An update of the genetic basis of pubertal timing: A mini review

Abstract

Puberty remains an intriguing mystery because the factors that initiate and modulate its progression are still largely unknown. Hypogonadotropic hypogonadism (HH) has long served as a model to understand the intricacies of the reproductive endocrine system. Studies suggest that pubertal timing in the general population may be controlled by hundreds of genetic regulators, while loss-of-function mutations in one gene can produce the phenotypic features of complete gonadotropin- releasing hormone (GnRH) deficiency. A genetic link between delayed puberty and HH has been suggested. Mutations in genes underlying HH might contribute to the pathogenesis of constitutional delay of growth and puberty (CDGP), with incomplete penetrance and/or variable expressivity. Therefore, the common, self-limited CDGP and the rare, often permanent HH share underlying pathophysiologic mechanisms. The current understanding of the genetic basis of pubertal timing is reported in the present short review. A practical diagnostic approach to pubertal delay is also suggested.