Pediatric Endocrinology, Gynecology, and Diabetology Department, Necker Children's University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
IMAGINE Institute affiliate, INSERM U1163, Paris, France.
Endocrine. 2021 Mar;71(3):696-705. doi: 10.1007/s12020-021-02646-9. Epub 2021 Mar 1.
Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder and one of the most common preventable forms of mental retardation worldwide. CH is due to thyroid development or thyroid function defects (primary) or may be of hypothalamic-pituitary origin (central). Primary CH is caused essentially by abnormal thyroid gland morphogenesis (thyroid dysgenesis, TD) or defective thyroid hormone synthesis (dyshormonogenesis, DH). TD accounts for about 65% of CH, however a genetic cause is identified in less than 5% of patients.
The pathogenesis of CH is largely unknown and may include the contribution of individual and environmental factors. During the last years, detailed phenotypic description of patients, next-generation sequence technologies and use of animal models allowed the discovery of novel candidate genes in thyroid development, function and pathways.
We provide an overview of recent genetic causes of primary and central CH. In addition, mode of inheritance and the oligogenic model of CH are discussed.
先天性甲状腺功能减退症（CH）是最常见的新生儿内分泌疾病，也是全世界最常见的可预防的智力障碍形式之一。CH 是由于甲状腺发育或甲状腺功能缺陷（原发性）引起，也可能是下丘脑-垂体起源（中枢性）。原发性 CH 主要由甲状腺形态发生异常（甲状腺发育不良，TD）或甲状腺激素合成缺陷（甲状腺激素生成障碍，DH）引起。TD 约占 CH 的 65%，然而，只有不到 5%的患者确定了遗传原因。
CH 的发病机制尚不清楚，可能包括个体和环境因素的共同作用。在过去的几年中，对患者的详细表型描述、下一代测序技术和动物模型的使用，使得甲状腺发育、功能和途径的新候选基因得以发现。
我们概述了原发性和中枢性 CH 的最新遗传原因。此外，还讨论了遗传方式和 CH 的多基因模型。
