RESUMO
Recent studies have identified molecular genetic defects in some cases of congenital hypothyroidism as well as in a few cases of central hypothyroidism. These studies have brought to light hitherto unexplained forms of both these disorders. In spite of early diagnosis by screening of newborns infants and early treatment, some patients with congenital hypothyroidism do not show normal mental development. This finding was subsequently attributed to molecular defects in transcription factors, which are important for both the embryonic development of the thyroid gland as well as the development of other organs, including the organs of the central nervous system (CNS). These findings will facilitate the understanding of the critical role of thyroid hormones in pre- and postnatal CNS development. However, the molecular basis of thyroid dysgenesis in most cases remains to be elucidated, and the identification and analysis of familial cases will be very useful for defining additional mechanisms of thyroid dysgenesis. In fact, these studies may provide crucial evidence for genetic counseling, as suggested by the possible dominant mode of inheritance of some forms of congenital hypothyroidism. This review focuses on the most recent advance in our understanding of the molecular basis of primary congenital hypothyroidism.