Table 1. The Epilepsy Genetics Initiative (EGI) participant phenotype and summary of cases previously described in the literature.

	Summary of SCN8A EE cases previously described in the literature1, 13, 14	EGI individual 1	EGI individual 2	EGI individual 3
Variant	—	c.667A>G (p.Arg223Gly)	c.632T>C (p.Val211Ala)	c.692T>C (p.Ile231Thr)
Inheritance	—	De novo	De novo	De novo
Sex	—	Female	Male	Male
Ethnicity	—	Paternal–European Maternal–Chinese	Paternal–European Maternal–Filipino	Paternal–European Maternal–European
Age at seizure onset	4–5 months on average	6 months	3 months	Febrile seizures at ~7–8 months; first unprovoked seizure at ~1 year of age
Seizure type(s)	Focal, tonic, clonic, myoclonic, and absence seizures reported; epileptic spasms; typically not associated with fever; convulsive or nonconvulsive status epilepticus in some	Clusters of head drops that evolved into extensor spasms	Tonic–clonic, then asymmetric supplementary motor seizures (left > right); tonic; focal dyscognitive	Febrile generalized tonic–clonic seizures, focal seizures, absence seizures
Development	Intellectual disability is common and may range from mild to severe; no speech for some; wheelchair dependence for some	Global developmental delay	Global developmental delay; never developed language	Global developmental delay; learning difficulty
Regression	In most cases, development is normal from birth to seizure onset; regression often slows or regresses following seizure onset	No	Yes; used to walk but regressed in setting of prolonged seizures	No
Electroencephalogram	Moderate to severe background slowing with focal or multifocal epileptiform discharges	Hypsarrhythmia with electroclinical spasms with electrodecrement	Left focal spikes, generalized spike/wave, background slowing and disorganization	Multifocal epileptiform discharges with background slowing
Magnetic resonance imaging	Variable degrees of generalized atrophy	Diffuse atrophy	Mild white matter volume loss; increased FLAIR hyperintensity in the left hemisphere in the acute setting of seizures	Normal
Other	Hypotonia, dystonia, ataxia, hyperreflexia, choreoathetosis	—	—	Hypotonia, ataxia
Diagnosis before exome sequencing	—	West syndrome of unknown cause	Epileptic encephalopathy of unknown cause	Epileptic encephalopathy of unknown cause
Response to treatment	Seizures refractory for many patients	Refractory to all anti- AEDs	Refractory to many AEDs; felbamate withdrawal precipitated convulsive status; addition of cannabidiol was reported to be helpful; once SCN8A diagnosis was made, phenytoin resulted in a >90% reduction in seizures	Responder to levetiracetam and topiramate; good seizure control since ~3 years of age; still has staring spells

AED, antiepileptic drug; EE, epileptic encephalopathy; FLAIR, fluid-attenuated inversion recovery.