Taming Idiopathic Central Precocious Puberty: High Frequency of Imprinting Disorders in Familial Forms

Abstract

Central precocious puberty (CPP) results from the abnormally early reactivation of the hypothalamic-pituitary-gonadal axis, leading to the appearance of secondary sexual characteristics before the age of 8 years in girls or 9 years in boys. The incidence of precocious puberty varies according to population, sex, and age at presentation (1), reaching 80/100 000 in girls between 5 and 9 years (2), but 10- to 25-fold lower in boys (1, 2). The etiologies of CPP include lesions of the central nervous system, such as congenital malformations, tumors or other insults (eg, infections, trauma, cranial radiotherapy, cerebral palsy), or conditions without organic lesions (3). The latter include early and chronic exposure to estrogens or androgens resulting in secondary CPP (eg, poorly controlled congenital adrenal hyperplasia), social exposures (eg, international adoption), and genetic disorders. Overall, an overt etiology is identified in 30% to 75% of boys and only 10% of girls (1, 3). Therefore, given that CPP is far more frequent in females, the majority of patients have traditionally been classified as having “idiopathic” CPP, meaning “unexplained” CPP. As usual, the term “idiopathic” has vague boundaries in medicine and, in the case of CPP, although organic lesions are always carefully ruled out, genetic studies have been performed erratically probably leading to an overestimation of the frequency of “idiopathic” CPP.