The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome describes a spectrum of Mullerian duct anomalies characterized by congenital aplasia of the uterus and upper 2/3 of the vagina in otherwise phenotypically normal females. It can be classified as either MRKH syndrome type 1 (corresponding to isolated utero-vaginal aplasia) or MRKH syndrome type 2 (utero-vaginal aplasia associated with other malformations) (see these terms).

MRKH syndrome has a worldwide incidence of 1/4500 live female births.

MRKH syndrome is most often diagnosed in adolescence as the first symptom is usually a primary amenorrhea in young women presenting otherwise with normal development of secondary sexual characteristics and normal external genitalia. MRKH syndrome type 1 and 2 patients lack the uterus and the upper 2/3 of the vagina leading to difficulties with sexual intercourse in some. Pelvic pain can be reported in those with uterine remnants. As the uterus is missing or not functional, women cannot bear children, but ovaries are normal and functional. Other associated malformations seen in MRKH type 2 include kidney abnormalities (40% of cases), skeletal abnormalities (20-25%), hearing impairment (10%), and, more rarely, heart defects.

The exact etiology is largely unknown, even if the spectrum of malformations encountered suggests a developmental defect of the intermediate mesoderm during embryogenesis (by the end of the 4th week of fetal life), leading to an alteration of the blastema of the cervicothoracic somites and the pronephric ducts. It is now clear that MRKH syndrome has a genetic origin through increasing family descriptions and numerous genetic studies already completed. These latter have led to reveal several chromosomal abnormalities associated with the disease and several putative candidate genes have been described.

The karyotype of MRKH patients is always 46, XX. Hormone levels are normal, showing normal and functional ovaries without hyperandrogenism. Transabdominal ultrasonography must be the first investigation in evaluating patients with suspected utero-vaginal aplasia. MRI can be performed to clearly visualize the malformation. A full check-up (renal ultrasonography, spine radiography, heart echography, audiogram) must be undertaken to search for any associated malformations.

Differential diagnosis includes isolated vaginal atresia, which is found in various syndromes such as McKusick-Kaufman syndrome, androgen insensitivity syndrome, Mullerian aplasia and hyperandrogenism, and renal-genital-middle ear anomalies (see these terms).

MRKH syndrome was thought to be purely sporadic but familial cases seem to be inherited autosomal dominantly with incomplete penetrance and variable expressivity, and in these cases genetic counseling can be beneficial.

The medical care of MRKH patients requires the coordinated efforts of pediatricians, gynecologists, surgeons, endocrinologists and psychologists. Treatment consisting in creating a neovagina must be offered to patients only when they are ready to start sexual activity and when emotionally mature (around 17-21 years). Frank's (nonsurgical) method requires the application of vaginal dilators on the vaginal dimple for at least 20 minutes/day for several months. If unsuccessful, various surgical procedures can be performed to create a neovagina. Clinical follow-up and regular intercourse are essential components to a successful outcome. Psychological support and counseling is strongly recommended for affected women and should provide patients with future fertility options (in vitro fertilization of one's own oocytes followed by surrogate pregnancy or adoption). For the associated malformations in MRKH type 2, specific medical care is directed toward the anomalies.

MRKH syndrome is not a life threatening disease. With treatment, sexual relationships are possible and fertility options are available.

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