Early sodium channel blocker initiation is associated with better outcomes in KCNQ2 disorders.
Early sodium channel blocker start linked to earlier seizure offset in KCNQ2-DEE
Early sodium channel blocker initiation is associated with better outcomes in KCNQ2 disorders.
Pathogenic KCNQ2 variants are the most common genetic cause of neonatal-onset epilepsies, with phenotypes ranging from self-limited (familial) neonatal epilepsy (SeL(F)NE) to severe developmental and epileptic encephalopathy (KCNQ2-DEE).
We leveraged a large, multicentre international cohort comprising 282 individuals with pathogenic KCNQ2 variants to retrospectively assess the effectiveness of antiseizure medications (antiseizure medications), particularly sodium channel blockers, on seizure control and neurodevelopment.
Epilepsy course, antiseizure medications effectiveness, and neurodevelopmental milestones were systematically collected and analysed, including time-to-event and adjusted outcome analyses.
Early sodium channel blockers initiation was also associated with significantly more favourable neurodevelopmental outcomes, including higher rates of attaining major motor milestones.
Considerable phenotypic variability persisted, with some individuals experiencing severe impairment despite early seizure control and sodium channel blockers initiation, suggesting that variant severity and additional genetic or biological modifiers contribute to outcome heterogeneity.
We however emphasise that early treatment is not universally transformative and further prospective work, including exploration of targeted therapies and standardised neurodevelopmental assessments, is needed to optimise long-term outcomes in this heterogeneous population.