CONGENITAL HYPOTYROIDISM WITH THYROID DYSGENESIS: CANDIDATE GENES, ANIMAL MODELS AND MOLECULAR MECHANISMS

Defect in morphogenesis (dysmorphogenesis) are a frequent event in pregnancies. It can be calculated that about 1 newborn out of 20 is affected. What are the genetic causes of these malformations is largely unknown. Thyroid hormones are produced by the thyroid gland and they play essential roles in body growth and brain development. Congenital hypothyroidism is a pathological condition characterized by reduced or absent hormone synthesis by the thyroid gland. If not treated shortly after birth with thyroid hormones, newborns with congenital hypothyroidism will develop irreversible brain damage (hypothyroid cretinism). About 1/3000 newborn present this condition. In the majority of these patients, hypothyroidism is a consequence of a reduced size or absent thyroid gland. The genetic basis of such a condition were completely unknown, till the discovery of a set of three genes that cause congenital hypothyroidism in mice and humans. Such a discovery opens the way to the understanding of a frequent dysmorphogenesis in humans and to the possibility of a prenatal diagnosis, that could allow to start hormone therapy at birth. However, for this to happen, it will be necessary to identify the genes responsible for most of the cases of congenital hypothyroidism. The three genes identified so far cover only a minority of the cases, even though they may allow for the discovery of others. Furthermore, the discovery of the genetic basis of congenital hypothyroidism will alert the carriers of this trait to follow their progeny with care, should they be located in parts of the world where the hormonal screening for congenital hypothyroidism is not implemented.