Differences in Clinical Presentation of Trisomy 21 with and without Autism

Background: Autism occurs ten times more often in children with Down syndrome than in the general population, but diagnosing co-occurring autism in children with Down syndrome and severe intellectual disability is challenging.

Objectives: The objective of this case-control study was to identify characteristics differentiating children with trisomy 21 with and without autism and to determine the extent to which severe cognitive impairment affects measures of autism symptomatology.

Methods: Twenty children with trisomy 21 and autism (cases) were compared to children with trisomy 21 without autism (controls) matched on chronologic age, race and gender.  Communication, cognitive and adaptive behavior skills were assessed with standardized instruments. Medical history was reviewed and medical records were examined for early head growth.  Scores on the diagnostic algorithm of the Autism Diagnostic Interview – Revised (ADI-R) were compared after adjusting for cognitive ability as measured by the Stanford-Binet (5^th ed.) nonverbal change-sensitive score.

Results: Cases performed significantly more poorly on all assessments. Mean case-control differences for matched pairs were all significant at p < 0.0001 for receptive and expressive language skills, cognitive skills and adaptive skills. Seven cases had a history of seizures compared to 1 control (p=0.01). After adjusting for cognitive ability, the mean scores on the Reciprocal Social Interaction, Communication, and Restricted, Repetitive and Stereotyped Behaviors domains of the ADI-R diagnostic algorithm remained significantly higher in cases compared to controls (p < 0.0001). All participants had decreased head size consistent with Down syndrome, with no case-control differences.

Conclusions: Children with trisomy 21 and autism have significantly more impaired brain function than children with trisomy 21 without autism. However, the deficits in the core domains of social reciprocity and communication, and the restricted and repetitive interests are not entirely explained by the more severe cognitive impairment. This autism phenotype in children with trisomy 21 which includes an increased risk for seizures may indicate a widespread loss of functional connectivity in the brain.