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Androgen Insensitivity Syndrome, Partial

Synonyms of Androgen Insensitivity Syndrome, Partial

  • Gilbert-Dreyfus Syndrome
  • Incomplete Testicular Feminization
  • Lubs Syndrome
  • Reifenstein Syndrome
  • Rosewater Syndrome
  • Type I Familial Incomplete Male Pseudohermaphroditism

Disorder Subdivisions

  • No subdivisions found.

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.

Related Disorders

Symptoms of the following disorders can be similar to those of partial androgen insensitivity syndrome. Comparisons may be useful for a differential diagnosis:

Complete androgen insensitivity syndrome (CAIS) is characterized by a shutdown of the androgen receptor gene. The fetus cannot respond at all to the presence of androgens in the fetal bloodstream. At birth, the infant appears female but there is no uterus, fallopian tubes, or ovaries. The diagnosis may be made at puberty, when menstruation does not occur.

Congenital adrenal hyperplasia (CAH) is a group of recessively inherited disorders caused by one of several enzyme deficiencies that impair the ability of the adrenal glands to produce corticosteroids. (For more information, use Adrenal Hyperplasia, Congenital (General) as your search term in the Rare Disease Database.)

Testicular feminization is a syndrome in which a person has one X and one Y sex chromosome (making the person genetically male), but is resistant to androgens (male hormones). As a result, the individual has some or all of the physical characteristics of a woman, but the genetic makeup of a man. The syndrome is divided into two main categories complete and incomplete. Complete testicular feminization results in someone who looks outwardly female. In the incomplete testicular feminization syndrome, the degree of sexual ambiguity varies widely from individual to individual.

Klinefelter syndrome is a disorder resulting from an excess of X chromosomes. Individuals with Klinefelter syndrome are genetically 47,XXY and live as men since this disorder affects only males. It is characterized by small testes, lack of sperm, enlarged mammary glands and an abnormally small penis. There may also be a retardation of sex organ development, an absence of facial and body hair, lack of muscular development and a high pitched voice. (For more information on this disorder, choose Klinefelter as your search term in the Rare Disease Database.)

Pseudovaginal perineoscrotal hypospadias is a rare autosomal recessive condition arising from the inability of the male fetus to convert testosterone into the more physiologically active dihydrotestosterone (DHT). DHT is essential for the development of normal external male genitalia in the uterus, and because DHT is absent in these cases, the child is born with ambiguous genitalia (male pseudohermaphroditism). Infants born with this disorder present with a wide range of clinical abnormalities ranging from infertility with normal male genitalia to underdeveloped male genitalia with hypospadias to predominantly female external genitalia.

Turner syndrome is a rare chromosomal disorder of females characterized by short stature and the lack of sexual development at puberty. Other physical features may include a short neck with a webbed appearance, heart defects, kidney abnormalities, and/or various other malformations. Among affected females, there is also a heightened incidence of osteoporosis, type II diabetes, and hypothyroidism. There appears to be great variability in the degree to which girls with Turner syndrome are affected by any of its manifestations.

Turner syndrome occurs when one of the two X chromosomes normally found in women is missing or incomplete. Although the exact cause of Turner syndrome is not known, it appears to occur as a result of a random error during the division (meiosis) of sex cells. (For more information on this disorder, choose Turner syndrome as your search term in the Rare Disease Database.)

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

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Androgen Insensitivity Syndrome, Partial Resources



Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:1290-92

Scriver CR, Beaudet AL, Sly WS, et al., eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:4130-32.

Mazen I, Lumbroso S, Abdel Ghaffar S, et al. Mutation of the androgen receptor (R840S) in an Egyptian patient with partial androgen insensitivity syndrome: review of the literature on the clinical expression of different R840 substitutions. J Endocrinol Invest. 2004;27:57-60.

Sultan C, Lumbroso S, Paris F, et al. Disorder of androgen action. Semin Reprod Med. 2002;20:217-28.

Brinkmann AO. Molecular basis of androgen insensitivity. Mol Cell Endocrinol. 2001;179:105-09.

Sultan C, Paris F, Terouanne B, et al. Disorders linked to insufficient androgen action in male children. Hum Reprod Update. 2001;7:314-22.

Lower KM, Kumar R, Woollatt E, et al. Partial Androgen Insensitivity Syndrome and t(X;5): Are There Upstream Regulatory Elements of the Androgen Receptor Gene? Horm Res. 2004;62:208-14.

Dessouky NM. Gender assignment for children with intersex problems: An Egyptian perspective. Saudi Med J. 2003;24 (5Suppl):S51-52.

Migeon CJ, Wisniewski AB, Gearhart JP, et al. Ambiguous genitalia with perineoscrotal hypospadias in 46,XY individuals: long-term medical, surgical, and psychosexual outcomes. Pediatrics. 2002;110:e31.

Foresta C, Betella A, Ferlin A, et al. Response to local dihydrotestosterone treatment ina patient with partial androgen insensitivity syndrome due to a novel mutation in the androgen receptor gene. Am J Med Genet. 2002;107:259-60.

Lundberg Giwercman Y, Nikoshkov A, Lindsten K, et al. Response to treatment in patients with partial androgen insensitivity syndrome due to mutations in the DNA-binding domain of the androgen receptor. Horm Res. 2000;53:83-88.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Androgen Receptor; AR. Entry Number; 313700: Last Edit Date; 12/14/2004.

Medical Encyclopedia: Reifenstein syndrome. Update Date: 1/30/2003. 3pp.

Medical Encyclopedia: Testicular feminization. Update Date: 10/6/2003. 3pp.

Wilson BE. Androgen Insensitivity Syndrome. emedicine. Last Updated: July 11, 2003. 14pp.

Wilson BE. 5-Alpha-Reductase Deficiency. emedicine. Last Updated:may 26,2004. 14pp.

Gottlieb B, Beitel LK, Trifiro MA. Androgen Insensitivity Syndrome. GENEReviews. Last Update: 8 April 2004. 16pp.

What is AIS. AIS Support Group. Last updated 12 Sept 2004. 8pp.

Partial AIS. AIS Support Group. Last updated 17 Feb 2003. 6pp.

What is the Androgen Insensitivity Syndrome? Intersex Society of North America. Posted Thu, Jan 01 2004.

Capelanes AR, Jeanty P. Partial androgen insensitivity syndrome. The Fetus Net. nd. 3pp.

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Report last updated: 2008/04/11 00:00:00 GMT+0

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