Table 1. Candidate variants and the feature of clinical profiles of studying patients.
| Proband ID | Gender/ Onset age | Variants | Inheritance | Diagnosis | Seizure type | Development | EEG/VEEG | Brain Imaging | Prognosis | Remark |
|---|---|---|---|---|---|---|---|---|---|---|
| Pathogenic variants | ||||||||||
| D1353 | M/6 m | SCN1A (c.311 C>T, p.Ala104Val) | de novo | Dravet syndrome | Febrile seizure and myoclonic seizure | ID, ASD Features | EEG: Epileptic discharge at 6 m; slow spike and weave at 1y; sharp wave, sharp and slow wave complex at 3y | Normal (MRI) | Intractable to OXC, LEV, VPA and vagus nerve stimulation; seizure free for 2 months to VPA+CLA+PB | Epilepsy family history |
| D1339 | M/8 m | SCN1A (c.181 C>T, p.Leu61Phe) | M | GEFS+ | Febrile seizures | Normal | EEG: Sharp waves and slow wave complex | Normal (MRI) | Seizure free for 2.5y with VAP+LEV | FS family history (mother, maternal aunt and grandma were diagnosed with FS) |
| KCNQ5 (c.7 C>T, p.Arg3Cys) | de novo | |||||||||
| UGT1A4/6 (c.1378 G>A, p.Val460Met) | de novo | |||||||||
| D1433 | M/5 m | SCN1A (c.2948delT, p.Val983Alafs*2) | de novo | Dravet Syndrome | Complex partial seizures, secondarily generalized status epilepticus | ID | VEEG: Mass of high δ and ϴ waves at 14 m; sharp waves, sharp and slow wave complex at 2.5y | Enlarged extracerebral gap (MRI, 15 m) | Intractable to VPA, OXC, CLZ, and LEV | |
| CACNA1H (c.4214 G>A, p.Arg1405Gln) | ||||||||||
| S92 | F/1.5 m | CDKL5 (c.216 T>G, p.Ile72Met) | de novo | IS | Spasms | GDD | EEG: Hyperarrhythmia | Cerebral dysplasia (MRI, 3 m) | Intractable to VPA+TPM | |
| S4 | M/4 m | TSC2 (c.2197 C>G, p.Leu733Val) | de novo | IS | Spasms change to myoclonic seizures | ID/GDD | EEG: Hyperarrhythmia | Enlarged extracerebral gap (CT, 4 m); subependymal nodules (CT, 9y) | Intractable to VPA+TPM+CLZ+LEV | 4 skin Hypomelanotic macules |
| D1358 | M/5 m | PRRT2 (c.649 C>T, p.Arg217x) | M | EP | Tonic-Clonic seizures | ID | EEG: Sharp and slow wave complex | Bilateral temporal angle hyperplasia, bilateral parietal lobe abnormal signal (MRI; 3y) | Seizure free for 2y to VPA; after recurrence, seizure free for 1y to VPA+OXC | Mother and maternal aunt diagnosed with PKD |
| S163 | F/6 m | STXBP1(c.54delG, p.Val18fs*1) | de novo | IS | Spasms in cluster; myoclonic seizures; Tonic-Clonic seizures | ID | EEG: Hypsarrhythmia | Enlarged extracerebral gap (MRI; 2y) | Seizure free for 1.5 years to VPA+TPM | |
| D1430 | F/3y | CHD2(c.5035 C>T, p.Arg1679x) | de novo | EP | Tonic-Clonic seizures | ID | EEG: Spike and sharp wave | Normal (MRI) | Seizure free for 1 year to VPA | The same mutation exists in his monozygotic sister with similar clinical feature |
| Likely pathogenic | ||||||||||
| D1346 | F/5y | SCN3A (c.1861 C>T, p.Arg621Cys) | M | BECTs | Tonic-Clonic seizures | Normal | EEG: Centro-temporal spikes | Normal (MRI) | Seizure free for 2 years to OXC | |
| D1422 | F/5y | SCN9A (c.121 G>C, p.Asp41His) SCN9A (c.3719 A>G, p.Lys1240Arg) | M | Jeavons syndrome | Absence, eyelid myoclonia | Normal | EEG: 3 Hz spike-wave | Normal (MRI) | Seizure free to VPA | |
| S23 | M/6 m | GABRE (c.1355 G>T, p.Arg452Leu) | M | IS | Spasms in cluster | GDD | EEG: Hyperarrhythmia at 7 m; multiple spike and slow wave complex at 1y | Myelin development delay (MRI, 7 m); brain dysplasia (MRI, 22 m) | Seizure reduction by >75% to VPA+TPM +CLZ | |
