Severe skeletal fragility in SCN8A ‐related developmental and epileptic encephalopathy

Abstract

Abstract In this child with a phenotype compatible with the SCN8A gain‐of‐function spectrum, more than 20 bone fractures were documented. Together with previously reported cases, these observations raise the possibility that skeletal fragility may represent an underrecognized feature of the clinical spectrum associated with pathogenic SCN8A variants. Experimental and clinical findings provide biological plausibility for altered bone remodeling, while the marked reduction in fracture burden following pamidronate therapy underscores the importance of early recognition and management of skeletal complications in this population.