Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes

Hilgo Bruining*, Leo de Sonneville, Hanna Swaab, Maretha de Jonge, Martien Kas, Herman van Engeland, Jacob Vorstman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 KSASD 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.

Original languageEnglish
Article numbere10887
JournalPLoS ONE
Volume5
Issue number5
DOIs
Publication statusPublished - 17 Sep 2010
Externally publishedYes

Cite this

Bruining, H., de Sonneville, L., Swaab, H., de Jonge, M., Kas, M., van Engeland, H., & Vorstman, J. (2010). Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. PLoS ONE, 5(5), [e10887]. https://doi.org/10.1371/journal.pone.0010887