Table 1.
Genotypic and phenotypic features of 11 patients with GNAO1 variants.
| Patient no. | Sex | Variant | Age at last follow-up | Onset age (symptom) | Seizure types | Movement disorders (symptom) | Developmental delay | EEG | MRI | Phenotypic diagnosis | Drugs |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | c.136A>G (p.K46E) | 1 y 11 m (death) | 6 h (seizure) | FS, SS, TS, TSS | – | ++ | 26 d: normal | Normal | West | VPA, TPM, PB, LEV, ACTH |
| 2 m 13 d: DSW, MFD | |||||||||||
| 2 m 24 d: Hypsarrhythmia | |||||||||||
| 11 m: SB, DSW, MFD | |||||||||||
| 2 | M | c.687C>G (p.S229R) | 1 y 9 m | 1.5 m (seizure) | FS, SS, AAS | +(dystonia) | ++ | 3 m, 5 m, and 1 y 1 m: Hypsarrhythmia | 5 m: normal | West and MD | VPA, TPM, ACTH, VGB |
| 1 y 2 m: DSW of δ, MFD, temporal sharp wave | 1 y 1 m: white matter delayed myelination | ||||||||||
| 3 | F | c.470T>C (p.L157R) | 1 y 5 m | 1 d (seizure) | FS, SS, TSS | +(dystonia) | ++ | 3 m: Hypsarrhythmia; few BS | Normal | West and MD | VGB, TPM, ACTH |
| 4 | M | c.118G>C (p.G40R) | 1 y 1 m | 4 m (seizure) | FS, SS | – | ++ | 6 m: Hypsarrhythmia | 4 m: wider extracerebral space | West | TPM, VPA, LEV |
| 1 y: SB, SSW of occiput | |||||||||||
| 5 | M | c.810C>A (p.N270K) | 1 y 7 m | 9 d (seizure) | FS, SS, TS, TSS | +(dystonia) | ++ | 1 m 19 d: BS mixed with few hypsarrhythmia | Normal | Ohtahara and MD | TPM, VPA, VGB, PER, LEV, LCM, PB, ACTH |
| 3 m 16 d and 4 m 13 d: BS | |||||||||||
| 6 | F | c.817G>T (p.D273Y) | 3 y 5 m | 2 d (seizure) | FS, GTCS | +(dystonia) | ++ | 1 y 1 m: DSW, occipital discharge | Normal | EIEE and MD | VPA, LEV, CZP, KD |
| 1 y 4 m: SB, right temporal discharge | |||||||||||
| 1 y 6 m: Occipital discharge | |||||||||||
| 7 | F | c.692A>G (p.Y231C) | 8 m | 3 d (seizure) | FS, SS, TSS | +(dystonia) | ++ | 1 m: DSW | 2 m: wider temporal extracerebral space | EIEE and MD | VPA, TPM, VGB |
| 2 m: parietal and occipital FW | |||||||||||
| 3 m: occiput FWR, MFD | |||||||||||
| 8 | M | c.607G>A (p.G203R) | 10 m (death) | 12 d (seizure) | FS | +(dystonia) | ++ | 5 m: MFD | Normal | EIEE and MD | TPM, Levodopa |
| 9 | M | c.736G>A (p.E246R) | 2 y 3 m (death) | 4 m (DD) | – | – | ++ | 4 m and 1 y 5 m: Normal | 4 m: slightly wider frontotemporal extracerebral space | DD | – |
| 1 y 5 m: white matter developmental delay | |||||||||||
| 10 | M | c.724-8G>A | 16 y | 5 m (DD) | – | +(dystonia, choreoathetosis) | + | 7 y: SB | 7 y: normal | MD and DD | Levodopa, CZP, Trihexyphenidyl |
| 11 | M | c.724-8G>A | 7 y 3 m | 4 m (DD) | – | +(dystonia) | + | 3 y: SB | 1 y 4 m: normal | MD and DD | Levodopa |
F, female; M, male; y, year; m, month; d, day; h, hour; DD, developmental delay; FS, focal seizures; TS, tonic seizures; SS, spasm seizures; TSS, tonic spasm seizures; AAS, atypical absence seizures; GTCS, generalized tonic-clonic seizures; DSW, diffuse slow wave; SSW, sharp slow wave; FW, fast wave; FWR, fast wave rhythm; MFD, multifocal discharge; SB, slow background; BS, burst-suppression pattern; EIEE, early infantile epileptic encephalopathy; MD, movement disorders; West, West syndrome; Ohtahara, Ohtahara syndrome; VPA, valproic acid; TPM, topiramate; PB, phenobarbital; PER, perampanel; LEV, levetiracetam; LCM, lacosamide; VGB, vigabatrin; CZP, clonazepam; KD, ketogenic diet; ACTH, adrenocorticotropic hormone.