Management Approach for Noonan Syndrome
The management of Noonan syndrome requires a multidisciplinary team approach addressing the specific cardiac, growth, developmental, and other manifestations that characterize this RASopathy.
Overview of Noonan Syndrome
Noonan syndrome (NS) is a genetic disorder belonging to the group of RASopathies, caused by mutations in genes involved in the Ras/mitogen-activated protein kinase (MAPK) pathway. It affects approximately 1 in 1,000-2,500 live births 1. The most common genetic causes include:
- PTPN11 mutations (50% of cases)
- SOS1 mutations (13%)
- RAF1 mutations (5%)
- RIT1 mutations (5%)
- Less commonly: KRAS, NRAS, BRAF, MAP2K1, and others 2
Diagnostic Evaluation
Initial evaluation should include:
- Genetic testing directed by a genetics provider using multigene Ras/MAPK pathway panel testing
- If panel testing unavailable, sequential gene testing: (1) BRAF, (2) MEK1 and MEK2, and (3) KRAS
- High-resolution chromosome microarray if gene testing is negative 3
Management Recommendations
1. Cardiac Management
- Complete cardiac evaluation including echocardiogram at diagnosis
- Most common cardiac issues:
- Pulmonary valvular stenosis (50-60%)
- Hypertrophic cardiomyopathy (20%)
- Other structural defects
- Regular cardiac follow-up based on findings
- Endocarditis prophylaxis as indicated
2. Growth and Endocrine Management
- Regular monitoring of growth parameters
- Growth hormone therapy consideration for significant short stature
- Note: Studies on growth hormone treatment have not provided definitive conclusions on final height outcomes 4
- Evaluation for delayed puberty
- Thyroid function testing
3. Developmental and Neurological Management
- Early developmental assessment
- Specific attention to non-verbal learning disabilities 4
- Neuropsychological evaluation for school-age children
- Speech therapy and physiotherapy as indicated
- Seizure management if present
4. Hematological Management
- Coagulation studies before any surgical procedures
- Monitoring for bleeding tendency
- Hematology consultation for abnormal findings
5. Feeding and Gastrointestinal Management
- Evaluation of feeding difficulties in infancy
- Note: These typically resolve spontaneously but require monitoring 4
- Nutritional support as needed
- Regular weight monitoring
6. Skeletal Management
- Evaluation for chest deformities
- Orthopedic consultation for skeletal malformations
- Scoliosis screening
7. Cancer Surveillance
- Increased risk for myeloproliferative disorders/juvenile myelomonocytic leukemia (JMML), particularly with specific PTPN11 or KRAS mutations 2
- Regular complete blood counts
- Prompt investigation of concerning symptoms
8. Reproductive Counseling
- Genetic counseling for affected individuals
- Pregnancy management for affected women requires coordinated multidisciplinary care 5
Special Considerations
Dental Management
- Regular dental evaluations
- Orthodontic assessment for malocclusion
- Comprehensive dental rehabilitation as needed 6
Surgical Considerations
- Preoperative coagulation studies
- Anesthesia consultation due to potential airway issues
- Cardiac evaluation before surgery
Transition to Adult Care
- Coordinated transition planning
- Continued cardiac surveillance
- Adult-focused genetic counseling
- Vocational and life skills support as needed
Common Pitfalls to Avoid
- Focusing only on cardiac issues while neglecting neurodevelopmental concerns
- Missing the diagnosis in milder cases with subtle features
- Inadequate preparation for surgical procedures given bleeding risks
- Failure to recognize that feeding difficulties typically improve with age
- Overlooking the need for psychosocial support for patients and families
Regular follow-up with a multidisciplinary team is essential for optimal management of individuals with Noonan syndrome, with care tailored to address the specific manifestations present in each patient.