Inheritance: autosomal recessive
Affected gene: CYP19A1
Affected enzyme: aromatase cytochrome P450 (P450arom)
Consequence of mutation: defect in the final step in the conversion of C19 steroids to estrogens, resulting in low estrogen and high androgen levels
Clinical features:
(1) delayed epiphyseal closure/fusion with delayed bone age
(2) tall stature with a eunuchoid body habitus, starting with puberty
(3) osteopenia and osteoporosis with recurrent bone fractures
(4) bone pain
(5) variable abnormalities of testicular size (including macroorchidism)
Laboratory findings:
(1) no excess in growth hormone
(2) high normal or elevated serum testosterone
(3) high normal or elevated gonadotropins (FSH, LH)
(4) low serum estrogens
(5) variable defect in spermatogenesis
