{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:09:55Z","timestamp":1791346195730,"version":"4.3.1"},"reference-count":167,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":336,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, and may be etiologically subdivided into thyroid dysgenesis, referring to abnormal thyroid development, and dyshormonogenesis, where a defective thyroid hormone biosynthesis pathway results in inadequate hormone production despite a structurally intact gland. Delayed treatment of neonatal hypothyroidism may result in irreversible neurodevelopmental impairment; therefore, where available, CH screening programs facilitate prompt diagnosis. However, the molecular basis for CH remains unclear in most of the cases. This review summarizes current understanding of the genetic etiologies underlying primary CH and associated phenotypes. Classical genetic causes are discussed in the context of their role in normal thyroid physiology. Genes recently reported to play a role in the pathogenesis of CH are discussed, and novel genomic mechanisms in CH are described.<\/jats:p>","DOI":"10.1530\/etj-24-0348","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T13:32:24Z","timestamp":1742304744000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":24,"title":["Genetics of primary congenital hypothyroidism: three decades of discoveries and persisting etiological challenges"],"prefix":"10.1530","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1164-5862","authenticated-orcid":true,"given":"Athanasia","family":"Stoupa","sequence":"first","affiliation":[{"name":"Paris regional screening program Department, Centre R\u00e9gional de D\u00e9pistage N\u00e9onatal (CRDN) Ile de France, Necker Children\u2019s University Hospital, Assistance Publique H\u00f4pitaux de Paris-APHP 1 , ,","place":["Paris, France"]},{"name":"Pediatric Endocrinology, Diabetology and Gynecology Department, Necker Children\u2019s University Hospital, APHP 2 , , Paris,","place":["ENDO-ERN (European Reference Network) center for rare endocrine diseases, France"]},{"name":"Cochin Institute and Imagine Institute Affiliate 3 , ,","place":["Paris, France"]},{"name":"Paris Cit\u00e9 University, Facult\u00e9 de M\u00e9decine 4 , ,","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-3629","authenticated-orcid":false,"given":"Aurore","family":"Carr\u00e9","sequence":"additional","affiliation":[{"name":"Cochin Institute and Imagine Institute Affiliate 3 , ,","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-352X","authenticated-orcid":false,"given":"Michel","family":"Polak","sequence":"additional","affiliation":[{"name":"Paris regional screening program Department, Centre R\u00e9gional de D\u00e9pistage N\u00e9onatal (CRDN) Ile de France, Necker Children\u2019s University Hospital, Assistance Publique H\u00f4pitaux de Paris-APHP 1 , ,","place":["Paris, France"]},{"name":"Pediatric Endocrinology, Diabetology and Gynecology Department, Necker Children\u2019s University Hospital, APHP 2 , , Paris,","place":["ENDO-ERN (European Reference Network) center for rare endocrine diseases, France"]},{"name":"Cochin Institute and Imagine Institute Affiliate 3 , ,","place":["Paris, France"]},{"name":"Paris Cit\u00e9 University, Facult\u00e9 de M\u00e9decine 4 , ,","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0559-2597","authenticated-orcid":false,"given":"Gabor","family":"Szinnai","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology and Diabetology, University Children\u2019s Hospital Basel UKBB and Department of Clinical Research, University Hospital Basel, 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