Costello Syndrome
Costello Syndrome
Overview
Costello Syndrome is a rare RASopathy characterized by failure to thrive in infancy, short stature, developmental delay, distinctive facial features, heart abnormalities, and an increased risk of certain tumors. It is caused by germline mutations in the HRAS gene.
Key Points
- Inheritance: Autosomal dominant
- Gene: HRAS (11p15.5)
- Prevalence: 1/300,000 to 1/1,000,000
- Most cases: De novo mutations
- Age of Onset: Prenatal/Birth
Clinical Features
Prenatal Findings
- Polyhydramnios (97%)
- Increased nuchal thickness
- Fetal macrosomia
- Hydrops fetalis
- Cardiac abnormalities
Growth & Development
- Birth weight often above 50th percentile
- Severe failure to thrive in infancy
- Feeding difficulties (>95%)
- Global developmental delay
- Short stature
- Delayed bone age
Craniofacial Features
- Coarse facial features
- Large mouth with full lips
- Thick nasal bridge
- Low-set, posteriorly rotated ears
- Epicanthal folds
- Strabismus
- High forehead
- Curly or sparse hair
Dermatologic Findings
- Soft, loose skin (especially hands and feet)
- Deep palmar and plantar creases
- Papillomas (perinasal/perioral)
- Acanthosis nigricans
- Hyperkeratosis
Musculoskeletal Features
- Joint laxity
- Ulnar deviation of wrists and fingers
- Tight achilles tendons
- Hip dysplasia
- Scoliosis
Diagnosis & Genetics
Diagnostic Criteria
- Clinical features constellation
- Molecular genetic testing
- HRAS gene sequencing
- Prenatal diagnosis possible
Common HRAS Mutations
- G12S (80% of cases)
- G12A
- G13C
- Other rare variants
Differential Diagnosis
- Noonan syndrome
- Cardiofaciocutaneous syndrome
- Beckwith-Wiedemann syndrome
- Multiple endocrine neoplasia
Management & Surveillance
Multidisciplinary Care Team
- Clinical geneticist
- Pediatric cardiologist
- Developmental pediatrician
- Gastroenterologist
- Orthopedic specialist
- Physical/occupational therapist
Regular Monitoring
- Growth parameters
- Developmental assessments
- Cardiac evaluation
- Echocardiogram
- ECG
- Blood pressure monitoring
- Tumor surveillance
- Abdominal/pelvic ultrasound
- Urine catecholamines
- Regular physical examination
Interventions
- Feeding support/G-tube if needed
- Physical therapy
- Occupational therapy
- Speech therapy
- Educational support
Complications & Prognosis
Cardiac Complications
- Hypertrophic cardiomyopathy (65%)
- Atrial tachycardia (30%)
- Valvular abnormalities
- Congenital heart defects
Tumor Risk
- Rhabdomyosarcoma (10-15%)
- Neuroblastoma (5%)
- Bladder carcinoma
- Benign tumors
- Papillomas
- Ganglioneuromas
Other Complications
- Sleep apnea
- Chiari I malformation
- Tethered cord
- Osteoporosis
- Hip dysplasia
