbone that plays an important role in immune system function. The thymus prepares immune cells called T cells for their role in fighting infection; this process is called thymic education.For a person to remain healthy, immune system cells such as T cells must be able to identify and destroy potentially harmful invaders (such as bacteria, fungi, and viruses) while sparing the body's normal tissues. The autoimmune regulator protein plays an important role in this process by helping T cells distinguish the body's own proteins from those of foreign invaders. When this system malfunctions, the immune system's ability to distinguish between the body's proteins and foreign invaders is impaired, and it may attack the body's own tissues and organs. This abnormal reaction is called autoimmunity. In the thymus, the autoimmune regulator protein destroys T cells that otherwise would cause autoimmune damage. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy https://medlineplus.gov/genetics/condition/autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy Alopecia areata https://medlineplus.gov/genetics/condition/alopecia-areata AIRE1 AIRE_HUMAN APECED APS1 APSI Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein PGA1 NCBI Gene 326 OMIM 607358 2016-10 2020-08-18 AKR1D1 aldo-keto reductase family 1 member D1 https://medlineplus.gov/genetics/gene/akr1d1 functionThe AKR1D1 gene provides instructions for making an enzyme called 3-oxo-5-beta(β)-steroid 4-dehydrogenase. This enzyme is found in liver cells. It participates in the production of bile acids, which are a component of a digestive fluid called bile. Bile acids stimulate bile flow and helps absorb fats and fat-soluble vitamins. Bile acids are produced from cholesterol in a multi-step process. The 3-oxo-5-β-steroid 4-dehydrogenase enzyme is responsible for the third step in that process, which converts 7alpha(α)-hydroxy-4-cholesten-3-one to 7α-hydroxy-5β-cholesten-3-one. Congenital bile acid synthesis defect type 2 https://medlineplus.gov/genetics/condition/congenital-bile-acid-synthesis-defect-type-2 3-oxo-5-beta-steroid 4-dehydrogenase 3o5bred 5-beta-reductase AK1D1_HUMAN aldo-keto reductase family 1, member D1 delta 4-3-ketosteroid-5-beta-reductase delta(4)-3-ketosteroid 5-beta-reductase delta(4)-3-oxosteroid 5-beta-reductase SRD5B1 steroid 5-beta-reductase NCBI Gene 6718 OMIM 604741 2015-04 2020-08-18 AKT1 AKT serine/threonine kinase 1 https://medlineplus.gov/genetics/gene/akt1 functionThe AKT1 gene provides instructions for making a protein called AKT1 kinase. This protein is found in various cell types throughout the body, where it plays a critical role in many signaling pathways. For example, AKT1 kinase helps regulate cell growth and division (proliferation), the process by which cells mature to carry out specific functions (differentiation), and cell survival. AKT1 kinase also helps control apoptosis, which is the self-destruction of cells when they become damaged or are no longer needed.Signaling involving AKT1 kinase appears to be essential for the normal development and function of the nervous system. Studies have suggested a role for AKT1 kinase in cell-to-cell communication among nerve cells (neurons), neuronal survival, and the formation of memories.The AKT1 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. Cowden syndrome https://medlineplus.gov/genetics/condition/cowden-syndrome Proteus syndrome https://medlineplus.gov/genetics/condition/proteus-syndrome Ovarian cancer https://medlineplus.gov/genetics/condition/ovarian-cancer AKT AKT1_HUMAN MGC99656 PKB PKB alpha PKB-ALPHA PRKBA protein kinase B alpha proto-oncogene c-Akt RAC rac protein kinase alpha RAC-ALPHA RAC-alpha serine/threonine-protein kinase RAC-PK-alpha v-akt murine thymoma viral oncogene homolog 1 NCBI Gene 207 OMIM 114480 OMIM 114500 OMIM 164730 OMIM 167000 OMIM 181500 2012-06 2026-03-24 AKT3 AKT serine/threonine kinase 3 https://medlineplus.gov/genetics/gene/akt3 functionThe AKT3 gene provides instructions for making a protein that is most active in the nervous system. The AKT3 protein is a key regulator of a chemical signaling pathway called the PI3K-AKT-mTOR pathway. This signaling influences many critical cell functions, including the creation (synthesis) of new proteins, cell growth and division (proliferation), and the survival of cells. The PI3K-AKT-mTOR pathway is essential for the normal development of many parts of the body, including the brain. Studies suggest that the AKT3 protein plays a critical role in determining brain size. Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome https://medlineplus.gov/genetics/condition/megalencephaly-polymicrogyria-polydactyly-hydrocephalus-syndrome PKB gamma PKB-GAMMA PKBG PRKBG RAC-gamma RAC-gamma serine/threonine protein kinase RAC-PK-gamma STK-2 v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) NCBI Gene 10000 OMIM 611223 2017-01 2020-08-18 ALAD aminolevulinate dehydratase https://medlineplus.gov/genetics/gene/alad functionThe ALAD gene provides instructions for making an enzyme known as delta-aminolevulinate dehydratase. This enzyme is involved in the production of a molecule called heme. Heme is vital for all of the body's organs, although it is found mostly in the blood, bone marrow, and liver. Heme is an essential component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).The production of heme is a multi-step process that requires eight different enzymes. Delta-aminolevulinate dehydratase is responsible for the second step in this process, which combines two molecules of delta-aminolevulinic acid (the product of the first step) to form a compound called porphobilinogen. In subsequent steps, four molecules of porphobilinogen are combined and then modified to produce heme. Porphyria https://medlineplus.gov/genetics/condition/porphyria 5-aminolevulinate dehydratase 5-Aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing) ALA-Dehydrase ALADH Aminolevulinate Hydro-Lyase aminolevulinate, delta-, dehydratase Aminolevulinic Acid Dehydratase delta-Aminolevulinate Dehydratase delta-Aminolevulinic Acid Dehydratase HEM2_HUMAN PBGS Porphobilinogen Synthase NCBI Gene 210 OMIM 125270 2009-07 2020-08-18 ALAS2 5'-aminolevulinate synthase 2 https://medlineplus.gov/genetics/gene/alas2 functionThe ALAS2 gene provides instructions for making an enzyme called 5-aminolevulinate synthase. This enzyme is found only in developing red blood cells called erythroblasts. The enzyme is located inside the energy-producing centers of these cells, which are called the mitochondria.5-aminolevulinate synthase plays an important role in the production of heme. Heme is a component of iron-containing proteins called hemoproteins. The most abundant of these proteins is hemoglobin, which is the protein that carries oxygen in the blood. Heme is essential for many of the body's organs, and it is primarily found in the blood, bone marrow, and liver.The production of heme is a multi-step process that requires several different enzymes. The 5-aminolevulinate synthase enzyme is responsible for the first step in this process. The enzyme uses vitamin B6 to form a compound called delta-aminolevulinic acid (ALA). In subsequent steps, other enzymes produce and modify compounds in a process that ultimately leads to heme production. Porphyria https://medlineplus.gov/genetics/condition/porphyria X-linked sideroblastic anemia https://medlineplus.gov/genetics/condition/x-linked-sideroblastic-anemia 5-aminolevulinate synthase, erythroid-specific, mitochondrial ALAS, erythroid ALAS-E aminolevulinate, delta-, synthase 2 ANH1 ASB HEM0_HUMAN NCBI Gene 212 OMIM 301300 2025-09 2025-09-19 ALDH18A1 aldehyde dehydrogenase 18 family member A1 https://medlineplus.gov/genetics/gene/aldh18a1 functionThe ALDH18A1 gene provides instructions for making a protein known as P5CS. This protein is found in cell structures called mitochondria, which are the energy-producing centers of cells. P5CS appears to be important for mitochondrial function, and it plays a role in the formation (synthesis) of the protein building block (amino acid) proline.The formation of proline is a multi-step process that converts the amino acid glutamate to the amino acid proline. The P5CS protein carries out the first step in this process by converting the amino acid glutamate to glutamate 5-semialdehyde. Subsequent steps convert this intermediate product to the amino acid proline. The conversion of glutamate to proline is important in maintaining a supply of the amino acids needed for protein production and for energy transfer within the cell. Cutis laxa https://medlineplus.gov/genetics/condition/cutis-laxa GSAS PYCS pyrroline-5-carboxylate synthetase (glutamate gamma-semialdehyde synthetase) ICD-10-CM MeSH NCBI Gene 5832 OMIM 138250 SNOMED CT 2022-03 2021-08-05 ALDH3A2 aldehyde dehydrogenase 3 family member A2 https://medlineplus.gov/genetics/gene/aldh3a2 functionThe ALDH3A2 gene is a member of the aldehyde dehydrogenase (ALDH) gene family. Genes in this family provide instructions for producing enzymes that alter molecules called aldehydes. The ALDH3A2 gene provides instructions for making an enzyme that breaks down fat molecules called fatty aldehydes into fatty acids. This is part of a multistep process called fatty acid oxidation in which fats are broken down and converted into energy.The ALDH3A2 enzyme is found in most tissues, but its activity (expression) is highest in the liver. Within cells, most of the ALDH3A2 enzyme is located in the endoplasmic reticulum, a structure that is involved in processing and transporting proteins. Sjögren-Larsson syndrome https://medlineplus.gov/genetics/condition/sjogren-larsson-syndrome aldehyde dehydrogenase 10 aldehyde dehydrogenase family 3, subfamily A, member A2 ALDH10 FALDH fatty aldehyde dehydrogenase NCBI Gene 224 OMIM 609523 2025-12 2025-12-19 ALDH4A1 aldehyde dehydrogenase 4 family member A1 https://medlineplus.gov/genetics/gene/aldh4a1 functionThe ALDH4A1 gene provides instructions for producing the enzyme pyrroline-5-carboxylate dehydrogenase, which is found in tissues throughout the body. Within the cells of these tissues, this enzyme functions in energy-producing structures called mitochondria.Pyrroline-5-carboxylate dehydrogenase starts the second step in the process that breaks down the protein building block (amino acid) proline. This step converts pyrroline-5-carboxylate, which is produced in the first step, to the amino acid glutamate. The conversion of proline to glutamate (and the conversion of glutamate to proline, which is controlled by different enzymes) is important for maintaining a supply of amino acids needed for protein production, and for energy transfer within the cell. Hyperprolinemia https://medlineplus.gov/genetics/condition/hyperprolinemia AL4H1_HUMAN aldehyde dehydrogenase 4 family, member A1 aldehyde dehydrogenase 4A1 ALDH4 mitochondrial delta-1-pyrroline 5-carboxylate dehydrogenase P5C dehydrogenase P5CD P5CDh P5CDhL P5CDhS NCBI Gene 8659 OMIM 606811 2007-06 2021-08-26 ALDH5A1 aldehyde dehydrogenase 5 family member A1 https://medlineplus.gov/genetics/gene/aldh5a1 functionThe ALDH5A1 gene provides instructions for producing the succinic semialdehyde dehydrogenase enzyme. This enzyme is found in the energy-producing centers of cells (mitochondria). Succinic semialdehyde dehydrogenase is involved in the breakdown of a chemical that transmits signals in the brain (neurotransmitter) called gamma-amino butyric acid (GABA). The primary role of GABA is to prevent the brain from being overloaded with too many signals. Once GABA molecules have been released from nerve cells, they are broken down by succinic semialdehyde dehydrogenase and other enzymes. Succinic semialdehyde dehydrogenase deficiency https://medlineplus.gov/genetics/condition/succinic-semialdehyde-dehydrogenase-deficiency aldehyde dehydrogenase 5 family, member A1 aldehyde dehydrogenase 5 family, member A1 (succinate-semialdehyde dehydrogenase) aldehyde dehydrogenase 5A1 mitochondrial succinate semialdehyde dehydrogenase NAD(+)-dependent succinic semialdehyde dehydrogenase SSADH SSDH SSDH_HUMAN NCBI Gene 7915 OMIM 610045 2024-03 2024-03-06 ALDH7A1 aldehyde dehydrogenase 7 family member A1 https://medlineplus.gov/genetics/gene/aldh7a1 functionThe ALDH7A1 gene is a member of the aldehyde dehydrogenase (ALDH) gene family. These genes provide instructions for producing enzymes that alter molecules called aldehydes. The ALDH7A1 gene provides instructions for making an enzyme called α-aminoadipic semialdehyde (α-AASA) dehydrogenase, also known as antiquitin. Within the cell, antiquitin is found in the internal fluid of the cell (cytosol) and in the nucleus. This enzyme is involved in the breakdown of the protein building block (amino acid) lysine in the brain. In one step in the breakdown of lysine to other molecules, antiquitin facilitates the conversion of α-aminoadipic semialdehyde to α-aminoadipate. The breakdown of lysine in the brain is necessary for energy production and to produce other needed molecules. Pyridoxine-dependent epilepsy https://medlineplus.gov/genetics/condition/pyridoxine-dependent-epilepsy AL7A1_HUMAN aldehyde dehydrogenase 7 family, member A1 aldehyde dehydrogenase 7A1 antiquitin antiquitin 1 ATQ1 EPD PDE NCBI Gene 501 OMIM 107323 2008-06 2020-08-18 ALDOB aldolase, fructose-bisphosphate B https://medlineplus.gov/genetics/gene/aldob functionThe ALDOB gene provides instructions for making the aldolase B enzyme. This enzyme is one of a group of three aldolase enzymes that are responsible for breaking down certain molecules in cells throughout the body. Four identical aldolase B enzymes need to be attached (bound) to each other in a four-enzyme unit called a tetramer to work.Aldolase B is found primarily in the liver, but it is also present at lower levels in kidney and intestinal cells. Aldolase B is involved in the breakdown (metabolism) of the simple sugar fructose, which is found mostly in fruits and is used in the body for energy. Aldolase B is responsible for the second step in the metabolism of fructose, which breaks down the molecule fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate. To a lesser degree, aldolase B is also involved in the breakdown of the simple sugar glucose. Hereditary fructose intolerance https://medlineplus.gov/genetics/condition/hereditary-fructose-intolerance ALDB ALDO2 ALDOB_HUMAN aldolase 2 aldolase B, fructose-bisphosphatase aldolase B, fructose-bisphosphate fructose-bisphosphate aldolase B liver-type aldolase NCBI Gene 229 OMIM 612724 2011-06 2023-07-25 ALG1 ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase https://medlineplus.gov/genetics/gene/alg1 functionThe ALG1 gene provides instructions for making an enzyme that is involved in a process called glycosylation. During this process, complex chains of sugar molecules (oligosaccharides) are attached to proteins and fats (lipids). Glycosylation modifies proteins so they can fully perform their functions and modifies lipids so they can help cells interact with each other. Oligosaccharides are made up of many sugar molecules that are attached to one another in a stepwise process, forming a complex chain. The enzyme produced from the ALG1 gene transfers a simple sugar called mannose to growing oligosaccharides at a particular step in the formation of the chain. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or lipid. ALG1-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/alg1-congenital-disorder-of-glycosylation asparagine-linked glycosylation 1 homolog (yeast, beta-1,4-mannosyltransferase) asparagine-linked glycosylation 1, beta-1,4-mannosyltransferase homolog asparagine-linked glycosylation protein 1 homolog beta-1,4 mannosyltransferase beta-1,4-mannosyltransferase chitobiosyldiphosphodolichol beta-mannosyltransferase GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase GDP-mannose-dolichol diphosphochitobiose mannosyltransferase hMat-1 HMAT1 HMT-1 HMT1 mannosyltransferase-1 Mat-1 MT-1 NCBI Gene 56052 OMIM 605907 2016-01 2022-07-05 ALG12 ALG12 alpha-1,6-mannosyltransferase https://medlineplus.gov/genetics/gene/alg12 functionThe ALG12 gene provides instructions for making an enzyme that is involved in a process called glycosylation. During this process, complex chains of sugar molecules (oligosaccharides) are attached to proteins and fats (lipids). Glycosylation modifies proteins so they can fully perform their functions. Oligosaccharides are made up of many sugar molecules that are attached to one another in a stepwise process, forming a complex chain. The enzyme produced from the ALG12 gene transfers a simple sugar called mannose to growing oligosaccharides at a particular step in the formation of the chain. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or lipid. ALG12-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/alg12-congenital-disorder-of-glycosylation asparagine-linked glycosylation 12 homolog (S. cerevisiae, alpha-1,6-mannosyltransferase) asparagine-linked glycosylation 12 homolog (yeast, alpha-1,6-mannosyltransferase) asparagine-linked glycosylation 12, alpha-1,6-mannosyltransferase homolog asparagine-linked glycosylation protein 12 homolog CDG1G dol-P-Man dependent alpha-1,6-mannosyltransferase dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase dolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichol alpha-1,6-mannosyltransferase dolichyl-P-Man:Man(7)GlcNAc(2)-PP-dolichyl-alpha-1,6-mannosyltransferase dolichyl-P-mannose:Man-7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase ECM39 hALG12 mannosyltransferase ALG12 homolog membrane protein SB87 PP14673 NCBI Gene 79087 OMIM 607144 2015-01 2022-07-05 ALG6 ALG6 alpha-1,3-glucosyltransferase https://medlineplus.gov/genetics/gene/alg6 functionThe ALG6 gene provides instructions for making an enzyme that is involved in a process called glycosylation. Glycosylation is a process by which sugar molecules (oligosaccharides) are attached to proteins and fats. Oligosaccharides are made up of many sugar molecules that are attached to one another in a stepwise process forming a complex chain. Glycosylation modifies proteins so they can perform a wider variety of functions. The enzyme produced from the ALG6 gene transfers a simple sugar called glucose to the growing oligosaccharide. Once the correct number of sugar molecules are linked together, the oligosaccharide is attached to a protein or fat. ALG6-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/alg6-congenital-disorder-of-glycosylation asparagine-linked glycosylation 6 homolog (S. cerevisiae, alpha-1,3-glucosyltransferase) asparagine-linked glycosylation 6 homolog (yeast, alpha-1,3-glucosyltransferase) asparagine-linked glycosylation 6, alpha-1,3-glucosyltransferase homolog asparagine-linked glycosylation protein 6 homolog dol-P-Glc:Man(9)GlcNAc(2)-PP-Dol alpha-1,3-glucosyltransferase dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase precursor dolichyl-P-Glc:Man(9)GlcNAc(2)-PP-dolichol alpha- 1->3-glucosyltransferase dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase dolichyl-P-Glc:Man9GlcNAc2-PP-dolichylglucosyltransferase Man(9)GlcNAc(2)-PP-Dol alpha-1,3-glucosyltransferase NCBI Gene 29929 OMIM 604566 2014-05 2022-07-05 ALK ALK receptor tyrosine kinase https://medlineplus.gov/genetics/gene/alk functionThe ALK gene provides instructions for making a protein called ALK receptor tyrosine kinase, which is part of a family of proteins called receptor tyrosine kinases (RTKs). Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The process begins when the kinase is stimulated at the cell surface and then attaches to a similar kinase (dimerizes). After dimerization, the kinase is tagged with a marker called a phosphate group (a cluster of oxygen and phosphorus atoms) in a process called phosphorylation. Phosphorylation turns on (activates) the kinase. The activated kinase is able to transfer a phosphate group to another protein inside the cell, which is activated as a result. The activation continues through a series of proteins in a signaling pathway. These signaling pathways are important in many cellular processes such as cell growth and division (proliferation) or maturation (differentiation).Although the specific function of ALK receptor tyrosine kinase is unknown, it is thought to act early in development to help regulate the proliferation of nerve cells. Neuroblastoma https://medlineplus.gov/genetics/condition/neuroblastoma Lung cancer https://medlineplus.gov/genetics/condition/lung-cancer ALK tyrosine kinase receptor anaplastic lymphoma kinase anaplastic lymphoma receptor tyrosine kinase CD246 CD246 antigen NBLST3 NCBI Gene 238 OMIM 105590 OMIM 211980 2011-03 2020-08-18 ALMS1 ALMS1 centrosome and basal body associated protein https://medlineplus.gov/genetics/gene/alms1 functionThe ALMS1 gene provides instructions for making a protein whose function is unknown. Researchers believe that the protein may play a role in hearing, vision, regulation of body weight, and functions of the heart, kidney, lungs, and liver. It may also affect how the pancreas regulates insulin, a hormone that helps control levels of blood glucose, also called blood sugar.The ALMS1 protein is present in most of the body's tissues, usually at low levels. Within cells, this protein is located in structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules, which are proteins that transport materials in cells and help the cell maintain its shape. The ALMS1 protein is also found at the base of cilia, which are finger-like projections that stick out from the surface of cells. Almost all cells have cilia at some stage of their life cycle. Cilia are involved in cell movement and many different chemical signaling pathways. Based on its location within cells, researchers suggest that the ALMS1 protein might be involved in the organization of microtubules, the transport of various materials, and the normal function of cilia. Alström syndrome https://medlineplus.gov/genetics/condition/alstrom-syndrome ALMS1_HUMAN Alstrom syndrome 1 Alstrom syndrome protein 1 KIAA0328 NCBI Gene 7840 OMIM 606844 2008-08 2023-07-26 ALOX12B arachidonate 12-lipoxygenase, 12R type https://medlineplus.gov/genetics/gene/alox12b functionThe ALOX12B gene provides instructions for making an enzyme called 12R-LOX. This enzyme is part of a family of enzymes called arachidonate lipoxygenases. Most of these enzymes help add an oxygen molecule to a particular fatty acid called arachidonic acid. Arachidonate lipoxygenases add oxygen molecules at different locations on the arachidonic acid molecule, producing a variety of substances called fatty acid hydroperoxides. The fatty acid hydroperoxides are then processed into molecules that play an important role in chemical signaling within cells.Specifically, the 12R-LOX enzyme helps add an oxygen molecule to arachidonic acid to make a substance called 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). 12R-HPETE is later converted to a signaling molecule that is involved in the formation of the layers of fats (lipids) within the outermost layer of the skin (the epidermis). The lipid layers are necessary to prevent water loss (dehydration) through the skin. Nonbullous congenital ichthyosiform erythroderma https://medlineplus.gov/genetics/condition/nonbullous-congenital-ichthyosiform-erythroderma 12R-lipoxygenase 12R-LOX arachidonate 12-lipoxygenase, 12R-type epidermis-type lipoxygenase 12 LX12B_HUMAN NCBI Gene 242 OMIM 603741 2017-07 2020-08-18 ALOXE3 arachidonate epidermal lipoxygenase 3 https://medlineplus.gov/genetics/gene/aloxe3 functionThe ALOXE3 gene provides instructions for making an enzyme called eLOX3. This enzyme is part of a family of enzymes called arachidonate lipoxygenases. Most enzymes in this family help add an oxygen molecule to certain fatty acids to produce substances called fatty acid hydroperoxides.Unlike other lipoxygenases, the eLOX3 enzyme does not act directly on fatty acids. Instead, it is involved in the step following the creation of fatty acid hydroperoxides. The eLOX3 enzyme processes fatty acid hydroperoxides, which are later converted to signaling molecules that are involved in the formation of the layers of fats (lipids) within the outermost layer of the skin (the epidermis). The lipid layers are necessary to prevent water loss (dehydration) through the skin. Nonbullous congenital ichthyosiform erythroderma https://medlineplus.gov/genetics/condition/nonbullous-congenital-ichthyosiform-erythroderma E-LOX e-LOX-3 eLOX3 epidermal lipoxygenase LOXE3_HUMAN NCBI Gene 59344 OMIM 607206 2017-07 2024-09-02 ALPL alkaline phosphatase, biomineralization associated https://medlineplus.gov/genetics/gene/alpl functionThe ALPL gene provides instructions for making an enzyme called tissue-nonspecific alkaline phosphatase (TNSALP). This enzyme plays an important role in the growth and development of bones and teeth. It is also active in many other tissues, particularly in the liver and kidneys. This enzyme acts as a phosphatase, which means that it removes clusters of oxygen and phosphorus atoms (phosphate groups) from other molecules.TNSALP is essential for the process of mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding. Hypophosphatasia https://medlineplus.gov/genetics/condition/hypophosphatasia alkaline phosphatase, liver/bone/kidney alkaline phosphomonoesterase AP-TNAP glycerophosphatase HOPS MGC161443 PPBT_HUMAN tissue non-specific alkaline phosphatase tissue-nonspecific ALP TNALP TNAP TNSALP NCBI Gene 249 OMIM 171760 2007-09 2020-08-18 ALS2 alsin Rho guanine nucleotide exchange factor ALS2 https://medlineplus.gov/genetics/gene/als2 functionThe ALS2 gene provides instructions for making a protein called alsin. Alsin is produced in a wide range of tissues, with highest amounts in the brain. This protein is particularly abundant in motor neurons, the specialized nerve cells in the brain and spinal cord that control the movement of muscles.Alsin turns on (activates) multiple proteins called GTPases that convert a molecule called GTP into another molecule called GDP. GTPases play important roles in cell division, the process by which cells mature to carry out specific functions (differentiation), and the self-destruction of cells (apoptosis). The GTPases play important roles in several cell processes. The GTPases that are activated by alsin are involved in the proper placement of the various proteins and fats that make up the cell membrane, the transport of molecules from the cell membrane to the interior of the cell (endocytosis), and the development of specialized structures called axons and dendrites that project from neurons and are essential for the transmission of nerve impulses. Amyotrophic lateral sclerosis https://medlineplus.gov/genetics/condition/amyotrophic-lateral-sclerosis Juvenile primary lateral sclerosis https://medlineplus.gov/genetics/condition/juvenile-primary-lateral-sclerosis Infantile-onset ascending hereditary spastic paralysis https://medlineplus.gov/genetics/condition/infantile-onset-ascending-hereditary-spastic-paralysis ALS2_HUMAN ALS2CR6 ALSJ amyotrophic lateral sclerosis 2 (juvenile) IAHSP KIAA1563 PLSJ NCBI Gene 57679 OMIM 606352 2016-04 2022-06-17 ALX1 ALX homeobox 1 https://medlineplus.gov/genetics/gene/alx1 functionThe ALX1 gene provides instructions for making a protein that is a member of the homeobox protein family. Homeobox proteins direct the formation of body structures during early embryonic development. The ALX1 protein is necessary for normal development of the head and face, particularly the formation of the eyes, nose, and mouth, which begins around the fourth week of development. The ALX1 protein is a transcription factor, which means that it attaches (binds) to DNA and controls the activity of certain genes. Specifically, the protein controls the activity of genes that regulate cell growth and division (proliferation) and movement (migration), ensuring that cells grow and stop growing at specific times and that they are positioned correctly during development. Anophthalmia/Microphthalmia https://medlineplus.gov/genetics/condition/anophthalmia-microphthalmia Frontonasal dysplasia https://medlineplus.gov/genetics/condition/frontonasal-dysplasia ALX homeobox protein 1 CART-1 CART1 cartilage paired-class homeoprotein 1 epididymis luminal protein 23 FND3 HEL23 NCBI Gene 8092 OMIM 601527 2014-04 2025-09-26 ALX3 ALX homeobox 3 https://medlineplus.gov/genetics/gene/alx3 functionThe ALX3 gene provides instructions for making a protein that is a member of the homeobox protein family. Homeobox proteins direct the formation of body structures during early embryonic development. The ALX3 protein is necessary for normal development of the head and face, particularly the formation of the nose, which begins around the fourth week of development. The ALX3 protein is a transcription factor, which means that it attaches (binds) to DNA and controls the activity of certain genes. Specifically, the protein controls the activity of genes that regulate cell growth and division (proliferation) and movement (migration), ensuring that cells grow and stop growing at specific times and that they are positioned correctly during development. Frontonasal dysplasia https://medlineplus.gov/genetics/condition/frontonasal-dysplasia aristaless-like homeobox 3 FND FND1 frontonasal dysplasia homeobox protein aristaless-like 3 proline-rich transcription factor ALX3 NCBI Gene 257 OMIM 606014 2014-04 2020-08-18 ALX4 ALX homeobox 4 https://medlineplus.gov/genetics/gene/alx4 functionThe ALX4 gene provides instructions for making a member of the homeobox protein family. Homeobox proteins direct the formation of body structures during early embryonic development. The ALX4 protein is necessary for normal development of the head.The ALX4 protein is a transcription factor, which means that it attaches (binds) to DNA and controls the activity of certain genes. Specifically, the protein controls the activity of genes that regulate cell growth and division (proliferation), cell maturation and specialization (differentiation), cell movement (migration), and cell survival. The ALX4 protein also interacts with other transcription factors to help regulate these functions and ensure that cells start and stop growing at specific times and that they are positioned correctly during development. Enlarged parietal foramina https://medlineplus.gov/genetics/condition/enlarged-parietal-foramina Potocki-Shaffer syndrome https://medlineplus.gov/genetics/condition/potocki-shaffer-syndrome Frontonasal dysplasia https://medlineplus.gov/genetics/condition/frontonasal-dysplasia homeodomain transcription factor ALX4 KIAA1788 PFM NCBI Gene 60529 OMIM 605420 2026-04 2026-04-07 AMACR alpha-methylacyl-CoA racemase https://medlineplus.gov/genetics/gene/amacr functionThe AMACR gene provides instructions for making an enzyme called alpha-methylacyl-CoA racemase (AMACR). This enzyme is found in the energy-producing centers in cells (mitochondria) and in cell structures called peroxisomes. Peroxisomes contain a variety of enzymes that break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production (synthesis) of fats (lipids) used in digestion and in the nervous system.In peroxisomes, the AMACR enzyme plays a role in the breakdown of a fatty acid called pristanic acid, which comes from meat and dairy foods in the diet. In mitochondria, AMACR is thought to help further break down the molecules derived from pristanic acid. Alpha-methylacyl-CoA racemase deficiency https://medlineplus.gov/genetics/condition/alpha-methylacyl-coa-racemase-deficiency 2-methylacyl-CoA racemase AMACR_HUMAN AMACRD CBAS4 RACE RM NCBI Gene 23600 OMIM 214950 OMIM 604489 2013-12 2020-08-18 AMELX amelogenin X-linked https://medlineplus.gov/genetics/gene/amelx functionThe AMELX gene provides instructions for making a protein called amelogenin, which is essential for normal tooth development. Amelogenin is involved in the formation of tooth enamel, which is the hard, white material that forms the protective outer layer of each tooth. Enamel is composed mainly of mineral crystals. These microscopic crystals are organized in a way to give enamel strength and durability. Amelogenin acts as a scaffold to separate and support the crystals as they grow. Amelogenin is removed from the developing crystals when it is no longer needed, leaving mature enamel that contains very little protein.The AMELX gene is located on the X chromosome. Males have a single copy of the X chromosome, and thus a single copy of the AMELX gene, in each cell. Females have two copies of the X chromosome, and thus two copies of the AMELX gene, in each cell. However, in females, the X chromosome undergoes a process called X-inactivation. Early in female embryonic development, one of the two X chromosomes is randomly and permanently inactivated in cells other than egg cells. X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Because of this, females also only have one active copy of the AMELX gene in each body cell. Amelogenesis imperfecta https://medlineplus.gov/genetics/condition/amelogenesis-imperfecta AIH1 ALGN AMELX_HUMAN AMG AMGL AMGX NCBI Gene 265 OMIM 300391 2025-12 2025-12-03 AMER1 APC membrane recruitment protein 1 https://medlineplus.gov/genetics/gene/amer1 functionThe AMER1 gene provides instructions for making a protein found in tissues throughout the body where it helps regulate the Wnt signaling pathway, which is a series of chemical signals that affect the way cells and tissues develop. Wnt signaling is important for cell division, attachment of cells to one another (adhesion), cell movement (migration), and many other cell activities. The AMER1 protein can promote cell growth by helping to turn on (activate) the Wnt pathway or prevent cell growth by helping to turn off (repress) the Wnt pathway. When repressing the pathway, the AMER1 protein is acting as a tumor suppressor, which means that it helps prevent cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way. Wilms tumor https://medlineplus.gov/genetics/condition/wilms-tumor adenomatous polyposis coli membrane recruitment 1 FAM123B family with sequence similarity 123B FLJ39827 OSCS protein FAM123B RP11-403E24.2 Wilms tumor gene on the X chromosome protein Wilms tumor on the X WTX NCBI Gene 139285 OMIM 300373 OMIM 300647 2018-09 2021-05-18 AMH anti-Mullerian hormone https://medlineplus.gov/genetics/gene/amh functionThe AMH gene provides instructions for making a protein that is involved in male sex differentiation. During development of male fetuses, the AMH protein is produced and released (secreted) by cells of the testes. The secreted protein attaches (binds) to its receptor, which is found on the surface of Müllerian duct cells. The Müllerian duct, found in both male and female fetuses, is the precursor to the female reproductive organs. Binding of the AMH protein to its receptor induces self-destruction (apoptosis) of the Müllerian duct cells. As a result, the Müllerian duct breaks down (regresses) in males. In females, who do not produce the AMH protein during fetal development, the Müllerian duct becomes the uterus and fallopian tubes. Persistent Müllerian duct syndrome https://medlineplus.gov/genetics/condition/persistent-mullerian-duct-syndrome anti-Muellerian hormone MIF MIS muellerian-inhibiting factor muellerian-inhibiting substance Mullerian inhibiting factor Mullerian inhibiting substance NCBI Gene 268 OMIM 600957 2011-03 2020-08-18 AMHR2 anti-Mullerian hormone receptor type 2 https://medlineplus.gov/genetics/gene/amhr2 functionThe AMHR2 gene provides instructions for making the anti-Müllerian hormone (AMH) receptor type 2, which is involved in male sex differentiation. The AMH receptor type 2 is found on the surface of Müllerian duct cells. The Müllerian duct, found in both male and female fetuses, is the precursor to the female reproductive organs. During development of male fetuses, cells of the testes release a protein called the AMH protein. The AMH protein attaches (binds) to the AMH receptor type 2, which signals self-destruction (apoptosis) of the Müllerian duct cells. As a result, the Müllerian duct breaks down (regresses) in males. In females, who do not produce the AMH protein during fetal development, the Müllerian duct becomes the uterus and fallopian tubes. Persistent Müllerian duct syndrome https://medlineplus.gov/genetics/condition/persistent-mullerian-duct-syndrome AMH type II receptor AMHR AMHR2_HUMAN anti-Muellerian hormone type II receptor anti-Muellerian hormone type-2 receptor anti-Mullerian hormone