Table 1.
Reported drug response in epileptic encephalopathy due to SCN8A mutations.
| Amino acid substitution | Channel domain | Effect on function | Effective treatment | Seizure response | Reference |
|---|---|---|---|---|---|
| p.Val216Asp | DIS3-4 | VPA | Seizure control | (23) | |
| p.Leu407Phe | DIS6 | CBZ | 75% reduction | (53) | |
| p.Phe846Ser | DIIS4 | PHT, LTG, PB KD, VNS | Temporarily effective | (53) | |
| p.Ala890Thr | DIIS5 | VPA | Seizure control | (25, 53) | |
| VPA, OXC | |||||
| p.Asn984Lys | Near DIIS6 | GOF | PHT, ZNS, PB LEV, CLB | Seizure control | (24) |
| p.Ile1327Val | DIIIS4-5 | High PHT | Temporarily effective | (27) | |
| p.Gly1451Ser | DIIIS6 | LOF | CBZ | Seizure control | (24) |
| p.Asn1466Lys | Inactivation gate | PHT, TPM, GBP, ACTH, MDL, LD | Temporarily effective | (23) | |
| p.Asn1466Thr | Inactivation gate | TPM, LEV | Seizure control | (23) | |
| p.Val1592Leu | DIVS3 | OXC | Seizure control | (25) | |
| p.Ser1596Cys | DIVS3 | OXC, LTG, PB, LEV | 75% reduction | (53) | |
| p.Ile1605Arg | DIVS3 | CBZ | Seizure control | (25) | |
| p.Arg1617Gln | DIVS4 | CBZ | Temp. effective | (23, 53) | |
| OXC | Seizure control | ||||
| p.Ala1650Thr | DIVS4-5 | CBZ, TPM | Seizure control | (23) | |
| p.Asn1768Asp | DIVS6 | GOF | VPA, LTG, CLB | Temporarily effective | (15) |
| p.Arg1872Trp | C-term | TPM, LCM, LEV, VGB, KD | Febrile breakthrough | (23) |
ACTH, adrenocorticotropic hormone; CBZ, carbamazepine; CLB, clobazam; GBP, gabapentin; KD, ketogenic diet; LCM, lacosamide; LD, lidocaine; LEV, levetiracetam; LTG, lamotrigine; MDL, midazolam; OXC, oxcarbazepine; PB, phenobarbital; PHT, phenytoin; TPM, topiramate; VGB, vigabatrin; VNS, vagal nerve stimulator; VPA, valproic acid; ZNS, zonisamide. Drugs classified as sodium channel blockers are indicated in bold.