Congenital hypothyroidism in two children affected by Sotos syndrome: a simple association?

Abstract

Background: Congenital hypothyroidism (CH) is the most common congenital endocrine disorder and one of the most preventable causes of intellectual disability. The underlying etiology of CH can be thyroid dysgenesis or dyshormonogenesis, and in rare cases, CH can occur as part of a genetic syndrome. Sotos syndrome is a rare overgrowth disorder caused by pathogenic variants in the NSD1 gene, characterized by excessive growth in infancy, distinctive facial features, and developmental delay.

Case presentation: We describe two unrelated children with permanent CH and genetically confirmed Sotos syndrome. Both children were referred to our Pediatric Endocrinology Centre due to abnormal thyroid-stimulating hormone (TSH) values detected through neonatal screening. A permanent CH was confirmed in both cases: one patient had thyroid hypoplasia with the presence of only the right thyroidal lobe; the other one had an in-situ thyroid gland. The diagnosis of Sotos syndrome was made later in infancy. In the first case, auxological parameters at birth were within normal ranges and overgrowth became apparent after six months of age; in the second case, overgrowth was already manifest at birth, but the diagnosis was guided primarily by the neurodevelopmental delay.

Conclusion: We describe two cases in which CH occurred with Sotos syndrome, and we hypothesize that this association may not be coincidental. To our knowledge, these are among the few reported cases of genetically confirmed Sotos syndrome associated with permanent congenital hypothyroidism. Further studies are needed to determine whether CH is a clinical feature of Sotos syndrome or an unrelated finding. We recommend early thyroid function testing in patients with Sotos syndrome and suggest suspecting Sotos syndrome in children presenting with CH, cognitive delay and overgrowth or additional congenital anomalies.