Expanding the phenotypic and genotypic spectrum of KCNT1-related epilepsies.

KCNT1 variants (a sodium-activated potassium channel); RCK1/RCK2 domain correlation, possible risk of vascular malformations (p.Arg474Cys).

Comprehensive review of reported KCNT1 pathogenic variants (a sodium-activated potassium channel), with updated follow-up: 316 patients from 88 publications, follow-up data for 60. Phenotypes span epilepsy of infancy with migrating focal seizures (EIMFS, 181 cases), sleep-related hypermotor epilepsy (SHE, 62) and various developmental and epileptic encephalopathies. Extra-neurological features (systemic-to-pulmonary collateral arteries, vascular or cardiac malformations) and mortality from pulmonary complications are noted, mainly in EIMFS. RCK1-domain variants trend toward EIMFS, RCK2 toward SHE, and p.Arg474Cys may increase the risk of vascular malformations.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The practical value lies in the domain-phenotype correlation and, above all, the signal of possibly under-recognised extra-neurological (vascular, cardiac) features in KCNT1 carriers — an argument for systematic screening. The limitations of retrospectively collecting published data are acknowledged. Useful for counselling and surveillance, without changing the diagnostic approach.

Analysis by Dr Thibaut Benquey