Hypogonadotropic Eunuchoidism. I. Clinical Study of the Mode of Inheritance

Abstract

Hypogonadotropic eunuchoidism is a well recognized form of familial hypogonadism characterized by selective gonadotropin deficiency and sexual infantilism. Often, olfactory dysfunction or cryptorchidism are also present. Six kindreds of patients with hypogonadotropic eunuchoidism were studied in order to ascertain the mode of inheritance in this disorder. Thirtyfive percent of the siblings of affected individuals exhibited either hypogonadism, olfactory dysfunction or cryptorchidism. Olfactory dysfunction and hypogonadism were expressed in both men and women, although more commonly in men. Male to male transmission of anosmia was observed. An autosomal dominant mode of inheritance with incomplete expressivity is suggested by analysis of the six kindreds studied, although genetic heterogeneity can not be excluded. The most common abnormalities detected among the kindred members were olfactory dysfunction (26 patients), hypogonadism (21 patients), and cryptorchidism (6 patients). Hare-lip or cleft palate, and congenital deafness occurred less commonly, and may not necessarily be related to the syndrome. The hypothesis that a common anatomic defect in neural pathways between the olfactory bulbs and hypothalamus produces both hypogonadism and olfactory dysfunction is discussed.