ABSTRACT
KATHARINA RALL, GIANMARIA BARRESI, MICHAEL WALTER, SVEN POTHS, KARINA HAEBIG, KARIN SCHAEFERHOFF, BIRGITT SCHOENFISCH, OLAF RIESS, DIETHELM WALLWIENER, MICHAEL BONIN, AND SARA BRUCKER
4.1 BACKGROUND
The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is the second most common cause of primary amenorrhea and affects at least 1 in 4,500 females. It is characterized by congenital absence of the uterus and the upper two thirds of the vagina in women with a normal female karyotype. As the ovaries are functional, women affected have physiological hormone levels and normal secondary sexual characteristics [1]. The MRKH syndrome may occur isolated (type I), or can be associated with renal or skeletal malformations, and, to a lesser extent, auditory and cardiac defects (type II) [2]. Although it is generally sporadic,
familial clustering has been described, indicating a genetic cause [3]. Familial cases have been explained by autosomal dominant inheritance with incomplete penetrance and variable expressivity or by small chromosomal aberrations undetectable in standard karyotypes [4]. However, the lack of families with informative genetic histories has not allowed the identification of any locus using standard genetic linkage analysis. Investigations have therefore used a candidate gene approach based on association with other genetic diseases or involvement during embryogenesis [4].
