Clinical and Molecular Analysis of Thyroid Hypoplasia: A Population-Based Approach in Southern Brazil

Background: 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).Methods: 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.Results: 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.Conclusions: 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao Araucaria, grant Programa de PesquisaUniversidade Federal de São Paulo, Mol Endocrinol Lab, Dept Med, Div Endocrinol, BR-04039032 São Paulo, BrazilUniv Fed Parana, Div Endocrinol & Metab, BR-80060000 Curitiba, Parana, BrazilUniv Fed Parana, Pediat Endocrinol Unit, BR-80060000 Curitiba, Parana, BrazilNeonatal Screening Program Fundacao Ecumen Protec, Curitiba, Parana, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, Dept Med, Div Endocrinol, BR-04039032 São Paulo, BrazilFAPESP: 06/54950-6Web of Scienc