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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Swyer syndrome

Reviewed December 2008

What is Swyer syndrome?

Swyer syndrome is a condition in which individuals with one X chromosome and one Y chromosome in each cell, the pattern normally found in males, have a female appearance. People with this disorder have female external genitalia and a normal uterus and Fallopian tubes. However, they do not have functional gonads (ovaries or testes). Instead, they have undeveloped clumps of tissue called streak gonads. These abnormal gonads often become cancerous, so they are usually removed surgically early in life.

People with Swyer syndrome are typically raised as females and have a female gender identity. Affected individuals usually begin hormone replacement therapy during adolescence to induce menstruation and development of female secondary sex characteristics such as breast enlargement and body hair. Hormone replacement therapy also helps prevent reduced bone density (osteopenia). Women with this disorder do not produce eggs, but may be able to become pregnant with a donated egg or embryo.

How common is Swyer syndrome?

Swyer syndrome has been estimated to occur in approximately 1 in 30,000 people.

What genes are related to Swyer syndrome?

People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males ordinarily have one X chromosome and one Y chromosome (46,XY).

Mutations in the SRY gene have been identified in between 15 percent and 20 percent of individuals with Swyer syndrome. The SRY gene, located on the Y chromosome, provides instructions for making the sex-determining region Y protein. This protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The sex-determining region Y protein causes a fetus to develop as a male. SRY gene mutations that cause Swyer syndrome prevent production of the sex-determining region Y protein or result in the production of a nonfunctioning protein. A fetus whose cells do not produce functional sex-determining region Y protein will develop as a female despite having a Y chromosome.

Mutations in the NR5A1 and DHH genes have also been identified in small numbers of people with Swyer syndrome. The NR5A1 gene provides instructions for producing another transcription factor called the steroidogenic factor 1. This protein helps control the activity of several genes related to the production of sex hormones and development of male sexual characteristics. The DHH gene provides instructions for making a member of the hedgehog protein family. Hedgehog proteins are important for early development in many parts of the body. Mutations in the NR5A1 and DHH genes impair the process of male sexual differentiation, causing affected individuals to develop a female appearance despite having a Y chromosome.

Changes affecting the NR0B1 gene have also been identified in a small number of people with Swyer syndrome. The NR0B1 gene provides instructions for making a protein called DAX1. This protein plays an important role in the development and function of several hormone-producing (endocrine) tissues in the body, including the gonads. Before birth, the DAX1 protein helps regulate genes that direct the formation of these tissues. DAX1 also helps regulate hormone production in endocrine tissues after they have been formed. A duplication of a region in the X chromosome can result in an extra copy of the NR0B1 gene, which leads to the production of extra DAX1 protein. Another mutation, which may also increase the amount of DAX1 protein that is produced, deletes a segment of DNA near the NR0B1 gene and probably disrupts the normal regulation of the gene. Before birth, an excess of DAX1 protein prevents the formation of male reproductive tissues, including the testes and male external genitalia.

Related Gene(s)

Changes in these genes are associated with Swyer syndrome.

  • DHH
  • NR0B1
  • NR5A1
  • SRY

How do people inherit Swyer syndrome?

Most cases of SRY-related Swyer syndrome result from new mutations and occur in people with no history of the disorder in their family. Some individuals with Swyer syndrome caused by an SRY gene mutation inherit the altered gene from an unaffected father who is mosaic for the mutation. Mosaic means that an individual has the mutation in some cells (including some sperm or egg cells), but not in others. In rare cases, a father may carry the mutation in each cell but also has other genetic variations that prevent him from being affected by the disorder. Because the SRY gene is on the Y chromosome, Swyer syndrome caused by SRY gene mutations is described as having a Y-linked inheritance pattern. In Y-linked inheritance, a mutation can only be passed from father to son.

When an NR5A1 gene mutation is responsible for Swyer syndrome, the condition is also usually caused by a new mutation. As with SRY gene mutations, an NR5A1 gene mutation may be inherited from an unaffected parent who is mosaic for the mutation. Since the NR5A1 gene is not on the Y chromosome, the mutation may be inherited from either parent. This pattern of inheritance is called autosomal dominant. In autosomal dominant inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder.

