Efficacy of Dravet Syndrome Treatments in a Subset of Individuals with 2q24.3 Deletion: A-5 Patient Case Series

Dravet syndrome (DS) is a developmental and epileptic encephalopathy often resulting from haploinsufficiency of the voltage-gated sodium channel (VGSC) gene <i>SCN1A</i> located on chromosome 2q24.3. Although single-nucleotide changes account for the majority of cases, rare cases are due to 2q24.3 microdeletions involving <i>SCN1A</i>. The 2q24.3 region surrounding <i>SCN1A</i> contains a cluster of VGSC genes including <i>SCN2A</i>, <i>SCN3A</i>, <i>SCN7A</i>, and <i>SCN9A</i>. Prior publications reported larger 2q24.3 deletions affecting multiple VGSC genes being associated with a more severe phenotype. Consensus recommendations for epilepsy therapies do not exist for DS patients with 2q24.3 deletion involving other VGSC genes. To address this gap, we qualitatively assessed the therapy response in 5 patients with 2q24.3 microdeletions. We found evidence of efficacy for valproic acid, clobazam, and cannabidiol whereas levetiracetam and phenobarbital were not beneficial. Additional studies are necessary to examine the efficacy of fenfluramine and the ketogenic diet.