Familial neonatal nonautoimmune hyperthyroidism due to a gain-of-function (D619G) thyrotropin-receptor mutation.

Objectives Activating germline mutations of the thyroid-stimulating hormone receptor (TSHR) are responsible for a rare form of neonatal nonautoimmune hyperthyroidism (NAH). We report the first case of familial neonatal neonatal nonautoimmune associated with c.1856A>G (p.Asp619Gly) variant in the TSHR gene. Case presentation We describe an eight-year-old African-American female presenting with neonatal NAH associated with an inherited heterozygous c.1856A>G (p.Asp619Gly) variant in the TSHR gene. This variant was previously described in one patient presenting with sporadic NAH in adolescence. Our patient was diagnosed with hyperthyroidism in the neonatal period. The mother had a history of hyperthyroidism and had thyroidectomy at the age of 4 years. The patient had goiter and elevated free thyroxine (FT4) and free triiodothyronine (FT3) levels that normalized with methimazole treatment; however, TSH level remained suppressed. Thyroid antibodies were negative. The patient also had bilateral exotropia, a trait shared by the mother and may represent a new association. Conclusions Familial neonatal NAH is associated with heterozygous c.1856A>G (p.Asp619Gly) variant of the TSHR gene.