What is the management plan for individuals with an SDHC (Succinate Dehydrogenase Complex Subunit C) gene mutation?

Management of Individuals with SDHC Gene Mutation

Individuals with SDHC gene mutations should undergo annual biochemical screening and whole-body MRI every 2-3 years, with surveillance beginning at least 5 years before the youngest age of onset in the family or by age 15. 1

Understanding SDHC Mutations

SDHC gene mutations are associated with hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndrome. These mutations affect the succinate dehydrogenase complex, which functions in the mitochondrial respiratory chain. SDHC mutations have distinct characteristics:

• Penetrance: Approximately 25% by age 60 1
• Tumor distribution: 77% of patients develop solitary tumors 1
• Common tumor locations:
  • Head and neck paragangliomas (65.2%)
  • Extra-adrenal paragangliomas (28.2%)
  • Pheochromocytomas (6.5%) 2
• Risk of malignancy: Approximately 4-19.6% 1, 2
• Associated tumors: Gastrointestinal stromal tumors (GIST) and renal cell carcinoma 2

Surveillance Protocol for SDHC Mutation Carriers

First-Degree Relatives (FDR)

• Biochemical screening: Annual measurement of plasma or urinary metanephrines (normetanephrine, metanephrine, and methoxytyramine) 1
• Imaging: Rapid whole-body MRI (RWB-MRI) every 2-3 years 1
• Clinical check-up: Every 2-3 years 1
• Starting age: By age 15, or 5 years before the earliest age of onset in the family 1

Second-Degree Relatives (SDR)

• One-time screening: One baseline biochemical test and one RWB-MRI 1
• Further surveillance: Not recommended if initial screening is normal 1

Comprehensive Surveillance Approach

Biochemical Testing

• What to measure: Plasma-free methoxycatecholamines (normetanephrine, metanephrine, and methoxytyramine) or urinary deconjugated methoxycatecholamines 1
• Sampling conditions:
  • Plasma: After 30 minutes of rest in supine position
  • 3-methoxytyramine: Overnight fast required 1

Imaging Protocol

• Recommended modality: Rapid whole-body MRI from skull base to pelvis 1, 3
• Benefits of whole-body MRI:
  • Sensitivity of 87.5% (higher than biochemical testing at 37.5%) 3
  • Reduces radiation exposure compared to CT 3
  • More time-efficient than separate dedicated MRIs 3
• Alternative/complementary imaging: Consider somatostatin receptor scintigraphy, especially for thoracic lesions 4

For Patients with Diagnosed Tumors

• Post-treatment follow-up:
  • For functional tumors: Measure plasma/urine metanephrines by 8 weeks post-treatment 1
  • Imaging at 3-6 months post-treatment 1
  • Annual blood pressure measurements and clinical assessment 1

Special Considerations

• Family screening: Genetic testing should be offered to all first-degree relatives of individuals with SDHC mutations 1
• Children: Surveillance in children under 15 should be individually designed with a pediatrician 1
• Multifocal disease: While less common than in SDHD mutations, be vigilant for multiple tumors 2
• Malignancy risk: Though lower than SDHB mutations, malignant transformation can occur in about 4-19.6% of cases 1, 2

Common Pitfalls to Avoid

1. Relying solely on biochemical testing: Many SDHC-related tumors may be non-secreting, making imaging essential 3
2. Discontinuing surveillance: Lifelong surveillance is necessary due to the risk of developing new tumors over time 1
3. Missing associated tumors: Be vigilant for non-paraganglioma tumors, especially GIST and renal cell carcinoma 2
4. Inadequate family screening: Ensure all at-risk family members receive genetic counseling and testing 5

By following this comprehensive surveillance protocol, early detection of tumors in SDHC mutation carriers can be achieved, potentially reducing morbidity and mortality through timely intervention.