Congenital Hypothyroidism Panel Genes DUOX2 IGSF1 NKX2-1 SLC16A2 THRA TSHR DUOXA2 IYD PAX8 SLC26A4 THRB UBR1 FOXE1 KDM6A POU1F1 SLC5A5 TPO GLIS3 KMT2D PROP1 TG TSHB Condition Genes Clinical and Molecular Findings

2/17 Clinical Features: Congenital hypothyroidism is a condition characterized by inadequate availability of active thyroid hormone to target tissues in the newborn period. It can be sporadic or inherited. In 80 to 85% of cases, congenital hypothyroidism is the consequence of thyroid dysgenesis due to absent (athyreosis), abnormally located (ectopic), or small (hypoplastic) thyroid gland (1). Congenital hypothyroidism may also be due to dyshormonogenesis, caused by a complete or partial defect in thyroid hormone synthesis (2). Rare causes of congenital hypothyroidism include defects in the effect of thyroid hormone on target tissues due to abnormalities in cell membrane transport, metabolism or action, and control of thyroid gland activity due to defects at the level of the hypothalamus or pituitary (central hypothyroidism) and more commonly the thyrotropin receptor. Congenital hypothyroidism may be a feature of a syndromic genetic condition; examples include Kabuki syndrome, Johanson-Blizzard syndrome, and Pendred syndrome. Congenital hypothyroidism may be transient or permanent. A genetic diagnosis can aid in determining whether lifelong thyroid hormone replacement is necessary (2), as well as provide risk information and the possibility of genetic counseling to families.