Paediatrics: Androgen insensitivity syndrome

Androgen insensitivity syndrome

This condition is due to defects in the androgen receptor and results in a spectrum of under-virilized phenotypes in the 46XY patient.

Complete AIS

Deletions of the gene and certain mutations can result in a completely female phenotype.

·  External genitalia are unambiguously female, with normal clitoris, hypoplastic labia majora, and blind-ending vaginal pouch. Müllerian structures are absent.

·  Testes may be located in the abdomen, inguinal canal, or labia.

·  AIS should be strongly suspected and excluded in any female presenting with inguinal hernia.

·  Patients with complete AIS often present in adolescence with primary amenorrhoea.

·  At puberty, serum levels of testosterone and LH are elevated. Conversion of testosterone to oestradiol in the testis and in peripheral tissues results in normal breast development.

·  Pubic and axillary hair development is absent or sparse.

·  Diagnosis is confirmed by demonstrating 46XY karyotype.

In view of the potential risk of malignant transformation if retained, removal of the testis either soon after diagnosis or after the completion of puberty is carried out. After gonadal removal, oestrogen replacement therapy is given.

Partial AIS

Certain mutations of the androgen receptor gene result in a partial form of AIS. There is a wide spectrum of phenotypic expression ranging from ambiguous genitalia to a normal male phenotype presenting with fertility difficulties. There is, however, poor genotype–phenotype correlation and patients with the same mutation present with different phenotypes.

Management is much more challenging. Sex assignment depends on the degree of genital ambiguity.

True hermaphroditism

Individuals have both ovarian tissue with follicles and testicular tissue with seminiferous tubules either in the same gonad (ovotestis) or with an ova-ry on one side and a testis on the other. The aetiology of this condi-tion is unclear. In 70% of cases the underlying karyotype is 46XX; 20% 46XX/46XY; 10% 46XY.

Ovotestes may be present bilaterally and may be located in the inguinal canal. The external genitalia are most often ambiguous, although in 10% phenotype may be female. The degree of feminization and virilization that occurs varies widely. Management is dictated by sex assignment. Dysgenetic testicular tissue should be removed because of the risk of malignant transformation.