The syndrome of aromatase deficiency

Aromatase deficiency results from autosomal recessive inheritance of mutations in the CYP19 gene. This deficiency induces female pseudohermaphroditism in 46,XX individuals, which illustrates the critical role that placental aromatase enzyme plays in protecting the fetus from excess androgen exposure in utero. At puberty, affected girls have hypergonadotropic hypogonadism, fail to develop secondary sexual characteristics, and exhibit progressive virilization. The male affected 46,XY individuals have normal male sexual differentiation and pubertal maturation, and increased follicle-stimulating hormone, luteinizing hormone, and testosterone levels. These men are extremely tall and have eunucoid proportions with continued linear growth into adulthood, lack of epiphyseal closure and osteoporosis due to estrogen deficiency. Circulating estrogen is undetectable in both male and female affected patients. Various aspects of this syndrome are discussed.