Mild Isolated Congenital Central Hypothyroidism Due to a Novel Homozygous Variant in TSHB: A Case Report

Pathogenic variants in TSHB are known to cause severe isolated central congenital hypothyroidism (CH). In this study, we present the clinical, biochemical, and genetic features of the first patient with a mild central CH phenotype. We identified a novel homozygous variant in TSHB: (Chr1: NM_000549.5):c.290A>G p.(Tyr97Cys) in a newborn girl detected by neonatal CH screening, whose central CH was initially overlooked because of misinterpretation of her plasma-free thyroxine (fT4) concentration. This report adds to the phenotypic spectrum of TSHB variants and underlines the importance of using age-specific fT4 reference intervals to diagnose central CH.