Prader-Willi Syndrome
Introduction
Prader-Willi syndrome (PWS) is a complex genetic disorder affecting multiple systems, characterized by hypotonia, feeding difficulties in infancy, followed by hyperphagia and obesity in childhood, developmental delay, and behavioral problems.
Key Points
- Prevalence: 1/10,000 to 1/30,000 births
- First described in 1956 by Prader, Labhart, and Willi
- Most common genetic cause of life-threatening obesity
- Complex hypothalamic dysfunction
- Distinct developmental phases
Clinical Features
Major Clinical Criteria
- Neonatal Period:
- Central hypotonia
- Poor feeding requiring special techniques
- Weak or absent cry
- Lethargy
- Developmental delay
- Early Childhood to Adult:
- Hyperphagia
- Food seeking behavior
- Central obesity
- Behavioral problems
- Global developmental delay
Physical Characteristics
- Facial Features:
- Almond-shaped eyes
- Narrow bifrontal diameter
- Thin upper lip
- Downturned mouth corners
- Narrow nasal bridge
- Other Physical Features:
- Short stature
- Small hands and feet
- Fair hair and skin
- Scoliosis
- Dental problems
- Hypogonadism
Behavioral Characteristics
- Cognitive:
- Mild to moderate intellectual disability
- Speech articulation problems
- Learning difficulties
- Behavioral:
- Food-seeking behaviors
- Skin picking
- Temper tantrums
- Obsessive-compulsive traits
- Anxiety
- Rigidity in routine
Diagnosis
Genetic Testing
- Primary Testing:
- DNA methylation analysis
- FISH analysis
- Microsatellite analysis
- Chromosome microarray
- Molecular Mechanisms:
- Paternal deletion (65-75%)
- Maternal uniparental disomy (20-30%)
- Imprinting defects (1-3%)
Clinical Assessment
- Initial Evaluation:
- Detailed family history
- Physical examination
- Growth parameters
- Developmental assessment
- Supporting Tests:
- Endocrine evaluation
- Sleep studies
- Body composition analysis
- Developmental assessment
Management
Multidisciplinary Care
- Medical Management:
- Growth hormone therapy
- Sex hormone replacement
- Thyroid function monitoring
- Weight management
- Sleep apnea treatment
- Developmental Support:
- Physical therapy
- Occupational therapy
- Speech therapy
- Special education services
- Behavioral Interventions:
- Food security measures
- Behavioral therapy
- Psychiatric support
- Family counseling
Environmental Management
- Food Management:
- Locked food access
- Strict meal planning
- Portion control
- Food diary maintenance
- Daily Structure:
- Regular exercise program
- Consistent routines
- Supervised activities
- Clear behavioral expectations
Genetics & Molecular Basis
Genetic Mechanisms
- Chromosomal Region:
- 15q11-q13 region
- Imprinted region
- Multiple genes involved
- Key Genes:
- SNRPN
- NDN
- MAGEL2
- MKRN3
- IPW
Inheritance Pattern
- Sporadic in most cases
- Rare familial cases with imprinting defects
- Recurrence risk varies by genetic mechanism
Developmental Phases
Phase 1 (0-9 months)
- Severe hypotonia
- Feeding difficulties
- Failure to thrive
- Poor weight gain
Phase 2 (9-25 months)
- Weight gain begins
- Improved appetite
- Motor development improving
- No hyperphagia yet
Phase 3 (2-8 years)
- Onset of hyperphagia
- Food seeking behavior
- Rapid weight gain
- Behavioral problems emerge
Phase 4 (Adult)
- Continued hyperphagia
- Established behavioral patterns
- Independent living challenges
Complications & Monitoring
Medical Complications
- Endocrine:
- Growth hormone deficiency
- Hypothyroidism
- Type 2 diabetes
- Adrenal insufficiency
- Respiratory:
- Sleep apnea
- Hypoventilation
- Respiratory infections
- Other:
- Osteoporosis
- Scoliosis
- Dental problems
- Skin lesions
Monitoring Protocol
- Regular Assessment:
- Growth monitoring
- Body composition
- Endocrine function
- Sleep studies
- Behavioral assessment
Prognosis & Support
Long-term Outcomes
- Variable prognosis depending on:
- Early diagnosis and intervention
- Weight management success
- Behavioral management
- Family support
Support Services
- Family Resources:
- Genetic counseling
- Support groups
- Educational advocacy
- Respite care
- Transition Planning:
- Vocational training
- Supported living options
- Adult healthcare transition
- Legal guardianship planning
