Recent advances in understanding the molecular basis of primary congenitalhypothyroidism

Primary congenital hypothyroidism is characterized by low levels of circula ting thyroid hormones and raised levels of thyrotropin at birth. It can be either permanent or transitory. Most permanent cases (80-85%) result from a lterations in the formation of the thyroid gland during embryogenesis (thyr oid dysgenesis), and several were shown recently to be produced by mutation s in genes responsible for the development of thyroid follicular cells (TIT F1, TITF2, PAX8 and TSHR). Less frequently, congenital hypothyroidism is de termined by defects in thyroid hormone synthesis (hormonogenesis defects). The latter are usually associated with goiter. Recently, the molecular mech anisms of two forms of hormonogenesis defects (iodine transport defects and Pendred syndrome) were elucidated.