Müllerian aplasia and hyperandrogenism

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Reviewed July 2014

What is Müllerian aplasia and hyperandrogenism?

Müllerian aplasia and hyperandrogenism is a condition that affects the reproductive system in females. This condition is caused by abnormal development of the Müllerian ducts, which are structures in the embryo that develop into the uterus, fallopian tubes, cervix, and the upper part of the vagina. Individuals with Müllerian aplasia and hyperandrogenism typically have an underdeveloped or absent uterus and may also have abnormalities of other reproductive organs. Women with this condition have normal female external genitalia, and they develop breasts and pubic hair normally at puberty; however, they do not begin menstruation by age 16 (primary amenorrhea) and will likely never have a menstrual period. Affected women are unable to have children (infertile).

Women with Müllerian aplasia and hyperandrogenism have higher-than-normal levels of male sex hormones called androgens in their blood (hyperandrogenism), which can cause acne and excessive facial hair (facial hirsutism). Kidney abnormalities may be present in some affected individuals.

How common is Müllerian aplasia and hyperandrogenism?

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

What genes are related to Müllerian aplasia and hyperandrogenism?

Mutations in the WNT4 gene cause Müllerian aplasia and hyperandrogenism. 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 ducts. This protein is also involved in development of the ovaries, from before birth through adulthood, and is important for development and maintenance of egg cells (oocytes) in the ovaries. In addition, the WNT4 protein regulates the production of androgens.

Mutations in the WNT4 gene change single protein building blocks (amino acids) in the WNT4 protein. Researchers suspect that the altered protein cannot be released from cells as it normally would be; the trapped protein is unable to perform its usual functions. Loss of regulation by WNT4 likely disrupts development of the female reproductive system and induces abnormal production of androgens, leading to the features of Müllerian aplasia and hyperandrogenism.

How do people inherit Müllerian aplasia and hyperandrogenism?

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. Girls with Müllerian aplasia and hyperandrogenism do not inherit the mutation from their mother, because women with this disorder cannot have children. It is unknown, though, if an affected person inherits the mutation from her father or if the condition is caused by new mutations in the gene. Müllerian aplasia and hyperandrogenism may occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of Müllerian aplasia and hyperandrogenism?

These resources address the diagnosis or management of Müllerian aplasia and hyperandrogenism and may include treatment providers.

You might also find information on the diagnosis or management of Müllerian aplasia and hyperandrogenism in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about Müllerian aplasia and hyperandrogenism?

You may find the following resources about Müllerian aplasia and hyperandrogenism helpful. These materials are written for the general public.

MedlinePlus - Health information (4 links)
Additional NIH Resources - National Institutes of Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development: Amenorrhea
Educational resources - Information pages (4 links)
Patient support - For patients and families (2 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for Müllerian aplasia and hyperandrogenism?

Biason-Lauber syndrome
Mayer-Rokitansky-Küster-Hauser-Biason-Lauber syndrome
Mayer-Rokitansky-Küster-Hauser-like syndrome
Mullerian aplasia and hyperandrogenism
Müllerian duct failure
WNT4 deficiency
WNT4 Müllerian aplasia
WNT4 Müllerian aplasia and ovarian dysfunction

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about Müllerian aplasia and hyperandrogenism?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding Müllerian aplasia and hyperandrogenism?

acids ; acne ; androgens ; autosomal ; autosomal dominant ; cell ; deficiency ; duct ; egg ; embryo ; gene ;genitalia ; hirsutism ; hormone ; infertile ; kidney ; menstruation ; mutation ; ovarian ; protein ; puberty ;syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (9 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.