Androgen Insensitivity Syndrome, Partial

National Organization for Rare Disorders, Inc.

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Disorder Subdivisions

  • None

General Discussion

Androgen insensitivity refers to an inability of the body to respond properly to male sex hormones (androgens) produced during pregnancy. This occurs because of a change (mutation) in a gene involved in the production of the protein inside cells that receives the androgen hormone and instructs the cell in how to use it.

Partial androgen insensitivity syndrome (pais) is part of a spectrum of syndromes that also includes androgen insensitivity syndrome (AIS) and mild androgen insensitivity syndrome (mais). In each case, the development of the reproductive and genital organs of the fetus is affected, as a result of the gene mutation.

During the first 10 weeks of pregnancy, the external anatomy of male and female embryos appears to be identical. The presence or absence of the male sex hormone testosterone determines whether male or female genitalia develop. In partial androgen insensitivity syndrome, the development of the external genitals will be intermediate between male and female (ambiguous genitalia).

Each of these forms of AIS is also a hereditary form of male pseudohermaphroditism, in which the baby is born with testes and possesses both male and female characteristics. The disorder is inherited as an X-linked, recessive trait.


The symptoms of partial androgen insensitivity syndrome can vary greatly. In the least severe cases, the only symptom that presents itself may be infertility which is related to hardening of the tubules in the testis (seminiferous tubular sclerosis), and either very little or no sperm in the semen.

In more severe cases, an abnormal penis in which the urethra opens on the underside (hypospadias), impaired production of male hormones due to dysfunction of gonads (hypogonadism), and excessive development of the male breasts (gynecomastia) may also occur. One or both testes may fail to descend normally, and a decrease in the functioning of the cells in the testis that produce androgens (leydic cell hyperplasia) may lead to impotence later in life. Facial and chest hair may be sparse or missing and the voice may have a high pitch.


Partial androgen insensitivity syndrome (PAIS) is inherited as an X-linked recessive genetic disorder. The gene involved is located on the long arm of the X chromosome (Xq11-q12).

The affected gene codes for, or stimulates the production of, a protein known as the androgen receptor. It is this protein that affects the developing fetus and signals the fetus to respond to the presence of the male hormones. When the AR gene is defective the development of the genitalia of either sex is interfered with.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes.

Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome Xq11-q12" refers to the region on the long arm of the X chromosome between bands 11 and 12. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off" and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is "turned off". A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Affected Populations

PAIS is a very rare genetic disorder. This disorder only occurs in males but females are the carriers of the genetic defect. There have been many reports of multiple males in a family inheriting the syndrome.

Standard Therapies

The use of drugs that replace testosterone at an early age may restore fertility in males with partian androgen insensitivity syndrome. Surgery may be undertaken to correct the condition in which the penis is drained through an opening on its underside (hypospadia). Corrective surgery may also be done on enlarged breasts in males. Patients with more severe defects may be raised as females and have corrective surgery performed before puberty. These patients may use estrogen therapy at puberty. Psychological counseling is recommended to help young males and teenagers through the problems associated with the disorder and the issues of gender determination.

Genetic counseling may be of benefit for patients and their families. The treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010


For information about clinical trials sponsored by private sources, contact:



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Supporting Organizations

AIS-DSD Support Group

P.O. Box 2148
Duncan, OK 73534-2148
Website: //

Accord Alliance

531 Route 22 East #244
Whitehouse Station, NJ 08889
Tel: (908) 349-0534
Fax: (801) 349-0534
Website: //

Genetic and Rare Diseases (GARD) Information Center

PO Box 8126
Gaithersburg, MD 20898-8126
Tel: (301)251-4925
Fax: (301)251-4911
Tel: (888)205-2311
Website: //

For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see