What is the treatment for Prader-Willi syndrome?

Treatment of Prader-Willi Syndrome

The treatment of Prader-Willi syndrome requires strict environmental food control combined with growth hormone therapy, multidisciplinary monitoring, and behavioral management—this comprehensive approach can extend life expectancy from the typical fourth decade to the seventh decade. 1

Core Treatment Pillars

Growth Hormone Therapy

• Initiate growth hormone (GH) therapy as early as 2-3 months of age, even though FDA approval is for children >2 years with documented growth failure 2
• GH therapy improves body composition, increases lean muscle mass, enhances motor development, and normalizes body habitus 2
• Mandatory polysomnography before starting GH and repeat 6-10 weeks after initiation, regardless of age, due to risk of adenotonsillar hypertrophy and obstructive apnea 2
• Monitor IGF-1 levels at least twice yearly, dosing to keep IGF-1 in physiologic range 2
• Monitor head circumference at each visit, as GH can cause abnormal head growth, especially if fontanelles are open 2
• Critical warning: Several deaths have occurred in children as young as 3 years within 6 months of initiating GH therapy, though the role of GH is unclear 2

Strict Dietary and Environmental Food Control

• The hyperphagia in PWS represents neurological inability to feel satiety due to hypothalamic dysfunction, not a behavioral choice—environmental controls are mandatory, not optional 3
• Implement physical barriers: locks on cabinets and refrigerators, supervised meal times with strict routines 2
• Schedule annual (or more frequent) meetings with a dietitian to review caloric intake and provide less calorically dense foods 2
• Educate all family members, caregivers, and school staff that "sneaking" food undermines the child's nutritional regimen and sense of well-being 2
• Life-threatening complication: High pain tolerance can mask symptoms of intestinal necrosis after binge-eating; vomiting after binge-eating is an ominous sign requiring immediate evaluation 2

Behavioral Management

• Skin-picking should be managed primarily with behavioral interventions; topiramate is reserved only for the most severe cases 2
• Selective serotonin-reuptake inhibitors (SSRIs) are used for behavior management in adolescents and adults 2
• Establish rigid daily routines early to minimize temper tantrums and oppositional behaviors 2
• Monitor for developing psychosis or increasing obsessive-compulsive behaviors, particularly in cases with maternal uniparental disomy (UPD) 2

Age-Specific Management Protocols

Infancy (Birth to 2 Years)

• Address severe hypotonia and poor feeding with nasogastric feedings using increased caloric-density formula if needed 2
• Use special nipples/feeders (Pigeon feeder, Haberman nipple) to reduce work of sucking 2
• Limit oral feeding time to maximum 20 minutes per feeding to avoid exhaustion 2
• Refer to early intervention services for physical therapy, occupational therapy, and speech therapy 2
• For males with undescended testes, trial human chorionic gonadotropin (hCG) before surgery to avoid general anesthesia in hypotonic infants 2

Early Childhood (2-6 Years)

• Transition from failure to thrive to weight gain prevention as hyperphagia begins 3
• Establish optimal dietary and physical exercise patterns before obesity develops 2
• Annual hearing and vision screening; refer to pediatric ophthalmologist for strabismus evaluation 2
• Refer to pediatric dentist for more frequent cleanings (every 3-4 months vs. every 6 months) due to reduced salivation and increased caries risk 2

Late Childhood (5-13 Years)

• Annual scoliosis evaluation; refer to pediatric orthopedist as indicated 2
• Screen for obstructive sleep apnea symptoms (snoring, restless sleep, excessive daytime sleepiness); refer to sleep or pulmonary specialist 2
• Annual vision screening with attention to strabismus recurrence 2
• Thyroid screening every 2-3 years or if symptomatic 2
• Monitor for premature adrenarche (usually requires only reassurance without treatment) 2

Adolescence and Adulthood

• Refer to pediatric endocrinology to discuss pros and cons of sex hormone therapy 2
• Discuss psychosexual development, contraception needs, and risk of genetic abnormalities if pregnancy occurs 2
• Regular monitoring for diabetes, hypertension, sleep apnea, heart failure, and peripheral edema 2
• Discuss financial planning and guardianship arrangements 2

Critical Monitoring Parameters

Ongoing Surveillance

• Weight control with maintenance or loss strategy as primary focus 2
• Physical examination emphasizing heart failure, peripheral edema, and skin-picking (especially perianal areas and intertriginous folds) 2
• Annual evaluation of diet, caloric intake, and exercise program 2
• Use PWS-specific growth curves only for children not treated with GH; use regular curves for those on GH therapy 2

Pharmacological Considerations

• Emerging therapies including metformin, topiramate, liraglutide, and setmelanotide show promise but lack widely accepted consensus guidelines for children with PWS 4
• Bariatric surgery remains controversial with conflicting data on safety and efficacy 5, 6

Prognosis Impact

• Without meticulous weight control, death typically occurs in the fourth decade from massive obesity, diabetes, obstructive sleep apnea, and right-sided heart failure 3, 1
• With comprehensive management including strict food control, individuals can remain healthy into their seventh decade 3, 1
• The single most important determinant of life expectancy is adequate control of hyperphagia and prevention of obesity-related complications 1