Clinical characteristics and treatment response of the previously unpublished patients: B(F)NIS
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy synd- rome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset/ follow-up | Neurol- ogical features | Additi- onal features | Age at last follow-up | Seizure outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Seizure reduction | No effect | ||||||||||||||
| 1 | A202V/maternal | 1 d | BFNS | F, GTC | NAV | N | NA/N | N | 4 y 6 m | Sz free (2 m) | PB, PHT, TPM, CBZ | VPA, LEV | ||||
| 2 | G828V/de novo | 2 d | BNS | F, C, AU (cluster) | TCS | MF spikes | N | NA/N | N | 14 m | Sz free (2 m) | PHT→OXC | PB, PP, TPM, LEV | |||
| 3 | Q1531K/de novo | 3 d | BNS | S, C, GTC | GTC | NAV | NA | NA/N | N | 14 m | Sz free (5 d) | PB | ||||
| 4 | S863F/de novo | 5 d | BNS→ other | GTC | GTCS, SE, FD | NA→ MF spikes, ESES-like | N | NA/N | N | ADS | 11 y | Sz free (3 m → 10 y) | OXC→ST | LTG, LEV | ||
| 5 | D343G/de novo | 6 d | BNS | GTC (cluster) | F | N | N | NA/N | N | 18 m | Sz free (6 m) | OXC | LEV, PB, PP, CLB | |||
| 6 | F207S/de novo | 9 d | BNS | C | TCS | Spikes par l | N | NA/N | N | 18 m | Sz free (6 m) | PHT | TPM | PB, CLZ, OXC | ||
| 7 | V261M/de novo | 9 d | BNS | GTC | N | N | NA/N | N | 20 m | Sz free (3 m) | CLB | PHT, LEV | B6, VPA | |||
| 8 | R36G/maternal | 16 m | BFIS | F (cluster) | None | NA | N/N | N | 3 y | Sz free (2 y) | ||||||
| 9 | R36G/maternal | 23 m | BFIS | F | C | Slowing | NA | N/N | N | 4 y 5 m | Sz free (NAV) | ZNS | ||||
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy synd- rome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset/ follow-up | Neurol- ogical features | Additi- onal features | Age at last follow-up | Seizure outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Seizure reduction | No effect | ||||||||||||||
| 1 | A202V/maternal | 1 d | BFNS | F, GTC | NAV | N | NA/N | N | 4 y 6 m | Sz free (2 m) | PB, PHT, TPM, CBZ | VPA, LEV | ||||
| 2 | G828V/de novo | 2 d | BNS | F, C, AU (cluster) | TCS | MF spikes | N | NA/N | N | 14 m | Sz free (2 m) | PHT→OXC | PB, PP, TPM, LEV | |||
| 3 | Q1531K/de novo | 3 d | BNS | S, C, GTC | GTC | NAV | NA | NA/N | N | 14 m | Sz free (5 d) | PB | ||||
| 4 | S863F/de novo | 5 d | BNS→ other | GTC | GTCS, SE, FD | NA→ MF spikes, ESES-like | N | NA/N | N | ADS | 11 y | Sz free (3 m → 10 y) | OXC→ST | LTG, LEV | ||
| 5 | D343G/de novo | 6 d | BNS | GTC (cluster) | F | N | N | NA/N | N | 18 m | Sz free (6 m) | OXC | LEV, PB, PP, CLB | |||
| 6 | F207S/de novo | 9 d | BNS | C | TCS | Spikes par l | N | NA/N | N | 18 m | Sz free (6 m) | PHT | TPM | PB, CLZ, OXC | ||
| 7 | V261M/de novo | 9 d | BNS | GTC | N | N | NA/N | N | 20 m | Sz free (3 m) | CLB | PHT, LEV | B6, VPA | |||
| 8 | R36G/maternal | 16 m | BFIS | F (cluster) | None | NA | N/N | N | 3 y | Sz free (2 y) | ||||||
| 9 | R36G/maternal | 23 m | BFIS | F | C | Slowing | NA | N/N | N | 4 y 5 m | Sz free (NAV) | ZNS | ||||
ADS = attention deficit disorder; AU = autonomic seizures; BFIS = benign familial infantile seizures; BNS = benign neonatal seizures; BFNS = benign familial neonatal seizures; C = clonic; F = focal; FD = focal dyscognitive; GTC = generalized tonic-clonic; l = left; m = months; MF = multifocal; N = normal; NA = not applicable; NAV = not available; Par = parietal; SE = status epilepticus; Sz = seizures; TCS = tonic-clonic seizures; y = years; → = change to.
Treatment (sodium channel blockers are highlighted in bold): B6 = vitamin B6; CBZ = carbamazepine; CLB = clobazam; CLZ = clonazepam; LTG = lamotrigine; LEV = levetiracetam; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; PP = pyridoxal phosphate; ST = sulthiame; TPM = topiramate; VPA = valproate; ZNS = zonisamide.
Clinical characteristics and treatment response of the previously unpublished patients: B(F)NIS
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy synd- rome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset/ follow-up | Neurol- ogical features | Additi- onal features | Age at last follow-up | Seizure outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Seizure reduction | No effect | ||||||||||||||
| 1 | A202V/maternal | 1 d | BFNS | F, GTC | NAV | N | NA/N | N | 4 y 6 m | Sz free (2 m) | PB, PHT, TPM, CBZ | VPA, LEV | ||||
| 2 | G828V/de novo | 2 d | BNS | F, C, AU (cluster) | TCS | MF spikes | N | NA/N | N | 14 m | Sz free (2 m) | PHT→OXC | PB, PP, TPM, LEV | |||
| 3 | Q1531K/de novo | 3 d | BNS | S, C, GTC | GTC | NAV | NA | NA/N | N | 14 m | Sz free (5 d) | PB | ||||
| 4 | S863F/de novo | 5 d | BNS→ other | GTC | GTCS, SE, FD | NA→ MF spikes, ESES-like | N | NA/N | N | ADS | 11 y | Sz free (3 m → 10 y) | OXC→ST | LTG, LEV | ||
| 5 | D343G/de novo | 6 d | BNS | GTC (cluster) | F | N | N | NA/N | N | 18 m | Sz free (6 m) | OXC | LEV, PB, PP, CLB | |||
| 6 | F207S/de novo | 9 d | BNS | C | TCS | Spikes par l | N | NA/N | N | 18 m | Sz free (6 m) | PHT | TPM | PB, CLZ, OXC | ||
| 7 | V261M/de novo | 9 d | BNS | GTC | N | N | NA/N | N | 20 m | Sz free (3 m) | CLB | PHT, LEV | B6, VPA | |||
| 8 | R36G/maternal | 16 m | BFIS | F (cluster) | None | NA | N/N | N | 3 y | Sz free (2 y) | ||||||
| 9 | R36G/maternal | 23 m | BFIS | F | C | Slowing | NA | N/N | N | 4 y 5 m | Sz free (NAV) | ZNS | ||||
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy synd- rome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset/ follow-up | Neurol- ogical features | Additi- onal features | Age at last follow-up | Seizure outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Seizure reduction | No effect | ||||||||||||||
| 1 | A202V/maternal | 1 d | BFNS | F, GTC | NAV | N | NA/N | N | 4 y 6 m | Sz free (2 m) | PB, PHT, TPM, CBZ | VPA, LEV | ||||
| 2 | G828V/de novo | 2 d | BNS | F, C, AU (cluster) | TCS | MF spikes | N | NA/N | N | 14 m | Sz free (2 m) | PHT→OXC | PB, PP, TPM, LEV | |||
| 3 | Q1531K/de novo | 3 d | BNS | S, C, GTC | GTC | NAV | NA | NA/N | N | 14 m | Sz free (5 d) | PB | ||||
| 4 | S863F/de novo | 5 d | BNS→ other | GTC | GTCS, SE, FD | NA→ MF spikes, ESES-like | N | NA/N | N | ADS | 11 y | Sz free (3 m → 10 y) | OXC→ST | LTG, LEV | ||
| 5 | D343G/de novo | 6 d | BNS | GTC (cluster) | F | N | N | NA/N | N | 18 m | Sz free (6 m) | OXC | LEV, PB, PP, CLB | |||
| 6 | F207S/de novo | 9 d | BNS | C | TCS | Spikes par l | N | NA/N | N | 18 m | Sz free (6 m) | PHT | TPM | PB, CLZ, OXC | ||
| 7 | V261M/de novo | 9 d | BNS | GTC | N | N | NA/N | N | 20 m | Sz free (3 m) | CLB | PHT, LEV | B6, VPA | |||
| 8 | R36G/maternal | 16 m | BFIS | F (cluster) | None | NA | N/N | N | 3 y | Sz free (2 y) | ||||||
| 9 | R36G/maternal | 23 m | BFIS | F | C | Slowing | NA | N/N | N | 4 y 5 m | Sz free (NAV) | ZNS | ||||
ADS = attention deficit disorder; AU = autonomic seizures; BFIS = benign familial infantile seizures; BNS = benign neonatal seizures; BFNS = benign familial neonatal seizures; C = clonic; F = focal; FD = focal dyscognitive; GTC = generalized tonic-clonic; l = left; m = months; MF = multifocal; N = normal; NA = not applicable; NAV = not available; Par = parietal; SE = status epilepticus; Sz = seizures; TCS = tonic-clonic seizures; y = years; → = change to.
Treatment (sodium channel blockers are highlighted in bold): B6 = vitamin B6; CBZ = carbamazepine; CLB = clobazam; CLZ = clonazepam; LTG = lamotrigine; LEV = levetiracetam; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; PP = pyridoxal phosphate; ST = sulthiame; TPM = topiramate; VPA = valproate; ZNS = zonisamide.
