Reifenstein syndrome is one of a group of diseases in which the body is unable to respond appropriately to the male sex hormones (androgens), which include testosterone.

In this genetic disease, the affected gene codes for the androgen receptor, which allows cells to respond to androgens. This particular mutation makes the cells less responsive to these hormones -- hence the alternative name, Partial Androgen Insensitivity Syndrome.

During normal fetal development, male hormones (androgens) are made by the testes of male fetuses and as a result, male sexual organs develop. If the hormones cannot be processed normally as a result of a genetic mutation in the androgen receptor, probelems occur with the development of the male sex organs. At birth, this may result in confusion over the sex of the baby due to ambiguous genitalia.

The disease is inherited in an X-linked recessive manner, which means that women are not affected but may carry the gene, and males who inherit the gene from their mothers will have the condition. There is a 1 in 2 (or 50%) chance that a male child of a carrier mother will be affected. Family history is important in determining risk factors.

It is estimated to affect 1 in 99,000 people.

• Abnormal male genitals, including undescended testes; a small scrotum, with a line down the middle (bifid) or incompletely closed; a small penis; and hypospadias (the urethra exits the body on the side of the penis, not the tip)
• Breast development in males at time of puberty
• Infertility
• Decreased body hair and beard with normal pubic and armpit hair

• Male chromosomes -- X,Y
• High testosterone and luteinizing hormone level in blood
• Low or absent sperm count
• Testicular biopsy shows no mature sperm despite normal precursors
• Decreased or absent vas deferens (the tubes through which sperm exit the testes)
• Partial development of female gonads/sex organs
• Decreased ability to bind androgen in cell culture tests
• Mutations in the androgen receptor gene can be tested for diagnosis, carrier detection and prenatal diagnosis.
• Family history of affected males who share a common, unaffected female relative consistent with X-linked recessive inheritance

Early and continuous testosterone treatment may improve the chance that a boy will grow up to be fertile.

Support can be obtained from the Androgen Insensitivity Syndrome Support Group (AISSG).

Intersex Society of North America (ISNA)

4500 9th Avenue NE,

Suite 300

Seattle, WA 98105

phone: 206-633-6077

fax: 206-633-6049

Androgens are most important during early development in the womb. A male with Reifenstein syndrome can have a normal lifespan and be totally healthy, with the exception of infertility and possible psychological problems related to gender identity.

In the most severe cases, feminized external genitalia or an extremely small penis tend to cause psychological and emotional problems for these boys. In these cases, some parents have tried to raise people with Reifenstein syndrome as girls; however, this is rarely effective.

Genital surgery should be postponed until the affected person can make an informed choice. There are numerous accounts of people with ambiguous genitalia who had surgery during infancy to feminize their organs (since it is easier to do this than to create male organs) who later feel maimed.

• Infertility and failure to develop normal male gonads/genitals.
• Breast development in men can be a cosmetic concern.
• Psychological problems like depression may occur.

Call your health care provider if you, your son, or a male family member has infertility or incomplete development of male external organs, despite high blood testosterone. Genetic testing and counseling is available if there is a strong suspicion that this disease is present.

Prenatal testing is available for known androgen receptor mutations. People with a family history of these conditions should consider genetic counseling. Testosterone treatment that is started early may prevent some infertility.