Familial Incomplete Male Pseudohermaphroditism, Type 1: Evidence for Androgen Resistance and Variable Clinical Manifestations in a Family with the Reifenstein Syndrome

Abstract

A family with incomplete male pseudohermaphroditism inherited as an apparent X-linked recessive trait was investigated. The phenotype in 11 affected family members ranged from a minimal defect in virilization in two (microphallus and bifid scrotum), to a more severe abnormality in eight (perineoscrotal hypospadias) and to almost complete male pseudohermaphroditism in one (perineoscrotal hypospadias, absent vas deferens and vaginal orifice). On the basis of these variable clinical findings, together with similar evidence from a previously reported pedigree, the four syndromes of defective virilization described by Reifenstein, Lubs, Gilbert-Dreyfus and Rosewater and their co-workers appear to represent variable manifestations of the same genetic defect, designated here as familial incomplete male pseudohermaphroditism, Type 1. Studies of blood testosterone and luteinizing hormone levels in nine affected family members and of androgen and estrogen production rates in two suggest that the underlying defect involves defective androgen action rather than decreased androgen synthesis. (N Engl J Med 290:1097–1103, 1974)