Sotos Syndrome With NSD1 Mutations in a Chinese Cohort: Identification of Two Novel Mutations and Literature Review

ABSTRACT Sotos syndrome is an autosomal dominant disorder resulting from pathogenic variants of the NSD1 gene. In this study, we present five Chinese paediatric cases, including two previously unreported NSD1 variants: a nonsense mutation (c.1486A > T p. Lys496*) and a missense mutation (c.6086C > T) (p. Thr2029Ile) respectively. Additionally, we analyzed the genotypic and phenotypic spectrum of 23 Chinese children with molecularly confirmed Sotos syndrome. Patients exhibited characteristic craniofacial features and significant overgrowth. All patients showed DD/ID and five patients (21.7%) showed symptoms of ASD. Febrile seizures occurred in six patients (26.1%). Abnormalities on cranial imaging were generally nonspecific. Other clinical features were also shown, such as atrial septal defect (5 cases), patent ductus arteriosus (3 cases), scoliosis (2 cases) and neonatal hypoglycemia (2 cases). These findings underscore the phenotypic variability of Sotos syndrome and highlight the necessity for long‐term multidisciplinary follow‐up to delineate its evolving natural history and optimize clinical management.