Clinical characteristics and treatment response of the previously unpublished patients: encephalopathy with early onset epilepsy
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy syndrome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset / follow-up | Neurological features | Additional features | Age at last follow-up | Seizure Outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Seizure reduction | No effect | Wor- sening | |||||||||||||
| 10 | V423L/de novo | 1 d | OS | M, AP | T | SB→MF spikes | NA | NA/SD | Hypotonia | MC | 34 m (deceased) | Intractable | BR | B6, PP, MDZ, LEV, PHT, RGB, KD, CBZ, LCM | ||
| 11 | E999K/de novo | 1 d | OS→other | T | M, TCS | SB→beta→f spikes | N | NA/SD | Dystonia | Oculogyric crises | 5 y | Sz free (1 m, relapses with low PHT levels) | PHT | PB, B6, PP, VGB, TPM, LEV | ||
| 12 | Q1811E/de novo | 1 d | OS→other | T | GTCS, S, F | SB→Spikes l | N | NA/MD | Hypotonia, unsteady gait | ASD | 8 y | Sz free (4 y) | LTG + VPA + LEV | PHT, TPM | VGB | |
| 13 | M1548V/de novo | 1 d | OS→WS | T | GTC | SB→HA→slowing | N | NA/SD | Hypotonia | ASD | 18 m | Intractable | TPM | PB, PHT, B6, PP, LEV, VGB, CBZ | ||
| 14 | I237N/de novo | 1 d | other | F | F (variable onset) | MF spikes, slowing | HM | NA/SD | Hypotonia | Poor eye contact | 3 y 9 m | Intractable | VPA, CBZ | VGB, LEV, TPM, LTG, B6, PHT, PB, CLZ | ||
| 15 | V887A/de novo | 1 d | OS→WS | M | S | SB→HA | N | NA/SD | Hypotonia | 15 m | Sz free (6 m, relapse with low PHT levels) | PHT | TPM | PB,ST,CS | ||
| 16 | G882R/de novo | 1 d | EIMFS | unilateral TC r/l | T | MF spikes, ictal pattern r / l | N | NA/SD | Hypotonia | MC | 10 m | Intractable | PHT, LCM, ZNS | LEV, CS, B6, PP | ||
| 17 | I1640S/de novo | 1 d | Other | T | F, TC | Spikes r | NA | NA/MD | NAV | 9 y | Sz free (7 y) | LCM | LTG, TPM | B6, PB, VPA, LEV | ||
| 18 | K908E/de novo | 1 d | Other | M | S | Gen+ MF spikes, slowing | At | NA/SD | Nystagmus, hypotonia, dystonia | MC | 8 y | Sz free (7 y 6 m) | LEV, ZNS | |||
| 19 | R1882Q/unknown | 1 d | Other | NA | F →; C | MF + bil spikes, poly spikes | Subtle CD | NA/SD | N | MC | 10 y 6 m | Intractable | CBZ | PB, LEV, OXC, TPM, VPA, CLB, LTG, PHT | ||
| 20 | V1627M/de novo | 2 d | EIMFS | T r/l migrating | F, AP | MF spikes→N | N | NA/MID | Hypotonia | 14 m | Sz free (2 m) | VGB | LEV, B6, PP, TPM, PB,VPA | |||
| 21 | R856Q/de novo | 2 d | OS | T | T | SB→SW | Sinus thrombosis, ischaemia CC | NA/NA | NAV | Connatal sinus thrombosis | 3 m (deceased) | Intractable | MDZ | LEV, PB, PHT, B6, VGB, TPM | ||
| 22 | A1500T/de novo | 2 d | OS→ other | F, T | C | SB→spikes l te→slowing | HM, At | NA/SD | Spasticity | Poor eye contact, MC | 13 y | Sz free (3 m), relapse (12 m), sz free(13 m), relapse (5 y), sz free (10 y) | TPM (3 m), ACTH (13 m) | LTG, VPA | ||
| 23 | M1545V/de novo | 2 d | EIMFS | T, C r/l migrating | F, TCS | SB→MF spikes→N | N | NA/MID | Hypotonia | 12 m | Sz free (3 m, relapses with low PHT levels) | PHT→CBZ | LEV | PB, B6, PP, VPA | ||
| 24 | E430A/de novo | 2 d | Other | F | MF spikes | N | NA/SD | Hypotonia | Regression, ASD | 22 m | Sz free (12m) | PHT | TPM, CLB | |||
| 25 | S1536R/de novo | 2 d | Other | T | AP, SE, TCS | MF spikes, occ slowing | N | NA/MD | Hypotonia | 2 y 8 m | Sz free (6 m, relapses with low PHT levels) | PHT | TPM, PB, LEV, B6 | |||
| 26 | F1597L/de novo | 3 d | EIMFS | T r/l migrating | T→S | SB→spikes r/l te, slowing | At, calcifications | NA/SD | Dystonia | Dysautonomia, irritability | 3 y | Intractable | PHT, CBZ, LTG, BR | B6, PB, LEV, VGB, KD, ST, VPA, LCM, ZNS | ||
| 27 | V424L/de novo | 3 d | Other | F | TCS | SB→MF biocc, slowing | HM | NA/SD | Hypotonia | Poor eye contact | 4 y | Sz free (15 m) | CBZ | CS | PB, VPA | |
| 28 | I891T/de novo | 3 d | Other | T | MF spikes, bisynchrony | N | NA/MD | Coordination difficulties | ADS | 3 y | Sz free (3 m) | PHT | B6, PP, CBZ, CLZ, MDZ, TPM, VPA, ACTH | |||
| 29 | E999K/de novo | 3 d | Other | T r/l | SB→gen SW | At, HM | NA/SD | Dystonia | ASD, nystagmus | 22 y | Sz free (3 y) | CBZ | PB | |||
| 30 | G882E/de novo | 4 d | EIMFS | F, AU, HC r/l M, C migrating | T, AA, | MF spikes, slowing | At, HM | NA/SD | Dystonia | Dysautonomia | 8 y | Intractable | PHT, LCM | VPA, LEV, FBM, GBP, CLB, CLZ, MSX, TPM, PB, KD, CS, LI, ME | ||
| 31 | R1319Q/unknown | 5 d | Other | M | S | MF spikes, slowing | HM | NA/SD | Hypotonia, limb hypertonia | 14 m | Sz free (13 m) | ACTH | TPM, others | |||
| 32 | R1629H/de novo | 6 d | other | S | GTCS, FM | SW fr-ce→MF spikes | N | NA/SD | Hypotonia | 8 y | Sz free (4 m) | PHT | CLZ, MDZ, VPA, LEV, VGB, B6 | |||
| 33 | V423L/de novo | 6 d | OS | F | TCS, T r/l | SB→MF spikes, slowing | T2H | NA/SD | Spasticity | MC | 4 y | Intractable | OXC | PB, LEV, VGB, CS, ZNS, RUF, VPA, TPM, LTG | ||
| 34 | A263V/de novo | 3 w | other | S | T, GTC | Atypical HA→MF spikes, slowing | At, HM | N/SD | Spasticity | MC, scoliosis | 13 y (deceased) | Intractable | ACTH,NZP, CS,MDZ, CLB, LTG, VPA, CLZ,TPM | PB, PHT, TPM, VNS | ||
| 35 | F1651C mosaic/de novo | 6 w | other | GTCS | C, SE | MF spikes | N | N/MID | Hypotonia | 9 m | Sz free (3 m, relapses with low PHT levels) | PHT | PB, OXC, TPM, LEV, B6, PP | |||
| 36 | R1319Q/de novo | 2 m | other | GTC | FC | SW, slowing | HM | N/MD | N | ASD | 3 y 10 m | Sz free (8 m) | VGB | LEV | ||
| 37 | F895S/de novo | 2 m | other | S, M | C, GTC | SB→MF spikes | N | SD/SD | Hypotonia | Optic atrophy | 4 y 8 m | Intractable | VGB, PB, TPM, VPA, CLB | |||
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy syndrome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset / follow-up | Neurological features | Additional features | Age at last follow-up | Seizure Outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Seizure reduction | No effect | Wor- sening | |||||||||||||
| 10 | V423L/de novo | 1 d | OS | M, AP | T | SB→MF spikes | NA | NA/SD | Hypotonia | MC | 34 m (deceased) | Intractable | BR | B6, PP, MDZ, LEV, PHT, RGB, KD, CBZ, LCM | ||
| 11 | E999K/de novo | 1 d | OS→other | T | M, TCS | SB→beta→f spikes | N | NA/SD | Dystonia | Oculogyric crises | 5 y | Sz free (1 m, relapses with low PHT levels) | PHT | PB, B6, PP, VGB, TPM, LEV | ||
| 12 | Q1811E/de novo | 1 d | OS→other | T | GTCS, S, F | SB→Spikes l | N | NA/MD | Hypotonia, unsteady gait | ASD | 8 y | Sz free (4 y) | LTG + VPA + LEV | PHT, TPM | VGB | |
| 13 | M1548V/de novo | 1 d | OS→WS | T | GTC | SB→HA→slowing | N | NA/SD | Hypotonia | ASD | 18 m | Intractable | TPM | PB, PHT, B6, PP, LEV, VGB, CBZ | ||
| 14 | I237N/de novo | 1 d | other | F | F (variable onset) | MF spikes, slowing | HM | NA/SD | Hypotonia | Poor eye contact | 3 y 9 m | Intractable | VPA, CBZ | VGB, LEV, TPM, LTG, B6, PHT, PB, CLZ | ||
| 15 | V887A/de novo | 1 d | OS→WS | M | S | SB→HA | N | NA/SD | Hypotonia | 15 m | Sz free (6 m, relapse with low PHT levels) | PHT | TPM | PB,ST,CS | ||
| 16 | G882R/de novo | 1 d | EIMFS | unilateral TC r/l | T | MF spikes, ictal pattern r / l | N | NA/SD | Hypotonia | MC | 10 m | Intractable | PHT, LCM, ZNS | LEV, CS, B6, PP | ||
| 17 | I1640S/de novo | 1 d | Other | T | F, TC | Spikes r | NA | NA/MD | NAV | 9 y | Sz free (7 y) | LCM | LTG, TPM | B6, PB, VPA, LEV | ||
| 18 | K908E/de novo | 1 d | Other | M | S | Gen+ MF spikes, slowing | At | NA/SD | Nystagmus, hypotonia, dystonia | MC | 8 y | Sz free (7 y 6 m) | LEV, ZNS | |||
| 19 | R1882Q/unknown | 1 d | Other | NA | F →; C | MF + bil spikes, poly spikes | Subtle CD | NA/SD | N | MC | 10 y 6 m | Intractable | CBZ | PB, LEV, OXC, TPM, VPA, CLB, LTG, PHT | ||
| 20 | V1627M/de novo | 2 d | EIMFS | T r/l migrating | F, AP | MF spikes→N | N | NA/MID | Hypotonia | 14 m | Sz free (2 m) | VGB | LEV, B6, PP, TPM, PB,VPA | |||
| 21 | R856Q/de novo | 2 d | OS | T | T | SB→SW | Sinus thrombosis, ischaemia CC | NA/NA | NAV | Connatal sinus thrombosis | 3 m (deceased) | Intractable | MDZ | LEV, PB, PHT, B6, VGB, TPM | ||
| 22 | A1500T/de novo | 2 d | OS→ other | F, T | C | SB→spikes l te→slowing | HM, At | NA/SD | Spasticity | Poor eye contact, MC | 13 y | Sz free (3 m), relapse (12 m), sz free(13 m), relapse (5 y), sz free (10 y) | TPM (3 m), ACTH (13 m) | LTG, VPA | ||
