Genetic etiologies of central precocious puberty

Pubertal onset is a complex process, which is influenced by genetic and environmental factors, such as obesity and endocrine-disrupting chemicals. In addition, the timing of normal puberty varies between individuals and is a highly polygenic trait with both rare and common variants. Central precocious puberty (CPP) is defined as the early activation of the hypothalamic-pituitary-gonadal axis. Genetic factors are suggested to account for 50% to 80% of the variation in puberty initiation, as indicated by the greater concordance of pubertal timing observed in monozygotic twins than in dizygotic twins. Although genetic factors play a crucial role in CPP development, only few associated genes have been identified. To date, four monogenic genes have been identified: KISS1, KISS1R, MKRN3, and DLK1. Moreover, mutation prevalence in these genes varies considerably depending on the ethnicity of patients with CPP. This article reviews the current knowledge on the normal pubertal timing and physiology and discusses the CPP-causing genes.