Genetic heterogeneity in infantile spasms

Epilepsy Res. 2019 Oct:156:106181. doi: 10.1016/j.eplepsyres.2019.106181. Epub 2019 Jul 29.

Abstract

Infantile spasms (IS) is a developmental and epileptic encephalopathy with heterogeneous etiologies including many genetic causes. Genetic studies have identified pathogenic variants in over 30 genes as causes of IS. Many of these genetic causes are extremely rare, with only one reported incidence in an individual with IS. To better understand the genetic landscape of IS, we used targeted sequencing to screen 42 candidate IS genes and 53 established developmental and epileptic encephalopathy genes in 92 individual with IS. We identified a genetic diagnosis for 7.6% of our cohort, including pathogenic variants in KCNB1 (n = 2), GNAO1 (n = 1), STXBP1 (n = 1), SLC35A2 (n = 1), TBL1XR1 (n = 1), and KIF1A (n = 1). Our data emphasize the genetic heterogeneity of IS and will inform the diagnosis and management of individuals with this devastating disorder.

Keywords: Epilepsy; Genetic diagnosis; Infantile spasms; Targeted sequencing; West syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics
  • Humans
  • Infant
  • Kinesins / genetics*
  • Monosaccharide Transport Proteins / genetics
  • Mutation / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Repressor Proteins / genetics
  • Shab Potassium Channels / genetics*
  • Spasms, Infantile / diagnosis
  • Spasms, Infantile / genetics*

Substances

  • GNAO1 protein, human
  • KCNB1 protein, human
  • KIF1A protein, human
  • Monosaccharide Transport Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Shab Potassium Channels
  • TBL1XR1 protein, human
  • UDP-galactose translocator
  • Kinesins
  • GTP-Binding Protein alpha Subunits, Gi-Go