| 23 | M1545V/de novo | 2 d | EIMFS | T, C r/l migrating | F, TCS | SB→MF spikes→N | N | NA/MID | Hypotonia | 12 m | Sz free (3 m, relapses with low PHT levels) | PHT→CBZ | LEV | PB, B6, PP, VPA | ||
| 24 | E430A/de novo | 2 d | Other | F | MF spikes | N | NA/SD | Hypotonia | Regression, ASD | 22 m | Sz free (12m) | PHT | TPM, CLB | |||
| 25 | S1536R/de novo | 2 d | Other | T | AP, SE, TCS | MF spikes, occ slowing | N | NA/MD | Hypotonia | 2 y 8 m | Sz free (6 m, relapses with low PHT levels) | PHT | TPM, PB, LEV, B6 | |||
| 26 | F1597L/de novo | 3 d | EIMFS | T r/l migrating | T→S | SB→spikes r/l te, slowing | At, calcifications | NA/SD | Dystonia | Dysautonomia, irritability | 3 y | Intractable | PHT, CBZ, LTG, BR | B6, PB, LEV, VGB, KD, ST, VPA, LCM, ZNS | ||
| 27 | V424L/de novo | 3 d | Other | F | TCS | SB→MF biocc, slowing | HM | NA/SD | Hypotonia | Poor eye contact | 4 y | Sz free (15 m) | CBZ | CS | PB, VPA | |
| 28 | I891T/de novo | 3 d | Other | T | MF spikes, bisynchrony | N | NA/MD | Coordination difficulties | ADS | 3 y | Sz free (3 m) | PHT | B6, PP, CBZ, CLZ, MDZ, TPM, VPA, ACTH | |||
| 29 | E999K/de novo | 3 d | Other | T r/l | SB→gen SW | At, HM | NA/SD | Dystonia | ASD, nystagmus | 22 y | Sz free (3 y) | CBZ | PB | |||
| 30 | G882E/de novo | 4 d | EIMFS | F, AU, HC r/l M, C migrating | T, AA, | MF spikes, slowing | At, HM | NA/SD | Dystonia | Dysautonomia | 8 y | Intractable | PHT, LCM | VPA, LEV, FBM, GBP, CLB, CLZ, MSX, TPM, PB, KD, CS, LI, ME | ||
| 31 | R1319Q/unknown | 5 d | Other | M | S | MF spikes, slowing | HM | NA/SD | Hypotonia, limb hypertonia | 14 m | Sz free (13 m) | ACTH | TPM, others | |||
| 32 | R1629H/de novo | 6 d | other | S | GTCS, FM | SW fr-ce→MF spikes | N | NA/SD | Hypotonia | 8 y | Sz free (4 m) | PHT | CLZ, MDZ, VPA, LEV, VGB, B6 | |||
| 33 | V423L/de novo | 6 d | OS | F | TCS, T r/l | SB→MF spikes, slowing | T2H | NA/SD | Spasticity | MC | 4 y | Intractable | OXC | PB, LEV, VGB, CS, ZNS, RUF, VPA, TPM, LTG | ||
| 34 | A263V/de novo | 3 w | other | S | T, GTC | Atypical HA→MF spikes, slowing | At, HM | N/SD | Spasticity | MC, scoliosis | 13 y (deceased) | Intractable | ACTH,NZP, CS,MDZ, CLB, LTG, VPA, CLZ,TPM | PB, PHT, TPM, VNS | ||
| 35 | F1651C mosaic/de novo | 6 w | other | GTCS | C, SE | MF spikes | N | N/MID | Hypotonia | 9 m | Sz free (3 m, relapses with low PHT levels) | PHT | PB, OXC, TPM, LEV, B6, PP | |||
| 36 | R1319Q/de novo | 2 m | other | GTC | FC | SW, slowing | HM | N/MD | N | ASD | 3 y 10 m | Sz free (8 m) | VGB | LEV | ||
| 37 | F895S/de novo | 2 m | other | S, M | C, GTC | SB→MF spikes | N | SD/SD | Hypotonia | Optic atrophy | 4 y 8 m | Intractable | VGB, PB, TPM, VPA, CLB | |||
AA = atypical absences; A = atonic; AB = absences; ADS = attention deficit disorder; ASD = autism spectrum disorder; AU = autonomic seizures; AP = apnoeic seizures; At = atrophy; Bifr = bifrontal; Bil = bilateral; C = clonic; CC = corpus callosum; CD = cortical dysplasia; Ce = central; DA = drop attacks; ED = epileptiform discharges; F = focal; FD = focal dyscognitive; FC = febrile convulsion; fr = frontal; Gen = generalized; GTC = generalized tonic-clonic; HA = hypsarrhythmia; HC = hemiclonic; HM = hypomyelination; IS = infantile spasms; L = left; m = months; MID = mild intellectual disability; MD = moderate intellectual disability; M = myoclonic; MC = microcephaly; MF = multifocal; N = normal; NA = not applicable; NAV = not available; NCSE = non-convulsive status epilepticus; Occ = occipital; OS = Ohtahara syndrome; Par = parietal; R = right; S = spasms; SE = status epilepticus; SB = suppression burst; SD = severe intellectual disability; SW = spike and waves; Sz = seizures; T = tonic; T2H = T2-hyperintensities; TCS = tonic-clonic seizures; Te = temporal; w = week; y = years; → = change to.
Treatment (sodium channel blockers are highlighted in bold): AZA = acetazolamide; B6 = vitamin B6; BR = bromide; CBZ = carbamazepine; CLB = clobazam; CLZ = clonazepam; CS = corticosteroids; ESM = ethosuximide; FBM = felbamate; GBP = gabapentin; IVIG = intravenous immunoglobulins; KD = ketogenic diet; LCM = lacosamide; LI = lidocaine; LTG = lamotrigine; LEV = levetiracetam; MDZ = Midazolam; ME = metilexine; MSX = mesuximide; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; PP = pyridoxal phosphate; RGB = retigabine; RUF = rufinamide; ST = sulthiame; STP = stiripentol; TPM = topiramate; VGB = vigabatrin; VNS = vagal nerve stimulation; VPA = valproate; ZNS = zonisamide.
Clinical characteristics and treatment response of the previously unpublished patients: encephalopathy with early onset epilepsy
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy syndrome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset / follow-up | Neurological features | Additional features | Age at last follow-up | Seizure Outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Seizure reduction | No effect | Wor- sening | |||||||||||||
| 10 | V423L/de novo | 1 d | OS | M, AP | T | SB→MF spikes | NA | NA/SD | Hypotonia | MC | 34 m (deceased) | Intractable | BR | B6, PP, MDZ, LEV, PHT, RGB, KD, CBZ, LCM | ||
| 11 | E999K/de novo | 1 d | OS→other | T | M, TCS | SB→beta→f spikes | N | NA/SD | Dystonia | Oculogyric crises | 5 y | Sz free (1 m, relapses with low PHT levels) | PHT | PB, B6, PP, VGB, TPM, LEV | ||
| 12 | Q1811E/de novo | 1 d | OS→other | T | GTCS, S, F | SB→Spikes l | N | NA/MD | Hypotonia, unsteady gait | ASD | 8 y | Sz free (4 y) | LTG + VPA + LEV | PHT, TPM | VGB | |
| 13 | M1548V/de novo | 1 d | OS→WS | T | GTC | SB→HA→slowing | N | NA/SD | Hypotonia | ASD | 18 m | Intractable | TPM | PB, PHT, B6, PP, LEV, VGB, CBZ | ||
| 14 | I237N/de novo | 1 d | other | F | F (variable onset) | MF spikes, slowing | HM | NA/SD | Hypotonia | Poor eye contact | 3 y 9 m | Intractable | VPA, CBZ | VGB, LEV, TPM, LTG, B6, PHT, PB, CLZ | ||
| 15 | V887A/de novo | 1 d | OS→WS | M | S | SB→HA | N | NA/SD | Hypotonia | 15 m | Sz free (6 m, relapse with low PHT levels) | PHT | TPM | PB,ST,CS | ||
| 16 | G882R/de novo | 1 d | EIMFS | unilateral TC r/l | T | MF spikes, ictal pattern r / l | N | NA/SD | Hypotonia | MC | 10 m | Intractable | PHT, LCM, ZNS | LEV, CS, B6, PP | ||
| 17 | I1640S/de novo | 1 d | Other | T | F, TC | Spikes r | NA | NA/MD | NAV | 9 y | Sz free (7 y) | LCM | LTG, TPM | B6, PB, VPA, LEV | ||
| 18 | K908E/de novo | 1 d | Other | M | S | Gen+ MF spikes, slowing | At | NA/SD | Nystagmus, hypotonia, dystonia | MC | 8 y | Sz free (7 y 6 m) | LEV, ZNS | |||
| 19 | R1882Q/unknown | 1 d | Other | NA | F →; C | MF + bil spikes, poly spikes | Subtle CD | NA/SD | N | MC | 10 y 6 m | Intractable | CBZ | PB, LEV, OXC, TPM, VPA, CLB, LTG, PHT | ||
| 20 | V1627M/de novo | 2 d | EIMFS | T r/l migrating | F, AP | MF spikes→N | N | NA/MID | Hypotonia | 14 m | Sz free (2 m) | VGB | LEV, B6, PP, TPM, PB,VPA | |||
| 21 | R856Q/de novo | 2 d | OS | T | T | SB→SW | Sinus thrombosis, ischaemia CC | NA/NA | NAV | Connatal sinus thrombosis | 3 m (deceased) | Intractable | MDZ | LEV, PB, PHT, B6, VGB, TPM | ||
| 22 | A1500T/de novo | 2 d | OS→ other | F, T | C | SB→spikes l te→slowing | HM, At | NA/SD | Spasticity | Poor eye contact, MC | 13 y | Sz free (3 m), relapse (12 m), sz free(13 m), relapse (5 y), sz free (10 y) | TPM (3 m), ACTH (13 m) | LTG, VPA | ||
| 23 | M1545V/de novo | 2 d | EIMFS | T, C r/l migrating | F, TCS | SB→MF spikes→N | N | NA/MID | Hypotonia | 12 m | Sz free (3 m, relapses with low PHT levels) | PHT→CBZ | LEV | PB, B6, PP, VPA | ||
| 24 | E430A/de novo | 2 d | Other | F | MF spikes | N | NA/SD | Hypotonia | Regression, ASD | 22 m | Sz free (12m) | PHT | TPM, CLB | |||
| 25 | S1536R/de novo | 2 d | Other | T | AP, SE, TCS | MF spikes, occ slowing | N | NA/MD | Hypotonia | 2 y 8 m | Sz free (6 m, relapses with low PHT levels) | PHT | TPM, PB, LEV, B6 | |||
| 26 | F1597L/de novo | 3 d | EIMFS | T r/l migrating | T→S | SB→spikes r/l te, slowing | At, calcifications | NA/SD | Dystonia | Dysautonomia, irritability | 3 y | Intractable | PHT, CBZ, LTG, BR | B6, PB, LEV, VGB, KD, ST, VPA, LCM, ZNS | ||
| 27 | V424L/de novo | 3 d | Other | F | TCS | SB→MF biocc, slowing | HM | NA/SD | Hypotonia | Poor eye contact | 4 y | Sz free (15 m) | CBZ | CS | PB, VPA | |
