Müllerian Aplasia and Hyperandrogenism

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Rita Xu	+ 502 word(s)	502	2020-12-15 07:32:42

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/mullerian-aplasia-and-hyperandrogenism

Müllerian aplasia and hyperandrogenism is a condition that affects the reproductive system in females.

genetic conditions

1. Introduction

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.

2. Frequency

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

3. Causes

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.

4. Inheritance

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.

5. Other Names for This Condition

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

References

Bernard P, Harley VR. Wnt4 action in gonadal development and sexdetermination. Int J Biochem Cell Biol. 2007;39(1):31-43.Review.
Biason-Lauber A, De Filippo G, Konrad D, Scarano G, Nazzaro A, Schoenle EJ.WNT4 deficiency--a clinical phenotype distinct from the classicMayer-Rokitansky-Kuster-Hauser syndrome: a case report. Hum Reprod. 2007Jan;22(1):224-9.
Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ. A WNT4 mutation associatedwith Müllerian-duct regression and virilization in a 46,XX woman. N Engl J Med.2004 Aug 19;351(8):792-8.
Biason-Lauber A, Konrad D. WNT4 and sex development. Sex Dev.2008;2(4-5):210-8. doi: 10.1159/000152037.
Biason-Lauber A. WNT4, RSPO1, and FOXL2 in sex development. Semin Reprod Med. 2012 Oct;30(5):387-95. doi: 10.1055/s-0032-1324722.
Philibert P, Biason-Lauber A, Gueorguieva I, Stuckens C, Pienkowski C,Lebon-Labich B, Paris F, Sultan C. Molecular analysis of WNT4 gene in fouradolescent girls with mullerian duct abnormality and hyperandrogenism (atypicalMayer-Rokitansky-Küster-Hauser syndrome). Fertil Steril. 2011 Jun30;95(8):2683-6. doi: 10.1016/j.fertnstert.2011.01.152.
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 genemutation among 28 adolescent girls with primary amenorrhea and müllerian ductabnormalities: a French collaborative study. J Clin Endocrinol Metab. 2008Mar;93(3):895-900. doi: 10.1210/jc.2007-2023.
Prunskaite-Hyyryläinen R, Shan J, Railo A, Heinonen KM, Miinalainen I, Yan W, Shen B, Perreault C, Vainio SJ. Wnt4, a pleiotropic signal for controlling cellpolarity, basement membrane integrity, and antimüllerian hormone expressionduring oocyte maturation in the female follicle. FASEB J. 2014 Apr;28(4):1568-81.doi: 10.1096/fj.13-233247.

©Text is available under the terms and conditions of the Creative Commons-Attribution ShareAlike (CC BY-SA) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Genetics & Heredity

Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Rita Xu

View Times: 318

Entry Collection: MedlinePlus

Update Date: 23 Dec 2020

Table of Contents

Video Upload Options

Confirm

1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

Video Upload Options

Confirm

1. Introduction

2. Frequency

3. Causes

3.1. The Gene Associated with Müllerian Aplasia and Hyperandrogenism

4. Inheritance

5. Other Names for This Condition

References