receptor type II anti-Mullerian hormone receptor, type II MIS type II receptor MISR2 MISRII MRII Mullerian inhibiting substance type II receptor NCBI Gene 269 OMIM 600956 2011-03 2020-08-18 AMN amnion associated transmembrane protein https://medlineplus.gov/genetics/gene/amn functionThe AMN gene provides instructions for making a protein called amnionless that spans the membranes of cells in the intestines and the kidneys. Amnionless helps the body absorb vitamin B12 (also called cobalamin) from food, which is important because the body cannot make this vitamin. Vitamin B12 is essential for the formation of DNA and for the chemical reactions that convert food into energy (energy metabolism). Vitamin B12 also plays a key role in making red blood cells and maintaining the nerve cells in the brain and spinal cord (central nervous system).Amnionless binds to another protein called cubilin to form a complex called the cubam receptor. In the small intestine, cubilin can interact with vitamin B12 while it is anchored to the cell membrane by amnionless.During digestion, vitamin B12 binds to intrinsic factor, which helps the intestines absorb vitamin B12. Vitamin B12 and intrinsic factor then bind to cubilin as they pass through the small intestine. Amnionless helps transfer this whole complex into the intestinal cells. Vitamin B12 is then released into the blood and travels throughout the body. In the kidneys, amnionless and cubilin help return proteins to the bloodstream (reabsorption) that would otherwise be released in the urine. Imerslund-Gräsbeck syndrome https://medlineplus.gov/genetics/condition/imerslund-grasbeck-syndrome amnionless NCBI Gene 81693 OMIM 605799 2026-04 2026-04-09 AMPD1 adenosine monophosphate deaminase 1 https://medlineplus.gov/genetics/gene/ampd1 functionThe AMPD1 gene provides instructions for producing an enzyme called adenosine monophosphate (AMP) deaminase. This enzyme is found in the muscles used for movement (skeletal muscles), where it plays a role in producing energy. Specifically, during physical activity, this enzyme converts a molecule called adenosine monophosphate (AMP) to a molecule called inosine monophosphate (IMP) as part of a process called the purine nucleotide cycle. This cycle reuses molecules called purines, which are a group of building blocks of DNA (nucleotides), its chemical cousin RNA, and molecules such as AMP that serve as energy sources in the cell. As part of the purine nucleotide cycle, AMP deaminase converts AMP to IMP, and as the cycle continues, molecules are produced that the muscle cells can use for energy. Skeletal muscle cells need energy to function and move the body. Adenosine monophosphate deaminase deficiency https://medlineplus.gov/genetics/condition/adenosine-monophosphate-deaminase-deficiency Adenosine monophosphate deaminase-1 (muscle) AMP deaminase AMPD1_HUMAN MAD MADA NCBI Gene 270 OMIM 102770 2008-07 2020-08-18 AMT aminomethyltransferase https://medlineplus.gov/genetics/gene/amt functionThe AMT gene provides instructions for making an enzyme called aminomethyltransferase. This protein is one of four enzymes that work together in a group called the glycine cleavage system. Within cells, this system is active in specialized energy-producing centers called mitochondria.As its name suggests, the glycine cleavage system breaks down a molecule called glycine by cutting (cleaving) it into smaller pieces. Glycine is an amino acid, which is a building block of proteins. This molecule also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. The breakdown of excess glycine when it is no longer needed is necessary for the normal development and function of nerve cells in the brain.The breakdown of glycine by the glycine cleavage system produces a molecule called a methyl group. This molecule is added to and used by a vitamin called folate. Folate is required for many functions in the cell and is important for brain development. Nonketotic hyperglycinemia https://medlineplus.gov/genetics/condition/nonketotic-hyperglycinemia GCE glycine cleavage system protein T NKH NCBI Gene 275 OMIM 238310 2020-05 2020-08-18 ANK1 ankyrin 1 https://medlineplus.gov/genetics/gene/ank1 functionThe ANK1 gene provides instruction for making a protein called ankyrin-1. This protein is primarily active (expressed) in red blood cells, but it is also found in muscle and brain cells. In red blood cells, ankyrin-1 is located at the cell membrane, where it attaches (binds) to other membrane proteins. The binding of membrane proteins to one another maintains the stability and structure of red blood cells but also allows for their flexibility. The proteins allow the cell to change shape without breaking when passing through narrow blood vessels.In muscle and brain cells, ankyrin-1 performs similar functions, binding to other membrane proteins to play a role in cell stability, cell movement, and other cell functions. Hereditary spherocytosis https://medlineplus.gov/genetics/condition/hereditary-spherocytosis ANK ANK-1 ANK1_HUMAN ankyrin 1, erythrocytic ankyrin-1 ankyrin-R erythrocyte ankyrin NCBI Gene 286 OMIM 612641 2010-10 2020-08-18 ANK2 ankyrin 2 https://medlineplus.gov/genetics/gene/ank2 functionThe ANK2 gene provides instructions for making a protein called ankyrin-B. Ankyrin-B is part of a family of ankyrin proteins, which interact with many other types of proteins in cells throughout the body. Ankyrins help organize the cell's structural framework (the cytoskeleton) and link certain proteins that span the cell membrane to this framework. Additionally, ankyrins play key roles in important functions including cell movement (migration) and cell growth and division (proliferation).The ankyrin-B protein is active in many cell types, particularly in the brain and in heart (cardiac) muscle. This protein mainly interacts with ion channels and ion transporters, which are complexes of proteins that move charged atoms (ions) across cell membranes. In the heart, the flow of ions (such as sodium, potassium, and calcium) through ion channels and ion transporters generates the electrical signals that control the heartbeat and maintain a normal heart rhythm. Ankyrin-B ensures these channels and transporters are in their proper locations in the cell membrane so they can regulate the flow of ions into and out of cardiac muscle cells. In addition, ankyrin-B helps ensure that signaling molecules that regulate the activity of ion channels and ion transporters are in the proper location. Ankyrin-B syndrome https://medlineplus.gov/genetics/condition/ankyrin-b-syndrome Autism spectrum disorder https://medlineplus.gov/genetics/condition/autism-spectrum-disorder ANK2_HUMAN ankyrin 2, neuronal ankyrin B ankyrin, brain ankyrin, nonerythroid ankyrin-2, nonerythrocytic brank-2 LQT4 NCBI Gene 287 OMIM 106410 2017-03 2020-08-18 ANKH ANKH inorganic pyrophosphate transport regulator https://medlineplus.gov/genetics/gene/ankh functionThe ANKH gene provides instructions for making a protein that is involved in skeletal development. The ANKH protein plays a role in the development and function of cells that build bones (osteoblasts) and cells that break down bone (osteoclasts). Osteoclasts are involved in bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. In addition, the ANKH protein transports a molecule called pyrophosphate out of cells to the intricate network of proteins that forms in the spaces between cells (extracellular matrix). This extracellular pyrophosphate helps regulate bone formation by preventing mineralization, the process by which minerals such as calcium and phosphorus are deposited in tissues. The ANKH protein may have other, unknown functions. Craniometaphyseal dysplasia https://medlineplus.gov/genetics/condition/craniometaphyseal-dysplasia ANK ANKH_HUMAN ankylosis, progressive homolog (mouse) FLJ27166 HANK MANK progressive ankylosis protein SLC62A1 NCBI Gene 56172 OMIM 118600 OMIM 605145 2018-06 2020-08-18 ANKRD11 ankyrin repeat domain 11 https://medlineplus.gov/genetics/gene/ankrd11 functionThe ANKRD11 gene provides instructions for making a protein called ankyrin repeat domain 11 (ANKRD11). As its name suggests, this protein contains multiple regions called ankyrin domains; proteins with these domains help other proteins interact with each other. The ANKRD11 protein interacts with certain proteins called histone deacetylases, which are important for controlling gene activity. Through these interactions, ANKRD11 affects when genes are turned on and off. For example, ANKRD11 brings together histone deacetylases and other proteins called p160 coactivators. This association regulates the ability of p160 coactivators to turn on gene activity. ANKRD11 may also enhance the activity of a protein called p53, which controls the growth and division (proliferation) and the self-destruction (apoptosis) of cells.The ANKRD11 protein is found in nerve cells (neurons) in the brain. During embryonic development, ANKRD11 helps regulate the proliferation of these cells and development of the brain. Researchers speculate that the protein may also be involved in the ability of neurons to change and adapt over time (plasticity), which is important for learning and memory. ANKRD11 may function in other cells in the body and appears to be involved in normal bone development. KBG syndrome https://medlineplus.gov/genetics/condition/kbg-syndrome ANCO-1 ANCO1 ankyrin repeat domain-containing protein 11 ankyrin repeat-containing cofactor 1 LZ16 nasopharyngeal carcinoma susceptibility protein T13 NCBI Gene 29123 OMIM 611192 2015-01 2025-12-01 ANO5 anoctamin 5 https://medlineplus.gov/genetics/gene/ano5 functionThe ANO5 gene provides instructions for making a protein called anoctamin-5. While the specific function of this protein is not well understood, it belongs to a family of proteins, called anoctamins, that act as chloride channels. Chloride channels, which transport negatively charged chlorine atoms (chloride ions) in and out of cells, play a key role in a cell's ability to generate and transmit electrical signals. Studies suggest that most anoctamin proteins function as chloride channels that are turned on (activated) in the presence of positively charged calcium atoms (calcium ions); these channels are known as calcium-activated chloride channels. The mechanism for this calcium activation is unclear. Anoctamin proteins are also involved in maintaining the membrane that surrounds cells and repairing the membrane if it gets damaged.The anoctamin-5 protein is most abundant in muscles used for movement (skeletal muscles). For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. The regulation of chloride flow within muscle cells plays a role in controlling muscle contraction and relaxation.The anoctamin-5 protein is also found in other cells including heart (cardiac) muscle cells and bone cells. Studies have suggested that the anoctamin-5 protein may be important for the development of muscle and bone before birth. Limb-girdle muscular dystrophy https://medlineplus.gov/genetics/condition/limb-girdle-muscular-dystrophy Miyoshi myopathy https://medlineplus.gov/genetics/condition/miyoshi-myopathy Gnathodiaphyseal dysplasia https://medlineplus.gov/genetics/condition/gnathodiaphyseal-dysplasia ANO5_HUMAN anoctamin-5 GDD1 gnathodiaphyseal dysplasia 1 protein integral membrane protein GDD1 LGMD2L TMEM16E transmembrane protein 16E NCBI Gene 203859 OMIM 608662 2014-12 2025-11-19 ANOS1 anosmin 1 https://medlineplus.gov/genetics/gene/anos1 functionThe ANOS1 gene, also known as KAL1, provides instructions for making a protein called anosmin-1. This protein is involved in development before birth. Anosmin-1 is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. Anosmin-1 is active in many parts of the developing embryo, including the respiratory tract, kidneys, digestive system, and certain regions of the brain.Researchers are working to determine the functions of anosmin-1. They have discovered that, in the developing brain, this protein is involved in the movement (migration) of nerve cells and the outgrowth of axons, which are specialized extensions of nerve cells that transmit nerve impulses. The protein also plays a role in regulating contact between nerve cells (cell adhesion).Anosmin-1 appears to help control the growth and migration of a group of nerve cells that are specialized to process the sense of smell (olfactory neurons). These nerve cells originate in the developing nose and then migrate together to a structure in the front of the brain called the olfactory bulb, which is critical for the perception of odors. Studies suggest that anosmin-1 is also involved in the migration of neurons that produce a hormone called gonadotropin-releasing hormone (GnRH). Like olfactory neurons, GnRH-producing neurons migrate from the developing nose to the front of the brain. GnRH controls the production of several hormones that direct sexual development before birth and during puberty. These hormones are important for the normal function of the ovaries in women and testes in men. Kallmann syndrome https://medlineplus.gov/genetics/condition/kallmann-syndrome adhesion molecule-like X-linked ADMLX anosmin-1 HHA KAL KAL1 KALIG-1 Kallmann syndrome 1 protein Kallmann syndrome protein KALM_HUMAN KMS WFDC19 NCBI Gene 3730 OMIM 300836 2016-12 2020-08-18 ANTXR2 ANTXR cell adhesion molecule 2 https://medlineplus.gov/genetics/gene/antxr2 functionThe ANTXR2 gene provides instructions for making a protein that is found at the surface of many types of cells. The ANTXR2 protein is believed to interact with components of the extracellular matrix, which is the lattice of proteins and other molecules outside the cell. This matrix strengthens and supports connective tissues, such as skin, bone, cartilage, tendons, and ligaments.The ANTXR2 protein is involved in the formation of tiny blood vessels (capillaries). It may also be important for maintaining the structure of basement membranes, which are thin, sheet-like extracellular matrix structures that separate and support cells in many connective tissues. Research suggests that the ANTXR2 protein aids in the breakdown of at least one type of extracellular matrix protein, ensuring the correct balance of proteins is maintained for normal functioning of muscles and connective tissues.The ANTXR2 protein also acts as a receptor for the toxin that causes anthrax, allowing the toxin to attach to cells and trigger disease. Hyaline fibromatosis syndrome https://medlineplus.gov/genetics/condition/hyaline-fibromatosis-syndrome anthrax toxin receptor 2 ANTR2_HUMAN capillary morphogenesis protein 2 CMG-2 CMG2 FLJ31074 ISH JHF MGC111533 MGC45856 NCBI Gene 118429 OMIM 608041 2019-03 2020-08-18 APC APC regulator of Wnt signaling pathway https://medlineplus.gov/genetics/gene/apc functionThe APC gene provides instructions for making the APC protein, which plays a critical role in several cellular processes. The APC protein acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. This protein blocks a chemical signaling pathway known as Wnt signaling. This pathway promotes cell growth and division (proliferation) and controls the activity (expression) of certain genes. The APC protein attaches (binds) to multiple proteins to form a complex that helps to control levels of another protein called beta-catenin. Beta-catenin is a key part of the Wnt pathway, and it helps control many cell functions, including cell proliferation, gene expression, and the process by which cells mature to carry out specific functions (differentiation). When the APC protein complex binds beta-catenin, it helps break the protein down when it is no longer needed.The APC protein also plays a role in regulating cell division. The protein interacts with parts of the cell's structural framework (cytoskeleton) to help with proper cell organization during cell division. This helps ensure that the number of chromosomes in a cell is correct after the cell divides.  Familial adenomatous polyposis https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis Desmoid tumor https://medlineplus.gov/genetics/condition/desmoid-tumor Primary macronodular adrenal hyperplasia https://medlineplus.gov/genetics/condition/primary-macronodular-adrenal-hyperplasia adenomatous polyposis coli APC_HUMAN WNT signaling pathway regulator NCBI Gene 324 OMIM 611731 2025-08 2025-08-26 APOA1 apolipoprotein A1 https://medlineplus.gov/genetics/gene/apoa1 functionThe APOA1 gene provides instructions for making a protein called apolipoprotein A-I (apoA-I). ApoA-I is a component of high-density lipoprotein (HDL). HDL is a molecule that transports cholesterol and certain fats called phospholipids through the bloodstream from the body's tissues to the liver. Once in the liver, cholesterol and phospholipids are redistributed to other tissues or removed from the body.ApoA-I attaches to cell membranes and promotes the movement of cholesterol and phospholipids from inside the cell to the outer surface. Once outside the cell, these substances combine with apoA-I to form HDL. ApoA-I also triggers a reaction called cholesterol esterification that converts cholesterol to a form that can be fully integrated into HDL and transported through the bloodstream.HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. The process of removing excess cholesterol from cells is extremely important for balancing cholesterol levels and maintaining cardiovascular health. Familial HDL deficiency https://medlineplus.gov/genetics/condition/familial-hdl-deficiency apo-AI apoA-I APOA1_HUMAN apolipoprotein A-I NCBI Gene 335 OMIM 105200 OMIM 107680 2012-11 2020-08-18 APOB apolipoprotein B https://medlineplus.gov/genetics/gene/apob functionThe APOB gene provides instructions for making two versions of the apolipoprotein B protein, a short version called apolipoprotein B-48 and a longer version known as apolipoprotein B-100. Both of these proteins are components of lipoproteins, which are particles that carry fats and fat-like substances (such as cholesterol) in the blood.Apolipoprotein B-48 is produced in the intestine, where it is a building block of a type of lipoprotein called a chylomicron. As food is digested after a meal, chylomicrons are formed to carry fat and cholesterol from the intestine into the bloodstream. Chylomicrons are also necessary for the absorption of certain fat-soluble vitamins such as vitamin E and vitamin A.Apolipoprotein B-100, which is produced in the liver, is a component of several other types of lipoproteins. Specifically, this protein is a building block of very low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs). These related molecules all transport fats and cholesterol in the bloodstream.LDLs are the primary carriers of cholesterol in the blood. Apolipoprotein B-100 allows LDLs to attach to specific receptors on the surface of cells, particularly in the liver. Once attached, the receptors transport LDLs into the cell, where they are broken down to release cholesterol. The cholesterol is then used by the cell, stored, or removed from the body. Familial hypercholesterolemia https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia Familial hypobetalipoproteinemia https://medlineplus.gov/genetics/condition/familial-hypobetalipoproteinemia apoB-100 apoB-48 APOB_HUMAN apolipoprotein B (including Ag(x) antigen) NCBI Gene 338 OMIM 107730 2020-01 2025-04-03 APOE apolipoprotein E https://medlineplus.gov/genetics/gene/apoe functionThe APOE gene provides instructions for making a protein called apolipoprotein E. This protein combines with fats (lipids) in the body to form molecules called lipoproteins. Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream. Maintaining normal levels of cholesterol is essential for the prevention of disorders that affect the heart and blood vessels (cardiovascular diseases), including heart attack and stroke.There are at least three slightly different versions (alleles) of the APOE gene. The major alleles are called e2, e3, and e4. The most common allele is e3, which is found in more than half of the general population. Alzheimer disease https://medlineplus.gov/genetics/condition/alzheimers-disease Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration Age-related hearing loss https://medlineplus.gov/genetics/condition/age-related-hearing-loss Dementia with Lewy bodies https://medlineplus.gov/genetics/condition/dementia-with-lewy-bodies Apo-E APOE_HUMAN Apolipoproteins E NCBI Gene 348 OMIM 107741 2018-10 2023-07-18 APP amyloid beta precursor protein https://medlineplus.gov/genetics/gene/app functionThe APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system). Little is known about the function of amyloid precursor protein. Researchers speculate that it may bind to other proteins on the surface of cells or help cells attach to one another. Studies suggest that in the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.Amyloid precursor protein is cut by enzymes to create smaller fragments (peptides), some of which are released outside the cell. Two of these fragments are called soluble amyloid precursor protein (sAPP) and amyloid beta (β) peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of neurons in the brain both before and after birth. The sAPP peptide may also control the function of certain other proteins by turning off (inhibiting) their activity. Amyloid β peptide is likely involved in the ability of neurons to change and adapt over time (plasticity). Other functions of sAPP and amyloid β peptide are under investigation. Alzheimer disease https://medlineplus.gov/genetics/condition/alzheimers-disease Hereditary cerebral amyloid angiopathy https://medlineplus.gov/genetics/condition/hereditary-cerebral-amyloid-angiopathy A4_HUMAN AAA ABETA ABPP AD1 amyloid beta (A4) precursor protein amyloid beta-peptide amyloid beta-protein precursor amyloid precursor protein APPI cerebral vascular amyloid peptide CVAP PN-II PN2 protease nexin 2 protease nexin-II NCBI Gene 351 OMIM 104760 2022-04 2023-07-18 APRT adenine phosphoribosyltransferase https://medlineplus.gov/genetics/gene/aprt functionThe APRT gene provides instructions for making an enzyme called adenine phosphoribosyltransferase (APRT). This enzyme is produced in all cells and is part of the purine salvage pathway, which recycles a group of DNA building blocks (nucleotides) called purines to make other molecules. The APRT enzyme helps to recycle the purine adenine to make a molecule called adenosine monophosphate (AMP). This conversion occurs when AMP is needed as a source of energy for cells. Adenine phosphoribosyltransferase deficiency https://medlineplus.gov/genetics/condition/adenine-phosphoribosyltransferase-deficiency AMP diphosphorylase AMP pyrophosphorylase APRTase APT_HUMAN NCBI Gene 353 OMIM 102600 2012-10 2020-08-18 APTX aprataxin https://medlineplus.gov/genetics/gene/aptx functionThe APTX gene provides instructions for making a protein called aprataxin that is involved in the repair of DNA damage in cells. Aprataxin is located in the nucleus of cells and is produced in various tissues, including the brain, spinal cord, and muscles. Different parts of the aprataxin protein allow the protein to interact with other DNA repair proteins to make repairs. At the site of the damage, aprataxin modifies the broken ends of the DNA strands so they can be joined back together correctly. Ataxia with oculomotor apraxia https://medlineplus.gov/genetics/condition/ataxia-with-oculomotor-apraxia AOA AOA1 APTX_HUMAN ataxia 1, early onset with hypoalbuminemia AXA1 EAOH EOAHA FHA-HIT NCBI Gene 54840 OMIM 606350 2018-06 2020-08-18 AQP2 aquaporin 2 https://medlineplus.gov/genetics/gene/aqp2 functionThe AQP2 gene provides instructions for making a protein called aquaporin 2. This protein forms a channel that carries water molecules across cell membranes. It is found in the kidneys in structures called collecting ducts, which are a series of small tubes that reabsorb water from the kidneys into the bloodstream.The aquaporin 2 water channel plays an essential role in maintaining the body's water balance. The placement of these channels is controlled by a hormone called arginine vasopressin (AVP), which is sometimes also called antidiuretic hormone (ADH). When a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), AVP is released from the brain, where it is produced and stored. This hormone triggers chemical reactions that ultimately insert aquaporin 2 water channels into the membrane of collecting duct cells. These channels allow water to be reabsorbed into the bloodstream, which makes the urine more concentrated. When fluid intake is adequate, less AVP is released, and aquaporin 2 water channels are removed from the membrane of collecting duct cells. At these times, less water is reabsorbed into the bloodstream and the urine is more dilute. Arginine vasopressin resistance https://medlineplus.gov/genetics/condition/arginine-vasopressin-resistance AQP-2 AQP-CD AQP2_HUMAN aquaporin-2 aquaporin-CD water-channel aquaporin 2 WCH-CD NCBI Gene 359 OMIM 107777 2024-08 2024-08-13 AR androgen receptor https://medlineplus.gov/genetics/gene/ar functionThe AR gene provides instructions for making a protein called an androgen receptor. Androgens are hormones (such as testosterone) that are important for normal male sexual development before birth and during puberty. Androgen receptors allow the body to respond appropriately to these hormones.  The receptors are present in many of the body's tissues, where they attach (bind) to androgens. The resulting androgen-receptor complex then binds to DNA and regulates the activity of certain genes that play a role in male sexual development. By turning the genes on or off as necessary, the androgen receptor complex helps direct the development of male sex characteristics. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive.In one region of the AR gene, a DNA segment known as CAG is repeated multiple times. This CAG segment is called a triplet or trinucleotide repeat. In most people, the number of CAG repeats in the AR gene ranges from fewer than 10 to about 36. Spinal and bulbar muscular atrophy https://medlineplus.gov/genetics/condition/spinal-and-bulbar-muscular-atrophy Androgen insensitivity syndrome https://medlineplus.gov/genetics/condition/androgen-insensitivity-syndrome Androgenetic alopecia https://medlineplus.gov/genetics/condition/androgenetic-alopecia Prostate cancer https://medlineplus.gov/genetics/condition/prostate-cancer Polycystic ovary syndrome https://medlineplus.gov/genetics/condition/polycystic-ovary-syndrome AIS ANDR_HUMAN DHTR NR3C4 TFM ICD-10-CM MeSH NCBI Gene 367 OMIM 313700 SNOMED CT 2024-04 2024-04-01 ARFGEF2 ARF guanine nucleotide exchange factor 2 https://medlineplus.gov/genetics/gene/arfgef2 functionThe ARFGEF2 gene provides instructions for making a protein that helps with the movement (trafficking) of small sac-like structures (vesicles) within the cell. The ARFGEF2 protein converts a molecule called guanine diphosphate (GDP) to another molecule called guanine triphosphate (GTP). This reaction activates an ADP-ribosylation factor, a molecule that is involved in vesicle trafficking. Vesicles transport many types of molecules from the interior of the cell to its surface, where they may attach and interact with other substances, or be secreted by the cell. Periventricular heterotopia https://medlineplus.gov/genetics/condition/periventricular-heterotopia ADP-ribosylation factor guanine nucleotide-exchange factor 2 BIG2 BIG2_HUMAN brefeldin A-inhibited guanine nucleotide-exchange protein 2 NCBI Gene 10564 OMIM 605371 2007-11 2024-10-01 ARG1 arginase 1 https://medlineplus.gov/genetics/gene/arg1 functionThe ARG1 gene provides instructions for producing the enzyme arginase. This enzyme participates in the urea cycle, a series of reactions that occurs in liver cells. The urea cycle processes excess nitrogen, which is generated when proteins and their building blocks (amino acids) are used by the body. The urea cycle produces a compound called urea from excess nitrogen. Urea is then excreted by the kidneys. Excreting the excess nitrogen prevents it from accumulating in the form of ammonia, which is toxic.Arginase facilitates the last step of the urea cycle, a reaction in which nitrogen is removed from the amino acid arginine and processed into urea. A compound called ornithine is also produced during this reaction; it is needed for the urea cycle to repeat. Arginase deficiency https://medlineplus.gov/genetics/condition/arginase-deficiency A-I ARGI1_HUMAN arginase, liver arginase, type I NCBI Gene 383 OMIM 608313 2024-02 2024-02-14 ARHGAP31 Rho GTPase activating protein 31 https://medlineplus.gov/genetics/gene/arhgap31 functionThe ARHGAP31 gene provides instructions for making a protein classified as a Rho GTPase activating protein (GAP). GAPs turn off (inactivate) proteins called GTPases, which play an important role in chemical signaling within cells. Often referred to as molecular switches, GTPases can be turned on and off. They are turned on (active) when they are attached (bound) to a molecule called GTP and are turned off when they are bound to another molecule called GDP. The ARHGAP31 protein inactivates GTPases known as Cdc42 and Rac1 by stimulating a reaction that turns the attached GTP into GDP. When active, Cdc42 and Rac1 transmit signals that are critical for various aspects of embryonic development. The ARHGAP31 protein appears to regulate these GTPases specifically during development of the limbs, skull, and heart. Adams-Oliver syndrome https://medlineplus.gov/genetics/condition/adams-oliver-syndrome AOS1 Cdc42 GTPase-activating protein CDGAP RHG31_HUMAN rho GTPase-activating protein 31 NCBI Gene 57514 OMIM 610911 2015-11 2020-08-18 ARID1A AT-rich interaction domain 1A https://medlineplus.gov/genetics/gene/arid1a functionThe ARID1A gene provides instructions for making a protein that forms one piece (subunit) of several different SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed.Through their ability to regulate gene activity, SWI/SNF complexes are involved in many processes, including repairing damaged DNA; copying (replicating) DNA; and controlling the growth, division, and maturation (differentiation) of cells. The ARID1A protein and other SWI/SNF subunits are thought to act as tumor suppressors, which keep cells from growing and dividing too rapidly or in an uncontrolled way.The ARID1A subunit is able to attach (bind) to DNA and is thought to help target SWI/SNF complexes to the chromatin location that needs to be remodeled. Bladder cancer https://medlineplus.gov/genetics/condition/bladder-cancer Coffin-Siris syndrome https://medlineplus.gov/genetics/condition/coffin-siris-syndrome Cholangiocarcinoma https://medlineplus.gov/genetics/condition/cholangiocarcinoma ARI1A_HUMAN ARID domain-containing protein 1A AT rich interactive domain 1A (SWI-like) AT-rich interactive domain-containing protein 1A B120 BAF250 BAF250a BM029 brain protein 120 BRG1-associated factor 250a C1orf4 chromatin remodeling factor p250 ELD hELD hOSA1 MRD14 osa homolog 1 OSA1 OSA1 nuclear protein P270 SMARCF1 SWI-like protein SWI/SNF complex protein p270 SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily F member 1 NCBI Gene 8289 OMIM 603024 2013-05 2021-08-30 ARID1B AT-rich interaction domain 1B https://medlineplus.gov/genetics/gene/arid1b functionThe ARID1B gene provides instructions for making a protein that forms one piece (subunit) of several different SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed.Through their ability to regulate gene activity, SWI/SNF complexes are involved in many processes, including repairing damaged DNA; copying (replicating) DNA; and controlling the growth, division, and maturation (differentiation) of cells. The ARID1B protein and other SWI/SNF subunits are thought to act as tumor suppressors, which keep cells from growing and dividing too rapidly or in an uncontrolled way.The ARID1B subunit is able to attach (bind) to DNA and is thought to help target SWI/SNF complexes to the chromatin location that needs to be remodeled. Coffin-Siris syndrome https://medlineplus.gov/genetics/condition/coffin-siris-syndrome Autism spectrum disorder https://medlineplus.gov/genetics/condition/autism-spectrum-disorder 6A3-5 ARI1B_HUMAN ARID domain-containing protein 1B AT rich interactive domain 1B (SWI1-like) AT-rich interactive domain-containing protein 1B BAF250B BRG1-associated factor 250b BRG1-binding protein ELD/OSA1 BRIGHT DAN15 ELD (eyelid)/OSA protein ELD/OSA1 KIAA1235 MRD12 OSA2 P250R NCBI Gene 57492 OMIM 614556 2017-06 2023-03-07 ARMC5 armadillo repeat containing 5 https://medlineplus.gov/genetics/gene/armc5 functionThe ARMC5 gene provides instructions for making a protein about which little is known. It is found mainly in the fluid surrounding the cell nucleus (cytoplasm), and studies suggest that its function depends on interacting with other proteins. It is thought to act as a tumor suppressor, which means that it helps to prevent cells from growing and dividing too rapidly or in an uncontrolled way. Primary macronodular adrenal hyperplasia https://medlineplus.gov/genetics/condition/primary-macronodular-adrenal-hyperplasia FLJ13063 NCBI Gene 79798 OMIM 615549 2015-05 2023-07-26 ARMS2 age-related maculopathy susceptibility 2 https://medlineplus.gov/genetics/gene/arms2 functionThe ARMS2 gene provides instructions for making a protein whose function is unknown. Studies suggest that the ARMS2 protein is found primarily in the placenta and in the specialized light-sensing tissue in the back of the eye (the retina). However, it is unclear what role, if any, the protein plays in early development or normal vision. Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration age-related maculopathy susceptibility protein 2 ARMD8 ARMS2_HUMAN LOC387715 NCBI Gene 387715 OMIM 611313 2011-06 2025-04-03 ARSA arylsulfatase A https://medlineplus.gov/genetics/gene/arsa functionThe ARSA gene provides instructions for making the enzyme arylsulfatase A. This enzyme is located in cellular structures called lysosomes, which are the cell's recycling centers. Within lysosomes, arylsulfatase A helps process substances known as sulfatides. Sulfatides are a subgroup of sphingolipids, a category of fats that are important components of cell membranes. Sulfatides are abundant in the nervous system's white matter, consisting of nerve fibers covered by myelin. Myelin, made up of multiple layers of membranes, insulates and protects nerves. Metachromatic leukodystrophy https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy ARSA_HUMAN cerebroside 3-sulfatase Cerebroside-3-sulfate 3-sulfohydrolase Cerebroside-Sulfatase MLD sulfatidase NCBI Gene 410 OMIM 607574 2007-09 2020-08-18 ARSB arylsulfatase B https://medlineplus.gov/genetics/gene/arsb functionThe ARSB gene provides instructions for producing an enzyme called arylsulfatase B, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). Specifically, arylsulfatase B removes a chemical group known as a sulfate from two GAGs called dermatan sulfate and chondroitin sulfate. Arylsulfatase B is located in lysosomes, compartments within cells that digest and recycle different types of molecules. Mucopolysaccharidosis type VI https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-vi ARSB_HUMAN arylsulfatase B isoform 1 precursor ASB chondroitinase chondroitinsulfatase G4S MPS6 N-acetylgalactosamine 4-sulfate sulfohydrolase N-acetylgalactosamine-4-sulfatase NCBI Gene 411 OMIM 611542 2010-06 2020-08-18 ARSL arylsulfatase L https://medlineplus.gov/genetics/gene/arsl functionThe ARSL gene provides instructions for making an enzyme called arylsulfatase L. This enzyme is part of a group known as sulfatases, which are enzymes that help process molecules that contain chemical groups known as sulfates. Sulfatases play important roles in cartilage and bone development.Within cells, arylsulfatase L is located in the Golgi apparatus, a structure that modifies newly produced enzymes and other proteins. The function of this enzyme is unknown, although researchers believe it participates in a chemical pathway involving vitamin K. Evidence suggests that vitamin K normally plays a role in bone growth and maintenance of bone density. X-linked chondrodysplasia punctata 1 https://medlineplus.gov/genetics/condition/x-linked-chondrodysplasia-punctata-1 ARSE ARSE_HUMAN arylsulfatase E CDPX CDPX1 CDPXR MGC163310 ICD-10-CM MeSH NCBI Gene 415 OMIM 300180 SNOMED CT 2011-11 2022-07-01 ARX aristaless related homeobox https://medlineplus.gov/genetics/gene/arx functionThe ARX gene provides instructions for producing a protein that regulates the activity of other genes. On the basis of this action, the ARX protein is called a transcription factor. The ARX gene is part of a larger family of homeobox genes, which act during early embryonic development to control the formation of many body structures. Specifically, the ARX protein is believed to be involved in the development of the brain, pancreas, testes, and muscles used for movement (skeletal muscles).In the pancreas, testes, and skeletal muscles, the ARX protein helps to regulate the process by which cells mature to carry out specific functions (differentiation). Within the developing brain, the ARX protein is involved with movement (migration) and communication of nerve cells (neurons). In particular, this protein regulates genes that play a role in the migration of specialized neurons (interneurons) to their proper location. Interneurons relay signals between other neurons. X-linked lissencephaly with abnormal genitalia https://medlineplus.gov/genetics/condition/x-linked-lissencephaly-with-abnormal-genitalia Early infantile epileptic encephalopathy 1 https://medlineplus.gov/genetics/condition/developmental-and-epileptic-encephalopathy-1 Partington syndrome https://medlineplus.gov/genetics/condition/partington-syndrome aristaless-related homeobox, X-linked ARX_HUMAN ISSX MRX29 MRX32 MRX33 MRX36 MRX38 MRX43 MRX54 MRXS1 PRTS NCBI Gene 170302 OMIM 300004 OMIM 300382 OMIM 300419 OMIM 308350 2017-11 2020-11-13 ASAH1 N-acylsphingosine amidohydrolase 1 https://medlineplus.gov/genetics/gene/asah1 functionThe ASAH1 gene provides instructions for making an enzyme called acid ceramidase. This enzyme is found in lysosomes, which are cell compartments that digest and recycle materials. Within lysosomes, acid ceramidase breaks down fats (lipids) called ceramides. Ceramides are typically found within the membranes that surround cells and play a role in regulating cell maturation (differentiation), growth and division of cells (proliferation), and controlled cell death (apoptosis). Additionally, ceramides are a component of a fatty substance called myelin that insulates and protects nerve cells. Ceramides also serve as building blocks for more complex lipids. When ceramides need to be replaced, they travel to lysosomes where acid ceramidase breaks them down into a fat called sphingosine and a fatty acid. These two breakdown products are recycled to create new ceramides for the body to use. Farber lipogranulomatosis https://medlineplus.gov/genetics/condition/farber-lipogranulomatosis Spinal muscular atrophy with progressive myoclonic epilepsy https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy AC ACDase acylsphingosine deacylase ASAH ASAH1_HUMAN FLJ21558 FLJ22079 N-acylsphingosine amidohydrolase (acid ceramidase) 1 PHP PHP32 NCBI Gene 427 OMIM 613468 2013-12 2021-11-10 ASH1L ASH1 like histone lysine methyltransferase https://medlineplus.gov/genetics/gene/ash1l functionThe ASH1L gene, also known as KMT2H, provides instructions for making an enzyme, called lysine-specific methyltransferase 2H, that is found in many organs and tissues of the body. Lysine-specific methyltransferase 2H functions as a histone methyltransferase. Histone methyltransferases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (a process called methylation), histone methyltransferases control (regulate) the activity of certain genes. Lysine-specific methyltransferase 2H appears to turn on (activate) certain genes that are especially important for development of the brain. Autism spectrum disorder https://medlineplus.gov/genetics/condition/autism-spectrum-disorder absent small and homeotic disks protein 1 homolog ASH1 ash1 (absent, small, or homeotic)-like ASH1-like protein ASH1L1 histone-lysine N-methyltransferase ASH1L huASH1 KMT2H lysine N-methyltransferase 2H probable histone-lysine N-methyltransferase ASH1L NCBI Gene 55870 OMIM 607999 2017-06 2020-08-18 ASL argininosuccinate lyase https://medlineplus.gov/genetics/gene/asl functionThe ASL gene provides instructions for making the enzyme argininosuccinate lyase. This enzyme primarily participates in the urea cycle, a series of reactions that occur in liver cells. The urea cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. Excreting the excess nitrogen prevents it from accumulating in the form of ammonia.The specific role of the argininosuccinate lyase enzyme is to start the reaction in which the amino acid arginine, a building block of proteins, is produced from argininosuccinate, the molecule that carries the waste nitrogen collected earlier in the urea cycle. The arginine is later broken down into urea, which is excreted, and ornithine, which restarts the urea cycle.In cells throughout the body, the argininosuccinate lyase enzyme is also involved in moving (transporting) arginine into cells to make a compound called nitric oxide. Nitric oxide is important for regulating blood flow and blood pressure. Argininosuccinic aciduria https://medlineplus.gov/genetics/condition/argininosuccinic-aciduria Argininosuccinase Arginosuccinase arginosuccinate lyase ARLY_HUMAN NCBI Gene 435 OMIM 608310 2020-03 2020-08-18 ASNS asparagine synthetase (glutamine-hydrolyzing) https://medlineplus.gov/genetics/gene/asns functionThe ASNS gene provides instructions for making an enzyme called asparagine synthetase. This enzyme is found in cells throughout the body, where it converts the protein building block (amino acid) aspartic acid to the amino acid asparagine. Another amino acid called glutamine helps in the conversion and is itself converted to the amino acid glutamic acid during the process. It is thought that asparagine synthetase helps to maintain the normal balance of these four amino acids in the body.Asparagine is needed to produce many proteins but also plays other roles. Asparagine helps to break down toxic ammonia within cells, is important for protein modification, and is needed for making a certain molecule that transmits signals in the brain (a neurotransmitter).Although asparagine can be obtained through the diet, the amino acid cannot cross the protective barrier that allows only certain substances to pass between blood vessels and the brain (the blood-brain barrier). As a result, brain cells rely solely on asparagine synthetase to produce asparagine. Asparagine synthetase deficiency https://medlineplus.gov/genetics/condition/asparagine-synthetase-deficiency aspartate ammonia ligase glutamine-dependent asparagine synthetase TS11 TS11 cell cycle control protein NCBI Gene 440 OMIM 108370 2018-11 2020-08-18 ASPA aspartoacylase https://medlineplus.gov/genetics/gene/aspa functionThe ASPA gene provides instructions for making an enzyme called aspartoacylase. In the brain, this enzyme breaks down a compound called N-acetyl-L-aspartic acid (NAA) into aspartic acid (an amino acid that is a building block of many proteins) and another molecule called acetic acid.The production and breakdown of NAA appears to be critical for maintaining the brain's white matter, which consists of nerve fibers surrounded by a myelin sheath. The myelin sheath is the covering that protects nerve fibers and promotes the efficient transmission of nerve impulses. The precise function of NAA is unclear. Researchers had suspected that it played a role in the production of the myelin sheath, but recent studies suggest that NAA does not have this function. The enzyme may instead be involved in the transport of water molecules out of nerve cells (neurons). Canavan disease https://medlineplus.gov/genetics/condition/canavan-disease ACY2 ACY2_HUMAN aminoacylase 2 aminoacylase II ASP N-acyl-L-aspartate amidohydrolase NCBI Gene 443 OMIM 608034 2015-04 2025-04-03 ASPM assembly factor for spindle microtubules https://medlineplus.gov/genetics/gene/aspm functionThe ASPM gene provides instructions for making a protein that is involved in cell division. This protein is found in cells and tissues throughout the body; however, it appears to be particularly important for the division of cells in the developing brain. Studies suggest that the ASPM protein helps maintain the orderly division of early brain cells called neural progenitor cells, which ultimately give rise to mature nerve cells (neurons). By promoting the division of neural progenitor cells during early brain development, the ASPM protein helps determine the total number of neurons and the overall size of the brain. Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration Autosomal recessive primary microcephaly https://medlineplus.gov/genetics/condition/autosomal-recessive-primary-microcephaly abnormal spindle-like microcephaly-associated protein ASP asp (abnormal spindle) homolog, microcephaly associated (Drosophila) ASPM_HUMAN Calmbp1 FLJ10517 FLJ10549 FLJ43117 MCPH5 NCBI Gene 259266 OMIM 605481 2011-04 2022-07-01 ASS1 argininosuccinate synthase 1 https://medlineplus.gov/genetics/gene/ass1 functionThe ASS1 gene provides instructions for making an enzyme called argininosuccinate synthase 1. This enzyme participates in the urea cycle, which is a sequence of chemical reactions that takes place in liver cells. The urea cycle processes excess nitrogen that is generated as the body breaks down proteins. The excess nitrogen is used to make a compound called urea, which is excreted from the body in urine.Argininosuccinate synthase 1 is involved in the third step of the urea cycle. This step combines two protein building blocks (amino acids), citrulline and aspartate, to form a molecule called argininosuccinic acid. A series of additional chemical reactions uses argininosuccinic acid to form urea. Citrullinemia https://medlineplus.gov/genetics/condition/citrullinemia argininosuccinate synthetase 1 ASS ASSY_HUMAN Citrulline-aspartate ligase CTLN1 NCBI Gene 445 OMIM 603470 2017-05 2020-08-18 ASXL1 ASXL transcriptional regulator 1 https://medlineplus.gov/genetics/gene/asxl1 functionThe ASXL1 gene provides instructions for making a protein that is involved in a process known as chromatin remodeling. Chromatin is the complex of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. When DNA is tightly packed, gene activity (expression) is lower than when DNA is loosely packed.Through its role in chromatin remodeling, the ASXL1 protein regulates the expression of many genes, including a group of genes known as HOX genes, which play important roles in development before birth. The ASXL1 protein can turn on (activate) or turn off (repress) HOX genes depending on when they are needed.The ASXL1 protein may have an additional role in gene regulation by signaling to molecules to add a methyl group (a process called methylation) to an area near a gene called the promoter region, which controls gene activity. When a promoter region is methylated, gene activity is repressed, and when a promoter region is not methylated, the gene is active. Bohring-Opitz syndrome https://medlineplus.gov/genetics/condition/bohring-opitz-syndrome Systemic mastocytosis https://medlineplus.gov/genetics/condition/systemic-mastocytosis additional sex combs like 1 additional sex combs like 1, transcriptional regulator additional sex combs like transcriptional regulator 1 KIAA0978 putative Polycomb group protein ASXL1 isoform 1 putative Polycomb group protein ASXL1 isoform 2 NCBI Gene 171023 OMIM 612990 2018-07 2020-08-18 ATG16L1 autophagy related 16 like 1 https://medlineplus.gov/genetics/gene/atg16l1 functionThe ATG16L1 gene provides instructions for making a protein that is required for a process called autophagy. Cells use this process to recycle worn-out cell parts and break down certain proteins when they are no longer needed. Autophagy also plays an important role in controlled cell death (apoptosis). Additionally, autophagy is involved in the body's inflammatory response and helps the immune system destroy some types of harmful bacteria and viruses. Crohn disease https://medlineplus.gov/genetics/condition/crohns-disease APG16 autophagy 16-like APG16L ATG16 autophagy related 16-like 1 (S. cerevisiae) ATG16 autophagy related 16-like protein 1 ATG16A ATG16L Autophagy 16-like 1 autophagy related 16-like 1 autophagy related 16-like 1 (S. cerevisiae) WD repeat domain 30 WDR30 NCBI Gene 55054 OMIM 610767 2017-12 2023-07-17 ATL1 atlastin GTPase 1 https://medlineplus.gov/genetics/gene/atl1 functionThe ATL1 gene provides instructions for producing a protein called atlastin-1. Atlastin-1 is produced primarily in the brain and spinal cord (central nervous system), particularly in nerve cells (neurons) that extend down the spinal cord (corticospinal tracts). These neurons send electrical signals that lead to voluntary muscle movement. In neurons, this protein is found mainly in the endoplasmic reticulum, which is a structure involved in protein processing and distribution. Atlastin-1 fuses together the network of tubules that make up the structure of the endoplasmic reticulum. Atlastin-1 is also active in compartments called axonal growth cones, which are located at the tip of neurons. The axonal growth cones direct the growth of specialized extensions, called axons, which transmit nerve impulses that signal muscle movement. Within axonal growth cones, atlastin-1 acts during development to help guide the growth of axons. Spastic paraplegia type 3A https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-3a AD-FSP ATLA1_HUMAN atlastin atlastin1 FSP1 GBP3 guanylate-binding protein 3 NCBI Gene 51062 OMIM 606439 OMIM 613708 2015-03 2020-08-18 ATM ATM serine/threonine kinase https://medlineplus.gov/genetics/gene/atm functionThe ATM gene provides instructions for making a protein that is located primarily in the nucleus of cells, where it helps control the rate at which cells grow and divide. This protein also plays an important role in the normal development and activity of several body systems, including the nervous system and the immune system. Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. DNA can be damaged by agents such as toxic chemicals or radiation. Breaks in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information.Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. Bladder cancer https://medlineplus.gov/genetics/condition/bladder-cancer Breast cancer https://medlineplus.gov/genetics/condition/breast-cancer Ataxia-telangiectasia https://medlineplus.gov/genetics/condition/ataxia-telangiectasia Melanoma https://medlineplus.gov/genetics/condition/melanoma AT mutated AT protein AT1 ATA ataxia telangiectasia mutated ATM_HUMAN human phosphatidylinositol 3-kinase homolog serine-protein kinase ATM TEL1 TELO1 ICD-10-CM MeSH NCBI Gene 472 OMIM 607585 SNOMED CT 2022-09 2022-09-19 ATN1 atrophin 1 https://medlineplus.gov/genetics/gene/atn1 functionThe ATN1 gene provides instructions for making a protein called atrophin 1. Although the exact function of this protein is unknown, it appears to play an important role in nerve cells (neurons) in many areas of the brain. Researchers speculate that atrophin 1 may act as a transcriptional co-repressor. A transcriptional co-repressor is a protein that interacts with other DNA-binding proteins to suppress the activity of certain genes, although it cannot attach (bind) to DNA by itself.One region of the ATN1 gene contains a particular DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. In most people, the number of CAG repeats in the ATN1 gene ranges from 6 to 35. Dentatorubral-pallidoluysian atrophy https://medlineplus.gov/genetics/condition/dentatorubral-pallidoluysian-atrophy ATN1_HUMAN atrophin-1 B37 D12S755E dentatorubral-pallidoluysian atrophy protein DRPLA NOD NCBI Gene 1822 OMIM 607462 2023-12 2023-12-05 ATP1A1 ATPase Na+/K+ transporting subunit alpha 1 https://medlineplus.gov/genetics/gene/atp1a1 functionThe ATP1A1 gene provides instructions for making one part (the alpha-1 subunit) of a protein pump known as a Na+/K+ ATPase. This protein uses energy from a molecule called adenosine triphosphate (ATP) to transport charged atoms (ions) into and out of cells. Specifically, the protein pumps sodium ions (Na+) out of cells and potassium ions (K+) into cells.Na+/K+ ATPases that include the alpha-1 subunit are found in many types of cells, although the pumps appear to play a particularly important role in the adrenal glands, which are small hormone-producing glands located on top of each kidney. In the adrenal glands, the flow of sodium and potassium ions helps regulate the production of the hormone aldosterone, which controls blood pressure by maintaining proper salt and fluid levels in the body. Charcot-Marie-Tooth disease https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease Aldosterone-producing adenoma https://medlineplus.gov/genetics/condition/aldosterone-producing-adenoma ATPase, Na+/K+ transporting, alpha 1 polypeptide Na(+)/K(+) ATPase alpha-1 subunit Na+/K+ ATPase 1 Na, K-ATPase, alpha-A catalytic polypeptide Na,K-ATPase alpha-1 subunit Na,K-ATPase catalytic subunit alpha-A protein sodium pump subunit alpha-1 sodium-potassium ATPase catalytic subunit alpha-1 sodium-potassium-ATPase, alpha 1 polypeptide NCBI Gene 476 OMIM 182310 2017-07 2023-03-07 ATP1A2 ATPase Na+/K+ transporting subunit alpha 2 https://medlineplus.gov/genetics/gene/atp1a2 functionThe ATP1A2 gene provides instructions for making one part (the alpha-2 subunit) of a protein known as a Na+/K+ ATPase. This protein uses energy from a molecule called adenosine triphosphate (ATP) to transport charged atoms (ions) into and out of cells. Specifically, it pumps sodium ions (Na+) out of cells and potassium ions (K+) into cells.Na+/K+ ATPases that include the alpha-2 subunit are primarily found in nervous system cells called glia, which protect and maintain nerve cells (neurons). Through its action in glia, the protein plays a critical role in the normal function of neurons. Communication between neurons depends on chemicals called neurotransmitters. To relay signals, a neuron releases neurotransmitters, which attach to receptor proteins on neighboring neurons. After the neurotransmitters have had their effect, they detach from their receptors and are removed from the spaces between neurons by glia. This process is carefully regulated to ensure that signals are transmitted accurately throughout the nervous system. The Na+/K+ ATPase helps regulate this process by stimulating glia to clear neurotransmitters from the spaces between neurons. This protein also removes excess potassium ions from these spaces. Familial hemiplegic migraine https://medlineplus.gov/genetics/condition/familial-hemiplegic-migraine Alternating hemiplegia of childhood https://medlineplus.gov/genetics/condition/alternating-hemiplegia-of-childhood Sporadic hemiplegic migraine https://medlineplus.gov/genetics/condition/sporadic-hemiplegic-migraine AT1A2_HUMAN ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide ATPase, Na+/K+ transporting, alpha 2 polypeptide FHM2 MHP2 Na+/K+ -ATPase alpha 2 subunit proprotein Na+/K+ ATPase 2 Na+/K+ ATPase, alpha-A(+) catalytic polypeptide Na+/K+ ATPase, alpha-B polypeptide sodium pump 2 sodium pump subunit alpha-2 sodium-potassium ATPase sodium/potassium-transporting ATPase alpha-2 chain NCBI Gene 477 OMIM 182340 2014-02 2023-03-07 ATP1A3 ATPase Na+/K+ transporting subunit alpha 3 https://medlineplus.gov/genetics/gene/atp1a3 functionThe ATP1A3 gene provides instructions for making one part (the alpha-3 subunit) of a protein known as Na+/K+ ATPase or the sodium pump. This protein uses energy from a molecule called adenosine triphosphate (ATP) to transport charged atoms (ions) into and out of cells. Specifically, it pumps sodium ions (Na+) out of cells and potassium ions (K+) into cells.Na+/K+ ATPases that include the alpha-3 subunit are critical for normal function of nerve cells in the brain (neurons). The movement of sodium and potassium ions helps regulate the electrical activity of these cells and plays an important role in the signaling process that controls muscle movement. The activity of Na+/K+ ATPase also helps regulate cell size (volume).Additionally, Na+/K+ ATPase helps regulate a process called neurotransmitter reuptake. Neurotransmitters are chemical messengers that transmit signals from one neuron to another. After a neurotransmitter has had its effect, it must be removed quickly from the space between the neurons. The reuptake of neurotransmitters is carefully controlled to ensure that signals are sent and received accurately throughout the nervous system. Rapid-onset dystonia parkinsonism https://medlineplus.gov/genetics/condition/rapid-onset-dystonia-parkinsonism Alternating hemiplegia of childhood https://medlineplus.gov/genetics/condition/alternating-hemiplegia-of-childhood AT1A3_HUMAN ATPase, Na+/K+ transporting, alpha 3 polypeptide Na+/K+ -ATPase alpha 3 subunit Na+/K+ ATPase 3 sodium pump 3 sodium-potassium-ATPase, alpha 3 polypeptide sodium/potassium-transporting ATPase alpha-3 chain ICD-10-CM MeSH NCBI Gene 478 OMIM 182350 SNOMED CT 2024-04 2024-04-23 ATP2A1 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 https://medlineplus.gov/genetics/gene/atp2a1 functionThe ATP2A1 gene provides instructions for making an enzyme called sarco(endo)plasmic reticulum calcium-ATPase 1 (SERCA1). This enzyme belongs to a family of ATPase enzymes that help control the level of positively charged calcium atoms (calcium ions) inside cells. The SERCA1 enzyme is found in skeletal muscle cells. (Skeletal muscles are the muscles used for movement.) Within muscle cells, the SERCA1 enzyme is located in the membrane of a structure called the sarcoplasmic reticulum. This structure plays a major role in muscle contraction and relaxation by storing and releasing calcium ions. When calcium ions are transported out of the sarcoplasmic reticulum, muscles contract; when calcium ions are transported into the sarcoplasmic reticulum, muscles relax. The SERCA1 enzyme transports calcium ions from the cell into the sarcoplasmic reticulum, triggering muscle relaxation. Brody myopathy https://medlineplus.gov/genetics/condition/brody-myopathy AT2A1_HUMAN ATP2A ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform 1 endoplasmic reticulum class 1 Ca2+ ATPase sarcoplasmic/endoplasmic reticulum calcium ATPase 1 SERCA1 SR Ca2+ ATPase 1 NCBI Gene 487 OMIM 108730 2012-01 2020-08-18 ATP2A2 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 https://medlineplus.gov/genetics/gene/atp2a2 functionThe ATP2A2 gene provides instructions for making an enzyme called sarco(endo)plasmic reticulum calcium-ATPase 2 (SERCA2). This enzyme belongs to a family of ATPase enzymes that helps control the level of positively charged calcium atoms (calcium ions) inside cells. SERCA2 is found in the endoplasmic reticulum inside the cell and in a related structure called the sarcoplasmic reticulum inside muscle cells. The endoplasmic reticulum is a structure that is involved in protein processing and transport. The sarcoplasmic reticulum assists with muscle contraction and relaxation by releasing and storing calcium ions. Calcium ions act as signals for a large number of activities that are important for the normal development and function of cells.  SERCA2 allows calcium ions to pass into and out of the cell in response to cell signals. Darier disease https://medlineplus.gov/genetics/condition/darier-disease AT2A2_HUMAN ATP2B ATPase, Ca++ dependent, slow-twitch, cardiac muscle-2 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform sarcoplasmic reticulum Ca(2+)-ATPase 2 sarcoplasmic/endoplasmic reticulum calcium ATPase 2 SERCA2 SR Ca(2+)-ATPase 2 NCBI Gene 488 OMIM 108740 2024-01 2024-01-15 ATP2C1 ATPase secretory pathway Ca2+ transporting 1 https://medlineplus.gov/genetics/gene/atp2c1 functionThe ATP2C1 gene provides instructions for making a protein called hSPCA1. This protein is an adenosine triphosphate (ATP)-powered calcium pump, which uses energy from ATP molecules to pump charged calcium atoms (calcium ions) across cell membranes. Specifically, the hSPCA1 protein transports calcium ions into a cell structure called the Golgi apparatus, where they are stored until needed. The appropriate storage and release of calcium is essential for many cell activities, including cell growth and division (proliferation), cell movement (migration), and attachment of cells to one another (cell adhesion).The hSPCA1 protein also transports manganese ions into the Golgi apparatus. Manganese works with a variety of enzymes and is involved in processing newly formed proteins.The hSPCA1 protein is present in cells throughout the body. It appears to be particularly important for the normal function of cells called keratinocytes, which are found in the outer layer of the skin (the epidermis). In addition to proliferation and adhesion, calcium regulation in these cells appears to play an important role in maintaining the skin's barrier function, helping to keep foreign invaders such as bacteria out of the body. Hailey-Hailey disease https://medlineplus.gov/genetics/condition/hailey-hailey-disease AT2C1_HUMAN ATP-dependent Ca(2+) pump PMR1 ATP2C1A ATPase 2C1 ATPase, Ca(2+)-sequestering ATPase, Ca++ transporting, type 2C, member 1 BCPM calcium-transporting ATPase type 2C member 1 HHD hSPCA1 HUSSY-28 KIAA1347 PMR1 secretory pathway Ca2+/Mn2+ ATPase 1 SPCA1 NCBI Gene 27032 OMIM 604384 2013-05 2020-08-18 ATP6V0A2 ATPase H+ transporting V0 subunit a2 https://medlineplus.gov/genetics/gene/atp6v0a2 functionThe ATP6V0A2 gene provides instructions for making one part, the a2 subunit, of a large protein complex (a group of proteins that work together). This protein complex is known as a vacuolar H+-ATPase (V-ATPase). A V-ATPase acts as a pump to move positively charged hydrogen atoms (protons) across cell membranes.V-ATPases are embedded in the membranes surrounding cells, where they transport protons into and out of cells. This movement of protons helps regulate the relative acidity (pH) of cells and their surrounding environment. Tight control of pH is necessary for most biological reactions to proceed properly.Within cells, V-ATPases help regulate the pH of particular cell compartments. These compartments include endosomes and lysosomes, which digest and recycle materials that the cell no longer needs. Studies suggest that V-ATPases are also involved in the movement (trafficking) of small sac-like structures called vesicles. Vesicles transport many types of molecules within cells.V-ATPases also play a key role in a complex process called glycosylation, in which proteins are modified by adding sugar molecules. Glycosylation is necessary for the normal function of many different kinds of proteins. V-ATPases regulate the pH of a cellular structure called the Golgi apparatus, where glycosylation occurs. Cutis laxa https://medlineplus.gov/genetics/condition/cutis-laxa A2V-ATPase ATP6a2 ATP6N1D ATPase, H+ transporting, lysosomal V0 subunit a2 J6B7 Stv1 TJ6 TJ6M TJ6s Vph1 VPP2_HUMAN ICD-10-CM MeSH NCBI Gene 23545 OMIM 611716 SNOMED CT 2022-03 2021-08-05 ATP6V0A4 ATPase H+ transporting V0 subunit a4 https://medlineplus.gov/genetics/gene/atp6v0a4 functionThe ATP6V0A4 gene provides instructions for making a part (subunit) of a large protein complex known as vacuolar H+-ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Because acids are substances that can "donate" protons to other molecules, this movement of protons helps regulate the relative acidity (pH) of cells and their surrounding environment. Tight control of pH is necessary for most biological reactions to proceed properly.The V-ATPase that includes the subunit produced from the ATP6V0A4 gene is found in the inner ear and in nephrons, which are the functional structures within the kidneys. The kidneys filter waste products from the blood and remove them in urine. They also reabsorb needed nutrients and release them back into the blood. Each nephron consists of two parts: a renal corpuscle (also known as a glomerulus) that filters the blood, and a renal tubule that reabsorbs substances that are needed and eliminates unneeded substances in urine. The V-ATPase is involved in regulating the amount of acid that is removed from the blood into the urine, and also in maintaining the proper pH of the fluid in the inner ear (endolymph). Renal tubular acidosis with deafness https://medlineplus.gov/genetics/condition/renal-tubular-acidosis-with-deafness A4 ATP6N1B ATP6N2 ATPase, H+ transporting, lysosomal (vacuolar proton pump) non-catalytic accessory protein 1B ATPase, H+ transporting, lysosomal V0 subunit a4 H(+)-transporting two-sector ATPase, noncatalytic accessory protein 1B RdRTA2 RTA1C RTADR STV1 V-ATPase 116 kDa V-type proton ATPase 116 kDa subunit a V-type proton ATPase 116 kDa subunit a isoform 4 vacuolar proton pump 116 kDa accessory subunit vacuolar proton pump, subunit 2 vacuolar proton translocating ATPase 116 kDa subunit a kidney isoform VPH1 VPP2 NCBI Gene 50617 OMIM 605239 2014-03 2020-08-18 ATP6V1B1 ATPase H+ transporting V1 subunit B1 https://medlineplus.gov/genetics/gene/atp6v1b1 functionThe ATP6V1B1 gene provides instructions for making a part (subunit) of a large protein complex known as vacuolar H+-ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Because acids are substances that can "donate" protons to other molecules, this movement of protons helps regulate the relative acidity (pH) of cells and their surrounding environment. Tight control of pH is necessary for most biological reactions to proceed properly.The V-ATPase that includes the subunit produced from the ATP6V1B1 gene is found in the inner ear and in nephrons, which are the functional structures within the kidneys. The kidneys filter waste products from the blood and remove them in urine. They also reabsorb needed nutrients and release them back into the blood. Each nephron consists of two parts: a renal corpuscle (also known as a glomerulus) that filters the blood, and a renal tubule that reabsorbs substances that are needed and eliminates unneeded substances in urine. The V-ATPase is involved in regulating the amount of acid that is removed from the blood into the urine, and also in maintaining the proper pH of the fluid in the inner ear (endolymph). Renal tubular acidosis with deafness https://medlineplus.gov/genetics/condition/renal-tubular-acidosis-with-deafness ATP6B1 ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B1 endomembrane proton pump 58 kDa subunit H(+)-transporting two-sector ATPase, 58kD subunit H+-ATPase beta 1 subunit RTA1B V-ATPase B1 subunit V-ATPase subunit B 1 V-type proton ATPase subunit B, kidney isoform vacuolar proton pump 3 vacuolar proton pump subunit B 1 vacuolar proton pump, subunit 3 VATB VMA2 VPP3 NCBI Gene 525 OMIM 192132 2014-03 2020-08-18 ATP7A ATPase copper transporting alpha https://medlineplus.gov/genetics/gene/atp7a functionThe ATP7A gene provides instructions for making a protein that is important for regulating copper levels in the body. Copper is necessary for many cellular functions, but it is toxic when present in excessive amounts. The ATP7A protein is found throughout the body, except in liver cells. In the small intestine, this protein helps control the absorption of copper from food. In other cells, the ATP7A protein has a dual role and shuttles between two cellular locations. The protein normally resides in a cell structure called the Golgi apparatus, which modifies newly produced proteins, including enzymes. In the Golgi apparatus, the ATP7A protein supplies copper to certain enzymes that are critical for the structure and function of bone, skin, hair, blood vessels, and the nervous system. If copper levels in the cell environment are elevated, however, the ATP7A protein moves to the cell membrane and eliminates excess copper from the cell. Charcot-Marie-Tooth disease https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease Menkes syndrome https://medlineplus.gov/genetics/condition/menkes-syndrome Cutis laxa https://medlineplus.gov/genetics/condition/cutis-laxa ATP7A_HUMAN ATPase, Cu++ transporting, alpha polypeptide ATPase, Cu++ transporting, alpha polypeptide (Menkes syndrome) ATPP1 copper pump 1 MC1 MK MNK OHS NCBI Gene 538 OMIM 300011 2022-03 2023-03-07 ATP7B ATPase copper transporting beta https://medlineplus.gov/genetics/gene/atp7b functionThe ATP7B gene provides instructions for making a protein called copper-transporting ATPase 2. This protein is part of the P-type ATPase family, a group of proteins that transport metals into and out of cells by using energy stored in the molecule adenosine triphosphate (ATP). Copper-transporting ATPase 2 is found primarily in the liver, with smaller amounts in the kidneys and brain. It plays a role in the transport of copper from the liver to other parts of the body. Copper is an important part of certain enzymes that maintain normal cell functions. Copper-transporting ATPase 2 is also important for the removal of excess copper from the body.Within liver cells, copper-transporting ATPase 2 is found in a structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. Here, copper-transporting ATPase 2 supplies copper to a protein called ceruloplasmin, which transports copper to other parts of the body via the blood. If copper levels in the liver get too high, copper-transporting ATPase 2 leaves the Golgi and transfers copper to small sacs (vesicles) for elimination through bile. Bile is a substance produced by the liver that is important for digestion and the removal of waste products. Wilson disease https://medlineplus.gov/genetics/condition/wilson-disease ATP7B_HUMAN ATPase, Cu++ transporting, beta polypeptide ATPase, Cu++ transporting, beta polypeptide (Wilson disease) Copper pump 2 PWD WC1 Wilson disease-associated protein WND NCBI Gene 540 OMIM 606882 2007-02 2020-08-18 ATP8B1 ATPase phospholipid transporting 8B1 https://medlineplus.gov/genetics/gene/atp8b1 functionThe ATP8B1 gene (also known as FIC1) provides instructions for making a protein that is found throughout the body. It is thought to control the distribution of certain fat molecules known as aminophospholipids on the inner surface of liver cell membranes. Based on this role, the ATP8B1 protein is sometimes known as an aminophospholipid translocase. In particular, this protein performs its function in the membranes of liver cells that transport fat-digesting acids called bile acids into bile, and it likely plays a role in maintaining an appropriate balance of bile acids. This process, known as bile acid homeostasis, is critical for the normal secretion of bile and the proper functioning of liver cells. Progressive familial intrahepatic cholestasis https://medlineplus.gov/genetics/condition/progressive-familial-intrahepatic-cholestasis Benign recurrent intrahepatic cholestasis https://medlineplus.gov/genetics/condition/benign-recurrent-intrahepatic-cholestasis AT8B1_HUMAN ATPase, aminophospholipid transporter, class I, type 8B, member 1 BRIC FIC1 PFIC PFIC1 NCBI Gene 5205 OMIM 602397 2012-04 2020-08-18 ATRX ATRX chromatin remodeler https://medlineplus.gov/genetics/gene/atrx functionThe ATRX gene provides instructions for making a protein that plays an essential role in normal development. Although the specific function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (expression) of other genes through a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed.The ATRX protein appears to regulate the expression of two genes, HBA1 and HBA2, that are necessary for the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body. Other genes regulated by the ATRX protein have not been identified. Alpha thalassemia X-linked intellectual disability syndrome https://medlineplus.gov/genetics/condition/alpha-thalassemia-x-linked-intellectual-disability-syndrome alpha thalassemia/mental retardation syndrome X-linked alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) ATR2 ATRX_HUMAN DNA dependent ATPase and helicase helicase 2, X-linked MGC2094 MRXHF1 RAD54 RAD54L SFM1 SHS transcriptional regulator ATRX X-linked nuclear protein XH2 XNP Zinc finger helicase ZNF-HX NCBI Gene 546 OMIM 300032 2009-08 2023-03-07 ATXN1 ataxin 1 https://medlineplus.gov/genetics/gene/atxn1 functionThe ATXN1 gene provides instructions for making a protein called ataxin-1. This protein is found throughout the body, but its function is unknown. Within cells, ataxin-1 is located in the nucleus. Researchers believe that ataxin-1 may be involved in regulating various aspects of producing proteins, including the first stage of protein production (transcription) and processing RNA, a chemical cousin of DNA.One region of the ATXN1 gene contains a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 4 to 39 times within the gene. Spinocerebellar ataxia type 1 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-1 ataxin-1 ATX1 ATX1_HUMAN SCA1 NCBI Gene 6310 OMIM 601556 2011-02 2020-08-18 ATXN2 ataxin 2 https://medlineplus.gov/genetics/gene/atxn2 functionThe ATXN2 gene provides instructions for making a protein called ataxin-2. This protein is found throughout the body, but its function is unknown. Ataxin-2 is found in the fluid inside cells (cytoplasm) and seems to interact with a cell structure called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein production, processing, and transport. Researchers believe that ataxin-2 may be involved in processing RNA, a chemical cousin of DNA. Ataxin-2 is also thought to play a role in the translation of genetic information to produce proteins.One region of the ATXN2 gene contains a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated approximately 22 times within the gene. Amyotrophic lateral sclerosis https://medlineplus.gov/genetics/condition/amyotrophic-lateral-sclerosis Spinocerebellar ataxia type 2 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-2 ataxin-2 ATX2 ATX2_HUMAN SCA2 NCBI Gene 6311 OMIM 601517 2011-02 2020-08-18 ATXN3 ataxin 3 https://medlineplus.gov/genetics/gene/atxn3 functionThe ATXN3 gene provides instructions for making an enzyme called ataxin-3, which is found in cells throughout the body. Ataxin-3 is involved in a mechanism called the ubiquitin-proteasome system that destroys and gets rid of excess or damaged proteins. The molecule ubiquitin attaches (binds) to unneeded proteins and tags them to be broken down (degraded) within cells. Ataxin-3 removes (cleaves) the ubiquitin from these unwanted proteins just before they are degraded so that the ubiquitin can be used again. Due to its role in cleaving ubiquitin from proteins, ataxin-3 is known as a deubiquitinating enzyme.Researchers believe that ataxin-3 also may be involved in regulating the first stage of protein production (transcription). Spinocerebellar ataxia type 3 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-3 AT3 ataxin-3 ATX3 ATX3_HUMAN NCBI Gene 4287 OMIM 607047 2011-02 2020-08-18 AUH AU RNA binding methylglutaconyl-CoA hydratase https://medlineplus.gov/genetics/gene/auh functionThe AUH gene provides instructions for producing an enzyme called 3-methylglutaconyl-CoA hydratase. This enzyme is found in cell structures called mitochondria, which convert energy from food into a form that cells can use. Within mitochondria, this enzyme plays an important role in breaking down proteins into smaller molecules that cells can use to produce energy. Specifically, 3-methylglutaconyl-CoA hydratase is responsible for the fifth step in breaking down the protein building block (amino acid) leucine. The enzyme converts a molecule called 3-methylglutaconyl-CoA into another molecule called 3-hydroxy-3-methylglutaryl-CoA.3-methylglutaconyl-CoA hydratase also has the ability to attach (bind) to RNA, a chemical cousin of DNA. Researchers are working to determine the purpose of this RNA-binding ability. 