Diagnoses and characteristics of autism spectrum disorders in children with Prader-Willi syndrome

Abstract

BackgroundA small percentage of people with autism spectrum disorders (ASD) have alterations in chromosome 15q11.2-q3, the critical region for Prader-Willi syndrome (PWS). Data are limited, however, on the rates and characteristics of ASD in PWS. Previous estimates of ASD in PWS (25 to 41%) are questionable as they are based solely on autism screeners given to parents. Inaccurate diagnoses of ASD in PWS can mislead intervention and future research.MethodsOne hundred forty-six children and youth with PWS aged 4 to 21 years (M = 11) were assessed with the Autism Diagnostic Observation Schedule-2 (ADOS-2). An expert clinical team-made best-estimate ASD diagnoses based on ADOS-2 videotapes, calibrated severity scores, and children’s developmental histories and indices of current functioning. Children were also administered the Kaufman Brief Intelligence Test-2, and parents completed the Repetitive Behavior Scale-Revised and Vineland Adaptive Behavior Scales. Scores were compared across children with PWS + ASD versus PWS only. The performance of an ASD screener, the Social Communication Questionnaire (SCQ) and the ADOS-2 were evaluated in relation to best-estimate diagnoses.ResultsBest-estimate diagnoses of ASD were made in 18 children, or 12.3% of the sample, and the majority of them had the maternal uniparental disomy (mUPD) PWS genetic subtype. Compared to the PWS-only group, children with PWS + ASD had lower verbal and composite IQ’s and adaptive daily living and socialization skills, as well as elevated stereotypies and restricted interests. Regardless of ASD status, compulsivity and insistence on sameness in routines or events were seen in 76–100% of children and were robustly correlated with lower adaptive functioning. The SCQ yielded a 29–49% chance that screen-positive cases will indeed have ASD. The ADOS-2 had higher sensitivity, specificity and predictive values. Communication problems were seen in children who were ADOS-2 positive but deemed not to have ASD by the clinical team.ConclusionsAutism screeners should not be the sole index of probable ASD in PWS; children need to be directly observed and evaluated. Compulsivity and insistence on sameness are salient in PWS and likely impede adaptive functioning. Most children with PWS only evidenced sub-threshold problems in social interactions that could signal risks for other psychopathologies.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-017-9200-2) contains supplementary material, which is available to authorized users.

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

“…There were some differences in our PWS cohort in regards to distribution of genetic subtype and prevalence of ASD among subtypes than previously reported (Cassidy, Schwartz, Miller, & Driscoll, ). In regards to genetic subtype, more recent studies describe different trends in genotype distribution than classically reported (65–75% deletion, 20–30% mUPD, and 2–5% imprinting defect) with higher percentages of mUPD, similar to our distribution (Butler et al, ; Butler et al, ; Dykens et al, ). This may be a reflection of improved diagnostic methods and need for updated epidemiological studies.…”

“…A review of 15 ASD studies in PWS found that children with PWS had high rates of restricted and repetitive behavior and impairment in social communication similar to general ASD populations (Bennett et al, ). A recent study found lower verbal and composite IQ scores, more social and communication impairments, more restricted behavior, and increased stereotypies in children with PWS + ASD compared to those with PWS only (Dykens et al, ). As none of these studies used the ABC as a measure, it would be difficult to compare these results with our findings.…”

“…Despite the reports of elevated ASD rates in PWS, there is still debate as to the best method of screening for ASD in PWS. A recent study showed high rates of false positive ASD when using screening methods only compared to clinical evaluation leading to a lower reported rate of ASD (12.3%) in their cohort (Dykens et al, ). As in PWS, higher rates of ASD have been reported among individuals with DS, with a wide variability, likely due to differences in sample populations as well as screening/diagnostic methodologies (Capone, Grados, Kaufmann, Bernad‐Ripoll, & Jewell, ; Carter, Capone, Gray, Cox, & Kaufmann, ; Hepburn, Philofsky, Fidler, & Rogers, ; Moss, Richards, Nelson, & Oliver, ; Oxelgren et al, ).…”

“…There is a wide variability in severity of core symptoms, level of adaptive and cognitive functioning, and co‐morbid neuropsychiatric disturbances among individuals with ASD. Best estimate diagnosis of ASD may require direct observation of the affected individual's behavior and comprehensive developmental history obtained from primary caregiver(s) by experienced clinician(s) (Dykens et al, ). Several clinical instruments validated and utilized frequently to assist with ASD ascertainment and/or screening include but are not limited to Autism Diagnostic Interview‐Revised (ADI‐R) (Lord, Rutter, & Le Couteur, ), Autism Diagnostic Observation Schedule (ADOS) (Lord et al, ), Social Communication Questionnaire (SCQ) (Rutter, Bailey, & Lord, ), and Social Responsiveness Scale‐2 (SRS‐2) [Constantino and Gruber, ], among others.…”

Genotype-Phenotype Relationships and Endocrine Findings in Prader-Willi Syndrome

“…Individuals with the larger type 1 deletion (Figure 1) have been reported to have better academic performance and intellectual abilities, and more compulsiveness when compared to type 2 deletion patients (69,70). Several other features are more common in mUPD individuals, such as post-term delivery, higher verbal IQ, psychosis and autism spectrum disorder (15,69,(71)(72)(73)(74)(75). On the other hand, mUPD patients are less likely to have the typical PWS facial appearance or hypopigmentation (16).…”