Table 1.
Clinical and molecular characteristics of nine patients with KCNQ2-related neonatal seizures.
| ID | Sex | GA at birth | Family history | Seizure onset | Semiologies | EEG | Neuroimaging (age) | Antiepileptic drugs | Age at last visit | Outcome | NGS | Variant (s) | Reported (PMID)/ Novel | Inheritance (allele from) | ACMG variant classification |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | Term | Neg | 4 days | Spasms | NA | NA | VGB, TPM, PB, LEV, VPA | 1 Y and 8 Mo | Severe GDD | ES-trio | c.601C > T (p.R201C) | Reported (25740509) | AD (de novo) | Pathogenic |
| 2 | F | Term | Neg | 2 days | GT, sequential | Multifocal IED | MRI: unremarkable | LEV Clonazepam | 9 Mo | Severe GDD | ES-trio | c.601C > T (p.R201C) | Reported (25740509) | AD (de novo) | Pathogenic |
| 3 | M | Term | Neg | 3 days | Myoclonus, eyes deviate left, head turn left | Multifocal IED | MRI: unremarkable (9 days) | LEV, PB | 1 Y and 6 Mo | Normal milestones | ES-trio | c.774C > G p.(N258K) * | Reported (35468861) | AD (de novo) | Pathogenic |
| 4 | F | Term (twin A; unaffected twin B) | Neg | 2 days | GT | Suppression-burst | MRI: cerebral atrophy, corpus callosum agenesis (7 Mo) | PHT, PB, TPM, LEV, VGB, perampanel | 2 Y and 9 Mo | Severe GDD | GS-trio | c.821C > T (p.T274M) | Reported (24318194) | AD (de novo) | Pathogenic |
| 5 | F | Term | Neg | 20 h | GT, Multifocal clonic | Suppression-burst | CT: unremarkable | PB, LEV, TPM, perampanel | 1 Y and 7 Mo | Severe GDD | ES-trio | c.821C > T, (p.T274M) | Reported (24318194) | AD (de novo) | Pathogenic |
| 6 | F | Term | Neg | 1 day | GT, sequential | Suppression-burst | MRI: unremarkable (1 Mo) | PB, LEV, TPM, PHT, Clonazepam, perampanel | 3 Y and 5 Mo | Severe GDD | ES-trio | c.836G > A p.(G279D) * | Novel | AD (de novo) | Likely pathogenic |
| 7 | M | Term | Neg | 36 h | GT | Multifocal IED | NA | LEV, PB | 1 month | NA | ES-trio |
c.881C > T (p.A294V) |
Reported (26138355) | AD (de novo) | Pathogenic |
| 8 | F | Term | Neg | 10 days | GT | Multifocal IED | MRI: cerebral atrophy (11 Mo) | PB, LEV, TPM, diazepam | 3 Y and 8 Mo | Severe GDD | ES-trio | c.1657C > T (p.R553W) | Reported (32117026) | AD (de novo) | Pathogenic |
| 9 | M | Term | Neg | 19 h | GT | Multifocal IED | MRI: unremarkable (2 weeks) | PB, TPM, LEV, CBZ | 4 Mo | Brief eye contact/not fix and follow, head lag | ES-trio | c.1687G > A (p.D563N) | Reported (30669290) | AD (de novo) | Pathogenic |
CBZ, carbamazepine; CT, computerized tomography; EEG, electroencephalogram; F, female; FLAIR, fluid attenuation inversion recovery; GDD, global developmental delay; GT, generalized tonic seizures; GTC, generalized tonic clonic seizures; rs, hours; ID, identification; IED, interictal epileptiform discharges; LEV, Levetiracetam; LGA, large for gestational age M, male; Mo, months; MRI, magnetic resonance imaging; NA, not available; NCSE, nonconvulsive status epilepticus; Neg, negative; NGS, next-generation sequencing; P5P, pyridoxal-5-phosphate; PB, phenobarbital; PHT, phenytoin; SE, status epilepticus; TPM, topiramate; VGB, vigabatrin; VPA, valproate; ES, whole-exome sequencing; GS, whole-genome sequencing; Y, year.
*The variants’ functional effects were studied.