Phenotypic Variation in Patients with Partial Androgen Insensitivity Syndrome

Abstract

We report the cases of two infants with ambiguous genitalia who were found to have partial androgen insensitivity syndrome by androgen receptor studies conducted on cells obtained from a genital skin biopsy. Both patients had been born at full term and appeared normal except for their external genitalia. One patient had a hooded phallus and scrotal hypospadias. The testes were found in the inguinal canals. The genitalia of the other patient appeared to be female, but testes were found in the labia majora. At genitography, the urogenital sinus was observed to be short and the vaginal cavity of normal size. The serum testosterone level of the first patient was significantly elevated. Androgen receptors were measured in skin with fibroblasts cultured from the prepuce. The maximum binding capacity of the dihydrotestosterone receptor for each patient was 263 and 340 fmol/mg DNA, respectively (normal mean±SD, 722±225 fmol/mg DNA). The dihydrotestosterone binding affinity of the receptor was significantly lower than normal, (Kd: mean±SD, 0.71±0.17 nM), i. e., 1.14 nM in the first patient and 1.26 nM in the other. These findings raise the question of the mechanism of the different degrees of masculinization of the external genitalia with a similar abnormality in the androgen receptor.