Testicular 17 ketosteroid reductase deficiency as a cause of male pseudohermaphroditism in 2 sibs

Two sibs have been reported in 1971 with the form of male pseudohermaphroditism (incompletely masculinized male) called pseudovaginal perineoscrotal hypospadias (PPSH). In that paper, and based upon previous reviews, PPSH was characterized as a condition involving severe hypospadias with dorsal prepuce, ventral urethral groove and opening of the urethra or urogenital sinus at the base of the phallus; the presence of a blind vaginal pouch of variable size, opening either into the urogenital sinus or onto the perineum immediately posterior to the urethral opening; the presence of welldeveloped and histologically normally differentiated testes with normal epididymes, vasa deferentia and seminal vesicles; the absence of female internal genitalia; and masculinization at the time of puberty with minimal or no breast development. In the 1971 paper on PPSH, the authors postulated autosomal recessive inheritance as the genetic mechanism responsible for PPSH. While current evidence indicates that what has been called PPSH is genetically and pathogenetically heterogeneous, available data still point to autosomal recessive inheritance as the responsible genetic mechanism. The family presented supports this concept. Two affected sibs are the only ones affected in the family. In contrast to the previously postulated localized resistance to testosterone as the pathogenetic mechanism in PPSH, our data point to a defect in testosterone biosynthesis, while data on other cases indicate a defect in the conversion of testosterone to dihydrotestosterone. These factors again point to the heterogeneous nature of PPSH. The continuing acquisition of information regarding the phenotypes, genetic mechanisms, etiology and pathogenesis of male pseudohermaphroditism has led to a need for a revised classification for this group of disorders. The authors propose a classification, based upon clinical, anatomic, hormonal and genetic information, as being of value in sorting out this confusing category of abnormalities.