Mayer-Rokitansky-Küster-Hauser Syndrome Type 1

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome type 1, a form of MRKH syndrome (see this term), is an isolated form of congenital aplasia of the uterus and 2/3 of the vagina occurring in otherwise phenotypically normal females.

Epidemiology

MRKH syndrome (including type 1 and type 2) has a worldwide prevalence of 1/4500 live female births. The rate of MRKH syndrome type 1 varies largely between different cohorts reported, therefore an accurate incidence of this type is not possible.

Clinical description

MRKH syndrome type 1 is most often diagnosed in adolescence as the first symptom is most commonly a primary amenorrhea in young women presenting with otherwise normal development of secondary sexual characteristics and normal external genitalia. Patients lack the uterus and the upper 2/3 of the vagina. Because of this, difficulties with sexual intercourse have been reported. Pelvic pain can be reported in those with uterine remnants. As the uterus is missing or not functional, women cannot bear children. However, the ovaries are normal and functional.

Etiology

The exact etiology of MRKH syndrome remains largely unknown. Initially, MRKH syndrome was considered to be of sporadic occurrence, suggesting the involvement of non-genetic or environmental factors. However, no link between an environmental cause and MRKH syndrome has ever been established. It is now clear that MRKH syndrome has a genetic origin, through increasing family descriptions and numerous genetic studies already completed. The latter have led to reveal several chromosomal abnormalities associated with the disease, such as small interstitial duplications in 1q21.1 and in Xpter-p22.32, or deletions in 4q34-qter, 8p23.1, 10p14, 16p11.2, 17q12, 22q11.21 and Xq21.31. These genomic rearrangements affect numerous genes. Putative candidate genes have been described, such as HNF1B (17q12), LHX1 (17q12), SHOX (Xp22.33 and Yp11.32), TBX6 (16p11.2), and ITIH5 (10p14). The phenotype-genotype correlations however, have not been established.

Genetic counseling

MRKH syndrome (type 1 or type 2) was thought to be purely sporadic but in familial cases it seems to be inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity. Genetic counseling can be beneficial in these familial cases.