Cornelia de Lange Syndrome
Cornelia de Lange Syndrome (CdLS)
Definition & Epidemiology
Cornelia de Lange Syndrome is a multisystem developmental disorder characterized by distinctive facial features, growth delays, intellectual disability, and limb defects. Incidence: 1:10,000 to 1:30,000 live births.
Genetic Basis
- Multiple genes involved:
- NIPBL (60% of cases)
- SMC1A (5%)
- SMC3 (<1%)
- RAD21 (<1%)
- HDAC8 (5%)
- BRD4 (rare cases)
- Most cases are de novo mutations
- Autosomal dominant or X-linked inheritance
Clinical Features
Craniofacial Features (>95%)
- Synophrys (confluent eyebrows)
- Long, thick eyelashes
- Depressed nasal bridge
- Anteverted nares
- Long philtrum
- Thin upper lip
- Downturned corners of mouth
- Micrognathia
- Low-set ears
- Low anterior/posterior hairline
Growth & Development
- Prenatal growth restriction
- Postnatal growth failure
- Microcephaly
- Developmental delay
- Speech delay (>90%)
- Motor delay (>90%)
- Intellectual disability (variable severity)
Limb Abnormalities
- Small hands and feet
- Fifth finger clinodactyly
- Proximally placed thumbs
- Upper limb reduction defects (severe cases)
- Single palmar crease
Diagnostic Approach
Clinical Diagnosis
- Consensus Diagnostic Criteria:
- Facial features score (≥4 points)
- Growth, development, and behavior (≥2 points)
- Musculoskeletal findings (≥3 points)
Genetic Testing
- Multi-gene panel testing
- Sequence analysis
- Deletion/duplication analysis
Additional Evaluations
- Cardiac assessment
- Gastrointestinal evaluation
- Ophthalmologic examination
- Audiological assessment
- Developmental evaluation
Differential Diagnosis
- Fetal alcohol syndrome
- KBG syndrome
- Coffin-Siris syndrome
- Rubinstein-Taybi syndrome
Comprehensive Management
Medical Management
- Gastrointestinal:
- GERD management
- Feeding support
- Constipation management
- Cardiac care:
- Regular monitoring
- Surgical intervention if needed
- Neurological:
- Seizure management
- Sleep disorders treatment
Developmental Support
- Physical therapy
- Occupational therapy
- Speech and language therapy
- Special education services
- Behavioral intervention
Surgical Interventions
- Gastrostomy tube placement
- Fundoplication if indicated
- Orthopedic procedures
- Dental/orthodontic care
Complications & Long-term Monitoring
Major Complications
- Gastrointestinal (>90%)
- GERD
- Feeding difficulties
- Pyloric stenosis
- Malrotation
- Cardiac (25%)
- Septal defects
- Pulmonary stenosis
- Tetralogy of Fallot
- Neurological
- Seizures (25%)
- Behavioral issues
- Sleep disturbances
Monitoring Protocol
- Growth monitoring (every 3-6 months)
- Annual developmental assessment
- Regular ophthalmological review
- Hearing evaluation
- Dental care
- Orthopedic monitoring
Prognosis
- Life expectancy
- Normal in mild cases
- Reduced in severe cases
- Quality of life varies with severity
- Most adults require supported living
