Ramos Helton E, Nesi-França Suzana, Boldarine Valter T, Pereira Rosana M, Chiamolera Maria Izabel, Camacho Cleber P, Graf Hans, de Lacerda Luiz, Carvalho Gisah A, Maciel Rui M B
Laboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine, Federal University of São Paulo , São Paulo, Brazil.
Thyroid. 2009 Jan;19(1):61-8. doi: 10.1089/thy.2008.0116.
Congenital hypothyroidism (CH) is mainly due to developmental abnormalities leading to thyroid dysgenesis (TD). TD encompasses very distinct morphologic subtypes of disease. This study examined and compared the phenotype in TD variants and searched for genetic alterations in sporadic thyroid hypoplasia (TH), the most misdiagnosed form of CH. This was a longitudinal study over a 14-year period (1990-2004).
A continuous series of 353 children with TD was identified using thyroid function tests [thyroxine (T4) and TSH], scintigraphy, and ultrasound as diagnostic tools. Individual phenotypes were analyzed in 253 children with TD. Mutations in the most likely candidate genes were studied in 35 cases of TH.
The overall birth prevalence of permanent CH was 1:4795. Ectopy represented 37% of all cases of permanent primary CH, dyshormonogenesis 28%, agenesis 24%, hypoplasia 10%, and hemiagenesis 1%. The lowest screening T4 level and the highest TSH level were in the agenetic group, followed by TH. The TH group had an improvement in the thyroid function showing less-severe phenotype with aging. In the molecular analysis, one patient was identified with a mutation in the PAX8 gene (155G>C; R52P); four patients had a heterozygous G>C substitution in position -569; two patients showed a (234C>A; P52T) or (2181C>G; D727E) polymorphic variants of the TSH-R gene; and one patient presented a novel heterozygous nonsynonymous substitution, 293G>A; S98N, in the NKX2.5 gene.
The prevalence of CH was within the previously reported range of 1:3000-4000. Ectopy was the most common etiology. Clinical analysis revealed distinct hormonal patterns in TH subgroup when compared with other variants of TD, with genetic abnormalities identified only in few cases in the TSH-R, PAX8, and NKX2.5 genes.
先天性甲状腺功能减退症（CH）主要是由于发育异常导致甲状腺发育不全（TD）。TD包含非常不同的疾病形态学亚型。本研究检查并比较了TD变异体的表型，并在散发性甲状腺发育不全（TH）中寻找基因改变，TH是CH最易误诊的形式。这是一项为期14年（1990 - 2004年）的纵向研究。
使用甲状腺功能测试[甲状腺素（T4）和促甲状腺激素（TSH）]、闪烁扫描和超声作为诊断工具，确定了连续的353例TD患儿。对253例TD患儿的个体表型进行了分析。对35例TH患儿研究了最可能的候选基因中的突变。
永久性CH的总体出生患病率为1:4795。异位占所有永久性原发性CH病例的37%，激素合成障碍占28%，发育不全占24%，发育不良占10%，半侧发育不全占1%。筛查时T4水平最低和TSH水平最高的是发育不全组，其次是TH组。TH组随着年龄增长甲状腺功能有所改善，表型较轻。在分子分析中，一名患者被鉴定出PAX8基因存在突变（155G>C；R52P）；四名患者在 - 569位存在杂合的G>C替代；两名患者表现出促甲状腺激素受体（TSH - R）基因的（234C>A；P52T）或（21,81C>G；D727E）多态性变异；一名患者在NKX2.5基因中出现了新的杂合非同义替代，293G>A；S98N。
CH的患病率在先前报道的1:3000 - 4000范围内。异位是最常见的病因。临床分析显示，与TD的其他变异体相比，TH亚组有独特的激素模式，仅在少数TSH - R、PAX8和NKX2.5基因病例中发现了基因异常。
