TSHRV656F Activating Variant of the Thyroid Stimulating Hormone Receptor Gene in Neonatal Onset Hyperthyroidism: A Case Review.

Kayaş L., Çamtosun E., Akıncı A., Bircan R.

Journal of clinical research in pediatric endocrinology, vol.14, pp.114-118, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 14
  • Publication Date: 2022
  • Doi Number: 10.4274/jcrpe.galenos.2020.2020.0229
  • Journal Name: Journal of clinical research in pediatric endocrinology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.114-118
  • Keywords: Neonatal hyperthyroidism, activating variant of TSHR gene, non-autoimmune hyperthyroidism, CONGENITAL HYPERTHYROIDISM, SOMATIC MUTATIONS, TSH RECEPTOR, NODULES, PREVALENCE
  • Inonu University Affiliated: Yes


An activating variant of the thyroid stimulating hormone receptor (TSHR) gene is one of the rare causes of neonatal hyperthyroidism. This disorder may occur as a result of an autosomal dominant inheritance or sporadically through de novo variation. Here we present a case of neonatal onset congenital non-autoimmune hyperthyroidism (NAH) with a sporadic germline activating TSHRV656F variant. A female infant with tachycardia, who was transferred due to hyperthyroidism in the first week of life, displayed no other symptoms or signs. The patient's mother did not have Graves' disease, and TSHR stimulating antibodies were not present in the mother or baby. Imaging showed thyroid gland hyperplasia and left ventricular hypertrophy, the patient was subsequently put on methimazole treatment. After six months undergoing treatment, a heterozygous p.Val656Phe (V656F) (c.1966G>T) variant was detected on exon 10 of the TSHR gene. The variant was not identified in the mother and father, so the case was assumed to be sporadic. In conclusion, although the literature describes V656F variant as a somatic variant in children and adults with toxic thyroid nodule(s) that results in the structural activation of the TSH receptor, no previous cases of neonatal hyperthyroidism due to TSHRV656F variant have been reported. This study is the first case review that highlights the relationship between TSHRV656F variant and neonatal onset NAH.