Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder that mainly affects the female reproductive system. This condition causes the vagina and uterus to be underdeveloped or absent, although external genitalia are normal. Affected individuals usually do not have menstrual periods due to the absence of a uterus. Often, the first noticeable sign of MRKH syndrome is that menstruation does not begin by age 16 (primary amenorrhea). People with MRKH syndrome have a female chromosome pattern (46,XX) and normally functioning ovaries. They also have normal breast and pubic hair development. Although people with this condition are usually unable to carry a pregnancy, they may be able to have children through assisted reproduction.
When only reproductive organs are affected, the condition is classified as MRKH syndrome type 1. Some individuals with MRKH syndrome also have abnormalities in other parts of the body; in these cases, the condition is classified as MRKH syndrome type 2. In this form of the condition, the kidneys may be abnormally formed or positioned, or one kidney may fail to develop (unilateral renal agenesis). Affected individuals commonly develop skeletal abnormalities, particularly of the spinal bones (vertebrae). People with MRKH syndrome type 2 may also have hearing loss or heart defects.
MRKH syndrome affects approximately 1 in 4,500 female newborns.
The cause of MRKH syndrome is unknown. Changes in several genes that are involved in development before birth have been identified in people with MRKH syndrome. However, each has been found in only a few affected individuals, and it is unclear whether these changes cause MRKH syndrome. Researchers are working to determine how genetic changes might lead to problems with development of the female reproductive system.
The reproductive abnormalities of MRKH syndrome are due to incomplete development of the Müllerian duct. This structure in the embryo develops into the uterus, fallopian tubes, cervix, and the upper part of the vagina. The cause of the abnormal development of the Müllerian duct in affected individuals is unknown. Originally, researchers suspected that MRKH syndrome was caused by environmental factors during pregnancy, such as medication or maternal illness. However, subsequent studies have not identified an association with any specific maternal drug use, illness, or other factor. Researchers now suggest that in combination, genetic and environmental factors contribute to the development of MRKH syndrome, although the specific factors are often unknown.
It is also unclear why some affected individuals have abnormalities in parts of the body other than the reproductive system. Certain tissues and organs, such as the kidneys, develop from the same embryonic tissue as the Müllerian duct, and researchers suspect that problems during development could affect these organs as well.
Most cases of MRKH syndrome occur in people with no history of the disorder in their family.
Less often, MRKH syndrome is passed through generations in families. Its inheritance pattern is usually unclear because the signs and symptoms of the condition frequently vary among affected individuals in the same family. However, in some families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is typically sufficient to cause the disorder, although the gene involved is usually unknown.
Other Names for This Condition
- 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
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Fontana L, Gentilin B, Fedele L, Gervasini C, Miozzo M. Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Clin Genet. 2017 Feb;91(2):233-246. doi: 10.1111/cge.12883. Epub 2016 Nov 16. Review. Citation on PubMed
- Gervasini C, Grati FR, Lalatta F, Tabano S, Gentilin B, Colapietro P, De Toffol S, Frontino G, Motta F, Maitz S, Bernardini L, Dallapiccola B, Fedele L, Larizza L, Miozzo M. SHOX duplications found in some cases with type I Mayer-Rokitansky-Kuster-Hauser syndrome. Genet Med. 2010 Oct;12(10):634-40. doi: 10.1097/GIM.0b013e3181ed6185. Citation on PubMed
- Herlin M, Højland AT, Petersen MB. Familial occurrence of Mayer-Rokitansky-Küster-Hauser syndrome: a case report and review of the literature. Am J Med Genet A. 2014 Sep;164A(9):2276-86. doi: 10.1002/ajmg.a.36652. Epub 2014 Jun 26. Review. Citation on PubMed
- Ledig S, Brucker S, Barresi G, Schomburg J, Rall K, Wieacker P. Frame shift mutation of LHX1 is associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Hum Reprod. 2012 Sep;27(9):2872-5. doi: 10.1093/humrep/des206. Epub 2012 Jun 26. Citation on PubMed
- Ledig S, Schippert C, Strick R, Beckmann MW, Oppelt PG, Wieacker P. Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky-Küster-Hauser syndrome. Fertil Steril. 2011 Apr;95(5):1589-94. doi: 10.1016/j.fertnstert.2010.07.1062. Epub 2010 Aug 24. Citation on PubMed
- Morcel K, Camborieux L; Programme de Recherches sur les Aplasies Müllériennes, Guerrier D. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Orphanet J Rare Dis. 2007 Mar 14;2:13. Review. Citation on PubMed or Free article on PubMed Central
- Pizzo A, Laganà AS, Sturlese E, Retto G, Retto A, De Dominici R, Puzzolo D. Mayer-rokitansky-kuster-hauser syndrome: embryology, genetics and clinical and surgical treatment. ISRN Obstet Gynecol. 2013;2013:628717. doi: 10.1155/2013/628717. Epub 2013 Feb 4. Citation on PubMed or Free article on PubMed Central
- Sandbacka M, Laivuori H, Freitas É, Halttunen M, Jokimaa V, Morin-Papunen L, Rosenberg C, Aittomäki K. TBX6, LHX1 and copy number variations in the complex genetics of Müllerian aplasia. Orphanet J Rare Dis. 2013 Aug 16;8:125. doi: 10.1186/1750-1172-8-125. Citation on PubMed or Free article on PubMed Central
- Sultan C, Biason-Lauber A, Philibert P. Mayer-Rokitansky-Kuster-Hauser syndrome: recent clinical and genetic findings. Gynecol Endocrinol. 2009 Jan;25(1):8-11. doi: 10.1080/09513590802288291. Review. Citation on PubMed
- Tewes AC, Rall KK, Römer T, Hucke J, Kapczuk K, Brucker S, Wieacker P, Ledig S. Variations in RBM8A and TBX6 are associated with disorders of the müllerian ducts. Fertil Steril. 2015 May;103(5):1313-8. doi: 10.1016/j.fertnstert.2015.02.014. Epub 2015 Mar 23. Citation on PubMed
- Wottgen M, Brucker S, Renner SP, Strissel PL, Strick R, Kellermann A, Wallwiener D, Beckmann MW, Oppelt P. Higher incidence of linked malformations in siblings of Mayer-Rokitansky-Küster-Hauser-syndrome patients. Hum Reprod. 2008 May;23(5):1226-31. doi: 10.1093/humrep/den059. Epub 2008 Mar 5. Citation on PubMed