Androgen insensitivity syndrome (AIS) is a genetic condition that mostly affects males. Some females may display very mild symptoms. Individuals with AIS have genetic defects that affect the development of physical traits and characteristics normally associated with males; traits and characteristics normally associated with females may develop in males with AIS.
Depending on the severity of the mutation affecting the androgen receptor, individuals with AIS can experience a range of symptoms. In the most severe cases, individuals with AIS have a completely female body with external female genitalia, but with no uterus, fallopian tube, or ovaries. However, they may have testes in the abdomen. In less severe cases, individuals with AIS have a normal male body, with internal and external male genitalia, but they have problems with sperm production and reduced fertility. The severity of the symptoms depends on the severity of the mutation affecting the androgen receptor, and how much activity the androgen receptor still has.
AIS is caused by mutations, or errors, in the androgen receptor, which is a protein on the surface of cells that responds to the hormone testosterone (and to a form of testosterone called dihydrotestosterone). In unaffected males, the androgen receptor plays an important role in initiating the development of male traits and characteristics. In males with AIS, the androgen receptor is not functioning properly so male traits do not develop normally.
Currently, there is no known cure for AIS. Depending on the specific symptoms, an individual with AIS may choose to identify with either the male gender or the female gender. Based on this decision, a number of options exist to treat the condition, including surgical procedures, such as vaginal construction, breast reduction, and gonadectomy (removal of the testes from patients that appear female). In addition, genetic and psychological counseling is available for patients and their parents.
Female symptoms: Androgen insensitivity syndrome (AIS) is known to be caused by mutations, or errors, in a gene for the androgen receptor. Women who have a mutation in the androgen receptor gene generally do not develop androgen insensitivity syndrome. However, they may develop some minor symptoms, including reduced pubic hair and reduced normal adolescent acne.
Male symptoms: Males with AIS may develop a range of different symptoms, depending on the severity of the mutation in the androgen receptor gene. A severe mutation that completely eliminates the ability of the androgen receptor to respond to testosterone results in complete AIS (CAIS). Partial AIS (PAIS) results when the androgen receptor has some remaining ability to respond to testosterone. Patients with PAIS can be affected with a spectrum of different symptoms.
Complete AIS: Patients with complete AIS (CAIS) have a completely female body with external female genitalia, but with no uterus, fallopian tube, or ovaries. However, they may have testes in the abdomen. Individuals with CAIS have minimal pubic hair and the vagina is often shallow. Additionally, the cervix is usually absent.
Partial AIS: In some forms of PAIS, patients have a female body, with slightly ambiguous female genitalia (an enlarged clitoris and partially fused labia), testes in the abdomen, and sparse to normal pubic hair.
Patients with Reifenstein syndrome (another form of PAIS) have very ambiguous external genitalia, and they may have testes in the scrotum. They have sparse to normal pubic hair and may be affected with gynecomastia (an abnormal enlargement of the mammary glands causing breast enlargement) at puberty.
In less severe forms of PAIS, patients may have a normal male body internally and externally, but they produce reduced numbers of sperm and have reduced fertility. Additionally, in some individuals, the size of the penis may be smaller than average.
Depending on the severity of the symptoms, diagnosis of androgen insensitivity syndrome (AIS) may vary from patient to patient. Genetic and chromosomal testing may be used to provide a more definitive diagnosis.
Physical signs: In individuals who appear to be female, AIS may be suspected because of a lack of menstruation and the presence of very little pubic hair during adolescence. The presence of testes or the absence of ovaries are other signs that may suggest complete AIS in individuals who appear to be female. Such a discovery could be made during a surgery, such as for a hernia, or during a routine pelvic exam. If the external genitalia of an individual are somewhat or highly ambiguous, it may suggest the individual has a less severe form of AIS, such as Reifenstein syndrome.
Hormone levels: Individuals with AIS produce high levels of testosterone, even if their external appearance resembles that of a female. Therefore, patients with AIS who appear female may have higher levels of testosterone in their blood. However, because the androgen receptor doesn't properly respond to testosterone in patients with AIS, they do not exhibit male traits, like body hair. Measuring the level of testosterone in the blood may indicate the presence of AIS. The levels of luteinizing hormone (LH), which is a hormone involved in reproduction, may be slightly higher in males with AIS as well.
Chromosome studies: If AIS is suspected, a karyotype test may be performed. This test provides a picture of the person's chromosomes. A sample of the patient's blood is taken and analyzed for the presence of one or two copies of chromosome X. If only one copy of chromosome X is detected in individuals who appear female, a diagnosis of AIS would be supported.
