Congenital neonatal hyperthyroidism caused by germline mutations in the TSH receptor gene

Neonatal hyperthyroidism, a rare and serious disorder, occurs in two forms. An autoimmune form associated with maternal Graves' disease, resulting from transplacental passage of maternal thyroid-stimulating antibodies, and a non-autoimmune form, resulting from mutations in the stimulatory G protein or the thyrotropin receptor (TSHR) causing constitutive activation of intracellular signaling cascades. To date, 29 separate cases of thyrotoxicosis caused by germline mutations of the TSHR have been documented. These cases have expressed themselves in a range of clinical consequences. This report describes a new case of a newborn with non-autoimmune hyperthyroidism secondary to a constitutively active TSHR mutation (S281N) whose clinical course was complicated by severe respiratory compromise. Typical clinical findings in this disorder are discussed by a review of all previously published cases.