Russell-Silver Syndrome
Russell-Silver Syndrome (RSS/SRS)
Russell-Silver syndrome is a rare genetic disorder characterized by intrauterine and postnatal growth restriction, distinctive facial features, and body asymmetry. First described independently by Silver et al. (1953) and Russell (1954).
Key Points
- Incidence: 1:30,000 to 1:100,000 births
- Complex genetic imprinting disorder
- Significant growth impairment
- Variable phenotypic expression
- Multidisciplinary management required
Genetic Basis
Molecular Genetics
- Primary Genetic Mechanisms:
- Loss of methylation on chromosome 11p15 (35-50%)
- Maternal uniparental disomy of chromosome 7 (7-10%)
- 11p15 duplications (rare)
- CDKN1C mutations (rare)
- Epigenetic Regulation:
- ICR1 region affects IGF2 expression
- ICR2 region affects CDKN1C expression
- Complex imprinting control regions
Inheritance Patterns
- Most cases sporadic
- Rare familial cases reported
- Risk of recurrence:
- Sporadic cases: <1%
- Familial cases: up to 50%
- Depends on genetic mechanism
Clinical Features
Growth Parameters
- Prenatal:
- Severe IUGR
- Birth weight ≤-2 SDS
- Birth length ≤-2 SDS
- Normal head circumference (relative macrocephaly)
- Postnatal:
- Persistent short stature
- Poor weight gain
- Delayed bone age
- Growth velocity below normal
Craniofacial Features
- Characteristic Facial Features:
- Triangular face
- Prominent forehead
- Small chin (micrognathia)
- Downturned corners of mouth
- Low-set, posteriorly rotated ears
- Blue sclera in infancy
Body Asymmetry
- Hemihypertrophy/Hemihypotrophy:
- Present in 60-80% of cases
- Can affect limbs, face, trunk
- May become more apparent with age
- Regular monitoring required
Other Physical Features
- Skeletal:
- Clinodactyly
- Camptodactyly
- Syndactyly
- Scoliosis risk
- Neurological:
- Normal intelligence (usually)
- Motor delays common
- Speech delays possible
Diagnosis
Clinical Diagnostic Criteria (Netchine-Harbison)
- Major Criteria:
- SGA (birth weight/length ≤-2 SDS)
- Postnatal growth failure
- Relative macrocephaly at birth
- Protruding forehead
- Body asymmetry
- Feeding difficulties/low BMI
- Diagnosis:
- Clinical: 4 out of 6 criteria
- Confirmed: Clinical + molecular testing
Molecular Testing
- First-Line Testing:
- 11p15 methylation analysis
- UPD(7)mat analysis
- Copy number variation analysis
- Additional Testing:
- CDKN1C sequencing
- Whole exome sequencing
- Chromosomal microarray
Differential Diagnosis
- Other Growth Disorders:
- 3M syndrome
- Mulibrey nanism
- IMAGe syndrome
- Bloom syndrome
- Feeding Disorders:
- Failure to thrive
- Gastrointestinal disorders
- Metabolic disorders
Management
Multidisciplinary Team
- Core Team Members:
- Pediatric endocrinologist
- Clinical geneticist
- Nutritionist
- Feeding specialist
- Physiotherapist
- Occupational therapist
Growth Hormone Therapy
- Indications:
- Height ≤-2.5 SDS
- Growth velocity ≤-1 SDS
- Protocol:
- Starting dose: 35-70 μg/kg/day
- Regular monitoring of IGF-1
- Adjust dose based on response
- Continue until final height
- Monitoring:
- Growth velocity
- Bone age advancement
- Side effects
- Metabolic parameters
Nutritional Management
- Early Intervention:
- Feeding assessment
- Caloric supplementation
- Texture modification
- Gastrostomy if needed
- Ongoing Support:
- Regular nutritional assessment
- BMI monitoring
- Dietary counseling
- Supplement recommendations
Growth & Development
Growth Patterns
- Birth Measurements:
- Weight: typically -3 to -4 SDS
- Length: typically -2 to -3 SDS
- Head circumference: -1 to 0 SDS
- Growth Trajectory:
- Poor catch-up growth
- Adult height prediction
- Impact of GH therapy
Developmental Milestones
- Motor Development:
- Delayed gross motor skills
- Fine motor challenges
- Need for early intervention
- Cognitive Development:
- Usually normal intelligence
- Learning difficulties possible
- Speech therapy often needed
Associated Conditions
Gastrointestinal Issues
- Feeding Difficulties:
- Poor appetite
- Oral aversion
- Reflux
- Hypoglycemia risk
Endocrine Abnormalities
- Common Issues:
- Early adrenarche
- Precocious puberty
- Insulin resistance
- Hypoglycemia
Orthopedic Concerns
- Skeletal Issues:
- Leg length discrepancy
- Scoliosis
- Joint problems
- Foot abnormalities
Long-term Monitoring
Regular Assessments
- Growth Monitoring:
- Height, weight, BMI
- Body asymmetry
- Pubertal development
- Bone age
- Medical Surveillance:
- Endocrine function
- Orthopedic evaluation
- Dental assessment
- Vision and hearing
Transition Care
- Adolescent Transition:
- Education about condition
- Reproductive counseling
- Psychosocial support
- Adult healthcare transition
