SDHC mutation in an elderly patient without familial antecedents

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Head and neck paragangliomas are typically benign tumors, often sporadic.
• Germline mutations in succinate dehydrogenase genes (SDHB, SDHC, SDHD) account for ~30% of hereditary cases.
• Hereditary factors include family history, multiple tumors, early onset, and co-occurring gastrointestinal stromal tumors.

Observation:

• A novel mutation (c.256-257insTTT) in the SDHC gene was found in a 60-year-old patient with a single head and neck paraganglioma.
• The patient had no family history of the disease, indicating a sporadic presentation.
• In silico analysis revealed the mutation created a cryptic splice acceptor site, and loss of heterozygosity supported its pathogenic role.

Findings:

• The identified SDHC mutation was absent in control populations.
• A novel SDHC polymorphism (0.3% frequency) was discovered in controls, underscoring the need for thorough variant assessment.
• This case demonstrates germline mutations can occur in older, seemingly sporadic patients.

Implications:

• Genetic screening for paraganglioma susceptibility genes may be warranted even in older patients without typical hereditary features.
• Distinguishing pathogenic mutations from benign polymorphisms is crucial for clinical relevance.
• Cost-effectiveness of genetic testing strategies needs consideration, balancing comprehensive screening with established risk criteria.