The Language Phenotype of the 16p11.2 Deletion and Duplication in Children with and without Autism Spectrum Disorders (ASD): The Svip Study

Background: Studies have shown that a significant number of individuals with the BP4-BP5 16p11.2 copy number variant (CNV), deletion or duplication, are more likely to show cognitive and language impairments (e.g., Hanson et al., 2014) and higher prevalence of Autism Spectrum Disorders (ASD). However, our understanding on the language phenotype of 16p11.2 CNV in children with/without ASD is still limited.

Objectives: To examine the patterns of language phenotype of 16p11.2 CNV with and without ASD based on clinician observations of spontaneous expressive language (Observation of Spontaneous Expressive Language [OSEL]; Kim, Junker, & Lord, 2014) and parent reports (Children’s Communication Checklist-2 [CCC-2], Bishop, 2003).

Methods: General Linear Model (GLM) was performed to examine the effects of 16p11.2 CNV and diagnosis (ASD/non-ASD) while controlling for gender, verbal IQ (VIQ), and chronological age in predicting OSEL syntax and OSEL pragmatic-semantic-profile (PSP) totals as well as CCC-2 scaled scores. The OSEL syntax totals are computed by combining grammatical usages of 24 items including different types of pronouns [e.g., subjective/objective/possessive], verb tenses [e.g., regular/irregular past, progressive], sentence forms [e.g., coordination/subordination]. The OSEL PSP totals include three domains. The first domain represents skills associated with Initiation of Reciprocal Communication, which includes items such as Verbal request and Asks for information about others’ experiences. The second domain, Narrative Skills, includes items such as Reporting main ideas and Reporting sequence of events. The third domain, Unusual Features, includes items such as Dominates conversations and Stereotyped/idiosyncratic language. The CCC-2 results in scaled scores for 10 domains targeting grammar (Syntax), phonology (Speech), and semantic (Semantics) and pragmatic skills (Initiation, Nonverbal Communication) as well as a Social interaction Difference Index (SIDI) created to measure communication impairments in ASD.

Results: The GLM revealed a significant effect of 16p11.2 CNV for OSEL syntax totals and several domains on the CCC-2. Children with 16p11.2 deletion demonstrated significantly lower OSEL syntax and CCC-2 Syntax scale scores compared to children with 16p11.2 duplication (p’s<0.05). Children with the deletion also scored significantly lower on CCC-2 Speech (phonology) scale. On the contrary, children with the duplication showed more impairments on CCC-2 Semantics and Initiation scales (p’s<0.05) and on the SIDI. Similar trends emerged for the OSEL PSP totals with children with the duplication scoring lower, but the effect did not reach statistical significance. A significant effect of ASD diagnosis emerged for the OSEL syntax and PSP domain totals as well as CCC-2 SIDI while controlling for the CNV. Children with ASD showed significantly lower OSEL syntax totals and higher scores (meaning more impairments) on the PSP Narrative Skills as well as more impairments in SIDI compared to the non-ASD group (p’s<0.05).

Conclusions: Both clinician observations and parent reports show children with 16p11.2 deletion demonstrate more limited syntactic and phonological skills compared to those with the duplication even while controlling for the presence of ASD; whereas children with the duplication show more impairments in pragmatic-semantic skills compared to the deletion group. Not surprisingly, children with ASD showed more impairments in syntactic and narrative skills while controlling for the CNV.