Prader-Willi Syndrome

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Prader-Willi syndrome (PWS) is a genetic disorder usually caused by deletion of a part of chromosome 15. It occurs in approximately one in every 15,000 births. 

Individuals with PWS often have the following characteristics: hypotonia, hypogonadism, hyperphagia, cognitive impairment, and difficult behaviors. Individuals also have the major medical concern of morbid obesity. 

Hypothalamic dysfunction is thought to be the cause of the disordered appetite/satiety function characteristic of PWS. Compulsive eating and obsession with food usually begin before age six. The urge to eat is physiological and overwhelming; it is difficult to control and requires constant vigilance. 

Compounding the pressure of excessive appetite is a decreased calorie utilization in those with PWS (typically 1,000-1,200 calories per day for adults), due to low muscle mass and inactivity. A balanced, low-calorie diet with vitamin and calcium supplementation is essential as is daily rigorous exercise and activity. Regular weigh-ins and periodic diet review are needed. The best meal and snack plan is one the family or caregiver is able to apply routinely and consistently. Weight control
depends on external food restriction and may require locking the kitchen and food storage areas.

To date, no medication or surgical intervention has been found that would eliminate the need for strict
dieting and supervision around food. Growth Hormone Therapy (GH) treatment, because it increases muscle mass and function, may allow a higher daily calorie level. 

Infants and young children with PWS are typically happy and loving, and exhibit few behavior problems. Most older children and adults with PWS, however, do have difficulties with behavior regulation, manifested as difficulties with transitions and unanticipated changes. Onset of behavioral symptoms usually coincides with onset of hyperphagia (although not all problem behaviors are food-related), and difficulties peak in adolescence or early adulthood. Daily routines and structure, firm rules and limits, and positive rewards work best for behavior management. Psychotropic medications, particularly serotonin reuptake inhibitors, such as fluoxetine and sertroline, are beneficial in treating obsessive-compulsive (OCD) symptoms, perseveration, and mood swings. Depression in adults is not uncommon. Psychotic episodes occur rarely. 

IQ scores are variable and can range from 40 to 115.Those with normal IQs typically have learning disabilities. Problem areas may include attention, short-term auditory memory, and abstract thinking.
Common strengths include long-term memory, reading ability, and receptive language. Early infant
stimulation should be encouraged and the need for special education services and supports assessed in preschool and beyond. 

Growth Hormone (GH) Therapy for young children with PWS will eliminate most motor skill problems. Prior to 2000, when the FDA approved the use of GH Therapy for all children diagnosed with PWS, deficits with coordination, balance, and motor planning was a universal part of the syndrome. Today, many adults with PWS are also on growth hormone therapy to improve their motor skills. Exercise and sports activities should be encouraged and a part of daily life for a child with PWS. The ability to play sports and exercise is vastly improved with GH Therapy. Physical and occupational therapies also help promote skill development and proper function. 

Decreased fetal movement, infantile lethargy, weak cry.

Characteristic behavior problems: temper tantrums, violent outbursts, obsessive/compulsive behavior; tendency to be argumentative, oppositional, rigid, manipulative, possessive, and stubborn; perseverating, stealing, lying.

* Sleep disturbance or sleep apnea
* Short stature for genetic background by age 15
* Hypopigmentation, fair skin and hair compared with family
* Small hands and/or feet for height age
* Narrow hands with straight ulnar border
* Eye abnormalities (esotropia, myopia)
* Thick, viscous saliva with crusting at corners of the mouth
* Speech articulation defects
* Skin picking 

General health is usually good in individuals with PWS. If weight is controlled, life expectancy may be normal, and the individual's health and functioning can be maximized.

The constant need for food restriction and behavior management may be stressful for family members. Family counseling may also be needed.

Adolescents and adults with PWS can function well in group and supported living programs, if the necessary diet control and structured environment are provided. Employment in sheltered workshops and other highly structured and supervised settings is successful for many. Residential and vocational providers must be fully informed regarding management of PWS. 

Strabismus Esotropia is common; requires early intervention, possibly surgery.

Scoliosis can occur unusually early; may be difficult to detect without X-ray; curve may progress with GH Therapy. Kyphosis is also common in teens and adults.

Osteoporosis can occur much earlier than usual and may cause fractures; ensure adequate calcium, vitamin D, and weight-bearing exercise; bone density test recommended

Diabetes mellitus, type II secondary to obesity; responds well to weight loss; screen obese patients regularly.

Other obesity-related problems include hypoventilation, hypertension, right-sided heart failure, stasis ulcers, cellulitis, and skin problems in fat folds.

Sleep disturbances hypoventilation and desaturation during sleep are common, as is daytime sleepiness; sleep apnea may develop with or without obesity; sleep studies may be needed.

Nighttime enuresis common at all ages; desmopressin acetate should be used in lower than normal doses.

Skin picking a common, sometimes severe habit; usually in response to an existing lesion or itch on face, arms, legs, or rectum. Best managed by ignoring behavior, treating and bandaging sores, and providing substitute activities for the hands.

Dental problems may include soft tooth enamel, thick sticky saliva, poor oral hygiene, teeth grinding, and infrequently rumination. Special toothbrushes can improve hygiene. Products to increase saliva flow are helpful. 

1. PWSAUSA  Prader-Willi Syndrome Association
2. PWCF  Prader-Willi Syndrome Foundation
3. FPWR  Foundation for Prader-Willi Research
4. Mayo Clinic