22q11.2 Duplication Syndrome: Assessment of Autism Spectrum Disorder, Other Neuropsychiatric Symptoms, and Adaptive Skills

Background:   Past research suggests that individuals with 22q11.2 Deletion Syndrome (22q11.2DS) have elevated rates of autism (~15%), ADHD (>50%), and schizophrenia (~25%). Recently widespread use of microarrays has identified duplication of the identical 2.54Mb region in a growing number of patients (22q11.2DupS). Case reports suggest heterogeneous medical and neuropsychiatric profiles, but there has not yet been systematic assessment of ASD and other neuropsychiatric symptoms.

Objectives:   To characterize the prevalence of ASD and the presentation of psychiatric symptoms and adaptive skills in individuals with 22q11.2DupS. 

Methods:   Youth with 22q11.2DupS or 22q11.2DS were recruited from a genetics specialty clinic at the Children’s Hospital of Philadelphia, and matching groups of ASD and typically developing controls (TDC) were formed form other studies at the Center for Autism Research. 22q11.2DupS participants (n=28) were matched 1:3 on age and sex, with 1:1 matching for children younger than four years, to participants in all three comparison groups: 22q11.2DS (n=62), ASD (n=70), and TDCs (n=73). Parents of all participants completed measures of social communication skills, psychiatric symptoms, and adaptive behavior skills (SCQ, SRS or SRS-2, CASI-4R, and Vineland-II). Parents of youth with 22q11.2DupS (but not deletions) also completed the ADI-R (n=20). A subset were also administered the ADOS (n= 8). All participants in the ASD comparison group were evaluated with both instruments.

Results:   Five of 20 individuals with 22q11.2DupS met research diagnostic standards and clinical judgment for a diagnosis of ASD (25%). All 5 carried a community diagnosis of ASD, as did 7 of the 15 participants who did not meet research diagnostic standards. Parent report questionnaires found that both the 22q11.2DupS and 22q11.2DS groups showed greater impairment than the TDC group on all social indices (all p’s < 0.001; d’s > 1.80). Duplication and deletion groups did not differ on any social measures. Both duplication and deletions showed impairment on the Vineland-II Adaptive Behavior Composite that was intermediate between TDCs and ASD. The ASD, 22q11.2DS, and 22q11.2DupS groups each demonstrated significantly elevated neuropsychiatric impairments compared to TDCs.

Conclusions: This report is the first study to assess ASD symptoms in a sample of individuals with the 22q11.2DupS. One quarter met gold-standard diagnostic criteria for ASD and showed similar levels of social communication impairment (SCQ and SRS/SRS-2) to children with idiopathic ASD. The estimated 25% rate of ASD observed in children with 22q11.2DupS is much higher than the population prevalence estimates of 1-2%, and is among the highest of any genetic syndrome associated with ASD.