[6] AIS is divided into three categories that are differentiated by the degree of genital masculinization: Androgen insensitivity syndrome is the largest single entity that leads to 46,XY undermasculinized genitalia.

The human androgen receptor (AR) is a protein encoded by a gene located on the proximal long arm of the X chromosome (locus Xq11-Xq12).

[10] The protein coding region consists of approximately 2,757 nucleotides (919 codons) spanning eight exons, designated 1-8 or A-H.[5][3] Introns vary in size between 0.7 and 26 kb.

[27][28] A comprehensive meta-analysis of the subject published in 2007 supports the existence of the correlation, and concluded these discrepancies could be resolved when sample size and study design are taken into account.

[11] Inheritance is typically maternal and follows an X-linked recessive pattern;[5][33] individuals with a 46,XY karyotype always express the mutant gene since they have only one X chromosome, whereas 46,XX carriers are minimally affected.

[45] In another patient, CAIS was the result of a deficit in the transmission of a transactivating signal from the N-terminal region of the androgen receptor to the basal transcription machinery of the cell.

[5] Depending on the mutation, a person with a 46,XY karyotype and AIS can have either a male (MAIS) or female (CAIS) phenotype,[47] or may have genitalia that are only partially masculinized (PAIS).

[5][54] A genetic male conceived by a man with AIS would not receive his father's X chromosome, thus would neither inherit nor carry the gene for the syndrome.

Some carriers have been noted to have slightly reduced body hair, delayed puberty, and/or tall stature, presumably due to skewed X-inactivation.

[citation needed] Individuals with partial AIS, unlike those with the complete or mild forms, present at birth with ambiguous genitalia, and the decision to raise the child as male or female is often not obvious.

[56][57] Exactly what causes this variation is not entirely understood, although factors contributing to it could include the lengths of the polyglutamine and polyglycine tracts,[58] sensitivity to and variations in the intrauterine endocrine milieu,[citation needed] the effect of coregulatory proteins active in Sertoli cells,[18][59] somatic mosaicism,[5] expression of the 5RD2 gene in genital skin fibroblasts,[56] reduced AR transcription and translation from factors other than mutations in the AR coding region,[60] an unidentified coactivator protein,[46] enzyme deficiencies such as 21-hydroxylase deficiency,[4] or other genetic variations such as a mutant steroidogenic factor-1 protein.

[67] Sertoli cells within the testes secrete anti-Müllerian hormone around this time to suppress the development of the Müllerian ducts, and cause their degeneration.

[67] Without this anti-Müllerian hormone, the Müllerian ducts develop into the female internal genitalia (uterus, cervix, fallopian tubes, and upper vaginal barrel).

[68] In the presence of testosterone and functional androgen receptors, the Wolffian ducts develop into the epididymides, vasa deferentia, and seminal vesicles.

[69] Masculinization of the male external genitalia (the penis, penile urethra, and scrotum), as well as the prostate, are dependent on the androgen dihydrotestosterone.

[70][71][72][73][74] As is the case with the internal male genitalia, a functional androgen receptor is needed for dihydrotestosterone to regulate the transcription of target genes involved in development.

[9][80] Clinical findings indicative of AIS include the presence of a short vagina [81] or undermasculinized genitalia,[5][57][70] partial or complete regression of Müllerian structures,[82] bilateral nondysplastic testes,[83] and impaired spermatogenesis and/or virilization.

[5][84][42][75] Laboratory findings include a 46,XY karyotype[11] and typical or elevated postpubertal testosterone, luteinizing hormone, and estradiol levels.

[3] The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS.

[96] A nationwide survey in the Netherlands based on patients with genetic confirmation of the diagnosis estimates that the minimal incidence of CAIS is one in 99,000.

[97] Due to its subtle presentation, MAIS is not typically investigated except in the case of male infertility,[70] thus its true prevalence is unknown.

[100][101][102] Recorded descriptions of the effects of AIS date back hundreds of years, although significant understanding of its underlying histopathology did not occur until the 1950s.

In 1839, Scottish obstetrician Sir James Young Simpson published one such description[112] in an exhaustive study of intersexuality that has been credited with advancing the medical community's understanding of the subject.

[90][123][124][125][126] "Pseudohermaphroditism" has, until very recently,[122] been the term used in the medical literature to describe the condition of an individual whose gonads do not match the expected external genitalia in of their sex.

[131][132][133][134] In 1953, American gynecologist John Morris provided the first full description of what he called "testicular feminization syndrome" based on 82 cases compiled from the medical literature, including two of his own patients.

[5] A few years before Morris published his landmark paper, Lawson Wilkins had shown through experiment that unresponsiveness of the target cell to the action of androgenic hormones was a cause of "male pseudohermaphroditism".

[142] Since it was not understood that these different presentations were all caused by the same set of mutations in the androgen receptor gene, a unique name was given to each new combination of symptoms, resulting in a complicated stratification of seemingly disparate disorders.

[80][143] Over the last 60 years, as reports of strikingly different phenotypes were reported to occur even among members of the same family, and as steady progress was made towards the understanding of the underlying molecular pathogenesis of AIS, these disorders were found to be different phenotypic expressions of one syndrome caused by molecular defects in the androgen receptor gene.

The character, Lauren Cooper, played by Bailey De Young, was the first intersex series regular on American television.

[160][161] In season 8, episode 11 ("Delko for the Defense") of the TV series CSI: Miami, the primary suspect has AIS which gets him off a rape charge.