Genetic tests: Mutations in the gene for the androgen receptor are known to cause AIS. Genetic tests can be used to check for these mutations and diagnose AIS.
Infertility: Males with androgen insensitivity syndrome (AIS) who have external female genitalia lack ovaries and a uterus, so they are infertile. Additionally, individuals with AIS who have external male genitalia may produce reduced numbers of sperm. This can lead to reduced fertility or infertility in these patients.
Cancer: Individuals who appear externally female often have testes within their abdomen. Although these testes do not function normally and do not produce any sperm, there is an increased risk that testicular cancer may develop in these patients.
Osteoporosis: Some individuals with AIS may develop osteoporosis, a condition in which the bones become weaker due to thinning and loss of density. It is not completely clear why this complication arises, but is thought to result from hormonal imbalances in patients with AIS.
Hernia: In individuals who have testes in the abdomen (instead of in the scrotum, where they are normally found), inguinal hernia may develop. Hernia is a condition where internal organs bulge out of their normal location and interfere with nearby muscles.
Psychological impact: Patients with androgen insensitivity syndrome (AIS) who appear externally to be female may not learn of their condition until the teenage years. This can create emotional distress for some patients. Counseling, therapy, and attending support groups may help individuals with AIS (and their families) become more comfortable with their condition.
There is currently no known cure for AIS. Based on the specific symptoms that an individual patient exhibits, a number of options are available that can help patients live more normal lives and a decision may need to be made whether to raise an individual with AIS as a male or a female.
Vaginal enlargement: For some patients with AIS, the shallowness of the vagina makes sexual intercourse difficult. Sometimes this problem can be treated in a non-surgical way, in which an individual applies pressure on the vagina in particular locations to dilate it. If this method is unsuccessful, constructive surgery may also be performed on the vagina to enlarge its size.
Gonadectomy: AIS patients with testes in their abdomen may have an increased risk of testicular cancer. To reduce this risk, surgical removal of the testes may be recommended. However, patients who undergo this procedure need to go on hormone replacement therapy and take estrogen. This is because the estrogen in patients with complete or more severe forms of partial AIS is generated by converting testosterone (which is made by the testes) into estrogen. With the testes removed, patients with complete or partial AIS are no longer able to produce any estrogen, which is needed for growth and bone development.
Breast surgery: Some patients with AIS have external male genitalia but also develop breasts. In these patients, surgery can be performed to remove excess breast tissue.
There are currently no known ways to prevent androgen insensitivity syndrome (AIS). However, several treatments exist that may help manage the symptoms of AIS. Additionally, genetic counseling is available for parents.
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Androgen insensitivity syndrome (AIS) is caused by mutations, or errors, in the androgen receptor, which is a protein on the surface of cells that responds to the hormone testosterone (and to a form of testosterone called dihydrotestosterone). In males, the androgen receptor plays an important role in initiating the development of male-associated physical traits and characteristics. In males with AIS, the androgen receptor is not functioning properly, so male traits do not properly develop.
About two-thirds of patients with AIS inherit a mutated androgen receptor gene from their mother. However, in about a third of cases, AIS is not inherited, but is caused by a new, spontaneously arising mutation in the mother's egg cell; this differs from inheritance because a spontaneously arising mutation is not present in the cells throughout the body of the mother.
There are a variety of different mutations that can occur and affect the androgen function receptor. Some mutations are more severe and completely eliminate the ability of the androgen receptor to function. Other mutations are less severe and may allow the androgen receptor to partially function and respond to testosterone. Therefore, some patients with AIS will have less severe symptoms than other patients, depending on the degree to which the androgen receptor is still able to function.
Androgen insensitivity syndrome (AIS) mostly affects males. It is known to be caused by mutations, or errors, in a gene for the androgen receptor. This gene is located on the X chromosome, which is one of the sex chromosomes.
Females have two copies of the X chromosome, whereas males have one copy of the X chromosome and one copy of the Y chromosome. Females pass on one of their X chromosomes to male children, whereas males pass on their only Y chromosome to male children. Therefore, females who have a mutated androgen receptor gene on one of their X chromosomes have a 50% risk of passing the mutated gene to a son, and having a son who is affected with AIS. Women who have mutated androgen receptors on both X chromosome have a 100% risk of passing the mutation to a son. On the other hand, males who have a mutated androgen receptor gene on their X chromosome are not at risk for passing the mutation to a son. Therefore, this is a condition that is genetically inherited by an individual from his or her mother.
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.