WNT4 Müllerian aplasia and ovarian dysfunction

WNT4 Müllerian aplasia and ovarian dysfunction is a disorder that occurs in females and affects the reproductive system. This condition is caused by abnormal development of the Müllerian duct, a structure present in the embryo that develops into the uterus, fallopian tubes, cervix, and the upper part of the vagina. Individuals with WNT4 Müllerian aplasia and ovarian dysfunction typically have an underdeveloped or absent uterus and may also have abnormalities of other reproductive organs. Women with this condition have normal female genitalia and normal breast and public hair development, but they do not begin menstruation by age 16 (primary amenorrhea). It is unknown if women with this disorder will ever menstruate.

Women with WNT4 Müllerian aplasia and ovarian dysfunction have higher than normal levels of male sex hormones (androgens) in their blood. These high levels of androgens cause acne and excessive facial hair (facial hirsutism). Kidney abnormalities may be present in some affected individuals.

WNT4 Müllerian aplasia and ovarian dysfunction is a very rare disorder; it has been identified in only a few individuals worldwide.

Mutations in the WNT4 gene cause WNT4 Müllerian aplasia and ovarian dysfunction. This gene belongs to a family of WNT genes that play critical roles in development before birth. The WNT4 gene provides instructions for producing a protein that is important for the formation of the female reproductive system, the kidneys, and several hormone-producing glands. During the development of the female reproductive system, the WNT4 protein regulates the formation of the Müllerian duct. This protein also regulates the production of androgens and the development and maintenance of egg cells (oocytes).

Mutations in the WNT4 gene change single protein building blocks (amino acids) in the WNT4 protein. Researchers suspect that the altered protein cannot be secreted, which would leave it trapped within cells and unable to perform its usual functions. It remains unclear how mutations in the WNT4 gene lead to the signs and symptoms of WNT4 Müllerian aplasia and ovarian dysfunction.

Read more about the WNT4 gene.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. It is unknown whether an affected person inherits the mutation from one parent or if the condition is caused by new mutations in the gene. WNT4 Müllerian aplasia and ovarian dysfunction may occur in people with no history of the disorder in their family.