Management Approach for Noonan Syndrome
The management of Noonan syndrome requires a multidisciplinary approach with specific focus on cardiac evaluation, growth monitoring, developmental assessment, bleeding risk evaluation, and cancer surveillance, as recommended by the American Academy of Pediatrics. 1
Initial Evaluation and Diagnosis
- Genetic testing directed by a genetics provider using multigene Ras/MAPK pathway panel testing
- If panel testing is unavailable, sequential gene testing should be performed
- High-resolution chromosome microarray if gene testing is negative
- Most common genetic mutations:
- PTPN11 (50% of cases)
- SOS1 (13%)
- RAF1 (5%)
- RIT1 (5%)
- Less commonly: KRAS, NRAS, BRAF, MAP2K1, RRAS, RASA2, A2ML1, SOS2, or LZTR1 1
Cardiac Management
- Complete cardiac evaluation including echocardiogram at diagnosis
- Focus on identifying common cardiac issues:
- Pulmonary valvular stenosis (50-60% of patients)
- Hypertrophic cardiomyopathy (20% of patients)
- Regular cardiac follow-up based on findings
- Endocarditis prophylaxis as indicated 1, 2
Growth and Endocrine Management
- Regular monitoring of growth parameters
- Consider growth hormone therapy for significant short stature
- Evaluation for delayed puberty
- Thyroid function testing 1
Neurodevelopmental Management
- Early developmental assessment
- Specific attention to non-verbal learning disabilities
- Neuropsychological evaluation for school-age children
- Speech therapy and physiotherapy as indicated 1
Hematologic Management
- Coagulation studies before any surgical procedures
- Monitor for bleeding tendency
- Hematology consultation for abnormal findings 1
Cancer Surveillance
- Increased risk for myeloproliferative disorders/juvenile myelomonocytic leukemia (JMML), particularly with specific PTPN11 or KRAS mutations
- Regular hematologic evaluation based on genetic findings 1
Transition to Adult Care
- Coordinated transition planning
- Continued cardiac surveillance
- Adult-focused genetic counseling
- Vocational and life skills support as needed 1
Dental Management
- Full mouth dental rehabilitation may be necessary
- Correction of orofacial and occlusal defects
- Regular dental follow-up 3
Special Considerations
- Care should be tailored to address the specific manifestations present in each patient
- Emerging molecular therapeutics inhibiting the RAS/MAPK pathway show promise for treating certain manifestations of Noonan syndrome 1, 2
The management of Noonan syndrome is complex due to the variety of systems affected. Careful coordination between specialists including cardiologists, endocrinologists, neurologists, hematologists, and geneticists is essential for optimal outcomes. Regular follow-up and monitoring for potential complications throughout the lifespan is crucial for improving quality of life and reducing morbidity and mortality.