| 28 | I891T/de novo | 3 d | Other | T | MF spikes, bisynchrony | N | NA/MD | Coordination difficulties | ADS | 3 y | Sz free (3 m) | PHT | B6, PP, CBZ, CLZ, MDZ, TPM, VPA, ACTH | |||
| 29 | E999K/de novo | 3 d | Other | T r/l | SB→gen SW | At, HM | NA/SD | Dystonia | ASD, nystagmus | 22 y | Sz free (3 y) | CBZ | PB | |||
| 30 | G882E/de novo | 4 d | EIMFS | F, AU, HC r/l M, C migrating | T, AA, | MF spikes, slowing | At, HM | NA/SD | Dystonia | Dysautonomia | 8 y | Intractable | PHT, LCM | VPA, LEV, FBM, GBP, CLB, CLZ, MSX, TPM, PB, KD, CS, LI, ME | ||
| 31 | R1319Q/unknown | 5 d | Other | M | S | MF spikes, slowing | HM | NA/SD | Hypotonia, limb hypertonia | 14 m | Sz free (13 m) | ACTH | TPM, others | |||
| 32 | R1629H/de novo | 6 d | other | S | GTCS, FM | SW fr-ce→MF spikes | N | NA/SD | Hypotonia | 8 y | Sz free (4 m) | PHT | CLZ, MDZ, VPA, LEV, VGB, B6 | |||
| 33 | V423L/de novo | 6 d | OS | F | TCS, T r/l | SB→MF spikes, slowing | T2H | NA/SD | Spasticity | MC | 4 y | Intractable | OXC | PB, LEV, VGB, CS, ZNS, RUF, VPA, TPM, LTG | ||
| 34 | A263V/de novo | 3 w | other | S | T, GTC | Atypical HA→MF spikes, slowing | At, HM | N/SD | Spasticity | MC, scoliosis | 13 y (deceased) | Intractable | ACTH,NZP, CS,MDZ, CLB, LTG, VPA, CLZ,TPM | PB, PHT, TPM, VNS | ||
| 35 | F1651C mosaic/de novo | 6 w | other | GTCS | C, SE | MF spikes | N | N/MID | Hypotonia | 9 m | Sz free (3 m, relapses with low PHT levels) | PHT | PB, OXC, TPM, LEV, B6, PP | |||
| 36 | R1319Q/de novo | 2 m | other | GTC | FC | SW, slowing | HM | N/MD | N | ASD | 3 y 10 m | Sz free (8 m) | VGB | LEV | ||
| 37 | F895S/de novo | 2 m | other | S, M | C, GTC | SB→MF spikes | N | SD/SD | Hypotonia | Optic atrophy | 4 y 8 m | Intractable | VGB, PB, TPM, VPA, CLB | |||
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy syndrome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset / follow-up | Neurological features | Additional features | Age at last follow-up | Seizure Outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Seizure reduction | No effect | Wor- sening | |||||||||||||
| 10 | V423L/de novo | 1 d | OS | M, AP | T | SB→MF spikes | NA | NA/SD | Hypotonia | MC | 34 m (deceased) | Intractable | BR | B6, PP, MDZ, LEV, PHT, RGB, KD, CBZ, LCM | ||
| 11 | E999K/de novo | 1 d | OS→other | T | M, TCS | SB→beta→f spikes | N | NA/SD | Dystonia | Oculogyric crises | 5 y | Sz free (1 m, relapses with low PHT levels) | PHT | PB, B6, PP, VGB, TPM, LEV | ||
| 12 | Q1811E/de novo | 1 d | OS→other | T | GTCS, S, F | SB→Spikes l | N | NA/MD | Hypotonia, unsteady gait | ASD | 8 y | Sz free (4 y) | LTG + VPA + LEV | PHT, TPM | VGB | |
| 13 | M1548V/de novo | 1 d | OS→WS | T | GTC | SB→HA→slowing | N | NA/SD | Hypotonia | ASD | 18 m | Intractable | TPM | PB, PHT, B6, PP, LEV, VGB, CBZ | ||
| 14 | I237N/de novo | 1 d | other | F | F (variable onset) | MF spikes, slowing | HM | NA/SD | Hypotonia | Poor eye contact | 3 y 9 m | Intractable | VPA, CBZ | VGB, LEV, TPM, LTG, B6, PHT, PB, CLZ | ||
| 15 | V887A/de novo | 1 d | OS→WS | M | S | SB→HA | N | NA/SD | Hypotonia | 15 m | Sz free (6 m, relapse with low PHT levels) | PHT | TPM | PB,ST,CS | ||
| 16 | G882R/de novo | 1 d | EIMFS | unilateral TC r/l | T | MF spikes, ictal pattern r / l | N | NA/SD | Hypotonia | MC | 10 m | Intractable | PHT, LCM, ZNS | LEV, CS, B6, PP | ||
| 17 | I1640S/de novo | 1 d | Other | T | F, TC | Spikes r | NA | NA/MD | NAV | 9 y | Sz free (7 y) | LCM | LTG, TPM | B6, PB, VPA, LEV | ||
| 18 | K908E/de novo | 1 d | Other | M | S | Gen+ MF spikes, slowing | At | NA/SD | Nystagmus, hypotonia, dystonia | MC | 8 y | Sz free (7 y 6 m) | LEV, ZNS | |||
| 19 | R1882Q/unknown | 1 d | Other | NA | F →; C | MF + bil spikes, poly spikes | Subtle CD | NA/SD | N | MC | 10 y 6 m | Intractable | CBZ | PB, LEV, OXC, TPM, VPA, CLB, LTG, PHT | ||
| 20 | V1627M/de novo | 2 d | EIMFS | T r/l migrating | F, AP | MF spikes→N | N | NA/MID | Hypotonia | 14 m | Sz free (2 m) | VGB | LEV, B6, PP, TPM, PB,VPA | |||
| 21 | R856Q/de novo | 2 d | OS | T | T | SB→SW | Sinus thrombosis, ischaemia CC | NA/NA | NAV | Connatal sinus thrombosis | 3 m (deceased) | Intractable | MDZ | LEV, PB, PHT, B6, VGB, TPM | ||
| 22 | A1500T/de novo | 2 d | OS→ other | F, T | C | SB→spikes l te→slowing | HM, At | NA/SD | Spasticity | Poor eye contact, MC | 13 y | Sz free (3 m), relapse (12 m), sz free(13 m), relapse (5 y), sz free (10 y) | TPM (3 m), ACTH (13 m) | LTG, VPA | ||
| 23 | M1545V/de novo | 2 d | EIMFS | T, C r/l migrating | F, TCS | SB→MF spikes→N | N | NA/MID | Hypotonia | 12 m | Sz free (3 m, relapses with low PHT levels) | PHT→CBZ | LEV | PB, B6, PP, VPA | ||
| 24 | E430A/de novo | 2 d | Other | F | MF spikes | N | NA/SD | Hypotonia | Regression, ASD | 22 m | Sz free (12m) | PHT | TPM, CLB | |||
| 25 | S1536R/de novo | 2 d | Other | T | AP, SE, TCS | MF spikes, occ slowing | N | NA/MD | Hypotonia | 2 y 8 m | Sz free (6 m, relapses with low PHT levels) | PHT | TPM, PB, LEV, B6 | |||
| 26 | F1597L/de novo | 3 d | EIMFS | T r/l migrating | T→S | SB→spikes r/l te, slowing | At, calcifications | NA/SD | Dystonia | Dysautonomia, irritability | 3 y | Intractable | PHT, CBZ, LTG, BR | B6, PB, LEV, VGB, KD, ST, VPA, LCM, ZNS | ||
| 27 | V424L/de novo | 3 d | Other | F | TCS | SB→MF biocc, slowing | HM | NA/SD | Hypotonia | Poor eye contact | 4 y | Sz free (15 m) | CBZ | CS | PB, VPA | |
| 28 | I891T/de novo | 3 d | Other | T | MF spikes, bisynchrony | N | NA/MD | Coordination difficulties | ADS | 3 y | Sz free (3 m) | PHT | B6, PP, CBZ, CLZ, MDZ, TPM, VPA, ACTH | |||
| 29 | E999K/de novo | 3 d | Other | T r/l | SB→gen SW | At, HM | NA/SD | Dystonia | ASD, nystagmus | 22 y | Sz free (3 y) | CBZ | PB | |||
| 30 | G882E/de novo | 4 d | EIMFS | F, AU, HC r/l M, C migrating | T, AA, | MF spikes, slowing | At, HM | NA/SD | Dystonia | Dysautonomia | 8 y | Intractable | PHT, LCM | VPA, LEV, FBM, GBP, CLB, CLZ, MSX, TPM, PB, KD, CS, LI, ME | ||
| 31 | R1319Q/unknown | 5 d | Other | M | S | MF spikes, slowing | HM | NA/SD | Hypotonia, limb hypertonia | 14 m | Sz free (13 m) | ACTH | TPM, others | |||
| 32 | R1629H/de novo | 6 d | other | S | GTCS, FM | SW fr-ce→MF spikes | N | NA/SD | Hypotonia | 8 y | Sz free (4 m) | PHT | CLZ, MDZ, VPA, LEV, VGB, B6 | |||
| 33 | V423L/de novo | 6 d | OS | F | TCS, T r/l | SB→MF spikes, slowing | T2H | NA/SD | Spasticity | MC | 4 y | Intractable | OXC | PB, LEV, VGB, CS, ZNS, RUF, VPA, TPM, LTG | ||
| 34 | A263V/de novo | 3 w | other | S | T, GTC | Atypical HA→MF spikes, slowing | At, HM | N/SD | Spasticity | MC, scoliosis | 13 y (deceased) | Intractable | ACTH,NZP, CS,MDZ, CLB, LTG, VPA, CLZ,TPM | PB, PHT, TPM, VNS | ||
| 35 | F1651C mosaic/de novo | 6 w | other | GTCS | C, SE | MF spikes | N | N/MID | Hypotonia | 9 m | Sz free (3 m, relapses with low PHT levels) | PHT | PB, OXC, TPM, LEV, B6, PP | |||
| 36 | R1319Q/de novo | 2 m | other | GTC | FC | SW, slowing | HM | N/MD | N | ASD | 3 y 10 m | Sz free (8 m) | VGB | LEV | ||
| 37 | F895S/de novo | 2 m | other | S, M | C, GTC | SB→MF spikes | N | SD/SD | Hypotonia | Optic atrophy | 4 y 8 m | Intractable | VGB, PB, TPM, VPA, CLB | |||
AA = atypical absences; A = atonic; AB = absences; ADS = attention deficit disorder; ASD = autism spectrum disorder; AU = autonomic seizures; AP = apnoeic seizures; At = atrophy; Bifr = bifrontal; Bil = bilateral; C = clonic; CC = corpus callosum; CD = cortical dysplasia; Ce = central; DA = drop attacks; ED = epileptiform discharges; F = focal; FD = focal dyscognitive; FC = febrile convulsion; fr = frontal; Gen = generalized; GTC = generalized tonic-clonic; HA = hypsarrhythmia; HC = hemiclonic; HM = hypomyelination; IS = infantile spasms; L = left; m = months; MID = mild intellectual disability; MD = moderate intellectual disability; M = myoclonic; MC = microcephaly; MF = multifocal; N = normal; NA = not applicable; NAV = not available; NCSE = non-convulsive status epilepticus; Occ = occipital; OS = Ohtahara syndrome; Par = parietal; R = right; S = spasms; SE = status epilepticus; SB = suppression burst; SD = severe intellectual disability; SW = spike and waves; Sz = seizures; T = tonic; T2H = T2-hyperintensities; TCS = tonic-clonic seizures; Te = temporal; w = week; y = years; → = change to.