3-methylglutaconyl-CoA hydratase deficiency https://medlineplus.gov/genetics/condition/3-methylglutaconyl-coa-hydratase-deficiency 3-methylglutaconyl Coenzyme A hydratase 3-methylglutaconyl-CoA hydratase AU RNA binding protein/enoyl-CoA hydratase AU RNA binding protein/enoyl-Coenzyme A hydratase AU RNA-binding protein/enoyl-Coenzyme A hydratase AU-specific RNA-binding protein AUMH_HUMAN enoyl-Coenzyme A hydratase methylglutaconyl-CoA hydratase NCBI Gene 549 OMIM 600529 2014-06 2020-08-18 AURKC aurora kinase C https://medlineplus.gov/genetics/gene/aurkc functionThe AURKC gene provides instructions for making a protein called aurora kinase C. This protein regulates certain events during cell division. Cell division occurs when a cell replicates and splits its contents, separating into two new cells. Aurora kinase C helps the two dividing cells separate from each other and ensures that these cells each contain a complete set of chromosomes. Aurora kinase C is most abundant in male testes, which are the male reproductive organs in which sperm are produced and stored. In the testes, this protein regulates the division of sperm cells, ensuring that every new sperm cell divides properly and contains one copy of each chromosome. Macrozoospermia https://medlineplus.gov/genetics/condition/macrozoospermia AIK3 AIK3 protein kinase ARK-3 ARK3 AurC aurora-related kinase 3 aurora/IPL1-like kinase 3 aurora/IPL1-related kinase 3 serine-threonine-protein kinase 13 serine/threonine-protein kinase aurora-C STK13 NCBI Gene 6795 OMIM 603495 2015-01 2020-08-18 AVP arginine vasopressin https://medlineplus.gov/genetics/gene/avp functionThe AVP gene provides instructions for making a hormone called arginine vasopressin (AVP), which is sometimes also called antidiuretic hormone (ADH). AVP starts out as a larger molecule called a preprohormone that is cut (cleaved) and modified to produce the active hormone and several related proteins. The preprohormone is made in a region of the brain called the hypothalamus. It is then transported to the nearby pituitary gland, where active AVP is stored until it is needed.The major function of AVP is to help control the body's water balance by determining how much water is released in urine. Normally, when a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), the pituitary gland releases more AVP into the bloodstream. High levels of this hormone direct the kidneys to reabsorb more water and make less urine. When fluid intake is adequate, the pituitary gland releases less AVP. Arginine vasopressin deficiency https://medlineplus.gov/genetics/condition/arginine-vasopressin-deficiency ADH ARVP AVP-NPII AVRP NEU2_HUMAN VP NCBI Gene 551 OMIM 192340 2024-07 2024-07-19 AVPR2 arginine vasopressin receptor 2 https://medlineplus.gov/genetics/gene/avpr2 functionThe AVPR2 gene provides instructions for making a protein known as the vasopressin V2 receptor. This receptor works together with a hormone called arginine vasopressin (AVP), which is sometimes also called antidiuretic hormone (ADH). The vasopressin V2 receptor is found in the kidneys in structures called collecting ducts, which are a series of small tubes that reabsorb water from the kidneys into the bloodstream.The interaction between AVP and the vasopressin V2 receptor triggers chemical reactions that control the body's water balance. When a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), AVP is released from the brain, where it is produced and stored. In the kidneys, this hormone attaches (binds) to the vasopressin V2 receptor and directs the kidneys to concentrate urine by reabsorbing some of the water back into the bloodstream. When fluid intake is adequate, the brain releases less AVP. At these times, less water is reabsorbed into the bloodstream and the urine is more dilute. Arginine vasopressin resistance https://medlineplus.gov/genetics/condition/arginine-vasopressin-resistance ADHR antidiuretic hormone receptor AVPR V2 V2R V2R_HUMAN vasopressin V2 receptor NCBI Gene 554 OMIM 300538 2024-08 2024-08-13 B3GLCT beta 3-glucosyltransferase https://medlineplus.gov/genetics/gene/b3glct functionThe B3GLCT gene (formerly known as B3GALTL) provides instructions for making an enzyme called beta 3-glucosyltransferase (B3Glc-T), which is involved in the complex process of adding sugar molecules to proteins (glycosylation). Glycosylation modifies proteins so they can perform a wider variety of functions. The B3Glc-T enzyme is involved in a two-step glycosylation pathway that results in the formation of a sugar structure, made up of the sugars fucose and glucose, on a specific location of several different proteins. The B3Glc-T enzyme is responsible for the second step, which adds a glucose molecule to the fucose molecule already attached to the protein. The B3GLCT gene is normally turned on (active) in most cells of the body, which suggests that the B3Glc-T enzyme plays an important role across many cell types. Peters plus syndrome https://medlineplus.gov/genetics/condition/peters-plus-syndrome B3GALTL B3Glc-T B3GLT_HUMAN B3GTL beta 1,3-galactosyltransferase-like beta-3-glycosyltransferase-like beta3Glc-T NCBI Gene 145173 OMIM 610308 2013-09 2020-08-18 BAP1 BRCA1 associated deubiquitinase 1 https://medlineplus.gov/genetics/gene/bap1 functionThe BAP1 gene provides instructions for making a protein called ubiquitin carboxyl-terminal hydrolase BAP1 (shortened to BAP1). This protein functions as a deubiquitinase, which means it removes a molecule called ubiquitin from certain proteins. The presence of ubiquitin molecules on a protein can affect the activity of the protein and its interactions with other proteins. The ubiquitin "tag" also promotes breakdown (degradation) of a protein. By removing ubiquitin, BAP1 helps regulate the function of many proteins involved in diverse cellular processes. The BAP1 protein is thought to help control cell growth and division (proliferation) and cell death. Studies suggest that it is involved in the progression of cells through the step-by-step process they take to replicate themselves (called the cell cycle) and that it plays roles in repairing damaged DNA and controlling the activity of genes.Although the exact mechanism is unclear, the BAP1 protein acts as a tumor suppressor. Tumor suppressor proteins help prevent cells from growing and dividing too rapidly or in an uncontrolled way. Cholangiocarcinoma https://medlineplus.gov/genetics/condition/cholangiocarcinoma BAP1 tumor predisposition syndrome https://medlineplus.gov/genetics/condition/bap1-tumor-predisposition-syndrome Melanoma https://medlineplus.gov/genetics/condition/melanoma BRCA1 associated protein 1 BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) HUCEP-13 hucep-6 KIAA0272 KURIS TPDS1 UBM2 UCHL2 UVM2 NCBI Gene 8314 OMIM 603089 2017-01 2024-08-01 BBS1 Bardet-Biedl syndrome 1 https://medlineplus.gov/genetics/gene/bbs1 functionThe BBS1 gene provides instructions for making a protein found in cells throughout the body. The BBS1 protein is part of a group (complex) of proteins that plays a critical role in the formation of cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of many types of cells. They are involved in cell movement and many different chemical signaling pathways. Cilia are also necessary for the perception of sensory input (such as sight, hearing, and smell). Bardet-Biedl syndrome https://medlineplus.gov/genetics/condition/bardet-biedl-syndrome BBS1_HUMAN BBS2L2 FLJ23590 NCBI Gene 582 OMIM 209901 2010-05 2020-08-18 BBS10 Bardet-Biedl syndrome 10 https://medlineplus.gov/genetics/gene/bbs10 functionThe BBS10 gene provides instructions for making a protein that is found in many types of cells. The BBS10 protein is part of a group (complex) of proteins that functions as a chaperonin. Chaperonins help fold other proteins into their correct 3-dimensional shapes so they can perform their usual functions in the body.Studies suggest that the BBS10 protein helps fold or stabilize certain proteins that are necessary for the normal formation of cilia. Cilia are microscopic, finger-like projections that stick out from the surface of many types of cells. They are involved in cell movement and many different chemical signaling pathways. Cilia are also necessary for the perception of sensory input (such as sight, hearing, and smell). Bardet-Biedl syndrome https://medlineplus.gov/genetics/condition/bardet-biedl-syndrome BBS10_HUMAN C12orf58 FLJ23560 NCBI Gene 79738 OMIM 610148 2010-05 2020-08-18 BCHE butyrylcholinesterase https://medlineplus.gov/genetics/gene/bche functionThe BCHE gene provides instructions for making an enzyme called pseudocholinesterase, also called butyrylcholinesterase. This enzyme is produced by the liver and circulates in the blood. Pseudocholinesterase is involved in the breakdown of certain substances, including the medications succinylcholine and mivacurium. These medications may be given during general anesthesia. General anesthesia is typically used during major surgeries and causes a brief period of unconsciousness. Succinylcholine and mivacurium relax the muscles used for movement (skeletal muscles), including the muscles involved in breathing. Pseudocholinesterase also helps protect the body by breaking down toxic substances, including some agricultural pesticides; certain street drugs; and a compound called solanine, which is found in green potato skin. Researchers also suspect that pseudocholinesterase plays a role in the growth and maturation of nerve cells (neurons) in the developing brain.  Pseudocholinesterase deficiency https://medlineplus.gov/genetics/condition/pseudocholinesterase-deficiency acylcholine acylhydrolase butyrylcholine esterase CHE1 CHE2 cholinesterase (serum) 2 E1 pseudocholinesterase E1 NCBI Gene 590 OMIM 177400 2025-09 2025-09-25 BCKDHA branched chain keto acid dehydrogenase E1 subunit alpha https://medlineplus.gov/genetics/gene/bckdha functionThe BCKDHA gene provides instructions for making one part, the alpha subunit, of a group of enzymes called the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex. Two alpha subunits connect with two beta subunits, which are produced from the BCKDHB gene, to form a critical piece of the enzyme complex called the E1 component.The BCKD enzyme complex is responsible for one step in the normal breakdown of three protein building blocks (amino acids). These amino acids—leucine, isoleucine, and valine—are obtained from the diet. They are present in many kinds of food, particularly protein-rich foods such as milk, meat, and eggs. The BCKD enzyme complex is active in mitochondria, which are specialized structures inside cells that serve as energy-producing centers. The breakdown of leucine, isoleucine, and valine produces molecules that can be used for energy. Maple syrup urine disease https://medlineplus.gov/genetics/condition/maple-syrup-urine-disease BCKDE1A BCKDH E1-alpha branched chain keto acid dehydrogenase E1, alpha polypeptide (maple syrup urine disease) MSUD1 ODBA_HUMAN NCBI Gene 593 OMIM 608348 2008-12 2022-06-21 BCKDHB branched chain keto acid dehydrogenase E1 subunit beta https://medlineplus.gov/genetics/gene/bckdhb functionThe BCKDHB gene provides instructions for making one part, the beta subunit, of a group of enzymes called the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex. Two beta subunits connect with two alpha subunits, which are produced from the BCKDHA gene, to form a critical piece of the enzyme complex called the E1 component.The BCKD enzyme complex is responsible for one step in the normal breakdown of three protein building blocks (amino acids). These amino acids—leucine, isoleucine, and valine—are obtained from the diet. They are present in many kinds of food, particularly protein-rich foods such as milk, meat, and eggs. The BCKD enzyme complex is active in mitochondria, which are specialized structures inside cells that serve as energy-producing centers. The breakdown of leucine, isoleucine, and valine produces molecules that can be used for energy. Maple syrup urine disease https://medlineplus.gov/genetics/condition/maple-syrup-urine-disease 2-oxoisovalerate dehydrogenase beta subunit BCKDH E1-beta branched chain keto acid dehydrogenase E1, beta polypeptide branched chain keto acid dehydrogenase E1, beta polypeptide (maple syrup urine disease) ODBB_HUMAN NCBI Gene 594 OMIM 248611 2008-12 2025-04-03 BCOR BCL6 corepressor https://medlineplus.gov/genetics/gene/bcor functionThe BCOR gene provides instructions for making a protein known as the BCL6 corepressor. A corepressor is a protein that cannot attach (bind) to DNA by itself, but it interacts with other DNA-binding proteins to suppress the activity of certain genes. In this case, the BCL6 corepressor partners with the DNA-binding protein produced from the BCL6 gene.The BCL6 corepressor appears to play a critical role in early development, including the formation of the eyes and several other tissues and organs. Scientists believe that the BCL6 corepressor may also be involved in specifying the left and right sides of the body in the developing embryo. Research also shows that this protein may regulate development by influencing the self-destruction of cells that are damaged or no longer needed (apoptosis). Oculofaciocardiodental syndrome https://medlineplus.gov/genetics/condition/oculofaciocardiodental-syndrome Anophthalmia/Microphthalmia https://medlineplus.gov/genetics/condition/anophthalmia-microphthalmia Coloboma https://medlineplus.gov/genetics/condition/coloboma BCL-6 interacting corepressor BCL6 co-repressor BCOR_HUMAN NCBI Gene 54880 OMIM 300485 2024-11 2025-09-30 BCR BCR activator of RhoGEF and GTPase https://medlineplus.gov/genetics/gene/bcr functionThe BCR gene provides instructions for making a protein whose function is not completely understood. Studies show that the BCR protein may act as a GTPase activating protein (GAP). GAPs turn off (inactivate) proteins called GTPases, which play an important role in chemical signaling within cells. Often referred to as molecular switches, GTPases can be turned on and off. They are turned on (active) when they are attached (bound) to a molecule called GTP and are turned off when they are bound to another molecule called GDP. The BCR protein inactivates a GTPase known as Rac1 by stimulating a reaction that turns the attached GTP into GDP. Through this activity, the BCR protein helps regulate the movement (migration) and function of cells.The BCR protein can also act as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. BCR's kinase activity is likely involved in regulating signaling within cells, although its exact role is unclear. Chronic myeloid leukemia https://medlineplus.gov/genetics/condition/chronic-myeloid-leukemia ALL BCR/FGFR1 chimera protein BCR1 breakpoint cluster region breakpoint cluster region protein isoform 1 breakpoint cluster region protein isoform 2 CML D22S11 D22S662 FGFR1/BCR chimera protein PHL renal carcinoma antigen NY-REN-26 NCBI Gene 613 OMIM 151410 2016-09 2022-07-05 BCS1L BCS1 ubiquinol-cytochrome c reductase complex chaperone https://medlineplus.gov/genetics/gene/bcs1l functionThe BCS1L gene provides instructions for making a protein that functions in cell structures called mitochondria, which convert the energy from food into a form that cells can use. The BCS1L protein is critical for the formation of a group of proteins known as complex III. Specifically, BCS1L adds a component called Rieske Fe/S protein to the complex. In mitochondria, complex III performs one step of the multistep process known as oxidative phosphorylation, in which oxygen and simple sugars are used to create adenosine triphosphate (ATP), the cell's main energy source.As a byproduct of its action in oxidative phosphorylation, complex III produces reactive oxygen species, which are harmful molecules that can damage DNA and tissues. The reactive oxygen species produced by complex III are thought to also play a role in normal cell signaling, particularly when levels of oxygen in the body are low (hypoxia).Some researchers believe the BCS1L protein is involved in the breakdown (metabolism) of iron, although the mechanism is unknown. Leigh syndrome https://medlineplus.gov/genetics/condition/leigh-syndrome Björnstad syndrome https://medlineplus.gov/genetics/condition/bjornstad-syndrome GRACILE syndrome https://medlineplus.gov/genetics/condition/gracile-syndrome Mitochondrial complex III deficiency https://medlineplus.gov/genetics/condition/mitochondrial-complex-iii-deficiency BC1 (ubiquinol-cytochrome c reductase) synthesis-like BCS1 BCS1-like protein BCS1_HUMAN h-BCS1 Hs.6719 mitochondrial chaperone BCS1 mitochondrial complex III assembly NCBI Gene 617 OMIM 124000 OMIM 603647 2014-04 2025-08-01 BDNF brain derived neurotrophic factor https://medlineplus.gov/genetics/gene/bdnf functionThe BDNF gene provides instructions for making a protein found in the brain and spinal cord called brain-derived neurotrophic factor. This protein promotes the survival of nerve cells (neurons) by playing a role in the growth, maturation (differentiation), and maintenance of these cells. In the brain, the BDNF protein is active at the connections between nerve cells (synapses), where cell-to-cell communication occurs. The synapses can change and adapt over time in response to experience, a characteristic called synaptic plasticity. The BDNF protein helps regulate synaptic plasticity, which is important for learning and memory.The BDNF protein is found in regions of the brain that control eating, drinking, and body weight; the protein likely contributes to the management of these functions. WAGR syndrome https://medlineplus.gov/genetics/condition/wagr-syndrome Opioid addiction https://medlineplus.gov/genetics/condition/opioid-addiction abrineurin ANON2 BDNF_HUMAN brain-derived neurotrophic factor BULN2 neurotrophin NCBI Gene 627 OMIM 113505 OMIM 607499 2013-03 2023-03-13 BEST1 bestrophin 1 https://medlineplus.gov/genetics/gene/best1 functionThe BEST1 gene provides instructions for making a protein called bestrophin-1, which appears to play a critical role in normal vision. Bestrophin-1 is found in a thin layer of cells at the back of the eye called the retinal pigment epithelium. This cell layer supports and nourishes the retina, which is the light-sensitive tissue that lines the back of the eye. The retinal pigment epithelium is involved in the growth and development of the eye, maintenance of the retina, and the normal function of specialized cells called photoreceptors that detect light and color.Bestrophin-1 functions as a channel across cell membranes in the retinal pigment epithelium. Charged chlorine atoms (chloride ions) are transported through these channels in response to cellular signals. Some studies suggest that bestrophin-1 may also help regulate the entry of charged calcium atoms (calcium ions) into cells of the retinal pigment epithelium. Other potential functions of bestrophin-1 are under study. Vitelliform macular dystrophy https://medlineplus.gov/genetics/condition/vitelliform-macular-dystrophy Retinitis pigmentosa https://medlineplus.gov/genetics/condition/retinitis-pigmentosa Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration Autosomal dominant vitreoretinochoroidopathy https://medlineplus.gov/genetics/condition/autosomal-dominant-vitreoretinochoroidopathy BEST BEST1_HUMAN BMD RP50 TU15B vitelliform macular dystrophy 2 (Best disease, bestrophin) VMD2 NCBI Gene 7439 OMIM 607854 OMIM 611809 2014-11 2023-03-13 BICD2 BICD cargo adaptor 2 https://medlineplus.gov/genetics/gene/bicd2 functionThe BICD2 gene provides instructions for making one of a family of proteins called golgins. Golgins help maintain the structure of a cell component called the Golgi apparatus, in which newly produced proteins are modified so they can carry out their functions.The BICD2 protein is found in all cells. The protein attaches (binds) to a group of proteins called the dynein complex, turning it on (activating it) and helping it bind to other cellular materials for transport. During transport, BICD2 stabilizes the dynein complex along a track-like system of small tubes called microtubules, similar to a conveyer belt. The BICD2 protein helps the dynein complex with protein transport, positioning of cell compartments, mobility of structures within the cell, and many other cell processes.In nerve cells (neurons), the BICD2 protein helps the dynein complex transport sac-like structures called synaptic vesicles. These structures contain chemical messengers that allow neighboring cells to communicate with one another. Spinal muscular atrophy with lower extremity predominance https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy-with-lower-extremity-predominance bA526D8.1 bic-D 2 bicaudal D homolog 2 coiled-coil protein BICD2 cytoskeleton-like bicaudal D protein homolog 2 homolog of Drosophila bicaudal D KIAA0699 NCBI Gene 23299 OMIM 609797 2018-05 2020-08-18 BIN1 bridging integrator 1 https://medlineplus.gov/genetics/gene/bin1 functionThe BIN1 gene provides instructions for making a protein that is found in tissues throughout the body, where it interacts with a variety of other proteins. The BIN1 protein is thought to be involved in the transportation of materials from the cell surface into the cell (endocytosis) and the self-destruction of cells (apoptosis). The BIN1 protein may act as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.Several different versions (isoforms) of the BIN1 protein are produced from the BIN1 gene. These isoforms vary by size and are active in different tissues. The BIN1 protein isoform that is expressed in muscle cells is thought to be involved in the formation of structures called transverse tubules or T tubules. These structures are found within the membrane of muscle cells, where they play a role in muscle tensing (contraction) and relaxation. Centronuclear myopathy https://medlineplus.gov/genetics/condition/centronuclear-myopathy AMPH2 amphiphysin II amphiphysin-like protein AMPHL BIN1_HUMAN box-dependent myc-interacting protein 1 myc box-dependent-interacting protein 1 SH3P9 NCBI Gene 274 OMIM 601248 2015-11 2020-08-18 BLM BLM RecQ like helicase https://medlineplus.gov/genetics/gene/blm functionThe BLM gene provides instructions for making a member of a protein family called RecQ helicases. Helicases are enzymes that attach (bind) to DNA and unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for several processes in the cell nucleus, including copying (replicating) DNA in preparation for cell division and repairing damaged DNA. Because RecQ helicases help maintain the structure and integrity of DNA, they are known as the "caretakers of the genome."When a cell prepares to divide to form two cells, the DNA that makes up the chromosomes is copied so that each new cell will have two copies of each chromosome, one from each parent. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Sister chromatids occasionally exchange small sections of DNA during this time, a process called sister chromatid exchange. Researchers suggest that these exchanges may be a response to DNA damage during the copying process. The BLM protein helps to prevent excess sister chromatid exchanges and is also involved in other processes that help maintain the stability of the DNA during the copying process. Bloom syndrome https://medlineplus.gov/genetics/condition/bloom-syndrome BLM_HUMAN Bloom syndrome Bloom syndrome protein Bloom syndrome RecQ like helicase Bloom syndrome, RecQ helicase-like BS MGC126616 RECQL3 NCBI Gene 641 OMIM 604610 2010-11 2025-04-03 BMPR1A bone morphogenetic protein receptor type 1A https://medlineplus.gov/genetics/gene/bmpr1a functionThe BMPR1A gene provides instructions for making a protein called bone morphogenetic protein receptor 1A. This receptor protein has a specific site into which certain other proteins, called ligands, fit like keys into locks. Specifically, the BMPR1A protein attaches (binds) to ligands in the transforming growth factor beta (TGF-β) pathway. This signaling pathway allows the environment outside the cell to affect how the cell produces other proteins. The BMPR1A receptor protein and its ligands are involved in transmitting chemical signals from the cell membrane to the nucleus.When the BMPR1A protein is bound to a ligand, it turns on (activates) a group of related proteins (a protein complex) called SMAD proteins. The activated SMAD protein complex is then transported into the cell's nucleus, where it regulates cell growth and division (proliferation) and the activity of particular genes. Juvenile polyposis syndrome https://medlineplus.gov/genetics/condition/juvenile-polyposis-syndrome activin A receptor, type II-like kinase 3 ACVRLK3 ALK3 BMR1A_HUMAN bone morphogenetic protein receptor type IA bone morphogenetic protein receptor, type IA bone morphogenetic protein receptor, type IA precursor CD292 serine/threonine-protein kinase receptor R5 SKR5 NCBI Gene 657 OMIM 601299 2009-05 2020-08-18 BMPR2 bone morphogenetic protein receptor type 2 https://medlineplus.gov/genetics/gene/bmpr2 functionThe BMPR2 gene provides instructions for making a protein called bone morphogenetic protein receptor type 2. The BMPR2 gene belongs to a family of genes originally identified for its role in regulating the growth and maturation (differentiation) of bone and cartilage. Recently, researchers have found that this gene family plays a broader role in regulating the growth and differentiation of numerous types of cells.Bone morphogenetic protein receptor type 2 spans the cell membrane, so that one end of the protein is on the outer surface of the cell and the other end remains inside the cell. This positioning allows the protein to receive and transmit signals that help the cell respond to its environment by growing and dividing (cell proliferation) or by undergoing controlled cell death (apoptosis). This balance of cell proliferation and apoptosis regulates the number of cells in tissues. Pulmonary arterial hypertension https://medlineplus.gov/genetics/condition/pulmonary-arterial-hypertension Pulmonary veno-occlusive disease https://medlineplus.gov/genetics/condition/pulmonary-veno-occlusive-disease BMPR-II BMPR2_HUMAN BMPR3 BMR2 bone morphogenetic protein receptor type II bone morphogenetic protein receptor, type II (serine/threonine kinase) BRK-3 PPH1 Receptor, Type II BMP serine/threonine kinase T-ALK type II activin receptor-like kinase NCBI Gene 659 OMIM 600799 2016-01 2023-03-13 BOLA3 bolA family member 3 https://medlineplus.gov/genetics/gene/bola3 functionThe BOLA3 gene provides instructions for making a protein whose function is not well understood. The BOLA3 protein is thought to be involved in the formation of molecules called iron-sulfur (Fe-S) clusters or in the attachment of these clusters to other proteins. Certain proteins require attachment of Fe-S clusters to function properly.Two versions (isoforms) of the BOLA3 protein are produced from the BOLA3 gene. One version is found in cellular structures called mitochondria. Mitochondria are the energy-producing centers of cells. In these structures, several proteins carry out a series of chemical steps to convert the energy in food into a form that cells can use. Many of the proteins involved in this process require Fe-S clusters to function, including protein complexes called complex I, complex II, and complex III.Fe-S clusters are also required for another mitochondrial protein to function; this protein is involved in the modification of additional proteins that aid in energy production in mitochondria, including the pyruvate dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex. This modification is also critical to the function of the glycine cleavage system, a set of proteins that breaks down a protein building block (amino acid) called glycine when levels become too high.The other version of the BOLA3 protein is found in the fluid-filled space inside the cell (the cytoplasm). While this protein is likely involved in Fe-S cluster formation in the cytoplasm, the role of this isoform is not well understood. Multiple mitochondrial dysfunctions syndrome https://medlineplus.gov/genetics/condition/multiple-mitochondrial-dysfunctions-syndrome bolA homolog 3 bolA-like protein 3 bolA-like protein 3 isoform 1 bolA-like protein 3 isoform 2 BOLA3_HUMAN MMDS2 NCBI Gene 388962 OMIM 613183 2015-05 2020-08-18 BRAF B-Raf proto-oncogene, serine/threonine kinase https://medlineplus.gov/genetics/gene/braf functionThe BRAF gene provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell's nucleus. This protein is part of a signaling pathway known as the RAS/MAPK pathway, which controls several important cell functions. Specifically, the RAS/MAPK pathway regulates the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis). Chemical signaling through this pathway is essential for normal development before birth.The BRAF gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. Noonan syndrome https://medlineplus.gov/genetics/condition/noonan-syndrome Cardiofaciocutaneous syndrome https://medlineplus.gov/genetics/condition/cardiofaciocutaneous-syndrome Noonan syndrome with multiple lentigines https://medlineplus.gov/genetics/condition/noonan-syndrome-with-multiple-lentigines Langerhans cell histiocytosis https://medlineplus.gov/genetics/condition/langerhans-cell-histiocytosis Gastrointestinal stromal tumor https://medlineplus.gov/genetics/condition/gastrointestinal-stromal-tumor Giant congenital melanocytic nevus https://medlineplus.gov/genetics/condition/giant-congenital-melanocytic-nevus Erdheim-Chester disease https://medlineplus.gov/genetics/condition/erdheim-chester-disease Lung cancer https://medlineplus.gov/genetics/condition/lung-cancer Multiple myeloma https://medlineplus.gov/genetics/condition/multiple-myeloma Cholangiocarcinoma https://medlineplus.gov/genetics/condition/cholangiocarcinoma Melanoma https://medlineplus.gov/genetics/condition/melanoma 94 kDa B-raf protein B-raf 1 B-Raf proto-oncogene serine/threonine-protein kinase BRAF1 BRAF1_HUMAN Murine sarcoma viral (v-raf) oncogene homolog B1 p94 RAFB1 v-raf murine sarcoma viral oncogene homolog B NCBI Gene 673 OMIM 164757 2018-07 2021-05-28 BRCA1 BRCA1 DNA repair associated https://medlineplus.gov/genetics/gene/brca1 functionThe BRCA1 gene provides instructions for making a protein that acts as a tumor suppressor. Tumor suppressor proteins help prevent cells from growing and dividing too rapidly or in an uncontrolled way.The BRCA1 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA1 protein interacts with several other proteins to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and they also occur when chromosomes exchange genetic material in preparation for cell division. By helping to repair DNA, the BRCA1 protein plays a critical role in maintaining the stability of a cell's genetic information.Research suggests that the BRCA1 protein also regulates the activity of other genes and plays an essential role in embryonic development. To carry out these functions, the BRCA1 protein interacts with many other proteins, including other tumor suppressors and proteins that regulate cell division. Breast cancer https://medlineplus.gov/genetics/condition/breast-cancer Fanconi anemia https://medlineplus.gov/genetics/condition/fanconi-anemia Prostate cancer https://medlineplus.gov/genetics/condition/prostate-cancer Ovarian cancer https://medlineplus.gov/genetics/condition/ovarian-cancer Cholangiocarcinoma https://medlineplus.gov/genetics/condition/cholangiocarcinoma BRCA1 gene BRCA1_HUMAN BRCC1 breast cancer 1 breast cancer 1 gene breast cancer 1, early onset breast cancer 1, early onset gene breast cancer type 1 susceptibility gene breast cancer type 1 susceptibility protein IRIS PPP1R53 PSCP RNF53 NCBI Gene 672 OMIM 113705 2015-09 2025-04-03 BRCA2 BRCA2 DNA repair associated https://medlineplus.gov/genetics/gene/brca2 functionThe BRCA2 gene provides instructions for making a protein that acts as a tumor suppressor. Tumor suppressor proteins help prevent cells from growing and dividing too rapidly or in an uncontrolled way.The BRCA2 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and they also occur when chromosomes exchange genetic material in preparation for cell division. By helping to repair DNA, the BRCA2 protein plays a critical role in maintaining the stability of a cell's genetic information.Researchers suspect that the BRCA2 protein has additional functions within cells. For example, the protein may help regulate cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. Researchers are investigating the protein's other potential activities. Breast cancer https://medlineplus.gov/genetics/condition/breast-cancer Fanconi anemia https://medlineplus.gov/genetics/condition/fanconi-anemia Prostate cancer https://medlineplus.gov/genetics/condition/prostate-cancer Ovarian cancer https://medlineplus.gov/genetics/condition/ovarian-cancer Cholangiocarcinoma https://medlineplus.gov/genetics/condition/cholangiocarcinoma brca 2 gene BRCA2_HUMAN BRCC2 breast cancer 2 breast cancer 2 gene breast cancer 2, early onset breast cancer 2, early onset gene breast cancer type 2 susceptibility gene breast cancer type 2 susceptibility protein FACD FAD FAD1 FANCB FANCD1 NCBI Gene 675 OMIM 600185 OMIM 605724 2015-09 2025-04-03 BSCL2 BSCL2 lipid droplet biogenesis associated, seipin https://medlineplus.gov/genetics/gene/bscl2 