Genetic Epilepsy with Febrile Seizures Plus (GEFS+)
• Management: treat per seizure type with standard antiseizure medications; most patients don’t require chronic therapy. Provide home rescue benzodiazepines and a clear action plan for prolonged febrile seizures. Antipyretics can be used to mitigate risk with immunizations.
• Surveillance: monitor for worsening on sodium-channel blockers; switch agents if exacerbation occurs. Routine developmental/academic surveillance and family counselling regarding variable expressivity and incomplete penetrance.
Dravet Syndrome (DS)
• Management: first-line ASM therapies include valproate, clobazam, fenfluramine, stiripentol, and pharmaceutical-grade cannabidiol. Ketogenic diet and vagus nerve stimulation are non-pharmacologic modalities. Avoid sodium-channel blockers (carbamazepine, oxcarbazepine, phenytoin, lamotrigine) and rufinamide as they worsen seizures in DS patients. Disease-modifying approaches aimed at boosting SCN1A are in development (ex: Zorevunersen and ETX101).
• Surveillance: fever management with NSAIDs (avoid acetaminophen due to hepatoxicity/interaction risk with certain ASMs), routine immunizations with individualized peri-vaccine plans, rescue protocols, caregiver CPR training, and monitoring of SUDEP risk, sleep, behavioral, mobility, and autonomic concerns. Cardiac monitoring is required if patient is taking fenfluramine.
Familial Hemiplegic Migraine, Type 3 (FHM3)
• Management: first-line therapy includes verapamil, acetazolamide, flunarizine (headache-predominant), or lamotrigine; many clinicians avoid vasoconstrictors (ex: triptans/ergots) in hemiplegic aura because of theoretical stroke risk.
• Surveillance: advise on head-injury avoidance and provide an individualized emergency plan for prolonged or severe attacks; educate families about stroke mimics and thresholds for emergent imaging.
Developmental and Epileptic Encephalopathy 6B (DEE6B)
• Management: broad-spectrum ASMs, ketogenic diet, and comprehensive supportive care (feeding, respiratory, tone/positioning). Many DEE6B alleles show Nav1.1 gain-of-function, so in contrast to DS, a carefully monitored trial of a sodium-channel blocker (ex: oxcarbazepine) may be appropriate in selected cases.
• Surveillance: close developmental and nutritional follow-up; repeat neuroimaging as indicated; individualized rescue plans and palliative support as needed.
SCN1A