{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T23:25:26Z","timestamp":1775690726544,"version":"3.50.1"},"reference-count":124,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Reprod Med"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by absent or incomplete pubertal development due to impaired production, secretion, or action of gonadotropin-releasing hormone (GnRH). When associated with anosmia or hyposmia, it is termed Kallmann syndrome. CHH exhibits striking clinical and genetic heterogeneity, encompassing either sporadic or familial cases, with inheritance patterns that include X-linked, autosomal dominant, and autosomal recessive transmission. Over the past few decades, major advances uncovered the molecular basis of CHH, shedding light on the intricate neuroendocrine regulation of human reproduction. A growing repertoire of genes has been implicated in CHH molecular pathogenesis, encoding proteins involved in the ontogeny and function of GnRH neurons. Notably, pathogenic variants in genes typically associated with complex syndromes have also been identified in patients with isolated CHH or subtle syndromic manifestations, suggesting a wide spectrum of expressivity and incomplete penetrance. Furthermore, spontaneous hypogonadism reversal, either permanent or temporary, may occur in some patients, suggesting a potential neuroplasticity within the GnRH neuronal network. This review summarizes recent advances in the molecular genetics of CHH, emphasizing the expanding spectrum of causative genes and their inheritance patterns.<\/jats:p>","DOI":"10.1055\/a-2806-2848","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T23:59:17Z","timestamp":1772495957000},"page":"282-295","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Basis and Heterogeneity of Congenital Hypogonadotropic Hypogonadism"],"prefix":"10.1055","volume":"43","author":[{"given":"Leticia Ferreira Gontijo","family":"Silveira","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednica M\u00e9dica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Eduardo","family":"Seraphim","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-693X","authenticated-orcid":false,"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"issue":"01","key":"ref1","first-page":"111","article-title":"Neurobiological mechanisms of the onset of puberty in primates","volume":"22","author":"E Terasawa","year":"2001","journal-title":"Endocr Rev"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000362414","article-title":"Activation of the hypothalamic-pituitary-gonadal axis in infancy: 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