functionThe BSCL2 gene provides instructions for making a protein called seipin. Seipin is located in the membrane of a cell structure called the endoplasmic reticulum. The endoplasmic reticulum modifies newly produced proteins and helps transport proteins, fats, and other molecules to where they are needed.Three different versions (isoforms) of the seipin protein can be produced from the BSCL2 gene. One isoform is found in most tissues, and the other two are specific to the brain and the nervous system outside of the brain.Studies suggest that seipin plays a critical role in the development and function of adipocytes, which are the major component of fatty (adipose) tissue. Within the endoplasmic reticulum of adipocytes, seipin is involved in the formation of lipid droplets, which are structures that store fat molecules. Charcot-Marie-Tooth disease https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease Distal hereditary motor neuropathy, type V https://medlineplus.gov/genetics/condition/distal-hereditary-motor-neuropathy-type-v Congenital generalized lipodystrophy https://medlineplus.gov/genetics/condition/congenital-generalized-lipodystrophy Silver syndrome https://medlineplus.gov/genetics/condition/silver-syndrome Berardinelli-Seip congenital lipodystrophy 2 (seipin) BSCL2_HUMAN GNG3LG seipin SPG17 NCBI Gene 26580 OMIM 606158 2025-03 2025-03-10 BSND barttin CLCNK type accessory subunit beta https://medlineplus.gov/genetics/gene/bsnd functionThe BSND gene provides instructions for making a protein called barttin. This protein is found primarily in the kidneys, where it attaches (binds) to two specific chloride channels: ClC-Ka (produced from the CLCNKA gene) and ClC-Kb (produced from the CLCNKB gene). The ClC-Ka and ClC-Kb channels transport charged atoms of chlorine (chloride ions) out of kidney cells.Barttin is essential for the normal placement of ClC-Ka and ClC-Kb channels in the cell membrane. It also regulates the channels' stability and function. The transport of chloride ions is part of the mechanism by which the kidneys reabsorb salt (sodium chloride or NaCl) from the urine back into the bloodstream. The retention of salt affects the body's fluid levels and helps maintain blood pressure.Barttin, ClC-Ka, and ClC-Kb are also found in the inner ear, where they play a role in normal hearing. Nonsyndromic hearing loss https://medlineplus.gov/genetics/condition/nonsyndromic-hearing-loss Bartter syndrome https://medlineplus.gov/genetics/condition/bartter-syndrome BART Bartter syndrome, infantile, with sensorineural deafness (Barttin) barttin barttin CLCNK-type chloride channel accessory beta subunit BSND_HUMAN deafness, autosomal recessive 73 DFNB73 NCBI Gene 7809 OMIM 606412 2011-02 2022-07-01 BTD biotinidase https://medlineplus.gov/genetics/gene/btd functionThe BTD gene provides instructions for making an enzyme called biotinidase. This enzyme recycles biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Biotinidase removes biotin that is bound to proteins in food, leaving the vitamin in its free (unbound) state. The body needs free biotin to activate enzymes called biotin-dependent carboxylases. These carboxylases are involved in many critical cellular functions, including the breakdown of proteins, fats, and carbohydrates.In addition to processing biotin obtained from the diet, biotinidase recycles biotin within the body. As biotin-dependent carboxylases are broken down, they release a molecule called biocytin. Biocytin is a complex made of up biotin and a protein building block (amino acid) called lysine. Biotinidase splits this complex, making free biotin available for reuse by other carboxylase enzymes.Researchers suspect that biotinidase may have several additional functions. This enzyme may transport free biotin through the bloodstream. It might also have the ability to attach biotin to certain proteins through a process called biotinylation. Within the nucleus, biotinylation of DNA-associated proteins called histones may help determine whether certain genes are turned on or off. It is unclear, however, whether biotinidase plays a role in regulating gene activity. Biotinidase deficiency https://medlineplus.gov/genetics/condition/biotinidase-deficiency Leigh syndrome https://medlineplus.gov/genetics/condition/leigh-syndrome Biocytin Hydrolase ICD-10-CM MeSH NCBI Gene 686 OMIM 609019 SNOMED CT 2014-12 2021-05-20 BTK Bruton tyrosine kinase https://medlineplus.gov/genetics/gene/btk functionThe BTK gene provides instructions for making a protein called Bruton tyrosine kinase (BTK), which is essential for the development and maturation of B cells. B cells are specialized white blood cells that help protect the body against infection. These cells can mature into cells that produce special proteins called antibodies or immunoglobulins. Antibodies attach to specific foreign particles and germs, marking them for destruction. The BTK protein transmits important chemical signals that instruct B cells to mature and produce antibodies. X-linked agammaglobulinemia https://medlineplus.gov/genetics/condition/x-linked-agammaglobulinemia Isolated growth hormone deficiency https://medlineplus.gov/genetics/condition/isolated-growth-hormone-deficiency AGMX1 AT ATK BPK Bruton agammaglobulinemia tyrosine kinase Bruton's tyrosine kinase BTK_HUMAN dominant-negative kinase-deficient Bruton's tyrosine kinase IMD1 MGC126261 MGC126262 PSCTK1 tyrosine-protein kinase BTK XLA NCBI Gene 695 OMIM 300300 2012-02 2020-08-18 BUB1B BUB1 mitotic checkpoint serine/threonine kinase B https://medlineplus.gov/genetics/gene/bub1b functionThe BUB1B gene provides instructions for making a protein called BUBR1, which is important for proper chromosome separation during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. The sets of chromosomes align within the cell, with each chromatid attached to a structure called a spindle microtubule; when all chromatids are correctly attached, the spindle microtubule pulls the two halves of the chromatid pair to opposite sides of the cell. The cell then divides in two such that each new cell contains one complete set of chromosomes.The BUBR1 protein helps ensure that each sister chromatid is attached to a spindle microtubule. If any chromatids remain unattached, the protein prevents cell division. Mosaic variegated aneuploidy syndrome https://medlineplus.gov/genetics/condition/mosaic-variegated-aneuploidy-syndrome Bub1A BUB1B, mitotic checkpoint serine/threonine kinase BUB1beta BUBR1 budding uninhibited by benzimidazoles 1 homolog beta hBUBR1 MAD3/BUB1-related protein kinase MAD3L mitotic checkpoint kinase MAD3L mitotic checkpoint serine/threonine-protein kinase BUB1 beta MVA1 SSK1 NCBI Gene 701 OMIM 602860 2017-06 2020-08-18 C19orf12 chromosome 19 open reading frame 12 https://medlineplus.gov/genetics/gene/c19orf12 functionThe C19orf12 gene provides instructions for making a protein whose function is unknown. The protein is found in the membrane of cellular structures called mitochondria, which are the cell's energy-producing centers. Researchers suggest that the C19orf12 protein plays a role in the maintenance of fat (lipid) molecules, a process known as lipid homeostasis. Mitochondrial membrane protein-associated neurodegeneration https://medlineplus.gov/genetics/condition/mitochondrial-membrane-protein-associated-neurodegeneration NBIA3 NBIA4 protein C19orf12 SPG43 NCBI Gene 83636 OMIM 614297 2014-04 2020-08-18 C2 complement C2 https://medlineplus.gov/genetics/gene/c2 functionThe C2 gene provides instructions for making the complement component 2 protein. This protein helps regulate a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. When a foreign invader is detected, the complement pathway is turned on (activated) and the complement component 2 protein attaches (binds) to a similar protein called complement component 4. Together, these proteins form a complex called C3 convertase, which triggers further activation of the pathway, allowing the proteins of the complement system to participate in an immune response. Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration Complement component 2 deficiency https://medlineplus.gov/genetics/condition/complement-component-2-deficiency ARMD14 C3/C5 convertase CO2 complement component 2 complement component C2 NCBI Gene 717 OMIM 613927 2014-06 2023-03-13 C3 complement C3 https://medlineplus.gov/genetics/gene/c3 functionThe C3 gene provides instructions for making a protein called complement component 3 (or C3). This protein plays a key role in a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues.The C3 protein is essential for turning on (activating) the complement system. The presence of foreign invaders triggers the C3 protein to be cut (cleaved) into two smaller pieces. One of these pieces, called C3b, interacts with several other proteins on the surface of cells to trigger the complement system's response. This process must be carefully regulated so the complement system targets only unwanted materials and does not damage the body's healthy cells.Researchers have identified two major forms (allotypes) of the C3 protein, which are known as C3S and C3F. In the general population, C3S is more common than C3F. The two allotypes differ by a single protein building block (amino acid), although it is unclear whether they function differently. Atypical hemolytic-uremic syndrome https://medlineplus.gov/genetics/condition/atypical-hemolytic-uremic-syndrome C3 glomerulopathy https://medlineplus.gov/genetics/condition/c3-glomerulopathy Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration acylation-stimulating protein cleavage product AHUS5 ARMD9 ASP C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1 C3a C3b CO3_HUMAN complement component 3 CPAMD1 NCBI Gene 718 OMIM 120700 OMIM 613779 2015-12 2020-08-18 C8A complement C8 alpha chain https://medlineplus.gov/genetics/gene/c8a functionThe C8A gene provides instructions for making one piece, the alpha subunit, of a protein complex called complement component 8. The alpha subunit is linked to another piece of the complex called the gamma subunit (produced from the C8G gene). These two proteins interact with the beta subunit (produced from the C8B gene) to form complement component 8.Complement component 8 aids in a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Complement component 8 combines with several other complement proteins to form the membrane attack complex (MAC), which inserts itself in the outer membrane of bacterial cells. This complex creates a hole (pore) in the membrane, which kills the bacterium. This part of the immune response appears to be especially important for fighting infection by bacteria in the Neisseria genus. C3 glomerulopathy https://medlineplus.gov/genetics/condition/c3-glomerulopathy Complement component 8 deficiency https://medlineplus.gov/genetics/condition/complement-component-8-deficiency complement component 8 alpha subunit complement component 8 subunit alpha complement component 8, alpha polypeptide complement component C8 alpha chain preproprotein NCBI Gene 731 OMIM 120950 2015-12 2020-08-18 C8B complement C8 beta chain https://medlineplus.gov/genetics/gene/c8b functionThe C8B gene provides instructions for making one piece, the beta subunit, of a protein complex called complement component 8. To form this complex, the beta subunit interacts with another piece made up of the alpha subunit (produced from the C8A gene) and the gamma subunit (produced from the C8G gene), which are linked.Complement component 8 aids in a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Complement component 8 combines with several other complement proteins to form the membrane attack complex (MAC), which inserts itself in the outer membrane of bacterial cells. This complex creates a hole (pore) in the membrane, which kills the bacterium. This part of the immune response appears to be especially important for fighting infection by bacteria in the Neisseria genus. Complement component 8 deficiency https://medlineplus.gov/genetics/condition/complement-component-8-deficiency C82 complement component 8 subunit beta complement component 8, beta polypeptide complement component C8 beta chain isoform 1 preproprotein complement component C8 beta chain isoform 2 complement component C8 beta chain isoform 3 NCBI Gene 732 OMIM 120960 2015-12 2020-08-18 C9orf72 C9orf72-SMCR8 complex subunit https://medlineplus.gov/genetics/gene/c9orf72 functionThe C9orf72 gene provides instructions for making a protein that is found in various tissues. The protein is abundant in nerve cells (neurons) in the outer layers of the brain (cerebral cortex) and in specialized neurons in the brain and spinal cord that control movement (motor neurons). The C9orf72 protein is thought to be located at the tip of the neuron in a region called the presynaptic terminal. This area is important for sending and receiving signals between neurons.The C9orf72 protein likely plays a role in many processes involving the chemical cousin of DNA, known as RNA. This protein is thought to influence the production of RNA from genes, the production of proteins from RNA, and the transport of RNA within the cell.The C9orf72 gene contains a segment of DNA made up of a series of six DNA building blocks (nucleotides), four guanines followed by two cytosines (written as GGGGCC). This segment (known as a hexanucleotide repeat) can occur once or be repeated multiple times in a row; estimates suggest repeats of up to 30 times have no negative effect on gene function. Amyotrophic lateral sclerosis https://medlineplus.gov/genetics/condition/amyotrophic-lateral-sclerosis CI072_HUMAN MGC23980 uncharacterized protein C9orf72 NCBI Gene 203228 OMIM 614260 2016-02 2022-07-05 CA12 carbonic anhydrase 12 https://medlineplus.gov/genetics/gene/ca12 functionThe CA12 gene provides instructions for making a protein called carbonic anhydrase 12 (CA 12), which belongs to a family of proteins known as carbonic anhydrases. These proteins carry out a chemical reaction that involves the molecules carbon dioxide and water and produces a negatively charged bicarbonate molecule (bicarbonate ion) and a positively charged hydrogen atom (known as a proton). Carbonic anhydrases can also carry out the reverse reaction, forming carbon dioxide and water from bicarbonate. Carbon dioxide, bicarbonate, and protons are involved in many functions in the body; by regulating the levels of these substances, carbonic anhydrases play roles in several important processes. The presence of protons and bicarbonate affect the relative acidity (pH) of cells; one function of some carbonic anhydrases is to help maintain the correct cellular pH.CA 12 is found in several tissues, including the sweat glands, kidneys, and large intestine. The protein likely helps regulate the transport of salt (sodium chloride or NaCl) in these tissues. Researchers suggest that channels that move salt in and out of cells are controlled in part by the pH of the cells. By regulating cellular pH, CA 12 may be able to control salt transport. In sweat glands, CA 12 is thought to play a role in determining how much salt is released from the body in sweat. Isolated hyperchlorhidrosis https://medlineplus.gov/genetics/condition/isolated-hyperchlorhidrosis CA XII CA-XII carbonate dehydratase XII carbonic anhydrase XII carbonic dehydratase CAXII tumor antigen HOM-RCC-3.1.3 NCBI Gene 771 OMIM 603263 2014-05 2020-08-18 CA5A carbonic anhydrase 5A https://medlineplus.gov/genetics/gene/ca5a functionThe CA5A gene provides instructions for making an enzyme called carbonic anhydrase VA. This enzyme helps convert carbon dioxide to a substance called bicarbonate. Bicarbonate is necessary to maintain the proper acid-base balance in the body, which is necessary for most biological reactions to proceed properly.The carbonic anhydrase VA enzyme is particularly important in the liver, where it provides bicarbonate needed by four enzymes in the energy-producing centers of cells (mitochondria): carbomoyl phosphate synthetase-1, pyruvate carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase. These enzymes help control the amount of certain other substances in the body. Carbomoyl phosphate synthetase-1 is involved in the urea cycle, which processes excess nitrogen and prevents it from accumulating as ammonia, a substance that is toxic to the brain. Pyruvate carboxylase is involved in the production of the simple sugar glucose (gluconeogenesis) in the liver. Propionyl-CoA carboxylase and 3-methylcrotonyl-CoA carboxylase help break down certain protein building blocks (amino acids). Carbonic anhydrase VA deficiency https://medlineplus.gov/genetics/condition/carbonic-anhydrase-va-deficiency CA-VA CA5 CA5AD carbonate dehydratase VA carbonic anhydrase 5A, mitochondrial precursor carbonic anhydrase V, mitochondrial carbonic anhydrase VA, mitochondrial carbonic dehydratase CAV CAVA GS1-21A4.1 NCBI Gene 763 OMIM 114761 2016-09 2020-08-18 CACNA1A calcium voltage-gated channel subunit alpha1 A https://medlineplus.gov/genetics/gene/cacna1a functionThe CACNA1A gene belongs to a family of genes that provide instructions for making calcium channels. These channels, which transport positively charged calcium atoms (calcium ions) across cell membranes, play a key role in a cell's ability to generate and transmit electrical signals. Calcium ions are involved in many different cellular functions, including cell-to-cell communication, the tensing of muscle fibers (muscle contraction), and the regulation of certain genes.The CACNA1A gene provides instructions for making one part (the alpha-1 subunit) of a calcium channel called CaV2.1. This subunit forms the hole (pore) through which calcium ions can flow. CaV2.1 channels play an essential role in communication between nerve cells (neurons) in the brain. These channels are especially abundant in neurons called Purkinje cells and granule cells. These neurons are found in the part of the brain that coordinates movement (the cerebellum) .CaV2.1 channels help control the release of neurotransmitters, which are chemicals that relay signals from one neuron to another. Researchers believe that CaV2.1 channels are also involved in the survival of neurons and the ability of these cells to change and adapt over time (plasticity).The CACNA1A gene also provides instructions for making another protein called alpha1-ACT (α1ACT). This protein acts as a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The α1ACT protein is important for the development of neurons, especially Purkinje cells.Near the tail end of the CACNA1A gene, a segment of three DNA building blocks (nucleotides) is repeated multiple times. This sequence, which is written as CAG, is called a triplet or trinucleotide repeat. The number of CAG repeats in this gene typically ranges from 4 to 18.  Familial hemiplegic migraine https://medlineplus.gov/genetics/condition/familial-hemiplegic-migraine Episodic ataxia https://medlineplus.gov/genetics/condition/episodic-ataxia Spinocerebellar ataxia type 6 https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-6 Sporadic hemiplegic migraine https://medlineplus.gov/genetics/condition/sporadic-hemiplegic-migraine 19p13.13 deletion syndrome https://medlineplus.gov/genetics/condition/19p1313-deletion-syndrome APCA brain calcium channel 1 CAC1A_HUMAN CACNL1A4 calcium channel, alpha 1A subunit calcium channel, L type, alpha-1 polypeptide, isoform 4 calcium channel, voltage-dependent, P/Q type, alpha 1A subunit CAV2.1 HPCA SCA6 Voltage-gated calcium channel subunit alpha Cav2.1 NCBI Gene 773 OMIM 601011 2023-05 2023-05-04 CACNA1C calcium voltage-gated channel subunit alpha1 C https://medlineplus.gov/genetics/gene/cacna1c functionThe CACNA1C gene provides instructions for making one of several calcium channels. Calcium channels, which transport positively charged calcium atoms (calcium ions) into cells, play a key role in a cell's ability to generate electrical signals. Calcium ions are important for many cellular functions, including regulating the electrical activity of cells, cell-to-cell communication, the tensing of muscle fibers (muscle contraction), and the regulation of certain genes, particularly those involved in the development of the brain and bones before birth.The calcium channel produced from the CACNA1C gene is known as CaV1.2. These channels are found in many types of cells, although they appear to be particularly important for the function of heart cells (cardiomyocytes) and nerve cells (neurons) in the brain. In the heart, CaV1.2 channels open and close at specific times to control the flow of calcium ions into cardiomyocytes at each heartbeat. How long the channels are open and closed is regulated to maintain normal heart function. In the brain, CaV1.2 channels are thought to be involved in memory, the fear response, and the rapid transmission of nerve signals; however, the role of these channels in the brain and other tissues is not completely understood.Researchers have discovered that many different versions (isoforms) of the CaV1.2 channel can be produced from the CACNA1C gene by a mechanism called alternative splicing. This mechanism produces different versions of the channel by cutting and rearranging the genetic instructions in different ways. Some versions of the CaV1.2 channel are more common than others in certain parts of the body. For example, in the heart and brain, about 80 percent of CaV1.2 channels are made with a particular segment known as exon 8. The other 20 percent of CaV1.2 channels contain a slightly different version of this segment, known as exon 8A. This difference becomes important when researchers are studying the effects of CACNA1C mutations in various tissues. Brugada syndrome https://medlineplus.gov/genetics/condition/brugada-syndrome Short QT syndrome https://medlineplus.gov/genetics/condition/short-qt-syndrome Timothy syndrome https://medlineplus.gov/genetics/condition/timothy-syndrome CAC1C_HUMAN CACH2 CACN2 CACNL1A1 calcium channel, cardic dihydropyridine-sensitive, alpha-1 subunit calcium channel, L type, alpha 1 polypeptide, isoform 1, cardic muscle calcium channel, voltage-dependent, L type, alpha 1C subunit CaV1.2 CCHL1A1 DHPR, alpha-1 subunit MGC120730 voltage-dependent L-type calcium channel alpha 1C subunit voltage-gated calcium channel alpha subunit Cav1.2 NCBI Gene 775 OMIM 114205 OMIM 618447 2020-02 2023-03-13 CACNA1D calcium voltage-gated channel subunit alpha1 D https://medlineplus.gov/genetics/gene/cacna1d functionThe CACNA1D gene belongs to a family of genes that provide instructions for making calcium channels. These channels transport positively charged calcium atoms (calcium ions) across cell membranes. The CACNA1D gene provides instructions for making one part (the alpha-1 subunit) of a calcium channel called CaV1.3. This subunit forms the hole (pore) through which calcium ions can flow. CaV1.3 channels are found in many types of cells, although they play a particularly important role in the adrenal glands, which are small hormone-producing glands located on top of each kidney. In the adrenal glands, the flow of calcium through CaV1.3 channels appears to help regulate the production of the hormone aldosterone, which helps control blood pressure by maintaining proper salt and fluid levels in the body. CaV1.3 channels are also found in the brain, heart, and inner ear, although their roles in these tissues are not well understood. Aldosterone-producing adenoma https://medlineplus.gov/genetics/condition/aldosterone-producing-adenoma CACH3 CACN4 CACNL1A2 calcium channel, neuroendocrine/brain-type, alpha 1 subunit calcium channel, voltage-dependent, L type, alpha 1D subunit Cav1.3 CCHL1A2 voltage-gated calcium channel alpha 1 subunit voltage-gated calcium channel alpha subunit Cav1.3 NCBI Gene 776 OMIM 114206 2017-07 2023-03-13 CACNA1F calcium voltage-gated channel subunit alpha1 F https://medlineplus.gov/genetics/gene/cacna1f functionThe CACNA1F gene belongs to a family of genes that provide instructions for making calcium channels. These channels, which transport positively charged calcium atoms (calcium ions) across cell membranes, play a key role in a cell's ability to generate and transmit electrical signals.The CACNA1F gene provides instructions for making one part (the alpha-1 subunit) of a calcium channel called CaV1.4. This subunit forms the hole (pore) in the cell membrane through which calcium ions can flow. CaV1.4 channels are found in many types of cells, although they play a particularly important role in a specialized tissue at the back of the eye called the retina. Within the retina, the channels are located in light-detecting cells called photoreceptors. The retina contains two types of photoreceptors: rods and cones. Rods are needed for vision in low light. Cones are needed for vision in bright light, including color vision.CaV1.4 channels play a critical role in normal vision. Studies suggest they help relay visual signals from rods and cones to other retinal cells called bipolar cells. This signaling is an essential step in the transmission of visual information from the eyes to the brain. X-linked congenital stationary night blindness https://medlineplus.gov/genetics/condition/x-linked-congenital-stationary-night-blindness Cone-rod dystrophy https://medlineplus.gov/genetics/condition/cone-rod-dystrophy CAC1F_HUMAN Cav1.4 Cav1.4alpha1 NCBI Gene 778 OMIM 300110 2024-06 2024-06-21 CACNA1S calcium voltage-gated channel subunit alpha1 S https://medlineplus.gov/genetics/gene/cacna1s functionThe CACNA1S gene provides instructions for making the main piece (subunit) of a structure called a calcium channel. Channels containing the CACNA1S protein are found in muscles used for movement (skeletal muscles). These skeletal muscle calcium channels play a key role in a process called excitation-contraction coupling, by which electrical signals (excitation) trigger muscle tensing (contraction).Calcium channels made with the CACNA1S subunit are located in the outer membrane of muscle cells, so they can transmit electrical signals from the cell surface to inside the cell. The channels interact with another type of calcium channel called ryanodine receptor 1 (RYR1) channels (produced from the RYR1 gene). RYR1 channels are located in the membrane of a structure inside the cell that stores calcium ions. Signals transmitted by CACNA1S-containing channels turn on (activate) RYR1 channels, which then release calcium ions inside the cells. The resulting increase in calcium ion concentration within muscle cells stimulates muscles to contract, allowing the body to move. Hypokalemic periodic paralysis https://medlineplus.gov/genetics/condition/hypokalemic-periodic-paralysis Malignant hyperthermia https://medlineplus.gov/genetics/condition/malignant-hyperthermia CAC1S_HUMAN CACH1 CACN1 CACNL1A3 calcium channel, voltage-dependent, L type, alpha 1S subunit Cav1.1 CCHL1A3 DHPR dihydropyridine receptor dihydropyridine-sensitive L-type calcium channel alpha-1 subunit HOKPP HypoKPP hypoPP MHS5 Voltage-dependent L-type calcium channel subunit alpha-1S voltage-gated calcium channel subunit alpha Cav1.1 NCBI Gene 779 OMIM 114208 2020-03 2020-08-18 CALR calreticulin https://medlineplus.gov/genetics/gene/calr functionThe CALR gene provides instructions for making a multi-functional protein called calreticulin. This protein is found in several parts of the cell, including inside a structure called the endoplasmic reticulum (ER), in the fluid-filled space inside the cell (the cytoplasm), and at the outer surface of the cell. The ER is involved in protein processing and transport, and within this structure, calreticulin plays a role in ensuring the proper folding of newly formed proteins. The ER is also a storage location for charged calcium atoms (calcium ions), and calreticulin is involved in maintaining the correct levels of calcium ions in this structure. Through calcium regulation and other mechanisms, calreticulin is thought to play a role in the control of gene activity, cell growth and division (proliferation) and movement (migration), the attachment of cells to one another (adhesion), and regulation of programmed cell death (apoptosis). The function of this protein is important for immune system function and wound healing. Primary myelofibrosis https://medlineplus.gov/genetics/condition/primary-myelofibrosis Essential thrombocythemia https://medlineplus.gov/genetics/condition/essential-thrombocythemia 19p13.13 deletion syndrome https://medlineplus.gov/genetics/condition/19p1313-deletion-syndrome calregulin calreticulin precursor cC1qR CRP55 CRT endoplasmic reticulum resident protein 60 epididymis secretory sperm binding protein Li 99n ERp60 FLJ26680 grp60 HACBP HEL-S-99n RO Sicca syndrome antigen A (autoantigen Ro; calreticulin) SSA NCBI Gene 811 OMIM 109091 2014-09 2020-08-18 CAPN3 calpain 3 https://medlineplus.gov/genetics/gene/capn3 functionThe CAPN3 gene provides instructions for making an enzyme called calpain-3, which is found within muscle fiber structures called sarcomeres. Sarcomeres are needed for the tensing of muscle fibers (contraction). When linked together, sarcomeres form myofibrils, which are the basic units of muscle fibers. Calpain-3 cuts (cleaves) damaged proteins into shorter segments so that they can be easily removed from the sarcomere. The process of making new proteins and breaking down older proteins within the sarcomere is known as sarcomere remodeling. This process enables the muscle cells to adapt to the body's needs. In addition to maintaining the sarcomeres, calpain-3 also interacts with other proteins to help regulate calcium transport within muscle fibers.  Limb-girdle muscular dystrophy https://medlineplus.gov/genetics/condition/limb-girdle-muscular-dystrophy calcium-activated neutral protease 3, muscle-specific, large subunit calpain calpain, large polypeptide L3 CANP3 CANPL3 nCL-1 p94 NCBI Gene 825 OMIM 114240 2025-11 2025-11-19 CARD11 caspase recruitment domain family member 11 https://medlineplus.gov/genetics/gene/card11 functionThe CARD11 gene provides instructions for making a protein involved in the function of immune system cells called lymphocytes, particularly certain types called T cells and B cells. These cells identify foreign substances such as bacteria, viruses, and fungi and defend the body against infection. When T or B cells recognize a foreign substance, the CARD11 protein is turned on (activated) and attaches (binds) to two other proteins, BCL10 and MALT1, to form the CBM signalosome complex. This complex in turn activates other protein complexes called nuclear factor-kappa-B (NF-κB) and mTOR complex 1 (mTORC1), which are important for cellular signaling. NF-κB and mTORC1 signaling direct the development and function of T and B cells so they can support an immune response against foreign invaders. Atopic dermatitis https://medlineplus.gov/genetics/condition/atopic-dermatitis Omenn syndrome https://medlineplus.gov/genetics/condition/omenn-syndrome bcl10-interacting maguk protein 3 BENTA BIMP3 CARD-containing MAGUK protein 1 carma 1 CARMA1 caspase recruitment domain-containing protein 11 IMD11 IMD11A PPBL NCBI Gene 84433 OMIM 603554 OMIM 607210 OMIM 615206 OMIM 616452 2017-10 2020-08-18 CARD14 caspase recruitment domain family member 14 https://medlineplus.gov/genetics/gene/card14 functionThe CARD14 gene provides instructions for making a protein that turns on (activates) a group of interacting proteins known as nuclear factor-kappa-B (NF-κB). The NF-κB protein complex regulates the activity of multiple genes, including genes that control the body's immune responses and inflammatory reactions. