Developmental Trajectories of Autism Spectrum Features and Sensory Behaviors In Angelman Syndrome

Background: Angelman syndrome (AS) is a neurogenetic disorder that is characterized by severe intellectual disability, lack of speech, seizures, and a low threshold for laughter. Previous studies have indicated overlap of autism spectrum features (ASD) and AS, primarily in individuals who are deletion positive, and primarily in those with larger deletions. Previous studies, however, did not control for the effects of cognition in examining ASD features, and did not examine longitudinal trajectories of ASD features or sensory behaviors.

Objectives: To examine: 1) Trajectories of autism spectrum features, sensory-seeking behaviors, and sensory-aversions within the context of development over time in individuals with AS who are deletion positive; and 2) Any differences in ASD features, sensory behaviors, and trajectories across patients who have Class 1 vs. Class 2 deletions.

Methods: Forty-two deletion positive patients with AS were enrolled as part of a larger natural history study of AS, including 17 patients with a larger, Class 1 deletion (extending from BP1-BP3) and 25 patients with a smaller Class II deletion (from BP2-BP3). Patients were between the ages of 2-25. The Bayley Scales of Infant Development-III, Vineland Adaptive Behavior Scales-II, Autism Diagnostic Observation Schedule, and the Behavior and Sensory Interests Questionnaire were given at baseline and after 12 months.

Results: The results of repeated measures ANOVA’s indicate, that after controlling for level of cognition and chronological age, patients with Class 1 deletions have higher levels of impairment in social affect (F= 8.65; p=.006), higher restricted/repetitive behaviors (F=7.92; p=.008), and higher sensory aversions (F=6.013; p=.02) as compared to patients with Class 2 deletions. Sensory-seeking behaviors increase over time in both groups (F=4.52; p=.04), while restricted-repetitive behaviors remain stable over time in both groups. After controlling for the effects of cognition and age, patients with Class 1 deletions show a trend toward greater impairment in social affect over time, while patients with Class 2 deletions show a trend toward improvement in their social affect over time (F=1.50). There are also significant differences in trajectories of sensory aversions across deletion class groups (F=3.23; p<.05).

Conclusions: The results indicate that even after controlling for the effects of cognition, patients with Class 1 deletions have greater severity in ASD features and sensory behaviors that remain over time. Our results also suggest that there may be different trajectories of sensory aversions and social affect across deletion class groups, even after controlling for the effects of cognition. This suggests that ASD features in AS are not solely related to level of intellectual disability and that perhaps other genes in the deleted region contribute to ASD features and sensory behaviors. There are four genes (NIPA 1, NIPA 2, CYFIP1, & GCP5) missing in Class I and present in Class Il deletions, one or more of which may have a role in the severity of social affect impairment, level of restricted/repetitive behaviors, and sensory aversions as well as the trajectories of these behaviors over time.