Abstract
BackgroundThe 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.MethodologyThe 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 FindingsThe 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.ConclusionThe 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.
Highlights
Autism spectrum disorders (ASDs) delineate a group of behaviorally-defined disorders including autism, PDD-NOS, and Asperger syndrome.Many efforts are being made to address the clinical heterogeneity of autism spectrum disorders (ASD)
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
Autism diagnostic interview-revised (ADI-R) algorithm variable scores were entered in the analyses to evaluate differences in symptom homogeneity and the feasibility of ASD genetic subphenotype discrimination
Summary
Many efforts are being made to address the clinical heterogeneity of ASDs. At the same time, the diversity of genetic findings in the past decade indicate that ASDs should be considered genetically heterogeneous [1,2]. The diversity of genetic findings in the past decade indicate that ASDs should be considered genetically heterogeneous [1,2] This raises the question to what extent the clinical heterogeneity can be explained by the underlying genetic heterogeneity of ASDs. In this study we will address this issue through the assessment of the homogeneity of the ASD phenotype in genetically more homogenous samples. 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. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
