Autism spectrum disorder in Prader–Willi syndrome: A systematic review

Abstract

Prader-Willi syndrome (PWS) is a rare genetic disorder that results from lack of expression of paternally-derived genes on chromosome 15q11-13; caused by a deletion (DEL), uniparental disomy (UPD), or a rare imprinting center defect. PWS is associated with a distinct behavioral phenotype that in some respects overlaps with autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by restricted or repetitive behaviors (RRBs) and social-communication impairment. The goal of this review was to (i) review published literature investigating core ASD symptoms in PWS and (ii) provide a prevalence estimate of ASD in PWS. Two independent reviewers searched Medline, CINAHL, PsychINFO, Embase, and Web of Science to find studies that answered the research questions. Individuals with PWS demonstrate significant levels of RRBs and social-communication impairment, in some reports reaching similar levels to those of non-PWS ASD comparison groups. Individuals with UPD had more social-communication impairment than those with DEL. Of 786 PWS participants, 210 (26.7%) were reported as meeting criteria for ASD, either based on clinical diagnosis or by exceeding clinical cut-points on relevant ASD symptom measures. In studies that distinguished genetic subtypes, rates of ASD were higher in individuals with PWS with UPD (67 of 190; 35.3%) than those with DEL (47 of 254; 18.5%). Published data on the association of PWS and ASD to date are limited to sample means of 8 years of age and older. Further research is needed to identify early markers of ASD in PWS children, to support earlier diagnosis and intervention for this important comorbidity.

The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families

“…This is a marked contrast to the 27% of PWS cases diagnosed with ASD. 13 Notable cognitive behavioral characteristics were described as being impulsive, compulsive, varying degrees of stubbornness, and being manipulative. Detailed neuropsychological phenotyping would be warranted to further delineate the behavioral phenotypes of individuals with MAGEL2 loss-of-function.…”

Feeding, eating and behavioral disturbances in Prader-Willi syndrome and non-syndromal obesity

“…The number of participants with PWS beyond the cut-off value of 15 for an autism spectrum disorder (ASD) was 50%, which is higher than generally assumed. According to most recent estimations of Bennet et al, 26.7% of persons with PWS meet the criteria for ASD [42]. Furthermore, our autism screening scores were correlated with the CBCL total problems T scores in the entire study group.…”

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

“…Notably, previous research in non-PWS samples indicates that both parent reports and observational data are essential to valid diagnostic assessment for ASD [22]. In a recent systematic review of ASD in PWS, Bennett et al [3] reported that most studies investigating ASD in PWS are based on single measures, with parent reports more common than observational assessment (i.e., ADOS-2). Given that parent reports may be less resource-intensive and require less specialized training, they may be more feasible to administer in a clinical program serving a rare population such as PWS.…”

“…Indeed, the prevalence of ASD in PWS has been estimated at 26.7% based on exceeding clinical cut-points on relevant ASD assessments [3]. Also, ASD in the UPD genetic subtype (35.3%; two maternal copies of chromosome 15 present) is almost twice as common as in the DEL subtype (18.3%) [3]. This may be partially due to a genetic finding that overexpression of chromosome 15 is associated with higher rates of ASD [4].…”

“…A recent systematic review [3] found that few studies investigating ASD in PWS have included the Autism Diagnostic Observation Schedule (ADOS) [18] or the Autism Diagnostic Interview-Revised (ADI-R) [19], considered to be gold standard measures of ASD symptoms based on excellent sensitivity and specificity in differentiating ASD from other developmental disorders [20]. Moreover, rates of ASD reported in PWS are generally not based on ICD or DSM-based clinical diagnoses, but are rather based on clinical cut-offs on proxy measures such as the Social Communication Questionnaire (SCQ) [3]. This is problematic, as no single measure can be used as a proxy for diagnosis.…”