Angelman Syndrome
Angelman Syndrome
Definition & Epidemiology
Angelman Syndrome (AS) is a complex genetic disorder affecting the nervous system, characterized by developmental delay, speech impairment, movement disorders, and a unique behavioral pattern. Incidence: 1:12,000 to 1:20,000 live births.
Genetic Mechanisms
- Chromosome 15q11.2-q13 region affected
- Multiple genetic mechanisms:
- Maternal deletion (65-75%)
- Paternal uniparental disomy (3-7%)
- Imprinting defects (3-5%)
- UBE3A mutations (10-15%)
- Unknown mechanism (10-15%)
- Genomic imprinting involved
Clinical Features
Core Clinical Features (100%)
- Developmental delay (profound)
- Movement disorders
- Ataxic gait
- Tremulous limb movements
- Unique behavioral patterns
- Frequent laughter/smiling
- Excitable personality
- Happy demeanor
- Easily provoked laughter
- Speech impairment
- Minimal to no use of words
- Better receptive than expressive language
Frequent Clinical Features (>80%)
- Microcephaly
- Seizures (onset < 3 years)
- Abnormal EEG patterns
- Sleep disorders
- Feeding problems in infancy
- Hypopigmentation
- Wide-based gait
- Uplifted, flexed arm position during walking
- Prominent mandible
- Wide mouth, widely spaced teeth
Associated Features (20-80%)
- Strabismus
- Occipital groove
- Protruding tongue
- Scoliosis
- Increased sensitivity to heat
- Attraction to/fascination with water
- Excessive chewing behaviors
- Obesity (in older children)
Diagnostic Approach
Clinical Diagnostic Criteria
- Consistent (100%)
- Developmental delay
- Movement disorder
- Unique behavioral characteristics
- Speech impairment
- Frequent (>80%)
- Growth retardation
- Seizures
- Abnormal EEG
Genetic Testing
- Methylation analysis
- FISH analysis
- Chromosomal microarray
- UBE3A sequence analysis
- MLPA testing
Differential Diagnosis
- Rett syndrome
- Mowat-Wilson syndrome
- Pitt-Hopkins syndrome
- Christianson syndrome
- 1p36 deletion syndrome
Management Strategies
Early Intervention
- Physical therapy
- Gross motor development
- Balance training
- Gait assistance
- Occupational therapy
- Fine motor skills
- Activities of daily living
- Feeding strategies
- Speech and communication therapy
- Alternative communication methods
- Augmentative communication devices
- Sign language adaptation
Medical Management
- Seizure control
- Anti-epileptic medications
- Regular EEG monitoring
- Sleep disorders
- Sleep hygiene
- Melatonin if indicated
- Gastrointestinal issues
- Feeding support
- Reflux management
- Constipation treatment
Monitoring & Long-term Outcomes
Regular Monitoring
- Growth parameters
- Developmental progress
- Seizure control
- Sleep patterns
- Orthopedic complications
- Feeding/nutrition
- Vision and hearing
Age-specific Issues
- Childhood
- Feeding difficulties
- Sleep disorders
- Seizure onset
- Adolescence
- Scoliosis
- Obesity risk
- Puberty issues
- Adulthood
- Mobility changes
- Continued care needs
- Medical complications
Prognosis
- Life expectancy near normal
- Ongoing support needed throughout life
- No regression of skills
- Continued learning possible
