Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Androgen Insensitivity Syndrome (AIS) [34.59]

OMIM numbers: 300068313700 (AR)

Dr. rer. nat. Annett Wagner, Dr. med. Dagmar Wahl

Scientific Background

In a 46,XY karyotype, androgen insensitivity is characterized by feminization of the external genitalia at birth, a disorder of puberty development resulting in infertility. The frequency among the Caucasian population is 1:20,000–40,000. The defect in the sexual differentiation caused by impaired androgen action has been categorized into three phenotypes:

  • Complete androgen insensitivity (CAIS) with female phenotype
  • Partial androgen insensitivity (PAIS) with predominantly female or male phenotype
  • Mild androgen insensitivity (MAIS) with male phenotype

Patients with CAIS have a male karyotype but exhibit female external genitalia with a usually blind ending vagina. In puberty absence in growth of pubic and axillary hair with normal female breast development is striking. 1/3 of all affected individuals develop rudimentary fallopian tubes and bilateral inguinal hernia occur frequently as manifestation of undescended testis. The phenotype of patients with PAIS varies considerably, ranging from predominantly female genitalia with hypertrophy of the clitoris to predominantly male genitalia with micropenis, hypospadia and cryptorchidism.

Patients with MAIS exhibit male external genitalia, sometimes with minimal abnormalities such as coronal hypospadias with or without reduced fertility.

AIS is inherited in an X-linked manner. The detection rate of mutations in the androgen receptor gene (AR) is 95% in CAIS patients, below 50% in PAIS patients and even lower in MAIS patients. There are more than 800 known pathogenic mutations, mainly located in the exons 2-8. Additionally, the AR gene contains 13-31 CAG repeats. A repeat expansion causes the spinobulbar muscular atrophy (Kennedy Disease).