GENETIC AND NEUROPEPTIDE ASPECTS IN CENTRAL PRECOCIOUS PUBERTY (CPP)

Background: Central precocious puberty (CPP) is defined by the premature activation of the hypothalamic pituitary gonadal (HPG) axis, leading to early development of secondary sexual characteristics. CPP is more common in girls and can adversely affect growth and psychosocial outcomes.

Objective: This review synthesizes current evidence on the genetic and neuropeptidergic mechanisms underlying CPP, focusing on their diagnostic and therapeutic relevance.

Methods: A comprehensive analysis of recent literature was conducted, including genetic studies on imprinted genes such as MKRN3 and DLK1, rare mutations in KISS1 and KISS1R, and the role of neuropeptides, particularly kisspeptin and neurokinin B, in HPG axis regulation. Diagnostic approaches, including clinical evaluation, biochemical markers, pelvic ultrasound parameters, and genetic testing, are discussed. Therapeutic strategies with gonadotropin-releasing hormone analogs (GnRHa) and emerging neuropeptide modulators are reviewed.

Results: Genetic mutations in MKRN3 and DLK1 are recognized as major monogenic causes of familial CPP, while rare activating mutations in KISS1 and KISS1R confirm the essential role of kisspeptin signaling. Advances in pelvic ultrasound and hormonal assays have improved diagnostic accuracy, although overlap with benign variants remains a challenge. GnRHa therapy is the gold standard for halting pubertal progression and optimizing final adult height. However, long-term psychosocial and metabolic outcomes warrant further research.