The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina) – phenotypic manifestations and genetic approaches

Daniel Guerrier, Thomas Mouchel, Laurent Pasquier, Isabelle Pellerin

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome affects at least 1 out of 4500 women and has for a long time been considered as a sporadic anomaly. Congenital absence of upper vagina and uterus is the prime feature of the disease which, in addition, is often found associated with unilateral renal agenesis or adysplasia as well as skeletal malformations (MURCS association). The phenotypic manifestations of MRKH overlap various other syndromes or associations and thus require accurate delineation. Since MRKH manifests itself in males, the term GRES syndrome (Genital, Renal, Ear, Skeletal) might be more appropriate when applied to both sexes. The MRKH syndrome, when described in familial aggregates, seems to be transmitted as an autosomal dominant trait with an incomplete degree of penetrance and variable expressivity. This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal deletion. Until recently progress in understanding the genetics of MRKH syndrome has been slow, however, now HOX genes have been shown to play key roles in body patterning and organogenesis, and in particular during genital tract development. Expression and/or function defects of one or several HOX genes may account for this syndrome.