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). The NF-κB protein complex also protects cells from certain signals that would otherwise cause them to self-destruct (undergo apoptosis).The CARD14 protein is found in many of the body's tissues, but it is particularly abundant in the skin. NF-κB signaling appears to play important roles in regulating inflammatory reactions in the skin and in promoting the survival of skin cells. Psoriatic arthritis https://medlineplus.gov/genetics/condition/psoriatic-arthritis Familial pityriasis rubra pilaris https://medlineplus.gov/genetics/condition/familial-pityriasis-rubra-pilaris Generalized pustular psoriasis https://medlineplus.gov/genetics/condition/generalized-pustular-psoriasis bcl10-interacting maguk protein 2 BIMP2 CAR14_HUMAN CARD-containing MAGUK protein 2 card-maguk protein 2 carma 2 CARMA2 caspase recruitment domain family, member 14 caspase recruitment domain-containing protein 14 NCBI Gene 79092 OMIM 607211 2017-05 2020-08-18 CARD9 caspase recruitment domain family member 9 https://medlineplus.gov/genetics/gene/card9 functionThe CARD9 gene provides instructions for making an immune system protein that is involved in the body's defense against fungal infections and is particularly important for fighting infection by a fungus called Candida. When the immune system recognizes Candida, it generates cells called Th17 cells. These cells produce signaling molecules (cytokines) called the interleukin-17 (IL-17) family as part of an immune process called the IL-17 pathway. The IL-17 pathway creates inflammation, sending other cytokines and white blood cells that fight foreign invaders and promote tissue repair. In addition, the IL-17 pathway promotes the production of certain antimicrobial protein segments (peptides) that control growth of Candida on the surface of mucous membranes.In its role in defending against Candida on the mucous membranes and skin, the CARD9 protein passes along signals from other types of immune system proteins. Each of these proteins recognizes a different component of the Candida cell wall to trigger the production of Th17 cells and launch the immune response.In addition to its role in protecting mucous membranes from fungal infection, the CARD9 protein is also important in recruiting neutrophils (immune cells that have strong anti-fungal activity) from the blood to protect the brain and other organs from fungal infection. Familial candidiasis https://medlineplus.gov/genetics/condition/familial-candidiasis caspase recruitment domain family, member 9 hCARD9 NCBI Gene 64170 OMIM 607212 2016-09 2020-08-18 CASK calcium/calmodulin dependent serine protein kinase https://medlineplus.gov/genetics/gene/cask functionThe CASK gene provides instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK). The CASK protein is primarily found in nerve cells (neurons) in the brain, where it helps control the activity (expression) of other genes that are involved in brain development. It also helps regulate the movement of chemicals called neurotransmitters and of charged atoms (ions), which are necessary for signaling between neurons. Research suggests that the CASK protein may also interact with the protein produced from another gene, FRMD7, to promote development of the nerves that control eye movement (the oculomotor neural network). FG syndrome https://medlineplus.gov/genetics/condition/fg-syndrome CASK-related intellectual disability https://medlineplus.gov/genetics/condition/cask-related-intellectual-disability calcium/calmodulin-dependent serine protein kinase (MAGUK family) CAMGUK CMG CSKP_HUMAN hCASK LIN2 protein lin-2 homolog TNRC8 NCBI Gene 8573 OMIM 300172 2014-03 2020-08-18 CASQ2 calsequestrin 2 https://medlineplus.gov/genetics/gene/casq2 functionThe CASQ2 gene provides instructions for making a protein called calsequestrin 2. This protein is found in heart (cardiac) muscle cells called myocytes, where it is involved in the storage and transport of positively charged calcium atoms (calcium ions).Within myocytes, calsequestrin 2 is located in a cell structure called the sarcoplasmic reticulum, which acts as a storage center for calcium ions. Most of these ions are stored by attaching (binding) to calsequestrin 2. This protein also helps regulate a protein called the RYR2 channel, which controls the flow of calcium ions out of the sarcoplasmic reticulum.For the heart to beat normally, the cardiac muscle must tense (contract) and relax in a coordinated way. This cycle of muscle contraction and relaxation results from the precise control of calcium ions within myocytes. In response to certain signals, calcium ions stored by calsequestrin 2 in the sarcoplasmic reticulum are released into the surrounding cell fluid (the cytoplasm). The resulting increase in calcium ion concentration triggers the cardiac muscle to contract, which pumps blood out of the heart. Calcium ions are then transported back into the sarcoplasmic reticulum, and the cardiac muscle relaxes. In this way, the release and reuptake of calcium ions in myocytes produces a regular heart rhythm. Catecholaminergic polymorphic ventricular tachycardia https://medlineplus.gov/genetics/condition/catecholaminergic-polymorphic-ventricular-tachycardia calsequestrin 2 (cardiac muscle) calsequestrin 2, fast-twitch, cardiac muscle cardiac calsequestrin 2 CASQ2_HUMAN PDIB2 ICD-10-CM MeSH NCBI Gene 845 OMIM 114251 SNOMED CT 2020-07 2021-05-20 CASR calcium sensing receptor https://medlineplus.gov/genetics/gene/casr functionThe CASR gene provides instructions for making a protein called the calcium-sensing receptor (CaSR). Calcium molecules bind to CaSR, which allows this protein to monitor and regulate the amount of calcium in the blood.The CaSR protein is found in cells of the parathyroid glands. The four parathyroid glands are located in the neck. These glands produce and release a hormone called parathyroid hormone, which regulates the levels of calcium in the blood. When blood calcium levels are high, calcium binds to CaSR in the parathyroid glands and blocks the production of parathyroid hormone. Without parathyroid hormone, calcium is not released into the blood. CaSR signaling also blocks the growth and division (proliferation) of the cells that make up the parathyroid glands.The CaSR protein is also found in kidney cells. Kidneys filter fluid and waste products in the body and can reabsorb needed nutrients and release them back into the blood. When calcium binds to CaSR in kidney cells, it blocks the reabsorption of calcium and allows it to be released in the urine. Familial isolated hyperparathyroidism https://medlineplus.gov/genetics/condition/familial-isolated-hyperparathyroidism Autosomal dominant hypocalcemia https://medlineplus.gov/genetics/condition/autosomal-dominant-hypocalcemia Kidney stones https://medlineplus.gov/genetics/condition/kidney-stones calcium-sensing receptor CAR extracellular calcium-sensing receptor GPRC2A parathyroid Ca(2+)-sensing receptor 1 parathyroid cell calcium-sensing receptor PCAR1 NCBI Gene 846 OMIM 601199 2026-01 2026-01-23 CAT catalase https://medlineplus.gov/genetics/gene/cat functionThe CAT gene provides instructions for making pieces (subunits) of an enzyme called catalase. Four identical subunits, each attached (bound) to an iron-containing molecule called a heme group, form the functional enzyme.Catalase is active in cells and tissues throughout the body, where it breaks down hydrogen peroxide (H2O2) molecules into oxygen (O2) and water (H2O). Hydrogen peroxide is produced through chemical reactions within cells. At low levels, it is involved in several chemical signaling pathways, but at high levels it is toxic to cells. If hydrogen peroxide is not broken down by catalase, additional reactions convert it into compounds called reactive oxygen species that can damage DNA, proteins, and cell membranes. Acatalasemia https://medlineplus.gov/genetics/condition/acatalasemia CATA_HUMAN EC 1.11.1.6 NCBI Gene 847 OMIM 115500 2014-09 2023-07-25 CATSPER1 cation channel sperm associated 1 https://medlineplus.gov/genetics/gene/catsper1 functionThe CATSPER1 gene provides instructions for producing a protein that is found in the tail (flagellum) of sperm cells. The CATSPER1 protein plays a role in sperm cell movement (motility). It is one of four proteins that together form a hole (pore) that allows for the movement of charged calcium atoms (Ca2+) across the sperm cell membrane. Ca2+ is needed for a type of sperm motility called hyperactivation. Hyperactivation is characterized by vigorous movements of the sperm tail, which allow the sperm to push through the membrane of the egg cell during fertilization. CATSPER1-related nonsyndromic male infertility https://medlineplus.gov/genetics/condition/catsper1-related-nonsyndromic-male-infertility cation channel, sperm associated 1 CATSPER CTSR1_HUMAN sperm ion channel sperm-associated cation channel 1 ICD-10-CM MeSH NCBI Gene 117144 OMIM 606389 SNOMED CT 2024-04 2024-04-30 CATSPER2 cation channel sperm associated 2 https://medlineplus.gov/genetics/gene/catsper2 functionThe CATSPER2 gene provides instructions for producing a protein that is found in the tail (flagellum) of sperm cells. The CATSPER2 protein plays a role in sperm cell movement (motility). It is one of four proteins that together form a hole (pore) that allows for the movement of charged calcium atoms (Ca2+) across the sperm cell membrane. Ca2+ is needed for a type of sperm motility called hyperactivation. Hyperactivation is characterized by vigorous movements of the sperm tail, allow the sperm to push through the membrane of the egg cell during fertilization. Deafness-infertility syndrome https://medlineplus.gov/genetics/condition/deafness-infertility-syndrome cation channel, sperm associated 2 CTSR2_HUMAN ICD-10-CM MeSH NCBI Gene 117155 OMIM 607249 SNOMED CT 2024-04 2024-04-26 CAV1 caveolin 1 https://medlineplus.gov/genetics/gene/cav1 functionThe CAV1 gene provides instructions for making a protein called caveolin-1. This protein appears to have diverse functions in cells and tissues throughout the body.Caveolin-1 is the major component of caveolae, which are small pouches in the membrane that surrounds cells. Caveolae have multiple functions, some of which are not well understood. They are known to be involved in the transport of molecules from the cell membrane to the interior of the cell (endocytosis), processing of molecules on their way into the cell, maintaining the cell structure, and regulating chemical signaling pathways. Studies suggest that caveolae are particularly numerous in adipocytes, which are cells that store fats for energy. Adipocytes make up most of the body's fatty (adipose) tissue. In these cells, caveolae appear to be essential for the normal transport, processing, and storage of fats.Caveolin-1 is also found in many other parts of cells, where it regulates various chemical signaling pathways. Through these pathways, caveolin-1 is involved in regulating cell growth and division (proliferation), the process by which cells mature to perform specific functions (differentiation), cell survival and the self-destruction of cells (apoptosis), and cell movement. The functions of caveolin-1 likely differ depending on the type of cell and the part of the cell where the protein is found. Pulmonary arterial hypertension https://medlineplus.gov/genetics/condition/pulmonary-arterial-hypertension Congenital generalized lipodystrophy https://medlineplus.gov/genetics/condition/congenital-generalized-lipodystrophy BSCL3 CAV caveolin 1, caveolae protein, 22kDa caveolin-1 isoform alpha caveolin-1 isoform beta cell growth-inhibiting protein 32 CGL3 LCCNS MSTP085 PPH3 VIP21 NCBI Gene 857 OMIM 601047 OMIM 606721 2015-12 2020-08-18 CAV3 caveolin 3 https://medlineplus.gov/genetics/gene/cav3 functionThe CAV3 gene provides instructions for making a protein called caveolin-3, which is found in the membrane surrounding muscle cells. This protein is the main component of caveolae, which are small pouches in the muscle cell membrane. Within the caveolae, the caveolin-3 protein acts as a scaffold to organize other molecules that are important for cell signaling and maintenance of the cell structure. These molecules include the proteins that make up sodium channels, which transport positively charged sodium atoms (sodium ions) into cells. Sodium channels play a key role in a cell's ability to generate and transmit electrical signals. In cardiac muscle, sodium channels are involved in maintaining the heart's normal rhythm. Caveolin-3 may also help regulate calcium levels in the muscle cell, which control muscle contraction and relaxation. Romano-Ward syndrome https://medlineplus.gov/genetics/condition/romano-ward-syndrome Rippling muscle disease https://medlineplus.gov/genetics/condition/rippling-muscle-disease Isolated hyperCKemia https://medlineplus.gov/genetics/condition/isolated-hyperckemia CAV3-related distal myopathy https://medlineplus.gov/genetics/condition/cav3-related-distal-myopathy CAV3_HUMAN caveolin-3 LGMD1C LQT9 M-caveolin MGC126100 MGC126101 MGC126129 VIP-21 VIP21 NCBI Gene 859 OMIM 601253 OMIM 611818 2014-05 2025-11-19 CAVIN1 caveolae associated protein 1 https://medlineplus.gov/genetics/gene/cavin1 functionThe CAVIN1 gene provides instructions for making a protein called cavin-1. This protein is found in cells and tissues throughout the body. It is most abundant in several types of cells: osteoblasts, which are cells that build bones; muscle cells; and adipocytes, which are cells that store fats for energy. Adipocytes make up most of the body's fatty (adipose) tissue.Studies suggest that cavin-1 plays an essential role in forming and stabilizing caveolae, which are small pouches in the membrane that surrounds cells. Caveolae have multiple functions, some of which are not well understood. They are known to be involved in the transport of molecules from the cell membrane to the interior of the cell (endocytosis), processing of molecules on their way into the cell, maintaining the cell structure, and regulating chemical signaling pathways. Caveolae are particularly numerous in adipocytes, where they appear to be essential for the normal transport, processing, and storage of fats.Within cells, cavin-1 is also found in the nucleus and in the fluid that surrounds the nucleus (the cytoplasm). In addition to its role in caveolae, studies suggest that this protein is involved in repairing damage to the outer cell membrane, cell growth and division (proliferation), cell movement, stopping cell division in older cells (senescence), and regulating various chemical signaling pathways. The functions of cavin-1 likely differ depending on the type of cell and the part of the cell where the protein is found. Congenital generalized lipodystrophy https://medlineplus.gov/genetics/condition/congenital-generalized-lipodystrophy CAVIN cavin-1 CGL4 FKSG13 polymerase I and transcript release factor PTRF RNA polymerase I and transcript release factor TTF-I interacting peptide 12 NCBI Gene 284119 OMIM 603198 2015-12 2020-08-18 CBFB core-binding factor subunit beta https://medlineplus.gov/genetics/gene/cbfb functionThe CBFB gene provides instructions for making a protein called core binding factor beta (CBFβ), which is one piece of a protein complex known as core binding factor (CBF). CBFβ attaches (binds) to one of three related RUNX proteins (RUNX1, RUNX2, or RUNX3) to form different versions of CBF. These protein complexes bind to specific regions of DNA and help turn on (activate) certain genes.The presence of CBFβ helps the complex bind to DNA and protects the RUNX protein from being broken down. The function of CBF depends on which RUNX protein it includes. Once bound to DNA, the RUNX1 protein controls the activity of genes involved in the development of blood cells (hematopoiesis). The RUNX2 protein regulates genes important for bone cell development and formation of the skeleton. The RUNX3 protein primarily affects genes involved in the development of nerve cells. Core binding factor acute myeloid leukemia https://medlineplus.gov/genetics/condition/core-binding-factor-acute-myeloid-leukemia CBF-beta core-binding factor beta subunit core-binding factor, beta subunit PEA2-beta PEBB_HUMAN PEBP2-beta PEBP2B polyomavirus enhancer binding protein 2, beta subunit polyomavirus enhancer-binding protein 2 beta subunit SL3-3 enhancer factor 1 beta subunit SL3-3 enhancer factor 1 subunit beta SL3/AKV core-binding factor beta subunit NCBI Gene 865 OMIM 121360 2013-11 2020-08-18 CBS cystathionine beta-synthase https://medlineplus.gov/genetics/gene/cbs functionThe CBS gene provides instructions for making an enzyme called cystathionine beta-synthase. This enzyme acts in a chemical pathway and is responsible for using vitamin B6 to convert building block of proteins (amino acid) called homocysteine and serine to a molecule called cytathionine. Another enzyme then converts cystathionine to the amino acid cysteine, which is used to build proteins or is broken down and excreted in urine. Additionally, other amino acids, including methionine, are produced in this pathway. Homocystinuria https://medlineplus.gov/genetics/condition/homocystinuria beta-thionase CBS_HUMAN HIP4 methylcysteine synthase serine sulfhydrase NCBI Gene 875 OMIM 613381 2011-07 2022-06-21 CCBE1 collagen and calcium binding EGF domains 1 https://medlineplus.gov/genetics/gene/ccbe1 functionThe CCBE1 gene provides instructions for making a protein that is found in the extracellular matrix, which is the lattice of proteins and other molecules that forms in the spaces between cells. Early in development, the CCBE1 protein is involved in the formation of the lymphatic system, which is a network of vessels that transport white blood cells (lymphocytes), nutrients, and proteins in a fluid called lymph.The CCBE1 protein helps guide the maturation (differentiation) and movement (migration) of immature cells called lymphangioblasts that will eventually form the lining (epithelium) of lymphatic vessels. Additionally, the CCBE1 protein works with a protein produced from the ADAMTS3 gene to help regulate the activity of a protein called vascular endothelial growth factor receptor 3 (VEGFR3). VEGFR3 plays a key role in the development and maintenance of the lymphatic system. Hennekam syndrome https://medlineplus.gov/genetics/condition/hennekam-syndrome FLJ30681 KIAA1983 NCBI Gene 147372 OMIM 612753 2026-03 2026-03-20 CCDC40 coiled-coil domain 40 molecular ruler complex subunit https://medlineplus.gov/genetics/gene/ccdc40 functionThe CCDC40 gene provides instructions for making a protein that is involved in the assembly of a larger group of proteins (a complex) called dynein. Dynein functions within cell structures called cilia and flagella. Cilia are microscopic, finger-like projections that stick out from the surface of cells. Coordinated back and forth movement of cilia can move the cell or the fluid surrounding the cell. Flagella are similar to cilia, but flagella are found only in sperm cells. Dynein makes up the structures (arms) that produce the force needed for cilia and flagella to move. Dynein forms structures known as inner dynein arms (IDAs) and outer dynein arms (ODAs) within the core of cilia and flagella (the axoneme). Coordinated movement of the dynein arms causes the entire axoneme to bend back and forth. The CCDC40 protein is necessary for the proper assembly of the IDAs, which play a central role in the coordinated movement of cilia and flagella. Researchers suspect that the CCDC40 protein is also involved in the proper assembly of the nexin-dynein regulatory complex, which helps regulate and coordinate the activity of the inner and outer dynein arms. By helping with the assembly of both the IDAs and the nexin-dynein regulatory complex, the CCDC40 protein plays a central role in the coordinated movement of cilia and flagella.  Primary ciliary dyskinesia https://medlineplus.gov/genetics/condition/primary-ciliary-dyskinesia CFAP172 coiled-coil domain containing 40 coiled-coil domain containing protein 40 FAP172 FLJ20753 FLJ32021 KIAA1640 NCBI Gene 55036 OMIM 613799 2025-09 2025-09-30 CCM2 CCM2 scaffold protein https://medlineplus.gov/genetics/gene/ccm2 functionThe CCM2 gene provides instructions for making a protein called malcavernin, which strengthens the interactions between cells that form blood vessels and limits leakage from the vessels. Malcavernin interacts with a number of other proteins to form a complex that is found in the junctions that connect neighboring cells. As part of this complex, malcavernin helps turn off (suppress) a signaling molecule known as RhoA-GTPase. This molecule plays a role in regulating the actin cytoskeleton, which is a network of fibers that makes up the cell's structural framework. When turned on, RhoA-GTPase stimulates the formation of actin fibers, which has been linked to weakened junctions between cells and increased leakage from blood vessels.Malcavernin is also involved in a process called angiogenesis, which is the formation of new blood vessels. Cerebral cavernous malformation https://medlineplus.gov/genetics/condition/cerebral-cavernous-malformation C7orf22 CCM2 scaffolding protein CCM2_HUMAN cerebral cavernous malformation 2 chromosome 7 open reading frame 22 MGC4067 MGC4607 OSM NCBI Gene 83605 OMIM 607929 2012-11 2020-08-18 CCN6 cellular communication network factor 6 https://medlineplus.gov/genetics/gene/ccn6 functionThe CCN6 gene provides instructions for making a protein that appears to be involved in bone growth and the maintenance of cartilage, which covers and protects the ends of bones. The function of the CCN6 protein is not well understood. It is part of a family of proteins that are involved in the growth and maintenance of connective tissues, such as bone, cartilage, and blood vessels. The CCN6 protein is made in cells called chondrocytes, which produce and maintain cartilage, and is associated with the production of certain proteins that make up cartilage, but its role in their production is unclear. CCN6 may also help control signaling pathways involved in the development of cartilage and bone and may help regulate the breakdown of cartilage components. Juvenile idiopathic arthritis https://medlineplus.gov/genetics/condition/juvenile-idiopathic-arthritis Progressive pseudorheumatoid dysplasia https://medlineplus.gov/genetics/condition/progressive-pseudorheumatoid-dysplasia CCN family member 6 LIBC PPAC PPD WISP-3 WISP3 WISP3_HUMAN WNT1 inducible signaling pathway protein 3 WNT1-inducible-signaling pathway protein 3 NCBI Gene 8838 OMIM 603400 2013-04 2020-08-18 CCND2 cyclin D2 https://medlineplus.gov/genetics/gene/ccnd2 functionThe CCND2 gene provides instructions for making a protein called cyclin D2. Cyclins are a family of proteins that control how cells proceed through the multi-step cycle of cell division. Cyclin D2 helps to regulate a step in the cycle called the G1-S transition, in which the cell moves from the G1 phase, when cell growth occurs, to the S phase, when the cell's DNA is copied (replicated) in preparation for cell division. Cyclin D2's role in the cell division cycle makes it a key controller of the rate of cell growth and division (proliferation) in the body.The cyclin D2 protein is regulated by a chemical signaling pathway called the PI3K-AKT-mTOR pathway. This signaling influences many critical cell functions, including the creation (synthesis) of new proteins, cell proliferation, and the survival of cells. The PI3K-AKT-mTOR pathway is essential for the normal development of many parts of the body, including the brain. Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome https://medlineplus.gov/genetics/condition/megalencephaly-polymicrogyria-polydactyly-hydrocephalus-syndrome G1/S-specific cyclin-D2 KIAK0002 MPPH3 NCBI Gene 894 OMIM 123833 2017-01 2023-03-20 CD40LG CD40 ligand https://medlineplus.gov/genetics/gene/cd40lg functionThe CD40LG gene provides instructions for making a protein called CD40 ligand, which is found on the surface of immune system cells known as T cells. CD40 ligand attaches like a key in a lock to its receptor protein, CD40, which is located on the surface of immune system cells known as B cells. B cells are involved in the production of proteins called antibodies or immunoglobulins that help protect the body against infection. There are several classes of antibodies, and each one has a different function in the immune system. B cells are able to mature into the cells that produce immunoglobulin M (IgM) without any signals from other cells. In order for B cells to mature into the cells that produce antibodies of a different class, the CD40 receptor must interact with CD40 ligand. When these two proteins are connected, they trigger a series of chemical signals that instruct the B cell to start making immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE).CD40 ligand is also necessary for T cells to interact with other cells of the immune system, and it plays a key role in T cell differentiation (the process by which cells mature to carry out specific functions). X-linked hyper IgM syndrome https://medlineplus.gov/genetics/condition/x-linked-hyper-igm-syndrome CD154 CD40 antigen ligand CD40L CD40L_HUMAN gp39 hCD40L HIGM1 IGM IMD3 T-B cell-activating molecule T-BAM TNF-related activation protein TNFSF5 TRAP tumor necrosis factor (ligand) superfamily member 5 NCBI Gene 959 OMIM 300386 2008-10 2020-08-18 CDAN1 codanin 1 https://medlineplus.gov/genetics/gene/cdan1 functionThe CDAN1 gene provides instructions for making a protein called codanin-1. Research suggests that codanin-1 plays an important role in maintaining the structure of the nucleus (where most of the cell's DNA is located). Specifically, codanin-1 is likely involved in putting together cell components called nucleosomes that help bundle DNA in a tight package. This tight packaging helps control gene expression.Because codanin-1 has the ability to regulate gene activity, it is involved in many processes during development, including the growth of cells as they progress through the step-by-step process for replication (the cell cycle). Codanin-1 is also thought to be involved in the differentiation and development of red blood cells (erythropoiesis), though the protein's specific role in this process is unclear. Congenital dyserythropoietic anemia https://medlineplus.gov/genetics/condition/congenital-dyserythropoietic-anemia CDA-I CDA1 CDAN1_HUMAN codanin NCBI Gene 146059 OMIM 607465 2025-03 2025-03-04 CDC6 cell division cycle 6 https://medlineplus.gov/genetics/gene/cdc6 functionThe CDC6 gene provides instructions for making a protein that is important in the copying of a cell's DNA before the cell divides (a process known as DNA replication). The protein produced from this gene, called cell division cycle 6 or CDC6, is one of a group of proteins known as the pre-replication complex. In a multi-step process, the components of this complex attach (bind) to certain regions of DNA known as origins of replication (or origins), where the process of DNA copying begins. When the pre-replication complex is attached to the origin, replication is able to begin at that location. This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide. Meier-Gorlin syndrome https://medlineplus.gov/genetics/condition/meier-gorlin-syndrome cdc18-related protein CDC18L CDC6 cell division cycle 6 homolog CDC6-related protein CDC6_HUMAN cell division control protein 6 homolog cell division cycle 6 homolog HsCDC18 HsCDC6 p62(cdc6) NCBI Gene 990 OMIM 602627 2014-02 2020-08-18 CDC73 cell division cycle 73 https://medlineplus.gov/genetics/gene/cdc73 functionThe CDC73 gene provides instructions for making a protein called parafibromin. This protein is found primarily in the nucleus of cells and is likely involved in regulating gene transcription, which is the first step in protein production. Parafibromin functions as a tumor suppressor, which means it keeps cells from growing and dividing (proliferating) too fast or in an uncontrolled way. When parafibromin is found outside the nucleus, it appears to be involved in the organization of the cell's structural framework (the cytoskeleton). Hyperparathyroidism-jaw tumor syndrome https://medlineplus.gov/genetics/condition/hyperparathyroidism-jaw-tumor-syndrome Familial isolated hyperparathyroidism https://medlineplus.gov/genetics/condition/familial-isolated-hyperparathyroidism Parathyroid cancer https://medlineplus.gov/genetics/condition/parathyroid-cancer C1orf28 CDC73_HUMAN cell division cycle protein 73 homolog HRPT2 hyperparathyroidism 2 protein hyrax HYX parafibromin NCBI Gene 79577 OMIM 607393 2026-01 2026-01-23 CDH1 cadherin 1 https://medlineplus.gov/genetics/gene/cdh1 functionThe CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body, such as the inside of the eyelids and mouth. E-cadherin belongs to a family of proteins called cadherins whose function is to help neighboring cells stick to one another (cell adhesion) to form organized tissues. Another protein called p120-catenin, produced from the CTNND1 gene, helps keep E-cadherin in its proper place in the cell membrane, preventing it from being taken into the cell through a process called endocytosis and broken down prematurely.E-cadherin is one of the best-understood cadherin proteins. In addition to its role in cell adhesion, E-cadherin is involved in transmitting chemical signals within cells, controlling cell maturation and movement, and regulating the activity of certain genes. Interactions between the E-cadherin and p120-catenin proteins, in particular, are thought to be important for normal development of the head and face (craniofacial development), including the eyelids and teeth. E-cadherin also acts as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. Breast cancer https://medlineplus.gov/genetics/condition/breast-cancer Hereditary diffuse gastric cancer https://medlineplus.gov/genetics/condition/hereditary-diffuse-gastric-cancer Prostate cancer https://medlineplus.gov/genetics/condition/prostate-cancer Ovarian cancer https://medlineplus.gov/genetics/condition/ovarian-cancer Blepharocheilodontic syndrome https://medlineplus.gov/genetics/condition/blepharocheilodontic-syndrome Arc-1 CADH1_HUMAN cadherin 1, E-cadherin (epithelial) cadherin 1, type 1 cadherin 1, type 1, E-cadherin (epithelial) calcium-dependent adhesion protein, epithelial CAM 120/80 CD324 CDHE cell-CAM 120/80 E-cadherin ECAD LCAM liver cell adhesion molecule UVO uvomorulin NCBI Gene 999 OMIM 192090 2017-07 2020-08-18 CDH23 cadherin related 23 https://medlineplus.gov/genetics/gene/cdh23 functionThe CDH23 gene provides instructions for making cadherin 23, a type of protein that helps cells stick together. Different versions of this protein are made in different cell types, including a short version in the retina, which is the light-sensitive layer in the back of the eye, and a longer version in the inner ear. Cadherin 23 interacts with other proteins in the cell membrane as part of a protein complex that is involved in cell attachment.Research suggests that the cadherin 23 protein complex helps to shape structures in the inner ear called hair bundles. These structures are made of stereocilia, which are hairlike projections that bend in response to sound waves. This bending motion is critical for converting sound waves to nerve impulses, which are then transmitted to the brain. Stereocilia are also elements of the vestibular system, the part of the inner ear that helps maintain the body's balance and orientation in space. Bending of these stereocilia is needed to transmit signals from the vestibular system to the brain.In the retina, the role of the cadherin 23 protein complex is less well understood. Studies suggest that it plays a critical role in the function of photoreceptor cells, which are specialized cells that detect light and color. Usher syndrome https://medlineplus.gov/genetics/condition/usher-syndrome Nonsyndromic hearing loss https://medlineplus.gov/genetics/condition/nonsyndromic-hearing-loss Age-related hearing loss https://medlineplus.gov/genetics/condition/age-related-hearing-loss CAD23_HUMAN cadherin-23 cadherin-like 23 cadherin-related 23 CDHR23 DFNB12 KIAA1774 KIAA1812 otocadherin USH1D NCBI Gene 64072 OMIM 605516 2016-05 2023-03-20 CDIN1 CDAN1 interacting nuclease 1 https://medlineplus.gov/genetics/gene/cdin1 functionThe CDIN1 gene provides instructions for making a protein called the CDAN1-interacting nuclease 1. This protein likely acts as a nuclease. Nucleases cut (cleave) building blocks called nucleotides one at a time from DNA and its chemical cousin RNA. CDAN1-interacting nuclease 1 is thought to play a role in correcting errors (DNA repair) that are made when DNA is copied (DNA replication) in preparation for cell division. This protein is also involved in the growth and development of red blood cells (erythropoiesis). Congenital dyserythropoietic anemia https://medlineplus.gov/genetics/condition/congenital-dyserythropoietic-anemia C15orf41 HH114 NCBI Gene 84529 OMIM 615626 2025-03 2025-03-04 CDKL5 cyclin dependent kinase like 5 https://medlineplus.gov/genetics/gene/cdkl5 functionThe CDKL5 gene provides instructions for making a protein that is found in cells and tissues throughout the body. However, it is most active in the brain and is essential for normal brain development and function. There are five versions (isoforms) of the CDKL5 protein. These isoforms vary in length and in the tissues in which they are most abundant.Studies suggest that the CDKL5 protein is involved in the formation, growth, and movement (migration) of nerve cells (neurons), as well as cell division. It also plays a role in the transmission of chemical signals at the connections (synapses) between neurons.The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. It is possible that one of the proteins targeted by the CDKL5 protein is MeCP2, which is produced from the MECP2 gene. The MeCP2 protein plays important roles in the function of neurons and other brain cells and in the maintenance of neuronal synapses. Researchers have not determined which other proteins are targeted by the CDKL5 protein. CDKL5 deficiency disorder https://medlineplus.gov/genetics/condition/cdkl5-deficiency-disorder CDKL5_HUMAN CFAP247 cyclin-dependent kinase-like 5 serine/threonine kinase 9 STK9 NCBI Gene 6792 OMIM 300203 2017-11 2023-03-20 CDKN1B cyclin dependent kinase inhibitor 1B https://medlineplus.gov/genetics/gene/cdkn1b functionThe CDKN1B gene provides instructions for making a protein called p27. This protein is found in cells and tissues throughout the body. Within cells, p27 is located primarily in the nucleus, where it plays a critical role in controlling cell growth and division. It helps regulate the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. Specifically, p27 normally blocks cells from entering the phase of the cell cycle when DNA is copied (replicated) in preparation for cell division. By blocking cell cycle progression, p27 prevents cells from dividing too quickly or at the wrong time. Based on this function, p27 is described as a tumor suppressor protein. Studies suggest that p27 is also involved in controlling cell differentiation, which is the process by which cells mature to carry out specific functions.Because p27 plays such a key role in controlling cell division, its activity is tightly regulated. Regulation can occur through modification of the p27 protein's structure, its interaction with other proteins, or its localization within the cell. For example, when p27 is held (sequestered) in the fluid that surrounds the nucleus (the cytoplasm) instead of being transported into the nucleus, the protein is unavailable to block cell cycle progression. Researchers believe that p27 may have other functions in the cytoplasm, but these functions have not been well described. Multiple endocrine neoplasia https://medlineplus.gov/genetics/condition/multiple-endocrine-neoplasia CDKN4 CDN1B_HUMAN cyclin-dependent kinase inhibitor 1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) KIP1 MEN1B MEN4 P27KIP1 NCBI Gene 1027 OMIM 600778 2013-08 2020-08-18 CDKN1C cyclin dependent kinase inhibitor 1C https://medlineplus.gov/genetics/gene/cdkn1c functionThe CDKN1C gene provides instructions for making a protein that helps regulate growth. This protein acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. It is also active before birth; it regulates growth and prevents the developing fetus from becoming too large.In most cases, one copy of each gene is derived from the sperm cell and one copy is derived from the egg cell. Both copies are typically active, or "turned on," in cells. However, the activity of the CDKN1C gene differs depending on whether the gene comes from the sperm cell or the egg cell. In most tissues, the copy of the gene that comes from the egg cell is more active than the copy that comes from the sperm cell. This sort of parent-specific difference in gene activation is called genomic imprinting.A nearby region of DNA undergoes a process called methylation in which small molecules called methyl groups are used to regulate the genomic imprinting of the CDKN1C gene. This region is known as an imprinting center or imprinting control region. In most cases, this imprinting center is methylated only when it comes from the egg cell.  Beckwith-Wiedemann syndrome https://medlineplus.gov/genetics/condition/beckwith-wiedemann-syndrome Silver-Russell syndrome https://medlineplus.gov/genetics/condition/silver-russell-syndrome IMAGe syndrome https://medlineplus.gov/genetics/condition/image-syndrome BWCR KIP2 p57 p57KIP2 NCBI Gene 1028 OMIM 600856 2025-03 2025-03-04 CDKN2A cyclin dependent kinase inhibitor 2A https://medlineplus.gov/genetics/gene/cdkn2a functionThe CDKN2A gene provides instructions for making several proteins. The most well-studied are the p16(INK4A) and the p14(ARF) proteins. Both function as tumor suppressors, which means they keep cells from growing and dividing too rapidly or in an uncontrolled way. Both proteins are also involved in stopping cell division in older cells (senescence).The p16(INK4A) protein attaches (binds) to two other proteins called CDK4 and CDK6. These proteins help regulate the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. CDK4 and CDK6 normally stimulate the cell to continue through the cycle and divide. However, binding of p16(INK4A) blocks CDK4's or CDK6's ability to stimulate cell cycle progression. In this way, p16(INK4A) controls cell division. Cells begin to produce p16(INK4A) when they are no longer able to undergo cell division.The p14(ARF) protein protects a different protein called p53 from being broken down. The p53 protein is an important tumor suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). By protecting p53, p14(ARF) also helps prevent tumor formation. The p14(ARF) and p53 proteins are often made in cells that are unable to undergo cell division. Bladder cancer https://medlineplus.gov/genetics/condition/bladder-cancer Head and neck squamous cell carcinoma https://medlineplus.gov/genetics/condition/head-and-neck-squamous-cell-carcinoma Lung cancer https://medlineplus.gov/genetics/condition/lung-cancer Melanoma https://medlineplus.gov/genetics/condition/melanoma ARF CDK4 inhibitor p16-INK4 CDK4I CDKN2 cell cycle negative regulator beta CMM2 cyclin-dependent kinase 4 inhibitor A cyclin-dependent kinase inhibitor 2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) cyclin-dependent kinase inhibitor 2A isoform p12 cyclin-dependent kinase inhibitor 2A isoform p14ARF cyclin-dependent kinase inhibitor 2A isoform p16gamma cyclin-dependent kinase inhibitor 2A isoform p16INK4a INK4 INK4A MLM MTS-1 MTS1 multiple tumor suppressor 1 P14 P14ARF P16 P16-INK4A P16INK4 P16INK4A P19 P19ARF TP16 NCBI Gene 1029 OMIM 155755 OMIM 260350 OMIM 600160 OMIM 606719 2018-07 2023-03-20 CDT1 chromatin licensing and DNA replication factor 1 https://medlineplus.gov/genetics/gene/cdt1 functionThe CDT1 gene provides instructions for making a protein that is important in the copying of a cell's DNA before the cell divides (a process known as DNA replication). The protein produced from this gene is one of a group of proteins known as the pre-replication complex. In a multi-step process, the components of this complex attach (bind) to certain regions of DNA known as origins of replication (or origins), where the process of DNA copying begins. When the pre-replication complex is attached to the origin, replication is able to begin at that location. This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide. Meier-Gorlin syndrome https://medlineplus.gov/genetics/condition/meier-gorlin-syndrome CDT1_HUMAN DNA replication factor Cdt1 Double parked, Drosophila, homolog of DUP RIS2 NCBI Gene 81620 OMIM 605525 2014-02 2020-08-18 CEBPA CCAAT enhancer binding protein alpha https://medlineplus.gov/genetics/gene/cebpa functionThe CEBPA gene provides instructions for making a protein called CCAAT enhancer-binding protein alpha. