What are the typical features and management strategies for a patient with Prader Willi syndrome?

Features of Prader-Willi Syndrome

Prader-Willi syndrome is a genetic disorder caused by loss of expression of paternal chromosome 15q11.2-q13, characterized by a biphasic feeding pattern (neonatal hypotonia with feeding failure followed by insatiable hyperphagia), developmental delays, endocrinopathies, and distinctive behavioral problems that evolve across the lifespan. 1

Genetic Basis

The syndrome occurs in approximately 1 in 10,000-15,000 individuals through three mechanisms: 1, 2

• Paternal deletion (70% of cases) 2
• Maternal uniparental disomy (20% of cases) 2
• Imprinting defects (1-3% of cases) 3

DNA methylation analysis of chromosome 15q11-q13 is the only diagnostic test that identifies all three genetic subtypes and should be performed immediately when PWS is suspected. 2, 3

Clinical Features by Age

Infancy (Birth to 2 Years)

The hallmark early features are profound hypotonia, poor suck, and excessive sleepiness with failure to awaken for feeding, resulting in failure to thrive. 1, 2

• Severe hypotonia requiring nasogastric feeding or special feeders (Pigeon feeder, Haberman nipple) 1
• Feeding sessions should not exceed 20 minutes to avoid exhaustion 1
• Hypogonadism in males (cryptorchidism, scrotal hypoplasia, micropenis) and females (clitoral and labia minora hypoplasia) 1
• Excessive sleepiness preventing normal feeding patterns 1

Early Childhood (2-6 Years)

This period marks the critical transition from failure to thrive to hyperphagia, with emergence of behavioral rigidity and developmental delays. 1, 2

• Persistent hypotonia with global developmental delay 2
• Beginning of hyperphagia and food-seeking behaviors 1, 2
• Behavioral rigidity, particularly around daily routines 1
• Prolonged temper tantrums and oppositional behaviors 1
• Childhood apraxia of speech 1

School Age (6-12 Years)

Hyperphagia becomes the dominant feature with obsessive food-seeking, rapid weight gain, and central obesity despite poor linear growth. 2

• Insatiable appetite with inability to feel satiety due to hypothalamic dysfunction 2
• Food-seeking behaviors including stealing food, eating spoiled food, searching garbage, and stealing money 1
• Skin-picking, particularly in perianal areas and intertriginous folds 1
• Compulsive behaviors (hoarding, concerns with symmetry, ordering) 4
• Short stature despite obesity 3

Adolescence and Adulthood

Behavioral problems intensify with increased risk of psychosis (especially in maternal uniparental disomy cases), while food-seeking behaviors may include running away from home. 1, 4

• Dangerous food-seeking including running away from home 1
• Increased risk of psychotic disorder or affective illness with psychotic features 1, 4
• Obsessive-compulsive disorder at markedly higher rates than other intellectual disabilities 4
• Lying and stealing to obtain food 1

Endocrine Abnormalities

Multiple endocrinopathies result from hypothalamic dysfunction and require systematic screening and treatment. 1, 3

• Growth hormone deficiency (universal finding requiring treatment) 3, 5
• Hypogonadism (both males and females) 1, 3
• Hypothyroidism (screen every 2-3 years or if symptomatic) 1
• Central adrenal insufficiency 3
• Premature adrenarche (often without progression of other pubertal features) 1

Sleep Disorders

Sleep disturbances affect >50% and possibly up to 95% of individuals with PWS, including central and obstructive sleep apnea, excessive daytime sleepiness, and narcolepsy-like phenotypes that persist despite treatment of apnea. 1

• Abnormal hypercapnic and hypoxic ventilatory responses independent of obesity 1
• Lower nocturnal oxygen saturation with clusters of desaturations 1
• Higher arousal threshold to hypercapnia 1
• Screen annually for snoring, restless sleep, and excessive daytime sleepiness with referral to sleep specialist 1

Critical Management Strategies

Food Control (Life-Saving Priority)

The single most important determinant of survival is strict environmental control of food access, as hyperphagia results from neurological inability to feel satiety, not behavioral choice. 6, 2

• Lock all cabinets, refrigerators, and food storage areas 1
• Limit exposures that trigger food thoughts (no birthday treats visible during school day) 1
• Maintain scrupulous mealtime routines to provide security 1
• Educate all relatives and contacts that "sneaking" food is dangerous, not affectionate 1
• Implement reduced-calorie diet with increased physical activity 4

Multidisciplinary Monitoring

Regular evaluation must address weight control, endocrine function, sleep disorders, behavioral management, and developmental progress. 1

• Annual (or more frequent) dietitian meetings to review caloric intake 1
• Thyroid screening every 2-3 years 1
• Annual vision screening with attention to strabismus recurrence 1
• Evaluation for diabetes, hypertension, heart failure, and peripheral edema 1
• Early intervention with physical therapy, occupational therapy, and speech therapy 1

Behavioral Management

Behavioral interventions focus on structure, predictability, and environmental modification rather than punishment, with SSRIs for severe compulsivity and skin-picking. 1, 4

• Structured, predictable routines with extra help during transitions 4
• Behavioral programming for skin-picking (topiramate reserved for most severe cases) 1
• SSRIs effective for reducing skin-picking, compulsivity, and aggressive episodes 4
• Atypical antipsychotics for psychotic features or extreme aggression 4

Growth Hormone Therapy

Growth hormone treatment is standard of care, improving linear growth, muscle mass, bone mineral density, and physical performance. 5

• Monitor for increased risk of obstructive sleep apnea when initiating therapy 1
• Benefits extend beyond growth to body composition and behavior regulation 7, 5

Critical Pitfall to Avoid

The most dangerous error is failing to recognize that hyperphagia represents hypothalamic dysfunction affecting the orexin-hormone system, not a behavioral problem amenable to punishment or reasoning. 6, 2 This requires absolute environmental controls, as individuals with PWS will eat until gastric necrosis occurs, and their high pain tolerance masks symptoms until death is imminent. 1 Vomiting after binge-eating is an ominous sign requiring immediate evaluation, as people with PWS rarely vomit. 1

Prognosis

Without adequate weight control, death typically occurs in the fourth decade from obesity-related complications (diabetes, obstructive sleep apnea, right-sided heart failure), but with meticulous weight control and comprehensive management, individuals can live into their seventh decade. 6