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All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and\/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP.<\/jats:p>","DOI":"10.1210\/endrev\/bnac020","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T11:25:59Z","timestamp":1659698759000},"page":"193-221","source":"Crossref","is-referenced-by-count":97,"title":["The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty"],"prefix":"10.1210","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4140-6296","authenticated-orcid":false,"given":"Vinicius N","family":"Brito","sequence":"first","affiliation":[{"name":"Discipline of Endocrinology & Metabolism, Department of Internal Medicine, University of Sao Paulo Medical School, University of Sao Paulo , Sao Paulo 01246 903 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Paula","family":"Abreu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6711-6097","authenticated-orcid":false,"given":"Delanie B","family":"Macedo","sequence":"additional","affiliation":[{"name":"Discipline of Endocrinology & Metabolism, Department of Internal Medicine, University of Sao Paulo Medical School, University of Sao Paulo , Sao Paulo 01246 903 ,","place":["Brazil"]},{"name":"Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"N\u00facleo de Aten\u00e7\u00e3o M\u00e9dica Integrada, Centro de Ci\u00eancias da Sa\u00fade, Universidade de Fortaleza , Fortaleza 60811 905 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