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity (expression) of certain genes. CCAAT enhancer-binding protein alpha is involved in the maturation (differentiation) of certain blood cells. It is also believed to act as a tumor suppressor, which means that it is involved in cellular mechanisms that help prevent the cells from growing and dividing too rapidly or in an uncontrolled way. Familial acute myeloid leukemia with mutated CEBPA https://medlineplus.gov/genetics/condition/familial-acute-myeloid-leukemia-with-mutated-cebpa Cytogenetically normal acute myeloid leukemia https://medlineplus.gov/genetics/condition/cytogenetically-normal-acute-myeloid-leukemia c/EBP alpha C/EBP-alpha CCAAT/enhancer binding protein (C/EBP), alpha CCAAT/enhancer binding protein alpha CCAAT/enhancer-binding protein alpha CEBP CEBPA_HUMAN NCBI Gene 1050 OMIM 116897 2013-12 2020-08-18 CEP290 centrosomal protein 290 https://medlineplus.gov/genetics/gene/cep290 functionThe CEP290 gene provides instructions for making a protein that is present in many types of cells, including in the eye's light receptor cells (photoreceptors). Although this protein's function is not well understood, studies suggest that it plays an important role in cell structures called centrosomes and cilia. Centrosomes are involved in cell division and the assembly of microtubules, which are proteins that transport materials in cells and help the cell maintain its shape. Cilia are microscopic, finger-like projections that stick out from the surface of cells. Cilia are involved in cell movement and many different chemical signaling pathways. They are also necessary for the perception of sensory input (such as vision, hearing, and smell). The CEP290 protein is likely necessary for vision by playing a role in transporting proteins within photoreceptors. Bardet-Biedl syndrome https://medlineplus.gov/genetics/condition/bardet-biedl-syndrome Leber congenital amaurosis https://medlineplus.gov/genetics/condition/leber-congenital-amaurosis Joubert syndrome https://medlineplus.gov/genetics/condition/joubert-syndrome Meckel syndrome https://medlineplus.gov/genetics/condition/meckel-syndrome Senior-Løken syndrome https://medlineplus.gov/genetics/condition/senior-loken-syndrome 3H11Ag BBS14 cancer/testis antigen 87 CE290_HUMAN centrosomal protein 290kDa centrosomal protein of 290 kDa CT87 CTCL tumor antigen se2-2 FLJ13615 FLJ21979 JBTS5 JBTS6 KIAA0373 LCA10 MKS4 monoclonal antibody 3H11 antigen nephrocytsin-6 NPHP6 POC3 POC3 centriolar protein homolog prostate cancer antigen T21 rd16 SLSN6 tumor antigen se2-2 NCBI Gene 80184 OMIM 610142 2022-10 2022-10-06 CEP57 centrosomal protein 57 https://medlineplus.gov/genetics/gene/cep57 functionThe CEP57 gene provides instructions for making a protein whose function is not completely understood. Within cells, the CEP57 protein is located in structures called centrosomes. Centrosomes have a role in cell division and the assembly of microtubules. Microtubules are fibers that help cells maintain their shape, assist in the process of cell division, and are essential for the movement (transport) of materials within cells. CEP57 seems especially important for the organization and stability of specialized microtubules called spindle microtubules, which are important for cell division. Before cells divide, they copy all of their chromosomes. Spindle microtubules, which are produced by centrosomes, attach to the duplicated chromosomes and pull one copy of each to opposite ends of the cell so that each new cell contains one complete set of chromosomes.The CEP57 protein is also involved in the transport of certain molecules along microtubules, particularly a protein called fibroblast growth factor 2 (FGF2). FGF2 is an important signaling molecule that helps regulate growth and development of cells and tissues, and its transport inside the cell is important for relaying signals that instruct the cell how to function. Mosaic variegated aneuploidy syndrome https://medlineplus.gov/genetics/condition/mosaic-variegated-aneuploidy-syndrome centrosomal protein 57kDa centrosomal protein of 57 kDa isoform a centrosomal protein of 57 kDa isoform b centrosomal protein of 57 kDa isoform c FGF2-interacting protein KIAA0092 MVA2 PIG8 proliferation-inducing protein 8 testis-specific protein 57 translokin TSP57 NCBI Gene 9702 OMIM 607951 2017-06 2020-08-18 CFH complement factor H https://medlineplus.gov/genetics/gene/cfh functionThe CFH gene provides instructions for making a protein called complement factor H. This protein helps regulate a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger an inflammatory response, and remove debris from cells and tissues. This system must be carefully regulated so it targets only unwanted materials and does not damage the body's healthy cells. Complement factor H, together with several related proteins, protects healthy cells by preventing the complement system from being turned on (activated) when it is not needed. Atypical hemolytic-uremic syndrome https://medlineplus.gov/genetics/condition/atypical-hemolytic-uremic-syndrome C3 glomerulopathy https://medlineplus.gov/genetics/condition/c3-glomerulopathy Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration age-related maculopathy susceptibility 1 AHUS1 ARMD4 ARMS1 beta-1-H-globulin beta-1H C3b inactivator accelerator CFAH_HUMAN CFHL3 factor H factor H-like 1 FH FHL1 H factor 1 (complement) H factor 2 (complement) HF HF1 HF2 HUS MGC88246 NCBI Gene 3075 OMIM 126700 OMIM 134370 2015-12 2025-04-03 CFHR5 complement factor H related 5 https://medlineplus.gov/genetics/gene/cfhr5 functionThe CFHR5 gene provides instructions for making a protein called complement factor H-related 5. The precise function of this protein is unknown. However, its structure is similar to that of a protein called complement factor H (which is produced from the CFH gene). This similarity provides clues to the probable function of complement factor H-related 5.Complement factor H regulates a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. This system must be carefully regulated so it targets only unwanted materials and does not damage the body's healthy cells. Complement factor H helps to protect healthy cells by preventing the complement system from being turned on (activated) when it is not needed. Studies suggest that complement factor H-related 5 also plays a role in controlling the complement system. Atypical hemolytic-uremic syndrome https://medlineplus.gov/genetics/condition/atypical-hemolytic-uremic-syndrome C3 glomerulopathy https://medlineplus.gov/genetics/condition/c3-glomerulopathy Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration CFHL5 complement factor H-related 5 complement factor H-related protein 5 factor H-related protein 5 FHR-5 FHR5 FHR5_HUMAN FLJ10549 MGC133240 NCBI Gene 81494 OMIM 608593 2015-12 2020-08-18 CFI complement factor I https://medlineplus.gov/genetics/gene/cfi functionThe CFI gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. This system must be carefully regulated so it targets only unwanted materials and does not attack the body's healthy cells. Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed. Atypical hemolytic-uremic syndrome https://medlineplus.gov/genetics/condition/atypical-hemolytic-uremic-syndrome Complement factor I deficiency https://medlineplus.gov/genetics/condition/complement-factor-i-deficiency C3 glomerulopathy https://medlineplus.gov/genetics/condition/c3-glomerulopathy Age-related macular degeneration https://medlineplus.gov/genetics/condition/age-related-macular-degeneration AHUS3 C3b-INA C3b-inactivator C3B/C4B inactivator C3BINA CFAI_HUMAN complement component I complement control protein factor I complement factor I heavy chain complement factor I preproprotein FI IF KAF Konglutinogen-activating factor light chain of factor I NCBI Gene 3426 OMIM 217030 2010-09 2020-08-18 CFTR CF transmembrane conductance regulator https://medlineplus.gov/genetics/gene/cftr functionThe CFTR gene provides instructions for making a protein called the CF transmembrane conductance regulator (CFTR). This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The channel transports negatively charged particles called chloride ions into and out of cells. The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. Mucus is a slippery substance that lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs and tissues.The CFTR protein also regulates the function of other channels, such as those that transport positively charged particles called sodium ions across cell membranes. These channels are necessary for the normal function of organs such as the lungs and pancreas. Cystic fibrosis https://medlineplus.gov/genetics/condition/cystic-fibrosis Congenital bilateral absence of the vas deferens https://medlineplus.gov/genetics/condition/congenital-bilateral-absence-of-the-vas-deferens Hereditary pancreatitis https://medlineplus.gov/genetics/condition/hereditary-pancreatitis ABC35 ABCC7 cAMP-dependent chloride channel CF CFTR_HUMAN cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7) cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) MRP7 NCBI Gene 1080 OMIM 602421 2008-01 2025-04-03 CHAT choline O-acetyltransferase https://medlineplus.gov/genetics/gene/chat functionThe CHAT gene provides instructions for making a protein called choline acetyltransferase. This protein is located at the ends of nerve cells in specialized areas called presynaptic terminals. Choline acetyltransferase facilitates the production of a molecule called acetylcholine. Acetylcholine is essential for normal muscle movement. When acetylcholine is released from the presynaptic terminal, it attaches (binds) to a receptor protein located in the membrane of muscle cells. When acetylcholine binds to its receptor protein, specialized channels in the receptor then open, allowing certain charged atoms (ions) to flow into and out of muscle cells. The flow of these ions allows for muscle contraction and relaxation, resulting in muscle movement. Congenital myasthenic syndromes https://medlineplus.gov/genetics/condition/congenital-myasthenic-syndrome acetyl CoA:choline O-acetyltransferase CHOACTASE choline acetylase CLAT_HUMAN CMS1A NCBI Gene 1103 OMIM 118490 2011-11 2026-02-13 CHD2 chromodomain helicase DNA binding protein 2 https://medlineplus.gov/genetics/gene/chd2 functionThe CHD2 gene provides instructions for making a protein called chromodomain DNA helicase protein 2. This protein is found in cells throughout the body and regulates gene activity (expression) through a process known as chromatin remodeling. Chromatin is the complex of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed. Chromodomain DNA helicase protein 2 appears to play an important role in the brain, although its function is not well understood. Research suggests that it may help control development or functioning of nerve cells (neurons). Lennox-Gastaut syndrome https://medlineplus.gov/genetics/condition/lennox-gastaut-syndrome CHD2 myoclonic encephalopathy https://medlineplus.gov/genetics/condition/chd2-myoclonic-encephalopathy Autism spectrum disorder https://medlineplus.gov/genetics/condition/autism-spectrum-disorder ATP-dependent helicase CHD2 CHD-2 EEOC FLJ38614 NCBI Gene 1106 OMIM 602119 2017-06 2020-08-18 CHD3 chromodomain helicase DNA binding protein 3 https://medlineplus.gov/genetics/gene/chd3 functionThe CHD3 gene provides instructions for making a protein that regulates gene activity (expression) by a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed. Chromatin remodeling is one way gene expression is regulated during development. The CHD3 protein helps with chromatin remodeling by moving components called nucleosomes, that help bundle DNA in a tight package. Moving nucleosomes helps make DNA more accessible for gene expression. The CHD3 protein provides energy for this remodeling by breaking down a molecule called ATP.Through its ability to regulate gene activity, the CHD3 protein is involved in many processes during development, including maintenance of the structure and integrity of DNA, the maturation process that determines the type of cell an immature cell will ultimately become (cell fate determination), and the growth of cells as they progress through the step-by-step process they take to replicate themselves (the cell cycle). Snijders Blok-Campeau syndrome https://medlineplus.gov/genetics/condition/snijders-blok-campeau-syndrome Mi-2a Mi2-ALPHA NCBI Gene 1107 OMIM 602120 2020-06 2020-08-18 CHD7 chromodomain helicase DNA binding protein 7 https://medlineplus.gov/genetics/gene/chd7 functionThe CHD7 gene provides instructions for making a protein called chromodomain helicase DNA binding protein 7. This protein is found in many parts of the body before birth, including the eye, the inner ear, and the brain. In the brain, the CHD7 protein is active in several areas, including a bundle of nerve cells (neurons) called the olfactory bulb that is critical for the perception of odors.The CHD7 protein belongs to a family of proteins that are thought to play a role in the organization of chromatin. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The CHD7 protein regulates the activity (expression) of several other genes through a process known as chromatin remodeling. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed. Researchers are working to determine which genes the CHD7 protein regulates. Kallmann syndrome https://medlineplus.gov/genetics/condition/kallmann-syndrome CHARGE syndrome https://medlineplus.gov/genetics/condition/charge-syndrome Anophthalmia/Microphthalmia https://medlineplus.gov/genetics/condition/anophthalmia-microphthalmia Coloboma https://medlineplus.gov/genetics/condition/coloboma CHD7_HUMAN FLJ20357 FLJ20361 IS3 KIAA1416 NCBI Gene 55636 OMIM 608892 2017-02 2025-09-26 CHD8 chromodomain helicase DNA binding protein 8 https://medlineplus.gov/genetics/gene/chd8 functionThe CHD8 gene provides instructions for making a protein that regulates gene activity (expression) by a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed. Chromatin remodeling is one way gene expression is regulated during development.The CHD8 protein is thought to affect the expression of many other genes that are involved in brain development before birth. In particular, the CHD8 protein and the genes it regulates likely help control the development of neural progenitor cells, which give rise to nerve cells (neurons), and the growth and division (proliferation) and maturation (differentiation) of neurons. In this way, the CHD8 protein helps to control the number of neurons in the brain and prevent overgrowth. Autism spectrum disorder https://medlineplus.gov/genetics/condition/autism-spectrum-disorder ATP-dependent helicase CHD8 AUTS18 axis duplication inhibitor chromodomain-helicase-DNA-binding protein 8 isoform 1 chromodomain-helicase-DNA-binding protein 8 isoform 2 duplin helicase with SNF2 domain 1 HELSNF1 KIAA1564 NCBI Gene 57680 OMIM 610528 2017-06 2020-08-18 CHM CHM Rab escort protein https://medlineplus.gov/genetics/gene/chm functionThe CHM gene provides instructions for producing the Rab escort protein-1 (REP-1), which is active (expressed) throughout the body. As an escort protein, REP-1 attaches (binds) to one of a number of Rab proteins. Following a chemical modification, REP-1 then directs the Rab protein to the membrane of one of the cell's compartments (organelles). While attached to the membrane, the Rab protein plays a role in directing the movement of proteins and organelles within cells (intracellular trafficking). After the Rab protein has reached its destination, it is released by REP-1 which then attaches to another Rab protein to begin the process again. Choroideremia https://medlineplus.gov/genetics/condition/choroideremia choroideremia choroideremia (Rab escort protein 1) DXS540 FLJ38564 GGTA HSD-32 MGC102710 RAE1_HUMAN REP-1 REP-1, Rab escort protein 1 TCD NCBI Gene 1121 OMIM 300390 2008-07 2022-06-28 CHMP2B charged multivesicular body protein 2B https://medlineplus.gov/genetics/gene/chmp2b functionThe CHMP2B gene provides instructions for making a protein called charged multivesicular body protein 2B. This protein is active in the brain, where it appears to be essential for the survival of nerve cells (neurons).Charged multivesicular body protein 2B forms one part (subunit) of a group of proteins known as the ESCRT-III complex. This complex helps transport other proteins from the cell membrane to the interior of the cell, a process known as endocytosis. In particular, the ESCRT-III complex is involved in the endocytosis of proteins that need to be broken down (degraded) by the cell. The complex helps sort these proteins into structures called multivesicular bodies (MVBs), which deliver them to lysosomes. Lysosomes are compartments within cells that digest and recycle many different types of molecules.Charged multivesicular body protein 2B is regulated by a segment at one end of the protein known as the C-terminal domain. This domain usually keeps the protein turned off (inactive). The inactive protein is unable to interact with other subunits of the ESCRT-III complex, which prevents the complex from forming when it is not needed. The C-terminal domain also plays an important role in disassembling the ESCRT-III complex through its interaction with a protein called vacuolar protein sorting 4 (Vps4). Amyotrophic lateral sclerosis https://medlineplus.gov/genetics/condition/amyotrophic-lateral-sclerosis CHMP2B-related frontotemporal dementia https://medlineplus.gov/genetics/condition/chmp2b-related-frontotemporal-dementia CHM2B_HUMAN CHMP family, member 2B CHMP2.5 chromatin modifying protein 2B DMT1 hVps2-2 vacuolar protein sorting-associated protein 2-2 VPS2 homolog B VPS2-2 VPS2B NCBI Gene 25978 OMIM 609512 2010-08 2020-08-18 CHN1 chimerin 1 https://medlineplus.gov/genetics/gene/chn1 functionThe CHN1 gene provides instructions for making a protein called N-chimaerin. This protein plays an important role in the early development of the nervous system. In particular, it helps regulate complex signaling pathways during the development of nerve cells (neurons). N-chimaerin helps guide the growth of axons and dendrites, which are specialized extensions of neurons that transmit and receive nerve impulses throughout the nervous system.N-chimaerin appears to be critical for the formation of certain nerves in the head and face, known as cranial nerves. The protein is necessary for the development and function of cranial nerve VI and, to a lesser extent, cranial nerve III. These two nerves emerge from the brain and control several of the muscles that surround the eyes (extraocular muscles). The extraocular muscles direct eye movement and determine the position of the eyes. Isolated Duane retraction syndrome https://medlineplus.gov/genetics/condition/isolated-duane-retraction-syndrome A-chimaerin alpha-chimerin CHIN_HUMAN CHN N-chimaerin n-chimerin RHOGAP2 NCBI Gene 1123 OMIM 118423 2024-05 2024-05-31 CHRNA2 cholinergic receptor nicotinic alpha 2 subunit https://medlineplus.gov/genetics/gene/chrna2 functionThe CHRNA2 gene provides instructions for making one part (subunit) of a larger protein complex called a neuronal nicotinic acetylcholine receptor (nAChR). Each nAChR complex is made up of a combination of five subunits, usually two alpha (α) and three beta (β) subunits.  Many different combinations are possible, and the characteristics of each nAChR complex depend on its specific subunits. The CHRNA2 gene is responsible for producing a subunit known as α2. Little is known about the specific function of nAChR proteins made with this subunit.In the brain, nAChR proteins are widely distributed and play an important role in chemical signaling between nerve cells (neurons).  The nAChR acts as a channel, allowing charged atoms (ions), including calcium, sodium, and potassium, to cross the cell membrane.  These channels open when they attach to a chemical messenger (neurotransmitter) called acetylcholine.  The channels also open in response to nicotine, the addictive substance in tobacco.Communication between neurons depends on neurotransmitters, which are released from one neuron and taken up by neighboring neurons. The release and uptake of these chemicals are tightly regulated to ensure that signals are passed efficiently and accurately between neurons. Researchers believe that nAChR channels play an important role in controlling the normal release and uptake of neurotransmitters.A wide range of brain functions depend on nAChR channels, including sleep and arousal, fatigue, anxiety, attention, pain perception, and memory. The channels are also active before birth, which suggests that they are involved in early brain development. Autosomal dominant sleep-related hypermotor epilepsy https://medlineplus.gov/genetics/condition/autosomal-dominant-sleep-related-hypermotor-epilepsy Acetylcholine receptor, neuronal nicotonic, alpha-2 subunit ACHA2_HUMAN Cholinergic receptor, neuronal nicotinic, alpha polypeptide 2 cholinergic receptor, nicotinic alpha 2 cholinergic receptor, nicotinic, alpha 2 cholinergic receptor, nicotinic, alpha 2 (neuronal) cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal) NCBI Gene 1135 OMIM 118502 2009-04 2025-08-08 CHRNA4 cholinergic receptor nicotinic alpha 4 subunit https://medlineplus.gov/genetics/gene/chrna4 functionThe CHRNA4 gene provides instructions for making one part (subunit) of a larger protein complex called a nicotinic acetylcholine receptor (nAChR). Each nAChR complex is made up of a combination of five subunits, usually two alpha (α) and three beta (β) subunits. Many different combinations are possible; the characteristics of each nAChR complex depend on its specific subunits. In the brain, the complex most commonly consists of two α4 subunits and three β2 subunits. The CHRNA4 gene is responsible for producing the α4 subunit.In the brain, the nAChR complex plays an important role in chemical signaling between nerve cells (neurons). The nAChR acts as a channel, allowing charged atoms (ions), including calcium, sodium, and potassium, to cross the cell membrane. These channels open when they attach to a chemical messenger (neurotransmitter) called acetylcholine. The channels also open in response to nicotine, the addictive substance in tobacco. As these channels open, the increased flow of ions across the cell membrane alters the release of neurotransmitters.Communication between neurons depends on neurotransmitters. The release and uptake of these chemicals are tightly regulated to ensure that signals are passed efficiently and accurately between neurons. Researchers believe that nAChR channels play an important role in controlling the normal release and uptake of neurotransmitters.A wide range of brain functions depend on nAChR channels, including sleep and arousal, fatigue, anxiety, attention, pain perception, and memory. The channels are also active before birth, which suggests that they are involved in early brain development. Autosomal dominant sleep-related hypermotor epilepsy https://medlineplus.gov/genetics/condition/autosomal-dominant-sleep-related-hypermotor-epilepsy acetylcholine receptor, neuronal nicotonic, alpha-4 subunit acetylcholine receptor, nicotinic, alpha 4 (neuronal) BFNC cholinergic receptor, neuronal nicotinic, alpha polypeptide 4 cholinergic receptor, nicotinic alpha 4 cholinergic receptor, nicotinic, alpha 4 (neuronal) EBN EBN1 NACHR NACHRA4 NACRA4 NCBI Gene 1137 OMIM 118504 OMIM 188890 2025-08 2025-08-14 CHRNB2 cholinergic receptor nicotinic beta 2 subunit https://medlineplus.gov/genetics/gene/chrnb2 functionThe CHRNB2 gene provides instructions for making one part (subunit) of a larger protein complex called a nicotinic acetylcholine receptor (nAChR). Each nAChR complex is made up of a combination of five subunits, usually two alpha (α) and three beta (β) subunits. Many different combinations are possible, and the characteristics of each nAChR complex depend on its specific subunits. In the brain, the complex most commonly consists of two α4 subunits and three β2 subunits. The CHRNB2 gene is responsible for producing the β2 subunit.In the brain, nAChR proteins are widely distributed and play an important role in chemical signaling between nerve cells (neurons). The nAChR acts as a channel, allowing charged atoms (ions), including calcium, sodium, and potassium, to cross the cell membrane. These channels open when they attach to a chemical messenger (neurotransmitter) called acetylcholine. The channels also open in response to nicotine, the addictive substance in tobacco.Communication between neurons depends on neurotransmitters, which are released from one neuron and taken up by neighboring neurons. The release and uptake of these chemicals are tightly regulated to ensure that signals are passed efficiently and accurately between neurons. Researchers believe that nAChR channels play an important role in controlling the normal release and uptake of neurotransmitters.A wide range of brain functions depend on nAChR channels, including sleep and arousal, fatigue, anxiety, attention, pain perception, and memory. The channels are also active before birth, which suggests that they are involved in early brain development. Autosomal dominant sleep-related hypermotor epilepsy https://medlineplus.gov/genetics/condition/autosomal-dominant-sleep-related-hypermotor-epilepsy acetylcholine receptor, neuronal nicotinic, beta-2 subunit cholinergic receptor, nicotinic beta 2 cholinergic receptor, nicotinic, beta 2 (neuronal) cholinergic receptor, nicotinic, beta polypeptide 2 (neuronal) EFNL3 nAChRB2 NCBI Gene 1141 OMIM 118507 2009-04 2025-08-08 CHRNE cholinergic receptor nicotinic epsilon subunit https://medlineplus.gov/genetics/gene/chrne functionThe CHRNE gene provides instructions for making the epsilon (ε) component (subunit) of the acetylcholine receptor (AChR) protein. The AChR protein consists of five subunits, each of which is produced from a different gene.The AChR protein is found on the surface of skeletal muscle cells, which are used to move the body. The AChR protein plays a critical role in the neuromuscular junction, which is the area between nerve and muscle cells where cell signaling occurs. Signaling between nerve and muscle cells is necessary for movement.The AChR protein subunits assemble into the protein in the endoplasmic reticulum, a cell structure involved in protein processing and transport. The AChR protein is then transported to the cell surface. There are two major forms of the AChR protein: a fetal type that is present before birth and an adult type. The ε subunit is found only in the adult AChR protein. At about the 33rd week of pregnancy, the ε subunit replaces the gamma (γ) subunit (which is found only in the fetal type of AChR) to form the adult AChR protein. Congenital myasthenic syndromes https://medlineplus.gov/genetics/condition/congenital-myasthenic-syndrome acetylcholine receptor subunit epsilon ACHE_HUMAN AchR epsilon subunit ACHRE cholinergic receptor, nicotinic epsilon NCBI Gene 1145 OMIM 100725 2026-02 2026-02-13 CHRNG cholinergic receptor nicotinic gamma subunit https://medlineplus.gov/genetics/gene/chrng functionThe CHRNG gene provides instructions for making the gamma (γ) protein component (subunit) of the acetylcholine receptor (AChR) protein. The AChR protein is found in the membrane of skeletal muscle cells and is critical for signaling between nerve and muscle cells. Signaling between these cells is necessary for movement. The AChR protein consists of five subunits, each of which is produced from a different gene. The subunits are assembled into the AChR protein in the endoplasmic reticulum, a cell structure involved in protein processing and transport, before being transported to the cell membrane. The γ subunit is found only in the fetal AChR protein. At about the thirty-third week of pregnancy, the γ subunit is replaced by the epsilon (ε) subunit, which is produced by the CHRNE gene, to form the adult AChR protein. Multiple pterygium syndrome https://medlineplus.gov/genetics/condition/multiple-pterygium-syndrome acetylcholine gamma muscle receptor subunit acetylcholine receptor subunit gamma acetylcholine receptor, muscle, gamma subunit ACHG_HUMAN ACHRG cholinergic gamma nicotinic receptor cholinergic receptor, nicotinic gamma cholinergic receptor, nicotinic, gamma cholinergic receptor, nicotinic, gamma (muscle) cholinergic receptor, nicotinic, gamma polypeptide NCBI Gene 1146 OMIM 100730 2011-11 2020-08-18 CHST3 carbohydrate sulfotransferase 3 https://medlineplus.gov/genetics/gene/chst3 functionThe CHST3 gene provides instructions for making an enzyme called chondroitin 6-O-sulfotransferase 1 or C6ST-1. This enzyme has an important role in the development and maintenance of the skeleton. In particular, it is essential for the normal development of cartilage, which is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.The C6ST-1 enzyme modifies molecules called chondroitin sulfate proteoglycans, which are abundant in cartilage and give this tissue its rubbery, gel-like consistency. The C6ST-1 enzyme carries out a process known as sulfation, in which a chemical group called a sulfate is transferred from one chemical compound to another. Specifically, the enzyme takes sulfate from a molecule called 3'-phosphoadenyl-5'-phosphosulfate (PAPS) and adds it to a specific location on chondroitin sulfate proteoglycans. Sulfation of these molecules is a critical step in cartilage formation. CHST3-related skeletal dysplasia https://medlineplus.gov/genetics/condition/chst3-related-skeletal-dysplasia C6ST C6ST-1 C6ST1 carbohydrate (chondroitin 6) sulfotransferase 3 chondroitin 6-O-sulfotransferase 1 CHST3_HUMAN galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 0 GST-0 HSD NCBI Gene 9469 OMIM 603799 2012-10 2020-08-18 CIITA class II major histocompatibility complex transactivator https://medlineplus.gov/genetics/gene/ciita functionThe CIITA gene provides instructions for making a protein that primarily helps control the activity (transcription) of genes called major histocompatibility complex (MHC) class II genes. Transcription is the first step in the production of proteins, and CIITA is critical for the production of specialized immune proteins called MHC class II proteins from these genes. The CIITA protein coordinates various proteins to turn on MHC class II gene transcription and allow the production of MHC class II proteins.MHC class II proteins are found on the surface of several types of immune cells, including white blood cells (lymphocytes) that are involved in immune reactions. These proteins play an important role in the body's immune response to foreign invaders, such as bacteria, viruses, and fungi. To help the body recognize and fight infections, MHC class II proteins bind to fragments of proteins (peptides) from foreign invaders so that other specialized immune system cells can interact with them. When these immune system cells recognize the peptides as harmful, they trigger the lymphocytes and other immune cells to launch immune responses to get rid of the foreign invaders.The CIITA protein also appears to play a role in enhancing the transcription of MHC class I genes, which provide instructions for making immune system proteins called MHC class I proteins. Like MHC class II proteins, MHC class I proteins attach to peptides from foreign invaders and present them to specific immune system cells. These cells then attack the foreign invaders to rid them from the body. While the CIITA protein is able to help promote MHC class I gene activity, it is not the primary regulator of these genes. Other proteins play a more prominent role in their transcription. Autoimmune Addison disease https://medlineplus.gov/genetics/condition/autoimmune-addison-disease Bare lymphocyte syndrome type II https://medlineplus.gov/genetics/condition/bare-lymphocyte-syndrome-type-ii C2TA CIITAIV MHC class II transactivator MHC2TA NLR family, acid domain containing NLRA nucleotide-binding oligomerization domain, leucine rich repeat and acid domain containing NCBI Gene 4261 OMIM 600005 2017-05 2020-08-18 CISD2 CDGSH iron sulfur domain 2 https://medlineplus.gov/genetics/gene/cisd2 functionThe CISD2 gene provides instructions for making a protein that is found in the outer membrane of cell structures called mitochondria. Mitochondria are involved in a wide variety of cellular activities, including energy production, chemical signaling, and regulation of cell growth and division. The exact function of the CISD2 protein is unknown, but it is thought to help keep mitochondria functioning normally. Wolfram syndrome https://medlineplus.gov/genetics/condition/wolfram-syndrome CDGSH iron-sulfur domain-containing protein 2 CISD2_HUMAN endoplasmic reticulum intermembrane small protein ERIS Miner1 NAF-1 nutrient-deprivation autophagy factor-1 WFS2 ZCD2 zinc finger, CDGSH-type domain 2 NCBI Gene 493856 OMIM 611507 2012-04 2023-07-26 CLCF1 cardiotrophin like cytokine factor 1 https://medlineplus.gov/genetics/gene/clcf1 functionThe CLCF1 gene provides instructions for making a protein called cardiotrophin-like cytokine factor 1 (CLCF1). This protein partners with a similar protein called cytokine receptor-like factor 1 (CRLF1), which is produced from the CRLF1 gene. Together, these two proteins form a unit known as the CRLF1/CLCF1 protein complex. This complex attaches (binds) to a receptor protein known as the ciliary neurotrophic factor receptor (CNTFR) on the surface of many types of cells. When the CRLF1/CLCF1 protein complex is bound to CNTFR, it triggers signaling inside the cell that affects cell development and function.The CNTFR signaling pathway is primarily involved in the development and maintenance of the nervous system. It promotes the survival of nerve cells (neurons), particularly nerve cells that control muscle movement (motor neurons). The CNTFR pathway also plays a role in a part of the nervous system called the sympathetic nervous system, specifically in the regulation of sweating in response to temperature changes and other factors. This signaling pathway appears to be critical for the normal development and maturation of nerve cells that control the activity of sweat glands.Studies suggest that the CNTFR signaling pathway also has functions outside the nervous system. It may be involved in the body's inflammatory response, which helps fight infection and facilitate tissue repair following an injury. This pathway may also be important for the development and maintenance of bone tissue. However, little is known about the role of CNTFR signaling in these processes. Cold-induced sweating syndrome https://medlineplus.gov/genetics/condition/cold-induced-sweating-syndrome B-cell stimulating factor 3 B-cell stimulatory factor 3 BSF-3 BSF3 cardiotrophin-like cytokine cardiotrophin-like cytokine factor 1 CISS2 CLC CLCF1_HUMAN CRLF1 associated cytokine-like factor 1 neurotrophin-1/B-cell stimulating factor-3 NNT-1 NNT-1/BSF-3 NNT1 novel neurotrophin-1 NR6 NCBI Gene 23529 OMIM 607672 2012-08 2020-08-18 CLCN1 chloride voltage-gated channel 1 https://medlineplus.gov/genetics/gene/clcn1 functionThe CLCN1 gene provides instructions for making a type of protein called a chloride channel. These channels, which transport negatively charged chlorine atoms (chloride ions), play a key role in a cell's ability to generate and transmit electrical signals.The CLCN1 gene provides instructions for making a chloride channel called ClC-1. These channels are found only in muscles used for movement (skeletal muscles). For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contraction and relaxation are controlled by the flow of certain ions into and out of muscle cells. ClC-1 channels, which span the cell membrane, control the flow of chloride ions into these cells. This influx stabilizes the cells' electrical charge, which prevents muscles from contracting abnormally.ClC-1 channels are made of two identical protein subunits, each produced from the CLCN1 gene. Although each subunit forms a separate opening (pore) that allows chloride ions to pass through, the two proteins work together to regulate the flow of chloride ions into skeletal muscle cells. Myotonia congenita https://medlineplus.gov/genetics/condition/myotonia-congenita chloride channel 1, skeletal muscle Chloride channel protein 1 Chloride channel protein, skeletal muscle chloride channel, voltage-sensitive 1 ClC-1 CLC1 CLCN1_HUMAN MGC138361 MGC142055 skeletal muscle chloride channel 1 NCBI Gene 1180 OMIM 118425 2020-02 2020-08-18 CLCN2 chloride voltage-gated channel 2 https://medlineplus.gov/genetics/gene/clcn2 functionThe CLCN2 gene belongs to the CLC family of genes, which provide instructions for making chloride channels. These channels, which transport negatively charged chlorine atoms (chloride ions), play a key role in a cell's ability to generate and transmit