KANSL1 variation is not a major contributing factor in self-limited focal epilepsy syndromes of childhood

PLoS One. 2018 Jan 19;13(1):e0191546. doi: 10.1371/journal.pone.0191546. eCollection 2018.


Background: KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS), characterized by dysmorphic features and intellectual disability; amiable personality, congenital malformations and seizures also commonly occur. The epilepsy phenotypic spectrum in KdVS is broad, but most individuals have focal seizures with some having a phenotype resembling the self-limited focal epilepsies of childhood (SFEC). We hypothesized that variants in KANSL1 contribute to pathogenesis of SFEC.

Materials and methods: We screened KANSL1 for single nucleotide variants in 90 patients with SFEC. We then screened a cohort of 208 patients with two specific SFEC syndromes, childhood epilepsy with centrotemporal spikes (CECTS) and atypical childhood epilepsy with centrotemporal spikes (ACECTS) for KANSL1 variants. The second cohort was also used to evaluate minor allelic variants that appeared overrepresented in the initial cohort.

Results: One variant, p.Lys104Thr, was predicted damaging and appeared overrepresented in our 90-patient cohort compared to Genome Aggregation Database (gnomAD) allele frequency (0.217 to 0.116, with no homozygotes in gnomAD). However, there was no difference in p.Lys104Thr allele frequency in the follow-up CECTS/ACECTS cohort and controls. Four rare KANSL1 variants of uncertain significance were identified in the CECTS/ACECTS cohort.

Discussion: Our data do not support a major role for KANSL1 variants in pathogenesis of SFEC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Amino Acid Substitution
  • Child
  • Chromosome Deletion
  • Chromosomes, Human, Pair 17 / genetics
  • Cohort Studies
  • Databases, Genetic
  • Epilepsies, Partial / genetics
  • Epilepsy, Rolandic / genetics
  • Epileptic Syndromes / etiology
  • Epileptic Syndromes / genetics*
  • Gene Frequency
  • Genetic Variation
  • Humans
  • Intellectual Disability / genetics
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*


  • NSL1 protein, human
  • Nuclear Proteins

Supplementary concepts

  • Chromosome 17q21.31 Deletion Syndrome

Grant support

This research was supported by a grant from Supporting Families with Koolen-de Vries syndrome (https://supportingkdvs.org/). Additional support came from an Australian National Health and Medical Research Council Program Grant (NHMRC; https://www.nhmrc.gov.au/; grant number 628952). Dr. Myers also holds a Taking Flight Award from Citizens United for Research in Epilepsy (CURE; http://www.cureepilepsy.org/; grant number 439534). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.