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PLoS One. 2010 May 28;5(5):e10887. doi: 10.1371/journal.pone.0010887.

Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes.

Author information

  • 1Department of Children and Adolescent Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands. h.bruining@Umcutrecht.nl

Abstract

BACKGROUND:

The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile.

METHODOLOGY:

The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles.

PRINCIPAL FINDINGS:

The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population.

CONCLUSION:

The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population.

PMID:
20526357
[PubMed - indexed for MEDLINE]
PMCID:
PMC2878316
Free PMC Article

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