Etiology of congenital hypothyroidism

Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency present at birth. According to the duration of thyroid hormone deficiency, it may be classified into permanent and transient CH. According to the anatomic location of the pathogenic defect, CH may be further classified into primary, secondary (or central), and peripheral CH. The most frequent cause of permanent primary CH is thyroid dysgenesis, which includes thyroid ectopy, agenesis, and hypoplasia. Thyroid dysgenesis is generally sporadic in occurrence, but in about 2 % of cases, mutations in genes PAX8, TTF-2, NKX2.1, and NXK2.5 may be detected. Dyshormonogenesis is the second most common cause and may be caused by mutations in genes encoding the sodium-iodide symporter, thyroperoxidase, hydrogen peroxide generation factors, thyroglobulin, iodothyronine deiodinase, and pendrin. Rare causes of CH include resistance to TSH binding or signaling, central CH, and peripheral CH caused by thyroid hormone syndrome or defects in thyroid hormone transport and metabolism.