Genetics and phenomics of hypothyroidism and thyroid dys- and agenesis due to PAX8 and TTF1 mutations

Thyroid dysgenesis (TD) is the most common cause of congenital hypothyroidism (CH), a relatively frequent endocrine disease in newborns (1 in 3000–4000 live births). TD is a defect in the organogenesis of the gland resulting in hypoplastic, ectopic or absent-thyroid gland. TD is usually sporadic but mutations in transcription factors (PAX8, TTF1, FOXE1 and NKX2-5) involved in thyroid development have been shown to cause a minority of cases transmitted as Mendelian diseases. This review focuses on the genetics and phenomics of hypothyroidism and TD due to PAX8 and TTF1 mutations.