What is the recommended management approach 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 initiated at diagnosis, comprehensive sleep disorder screening, and aggressive obesity prevention—these interventions directly impact mortality, which without proper management occurs in the fourth decade but can extend into the seventh decade with meticulous care. 1

Immediate Priorities at Diagnosis

Neonatal Period

• Initiate growth hormone (GH) therapy at diagnosis regardless of age, as it is the only FDA-approved treatment and improves metabolic function, ventilatory control, and cardiovascular function during sleep 2
• Consider polysomnography (PSG) prior to GH initiation to evaluate for central sleep apnea (present in 43% of infants with PWS), though testing should not delay GH therapy 2
• Address profound hypotonia and feeding difficulties with early intervention including physical therapy, occupational therapy, and speech therapy 2
• Monitor for excessive sleepiness in infants who do not awaken or express interest in feeding 2

Endocrine Management

• Screen for and treat growth hormone deficiency (universal in PWS), hypothyroidism (up to 30% of children), and hypogonadism 2, 3
• Perform thyroid screening every 2-3 years or when symptomatic 2
• Evaluate pubertal status and refer to pediatric endocrinology for discussion of sex hormone therapy pros and cons 2

Weight and Nutrition Management (Critical for Survival)

Implement strict environmental food controls immediately—this is the single most important determinant of life expectancy, as hyperphagia results from hypothalamic dysfunction affecting the orexin-hormone system, not behavioral choice. 1

• Establish calorie-restricted diet with locked food storage and supervised meal times from early childhood 2
• Schedule meetings with dietitian at least annually (or more frequently) to review caloric intake and provide less calorically dense foods 2
• Implement regular exercise programs as part of obesity prevention strategy 2
• Monitor weight closely; changes across 1-2 percentiles or rapid weight gain should prompt comprehensive sleep evaluation 2

Critical Pitfall

• Uncontrolled hyperphagia leads to massive obesity, diabetes mellitus, obstructive sleep apnea, and right-sided heart failure, resulting in death typically in the fourth decade 1
• Recognize increased pain tolerance can mask intestinal necrosis after binge-eating; vomiting after binge-eating is an ominous sign requiring immediate evaluation, as people with PWS rarely vomit 2

Comprehensive Sleep Disorder Management

All patients with PWS must be evaluated at least annually for the full spectrum of sleep disorders—not just sleep apnea—as excessive daytime sleepiness (EDS) affects >50% and possibly up to 95% of individuals, persisting despite adequate OSA treatment. 2

Screening and Diagnosis

• Include sleep specialists in the multidisciplinary team, as sleep problems are complex and common 2
• Screen annually for sleep-disordered breathing, excessive daytime sleepiness, narcolepsy, cataplexy, and insomnia 2
• Perform PSG for evaluation of sleep-disordered breathing 2
• Consider sleep diary, actigraphy with overnight PSG followed by Multiple Sleep Latency Test (MSLT) for evaluation of EDS 2
• When EDS is out of proportion to OSA control, assess using MSLT 2

Indications for Urgent Sleep Evaluation

• Change in weight across 1-2 percentiles or rapid weight gain 2
• Change in school performance or new onset attention concerns 2
• Worsening EDS, increased irritability, or behavioral changes 2
• Lack of developmental progression 2

Treatment Considerations

• Treat identified sleep disorders using currently accepted guidelines in consultation with sleep specialists 2
• Consider practice parameters for narcolepsy when treating PWS patients with EDS 2
• Recognize that sleep disorders contribute to behavioral concerns and nighttime food-seeking 2

Behavioral and Psychiatric Management

• Screen for common behaviors including skin-picking, temper tantrums, food-seeking, anxiety, behavioral rigidity, and obsessive-compulsive symptoms 2
• Manage skin-picking primarily with behavioral interventions; reserve medications (including topiramate) only for most severe cases 2
• Monitor for early signs of developing psychosis or increasing obsessive-compulsive behaviors (risk higher with uniparental disomy than deletion) 2
• Consider selective serotonin-reuptake inhibitors for behavior management when indicated 2

Routine Monitoring and Screening

Annual Assessments

• Vision screening annually with attention to strabismus recurrence 2
• Scoliosis evaluation (affects 15-86% of individuals and worsens sleep-disordered breathing) 2
• Assessment for diabetes, hypertension, heart failure, and peripheral edema 2
• Dental evaluation with consideration for more frequent cleanings (every 3-4 months vs. every 6 months) due to reduced salivation and increased caries risk 2

Sleep-Related Monitoring

• Evaluate for snoring, restless sleep, and excessive daytime sleepiness at every visit 2
• Refer to sleep or pulmonary specialist when symptoms identified 2

Transition to Adult Care

• Identify healthcare providers willing to learn about PWS, ideally with training in special needs care 2
• Ensure continuity of weight control, diabetes screening, hypertension monitoring, sleep apnea management, and behavioral support 2
• Discuss sexuality, contraception needs, and genetic risks if pregnancy occurs 2
• Address intrafamily relationships, financial planning, and guardianship 2

Key Clinical Pearls

• GH therapy should be maintained through life for metabolic benefits and improved ventilatory control 2
• Central sleep apnea is more common in infants (43%) compared to older children (5%) 2
• Premature adrenarche often occurs without progression of other aspects of precocious puberty; reassurance is often the only intervention needed 2
• With meticulous weight control and comprehensive management, individuals can remain healthy into their seventh decade (60-70 years) 1