Comparison of PWS and PWS-Like Individuals Clinically, Cognitively and Biochemically 

Ann S. Hatfield^1,3, Sarah Graman², Helen McCune¹, John H. Kranzler², and Daniel J. Driscoll¹

¹Pediatric Genetics and the Center for Mammalian Genetics, University of Florida College of Medicine: Box 100296, Gainesville, FL 32610-0296.

²College of Education, Univ. of Florida, Gainesville, FL; ³Duke Univ. School of Medicine, Durham, NC 

Introduction: Prader-Willi syndrome (PWS) is a complex neurobehavioral syndrome whose main clinical features include obesity, mild-moderate mental retardation, obsessive-compulsive behavior, hyperphagia, neonatal failure-to-thrive and hypotonia.  PWS is a result of the loss of paternally inherited gene expression in chromosome 15q11-q13.  A growing body of evidence strongly suggests that PWS is a contiguous gene syndrome with loss of expression of several genes resulting in the complete phenotype.  Loss of expression of one gene in this region may lead to some, but not all the features of PWS (i.e., “PWS-like”). 

In our clinics over the past several years we have seen approximately 50 individuals with early childhood obesity (PWS-like) that do not have PWS clinically or molecularly, but do have many features in common as a group with each other and share many characteristics of individuals with PWS.  In particular we have noticed that there is an apparent correlation between early childhood morbid obesity and learning impairment/developmental delay.  We hypothesize that early onset obesity may cause abnormal levels of neuropeptides that may cause learning impairment.  Therefore, we have recently commenced a 5 year study on the Clinical Research Center to investigate the PWS-like patients further and compare them to PWS individuals.   

Methods:  The 5 year study will include 30 deletion PWS patients, 30 UPD PWS patients, and 30 morbidly obese PWS-like patients.  The control group will consist of one sibling per patient.  Study participants will be between the ages of 3 and 70 years, with most between the ages of 5 and 21.  A complete history and physical examination, including education history, diet records, past and present medication use, and skin fold measurements, will be collected on all study participants.  The Woodcock-Johnson Psycho-Educational Battery III will be administered to test cognitive abilities and achievement levels, and the Behavior Assessment System for Children (BASC) to determine psychosocial adaptation of participants.  The Severity of Symptoms Scale will be used to quantify problem behaviors in common between PWS and PWS-like subjects.  All study participants will have fasting blood work for routine tests, including a lipid profile, basic chemistries, complete blood count, insulin, and thyroid panel, as well as specialized measurements of neuropeptides involved in satiety and obesity, such as leptin, neuropeptide Y (NPY) and ghrelin.  Willing PWS and PWS-like participants will also undergo a fasting lumbar puncture to measure leptin, NPY and ghrelin in the cerebrospinal fluid.  All procedures will be repeated in one year.  Blood will also obtained for additional DNA and RNA analyses. 

Results and Discussion:  We have found certain commonalties within the PWS-like group.  Many of these subjects were obese from infancy, have insatiable appetites and/or thirsts, and show signs of insulin-insensitivity, such as acanthosis nigricans.  Additionally, many of the PWS-like individuals are tall for their age, have increased bone age and very large head circumferences.  Some of the PWS-like individuals demonstrate behaviors similar to PWS patients such as skin picking and explosive tempers, and many have learning impairments similar to PWS individuals.  In addition, we will present the preliminary results of our ongoing cognitive and biochemical testing comparing the PWS and PWS-like groups.    

This research is supported by the American Diabetes Association, NIH grant K24HD1361 and the NIH funded General Clinical Research Center at the University of Florida.

July 2002