Symptom domains in autism and related conditions: evidence for familiality

Am J Med Genet. 2002 Jan 8;114(1):64-73. doi: 10.1002/ajmg.10048.


Heterogeneity in autism impairs efforts to localize and identify the genes underlying this disorder. As autism comprises severe but variable deficits and traits in three symptom domains (social interaction, communication, and repetitive behaviors) and shows variability in the presence and emergence of useful phrase speech, different genetic factors may be associated with each. The affected cases (n=457) in multiply affected siblingships (n=212), including a proband with autism and one or more siblings with either autism or marked deficits in autism symptom domains, were assessed using the Autism Diagnostic Interview, Revised. Symptom domain scores and language features were examined to determine their similarity within siblingships. The variance within siblingships was reduced for the repetitive behavior domain and for delays in and the presence of useful phrase speech. These features and the nonverbal communication subdomain provided evidence of familiality when we considered only the diagnosis of autism to define multiply affected siblingships (cases: n=289; siblingships: n=136). In addition, the same familial features identified also appeared familial for those with autism-related conditions. Finally, the level of severity of almost all of the familial features varied within multiplex siblingships independently. The features identified as familial replicate the combined set suggested in earlier, smaller studies. Furthermore, the familiality of these features extend to related conditions of milder severity than autism and appear to be independent. Making distinctions among families by the severity of these features may be useful for identifying more genetically homogeneous subgroups in studies targeted at genes for specific autism-related symptom domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder / epidemiology
  • Autistic Disorder / genetics*
  • Autistic Disorder / physiopathology
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Incidence
  • Infant
  • Ireland / epidemiology
  • Male
  • Phenotype
  • United States / epidemiology