[Molecular-genetic aspects of congenital hypothyroidism]

Congenital hypothyroidism manifests a complex of symptoms caused by a total lack or significant deficiency of thyroxine (T4) and triiodothyronine (T3) in foetal life and in the first years of child's life. The incidence of congenital hypothyroidism is 1 per 3000-4000 newborns in the world and l per 4800 in Poland. There are two main causes of congenital hypothyroidism: defects of thyroid development (about 90%), defects of thyroid hormones biosynthesis (~10%), and the more seldom occurring defects of the TBG proteins (thyroxine binding globulin) or resistance. syndrome to thyroid hormones. Defects of thyroid gland development include ectopia, hypoplasia or complete lack of the thyroid (athyreosis). These defects are caused by immunological, factors, drugs as well as genetic factors such as: TSH receptor gene or thyroid transcription factors: PAX 8. TTF l, TTF 2, Pit 1, Prop 1. Defects of thyroid hormones biosynthesis are inherited as autosomal recessive. There are 5 main defects of thyroid hormones biosynthesis: iodide transport (mutation of hNIS gene), iodine oxygenation (mutation of TPO, THOX, PDS genes), the iodination of the tyrosine of thyroglobulin and their conjunction (the mutation of TPO TG, PDS genes), the hydrolysis of the T3 and T4 as well as deiodination. Searching molecular-genetic basis of congenital hypothyroidism may improve its diagnostics, make possible to introduce genetic examination among patients with congenital hypothyroidism and their family members and may make gene therapy possible in the future.