A review of the genetics and epigenetics of central precocious puberty

Abstract

Gonadotrophin dependent sexual precocity, commonly referred to as central precocious puberty (CPP), results from a premature reactivation of the hypothalamic-pituitary-gonadal (HPG) axis before the normal age of pubertal onset. CPP is historically described as girls who enter puberty before the age of eight, and boys before the age of nine. Females are more likely to be diagnosed with idiopathic CPP; males diagnosed with CPP have a greater likelihood of a defined etiology. These etiologies may include underlying CNS congenital defects, tumors, trauma, or infections as well as environmental, genetic, and epigenetic factors. Recently, genetic variants and mutations which may cause CPP have been identified at both the level of the hypothalamus and the pituitary. Single nucleotide polymorphisms (SNPs), monogenetic mutations, and modifications of the epigenome have been evaluated in relationship to the onset of puberty; these variants are thought to affect the development, structure and function of GnRH neurons which may lead to either precocious, delayed, or absent pubertal reactivation. This review will describe recent advances in the field of the genetic basis of puberty and provide a clinically relevant approach to better understand these varying etiologies of CPP.

Kisspeptin and DLK1 levels for monitoring treatment of girls with central precocious puberty

“…A defect in kisspeptin signaling might result in precocious or delayed puberty. [13][14][15][16] The hypothalamus secretes dynorphin, neurokinin B, and kisspeptin, which interact with the kisspeptin receptor (KISS1R) in GnRH-secreting neurons to enhance the amplitude and frequency of GnRH pulsatility and initiate pubertal development. 2) The correspondence between blood levels of kisspeptin and their levels in the hypothalamus remains unknown.…”

Elevated Immunoglobulin E Serum Levels: Possible Underlying Factors That Can Cause an Inborn Error of Immunity in the Pediatric Population with Recurrent Infections

“…The second largest age group of patients was 10 to 15 years old. During this time, children are more likely to develop infections due to hormonal changes that indirectly impair the immune system [45]. This phase makes children's immune systems more vulnerable and susceptible to several forms of infections [46].…”

Childhood Obesity, Hypothalamic Inflammation, and the Onset of Puberty: A Narrative Review

“…Puberty, a multifaceted and coordinated biological process, displays considerable variation in onset among children due to influences from environmental, endocrine, and genetic factors. The overall prevalence of PP is estimated to be 1:5000 to 1:10,000 [ 18 ], with a female-to-male ratio of approximately 10:1, yet the exact pathophysiologic mechanism responsible for PP remains unknown [ 19 ]. Epidemiological data indicate that there is a direct correlation between early pubertal development and obesity [ 20 , 21 ].…”