Aarskog-Scott syndrome is a genetic disorder that affects the development of many parts of the body. 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. 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. Some may have mild learning and behavior problems, while others have normal intelligence. In rare cases, severe intellectual disability has been reported.
Aarskog-Scott syndrome is believed to be a rare disorder; however, its prevalence is unknown because mildly affected people may not be diagnosed.
Mutations in the FGD1 gene are the only known genetic cause of Aarskog-Scott syndrome. The FGD1 gene provides instructions for making a protein that turns on (activates) another protein called Cdc42, which transmits signals that are important for various aspects of development before and after birth.
Mutations in the FGD1 gene lead to the production of an abnormally functioning protein. These mutations disrupt Cdc42 signaling, leading to the wide variety of abnormalities that occur in people with Aarskog-Scott syndrome.
Only about 20 percent of people with this disorder have identifiable mutations in the FGD1 gene. The cause of Aarskog-Scott syndrome in other affected individuals is unknown.
When caused by FGD1 gene mutations, Aarskog-Scott syndrome is inherited in an X-linked recessive pattern. The FGD1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause Aarskog-Scott syndrome. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females who carry one altered copy of the FGD1 gene may show mild signs of the condition, such as hypertelorism, short stature, or a widow's peak hairline. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
Evidence suggests that Aarskog-Scott syndrome is inherited in an autosomal dominant or autosomal recessive pattern in some families, although the genetic cause of these cases is unknown. In autosomal dominant inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Aarskog syndrome
- facio-digito-genital dysplasia
- faciodigitogenital syndrome
- faciogenital dysplasia
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Daubon T, Buccione R, Génot E. The Aarskog-Scott syndrome protein Fgd1 regulates podosome formation and extracellular matrix remodeling in transforming growth factor β-stimulated aortic endothelial cells. Mol Cell Biol. 2011 Nov;31(22):4430-41. doi: 10.1128/MCB.05474-11. Epub 2011 Sep 12. Citation on PubMed or Free article on PubMed Central
- Estrada L, Caron E, Gorski JL. Fgd1, the Cdc42 guanine nucleotide exchange factor responsible for faciogenital dysplasia, is localized to the subcortical actin cytoskeleton and Golgi membrane. Hum Mol Genet. 2001 Mar 1;10(5):485-95. Citation on PubMed
- Gao L, Gorski JL, Chen CS. The Cdc42 guanine nucleotide exchange factor FGD1 regulates osteogenesis in human mesenchymal stem cells. Am J Pathol. 2011 Mar;178(3):969-74. doi: 10.1016/j.ajpath.2010.11.051. Citation on PubMed or Free article on PubMed Central
- Hou P, Estrada L, Kinley AW, Parsons JT, Vojtek AB, Gorski JL. Fgd1, the Cdc42 GEF responsible for Faciogenital Dysplasia, directly interacts with cortactin and mAbp1 to modulate cell shape. Hum Mol Genet. 2003 Aug 15;12(16):1981-93. Citation on PubMed
- Orrico A, Galli L, Buoni S, Hayek G, Luchetti A, Lorenzini S, Zappella M, Pomponi MG, Sorrentino V. Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog-Scott syndrome due to a novel FGD1 gene mutation (R408Q). Am J Med Genet A. 2005 May 15;135(1):99-102. Citation on PubMed
- Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E, Rinaldi MM, Medeira A, Sorrentino V. Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. Eur J Hum Genet. 2004 Jan;12(1):16-23. Citation on PubMed
- Orrico A, Galli L, Faivre L, Clayton-Smith J, Azzarello-Burri SM, Hertz JM, Jacquemont S, Taurisano R, Arroyo Carrera I, Tarantino E, Devriendt K, Melis D, Thelle T, Meinhardt U, Sorrentino V. Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene. Am J Med Genet A. 2010 Feb;152A(2):313-8. doi: 10.1002/ajmg.a.33199. Citation on PubMed
- Oshima T, Fujino T, Ando K, Hayakawa M. Role of FGD1, a Cdc42 guanine nucleotide exchange factor, in epidermal growth factor-stimulated c-Jun NH2-terminal kinase activation and cell migration. Biol Pharm Bull. 2011;34(1):54-60. Citation on PubMed