Prader-Willi Syndrome: Medical Prevention and Behavioral Challenges

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In this article the authors discuss the genetic, medical, and endocrinologic issues of Prader-Willi syndrome and their treatment. The authors also present the typical cognitive profile characterized by specific strengths and areas of disability. The behavioral phenotype of Prader-Willi syndrome affects four domains: food-seeking related behaviors; traits that indicate lack of flexibility; oppositional behaviors, and interpersonal problems. The management of the maladaptive behaviors is challenging and requires lifelong restrictive supervision (to prevent morbid obesity), addressing psychiatric comorbidity, psychopharmacologic management exacerbated by metabolic abnormalities, ongoing medical care, and, in many cases, institutional treatment. The multiple facets of the clinical problems demand a multidisciplinary approach with anticipatory medical and psychiatric care, oriented to enhancing the quality of life of individuals who have Prader-Willi syndrome.

Section snippets

Genetics

Deletion or abnormal expression of paternal genes in chromosome 15q11-13 can result in the Prader-Willi phenotype. Complete or partial deletion of paternal 15q11-q13 accounts for 70% of affected patients, whereas approximately 25% have uniparental maternal disomy (UPD). In normal chromosome pairs, each chromosome is derived from a different parent. The term “uniparental disomy” indicates that both copies of a particular chromosome derive from only one of the parents. Inheriting both copies of

Medical considerations

Medical problems are inherent within the clinical diagnostic criteria of PWS and differ according to the stage of life [7]. Perinatally, the manifestations are difficult delivery, central hypotonia, poor sucking, motor delay, and failure to thrive, which often necessitate special feeding techniques such as nasogastric tubes. The characteristic dysmorphic features include dolichocephaly and almond-shaped eyes. Small mouth, hands, and feet, speech articulation defects, and a distinct prosody

Endocrine disorders and hormonal treatment

Children who have PWS show variable degrees of impaired growth hormone (GH) secretion along with low levels of serum insulin and insulin-like growth factors. If untreated, 50% of individuals who have PWS fail to reach a normal adult height. GH treatment of these children results in a significant and persistent increase in height velocity and height standard deviation scores [14].

Beyond increasing final height, GH has other important beneficial effects in patients who have PWS. Infants in whom

Cognition

Mental retardation is a major characteristic of PWS. In a meta-analysis of 575 people who have PWS, only 5% were of normal intelligence, one third were found to be moderately retarded, and most were in the borderline mildly retarded range. No IQ decline was seen with age [21]. Unfortunately, their immature social behavior often masks their intellectual abilities [22].

A pattern of cognitive strengths and weaknesses is apparent, although not all individuals who have PWS show this profile [21]. As

Behavioral characteristics and psychiatric issues in Prader-Willi syndrome

Behavioral patterns are remarkably consistent among persons who have PWS, albeit with a wide spectrum of intensity and frequency. The characteristic symptom complex is often termed “the behavioral phenotype of PWS,” which qualifies persons who have PWS for an Axis I diagnosis of “personality change due to a medical condition” [29]. Forster and Gourash [30] suggested a useful classification in domains that we have modified in accordance with our clinical experience.

Comorbid psychiatric disorders

Levels of psychopathology are found to be higher among persons who have PWS than among persons with intellectual disability of other origins [42]. Attention deficit hyperactivity disorder and obsessive-compulsive disorder already have been discussed, and this section focuses on mood and psychotic disorders.

Sudden bursts of disturbed mood, as part of the “normal” behavioral pattern in PWS, are generally trigger-dependent and short lived. During adolescence, prolonged waves of restlessness and

Psychopharmacology

The therapeutic and side effects of medications in patients who have PWS often can be greater than expected, even in severely obese patients who receive low dosages when considering their body weight. For many patients, one fourth to one half of the normally prescribed dose is sufficient, whereas usual dosage levels may cause toxic reactions or exacerbation of behavior problems [9]. Severely reduced metabolism by some components of cytochrome 450, a metabolic abnormality documented in one third

Behavioral and institutional treatment

Managing behaviors of people who have PWS can be successful in the long-term if a comprehensive and consistent approach is implemented [9], [47]. The treatment should focus on food- and non–food-related behaviors. As for the food-related issues, the most basic aspect of any program is having all food under lock and key and granting no access without parental or staff supervision. It is critical that all food-related activities be structured and consistent, including meal times, the particular

The multidisciplinary approach

The complexity of the clinical problems in patients who have PWS requires an approach that integrates the different professional fields involved. The PWS multidisciplinary clinic at our institution is one model of integrated care. The clinic staff includes specialists in pediatric neurology, child psychiatry, endocrinology, psychology, orthopedics, and nutrition during a single clinic visit. Consultations with pulmonary and ear, nose, and throat physicians who are familiar with PWS are obtained

Acknowledgments

The authors are deeply grateful to Professor Ruth Shalev for her thoughtful comments and suggestions in revising the manuscript.

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    This study was supported in part by grants from the Peretz Naftali Foundation and the Mirsky Foundation.

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