What are the management strategies for a patient with Prader-Willi syndrome?

Management of Prader-Willi Syndrome

Prader-Willi syndrome requires lifelong multidisciplinary management centered on strict environmental food control, growth hormone therapy, sleep disorder screening, and behavioral interventions to prevent life-threatening obesity and its complications. 1

Immediate Diagnostic Confirmation and Initial Assessment

• Confirm genetic diagnosis through chromosome 15q11.2-q13 testing if not already done, as this guides prognosis (uniparental disomy carries higher psychosis risk than deletion). 2, 1
• Assess current nutritional phase (0-4), as management differs dramatically between failure-to-thrive infancy versus hyperphagic childhood/adulthood. 3, 4

Critical Life-Saving Intervention: Food Security

Implement immediate environmental food control - this is non-negotiable and directly impacts mortality. 1, 5

• Lock all food storage areas (refrigerators, pantries, cabinets) with keys kept by caregivers only. 2
• Educate all family members, school staff, and caregivers that unsupervised food access can lead to fatal binge-eating with intestinal necrosis. 2
• Establish structured meal times with portion control - patients require only 60% of calories compared to age-matched peers. 5
• Work with a PWS-experienced dietitian to create a fat-reduced, carbohydrate-modified diet with adequate micronutrient supplementation. 5

Growth Hormone Therapy

Initiate growth hormone therapy at diagnosis and continue lifelong - this is the only FDA-approved treatment and improves body composition, metabolic function, and developmental outcomes. 2, 1, 5

• Refer to pediatric endocrinology for GH evaluation in all patients. 2, 5
• Perform polysomnography before starting GH to rule out sleep-disordered breathing, though testing should not delay GH initiation. 2
• GH improves lean body mass, energy expenditure, ventilatory control, and prevents severe short stature from caloric restriction. 2, 5, 3

Sleep Disorder Management

Screen annually for sleep disorders - these affect >50% of patients and contribute to behavioral problems, daytime dysfunction, and mortality risk. 2, 1

Screening Protocol:

• Ask about snoring, restless sleep, excessive daytime sleepiness, and witnessed apneas at every visit. 2
• Obtain baseline polysomnography in infancy (43% have central sleep apnea) and repeat if symptoms develop or worsen. 2
• Perform Multiple Sleep Latency Test when excessive daytime sleepiness persists despite treated obstructive sleep apnea. 2

Treatment Approach:

• Refer to sleep medicine specialist for comprehensive evaluation and management. 2
• Treat obstructive sleep apnea per standard guidelines (CPAP, adenotonsillectomy). 2
• Consider narcolepsy treatment protocols for persistent excessive daytime sleepiness. 2
• Monitor closely after any intervention - PWS patients have abnormal ventilatory responses and increased arousal thresholds. 2

Endocrine Surveillance

Screen for multiple endocrinopathies as these are nearly universal and impact quality of life. 1, 4

• Evaluate growth hormone deficiency at diagnosis (present in almost all patients). 2, 4
• Screen thyroid function every 2-3 years or when symptomatic (hypothyroidism occurs in up to 30%). 2, 4
• Assess for hypogonadism and discuss sex hormone replacement in adolescence/adulthood. 2, 4
• Monitor for premature adrenarche (common but usually requires only reassurance). 2
• Screen for diabetes in obese patients (affects up to 25% of obese adults). 4

Musculoskeletal Monitoring

Evaluate annually for scoliosis starting in childhood - prevalence ranges from 15-86% and impacts respiratory function. 2

• Refer to pediatric orthopedics when scoliosis is detected. 2
• Monitor muscle tone regularly as hypotonia persists lifelong. 2

Behavioral and Psychiatric Management

Implement structured behavioral interventions early - behavioral rigidity, temper tantrums, skin-picking, and psychiatric disorders worsen with age. 2, 1

• Establish rigid daily routines as patients have extreme difficulty with schedule changes. 2, 1
• Address skin-picking primarily through behavioral modification; reserve topiramate for severe cases only. 2
• Screen for emerging psychosis and obsessive-compulsive symptoms in adolescence/adulthood, particularly in uniparental disomy cases. 2, 1
• Provide early intervention services (physical therapy, occupational therapy, speech therapy) from infancy. 2

Dental Care

Refer to pediatric dentist by age 1 year - reduced salivation increases caries risk dramatically. 2

• Schedule dental cleanings every 3-4 months (not standard 6-month intervals). 2

Vision and Hearing

• Screen vision annually with attention to strabismus recurrence. 2
• Refer to pediatric ophthalmology if strabismus or other concerns arise. 2
• Perform annual hearing screening. 2

Critical Safety Considerations

Educate families about high pain tolerance - this masks serious complications and delays treatment. 2

• Vomiting after binge-eating is an ominous sign requiring immediate evaluation for intestinal necrosis (patients rarely vomit). 2
• Any acute abdominal symptoms warrant urgent surgical evaluation despite minimal pain complaints. 2

Perioperative Management:

• Admit all PWS patients to ICU/high-dependency unit for 24-48 hours continuous monitoring after any surgical procedure, regardless of complexity. 6
• Reduce opioid doses by 50% or avoid completely - respiratory depression occurs at much lower doses. 6
• Use non-opioid analgesia as primary pain management. 6
• Obtain preoperative sleep study and optimize sleep apnea treatment before elective surgery. 6

Weight Management Algorithm

Prevent obesity through caloric restriction and exercise - without adequate control, death typically occurs in the fourth decade from obesity complications. 1, 4

Caloric Requirements:

• Infants: May need nasogastric feeding with high-calorie formula due to poor suck. 2
• Children/adults: Require approximately 60% of standard caloric needs (8-10 kcal/cm height for weight maintenance). 5

Exercise Program:

• Establish daily physical activity routines from early childhood. 2
• Schedule regular meetings with dietitian (at minimum annually, more often if weight gain occurs). 2

Pharmacological Considerations:

• Growth hormone is the cornerstone - improves body composition and metabolic parameters. 2, 5, 3
• Emerging evidence supports metformin, topiramate, liraglutide, and setmelanotide, but no consensus guidelines exist for children. 3
• Bariatric surgery remains controversial and should be avoided given perioperative risks. 7

Transition to Adult Care

Establish transition plan by adolescence - adult services must maintain the same strict food control and behavioral policies. 8, 9

• Discuss sexuality, contraception, and fertility (patients often desire children but cannot safely parent). 2
• Address vocational planning and supervised living arrangements. 2
• Ensure adult providers understand PWS-specific risks (high pain tolerance, opioid sensitivity, food security needs). 6, 9

Prognosis

With meticulous weight control and comprehensive management, individuals can live into their seventh decade; without adequate control, death typically occurs in the fourth decade from obesity-related complications. 1