Table 1.
The information of genotype and clinical phenotype in patients associated with GNAO1 gene mutations in China.
| ID | Gender | Onset age | Age at last follow-up | GNAO1 mutations | Mutation type | Pathogenicity | Function of mutation | Seizure types | Epileptic syndrome | MD (symptom) | DD | Interictal EEG | MRI | Treatment | Seizures or MD at last follow-up | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| epilepsy | MD | Dystonia | Chorea | Other | ||||||||||||||
| 1 | F | 3m | 2y | 4y | c.607G>A (p.G203R) | Missense | Pathogenic | GOF | FS, GTCS, SE | - | + (hypotonia) | + | - | delay | MFD, FWR | Widened extracerebral space | VPA, LEV, LD, GBP | Died |
| 2 | F | - | 8m | 2y5m | c.709G>A (p.E237K) | Missense | Pathogenic | UF | - | - | + (appendicular hypertonia) | + | - | delay | N | Widened extracerebral space | None | Died |
| 3 | F | 31d | 5m | 4y1m | c.680C>T (p.A227V) | Missense | Pathogenic | PLOF | FS, MS, TS | EIDEE | + (hypotonia, appendicular hypertonia) | - | - | delay | SSW | Widened subdural space | VPA, LEV, PB | Seizure-relief, but dystonia persisted |
| 4 | F | 4m | 1y2m | 2y3m | c.140G>A (p.S47N) | Missense | Likely pathogenic | UF | FS, GTCS, SE | IESS | + (axial and appendicular hypertonia) | - | - | delay | MFD, SSW | Subdural effusion, widened extracerebral space | VPA, LEV, TPM, OXC, PB, LTG, PER, VGB, TBZ, KD | FS occurred 2–10 times a day, severe dystonia |
| 5 | M | 12y | 12y | 12y9m | c.717_723+1del | Deletion | Pathogenic | LOF | FS, TS | - | - | + | orofacial dyskinesia | delay | MFD | Abnormal corpus callosum | VPA, ACTH, CZP, RPD, LD | Died |
| 6 | F | 30d | 6m | 2y3m | c.143C>T (p.T48I) | Missense | Pathogenic | UF | FS, GTCS | EIDEE | + (axial and appendicular hypertonia, opisthotonos position) | - | - | delay | MFD, SSW | Arachnoid cyst, Smaller temporal lobe gyrus | VPA, LEV, TPM, PB, CZP, VGB, PER, KD | Seizure-free for 10 months, but MD persisted |
| 7 | F | - | 5m | 4y7m | c.709G>A (p.E237K) | Missense | Pathogenic | UF | - | - | + (thumb adduction) | + | - | delay | N | N | LD | Severe chorea and dystonia |
| 8 | M | - | 9m | 3y7m | c.709G>A (p.E237K) | Missense | Pathogenic | UF | - | - | + (axial and appendicular hypertonia, opisthotonos position) | + | - | delay | N | N | THX, TIZ | Severe chorea and dystonia |
| 9 | M | 2m | 5m | 7m | c.808A>G (p.N270D) | Missense | Likely pathogenic | LOF | ES, TS, GTCS | IESS | + (axial and appendicular hypertonia) | - | - | delay | BS, hypsarrhythmia | N | VPA, TPM, LD, VGB, PER, CZP, ATCH | Seizure occurred 2–3 times a day, and dystonia persisted |
| 10 | F | 5d | 2m | 1y5m | c.133G>C (p.G45R) | Missense | Likely pathogenic | UF | FS, ES, TS | IESS | + (appendicular hypertonia) | - | - | delay | MFD, SSW, BS | N | VPA, LEV, OXC, VGB, TPM, LTG | Poor seizure control |
| 11 (15) | F | 12d | - | 1y | c.607G>A (p.G203R) | Missense | Pathogenic | GOF | FS, ES | IESS | - | - | - | delay | hypsarrhythmia | N | LEV, VPA, TPM, VGB | Died |
| 12 (14) | M | 5m | NA | NA | c.607G>A (p.G203R) | Missense | Pathogenic | GOF | FS | - | + | + | Orofacial dyskinesia | delay | MFD, SB | Widened extracerebral space | TPM, VPA, OXC, CZP | Seizure-relief, but MD persisted |
| 13 (12) | F | 1m23d | - | 5m17d | c.143C>T (p.T48I) | Missense | Pathogenic | UF | FS | - | - | - | - | delay | SB, FWR | Increased water content in the white matter | TPM, LEV | Poor seizure control |
| 14 (13) | F | 6h | - | 1y11m | c.136A>G (p.K46E) | Missense | Pathogenic | UF | FS, ES, TS | IESS | - | - | - | delay | FMD, DSW, SB, hypsarrhythmia | N | VPA, TPM, PB, LEV, ACTH | Died |
