Prader-Willi Syndrome

Prader-Willi Syndrome (PWS) is a relatively rare genetically determined neurodevelopmental disorder. People with the syndrome have their own individual characteristics but share in common particular physical features, specific cognitive strengths and weaknesses, and a propensity to particular behaviors and mental health problems that change with age and together make up the early and later physical and behavioral phenotypes of the syndrome.

Prader-Willi is caused by the deletion of a gene on chromosome 15. The majority of patients have a deletion of the father's DNA in this region. The remaining patients frequently have two copies of the mother's chromosome 15. The maternal copy of this gene is turned off in all people. When there is a deletion of the father's DNA (approximately 70% of patients), the disease occurs. This is because the patient is left with only the inactive, maternal copy.

The manifestations of PWS are generally evident at birth. Babies with the condition are often small and very floppy (hypotonic). Males may have undescended testicles. The growing child exhibits slow mental and delayed motor development, increasing obesity, and characteristically small hands and feet. Mental development is slow, and the IQ seldom exceeds 80.

After an initial unwillingness to feed, children with PWS develop an intense craving for food, which leads to morbid obesity. This is a life-long problem that, without intervention, results in uncontrollable weight gain. Morbid obesity (the degree of obesity that seriously affects health) may lead to respiratory failure with hypoxia (low blood oxygen levels), cor pulmonale (right-sided heart failure), and death. Appetite suppressants are shown not to work, and stomach stapling is ineffective. While people with PWS can demonstrate will power in other areas of their life, food seeking and eating (even out of waste receptacles) cannot be controlled. Sufferers will go to great lengths to obtain anything even vaguely edible. Unless their diet is carefully controlled (locks on cupboards and the fridge, and even the doors to the house, for example) weight gain can be very rapid.  Coupled with an inability to recognize when they are full, PWS sufferers have a greatly reduced capacity to feel pain. People with the syndrome have been known to walk around with a broken arm hanging limply by their side without any recognition that it is damaged.

Psychiatric disorders are common in people with PWS, with obsessive behaviors most evident. A propensity for affective disorders (e.g., rage, anxiety and panic attacks) appears to be higher in PWS sufferers than in the normal population.

This book, Prader-Willi Syndrome follows a process of discovery that included getting to know many people with PWS and their families through the undertaking of a population-based study of children and adults with PWS living in the then Anglia and Oxford Health Region of the United Kingdom. The aims of this study were to systematically investigate many aspects of the syndrome free from the selection biases that may have influenced previous clinic and volunteer-based studies. The in-depth knowledge gained from this Cambridge study through direct contact with people with PWS, their families and other carers, and the integration of this knowledge with that in the literature, has led in turn to new hypotheses and new interpretations of some aspects of PWS.

The authors of this book, both Cambridge University scholars, were motivated to do this study because they recognized that to understand PWS fully there is the need to integrate research from the diverse fields of genetics and the behavioral, medical and neurosciences. The integration of these scattered and still incomplete areas of knowledge is the central aim of this book. By doing this the pathophysiological mechanisms linking the observed genetic abnormality (genotype) to the physical, behavioral, and psychiatric manifestations (phenotype) of the syndrome are well elucidated (though personal accounts of PWS sufferers would have supplied yet another valuable dimension to the study). The study, as is, enables the development of interventions to modify aspects of the phenotype and thereby increase the possibility of a good quality of life for those with the syndrome and their families.  Highly recommended.

© 2005 Elizabeth McCardell

Elizabeth McCardell, PhD, Independent scholar, Australia.