The majority of MRKH syndrome cases are characterized as sporadic, but familial cases have provided evidence that, at least for some patients, MRKH is an inherited disorder. The underlying causes of MRKH syndrome is still being investigated, but several causative genes have been studied for their possible association with the syndrome. Most of these studies have served to rule-out genes as causative factors in MRKH, but thus far, only WNT4 has been associated with MRKH with hyperandrogenism.Reports of MRKH syndrome can be traced back to Hippocrates (460 B.C.–377 B.C.). The medical eponym honors August Franz Josef Karl Mayer (1787–1865), Carl Freiherr von Rokitansky (1804–1878), Hermann Küster (1879–1964) and Georges Andre Hauser (1921–2009). Signs and symptoms
A female with this condition is hormonally normal; that is, the woman will enter puberty with development of secondary sexual characteristics including thelarche and pubarche (pubic hair). The womans karyotype will be 46,XX. At least one ovary is intact, if not both, and ovulation usually occurs. Typically, the vagina is shortened and intercourse may, in some cases, be difficult and painful. Medical examination supported by gynecologic ultrasonography demonstrates a complete or partial absence of the cervix, uterus, and vagina.If there is no uterus, a woman with MRKH cannot carry a pregnancy without intervention. It is possible for the woman to have genetic offspring by in vitro fertilization (IVF) and surrogacy.
Successful uterine transplant has been performed in limited numbers of patients, resulting in several live births, but the technique is not widespread or accessible to many women.A woman with MRKH typically discovers the condition when, during puberty years, the menstrual cycle does not start (primary amenorrhoea). Some find out earlier through surgeries for other conditions, such as a hernia. Causes
The etiology of MRKH syndrome in many cases remains elusive. However, mutations in a variety of different genes have been implicated in causing MRKH syndrome. The typical and atypical forms of the disorder are presumably caused by mutations in different genes.WNT4 (found on the short arm (p) of chromosome 1) has been clearly implicated in the atypical version of this disorder. A genetic mutation causes a leucine to proline residue substitution at amino acid position 12. This occurrence reduces the intranuclear levels of β catenin. In addition, it removes the inhibition of steroidogenic enzymes like 3β-hydroxysteriod dehydrogenase and 17α-hydroxylase. Patients therefore have androgen excess. Furthermore, without WNT4, the Müllerian duct is either deformed or absent. Female reproductive organs, such as the cervix, fallopian tubes, and much of the vagina, are hence affected.An association with 17q12 microdeletion syndrome, a deletion mutation in the long arm (q) of chromosome 17, has been reported. The gene LHX1 is located in this region and may be the cause of a number of these cases.