electrical signals. Some chloride channels regulate the flow of chloride ions across cell membranes, while others transport chloride ions within cells.The CLCN2 gene provides instructions for making a chloride channel called ClC-2. These channels are embedded within the outer membrane of most cells, and they transport chloride ions in and out of cells. The channel's function is thought to be particularly important in nerve cells (neurons) in the brain. The ClC-2 channel regulates the size (volume) of neurons by playing a role in the intake and release of water as well as maintaining a normal balance of ions in cells. Juvenile myoclonic epilepsy https://medlineplus.gov/genetics/condition/juvenile-myoclonic-epilepsy CLCN2-related leukoencephalopathy https://medlineplus.gov/genetics/condition/clcn2-related-leukoencephalopathy chloride channel 2 chloride channel, voltage-sensitive 2 CIC-2 clC-2 CLC2 ECA2 ECA3 EGI11 EGI3 EGMA EJM6 EJM8 LKPAT NCBI Gene 1181 OMIM 600570 2017-12 2020-08-18 CLCN5 Cl-/H+ antiporter 5 https://medlineplus.gov/genetics/gene/clcn5 functionThe CLCN5 gene provides instructions for making a protein that transports charged molecules (ions) across cell membranes. Specifically, the CLCN5 protein exchanges negatively charged chloride ions for positively charged hydrogen ions.The CLCN5 protein is found primarily in structures called proximal tubules in the kidneys. The proximal tubules help to reabsorb protein and other important substances back into the bloodstream. Substances that are not reabsorbed by the kidneys are released into the urine. Thus, the CLCN5 protein helps prevent protein loss in the urine (proteinuria).Within proximal tubular cells, the CLCN5 protein is found in specialized compartments called endosomes. Endosomes at the proximal tubular cell surface are involved in the reabsorption of proteins. They also help transport proteins and other molecules to their proper locations within the cell. The process of transporting proteins from the outer cell membrane to the inside of the cell is called endocytosis. By transporting hydrogen ions into endosomes and chloride ions out, the CLCN5 protein helps endosomes maintain the proper acidity level (pH). Endosomal pH levels must be acidic for the proximal tubular cells to function properly. Dent disease https://medlineplus.gov/genetics/condition/dent-disease ClC-5 CLC5 Dent disease DENTS hCIC-K2 XLRH XRN NCBI Gene 1184 OMIM 300008 2026-04 2026-04-10 CLCN7 Cl-/H+ antiporter 7 https://medlineplus.gov/genetics/gene/clcn7 functionThe CLCN7 gene belongs to the CLC family of genes, which provide instructions for making chloride channels. These channels, which transport negatively charged chlorine atoms (chloride ions), play a key role in a cell's ability to generate and transmit electrical signals. Some CLC channels regulate the flow of chloride ions across cell membranes, while others transport chloride ions within cells.The CLCN7 gene provides instructions for making a chloride channel called ClC-7. These channels are abundant in cells throughout the body. They are particularly important for the normal function of osteoclasts, which are specialized cells that break down bone tissue. Osteoclasts are involved in bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy.ClC-7 channels help regulate the relative acidity (pH) of osteoclasts. These channels transport two negatively charged chloride ions out of these cells for every positively charged hydrogen atom (hydrogen ion) that flows in. In this way, ClC-7 channels help balance the acidic environment that osteoclasts use to dissolve bone tissue. The pH inside and outside osteoclasts must be carefully controlled for these cells to break down bone effectively. Osteopetrosis https://medlineplus.gov/genetics/condition/osteopetrosis chloride channel 7 chloride channel protein 7 chloride channel, voltage-sensitive 7 CLC-7 CLC7 OPTA2 PPP1R63 NCBI Gene 1186 OMIM 602727 2010-09 2026-03-02 CLCNKA chloride voltage-gated channel Ka https://medlineplus.gov/genetics/gene/clcnka functionThe CLCNKA gene belongs to the CLC family of genes, which provide instructions for making chloride channels. These channels, which transport negatively charged chlorine atoms (chloride ions), play a key role in a cell's ability to generate and transmit electrical signals. Some CLC channels regulate the flow of chloride ions across cell membranes, while others transport chloride ions within cells.The CLCNKA gene provides instructions for making a chloride channel called ClC-Ka. These channels are found predominantly in the kidneys. ClC-Ka is one of several proteins that work together to regulate the movement of ions into and out of kidney cells. The transport of chloride ions by ClC-Ka channels is part of the mechanism by which the kidneys reabsorb salt (sodium chloride or NaCl) from the urine back into the bloodstream. The retention of salt affects the body's fluid levels and helps maintain blood pressure.ClC-Ka channels are also located in the inner ear, where they play a role in normal hearing. Bartter syndrome https://medlineplus.gov/genetics/condition/bartter-syndrome chloride channel Ka chloride channel protein ClC-Ka chloride channel, kidney, A chloride channel, voltage-sensitive Ka ClC-K1 CLCK1 CLCKA_HUMAN hClC-Ka NCBI Gene 1187 OMIM 602024 2011-02 2023-03-20 CLCNKB chloride voltage-gated channel Kb https://medlineplus.gov/genetics/gene/clcnkb functionThe CLCNKB gene belongs to the CLC family of genes, which provide instructions for making chloride channels. These channels, which transport negatively charged chlorine atoms (chloride ions), play a key role in a cell's ability to generate and transmit electrical signals. Some CLC channels regulate the flow of chloride ions across cell membranes, while others transport chloride ions within cells.The CLCNKB gene provides instructions for making a chloride channel called ClC-Kb. These channels are found predominantly in the kidneys. ClC-Kb is one of several proteins that work together to regulate the movement of ions into and out of kidney cells. The transport of chloride ions by ClC-Kb channels is part of the mechanism by which the kidneys reabsorb salt (sodium chloride or NaCl) from the urine back into the bloodstream. The retention of salt affects the body's fluid levels and helps maintain blood pressure.ClC-Kb channels are also located in the inner ear, where they play a role in normal hearing. Bartter syndrome https://medlineplus.gov/genetics/condition/bartter-syndrome Gitelman syndrome https://medlineplus.gov/genetics/condition/gitelman-syndrome chloride channel Kb chloride channel protein ClC-Kb chloride channel, kidney, B chloride channel, voltage-sensitive Kb ClC-K2 ClC-Kb CLCKB CLCKB_HUMAN hClC-Kb NCBI Gene 1188 OMIM 602023 2011-02 2023-03-20 CLIP2 CAP-Gly domain containing linker protein 2 https://medlineplus.gov/genetics/gene/clip2 functionThe CLIP2 gene provides instructions for making a protein called CAP-Gly domain containing linker protein 2. The protein is also known as CLIP-115. This protein is found predominantly in the brain, where it likely plays a role in the normal structure and function of nerve cells. Within cells, this protein is thought to regulate aspects of the cytoskeleton, the structural framework that helps to determine cell shape, size, and movement. The protein is associated with microtubules, which are rigid, hollow fibers that make up a significant part of the cytoskeleton. Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells. Williams syndrome https://medlineplus.gov/genetics/condition/williams-syndrome CAP-GLY domain containing linker protein 2 CLIP-115 CLIP2_HUMAN CYLN2 Cytoplasmic linker protein 115 Cytoplasmic linker protein 2 KIAA0291 MGC11333 WBSCR4 WSCR4 NCBI Gene 7461 OMIM 603432 2022-03 2020-08-18 CLN3 CLN3 lysosomal/endosomal transmembrane protein, battenin https://medlineplus.gov/genetics/gene/cln3 functionThe CLN3 gene provides instructions for making a protein that is found in tissues throughout the body, yet its function is unclear. The CLN3 protein is found in many compartments within cells, but its role in lysosomes is most well-studied. Lysosomes are cellular compartments that digest and recycle different types of molecules. The CLN3 protein spans the membrane surrounding lysosomes, helping to facilitate communication between it and the rest of the cell.Studies have associated the CLN3 protein with many cellular processes, including recycling of worn-out cell parts and unneeded proteins (autophagy), maintenance of the relative acidity (pH) of lysosomes, the movement of molecules from the cell surface into the cell (endocytosis), transportation (trafficking) of proteins to where they are needed in the cell, self-destruction of cells (apoptosis), cell growth and division (proliferation), and maintenance of the body's water balance (osmoregulation). It is uncertain which of these varied functions is the primary role of the CLN3 protein, or if these processes instead represent downstream effects. CLN3 disease https://medlineplus.gov/genetics/condition/cln3-disease BATTENIN BTN1 BTS ceroid-lipofuscinosis, neuronal 3 CLN3_HUMAN JNCL MGC102840 NCBI Gene 1201 OMIM 607042 2020-02 2022-06-28 CLN5 CLN5 lysosomal BMP synthase https://medlineplus.gov/genetics/gene/cln5 functionThe CLN5 gene provides instructions for making a protein whose function is not well understood. Cells produce a CLN5 protein that is inactive and contains extra protein segments. This inactive protein is called a preprotein. For the CLN5 preprotein to become active, the additional segments must be removed, followed by additional processing steps. The active CLN5 protein is then transported to cell compartments called lysosomes, which digest and recycle different types of molecules. Research suggests that the CLN5 protein may play a role in the process by which lysosomes break down or recycle damaged or unneeded proteins within cells. CLN5 disease https://medlineplus.gov/genetics/condition/cln5-disease ceroid-lipofuscinosis neuronal protein 5 ceroid-lipofuscinosis, neuronal 5 CLN5 intracellular trafficking protein NCBI Gene 1203 OMIM 608102 2016-11 2025-06-02 CLN6 CLN6 transmembrane ER protein https://medlineplus.gov/genetics/gene/cln6 functionThe CLN6 gene provides instructions for making a protein whose function is not well understood. Within cells, the CLN6 protein is found in a structure called the endoplasmic reticulum, which is involved in protein processing and transport. Research suggests that the CLN6 protein regulates the transportation of certain proteins and fats from the endoplasmic reticulum to lysosomes. Lysosomes are compartments in the cell that digest and recycle materials. Based on this function, the CLN6 protein appears to help cells get rid of materials they no longer need. CLN6 disease https://medlineplus.gov/genetics/condition/cln6-disease ceroid-lipofuscinosis neuronal protein 6 ceroid-lipofuscinosis, neuronal 6, late infantile, variant CLN4A CLN6_HUMAN FLJ20561 HsT18960 nclf NCBI Gene 54982 OMIM 606725 2017-01 2022-07-05 CLN8 CLN8 transmembrane ER and ERGIC protein https://medlineplus.gov/genetics/gene/cln8 functionThe CLN8 gene provides instructions for making a protein whose precise function is not known but that is thought to play a transport role within cells. Specifically, the CLN8 protein likely helps to move materials in and out of a cell structure called the endoplasmic reticulum, which is involved in protein production, processing, and transport. The CLN8 protein may also play a role in helping the endoplasmic reticulum regulate levels of fats (lipids) in cells. In certain cells, including nerve cells, the CLN8 protein is thought to be active outside of the endoplasmic reticulum, but its function is unknown. CLN8 disease https://medlineplus.gov/genetics/condition/cln8-disease C8orf61 ceroid-lipofuscinosis, neuronal 8 ceroid-lipofuscinosis, neuronal 8 (epilepsy, progressive with mental retardation) CLN8_HUMAN EPMR FLJ39417 NCBI Gene 2055 OMIM 607837 2016-12 2022-07-05 CLPB ClpB family mitochondrial disaggregase https://medlineplus.gov/genetics/gene/clpb functionThe CLPB gene provides instructions for making a protein whose function is unknown. The CLPB protein is found in cells throughout the body but is most abundant in the brain. Based on its similarity to a protein in other organisms, researchers speculate that the CLPB protein helps unfold misfolded proteins so they can be refolded correctly. When misfolded, proteins cannot function properly and may be damaging to cells. CLPB deficiency https://medlineplus.gov/genetics/condition/clpb-deficiency ANKCLB ankyrin-repeat containing bacterial clp fusion caseinolytic peptidase B protein homolog isoform 1 caseinolytic peptidase B protein homolog isoform 2 caseinolytic peptidase B protein homolog isoform 3 caseinolytic peptidase B protein homolog isoform 4 ClpB caseinolytic peptidase B homolog FLJ13152 HSP78 SKD3 suppressor of potassium transport defect 3 testicular secretory protein Li 11 NCBI Gene 81570 OMIM 616254 2017-02 2023-04-03 CLPP caseinolytic mitochondrial matrix peptidase proteolytic subunit https://medlineplus.gov/genetics/gene/clpp functionThe CLPP gene provides instructions for making the ClpP subunit protein. Multiple copies of this protein interact with each other to form a barrel-shaped chamber known as the ClpP complex. This complex is one of two parts of the ClpXP protease, which breaks down abnormally folded proteins. The other part of the ClpXP protease, called the ClpX complex, unfolds the abnormal proteins and feeds them into the chamber formed by the ClpP complex, where they are broken down into small fragments.The ClpP complex is found in structures in the cell called mitochondria, which are the energy-producing centers of cells. Perrault syndrome https://medlineplus.gov/genetics/condition/perrault-syndrome ATP-dependent Clp protease proteolytic subunit, mitochondrial ATP-dependent protease ClpAP, proteolytic subunit, human ClpP caseinolytic peptidase ATP-dependent, proteolytic subunit ClpP caseinolytic protease, ATP-dependent, proteolytic subunit homolog endopeptidase Clp PRLTS3 putative ATP-dependent Clp protease proteolytic subunit, mitochondrial NCBI Gene 8192 OMIM 601119 2014-12 2020-08-18 CLRN1 clarin 1 https://medlineplus.gov/genetics/gene/clrn1 functionThe CLRN1 gene provides information for making a protein called clarin 1. This protein is probably involved in normal hearing and vision. Clarin 1 has been found in several areas of the body, including sensory cells in the inner ear called hair cells. These cells help transmit sound and motion signals to the brain. This protein is also active in the retina, which is the light-sensing tissue that lines the back of the eye. Although the function of clarin 1 has not been determined, studies suggest that it plays a role in communication between nerve cells (neurons) in the inner ear and in the retina. Clarin 1 may be important for the development and function of synapses, which are junctions between neurons where cell-to-cell communication occurs. Usher syndrome https://medlineplus.gov/genetics/condition/usher-syndrome Retinitis pigmentosa https://medlineplus.gov/genetics/condition/retinitis-pigmentosa USH3 USH3A USH3A_HUMAN Usher syndrome 3A Usher syndrome type 3 protein NCBI Gene 7401 OMIM 606397 2016-05 2025-04-03 CNBP CCHC-type zinc finger nucleic acid binding protein https://medlineplus.gov/genetics/gene/cnbp functionThe CNBP gene provides instructions for making a protein called CCHC-type zinc finger nucleic acid binding protein. This protein has seven regions, called zinc finger domains, which are thought to attach (bind) to specific sites on DNA and its chemical cousin, RNA.The CNBP protein is found in many of the body's tissues, but it is most abundant in the heart and in muscles used for movement (skeletal muscles). The CNBP protein regulates the activity of other genes and is necessary for normal development before birth, particularly of muscles.One region of the CNBP gene contains a segment of four DNA building blocks (nucleotides) that is repeated multiple times. This sequence, which is written as CCTG, is called a tetranucleotide repeat. In most people, the CCTG sequence is repeated fewer than 26 times. Myotonic dystrophy https://medlineplus.gov/genetics/condition/myotonic-dystrophy CCHC-type zinc finger, nucleic acid binding protein cellular nucleic acid binding protein cellular retroviral nucleic acid-binding protein 1 CNBP1 CNBP_HUMAN DM2 ZCCHC22 zinc finger 9 protein zinc finger protein 273 zinc finger protein 9 zinc finger protein 9 (a cellular retroviral nucleic acid binding protein) ZNF9 NCBI Gene 7555 OMIM 116955 2010-10 2020-08-18 CNGA3 cyclic nucleotide gated channel subunit alpha 3 https://medlineplus.gov/genetics/gene/cnga3 functionThe CNGA3 gene provides instructions for making one part (the alpha subunit) of the cyclic nucleotide-gated (CNG) channel. These channels are found exclusively in light-sensing (photoreceptor) cells called cones, which are located in a specialized tissue at the back of the eye (retina). Cones provide color vision and vision in bright light (daytime vision). Other photoreceptor cells, called rods, provide vision in low light (night vision).CNG channels are openings in the cell membrane that transport positively charged atoms (ions) into cells. The CNG channels in cones remain open in low light, allowing ions to flow in. When light enters the eye, these channels close, stopping the flow of ions. This change in ion transport alters the cone's electrical charge, which ultimately generates a signal. This signal is sent to the brain, where it combines with other visual information and is interpreted as vision. The process of translating light into an electrical signal is called phototransduction. Achromatopsia https://medlineplus.gov/genetics/condition/achromatopsia Cone-rod dystrophy https://medlineplus.gov/genetics/condition/cone-rod-dystrophy ACHM2 cyclic nucleotide-gated channel, alpha-3 NCBI Gene 1261 OMIM 600053 2025-08 2025-08-14 CNGB3 cyclic nucleotide gated channel subunit beta 3 https://medlineplus.gov/genetics/gene/cngb3 functionThe CNGB3 gene provides instructions for making one part (the beta subunit) of the cyclic nucleotide-gated (CNG) channel. These channels are found exclusively in light-sensing (photoreceptor) cells called cones, which are located in a specialized tissue at the back of the eye (retina). Cones provide color vision and vision in bright light (daytime vision). Other photoreceptor cells, called rods, provide vision in low light (night vision).CNG channels are openings in the cell membrane that transport positively charged atoms (ions) into cells. The CNG channels in cones remain open in low light, allowing ions to flow in. When light enters the eye, these channels close, stopping the flow of ions. This change in ion transport alters the cone's electrical charge, which ultimately generates a signal. This signal is sent to the brain, where it combines with other visual information and is interpreted as vision. The process of translating light into an electrical signal is called phototransduction. Achromatopsia https://medlineplus.gov/genetics/condition/achromatopsia Cone-rod dystrophy https://medlineplus.gov/genetics/condition/cone-rod-dystrophy ACHM3 achromatopsia (rod monochromacy) 3 cyclic nucleotide gated channel beta 3 NCBI Gene 54714 OMIM 605080 2025-08 2025-08-14 COG4 component of oligomeric golgi complex 4 https://medlineplus.gov/genetics/gene/cog4 functionThe COG4 gene provides instructions for making a protein called component of oligomeric Golgi complex 4 (COG4). As its name suggests, COG4 is one piece of a group of proteins known as the conserved oligomeric Golgi (COG) complex. This complex is important for maintaining normal functions in the Golgi apparatus, which is a cell structure in which newly produced proteins are modified so they can carry out their functions. An example of a protein modification process that occurs in the Golgi apparatus is glycosylation, by which sugar molecules (oligosaccharides) are attached to proteins and fats. Glycosylation modifies proteins so they can perform a wider variety of functions.The COG complex plays an important role in a process called retrograde transport, through which proteins are moved from the Golgi apparatus to another cellular structure called the endoplasmic reticulum. Among its many functions, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape. This transport pathway is called retrograde because it is in reverse order of the usual process for newly produced proteins. New proteins undergo initial processing in the endoplasmic reticulum then move to the Golgi apparatus for further modification before being released from the cell (secreted). Retrograde transport is important for sending unneeded proteins to the endoplasmic reticulum to get recycled and for relocating misplaced proteins within the cell.For retrograde transport, proteins first must be incorporated into sac-like structures called vesicles that get attached to the Golgi apparatus membrane. The COG complex controls the attachment (tethering) of the vesicles to the Golgi membrane in preparation for transport. Once the proteins are incorporated, the vesicles detach and carry the proteins to the endoplasmic reticulum. Saul-Wilson syndrome https://medlineplus.gov/genetics/condition/saul-wilson-syndrome COD1 COD1, S. CEREVISIAE, HOMOLOG OF COG4 gene NCBI Gene 25839 OMIM 606976 2020-04 2020-08-18 COG5 component of oligomeric golgi complex 5 https://medlineplus.gov/genetics/gene/cog5 functionThe COG5 gene provides instructions for making a protein called component of oligomeric Golgi complex 5 (COG5). As its name suggests, COG5 is one piece of a group of proteins known as the conserved oligomeric Golgi (COG) complex. This complex functions in the Golgi apparatus, which is a cell structure in which newly produced proteins are modified. One process that occurs in the Golgi apparatus is glycosylation, by which sugar molecules (oligosaccharides) are attached to proteins and fats. Glycosylation modifies proteins so they can perform a wider variety of functions.The COG complex takes part in the transport of proteins, including the enzymes that perform glycosylation, within the Golgi apparatus. COG is specifically involved in retrograde transport, which moves proteins backward through the Golgi apparatus. Retrograde transport is important for recycling Golgi proteins and ensuring that they are in the correct location in the structure, which is key to proper glycosylation. The proteins are transported in sac-like structures called vesicles that attach to the Golgi membrane and release the contents into the Golgi apparatus. The COG complex controls the attachment (tethering) of the vesicles to the Golgi membrane. COG5-congenital disorder of glycosylation https://medlineplus.gov/genetics/condition/cog5-congenital-disorder-of-glycosylation 13S golgi transport complex 1 90 kDa subunit CDG2I COG complex subunit 5 conserved oligomeric Golgi complex protein 5 conserved oligomeric Golgi complex subunit 5 GOLTC1 GTC90 NCBI Gene 10466 OMIM 606821 2014-08 2020-08-18 COL11A1 collagen type XI alpha 1 chain https://medlineplus.gov/genetics/gene/col11a1 functionThe COL11A1 gene provides instructions for making a component of type XI collagen called the pro-alpha1(XI) chain. Collagens are molecules that provide structure and strength to the connective tissues that support the body's muscles, joints, organs, and skin. Type XI collagen is normally found in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type XI collagen is also part of the inner ear; the vitreous, which is the clear gel that fills the eyeball; and the nucleus pulposus, which is the center portion of the discs between the bones of the spine (vertebrae).Collagens begin as rope-like procollagen molecules that are each made up of three chains. The pro-alpha1(XI) chain combines with two other collagen chains, pro-alpha2(XI) and pro-alpha1(II), to form a triple-stranded procollagen molecule. Then the ropelike procollagen is processed by enzymes to create mature collagen. Mature collagen molecules arrange themselves into long, thin fibrils that form stable interactions (cross-links) with one another in the spaces between cells (the extracellular matrix). The cross-links result in the formation of very strong type XI collagen fibers.Type XI collagen also helps maintain the spacing and width (diameter) of another type of collagen molecule, type II collagen. Type II collagen is an important component of the vitreous and cartilage. The arrangement and size of type II collagen fibrils is essential for the normal structure of these tissues. Stickler syndrome https://medlineplus.gov/genetics/condition/stickler-syndrome Fibrochondrogenesis https://medlineplus.gov/genetics/condition/fibrochondrogenesis Intervertebral disc disease https://medlineplus.gov/genetics/condition/intervertebral-disc-disease Osteoarthritis https://medlineplus.gov/genetics/condition/osteoarthritis Carpal tunnel syndrome https://medlineplus.gov/genetics/condition/carpal-tunnel-syndrome COLL6 collagen type XI alpha 1 collagen XI, alpha-1 polypeptide collagen, type XI, alpha 1 STL2 NCBI Gene 1301 OMIM 120280 2016-04 2024-12-19 COL11A2 collagen type XI alpha 2 chain https://medlineplus.gov/genetics/gene/col11a2 functionThe COL11A2 gene provides instructions for making a component of type XI collagen called the pro-alpha2(XI) chain. Collagens are molecules that provide structure and strength to the connective tissues that support the body's muscles, joints, organs, and skin. Type XI collagen is normally found in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type XI collagen made with the pro-alpha2(XI) chain is also part of the inner ear and the nucleus pulposus, which is the center portion of the discs between the bones of the spine (vertebrae).Collagens begin as rope-like procollagen molecules that are each made up of three chains. The pro-alpha2(XI) chain combines with two other collagen chains, pro-alpha1(XI) and pro-alpha1(II), to form a triple-stranded procollagen molecule. Then the ropelike procollagen is processed by enzymes to create mature collagen. Mature collagen molecules arrange themselves into long, thin fibrils that form stable interactions (cross-links) with one another in the spaces between cells (the extracellular matrix). The cross-links result in the formation of very strong type XI collagen fibers.Type XI collagen also helps maintain the spacing and width (diameter) of another type of collagen molecule, type II collagen. Type II collagen is an important component of mature cartilage. The arrangement and size of type II collagen fibrils is essential for the normal structure of these tissues. Stickler syndrome https://medlineplus.gov/genetics/condition/stickler-syndrome Otospondylomegaepiphyseal dysplasia https://medlineplus.gov/genetics/condition/otospondylomegaepiphyseal-dysplasia Weissenbacher-Zweymüller syndrome https://medlineplus.gov/genetics/condition/weissenbacher-zweymuller-syndrome Nonsyndromic hearing loss https://medlineplus.gov/genetics/condition/nonsyndromic-hearing-loss Fibrochondrogenesis https://medlineplus.gov/genetics/condition/fibrochondrogenesis collagen type XI alpha 2 collagen, type XI, alpha 2 HKE5 PARP STL3 NCBI Gene 1302 OMIM 120290 2016-05 2024-08-23 COL17A1 collagen type XVII alpha 1 chain https://medlineplus.gov/genetics/gene/col17a1 functionThe COL17A1 gene provides instructions for making a protein that is used to assemble type XVII collagen. Collagens are a family of proteins that strengthen and support connective tissues, such as skin, bone, tendons, and ligaments, throughout the body. In particular, type XVII collagen plays an essential role in strengthening and stabilizing the skin.The protein produced from the COL17A1 gene is known as a pro-α1(XVII) chain. Three identical pro-α1(XVII) chains twist together to form a triple-stranded, ropelike molecule known as a procollagen. Procollagen molecules are released from the cell and processed by enzymes to remove extra protein segments from the ends. Once these molecules are processed, they arrange themselves into long, thin bundles of mature type XVII collagen.Type XVII collagen is a major component of hemidesmosomes, which are microscopic structures on the inner surface of the top layer of skin (the epidermis). These structures help to anchor the epidermis to underlying layers of skin. Type XVII collagen is critical for the stability of hemidesmosomes, and therefore it plays an important role in holding the layers of skin together. Junctional epidermolysis bullosa https://medlineplus.gov/genetics/condition/junctional-epidermolysis-bullosa alpha 1 type XVII collagen BA16H23.2 BP180 BPAG2 bullous pemphigoid antigen 2 (180kD) COHA1_HUMAN collagen type XVII alpha 1 collagen XVII, alpha-1 polypeptide collagen, type XVII, alpha 1 FLJ60881 KIAA0204 LAD-1 NCBI Gene 1308 OMIM 113811 2009-09 2020-08-18 COL18A1 collagen type XVIII alpha 1 chain https://medlineplus.gov/genetics/gene/col18a1 functionThe COL18A1 gene provides instructions for making a protein that forms collagen XVIII. Three COL18A1 proteins, called alpha 1 subunits, attach to each other to form collagen XVIII. Collagen XVIII is found in the basement membranes of tissues throughout the body. Basement membranes are thin, sheet-like structures that separate and support cells in these tissues.There are three versions (isoforms) of the alpha 1 subunit of collagen XVIII, which form three different lengths of the collagen XVIII protein. The short version of collagen XVIII is found in basement membranes throughout the body, including several parts of the eye. The two longer versions are found primarily in the liver. In addition, a piece of collagen XVIII can be cut off to form the protein endostatin. Endostatin is able to block the formation of blood vessels (angiogenesis) and is known as an anti-angiogenic factor.Little is known about the function of collagen XVIII, but it appears that all of the isoforms are involved in normal development of the eye. Knobloch syndrome https://medlineplus.gov/genetics/condition/knobloch-syndrome antiangiogenic agent collagen alpha-1(XVIII) chain collagen type XVIII alpha 1 collagen, type XVIII, alpha 1 endostatin FLJ27325 FLJ34914 KNO KNO1 KS MGC74745 multi-functional protein MFP NCBI Gene 80781 OMIM 120328 2011-06 2020-08-18 COL1A1 collagen type I alpha 1 chain https://medlineplus.gov/genetics/gene/col1a1 functionThe COL1A1 gene provides instructions for making part of a large molecule called type I collagen. Collagens are a family of proteins that strengthen and support many tissues in the body, including cartilage, bone, tendon, skin, and the white part of the eye (the sclera). Type I collagen is the most abundant form of collagen in the human body.A component of type I collagen called the pro-α1(I) chain is produced from the COL1A1 gene. Collagens begin as rope-like procollagen molecules that are each made up of three chains. Type I collagen is composed of two pro-α1(I) chains and one pro-α2(I) chain (which is produced from the COL1A2 gene).The triple-stranded procollagen molecules are processed by enzymes in a series of steps inside and outside the cell to create mature collagen. The collagen molecules then arrange themselves into long, thin fibrils that form stable interactions (cross-links) with one another in the spaces between cells. The cross-links result in the formation of very strong type I collagen fibers. Ehlers-Danlos syndrome https://medlineplus.gov/genetics/condition/ehlers-danlos-syndrome Osteogenesis imperfecta https://medlineplus.gov/genetics/condition/osteogenesis-imperfecta Dermatofibrosarcoma protuberans https://medlineplus.gov/genetics/condition/dermatofibrosarcoma-protuberans Caffey disease https://medlineplus.gov/genetics/condition/caffey-disease Intervertebral disc disease https://medlineplus.gov/genetics/condition/intervertebral-disc-disease Carpal tunnel syndrome https://medlineplus.gov/genetics/condition/carpal-tunnel-syndrome alpha 1 type I collagen preproprotein CO1A1_HUMAN COL1A1 protein collagen I, alpha-1 polypeptide collagen of skin, tendon and bone, alpha-1 chain collagen type I alpha 1 collagen, type I, alpha 1 type I collagen alpha 1 NCBI Gene 1277 OMIM 120150 OMIM 166710 2019-11 2023-03-21 COL1A2 collagen type I alpha 2 chain https://medlineplus.gov/genetics/gene/col1a2 functionThe COL1A2 gene provides instructions for making part of a large molecule called type I collagen. Collagens are a family of proteins that strengthen and support many tissues in the body, including cartilage, bone, tendon, skin, and the white part of the eye (the sclera). Type I collagen is the most abundant form of collagen in the human body.A component of type I collagen called the pro-α2(I) chain is produced from the COL1A2 gene. Collagens begin as rope-like procollagen molecules that are each made up of three chains. Type I collagen is composed of two pro-α1(I) chains (which are produced from the COL1A1 gene) and one pro-α2(I) chain.The triple-stranded procollagen molecules are processed by enzymes in a series of steps inside and outside the cell to create mature collagen. The collagen molecules then arrange themselves into long, thin fibrils that form stable interactions (cross-links) with one another in the spaces between cells. The cross-links result in the formation of very strong type I collagen fibers. Ehlers-Danlos syndrome https://medlineplus.gov/genetics/condition/ehlers-danlos-syndrome Osteogenesis imperfecta https://medlineplus.gov/genetics/condition/osteogenesis-imperfecta alpha 2 collagen type I CO1A2_HUMAN collagen I, alpha-2 polypeptide collagen of skin, tendon and bone, alpha-2 chain collagen type I alpha 2 collagen, type I, alpha 2 NCBI Gene 1278 OMIM 120160 2019-11 2020-08-18 COL2A1 collagen type II alpha 1 chain https://medlineplus.gov/genetics/gene/col2a1 functionThe COL2A1 gene provides instructions for making the basic component of type II collagen, called the alpha-1(II) chain. Type II collagen adds structure and strength to connective tissues and plays an important role in the normal development of joints, eyes, and the inner ear. Type II collagen is found primarily in cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later replaced by bone, except for the cartilage that covers and protects the ends of bones and the cartilage that is present in the nose and external ears. Type II collagen is particularly abundant in a form of cartilage known as hyaline cartilage, which is found in the developing skeleton, joints, and at the end of the long bones of the arms and legs where new bone is produced (growth plates). Type II collagen is also part of the inner ear, the clear gel that fills the eyeball (the vitreous), and the center portion (nucleus pulposus) of the discs between the bones of the spine (vertebrae).To construct type II collagen, three alpha-1(II) chains twist together to form a procollagen molecule. Procollagen molecules are then processed by enzymes in the cell. Once processed, the modified collagen molecules leave the cell and arrange themselves into long, thin fibrils that attach (bind) to one another in a lattice pattern (cross-link) in the spaces around cells. The cross-linkages result in the formation of very strong, mature type II collagen fibers. Stickler syndrome https://medlineplus.gov/genetics/condition/stickler-syndrome Kniest dysplasia https://medlineplus.gov/genetics/condition/kniest-dysplasia Spondyloepiphyseal dysplasia congenita https://medlineplus.gov/genetics/condition/spondyloepiphyseal-dysplasia-congenita Spondyloepiphyseal dysplasia with marked metaphyseal changes https://medlineplus.gov/genetics/condition/spondyloepiphyseal-dysplasia-with-marked-metaphyseal-changes Spondyloperipheral dysplasia https://medlineplus.gov/genetics/condition/spondyloperipheral-dysplasia Platyspondylic dysplasia, Torrance type https://medlineplus.gov/genetics/condition/platyspondylic-dysplasia-torrance-type Achondrogenesis https://medlineplus.gov/genetics/condition/achondrogenesis Spondyloepiphyseal dysplasia with metatarsal shortening https://medlineplus.gov/genetics/condition/spondyloepiphyseal-dysplasia-with-metatarsal-shortening collagen of cartilage collagen, type II collagen, type II, alpha 1 collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital) NCBI Gene 1280 OMIM 120140 2024-12 2024-12-20 COL3A1 collagen type III alpha 1 chain https://medlineplus.gov/genetics/gene/col3a1 functionThe C