Androgen Insensitivity Syndrome

Androgen insensitivity syndrome (AIS) occurs when a person with a 46,XY karyotype has a pathogenic loss-of-function variant in the X-linked androgen receptor (AR) gene. The testes can produce testosterone, but the body’s cells cannot respond normally to testosterone or dihydrotestosterone (DHT). The problem is therefore not necessarily inadequate hormone production; it is ineffective androgen signalling at the receptor. The degree of receptor dysfunction determines the phenotype: - Complete AIS (CAIS): androgen signalling is essentially absent. External genital development is typically female. - Partial AIS (PAIS): some androgen response remains. External genitalia may be variably under-masculinized, ranging from predominantly female to ambiguous or predominantly male with hypospadias or undescended testes. During fetal development, the testes produce anti-Müllerian hormone, also called Müllerian-inhibiting substance. This hormone causes regression of the uterus, fallopian tubes, and upper vagina. In CAIS, the person therefore has typical female external genitalia but usually has no uterus, cervix, or upper vagina; a short lower vagina is present. The testes may remain in the abdomen, inguinal canals, or labial region. This explains a classic diagnostic tension: breast development can be...