What are the clinical features of Prader-Willi syndrome?

Clinical Features of Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is characterized by distinct age-specific clinical features, including significant hypotonia and poor feeding in infancy, followed by hyperphagia leading to obesity in childhood, along with cognitive impairment, hypogonadism, and characteristic behavioral problems. 1, 2

Infant Presentation (Birth to 2 years)

• Significant hypotonia (nearly universal - 97% of patients) 1, 3
• Poor suck reflex leading to feeding difficulties 1
• Failure to thrive in early infancy 1, 4
• Hypogonadism/hypogenitalism 1
  • Undescended testes in males
  • Small phallus in males
  • Small clitoris in females

Early Childhood Features (2-6 years)

• Global developmental delay (present in 98% of patients) 1, 3
• Short stature due to growth hormone deficiency 1, 2
• Transition to hyperphagia (excessive appetite) 1
• Small hands and feet (acromicria) 4, 5
• Characteristic facial features (49% sensitivity) 3
  • Almond-shaped eyes
  • Thin upper lip
  • Narrow bifrontal diameter

Later Childhood Features (6-12 years)

• Excessive eating (hyperphagia) with obsession for food 1, 2
• Central obesity if eating is uncontrolled 1
• Persistent hypotonia (though less severe than infancy) 1
• Speech and articulation defects (93% sensitivity) 3
• Behavioral problems beginning to emerge 2
• Continued developmental delay 1

Adolescent and Adult Features (13+ years)

• Cognitive impairment (usually mild intellectual disability) 1, 2
• Hypothalamic hypogonadism 1, 5
• Characteristic behavioral problems 1, 2
  • Temper tantrums
  • Obsessive-compulsive features
  • Compulsive skin picking
  • Rigidity and stubbornness
• Continued hyperphagia with severe obesity if uncontrolled 1
• Sleep disorders including excessive daytime sleepiness (>50% of patients) 2

Complications

• Obesity-related health problems if weight is uncontrolled 1, 2
  • Diabetes mellitus
  • Obstructive sleep apnea
  • Right-sided heart failure
• Respiratory complications (particularly with initiation of growth hormone therapy) 2
• Reduced life expectancy (typically fourth decade) without proper management 1

Genetic Basis

• Lack of expression of genes from paternally inherited chromosome 15q11-q13 region 1
• Three main genetic mechanisms:
  • Paternal 15q11-q13 deletion (approximately 70% of cases) 5, 6
  • Maternal uniparental disomy 15 (approximately 28% of cases) 5, 6
  • Imprinting center defects (<2% of cases) 5, 6

Clinical Pitfalls and Important Considerations

• The clinical presentation evolves significantly with age, making diagnosis challenging at different life stages 1, 3
• Hypotonia and poor feeding in infancy may not initially raise suspicion for PWS without other features 3
• The sensitivity of clinical features varies widely (49-98%), with developmental delay and hypotonia being the most consistent 3
• Approximately 17% of genetically confirmed PWS patients may not meet strict clinical diagnostic criteria, highlighting the importance of genetic testing when suspicion exists 3
• Vomiting after binge-eating can be an ominous sign due to high pain tolerance in PWS patients 2
• Early diagnosis is crucial for implementing interventions that can significantly improve long-term outcomes 1, 2

With proper weight control and management, individuals with PWS can remain healthy well into older adult life, with some living into their seventh decade 1, 2.