Sotos Syndrome
Sotos Syndrome (Cerebral Gigantism)
Introduction
Sotos syndrome is a genetic disorder characterized by overgrowth in childhood, distinctive facial features, and developmental delay. First described by Juan Sotos in 1964.
Key Points
- Incidence: 1 in 14,000 births
- Affects males and females equally
- Autosomal dominant inheritance
- 90% of cases due to NSD1 gene mutations
- Characterized by prenatal and postnatal overgrowth
Pathophysiology
- Genetic basis:
- NSD1 gene mutations (5q35 deletion)
- Histone methyltransferase dysfunction
- Altered gene expression regulation
- Epigenetic modifications
- Growth dysregulation:
- Enhanced cellular growth
- Accelerated skeletal maturation
- Advanced bone age
- Altered brain development
Clinical Features
Cardinal Features (4 Major Criteria)
- 1. Overgrowth:
- Height and weight >97th percentile
- Accelerated growth in infancy
- Advanced bone age
- Large hands and feet
- Macrocephaly
- 2. Characteristic Facial Features:
- High, broad forehead
- Sparse frontotemporal hair
- Downslanting palpebral fissures
- Prominent chin
- Malar flushing
- Long, narrow face
- High-arched palate
- 3. Learning Disability:
- Variable intellectual disability
- Speech and language delays
- Motor skill delays
- Social communication difficulties
- 4. Advanced Bone Age:
- Typically 2-3 years ahead
- Evident on radiographs
- Contributes to final height prediction
Associated Features
- Neurological:
- Hypotonia in infancy
- Poor coordination
- Seizures (in ~25%)
- Behavioral problems
- ADHD symptoms
- Anxiety
- Musculoskeletal:
- Scoliosis
- Joint hyperlaxity
- Pes planus
- Genu valgum
- Cardiac:
- Patent ductus arteriosus
- Septal defects
- Aortic dilation
- Other Systems:
- Renal anomalies
- Jaundice in newborns
- Feeding difficulties
- Vision problems
- Dental anomalies
Diagnosis & Genetics
Diagnostic Criteria
- Major Criteria (All Required):
- Characteristic facial features
- Learning disability/developmental delay
- Overgrowth/macrocephaly
- Advanced bone age
- Supporting Features:
- Family history
- NSD1 abnormality
- Neonatal complications
- Associated medical problems
Genetic Testing
- Molecular Analysis:
- NSD1 gene sequencing
- Deletion/duplication analysis
- Array CGH
- MLPA analysis
- Geographic Variations:
- Japanese: 5q35 microdeletions more common
- Non-Japanese: Point mutations more common
Differential Diagnosis
- Other Overgrowth Syndromes:
- Weaver syndrome
- Beckwith-Wiedemann syndrome
- Marshall-Smith syndrome
- Simpson-Golabi-Behmel syndrome
- Distinguishing Features:
- Facial phenotype
- Growth pattern
- Associated anomalies
- Genetic basis
Management
Multidisciplinary Approach
- Core Team:
- Clinical geneticist
- Developmental pediatrician
- Neurologist
- Orthopedic specialist
- Physical/occupational therapist
- Speech therapist
- Additional Specialists:
- Cardiologist
- Ophthalmologist
- Dentist
- Behavioral health specialist
- Educational specialist
Interventional Strategies
- Early Intervention:
- Physical therapy
- Occupational therapy
- Speech and language therapy
- Behavioral interventions
- Medical Management:
- Seizure control if needed
- Cardiac monitoring
- Scoliosis management
- Vision correction
Development & Prognosis
Developmental Trajectory
- Early Childhood:
- Motor delays common
- Speech delay typical
- Variable learning difficulties
- Social interaction challenges
- School Age:
- Academic support often needed
- Social skills development
- Behavioral interventions
- Physical activity adaptation
- Adolescence/Adulthood:
- Variable independence levels
- Ongoing support needs
- Vocational training
- Social integration
Long-term Outcomes
- Physical:
- Final height often above average
- Possible orthopedic complications
- Variable medical needs
- Cognitive:
- Range from mild to moderate ID
- Some achieve normal intelligence
- Verbal ability often stronger than performance
- Social:
- Variable independence
- Many form relationships
- Some live independently
- Employment possible with support
Surveillance Guidelines
Regular Monitoring
- Growth Parameters:
- Height, weight, head circumference
- Growth velocity
- Bone age assessment
- Pubertal development
- Development:
- Developmental assessments
- Educational progress
- Behavioral evaluation
- Social skills assessment
- Medical Surveillance:
- Annual physical examination
- Cardiac evaluation
- Spine examination
- Vision screening
- Dental care
Age-Specific Recommendations
- Infancy (0-2 years):
- Frequent growth monitoring
- Developmental screening
- Feeding assessment
- Cardiac evaluation
- Early Childhood (2-5 years):
- Speech assessment
- Behavioral evaluation
- Educational planning
- Orthopedic screening
- School Age (5-12 years):
- Educational support
- Social skills development
- Scoliosis monitoring
- Psychological support
- Adolescence (12+ years):
- Transition planning
- Vocational assessment
- Independence skills
- Sexual health education
