Definition: The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part (2/3) of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype.
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.
MRKH may be isolated (type I) but it is more frequently associated with renal, vertebral, and, to a lesser extent, auditory and cardiac defects (MRKH type II or MURCS association).
The first sign of MRKH syndrome is a primary amenorrhea in young women presenting otherwise with normal development of secondary sexual characteristics and normal external genitalia, with normal and functional ovaries, and karyotype 46, XX without visible chromosomal anomaly.
The phenotypic manifestations of MRKH syndrome overlap with various other syndromes or associations and thus require accurate delineation. For a long time the syndrome has been considered as a sporadic anomaly, but increasing number of familial cases now support the hypothesis of a genetic cause.
In familial cases, the syndrome appears to be transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity.
This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal imbalance. However, the etiology of MRKH syndrome still remains unclear.
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.
References
Morcel K, Camborieux L; Programme de Recherches sur les Aplasies Mulleriennes (PRAM), Guerrier D. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Orphanet J Rare Dis. 2007 Mar 14;2:13. PMID: 17359527
Guerrier D, Mouchel T, Pasquier L, Pellerin I. The Mayer-Rokitansky-Kuster-Hauser syndrome (congenital absence of uterus and vagina)—phenotypic manifestations and genetic approaches. J Negat Results Biomed. 2006 Jan 27;5:1. PMID: 16441882
Pavanello Rde C, Eigier A, Otto PA. Relationship between Mayer-Rokitansky-Kuster (MRK) anomaly and hereditary renal adysplasia (HRA). Am J Med Genet. 1988 Apr;29(4):845-9. PMID: 3400728