Treatment (sodium channel blockers are highlighted in bold): AZA = acetazolamide; B6 = vitamin B6; BR = bromide; CBZ = carbamazepine; CLB = clobazam; CLZ = clonazepam; CS = corticosteroids; ESM = ethosuximide; FBM = felbamate; GBP = gabapentin; IVIG = intravenous immunoglobulins; KD = ketogenic diet; LCM = lacosamide; LI = lidocaine; LTG = lamotrigine; LEV = levetiracetam; MDZ = Midazolam; ME = metilexine; MSX = mesuximide; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; PP = pyridoxal phosphate; RGB = retigabine; RUF = rufinamide; ST = sulthiame; STP = stiripentol; TPM = topiramate; VGB = vigabatrin; VNS = vagal nerve stimulation; VPA = valproate; ZNS = zonisamide.
Clinical characteristics and treatment response of the previously unpublished patients: encephalopathy with late onset epilepsy
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy syndrome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset /follow-up | Neurological features | Additional features | Age at last follow-up | Seizure outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Sz reduction | No effect | Wors- ening | |||||||||||||
| 38 | G899S/de novo | 3 m | Other | HC | GTC, FD, AA | Bifr SW | N | NA/SD | N | ASD | 7 y | Intractable | TPM, LEV, RUF, CLZ, CLB | PB, B6, VPA, LCM, ZNS, KD | OXC | |
| 39 | T227I/de novo | 3 m | WS | T, AP | S | HA→post spikes, slowing | N | SD/SD | Hypotonia | MC | 2 y | Intractable | LEV, ZNS | B6, VGB, CS, ACTH, TPM, KD, PB, OXC | ||
| 40 | A733T/de novo | 3 m | Other | HC r/l | AA, DA, FD | MF spikes, slowing | N | MD/MD | N | 12 y | Intractable | LEV | VPA, ESM, LTG, OXC | |||
| 41 | R1882P/de novo | 4 m | Other | T, C r | MF spikes, SW- status te→ESES-like | N | N/SD | N | Regression, ASD, aggression | 6 y | Sz free (8 m) | LEV | PB, VPA, ST, KD, LTG | |||
| 42 | L1665F/de novo | 4 m | Other | TS, SE | GTC (series) | N | N | N/SD | N | Stereotyped behaviour | 6 y 3 m | Sz free (7 m) | CBZ | VPA | PB | |
| 43 | L1342P/de novo | 6 m | WS | S | HA→MF spikes, slowing | At | SD/SD | Axial hypotonia, limb spasticity | Apnoeas, no eye contact | 16 y | Intractable | VGB, CS | ||||
| 44 | L881P/de novo | 6 m | WS→LGS | S | T, TC, AA | HA→MF spikes | At, HM, cerebellar at | SD/SD | Spasticity, hemiparesis | Small stature, early puberty | 18 y | Intractable | TPM, MDZ, CLB | VPA, LTG, PB, LEV, VGB, KD | RUF | |
| 45 | I1281F/de novo | 7 m | WS→LGS | S | T, TC | HA→MF spikes, slowing, diffuse SW | At | NA/SD | 16 y | Intractable | VNS, VPA, CLZ, RUF, TPM, LTG | |||||
| 46 | R853Q/de novo | 8 m | WS→LGS | S | AA, T, F (4 y) | HA→for bil spikes, SW, Slowing | T2H, at | N/SD | Dystonia | Preterm 28 w, MC, regression | 6 y 6 m | Intractable | ACTH | VPA, CLB, TPM | LTG, FBM, LEV | CBZ |
| 47 | A1652P/de novo | 9 m | WS | S | atypical HA→ slowing | HM | SD/SD | Hypotonia | ASD | 3 y | Intractable | VGB, LEV, NZP | VPA, TPM, CS | PHT | ||
| 48 | R1319W/de novo | 10 m | WS→LGS | T, S | TCS, A, AA | HA→spikes occ →spikes cue-par r | N | SD/SD | Hypotonia | Diabetes, ASD | 10 y | Sz free (7 y) | CBZ, TPM, ESM, ZNS, VPA, FBM, LEV, B6, KD, CS, LTG | |||
| 49 | E1211K / de novo | 11 m | WS→other | S | FC, SE, M | HA→MF spikes, slowing | N | SD/SD | Hypotonia | 4 y | Intractable | LEV, LTG, PB, KD | ST, VGB, CS | |||
| 50 | R853Q/de novo | 13 m | WS | S | T, AU, M | HA→MF spikes, ESES-like | N | MD/SD | Hypotonia, choreo-athetosis | 8 y | Intractable | VGB, PB, CLB | ST, TPM, LEV, ZNS, ESM, LTG, PHT, OXC, CS, KD,AZA | |||
| 51 | H930Q/de novo | 15 m | MAE | TCS | A, MAS, T, AA | slowing occ | N | N/MD | N | ASD | 6 y | Sz free (18 m) | LEV + TPM | VPA, OXC, CLB | ||
| 52 | P1622S/de novo | 2 y | MAE | MA, DA | T, AA, M | Spike-slow-waves te-par bil | N | MD/MD | Ataxia | ASD, MC | 3 y | Intractable | TPM | LEV, ESM, B6, PB, CLB, VGB, PP, KD | OXC, LTG | |
| 53 | F612S/de novo | 2 y 6 m | Other | TCS | M | fr spikes r/l, fr delta | N | MD/MD | N | 3 y | Intractable | CLB, LEV, RUF | ||||
| 54 | c.605 + 1G > T/ de novo | 2 y 6 m | Other | TCS | T, A | midline spikes ce, slowing→ bitemp spikes | N | N/SD | Hypotonia | ASD, regression | 7 y | Intractable | LEV, CLB, KD | ZNS, LTG, FBM, TPM, RUF, B6, IVIG, VPA, PB, CS | ||
| 55 | V1528Cfs*7/de novo | 3 y | LGS | TCS | T, SE | Spike-slow-waves, Beta (sleep) | N | SD/SD | Spasticity | ASD, MC | 9 y | Sz free (6 y) | VPA + LTG | CLZ, ESM | ||
| 56 | R853Q/unknown | 3 y | Other | TS | S | HA | CC hypoplasia | SD/SD | Pyramidal signs, hand dystonia | Arachnodactyly | 25 y | Intractable | VPA, ACTH | |||
| 57 | C1170Vfs*15/de novo | 3 y | Other | TCS | M, AB | gen SW, l fr SW, high voltage theta | HiS | MD/SD | Hypertonic limbs | ASD | 17 y | Intractable | VPA, LTG, Br, LEV, CLB | CBZ, OXC, TPM, STP, ST, KD | ||
| 58 | G1223R/de novo | 3 y | Other | F, M | TCS, M, A, AA, NCSE | gen SW, PSW, slowing | N | N/MD | Ataxia | Regression | 19 y | Intractable | VPA, CLZ, CLB, LTG, LEV | PHT, PB, CBZ, TPM, VNS, CS | ||
| 59 | R1235*/de novo | 3 y 4 m | Other | FC | GTC, DA | gen SW, PSW | HM | MD/MD | N | ASD | 14 y | Intractable | LEV, ZNS | VPA, CLB, LTG | ||
| 60 | A1773V/de novo | 3 y 6 m | Other | F | Sharp waves r fr (sleep), slowing | N | MD/SD | N | ASD | 4 y | Sz free (4 y) | LEV | ||||
| 61 | K1933M/de novo | 4 y | Other | F, TCS | AA | MF spikes, bil SW→ESES-like | N | SD/SD | Ataxia, parkinsonian gait | ASD, hyperkinetic and aggressive behaviour | 17 y | Intractable | ST, VPA, TPM, CLB, CS | LTG, LCM | CBZ | |
| 62 | c.698‐1G>T, splice site/de novo | 4 y 6 m | Other | F | f spikes→MF, ESES-like→N | N | N/MID | N | 10 y | Sz free (9 y) | TPM | others | ||||
| 63 | W1716*/de novo | 4 y 7 m | Other | Febrile T (cluster) | AA | Gen SW | N | MD/MD | N | Psychosis (17 y) | 25 y | Sz free (9 y) | VPA | PB | CBZ | |
| 64 | N503Kfs*19/de novo | 6 y | Other | TCS (cluster) | Bil sharp waves | N | SD/SD | ASD | 20 y | Sz free (6 y) | VPA | |||||
| 65 | W281*/de novo | 7y | Other | F | sec. Gen. TCS | MF spikes→ESES- like | N | MD/MD | Clumsiness | 13 y | Sz free (10 y) | ST | ||||
| 66 | S1656F/de novo | 8 y 11 m | LGS | GTC | AA | Bifr SW, slowing | N | MD/MD | Hypotonia, crouched gait | Agitation | 12 y | Intractable | LLTG, VPA | TTPM | ||
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy syndrome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset /follow-up | Neurological features | Additional features | Age at last follow-up | Seizure outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Sz reduction | No effect | Wors- ening | |||||||||||||
| 38 | G899S/de novo | 3 m | Other | HC | GTC, FD, AA | Bifr SW | N | NA/SD | N | ASD | 7 y | Intractable | TPM, LEV, RUF, CLZ, CLB | PB, B6, VPA, LCM, ZNS, KD | OXC | |
