Clinical characterization and developmental follow-up of a child with Sotos syndrome carrying a novel NSD1 variant.

BACKGROUND

Sotos syndrome is a rare overgrowth-intellectual disability(OGID) disorder typically associated with developmental delay that stabilizes or improves with early intervention.

CASE PRESENTATION: We report a 17-month-old boy with classic clinical features of Sotos syndrome who presented with severe speech and motor delay. Whole-exome sequencing(WES) revealed a novel de novo nonsense pathogenic variant in NSD1:c.3910 C > T (p.Gln1304Ter), which is predicted to truncate multiple functional domains, including the SET(Su(var)3-9, Enhancer-of-zeste, and Trithorax) catalytic domain. Despite early and continuous rehabilitation, his developmental quotient(DQ) decreased from 45.8 at 17 months to 39.9 at 28 months, indicating slow and limited developmental progress over time. Brain MRI (magnetic resonance imaging) revealed corpus callosum abnormalities and reduced white matter volume.

CONCLUSIONS

This is the first report of Sotos syndrome caused by the NSD1:c.3910 C > T (p.Gln1304Ter) pathogenic variant. Beyond expanding the spectrum of pathogenic variants, this case highlights a relatively severe neurodevelopmental profile with persistently limited progress, underscoring the importance of early genetic diagnosis, sustained multidisciplinary rehabilitation, and long-term follow-up to optimize outcomes in affected children.