The causes of<unk>  are not well-understood. The aetiology of this congenital disease may be multifactorial, with genetics, socioeconomic factors and geographic factors playing a role in dysfunctional<unk>  duct development.<unk>  likely occur early in development, as the congenital disorder often occurs in association with renal and anorectal disorders. Typically, women with<unk>  abnormalities have a normal female karyotype (46, XX). Most incidences of<unk>  occur sporadically, with instances of familial inheritance patterns being less common. The genetic component of the disease classically follows an autosomal dominant pattern, with variable rates of genotypic expression. WNT4 signalling WNT4 is a gene that has a crucial role in embryonic development, particularly to ensure the normal formation of the female reproductive system, the kidneys and several endocrine organs. The Wnt4 gene pathway promotes female sexual differentiation, while suppressing male sexual differentiation. Mice lacking Wnt4 display androgenisation, the presence of Wolffian ducts and absence of<unk>  ducts. This effect is mirrored in humans, where mutations in the WNT4 gene has been observed in MRKH syndrome patients, who display hyperandrogenism. Mutations in WNT4 gene are not always present in individuals with<unk>  or MRKH syndrome, but the WNT4 gene is the only gene that has been clearly implicated in MRKH. TP63 TP63 is a tumour protein encoded by the EMX2 gene, which is expressed in uterine and vaginal epithelium. The TP63 protein is required for epithelial differentiation during<unk>  duct development in utero, by promoting the transcription of particular genes. EMX2 mutations result in incomplete<unk>  fusion. Some women with unicornuate uteri exhibit mutant EMX2 and significantly decreased expression of TP63, implicating TP63 in the fusion stage of<unk>  development. Diethylstilbestrol (DES) DES is a synthetic non-steroidal estrogen that was used during 1940–1971, to prevent premature births, miscarriage and other pregnancy complications. The use of DES was discontinued after it was established that approximately 69% of females who were exposed to DES in utero had uterine abnormalities. DES has been marked as a teratogen as it results in malformation of the embryo. DES is more potent than steroidal estrogen and binds to cytosolic receptors after crossing the placenta. DES is not metabolised as quickly as endogenous estrogen. DES remains bound to cytosolic receptors for a longer period of time. The extended binding time of DES and the subsequent prolonged activation of its cognate receptors has been suggested to disrupt<unk>  development, resulting in uterine abnormalities. Exposure to DES induced multiple uterine abnormalities including constriction bands, hypoplasticity in the uterine cavity and irregular borders. Females exposed to this teratogen in utero presented most commonly with a T-shaped uterus, resulting in increased rates of ectopic pregnancy, spontaneous abortions, and an overall increased risk of adverse pregnancy outcome.
Mullerian anomalies
Sex chromosome anomalies
Ovarian disease
Lactational amenorrhea
Sexual anomalies
Tubal factor infertility
Blighted ovum
Female infertility