Table 1.
Features of patients with pathogenic/likely pathogenic SCN3A variants
| Patient | Age (sex) | Variant (NM_006922.3) | Seizure types (onset of first seizure) |
EEG | Brain MRI | Neurological exam |
|---|---|---|---|---|---|---|
| 1 | 17w fetus (F) | c.25647T>C; p.Leu855Pro de novo | NA | NA | NA | NA |
| 27 | 13y (M) | c.2624T>C; p.Ile875Thr de novo | T w/autonomic features (2w), Myo | Multifocal | Bilateral PMG | Central hypotonia, spastic quadriplegia; profound ID: NV, NW |
| 37 | 3y (F) | c.2624T>C; p.Ile875Thr de novo | T (2w) | Multifocal | Bilateral PMG | Central hypotonia, spastic quadriplegia; severe DD |
| 4 | 2y (F) | c.2624T>C; p.Ile875Thr de novo | FA (2w), T (2w) | Multifocal | Cortical thickening; diffuse PMG | Central hypotonia; severe DD |
| 5 | 16y (F) | c.2624T>C; p.Ile875Thr unknown inheritance | FA (1w), T, FMyo, GTCS | GSSW, GPSW | Bilateral PMG | Spastic quadriplegia; severe ID |
| 6 | 12y (M) | c.2624T>C; p.Ile875Thr de novo | Unknown (1w) | NA | Bilateral PMG | Spasticity; profound ID |
| 7 | 1.5y (M) | c.2624T>C; p.Ile875Thr de novo | FIAS (8m) | Multifocal | Bilateral PMG | Central hypotonia; profound DD |
| 8 | 1.2y (F) | c.2653C>T; p.Leu885Phe de novo | HC (2d), T, C, SE | Burst suppression; hyps | Frontal pachygyria; Hypoplastic CC | Spastic quadriplegia, axial hypotonia; profound DD |
| 97 | <4y‡ (M) | c.3998C>T; p.Pro1333Leu de novo | T (1d), FM, HC, GTCS | Hyps; multifocal | Hypoplastic CC | Hypotonia; profound DD |
| 10 | 10m‡ (F) | c.4403T>G; p.Ile1468Arg de novo | ES (6m), T, FT | Modified hyps; multifocal | Normal | Profound axial hypotonia; profound DD |
| 11 | 6y (M) | c.4457C>T; p.Thr1486Ile de novo | FA (1w) | GSSW | Bilateral PMG | Pseudobulbar palsy; Severe ID |
| 12 | 4y (F) | c.4518delA; p.Lys1506Asnfs*18 de novo | ES (2m), T | Hyps; multifocal | Hypoplastic CC; bilateral frontal atrophy | Hypotonia; profound DD |
| 13 | 15y (M) | c.4861C>G; p.Arg1621Gly not maternally inherited | T (4m), T w/autonomic features, FIAS | Bilateral SW | Bilateral PMG | Pseudobulbar palsy; severe ID |
| 14 | 29y (M) | c.4862G>A; p.Arg1621Gln de novo | FS (5y), Single GTCS | Normal | Bilateral PMG (Head CT) | Severe ID |
| 15 | 4y (M) | c.4937T>G; p.Phe1646Cys Maternally inherited (mother is Patient 16) | No seizures | Not done | Bilateral PMG | Pseudobulbar palsy; right hemiparesis; moderate DD |
| 16 | 37y (F) | c.4937T>G; p.Phe1646Cys Maternally inherited | GTCS (5y) | NA | Bilateral PMG | Pseudobulbar palsy; brisk reflexes; mild ID |
| 17 | 14y (F) | c.4937T>G; p.Phe1646Cys unknown inheritance | No seizures | Normal | Bilateral PMG | Oromotor dysfunction; normal strength and tone; mild ID |
| 18 | 36y (F) | c.4937T>C; p.Phe1646Ser de novo | Unknown (8d), FIAS, GTCS | Bitemporal epileptiform discharges | Bilateral PMG | Dysarthria, facial paresis, brisk reflexes; mild ID |
| 19 | 6y (M) | c.5006A>G; p.Tyr1669Cys de novo | No seizures | Not done | Not done | Mild DD; autism spectrum disorder |
| 2035 | 4y (M) | c.5295G>A; p.Met1765Ile de novo | T (1w), FM, ES | NA | Bilateral PMG | Generalized hypotonia; profound DD |
| 217 | NA (F) | c.5306T>C; p.Val1769Ala de novo | Onset <12m | Multifocal | NA | DD |
| 22 | 2y (F) | c.5306T>C; p.Val1769Ala de novo | T (4d), ES, FA | Hyps; GSW | Normal | Hypotonia with head lag; severe DD, autism |
Deceased, age at death; C, clonic seizures; CC, corpus callosum; d, days; DD: developmental delay; ES, epileptic spasms; FA, focal autonomic seizures; FIAS, focal impaired awareness seizures; FM, focal motor seizures; FMyo, focal myoclonic seizures; FS, febrile seizures; FT, focal tonic seizures; GPSW, generalized polyspike-wave discharges; GSSW, generalized slow spike-wave discharges; GSW, generalized spike-wave discharges; GTCS, generalized tonic-clonic seizures; hyps; hypsarrhythmia; HC, hemiclonic seizures; ID, intellectual disability; m, months; Myo, myoclonic seizures; NA: not available; PMG, polymicrogyria; SE, status epilepticus; SW, spike-and-slow wave complexes; T, generalized tonic seizures; w, weeks; y, years. Further clinical details are provided in Supplementary Tables 1-3