Phenotypic Variation in a Family With Partial Androgen Insensitivity Syndrome

A family with partial androgen insensitivity syndrome exhibited considerable variation in phenotypic expression of their androgen resistance. One subject died at 2½ years of age of a Wilms’ tumor. In the two living members, one had a micropenis with otherwise normal genitalia, while the other had a small phallus, perineoscrotal hypospadias, bifid scrotum, and persistence of a vaginoutricular pouch. At puberty, plasma androgens and serum gonadotropins increased to normal or elevated values. However, despite adequate endogenous plasma testosterone levels and testosterone therapy, these patients showed poor virilization and were sterile. Studies of cultured sexual skin fibroblasts showed adequate 5α-reductase activity and normal receptor affinity and capacity for dihydrotestosterone. An X-linked mode of inheritance is postulated, although autosomal dominance cannot be ruled out.