Exploring Autism Symptoms in Individuals with Prader-Willi and Angelman Syndromes

Background: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are imprinting disorders that are caused by genetic or epigenetic changes at the same locus on chromosome 15. PWS results from the loss of paternal genes from chromosome 15q11.2-q13 while AS from the absence of the maternal genes in the same region. Overexpression of maternally imprinted genes in the 15q11-13 region is also a susceptibility factor for autism spectrum disorder (ASD), which is observed in both PWS and AS. Individuals with PWS are reported to have social withdrawal, compulsive behaviours and repetitive speech. In contrast, those with AS are more likely to be eager to communicate and engage socially. However most research to date has relied on parent-report rather than through objective assessment.

Objectives: (1) to explore symptoms of ASD in well-characterized samples of individuals with PWS and AS; (2) to compare rates of ASD between individuals with PWS and AS; and (3) to compare intellectual functioning between those meeting criteria for ASD compared to those classified as non-ASD.

Methods: Twenty-three individuals with PWS (47.8% male; age 1.5 – 32.2 years) and 14 individuals with AS (50.0% male; age 2.8 – 39.7 years) participated in the study. The Autism Diagnostic Observation Schedule-2^nd Edition (ADOS-2) was used to assess ASD symptoms. The Mullen Scales of Early Learning was used to assess intellectual functioning in PWS children aged under 3 years and all individuals with AS. For the remaining PWS participants, the age appropriate Wechsler intelligence scale was used to assess intellectual functioning.

Results: The criteria for ASD were met by 16 (69.6%) PWS participants compared to five (35.7%) AS participants, however the difference was not significant (χ² = 2.801, p = .094). The mean Calibrated Severity Score (CSS) for the total (PWS: Median [Md] = 7.00; AS: Md = 3.00) and the Social Affect (SA; PWS: Md = 6.00; AS: Md = 3.00) domains of the ADOS-2 were significantly higher in PWS participants (p = .003 and .001, respectively); however the two groups did not differ on Repetitive and Restricted Behaviour (RRB) CSS scores (PWS: Md = 6.00; AS: Md = 6.00; p = .408). Individuals with PWS meeting criteria for ASD on the ADOS-2 had significantly lower VIQ (p = .006) and FSIQ (p = .018) scores compared to PWS patients not meeting criteria for ASD. In the AS group, no significant differences were found between the two groups on the intellectual functioning domains (p > .05). Exploratory analyses revealed that SA behaviours tended to differentiate those meeting criteria for ASD compared to Non-Spectrum cases, rather than RRBs.

Conclusions: ASD symptoms, particularly SA deficits were more common in individuals with PWS compared to individuals with AS; though the rate of ASD did not significantly differ between the two groups. Meeting criteria for ASD was associated with lower intellectual functioning scores in individuals with PWS, but not those with AS; though effect sizes were moderate to large.