Abstract
The Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome [MIM 277000] is characterised by the absence of a uterus and vagina in otherwise phenotypically normal women with karyotype 46,XX. Clinically, the MRKH can be subdivided into two subtypes: an isolated or type I form can be delineated from a type II form, which is characterised by extragenital malformations. The so-called Müllerian hypoplasia, renal agenesis, cervicothoracic somite dysplasia (MURCS) association can be seen as the most severe phenotypic outcome.The MRKH syndrome affects at least 1 in 4000 to 5000 female new-borns. Although most of the cases are sporadic, familial clustering has also been described, indicating a genetic cause of the disease. However, the mode of inheritance is autosomal-dominant inheritance with reduced penetrance. High-resolution array-CGH and MLPA analysis revealed recurrent aberrations in different chromosomal regions such as TAR susceptibility locus in 1q21.1, chromosomal regions 16p11.2, and 17q12 and 22q11.21 microduplication and -deletion regions in patients with MRKH. Sequential analysis of the genes LHX1, TBX6 and RBM8A, which are located in chromosomal regions 17q12, 16p11.2 and 1q21.1, yielded in the detection of MRKH-associated mutations. In a subgroup of patients with signs of hyperandrogenaemia mutations of WNT4 have been found to be causative. Analysis of another member of the WNT family, WNT9B, resulted in the detection of some causative mutations in MRKH patients.
Highlights
The first clinical feature is generally primary amenorrhea
It was shown that the expression of Wnt9b in Lhx1deficient mice is markedly altered [34]. All of these findings suggest a common pathway in MRKH syndrome with WNT9B acting upstream of WNT4 and LHX1
As array comparative genomic hybridisation (CGH) analyses in MRKH patients identified recurrent aberrations in chromosomal regions 1q21.1, 16p11.2, 17q12 and 22q11.21 respectively, array CGH analyses should be performed in women with the suspected diagnosis of MRKH syndrome
Summary
The Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome [MIM 277000] is characterised by the congenital absence of the uterus and the upper two thirds of the vagina in 46,XX females with mostly normal ovarian function and normal breast and pubic hair development. The Fallopian tubes can be affected, but the lower part of the vagina is usually unaffected This is in good agreement with the hypothesis that the lower part of the vagina might develop from the urogenital sinus and might not be a derivative of the Müllerian ducts (MDs). Renal agenesis, cervicothoracic somite dysplasia (MURCS) association is the most severe form of MRKH II characterised by MD aplasia, renal dysplasia and cervical somite dysplasia. MRKH can be associated with hearing defects including conduction defects such as stapes fixation or sensorineural deafness. Associations with situs inversus, Dandy–Walker malformation, Meckel–Gruber syndrome, Bardet–Biedl syndrome, Holt–Oram syndrome or McKusick–Kaufman syndrome have been reported, leading to the assumption that—in at least some cases—MRKH can be seen as a ciliopathy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