| 15 (13) | M | 1.5m | NA | 1y9m | c.687C>G (p.S229R) | Missense | Pathogenic | UF | FS, ES, AAS | IESS | + | - | - | delay | hypsarrhythmia, DSW, MFD | White matter delayed myelination | VPA, TPM, ACTH, VGB | Seizure occurred 10 times a day, and dystonia persisted |
| 16 (13) | F | 1d | NA | 1y5 m | c.470T>C (p.L157R) | Missense | Pathogenic | UF | FS, ES | IESS | + | - | - | delay | hypsarrhythmia, BS | N | VGB, TPM, ACTH | Seizure-free, but dystonia persisted |
| 17 (13) | M | 4m | - | 1y1m | c.118G>C (p.G40R) | Missense | Pathogenic | LOF | FS, ES | IESS | - | - | - | delay | hypsarrhythmia, SB, SSW | Widened extracerebral space | TPM, VPA, LEV | Seizure-free |
| 18 (13) | M | 9d | NA | 1y7m | c.810C>A (p.N270K) | Missense | Pathogenic | LOF | FS, ES, TS | IESS | + | - | - | delay | BS, hypsarrhythmia | N | TPM, VPA, VGB, PER, LEV, LCM, PB, ACTH, LD | Seizure occurred 10 times a day, and dystonia persisted |
| 19 (13) | F | 2d | NA | 3y5m | c.817G>T (p.D273Y) | Missense | Pathogenic | UF | FS, GTCS | EIDEE | + | - | - | delay | DSW, SB | N | VPA, LEV, CZP, KD | Seizure-free, but dystonia persisted |
| 10 (13) | F | 3d | NA | 8m | c.692A>G (p.Y231C) | Missense | Pathogenic | PLOF | FS, ES | EIDEE | + | - | - | delay | DSW, FWR, MFD | Widened extracerebral space | VPA, TPM, VGB | Seizure-free, but dystonia persisted |
| 21 (13) | M | 12d | NA | 10m | c.607G>A (p.G203R) | Missense | Pathogenic | GOF | FS | - | + | - | - | delay | MFD | N | TPM, LD | Died |
| 22 (13) | M | - | - | 2y3m | c.736G>A (p.E246K) | Missense | Pathogenic | GOF | - | - | - | - | - | delay | N | Widened extracerebral space, white matter developmental delay | None | Died |
| 23 (13) | M | - | 4m | 7y3m | c.724-8G>A | Splice site | Pathogenic | UF | - | - | + | - | - | delay | SB | N | LD | MD persisted |
| 24 (10) | F | - | 3m | 8m | c.626G>A (p.R209H) | Missense | Pathogenic | NF | - | - | - | + | - | delay | N | N | None | NA |
| 25 (11) | F | - | 6m | 6y | c.124G>A (p.G42R) | Missense | Pathogenic | GOF | - | - | + | - | trunk torsion | delay | N | N | GPI-DBS | BFMDRS score from 77 dropped to 63 after 24 months, useful grasping |
| 26 (11) | M | - | 6m | 6y | c.724-8G>A | Splice site | Pathogenic | UF | - | - | + | - | trunk torsion | delay | N | N | STN-DBS | BFMDRS score from 62 dropped to 35 after 15 months, walk independently |
| 27 (11) | M | - | 2y | 18y | c.724-8G>A | Splice site | Pathogenic | UF | - | - | + | - | trunk torsion | NA | N | N | LD, CZP, THX, GPI-DBS | BFMDRS score from 86 dropped to 41 after 14 months |
m, months; y, years; d, days; h, hours; GOF, gain-of-function; UF, unknown-function; PLOF, partial-loss-of-function; LOF, loss-of-function; NF, normal-function; FS, focal seizure; CTCS, generalized tonic clonic seizure; SE, status epilepticus; MS, myoclonic seizure; TS, tonic seizure; ES, epileptic spasm; AAS, atypical absence seizures; EIDEE, early infantile developmental and epileptic encephalopathy; IESS, infantile epileptic spasm syndrome; MD, movement disorders; DD, developmental delay; MFD, multifocal discharge; FWR, fast wave rhythm; SSW, sharp slow wave; BS, burst-suppression pattern; SB, slow background; DSW, diffuse slow wave; MRI, magnetic resonance imaging; ASMs, anti-seizure medications; VPA, valproate; LEV, levetiracetam; LD, levodopa; GBP, gabapentin; PB, phenobarbital; TPM, topiramate; OXC, oxcarbazepine; LTG, lamotrigine; PER, perampanel; VGB, vigabatrin; TBZ, tetrabenazine; KD, ketogenic diet; ACTH, adrenocorticotropic hormone; CZP, clonazepam; LCM, lacosamide; RPD, risperidone.; THX, trihexyphenidyl; TIZ, tizanidine; GPI-DBS, globus pallidus interna-deep brain stimulation; STN-DBS, subthalamic nucleus-deep brain stimulation; -, absent; NA, not available; N, normal value.