Swyer syndrome caused by mutations in the DHH gene is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene. Female carriers of a DHH gene mutation do not generally have any abnormalities of sex development. Male carriers of a mutated DHH gene may also be unaffected, or they may have genital abnormalities such as the urethra opening on the underside of the penis (hypospadias).

Swyer syndrome caused by changes affecting the NR0B1 gene may be inherited in an X-linked pattern. The NR0B1 gene is located on the X chromosome. In males (who have only one X chromosome), a change in the only copy of the gene in each cell causes the disorder. Changes affecting the NR0B1 gene do not seem to disrupt the sexual development of females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of Swyer syndrome?

These resources address the diagnosis or management of Swyer syndrome and may include treatment providers.

  • Gene Review: 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis (
  • Genetic Testing Registry: 46,XY sex reversal, type 1 (
  • Genetic Testing Registry: 46,XY sex reversal, type 2 (
  • Genetic Testing Registry: 46,XY sex reversal, type 7 (
  • Genetic Testing Registry: Pure gonadal dysgenesis 46,XY (
  • MedlinePlus Encyclopedia: Intersex (
  • University College London Hospitals: Disorders of Sexual Development (

You might also find information on the diagnosis or management of Swyer syndrome 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 Swyer syndrome?

You may find the following resources about Swyer syndrome helpful. These materials are written for the general public.

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

What other names do people use for Swyer syndrome?

  • 46,XY CGD
  • 46,XY complete gonadal dysgenesis
  • 46,XY sex reversal
  • GDXY
  • Gonadal Dysgenesis, 46,XY
  • Pure gonadal dysgenesis 46,XY
  • XY pure gonadal dysgenesis

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 Swyer syndrome?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding Swyer syndrome?

autosomal ; autosomal dominant ; autosomal recessive ; bone density ; cell ; chromosome ; differentiation ; DNA ; duplication ; dysgenesis ; egg ; embryo ; fetus ; gene ; genitalia ; hormone ; hormone replacement therapy ; hypospadias ; inherit ; inheritance ; inheritance pattern ; inherited ; menstruation ; mosaic ; mutation ; new mutation ; osteopenia ; pattern of inheritance ; protein ; recessive ; sex chromosomes ; sperm ; syndrome ; testes ; tissue ; transcription ; transcription factor

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


  • Barbaro M, Oscarson M, Schoumans J, Staaf J, Ivarsson SA, Wedell A. Isolated 46,XY gonadal dysgenesis in two sisters caused by a Xp21.2 interstitial duplication containing the DAX1 gene. J Clin Endocrinol Metab. 2007 Aug;92(8):3305-13. Epub 2007 May 15. (
  • Canto P, Söderlund D, Reyes E, Méndez JP. Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis. J Clin Endocrinol Metab. 2004 Sep;89(9):4480-3. Erratum in: J Clin Endocrinol Metab. 2004 Nov;89(11):5453. (
  • Gimelli G, Gimelli S, Dimasi N, Bocciardi R, Di Battista E, Pramparo T, Zuffardi O. Identification and molecular modelling of a novel familial mutation in the SRY gene implicated in the pure gonadal dysgenesis. Eur J Hum Genet. 2007 Jan;15(1):76-80. Epub 2006 Oct 25. (
  • Köhler B, Lin L, Ferraz-de-Souza B, Wieacker P, Heidemann P, Schröder V, Biebermann H, Schnabel D, Grüters A, Achermann JC. Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Hum Mutat. 2008 Jan;29(1):59-64. (
  • Michala L, Goswami D, Creighton SM, Conway GS. Swyer syndrome: presentation and outcomes. BJOG. 2008 May;115(6):737-41. doi: 10.1111/j.1471-0528.2008.01703.x. (
  • Smyk M, Berg JS, Pursley A, Curtis FK, Fernandez BA, Bien-Willner GA, Lupski JR, Cheung SW, Stankiewicz P. Male-to-female sex reversal associated with an approximately 250 kb deletion upstream of NR0B1 (DAX1). Hum Genet. 2007 Aug;122(1):63-70. Epub 2007 May 15. (
  • Zieliñska D, Zajaczek S, Rzepka-Górska I. Tumors of dysgenetic gonads in Swyer syndrome. J Pediatr Surg. 2007 Oct;42(10):1721-4. (


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.

Reviewed: December 2008
Published: March 2, 2015