Jennifer R. Zarcone¹, Deborah Napolitano¹, Christine Peterson¹, Jean Guadagnino¹, Douglas C. Bittel², Merlin G. Butler², Travis I. Thompson³

 ¹Strong Center for Dev. Disabilities, Univ. of Rochester Medical Center, Rochester, NY
²Children’s Mercy Hospital and University of Missouri-Kansas City, Kansas City, MO
³Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 

Introduction: There are clear behavioral phenotypes associated with each of the genetic subtypes of Prader-Willi syndrome (PWS) not only associated with the maternal disomy (UPD) and deletion subtypes but also within the deletion subtype (long/Type I deletion and short/Type II deletion). By delineating the behavioral phenotype associated with each subtype, preventive strategies can be employed for individuals with PWS as well as more successful psychiatric, psychological and behavioral treatment strategies.  

Methods: Behavioral data were collected with 96 individuals with PWS and 62 control participants across three sites (Vanderbilt University, University of Kansas Medical Center, and the University of Rochester Medical Center). Genetic subtype was confirmed through the use of high-resolution chromosome analysis, florescent in situ hybridization (FISH) and DNA microsatellite analysis. Microsatellite markers were used to identify Type I and Type II deletions. Measures included the Reiss Screen and Aberrant Behavior Checklist (for maladaptive behavior), Yale-Brown Obsessive Compulsive Scale, Compulsive Behavior Scale, and Repetitive Behavior Scale for compulsive behavior), the Scales of Independent Behavior (for adaptive behavior), the Woodcock Johnson Tests for Achievement (for academic behavior), Wechsler Adult Intelligence Scale or Wechsler Intelligence Scale for Children – III and modified executive function tasks (for cognitive skills) and the Visual Motor Integration Scale (for visual-spatial skills).   

Results: Results support previous findings that individuals with the UPD subtype tend to have better verbal skills and better adaptive behavior scores, although individuals with the deletion (Type II) subtype tend to have better broad independence scores, better social communication scores, and better motor skills than both UPD and the Type I deletion participants. With regard to problem behavior, individuals with a deletion are more likely to have self-injury (skin picking), to steal and hoard, and are more withdrawn although they have better visual motor skills. There were no differences in level of aggression or in activity level between the subtypes. Additional analyses of compulsive behavior indicate that individuals with the Type I deletion have more hand washing and bathing/grooming compulsions than the other two groups. Individuals with the Type II deletion had more “academic” compulsions such as rereading, erasing, and repeatedly counting numbers and objects. There were no significant differences between the three groups on number of compulsions endorsed or global severity of compulsive behavior.  

Discussion: These data indicate that the behavioral phenotype across the three genetic subtypes may actually fall on a spectrum with a degree of overlap in compulsivity, cognitive skills, and adaptive behavior. Additional analyses of frequency and severity of psychiatric disorders, symptoms of autism, and food motivation are also warranted to evaluate both behavioral and biological characteristics related to each phenotype.

edited: 02/09/2012