Recent advances in understanding the molecular basis of primary congenital hypothyroidism

Primary congenital hypothyroidism is characterized by low levels of circulating thyroid hormones and raised levels of thyrotropin at birth. It can be either permanent or transitory. Most permanent cases (80-85%) result from alterations in the formation of the thyroid gland during embryogenesis (thyroid dysgenesis), and several were shown recently to be produced by mutations in genes responsible for the development of thyroid follicular cells (TITF1, TITF2, PAX8 and TSHR). Less frequently, congenital hypothyroidism is determined by defects in thyroid hormone synthesis (hormonogenesis defects). The latter are usually associated with goiter. Recently, the molecular mechanisms of two forms of hormonogenesis defects (iodine transport defects and Pendred syndrome) were elucidated.