Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome

Int J Mol Sci. 2020 Jun 23;21(12):4447. doi: 10.3390/ijms21124447.


Complex neurodevelopmental syndromes frequently have an unknown etiology, in which genetic factors play a pathogenic role. This study utilizes whole-exome sequencing (WES) to examine four members of a family with a son presenting, since birth, with epileptic-like crises, combined with cerebral palsy, severe neuromotor and developmental delay, dystonic tetraparexia, axonal motor affectation, and hyper-excitability of unknown origin. The WES study detected within the patient a de novo heterozygous in-frame duplication of thirty-six nucleotides within exon 7 of the human KCNQ2 gene. This insertion duplicates the first twelve amino acids of the calmodulin binding site I. Molecular dynamics simulations of this KCNQ2 peptide duplication, modelled on the 3D structure of the KCNQ2 protein, suggest that the duplication may lead to the dysregulation of calcium inhibition of this protein function.

Keywords: KCNQ2; cerebral palsy; dystonia; epilepsy; neuromotor delay.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Developmental Disabilities / complications
  • Developmental Disabilities / genetics
  • Developmental Disabilities / pathology*
  • Epileptic Syndromes / complications
  • Epileptic Syndromes / genetics
  • Epileptic Syndromes / pathology*
  • Exons*
  • Gene Duplication*
  • Humans
  • KCNQ2 Potassium Channel / genetics*
  • Male
  • Mutation*
  • Neurodevelopmental Disorders / complications
  • Neurodevelopmental Disorders / genetics
  • Neurodevelopmental Disorders / pathology*
  • Phenotype
  • Prognosis


  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human