| 39 | T227I/de novo | 3 m | WS | T, AP | S | HA→post spikes, slowing | N | SD/SD | Hypotonia | MC | 2 y | Intractable | LEV, ZNS | B6, VGB, CS, ACTH, TPM, KD, PB, OXC | ||
| 40 | A733T/de novo | 3 m | Other | HC r/l | AA, DA, FD | MF spikes, slowing | N | MD/MD | N | 12 y | Intractable | LEV | VPA, ESM, LTG, OXC | |||
| 41 | R1882P/de novo | 4 m | Other | T, C r | MF spikes, SW- status te→ESES-like | N | N/SD | N | Regression, ASD, aggression | 6 y | Sz free (8 m) | LEV | PB, VPA, ST, KD, LTG | |||
| 42 | L1665F/de novo | 4 m | Other | TS, SE | GTC (series) | N | N | N/SD | N | Stereotyped behaviour | 6 y 3 m | Sz free (7 m) | CBZ | VPA | PB | |
| 43 | L1342P/de novo | 6 m | WS | S | HA→MF spikes, slowing | At | SD/SD | Axial hypotonia, limb spasticity | Apnoeas, no eye contact | 16 y | Intractable | VGB, CS | ||||
| 44 | L881P/de novo | 6 m | WS→LGS | S | T, TC, AA | HA→MF spikes | At, HM, cerebellar at | SD/SD | Spasticity, hemiparesis | Small stature, early puberty | 18 y | Intractable | TPM, MDZ, CLB | VPA, LTG, PB, LEV, VGB, KD | RUF | |
| 45 | I1281F/de novo | 7 m | WS→LGS | S | T, TC | HA→MF spikes, slowing, diffuse SW | At | NA/SD | 16 y | Intractable | VNS, VPA, CLZ, RUF, TPM, LTG | |||||
| 46 | R853Q/de novo | 8 m | WS→LGS | S | AA, T, F (4 y) | HA→for bil spikes, SW, Slowing | T2H, at | N/SD | Dystonia | Preterm 28 w, MC, regression | 6 y 6 m | Intractable | ACTH | VPA, CLB, TPM | LTG, FBM, LEV | CBZ |
| 47 | A1652P/de novo | 9 m | WS | S | atypical HA→ slowing | HM | SD/SD | Hypotonia | ASD | 3 y | Intractable | VGB, LEV, NZP | VPA, TPM, CS | PHT | ||
| 48 | R1319W/de novo | 10 m | WS→LGS | T, S | TCS, A, AA | HA→spikes occ →spikes cue-par r | N | SD/SD | Hypotonia | Diabetes, ASD | 10 y | Sz free (7 y) | CBZ, TPM, ESM, ZNS, VPA, FBM, LEV, B6, KD, CS, LTG | |||
| 49 | E1211K / de novo | 11 m | WS→other | S | FC, SE, M | HA→MF spikes, slowing | N | SD/SD | Hypotonia | 4 y | Intractable | LEV, LTG, PB, KD | ST, VGB, CS | |||
| 50 | R853Q/de novo | 13 m | WS | S | T, AU, M | HA→MF spikes, ESES-like | N | MD/SD | Hypotonia, choreo-athetosis | 8 y | Intractable | VGB, PB, CLB | ST, TPM, LEV, ZNS, ESM, LTG, PHT, OXC, CS, KD,AZA | |||
| 51 | H930Q/de novo | 15 m | MAE | TCS | A, MAS, T, AA | slowing occ | N | N/MD | N | ASD | 6 y | Sz free (18 m) | LEV + TPM | VPA, OXC, CLB | ||
| 52 | P1622S/de novo | 2 y | MAE | MA, DA | T, AA, M | Spike-slow-waves te-par bil | N | MD/MD | Ataxia | ASD, MC | 3 y | Intractable | TPM | LEV, ESM, B6, PB, CLB, VGB, PP, KD | OXC, LTG | |
| 53 | F612S/de novo | 2 y 6 m | Other | TCS | M | fr spikes r/l, fr delta | N | MD/MD | N | 3 y | Intractable | CLB, LEV, RUF | ||||
| 54 | c.605 + 1G > T/ de novo | 2 y 6 m | Other | TCS | T, A | midline spikes ce, slowing→ bitemp spikes | N | N/SD | Hypotonia | ASD, regression | 7 y | Intractable | LEV, CLB, KD | ZNS, LTG, FBM, TPM, RUF, B6, IVIG, VPA, PB, CS | ||
| 55 | V1528Cfs*7/de novo | 3 y | LGS | TCS | T, SE | Spike-slow-waves, Beta (sleep) | N | SD/SD | Spasticity | ASD, MC | 9 y | Sz free (6 y) | VPA + LTG | CLZ, ESM | ||
| 56 | R853Q/unknown | 3 y | Other | TS | S | HA | CC hypoplasia | SD/SD | Pyramidal signs, hand dystonia | Arachnodactyly | 25 y | Intractable | VPA, ACTH | |||
| 57 | C1170Vfs*15/de novo | 3 y | Other | TCS | M, AB | gen SW, l fr SW, high voltage theta | HiS | MD/SD | Hypertonic limbs | ASD | 17 y | Intractable | VPA, LTG, Br, LEV, CLB | CBZ, OXC, TPM, STP, ST, KD | ||
| 58 | G1223R/de novo | 3 y | Other | F, M | TCS, M, A, AA, NCSE | gen SW, PSW, slowing | N | N/MD | Ataxia | Regression | 19 y | Intractable | VPA, CLZ, CLB, LTG, LEV | PHT, PB, CBZ, TPM, VNS, CS | ||
| 59 | R1235*/de novo | 3 y 4 m | Other | FC | GTC, DA | gen SW, PSW | HM | MD/MD | N | ASD | 14 y | Intractable | LEV, ZNS | VPA, CLB, LTG | ||
| 60 | A1773V/de novo | 3 y 6 m | Other | F | Sharp waves r fr (sleep), slowing | N | MD/SD | N | ASD | 4 y | Sz free (4 y) | LEV | ||||
| 61 | K1933M/de novo | 4 y | Other | F, TCS | AA | MF spikes, bil SW→ESES-like | N | SD/SD | Ataxia, parkinsonian gait | ASD, hyperkinetic and aggressive behaviour | 17 y | Intractable | ST, VPA, TPM, CLB, CS | LTG, LCM | CBZ | |
| 62 | c.698‐1G>T, splice site/de novo | 4 y 6 m | Other | F | f spikes→MF, ESES-like→N | N | N/MID | N | 10 y | Sz free (9 y) | TPM | others | ||||
| 63 | W1716*/de novo | 4 y 7 m | Other | Febrile T (cluster) | AA | Gen SW | N | MD/MD | N | Psychosis (17 y) | 25 y | Sz free (9 y) | VPA | PB | CBZ | |
| 64 | N503Kfs*19/de novo | 6 y | Other | TCS (cluster) | Bil sharp waves | N | SD/SD | ASD | 20 y | Sz free (6 y) | VPA | |||||
| 65 | W281*/de novo | 7y | Other | F | sec. Gen. TCS | MF spikes→ESES- like | N | MD/MD | Clumsiness | 13 y | Sz free (10 y) | ST | ||||
| 66 | S1656F/de novo | 8 y 11 m | LGS | GTC | AA | Bifr SW, slowing | N | MD/MD | Hypotonia, crouched gait | Agitation | 12 y | Intractable | LLTG, VPA | TTPM | ||
AA = atypical absences; A = atonic; AB = absences; ADS = attention deficit disorder; ASD = autism spectrum disorder; AU = autonomic seizures; AP = apneic seizures; At = atrophy; Bifr = bifrontal; Bil = bilateral; C = clonic; CC = corpus callosum; Ce = central; DA = drop attacks; ED = epileptiform discharges; F = focal; FD = focal dyscognitive; FC = febrile convulsion; fr = frontal; Gen = generalized; GTC = generalized tonic-clonic; HA = hypsarrhythmia; HC = hemiclonic; HiS = hippocampal sclerosis; HM = hypomyelination; IS = infantile spasms; L = left; LGS = Lennox-Gastaut syndrome; MAS = myoclonic-atonic seizures; = MAE = myoclonic-atonic epilepsy; m = months; MID = mild intellectual disability; MD = moderate intellectual disability; M = myoclonic; MC = microcephaly; MF = multifocal; N = normal; NA = not applicable; NAV = not available; NCSE = non-convulsive status epilepticus; Occ = occipital; Par = parietal; R = right; S = spasms; SE = status epilepticus; SD = severe intellectual disability; SW = spike and waves; Sz = seizures; T = tonic; T2H = T2-hyperintensities; TCS = tonic-clonic seizures; Te = temporal; w = week; WS = West syndrome; y = years;→ = change to.
Treatment (sodium channel blockers are highlighted in bold): AZA = acetazolamide; B6 = vitamin B6; BR = bromide; CBZ = carbamazepine; CLB = clobazam; CLZ = clonazepam; CS = corticosteroids; ESM = ethosuximide; FBM = felbamate; GBP = gabapentin; IVIG = intravenous immunoglobulins; KD = ketogenic diet; LCM = lacosamide; LTG = lamotrigine; LEV = levetiracetam; MDZ = midazolam; MSX = mesuximide; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; PP = pyridoxal phosphate; RGB = retigabine; RUF = rufinamide; ST = sulthiame; STP = stiripentol; TPM = topiramate; VGB = vigabatrin; VNS = vagal nerve stimulation; VPA = valproate; ZNS = zonisamide.
