Objectives: To evaluate in a quantitative manner the impact of deletion 16p11.2 on autism features, social functioning, cognitive abilities, and body mass index.
Methods: We studied 30 individuals with de novo del 16p11.2 from the Simons Variation in Individuals Project and their non-carrier parents (n=58) and siblings (n=19). We examined parent reports from the Social Responsiveness Scale (SRS), a quantitative scale that evaluates social awareness, reciprocal social communication, social information processing, and social anxiety, resulting in a T-score ranging from 30 (highly sociable) to 90 (severe social impairment) with a mean of 50 and a standard deviation (SD) of 10. SRS scores are highly heritable, commonly unrelated to intelligence quotient (IQ), and continuously distributed in the general population. We also evaluated full-scale IQ (FSIQ), a quantitative measure with a mean of 100 and a SD of 15, and body mass index (BMI), a proxy for human body fat based on an individual’s weight and height.
Results: Within this group, 32% of probands met full criteria for autism spectrum disorders using categorical diagnostic tools (ADI-R and ADOS). For the SRS, the mean T-score for probands was 71.9 compared to 46.8 in parents, and 44.7 in siblings. Moreover, scores in probands correlate with paternal scores (Spearman: rho (20) = .56, p = 0.1). Therefore, this quantitative trait revealed a 2.2 SD shift of mean SRS scores of probands relative to unaffected intrafamilial controls (p=4.44x10-16). These results are very similar to those obtained using FSIQ to assess cognitive functioning in this subset of cases: 16.6% met a categorical diagnostic criteria for ID (FSIQ ≤70); however, if viewed as a quantitative trait, FSIQ was 1.8 SD lower in probands compared to their parents (p=6.66x10-16) with a significant correlation between proband and maternal scores (Spearman: rho (29) = .43, p = .01). Finally, proband BMI z-scores were found to be 0.74 SD higher than parental scores and positively correlated with paternal BMI (Spearman: rho (24) = .55, p= .005).
Conclusions: By using continuous, quantitative traits such as FSIQ, SRS, and BMI scores to compare probands with their unaffected, non-carrier relatives, rather than using categorical variables such as DSM diagnoses or qualitative, dichotomous traits (i.e., normal vs. abnormal), we showed that parent-reported social behavior, cognitive function, and BMI are significantly impacted in a deleterious fashion among children with deletion 16p11.2 when compared to non-carrier relatives. These data may be more consistent with phenotypic heterogeneity related to genetic/family background rather than evidence of incomplete penetrance.
See more of: Genetic Factors in ASD
See more of: Biological Mechanisms