Objectives: To compare symptoms of autism and associated developmental and behavioral domains among the molecular subtypes and deletion subclasses of AS.
Methods: Patients were assessed with the ADI-R and ADOS-G, the Bayley Scales of Infant Development-III, Vineland Adaptive Behavior Scales, and the Aberrant Behavior Checklist (ABC). Deletion-positive patients underwent a microarray-based comparative genomic hybridization assay.
Results: 72 patients with AS (53 deletion, 11 UBE3A mutation, 4 uniparental disomy, and 4 imprinting center defect) were evaluated. Only deletion positive patients exceeded ADOS cutoff scores for autism or autism spectrum disorder (ASD). Those with larger, Class I deletions were more likely to exceed criteria for autism/ASD (p=.05) compared to smaller, Class II deletions. Differences in ADOS socialization scores accounted for differences in autism diagnosis by deletion class, with Class I patients achieving more severe scores (p=.05). Significant differences were noted for cognition (p<.01), expressive language (p<.01), and fine motor skills (p<.05) between AS patients with co-morbid autism/ASD and those without. Significant, positive partial correlations were noted between ADOS communication and socialization scores and the Lethargy/Withdrawal domain of the ABC (r=.30; r=.35) and the Stereotypy domain (r=.25; r=.34) of the ABC.
Conclusions: Severity of autism symptoms in AS is associated with deletion size and with a more aloof/withdrawn behavioral phenotype. There are four genes (NIPA 1, NIPA 2, CYFIP1, & GCP5) missing in Class I and present in Class II deletions, one or more of which may have a role in the development of socialization skills.