Autism Spectrum Symptomatology in Children with 7q11.23 Duplication Syndrome

Background:  Recent findings from studies of de novocopy number variants (CNVs) in a large sample of children in the Simons Simplex Collection identified a strong association between duplication of the Williams syndrome region (Dup7q11.23) and autism (Levy et al., 2011; Sanders et al., 2011).

Objectives:  Gold-standard diagnostic assessments of ASD symptomatology were conducted for a group of children with Dup7q11.23 who participated in a specialty research clinic for individuals with this syndrome.

Methods:  Participants were 63 children with genetically confirmed Dup7q11.23 (25 girls, 38 boys), ranging in age between 4 and 17 years (M age = 8.64 years, SD = 3.77). A comprehensive battery assessing cognitive, language, and psychosocial functioning was administered by a multidisciplinary team, including autism spectrum diagnosis by a Licensed Psychologist with specialized training in the diagnosis of ASD. Parents were interviewed about ASD-related symptomatology with the Autism Diagnostic Interview – Revised (ADI-R). The appropriate module of the Autism Diagnostic Observation Schedule – 2 was administered (ADOS-2; Mod 1 n = 9, Mod 2 n = 21, Mod 3 n = 33).

Results:  Based on the ADI-R diagnostic algorithm, which heavily weights retrospective accounts of functioning, 25 participants (39.6%) were classified “autism.” Based on the ADOS-2 algorithm, 16 (25.4%) were classified “autism spectrum (AS)” (5 “AS”, 11 “autism”) and 47 children (74.6%) were classified as “nonspectrum” (NS). Of the children classified “NS,” 29 had severity scores of 1 (minimal to no evidence), ten had severity scores of 2, and eight had severity scores of 3. Based on a combination of the ADI-R, ADOS-2, and clinical judgment, 12 participants (19.0%) were clinically diagnosed with ASD. All 12 were classified “AS” or “autism” on the ADOS-2; 9 were classified “autism” on the ADI-R. Of the remaining 47 participants, 16 were classified “autism” on the ADI-R and 4 were classified “AS” or “autism” on the ADOS-2.

Conclusions:  Careful characterization of ASD-related symptomatology using gold-standard ASD assessment measures combined with clinical judgment indicated that about 19% of children with Dup7q11.23 showed symptomatology consistent with an ASD clinical diagnosis. This rate indicates an elevated risk in comparison to the general population but also suggests that the presence of Dup7q11.23 by itself is not strongly indicative of the presence of an ASD. Reliance on retrospective parental report alone results in a higher rate (39.7%) of identified ASD-related symptomatology. The potential contribution of the history of language delays coupled with extreme social anxiety and/or shyness characteristic of the syndrome to parental observations of sociocommunicative challenges will be discussed. Additionally, implications of these findings for clinical management of children with Dup7q11.23 and for genotype-phenotype investigations will be addressed.