Swyer syndrome.

Alternative Names

GDXY; Gonadal Dysgenesis, 46,XY; GONADAL DYSGENESIS, XY FEMALE TYPE; Pure gonadal dysgenesis 46,XY; 46,XY CGD; 46,XY complete gonadal dysgenesis; XY pure gonadal dysgenesis

Symptoms & Characteristics

Swyer syndrome is a genetic 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 It?

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

Genetics & Inheritance

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 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.

·         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 mutations is described as having a Y-linked inheritance pattern. In Y-linked inheritance, a mutation can only be passed from father to son.

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 malesexual 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.

·         When an NR5A1 mutation is responsible for Swyer syndrome, the condition is also usually caused by a new mutation. As with SRY gene mutations, an NR5A1 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).

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.

·         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 striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Genetic Testing

Clinical genetic testing for Swyer syndrome may be available through an in person genetic consultation for people who are considered at risk. 

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