| S86 | F/4 m | MYH1 (c.3947 T>C, p.Ile1316Thr) MYH1 (c.92 C>T, p.Pro31Leu) | F/M | IS | Spasms in cluster | GDD | EEG: Hyperarrhythmia | Normal (MRI) | Intractable to VPA+TPM+CLZ and 6-months ketogenic diet | |
| S160 | F/3 m | SLC2A1 (c.740 A>G, p.Glu247Gly) | de novo | IS | Spasms in cluster; myoclonic seizures; Tonic-Clonic seizures | ID | EEG: Atypical hyper arrhythmia | Normal (CT) | Seizure reduction by75% to VPA+TPM | Skin cafe-au-lait spots |
| S183 | M/5 m | POLG (c.868 C>T, p.Arg290Cys) | de novo | IS | Spasms in cluster; myoclonic seizures; Tonic-Clonic seizures | GDD | EEG: Hyperarrhythmia | Normal (MRI) | Seizure free for one year to VPA+TPM | Unable to walk and self-feed until 4-years old; cannot talk and showed poor eye contact. |
| D1435 | M/5 m | CLCN6 (c.533 A>C, p.Glu178Ala) | de novo | IS | Spasms in cluster change to Tonic-Clonic and myclonic seizure | ID | EEG: Hyperarrhythmia | Enlarged subarachnoidale (MRI) | Seizure free for two month to ACTH, and then recurred. Intractable to VPA+TPM+NZP. Spasms stopped at 2.5y without AED and then recurred at 6y | microcephaly (<3 SD) |
| Variant of Unknown significance (VUS) | ||||||||||
| D1383 | M/6y | CYP2C9 (c.445 G>A, p.Ala149Thr) | M | CAE | Absence | Normal | EEG: 3 Hz spike-wave | Normal (MRI) | Seizure free for 2 years to VPA | Father has CAE |
| EFHC1 (c.1906 C>T, p.Arg636Cys) | ||||||||||
| KCNN4 (c.766 G>A, p.Val256Met) | ||||||||||
| RYR2(c.7052 T, p.Ile2351Thr) | ||||||||||
| D1426 | F/15 m | MBD5 (c.365 C>T, p.Ser122Phe) | F | EP | Tonic-Clonic seizures | ID | EEG: No epileptic discharge | Bilateral ventricle and three ventricle enlargement, periventricular white matter less (MRI) | About two times of epileptic seizures annually without AED drugs | Congenital heart disease(patent ductus arteriosus, atrialseptal defect), craniofacial abnormalities |
| D1471 | M/1.5y | MBD5 (c.1885 A>G, p.Asn629Asp) | M | EIEE | Tonic-clonic seizures with fever and status epilepticus; transformed to myoclonic seizures and spasms | GDD | VEEG: Spike wave, sharp wave at left frontal lobe, frontal lobe | Absence of septum pellucidum, enlarged bilateral ventricle, finer bilateral artery (MRI) | Intractable to VPA+TPM; response to ACTH initially but relapsed 6 months later | developmental regression and loss of language after 2.5y. Partial recovery was observed after ACTH |
Note: M, F in the column of Gender/Onset represent male and female respectively. In all part of this table, m and y following number represent month and year. M, F in the column of inheritance represent mother and father respectively. Generalized epilepsy with febrile seizures plus (GEFS+), Infantile spasm (IS), Early Infantile Epileptic encephalopathy (EIEE), and Epilepsy (EP). Intelligence disability (ID), Autism spectrum disorders (ASD), and Globel development delay (GDD). Electroencephalograph (EEG), Video electroencephalograph (VEEG). Magnetic Resonance Imaging (MRI), Computed Tomography (CT). Oxcarbazepine (OXC), Valproate (VPA), Levetiracetam (LEV), Clonazepam (CLZ), PB (Phenobarbital), Topamax (TPM), and ACTH (adreno-cortico-tropic-hormone). Febrile seizure (FS), Paroxysmal Kinesigenit Dyskinesia (PKD).