Clinical characteristics and treatment response of the previously unpublished patients: encephalopathy with late onset epilepsy
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy syndrome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset /follow-up | Neurological features | Additional features | Age at last follow-up | Seizure outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Sz reduction | No effect | Wors- ening | |||||||||||||
| 38 | G899S/de novo | 3 m | Other | HC | GTC, FD, AA | Bifr SW | N | NA/SD | N | ASD | 7 y | Intractable | TPM, LEV, RUF, CLZ, CLB | PB, B6, VPA, LCM, ZNS, KD | OXC | |
| 39 | T227I/de novo | 3 m | WS | T, AP | S | HA→post spikes, slowing | N | SD/SD | Hypotonia | MC | 2 y | Intractable | LEV, ZNS | B6, VGB, CS, ACTH, TPM, KD, PB, OXC | ||
| 40 | A733T/de novo | 3 m | Other | HC r/l | AA, DA, FD | MF spikes, slowing | N | MD/MD | N | 12 y | Intractable | LEV | VPA, ESM, LTG, OXC | |||
| 41 | R1882P/de novo | 4 m | Other | T, C r | MF spikes, SW- status te→ESES-like | N | N/SD | N | Regression, ASD, aggression | 6 y | Sz free (8 m) | LEV | PB, VPA, ST, KD, LTG | |||
| 42 | L1665F/de novo | 4 m | Other | TS, SE | GTC (series) | N | N | N/SD | N | Stereotyped behaviour | 6 y 3 m | Sz free (7 m) | CBZ | VPA | PB | |
| 43 | L1342P/de novo | 6 m | WS | S | HA→MF spikes, slowing | At | SD/SD | Axial hypotonia, limb spasticity | Apnoeas, no eye contact | 16 y | Intractable | VGB, CS | ||||
| 44 | L881P/de novo | 6 m | WS→LGS | S | T, TC, AA | HA→MF spikes | At, HM, cerebellar at | SD/SD | Spasticity, hemiparesis | Small stature, early puberty | 18 y | Intractable | TPM, MDZ, CLB | VPA, LTG, PB, LEV, VGB, KD | RUF | |
| 45 | I1281F/de novo | 7 m | WS→LGS | S | T, TC | HA→MF spikes, slowing, diffuse SW | At | NA/SD | 16 y | Intractable | VNS, VPA, CLZ, RUF, TPM, LTG | |||||
| 46 | R853Q/de novo | 8 m | WS→LGS | S | AA, T, F (4 y) | HA→for bil spikes, SW, Slowing | T2H, at | N/SD | Dystonia | Preterm 28 w, MC, regression | 6 y 6 m | Intractable | ACTH | VPA, CLB, TPM | LTG, FBM, LEV | CBZ |
| 47 | A1652P/de novo | 9 m | WS | S | atypical HA→ slowing | HM | SD/SD | Hypotonia | ASD | 3 y | Intractable | VGB, LEV, NZP | VPA, TPM, CS | PHT | ||
| 48 | R1319W/de novo | 10 m | WS→LGS | T, S | TCS, A, AA | HA→spikes occ →spikes cue-par r | N | SD/SD | Hypotonia | Diabetes, ASD | 10 y | Sz free (7 y) | CBZ, TPM, ESM, ZNS, VPA, FBM, LEV, B6, KD, CS, LTG | |||
| 49 | E1211K / de novo | 11 m | WS→other | S | FC, SE, M | HA→MF spikes, slowing | N | SD/SD | Hypotonia | 4 y | Intractable | LEV, LTG, PB, KD | ST, VGB, CS | |||
| 50 | R853Q/de novo | 13 m | WS | S | T, AU, M | HA→MF spikes, ESES-like | N | MD/SD | Hypotonia, choreo-athetosis | 8 y | Intractable | VGB, PB, CLB | ST, TPM, LEV, ZNS, ESM, LTG, PHT, OXC, CS, KD,AZA | |||
| 51 | H930Q/de novo | 15 m | MAE | TCS | A, MAS, T, AA | slowing occ | N | N/MD | N | ASD | 6 y | Sz free (18 m) | LEV + TPM | VPA, OXC, CLB | ||
| 52 | P1622S/de novo | 2 y | MAE | MA, DA | T, AA, M | Spike-slow-waves te-par bil | N | MD/MD | Ataxia | ASD, MC | 3 y | Intractable | TPM | LEV, ESM, B6, PB, CLB, VGB, PP, KD | OXC, LTG | |
| 53 | F612S/de novo | 2 y 6 m | Other | TCS | M | fr spikes r/l, fr delta | N | MD/MD | N | 3 y | Intractable | CLB, LEV, RUF | ||||
| 54 | c.605 + 1G > T/ de novo | 2 y 6 m | Other | TCS | T, A | midline spikes ce, slowing→ bitemp spikes | N | N/SD | Hypotonia | ASD, regression | 7 y | Intractable | LEV, CLB, KD | ZNS, LTG, FBM, TPM, RUF, B6, IVIG, VPA, PB, CS | ||
| 55 | V1528Cfs*7/de novo | 3 y | LGS | TCS | T, SE | Spike-slow-waves, Beta (sleep) | N | SD/SD | Spasticity | ASD, MC | 9 y | Sz free (6 y) | VPA + LTG | CLZ, ESM | ||
| 56 | R853Q/unknown | 3 y | Other | TS | S | HA | CC hypoplasia | SD/SD | Pyramidal signs, hand dystonia | Arachnodactyly | 25 y | Intractable | VPA, ACTH | |||
| 57 | C1170Vfs*15/de novo | 3 y | Other | TCS | M, AB | gen SW, l fr SW, high voltage theta | HiS | MD/SD | Hypertonic limbs | ASD | 17 y | Intractable | VPA, LTG, Br, LEV, CLB | CBZ, OXC, TPM, STP, ST, KD | ||
| 58 | G1223R/de novo | 3 y | Other | F, M | TCS, M, A, AA, NCSE | gen SW, PSW, slowing | N | N/MD | Ataxia | Regression | 19 y | Intractable | VPA, CLZ, CLB, LTG, LEV | PHT, PB, CBZ, TPM, VNS, CS | ||
| 59 | R1235*/de novo | 3 y 4 m | Other | FC | GTC, DA | gen SW, PSW | HM | MD/MD | N | ASD | 14 y | Intractable | LEV, ZNS | VPA, CLB, LTG | ||
| 60 | A1773V/de novo | 3 y 6 m | Other | F | Sharp waves r fr (sleep), slowing | N | MD/SD | N | ASD | 4 y | Sz free (4 y) | LEV | ||||
| 61 | K1933M/de novo | 4 y | Other | F, TCS | AA | MF spikes, bil SW→ESES-like | N | SD/SD | Ataxia, parkinsonian gait | ASD, hyperkinetic and aggressive behaviour | 17 y | Intractable | ST, VPA, TPM, CLB, CS | LTG, LCM | CBZ | |
| 62 | c.698‐1G>T, splice site/de novo | 4 y 6 m | Other | F | f spikes→MF, ESES-like→N | N | N/MID | N | 10 y | Sz free (9 y) | TPM | others | ||||
| 63 | W1716*/de novo | 4 y 7 m | Other | Febrile T (cluster) | AA | Gen SW | N | MD/MD | N | Psychosis (17 y) | 25 y | Sz free (9 y) | VPA | PB | CBZ | |
| 64 | N503Kfs*19/de novo | 6 y | Other | TCS (cluster) | Bil sharp waves | N | SD/SD | ASD | 20 y | Sz free (6 y) | VPA | |||||
| 65 | W281*/de novo | 7y | Other | F | sec. Gen. TCS | MF spikes→ESES- like | N | MD/MD | Clumsiness | 13 y | Sz free (10 y) | ST | ||||
| 66 | S1656F/de novo | 8 y 11 m | LGS | GTC | AA | Bifr SW, slowing | N | MD/MD | Hypotonia, crouched gait | Agitation | 12 y | Intractable | LLTG, VPA | TTPM | ||
| Patient | Mutation/ inheritance | Age at seizure onset | Epilepsy syndrome | Initial seizure type | Other seizure types | EEG | MRI | Cognition onset /follow-up | Neurological features | Additional features | Age at last follow-up | Seizure outcome (offset: age) | Treatment effects | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Seizure- free | Sz reduction | No effect | Wors- ening | |||||||||||||
| 38 | G899S/de novo | 3 m | Other | HC | GTC, FD, AA | Bifr SW | N | NA/SD | N | ASD | 7 y | Intractable | TPM, LEV, RUF, CLZ, CLB | PB, B6, VPA, LCM, ZNS, KD | OXC | |
| 39 | T227I/de novo | 3 m | WS | T, AP | S | HA→post spikes, slowing | N | SD/SD | Hypotonia | MC | 2 y | Intractable | LEV, ZNS | B6, VGB, CS, ACTH, TPM, KD, PB, OXC | ||
| 40 | A733T/de novo | 3 m | Other | HC r/l | AA, DA, FD | MF spikes, slowing | N | MD/MD | N | 12 y | Intractable | LEV | VPA, ESM, LTG, OXC | |||
| 41 | R1882P/de novo | 4 m | Other | T, C r | MF spikes, SW- status te→ESES-like | N | N/SD | N | Regression, ASD, aggression | 6 y | Sz free (8 m) | LEV | PB, VPA, ST, KD, LTG | |||
| 42 | L1665F/de novo | 4 m | Other | TS, SE | GTC (series) | N | N | N/SD | N | Stereotyped behaviour | 6 y 3 m | Sz free (7 m) | CBZ | VPA | PB | |
| 43 | L1342P/de novo | 6 m | WS | S | HA→MF spikes, slowing | At | SD/SD | Axial hypotonia, limb spasticity | Apnoeas, no eye contact | 16 y | Intractable | VGB, CS | ||||
| 44 | L881P/de novo | 6 m | WS→LGS | S | T, TC, AA | HA→MF spikes | At, HM, cerebellar at | SD/SD | Spasticity, hemiparesis | Small stature, early puberty | 18 y | Intractable | TPM, MDZ, CLB | VPA, LTG, PB, LEV, VGB, KD | RUF | |
| 45 | I1281F/de novo | 7 m | WS→LGS | S | T, TC | HA→MF spikes, slowing, diffuse SW | At | NA/SD | 16 y | Intractable | VNS, VPA, CLZ, RUF, TPM, LTG | |||||
| 46 | R853Q/de novo | 8 m | WS→LGS | S | AA, T, F (4 y) | HA→for bil spikes, SW, Slowing | T2H, at | N/SD | Dystonia | Preterm 28 w, MC, regression | 6 y 6 m | Intractable | ACTH | VPA, CLB, TPM | LTG, FBM, LEV | CBZ |
| 47 | A1652P/de novo | 9 m | WS | S | atypical HA→ slowing | HM | SD/SD | Hypotonia | ASD | 3 y | Intractable | VGB, LEV, NZP | VPA, TPM, CS | PHT | ||
| 48 | R1319W/de novo | 10 m | WS→LGS | T, S | TCS, A, AA | HA→spikes occ →spikes cue-par r | N | SD/SD | Hypotonia | Diabetes, ASD | 10 y | Sz free (7 y) | CBZ, TPM, ESM, ZNS, VPA, FBM, LEV, B6, KD, CS, LTG | |||
| 49 | E1211K / de novo | 11 m | WS→other | S | FC, SE, M | HA→MF spikes, slowing | N | SD/SD | Hypotonia | 4 y | Intractable | LEV, LTG, PB, KD | ST, VGB, CS | |||
