A Conceptual Framework for Understanding Symptoms of Autistic Disorder in the PWS Phenotype

Janice Forster, Linda Gourash

Pittsburgh Partnership, Specialists in Prader-Willi Syndrome, Pittsburgh, PA

Introduction: Autism is a syndrome defined by observable and quantifiable behavioral parameters associated with developmental onset. Autistic Disorder is diagnosed by the presence of 1) qualitative impairment in social interaction, 2) qualitative impairment in communication, 3) restricted/repetitive and stereotypic patterns of behavior, and 4) developmental delay with onset of symptoms occurring prior to 3 years of age. The multi-factorial etiology is believed to be a combination of genetic and environmental factors. The use of research diagnostic instruments such as the Autism Diagnostic Interview-Revised (ADI-R, Lord et al 1994) has resulted in better definition of the autistic phenotype. This instrument was not intended to provide quantitative measures of dimensions to be interpreted as severity. However, others have applied this instrument to heterogeneous populations of individuals with pervasive developmental disorder leading to the conceptualization of a spectrum of autistic disorders. The application of this instrument to individuals with developmental disabilities due to specific genetic syndromes has led to the opinion that the behavioral phenotype of some syndromes may fall on the autistic spectrum. In this presentation, a conceptual framework will be described to understand the overlap between the autism phenotype and the behavioral phenotype of PWS. The benefits and short-comings of this association will be discussed.

Methods: Literature review and clinical practice will inform this presentation.

Results: Most of the studies examining the phenomenology of autistic symptoms within the PWS phenotype have used the DSM-IV diagnostic criteria (qualitative symptoms) for autistic disorder. Sample size has been small and the population of individuals with PWS has been heterogeneous for age, gender, IQ, and genotype. Some studies have attempted to use adaptive behavior scales to quantify the level of functioning. Overall, the use of different scales makes difficult the task of comparing results. Many genetic studies have used the ADI-R to explore the association between phenotypic symptoms among individuals with pervasive developmental disorder and specific linkage sites in the 15 q11-q13 region. In particular, the repetitive motor activity in the autistic phenotype has been associated with the GABA locus distal to the PWS region. The domains of language form/use and social communication have been more difficult to study. Among individuals with pervasive developmental disorders, social behavior appears to occur along a continuum with the highest deficits noted among individuals with Autistic Disorder and Asperger’s Disorder. Language form and use appear to have the greatest familial aggregation. Individuals with pragmatic language disorder are at greater risk for concurrent social communication problems. Individuals with non-verbal learning disorders (NVLD) also have pragmatic language deficits and motor problems often seen in Asperger’s Disorder.

Discussion: Although a few individuals with PWS undoubtedly meet criteria for Autistic Disorder by DSM-IV criteria and ADI-R, the majority of individuals reflect the heterogeneity of the PWS phenotype and the autistic spectrum. Defining domains of overlap as well as of difference and combining these results with studies of first-degree relatives will inform results in the social communication and language domains. Understanding the genetic contribution to the heterogeneity of PWS phenotype will enhance our understanding of the genetic etiology of autistic spectrum disorders overall.