X-linked Mental Retardation and Epilepsy: Pathogenetic Significance of ARX Mutations

Brain Dev. 2003 Apr;25(3):161-5. doi: 10.1016/s0387-7604(02)00169-9.


Mental retardation (MR) and epilepsy are both heterogeneous syndromes based on dysfunction in the brain and they are often closely associated. Hence, there should be some overlap in the underlying pathomechanisms, particularly when both syndromes result from genetic abnormalities, either polygenic or monogenic. Some 50 monogenic causes of MR have been found in genes localized on the X-chromosome and are responsible for X-linked MR. In contrast, monogenic causes of about 30 epilepsy syndromes are transmitted as an autosomal trait. Early this year, an X-chromosome-linked, Aristaless-related, homeobox gene, ARX, was found to be associated with both X-linked MR and epilepsy. The epilepsy phenotypes included West syndrome and other epilepsy phenotypes, indicating the genetic basis of the X-linked West syndrome. Another report implied that the ARX molecule plays a crucial role in cognitive function. These findings provide solid evidence for the relationship between MR and epilepsy at a molecular level, opening a new avenue for understanding the pathogeneses of MR associated with epilepsy.

Publication types

  • Review

MeSH terms

  • Epilepsy / genetics*
  • Genes, Homeobox
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Mental Retardation, X-Linked / genetics*
  • Mutation
  • Phenotype
  • Spasms, Infantile / genetics
  • Transcription Factors / genetics*


  • ARX protein, human
  • Homeodomain Proteins
  • Transcription Factors