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

Abstract

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.

Mayer–Rokitansky–Kuster–Hauser Type-B Anomaly with MURCS Association and Gonadal Dysgenesis

“…The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome affects 1 out of 4,500 women [1]. It is a malformation of the female genitals due to interrupted embryonic development of the mullerian (paramesonephric) ducts in otherwise chromosomally, phenotypically, and endocrinologically normal female.…”

Gestational surrogacy and the role of routine embryo screening: Current challenges and future directions for preimplantation genetic testing

“…Thus, either monoallelic dominant mutations within HOXA9/10/ 11 might be causing the MRKH phenotype, or perhaps other disruptions of HOX are altering its transcription (Innis, 2002;Guerrier et al, 2006).…”

Family case of Mayer—Rokitansky—Kuster—Hauser syndrome and literature review

“…Некоторые исследователи [7,24] предполагали, что аплазия влагалища и матки может также возни-кать как результат изменчивой экспрессии гена и передаваться как аутосомно-доминантный признак с неполной пенетрантностью в сочетании с измен-чивой выраженностью одного единственного му-тантного гена или быть результатом ограниченной хромосомной нестабильности, не выявляемой стан-дартным кариотипированием. Возможность доми-нантного наследования синдрома МРКХ дискутиро-валась в связи с увеличивающейся частотой семей-ных случаев этой патологии и противоречием для такого вида наследования послужил тот факт, что лишь у одного близнеца монозиготной двойни был обнаружен синдром МРКХ [25][26][27].…”