Autism-lessons from the X chromosome

Soc Cogn Affect Neurosci. 2006 Dec;1(3):183-93. doi: 10.1093/scan/nsl028.


Recognized cases of autism spectrum disorders are on the rise. It is unclear whether this increase is attributable to secular trends in biological susceptibility, or to a change in diagnostic practices and recognition. One hint concerning etiological influences is the universally reported male excess (in the range of 4:1 to 10:1). Evidence suggests that genetic influences from the X chromosome play a crucial role in engendering this male vulnerability. In this review, we discuss three categories of genetic disease that highlight the importance of X-linked genes in the manifestation of an autistic phenotype: aneuploides (Turner syndrome and Klinefelter syndrome), trinucleotide expansions (Fragile X syndrome) and nucleotide mutations (Rett Syndrome, Neuroligins 3 & 4, and SLC6A8). The lessons from these diseases include an understanding of autistic features as a broad phenotype rather than as a single clinical entity, the role of multiple genes either alone or in concert with the manifestation of autistic features, and the role of epigenetic factors such as imprinting and X-inactivation in the expression of disease severity. Better understanding of the clinical phenotypes of social cognition and the molecular neurogenetics of X-linked gene disorders will certainly provide additional tools for understanding autism in the years to come.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autistic Disorder / genetics*
  • Child
  • Child, Preschool
  • Chromosomes, Human, X / genetics*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology
  • Female
  • Genotype
  • Humans
  • Male
  • Methyl-CpG-Binding Protein 2 / genetics
  • Phenotype
  • Point Mutation / genetics
  • Psychomotor Disorders / epidemiology
  • Psychomotor Disorders / genetics
  • Sex Chromosomes / genetics
  • Sex Factors
  • Syndrome


  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2