De novo KCNT1 mutations in early-onset epileptic encephalopathy

Epilepsia. 2015 Sep;56(9):e121-8. doi: 10.1111/epi.13072. Epub 2015 Jul 3.


KCNT1 mutations have been found in epilepsy of infancy with migrating focal seizures (EIMFS; also known as migrating partial seizures in infancy), autosomal dominant nocturnal frontal lobe epilepsy, and other types of early onset epileptic encephalopathies (EOEEs). We performed KCNT1-targeted next-generation sequencing (207 samples) and/or whole-exome sequencing (229 samples) in a total of 362 patients with Ohtahara syndrome, West syndrome, EIMFS, or unclassified EOEEs. We identified nine heterozygous KCNT1 mutations in 11 patients: nine of 18 EIMFS cases (50%) in whom migrating foci were observed, one of 180 West syndrome cases (0.56%), and one of 66 unclassified EOEE cases (1.52%). KCNT1 mutations occurred de novo in 10 patients, and one was transmitted from the patient's mother who carried a somatic mosaic mutation. The mutations accumulated in transmembrane segment 5 (2/9, 22.2%) and regulators of K(+) conductance domains (7/9, 77.8%). Five of nine mutations were recurrent. Onset ages ranged from the neonatal period (<1 month) in five patients (5/11, 45.5%) to 1-4 months in six patients (6/11, 54.5%). A generalized attenuation of background activity on electroencephalography was seen in six patients (6/11, 54.5%). Our study demonstrates that the phenotypic spectrum of de novo KCNT1 mutations is largely restricted to EIMFS.

Keywords: De novo mutation; Early onset epileptic encephalopathies; Epilepsy of infancy with migrating focal seizures; KCNT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Electroencephalography
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Mutation / genetics*
  • Nerve Tissue Proteins / genetics*
  • Potassium Channels / genetics*
  • Potassium Channels, Sodium-Activated
  • Spasms, Infantile / genetics*


  • KCNT1 protein, human
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Sodium-Activated

Associated data

  • RefSeq/NM_020822