ANDROGEN RECEPTOR DISORDER IN 3 BROTHERS WITH BIFID PREPENILE SCROTUM AND HYPOSPADIAS

Three brothers with congenital transposition of the penis, scrotal hypospadias, bifid scrotum, and bilateral undescended testes are described. Further signs of incomplete virilization, but no gynecomastia were seen. LH and FSH were elevated, whereas testosterone levels were reduced or in the normal range. Serum concentrations of 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 5α-dihydrotestosterone and estradiol measured in two affected brothers were in the normal range. Fibroblasts from scrotal skin biopsies performed in two patients showed normal 5α-reductase activity (419 and 214 pmol · (mg protein)-1 · h-1; normal >1), whereas androgen receptors had reduced maximal binding capacity (B(max) 4 and 14 fmol · (mg protein)-1; normal ≥ 18) and an increased equilibrium dissociation constant (0.7 and 1.26 nmol/l; normal 0.2 ± 0.08) indicating a quantitative and qualitative androgen receptor defect. These patients represent a further variant of androgen insensitivity.