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Genetics Home Reference: your guide to understanding genetic conditions
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WNT4 Müllerian aplasia and ovarian dysfunction

Reviewed February 2009

What is 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.

How common is WNT4 Müllerian aplasia and ovarian dysfunction?

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

What genes are related to WNT4 Müllerian aplasia and ovarian dysfunction?

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.

Related Gene(s)

Changes in this gene are associated with WNT4 Müllerian aplasia and ovarian dysfunction.

  • WNT4

How do people inherit WNT4 Müllerian aplasia and ovarian dysfunction?

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.

Where can I find information about diagnosis or management of WNT4 Müllerian aplasia and ovarian dysfunction?

These resources address the diagnosis or management of WNT4 Müllerian aplasia and ovarian dysfunction and may include treatment providers.

  • Gene Tests: Mullerian Aplasia And Hyperandrogenism (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319264)
  • MedlinePlus Encyclopedia: Excessive or unwanted hair in women (http://www.nlm.nih.gov/medlineplus/ency/article/003148.htm)
  • MedlinePlus Encyclopedia: Ovarian overproduction of androgens (http://www.nlm.nih.gov/medlineplus/ency/article/001165.htm)
  • MedlinePlus Encyclopedia: Primary Amenorrhea (http://www.nlm.nih.gov/medlineplus/ency/article/001218.htm)

You might also find information on the diagnosis or management of WNT4 Müllerian aplasia and ovarian dysfunction in Educational resources (http://ghr.nlm.nih.gov/condition/wnt4-mullerian-aplasia-and-ovarian-dysfunction/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/wnt4-mullerian-aplasia-and-ovarian-dysfunction/show/Patient+support).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about WNT4 Müllerian aplasia and ovarian dysfunction?

You may find the following resources about WNT4 Müllerian aplasia and ovarian dysfunction helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Encyclopedia: Excessive or unwanted hair in women (http://www.nlm.nih.gov/medlineplus/ency/article/003148.htm)
    • Encyclopedia: Ovarian overproduction of androgens (http://www.nlm.nih.gov/medlineplus/ency/article/001165.htm)
    • Encyclopedia: Primary Amenorrhea (http://www.nlm.nih.gov/medlineplus/ency/article/001218.htm)
    • Health Topic: Uterine Diseases (http://www.nlm.nih.gov/medlineplus/uterinediseases.html)
  • Additional NIH Resources - National Institutes of Health
    Eunice Kennedy Shriver National Institute of Child Health and Human Development: Amenorrhea (http://www.nichd.nih.gov/health/topics/amenorrhea.cfm)

  • Educational resources - Information pages

    • American Urological Association Foundation: Vaginal Agenesis (http://www.urologyhealth.org/urology/index.cfm?article=50)
    • Kids Health: Female Reproductive System (http://kidshealth.org/parent/general/body_basics/female_reproductive_system.html)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=73217)

  • Patient support - For patients and families

    • AIS-DSD Support Group for Women (http://www.aisdsd.org/)
    • National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1018/viewAbstract)

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

  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/319264)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((m%C3%BCllerian%20aplasia%5BTIAB%5D)%20OR%20(mullerian%20aplasia%5BTIAB%5D)%20OR%20(wnt4%20deficiency%5BTIAB%5D)%20OR%20(WNT4))%20NOT%20((tendon)%20OR%20(muscle))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/158330)

What other names do people use for WNT4 Müllerian aplasia and ovarian dysfunction?

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

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about WNT4 Müllerian aplasia and ovarian dysfunction?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding WNT4 Müllerian aplasia and ovarian dysfunction?

acids ; acne ; amino acid ; androgens ; autosomal ; autosomal dominant ; cell ; deficiency ; duct ; egg ; embryo ; gene ; genitalia ; hirsutism ; hormone ; kidney ; menstruation ; mutation ; new mutation ; ovarian ; protein ; sex hormone ; sign ; symptom ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Bernard P, Harley VR. Wnt4 action in gonadal development and sex determination. Int J Biochem Cell Biol. 2007;39(1):31-43. Epub 2006 Jul 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16905353?dopt=Abstract)
  • Biason-Lauber A, De Filippo G, Konrad D, Scarano G, Nazzaro A, Schoenle EJ. WNT4 deficiency--a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report. Hum Reprod. 2007 Jan;22(1):224-9. Epub 2006 Sep 7. (http://www.ncbi.nlm.nih.gov/pubmed/16959810?dopt=Abstract)
  • Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ. A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman. N Engl J Med. 2004 Aug 19;351(8):792-8. (http://www.ncbi.nlm.nih.gov/pubmed/15317892?dopt=Abstract)
  • Biason-Lauber A, Konrad D. WNT4 and sex development. Sex Dev. 2008;2(4-5):210-8. Epub 2008 Nov 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18987495?dopt=Abstract)
  • OMIM: MULLERIAN APLASIA AND HYPERANDROGENISM (http://omim.org/entry/158330)
  • Philibert P, Biason-Lauber A, Rouzier R, Pienkowski C, Paris F, Konrad D, Schoenle E, Sultan C. Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and müllerian duct abnormalities: a French collaborative study. J Clin Endocrinol Metab. 2008 Mar;93(3):895-900. Epub 2008 Jan 8. (http://www.ncbi.nlm.nih.gov/pubmed/18182450?dopt=Abstract)

 

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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2009
Published: May 21, 2012