Thyroid dysgenesis: current knowledge of the role of transcription factors in the pathogenesis of congenital hypothyroidism
Abstract
Primary permanent congenital hypothyroidism is caused by an impaired thyroid development in 80 - 85 % of all cases. Ectopic thyroid gland, athyreosis and hypoplasia are the most frequent forms of thyroid dysgenesis.
Thyroid dysgenesis has been considered to be only a sporadic disease for a long time. Familial cases of dysgenesis, an increased frequency of associated congenital malformations, a significant female predominance, and racial differences in the incidence suggest the involvement of genetic factors in the pathogenesis of this disease.
Thyroid development is regulated by transcription factors that are expressed transiently or permanently. Therefore, transcription factors' gene mutations may lead to various disorders of thyroid development.
Mutations of genes encoding TTF-1, TTF-2 and PAX-8 have been already identified in several patients with thyroid dysgenesis. Additionaly, these transcription factors are expressed during the development of other organs that may be also affected (cleft palate or epiglottis in TTF-2 gene mutations, kidney malformations in PAX-8 mutations, lung and neurological impairment in TTF-1 mutations).
Other candidate genes are intensively investigated.