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). HEREDITARY male pseudohermaphroditism in which genetic males differentiate partly or completely as phenotypic females can result from disturbances in any of the three physiologic events necessary for virilization of the male embryo — namely, defects in androgen synthesis, defects in androgen action and defects in müllerian-duct regression.1 2 3 4 Disorders of androgen synthesis are inherited as autosomal recessive traits and are due to defects in one of the five enzymatic reactions required for testosterone formation from cholesterol, which are sequentially the 21,22-desmolase,5 6 7 3β-hydroxysteroid dehydrogenase,8 9 10 11 17-hydroxylase, 12 13 14 15 17,20-desmolase16 and 17-ketosteroid reductase17 18 19 reactions. Depending on the quantitative abnormality in testosterone production and on the biologic.
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