| 50 | R853Q/de novo | 13 m | WS | S | T, AU, M | HA→MF spikes, ESES-like | N | MD/SD | Hypotonia, choreo-athetosis | 8 y | Intractable | VGB, PB, CLB | ST, TPM, LEV, ZNS, ESM, LTG, PHT, OXC, CS, KD,AZA | |||
| 51 | H930Q/de novo | 15 m | MAE | TCS | A, MAS, T, AA | slowing occ | N | N/MD | N | ASD | 6 y | Sz free (18 m) | LEV + TPM | VPA, OXC, CLB | ||
| 52 | P1622S/de novo | 2 y | MAE | MA, DA | T, AA, M | Spike-slow-waves te-par bil | N | MD/MD | Ataxia | ASD, MC | 3 y | Intractable | TPM | LEV, ESM, B6, PB, CLB, VGB, PP, KD | OXC, LTG | |
| 53 | F612S/de novo | 2 y 6 m | Other | TCS | M | fr spikes r/l, fr delta | N | MD/MD | N | 3 y | Intractable | CLB, LEV, RUF | ||||
| 54 | c.605 + 1G > T/ de novo | 2 y 6 m | Other | TCS | T, A | midline spikes ce, slowing→ bitemp spikes | N | N/SD | Hypotonia | ASD, regression | 7 y | Intractable | LEV, CLB, KD | ZNS, LTG, FBM, TPM, RUF, B6, IVIG, VPA, PB, CS | ||
| 55 | V1528Cfs*7/de novo | 3 y | LGS | TCS | T, SE | Spike-slow-waves, Beta (sleep) | N | SD/SD | Spasticity | ASD, MC | 9 y | Sz free (6 y) | VPA + LTG | CLZ, ESM | ||
| 56 | R853Q/unknown | 3 y | Other | TS | S | HA | CC hypoplasia | SD/SD | Pyramidal signs, hand dystonia | Arachnodactyly | 25 y | Intractable | VPA, ACTH | |||
| 57 | C1170Vfs*15/de novo | 3 y | Other | TCS | M, AB | gen SW, l fr SW, high voltage theta | HiS | MD/SD | Hypertonic limbs | ASD | 17 y | Intractable | VPA, LTG, Br, LEV, CLB | CBZ, OXC, TPM, STP, ST, KD | ||
| 58 | G1223R/de novo | 3 y | Other | F, M | TCS, M, A, AA, NCSE | gen SW, PSW, slowing | N | N/MD | Ataxia | Regression | 19 y | Intractable | VPA, CLZ, CLB, LTG, LEV | PHT, PB, CBZ, TPM, VNS, CS | ||
| 59 | R1235*/de novo | 3 y 4 m | Other | FC | GTC, DA | gen SW, PSW | HM | MD/MD | N | ASD | 14 y | Intractable | LEV, ZNS | VPA, CLB, LTG | ||
| 60 | A1773V/de novo | 3 y 6 m | Other | F | Sharp waves r fr (sleep), slowing | N | MD/SD | N | ASD | 4 y | Sz free (4 y) | LEV | ||||
| 61 | K1933M/de novo | 4 y | Other | F, TCS | AA | MF spikes, bil SW→ESES-like | N | SD/SD | Ataxia, parkinsonian gait | ASD, hyperkinetic and aggressive behaviour | 17 y | Intractable | ST, VPA, TPM, CLB, CS | LTG, LCM | CBZ | |
| 62 | c.698‐1G>T, splice site/de novo | 4 y 6 m | Other | F | f spikes→MF, ESES-like→N | N | N/MID | N | 10 y | Sz free (9 y) | TPM | others | ||||
| 63 | W1716*/de novo | 4 y 7 m | Other | Febrile T (cluster) | AA | Gen SW | N | MD/MD | N | Psychosis (17 y) | 25 y | Sz free (9 y) | VPA | PB | CBZ | |
| 64 | N503Kfs*19/de novo | 6 y | Other | TCS (cluster) | Bil sharp waves | N | SD/SD | ASD | 20 y | Sz free (6 y) | VPA | |||||
| 65 | W281*/de novo | 7y | Other | F | sec. Gen. TCS | MF spikes→ESES- like | N | MD/MD | Clumsiness | 13 y | Sz free (10 y) | ST | ||||
| 66 | S1656F/de novo | 8 y 11 m | LGS | GTC | AA | Bifr SW, slowing | N | MD/MD | Hypotonia, crouched gait | Agitation | 12 y | Intractable | LLTG, VPA | TTPM | ||
AA = atypical absences; A = atonic; AB = absences; ADS = attention deficit disorder; ASD = autism spectrum disorder; AU = autonomic seizures; AP = apneic seizures; At = atrophy; Bifr = bifrontal; Bil = bilateral; C = clonic; CC = corpus callosum; Ce = central; DA = drop attacks; ED = epileptiform discharges; F = focal; FD = focal dyscognitive; FC = febrile convulsion; fr = frontal; Gen = generalized; GTC = generalized tonic-clonic; HA = hypsarrhythmia; HC = hemiclonic; HiS = hippocampal sclerosis; HM = hypomyelination; IS = infantile spasms; L = left; LGS = Lennox-Gastaut syndrome; MAS = myoclonic-atonic seizures; = MAE = myoclonic-atonic epilepsy; m = months; MID = mild intellectual disability; MD = moderate intellectual disability; M = myoclonic; MC = microcephaly; MF = multifocal; N = normal; NA = not applicable; NAV = not available; NCSE = non-convulsive status epilepticus; Occ = occipital; Par = parietal; R = right; S = spasms; SE = status epilepticus; SD = severe intellectual disability; SW = spike and waves; Sz = seizures; T = tonic; T2H = T2-hyperintensities; TCS = tonic-clonic seizures; Te = temporal; w = week; WS = West syndrome; y = years;→ = change to.
Treatment (sodium channel blockers are highlighted in bold): AZA = acetazolamide; B6 = vitamin B6; BR = bromide; CBZ = carbamazepine; CLB = clobazam; CLZ = clonazepam; CS = corticosteroids; ESM = ethosuximide; FBM = felbamate; GBP = gabapentin; IVIG = intravenous immunoglobulins; KD = ketogenic diet; LCM = lacosamide; LTG = lamotrigine; LEV = levetiracetam; MDZ = midazolam; MSX = mesuximide; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; PP = pyridoxal phosphate; RGB = retigabine; RUF = rufinamide; ST = sulthiame; STP = stiripentol; TPM = topiramate; VGB = vigabatrin; VNS = vagal nerve stimulation; VPA = valproate; ZNS = zonisamide.
Clinical characteristics of the previously unpublished patients: intellectual disability and/or autism without epilepsy
| Patient | Mutation/ inheritance | EEG | MRI | Cognition onset/ follow-up | Neurological features | Additional features | Age at follow-up |
|---|---|---|---|---|---|---|---|
| 67 | K1387Sfs*4/de novo | NA | NA | MD | N | ASD | 5 y 4 m |
| 68 | R1435*/de novo | N | T2H | SD | N | ASD, early puberty | 7 y 8 m |
| 69 | T1711Lfs*8/de novo | Slowing | N | SD | Hypotonia | Rett-like, ASD | 9 y 8 m |
| 70 | G1744E/de novo | N | N | MD | N | ASD | 4 y |
| 71 | c.386+2T > C/de novo | NA | NA | MD | NAV | Episodic ataxia, ASD | 13 y |
| Patient | Mutation/ inheritance | EEG | MRI | Cognition onset/ follow-up | Neurological features | Additional features | Age at follow-up |
|---|---|---|---|---|---|---|---|
| 67 | K1387Sfs*4/de novo | NA | NA | MD | N | ASD | 5 y 4 m |
| 68 | R1435*/de novo | N | T2H | SD | N | ASD, early puberty | 7 y 8 m |
| 69 | T1711Lfs*8/de novo | Slowing | N | SD | Hypotonia | Rett-like, ASD | 9 y 8 m |
| 70 | G1744E/de novo | N | N | MD | N | ASD | 4 y |
| 71 | c.386+2T > C/de novo | NA | NA | MD | NAV | Episodic ataxia, ASD | 13 y |
ASD = autism spectrum disorder; m = months; MD = moderate intellectual disability; N = normal; NA = not applicable; NAV = not available; SD = severe intellectual disability; T2H = T2-hyperintensities; y = years.
Clinical characteristics of the previously unpublished patients: intellectual disability and/or autism without epilepsy
| Patient | Mutation/ inheritance | EEG | MRI | Cognition onset/ follow-up | Neurological features | Additional features | Age at follow-up |
|---|---|---|---|---|---|---|---|
| 67 | K1387Sfs*4/de novo | NA | NA | MD | N | ASD | 5 y 4 m |
| 68 | R1435*/de novo | N | T2H | SD | N | ASD, early puberty | 7 y 8 m |
| 69 | T1711Lfs*8/de novo | Slowing | N | SD | Hypotonia | Rett-like, ASD | 9 y 8 m |
| 70 | G1744E/de novo | N | N | MD | N | ASD | 4 y |
| 71 | c.386+2T > C/de novo | NA | NA | MD | NAV | Episodic ataxia, ASD | 13 y |
| Patient | Mutation/ inheritance | EEG | MRI | Cognition onset/ follow-up | Neurological features | Additional features | Age at follow-up |
|---|---|---|---|---|---|---|---|
| 67 | K1387Sfs*4/de novo | NA | NA | MD | N | ASD | 5 y 4 m |
| 68 | R1435*/de novo | N | T2H | SD | N | ASD, early puberty | 7 y 8 m |
| 69 | T1711Lfs*8/de novo | Slowing | N | SD | Hypotonia | Rett-like, ASD | 9 y 8 m |
| 70 | G1744E/de novo | N | N | MD | N | ASD | 4 y |
| 71 | c.386+2T > C/de novo | NA | NA | MD | NAV | Episodic ataxia, ASD | 13 y |
ASD = autism spectrum disorder; m = months; MD = moderate intellectual disability; N = normal; NA = not applicable; NAV = not available; SD = severe intellectual disability; T2H = T2-hyperintensities; y = years.
Distribution of patients according to phenotype and age at epilepsy onset. (A) Epilepsy phenotypes in the previously unpublished cohort (n = 66). ‘Patients with Lennox-Gastaut syndrome’ refers to patients with Lennox-Gastaut syndrome not evolving from West syndrome. (B) Phenotypes in the overall cohort (n = 201). LGS = Lennox-Gastaut syndrome; MAE = myoclonic-atonic epilepsy; OS = Ohtahara syndrome; WS = West syndrome.
