Table 2:
Clinical features of individuals with identified pathogenic variants
| Variant | GNAO1 p.(Arg177Pro) | KCNB1 p.(Arg583*) | KCNB1 p.(Trp370*) | KIF1A p.(Glu253Lys) | SLC35A2 p.(Tyr130Cys) | STXBP1 p.(Leu41Pro) | TBL1XR1 p.(Gly29Asp) |
|---|---|---|---|---|---|---|---|
| Age (gender) | - | - | 4 y (M) | 4 y (F) | F (5 y) | - | - |
| Epilepsy syndrome | WS, LGS | WS | WS | IS | IS | WS | WS |
| Presenting sz (age) | IS (6 w) | IS (5 m) | IS (4 m) | IS (6 m) | IS (1 m) | IS (4 m) | IS (6 m) |
| EEG at onset | Suppression-burst | Hypsarrhythmia | Hypsarrhythmia | Multifocal epileptic abnormalities | Multifocal epileptic abnormalities | Hypsarrhythmia | Hypsarrhythmia |
| Further sz types | Myoclonic | No | - | - | Focal motor | Tonic, absence, myoclonic-astatic, myoclonic | - |
| EEG at follow-up (age) | Slow background, no epileptiform discharges (8 y, 11 y, 13 y, 14 y) | Normal | Normal (3 y) | Multifocal epileptic abnormalities (4 y) | Fronto-temporal L epileptic abnormalities (5 y) | Monomorphic slow background, multifocal spikes, generalized fast paroxysmal activity in sleep (14 y), slow background, fronto-temporal spikes (16 y) | Normal |
| Neuroimaging (age) | Normal (3 m) | Normal (5 m, 2 y) | Normal (2 y) | Multiple signal hyperintensities, thin corpus callosum, cerebellar atrophy (3 y) | Enlarged ventricles, large cerebellar cystic dilation (4 y) | Normal (8 y) | Mild delayed myelination; poor white matter development; mild vermis hyoplasia and thin corpus callosum (6 m, 30 m, 5y) |
| Cognition before sz onset | NA | Normal | Normal | Delayed milestones | Delayed milestones | Normal | Mild DD |
| Cognition after onset | Severe ID | Severe ID | Stagnation, mild ID | Cognitive regression, severe ID | Stagnation, severe ID | Severe ID | Moderate ID |
| Behavioral issues | Hyperactivity | No | Autistic Features | No | No | Autism | Hyperactive behavior and attention deficit disorder |
| Neurological examination | Microcephaly, ataxia, spastic gait, walks a few steps | No speech | - | Microcephaly, hypotonia, absent language, nystagmus | Microcephaly, hypotonia, absent language, nystagmus, strabismus | Spasticity, ataxia, hypotonia | - |
| Treatment response | Long term sz free on VGB and VPA, no AEDs in the last 9 y | Response to ACTH, no AEDs at present, no further sz | Good response | Poor response | Partial benefit | Response to ACTH, sz free form the age of 7 m to 6 y, later drug-resistant | Response to ACTH, no AEDs at present |
| Other features | Facial dysmorphia (telecanthus, short philtrum, large ear lobe, low set ears, long thumbs and short Vth finger on hands), scoliosis | R leg hyperchromic skin spot, bilateral hands clinodactyly | - | Dysmorphic features, optic atrophy | - | - | No |
Abbreviations are as follows: ACTH, adrenocorticotropic hormone; AEDs, antiepileptic drugs; CBZ, carbamazepine; DD, developmental delay; DTP, diphtheria pertussis tetanus; F, female; hrs, hours; ID, intellectual disability; IS, infantile spasms; L, left; LEV, levetiracetam; LGS, Lennox-Gastaut Syndrome; LTG, lamotrigine; M, male; m, months; NA, not applicable; R, right; Sz, seizure; w, weeks; WS, West Syndrome; VGB, vigabatrin; VPA, valproate; y, years; -, information unavailable