Neurodevelopmental disorder associated with de novo SCN3A pathogenic variants: two new cases and review of the literature

Brain Dev. 2020 Feb;42(2):211-216. doi: 10.1016/j.braindev.2019.09.004. Epub 2019 Oct 31.


SCN3A was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy. We present two additional patients with a novel de novo SCN3A pathogenic variant, and a review of all published cases of de novo variants. In one of our patients brain magnetic resonance imaging (MRI) disclosed a severe polymicrogyria and in the other it was normal. The clinical phenotype was characterized by a severe developmental delay and refractory epilepsy in the patient with polymicrogyria and intellectual disability with autistic features and pharmacoresponsive epilepsy in the subject with normal MRI. Polymicrogyria, a disorder of progenitor cells proliferation and migration, is an unanticipated finding for an ion channel dysfunction.

Keywords: Epilepsy; Epileptic encephalopathy; Polymicrogyria; SCN3A.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child, Preschool
  • Epilepsy / genetics
  • Female
  • Genotype
  • Humans
  • Intellectual Disability / genetics
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics
  • NAV1.3 Voltage-Gated Sodium Channel / genetics*
  • NAV1.3 Voltage-Gated Sodium Channel / metabolism
  • Neurodevelopmental Disorders / genetics*
  • Neurodevelopmental Disorders / physiopathology
  • Phenotype
  • Polymicrogyria / genetics
  • Sodium Channels / genetics*
  • Sodium Channels / metabolism


  • NAV1.3 Voltage-Gated Sodium Channel
  • SCN3A protein, human
  • Sodium Channels