Genetic Epilepsy with Febrile Seizures Plus (GEFS+)
• Seizures: families show broad expressivity from isolated febrile seizures, febrile seizures plus (onset < 1 year, persistence > 6 years, risk of status epilepticus), and generalized or focal epilepsies. Febrile triggers are common (ex: immunization), but afebrile tonic-clonic, myoclonic, absence, or focal seizures can occur. Most individuals respond to antiseizure medication and seizures tend to remit by adolescence.
• Non-Seizure Features: development/cognition are usually unaffected, though variability occurs within families
• Morbidity/Mortality: prolonged febrile seizures can progress to status epilepticus in a subset of patients; mortality risk is substantially lower than in DS.
• Prognosis: generally favorable, with age-related improvement; some patients require intermittent or maintenance therapy depending on afebrile seizure burden.
Dravet Syndrome (DS)
• Seizures: onset in infancy (generally < 1 year, rarely onset occurs in second year of life) with prolonged febrile and afebrile hemiclonic or generalized tonic-clonic seizures; common triggers include thermosensitivity and photosensitivity. In early childhood, polymorphic seizures (myoclonic, atypical absence, focal) may present as EEG evolves from normal/slowing to generalized spike/polyspike-wave pattern. By adolescence the convulsive seizures may lessen but rarely remit.
• Non-Seizure Features: developmental slowing/regression, language impairment, gait phenotype (crouched gait, hypotonia, ataxia, parkinsonian features in adults), behavioral and sleep problems, autonomic dysregulation.
• Morbidity/Mortality: recurrent status epilepticus and elevated SUDEP risk.
• Prognosis: lifelong disorder with variable seizure burden and neurodevelopmental outcomes; complex multidisciplinary care is typical continuing throughout adulthood.
Familial Hemiplegic Migraine, Type 3 (FHM3)
• Migraines: onset often in first/second decade. Episodes feature visual/sensory/language aura plus transient hemiparesis (lasting minutes – hours) followed by headache and recovery. FHM3 patients can have a novel phenotype of elicited repetitive daily blindness (bilateral 30 second spells of blindness). Attacks may be triggered by typical migraine precipitants or minor head trauma; frequency often declines with age.
• Comorbidities: seizures can occur in some families.
• Morbidity/Mortality: attacks can mimic stroke symptoms; prolonged neurologic deficits merit urgent evaluation
• Prognosis: neurological status between episodes is typically normal; quality-of-life burden can be substantial when attacks are frequent and severe.
Developmental and Epileptic Encephalopathy 6B (DEE6B)
• Epileptic Encephalopathy: <3 month onset with medication-resistant multifocal and migrating seizures; epileptic spasms and tonic seizures are prominent and typically not fever-sensitive.
• Non-seizure features: profound developmental impairment, feeding/respiratory complications, hyperkinetic movement disorder (dystonia/chorea). MRI may show progressive atrophy in some patients.
• Prognosis: poor neurodevelopmental outcome and high care complexity; generally more severe than DS.
SCN1A