Interneuron, interrupted: molecular pathogenesis of ARX mutations and X-linked infantile spasms

Curr Opin Neurobiol. 2012 Oct;22(5):859-65. doi: 10.1016/j.conb.2012.04.006. Epub 2012 May 5.

Abstract

X-linked Infantile Spasms Syndrome (ISSX) is a catastrophic epilepsy of early childhood with intractable seizures, intellectual disability, and poor prognosis. A spectrum of mutations in the Aristaless-Related Homeobox gene (ARX) has been linked to ISSX, and downstream targets of this interneuron-expressed transcription factor are being defined. Recent advances combining in vitro and in vivo methods have unveiled complex interactions between Arx and its binding partners and their effects on cell migration and maturation that can help explain the diversity of ARX phenotypes. New mutant mouse models of Arx-induced pathology, including a recent human triplet-repeat expansion mutation with a phenotype of infantile spasms and electrographic seizures, provide valuable tools for exploring the pathophysiology of Arx and substrates for testing novel therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aicardi Syndrome / genetics*
  • Aicardi Syndrome / pathology*
  • Animals
  • Disease Models, Animal
  • Homeodomain Proteins / genetics*
  • Humans
  • Interneurons / physiology*
  • Mice
  • Mutation / genetics*
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / pathology*
  • Transcription Factors / genetics*

Substances

  • ARX protein, human
  • Homeodomain Proteins
  • Transcription Factors

Supplementary concepts

  • Infantile Epileptic-Dyskinetic Encephalopathy