A novel homozygous SCN2B variant associated with early-onset developmental and epileptic encephalopathy in two...

To describe the clinical and genetic findings of two siblings with developmental and epileptic encephalopathy carrying a novel homozygous SCN2B variant, and to further delineate the phenotypic spectrum and possible inheritance pattern of SCN2B-related epilepsy.

We evaluated the clinical, developmental, and genetic findings of two affected siblings born to consanguineous parents. Seizure history, treatment response, and developmental features were reviewed. Genetic testing was performed using next-generation sequencing, followed by segregation analysis within the family.

Both siblings presented with infantile-onset seizures characterized by epileptic spasms, global developmental delay, and persistent epilepsy during infancy despite treatment with multiple antiseizure medications. Genetic analysis identified a novel homozygous missense variant in SCN2B (NM_004588.4: c.295G>A, p.Val99Met). Segregation analysis showed that both affected siblings were homozygous for the variant, whereas both parents were heterozygous carriers. The variant is absent or extremely rare in population databases and is predicted to be deleterious by multiple in silico tools.

This report expands the genotypic and phenotypic spectrum of SCN2B-related epilepsy and supports a possible autosomal recessive inheritance pattern. SCN2B variants should be considered in patients with early-onset developmental and epileptic encephalopathy, particularly in consanguineous families.