Investigating Autism-Related Symptoms in Children with Prader-Willi Syndrome: A Case Study

Abstract

Prader-Willi syndrome (PWS), a rare genetic disorder caused by the lack of expression of paternal genes from chromosome 15q11-13, has been investigated for autism spectrum disorder (ASD) symptomatology in various studies. However, previous findings have been variable, and no studies investigating ASD symptomatology in PWS have exclusively studied children. We aimed to characterize social communication functioning and other ASD-related symptoms in children with PWS, and assessed agreement across measures and rates of ASD diagnosis. Measures included the Autism Diagnostic Observation Schedule-2 (ADOS-2), the Social Communication Questionnaire (SCQ), Social Responsiveness Scale-2 (SRS-2), Social Skills Improvement System-Rating Scales (SSIS-RS), and the Vineland Adaptive Behavioral Scales-II (VABS-II). General adaptive and intellectual skills were also assessed. Clinical best estimate (CBE) diagnosis was determined by an experienced developmental pediatrician, based on history and review of all available study measures, and taking into account overall developmental level. Participants included 10 children with PWS, aged 3 to 12 years. Three of the 10 children were male and genetic subtypes were two deletion (DEL) and eight uniparental disomy (UPD) (with a total of 6 female UPD cases). Although 8 of the 10 children exceeded cut-offs on at least one of the ASD assessments, agreement between parent questionnaires (SCQ, SRS-2, SSIS-RS) and observational assessment (ADOS-2) was very poor. None of the children were assigned a CBE diagnosis of ASD, with the caveat that the risk may have been lower because of the predominance of girls in the sample. The lack of agreement between the assessments emphasizes the complexity of interpreting ASD symptom measures in children with PWS.

The RDoC approach for translational psychiatry: Could a genetic disorder with psychiatric symptoms help fill the matrix? the example of Prader–Willi syndrome

“…Conversely, in childhood and adulthood, the patients display hyperphagia and poor satiety, which leads to early severe obesity with endocrine dysfunction (impaired sexual development and growth, central hypothyroidism) and intellectual disabilities. This syndrome is also associated with psychiatric manifestations, including symptoms that can be connected with several DSM and ICD diagnoses, such as intellectual disability, autism spectrum disorders 7 , schizophrenic disorders 8 , addictive behaviors 9 , 10 , obsessive-compulsive disorders 11 , attention deficit hyperactivity disorder (ADHD), and mood disorders 12 . Besides ID that is common, the heterogeneity in these potential ICD and DSM diagnoses indicates the limitations of these classifications, especially for comprehensive genetic models.…”

Comparison of Aberrant Behavior Checklist profiles across Prader–Willi syndrome, Down syndrome, and autism spectrum disorder

“…A recent study by Bennett et al, tried to characterize ASD symptoms in children with PWS using Autism Diagnostic Observation Schedule‐2 (ADOS‐2), the Social Communication Questionnaire (SCQ), Social Responsiveness Scale‐2 (SRS‐2), Social Skills Improvement System‐Rating Scales (SSIS‐RS), and the Vineland Adaptive Behavioral Scales‐II (VABS‐II). They found discrepancy in parent‐reported measurements of ASD symptom severity and observation‐based diagnosis through ADOS‐2 (Bennett, Hodgetts, Mackenzie, Haqq, & Zwaigenbaum, ). As the ABC is a parent/caregiver reported measure, this may have influenced the accuracy of our scores in comparison to a validated provider based tool.…”

“…A recent study comparing SCQ, ADOS‐2 and clinical diagnosis of ASD in PWS found that SCQ and ADOS‐2 had high negative predictive values but also had high false positive rates leading to an overestimation of ASD diagnosis (Dykens et al, ). In addition, Bennet et al noted that none of the children who met ASD cut‐off with screening tools such as SCQ or ADOS met clinical best estimate criteria for ASD based on DSM‐5 because of inconsistencies among measures (Bennett et al, ). This may be why we had different rates of ASD in our PWS cohorts than previously reported.…”

Risk Factors for Unhealthy Weight Gain and Obesity among Children with Autism Spectrum Disorder

“…PWS is characterized by hyperphagia, elevated ghrelin concentrations, and increased risk for obesity [93,94]. PWS is also associated with higher rates of social-communication impairments and repetitive behaviors [95], although the degree to which symptoms meet diagnostic criteria for ASD varies across studies, emphasizing that ASD symptom measures require careful consideration of developmental profile and overall clinical context [95,96]. That said, genetic mechanisms underlying the association between Prader Willi and ASD may underlie obesity risk related to hyperphagia in a subset of individuals with ASD [97].…”