Pheochromocytoma is characterized by the 'rule of 10s' classically. Modern genetic data has revised the hereditary rate. According to current evidence, what proportion of pheochromocytomas/paragangliomas are associated with germline mutations?
- A ~30–40%, with the most common germline mutations in SDHB, SDHD, VHL, RET, and NF1 ✓
- B ~10%, consistent with the classical 'rule of 10s'
- C ~5%, limited to MEN2 syndromes
- D ~60%, reflecting near-universal syndromic association
Correct answer: A. ~30–40%, with the most common germline mutations in SDHB, SDHD, VHL, RET, and NF1
Explanation
Modern genomic studies have shown that approximately 30–40% of pheochromocytomas and paragangliomas harbor germline mutations — far exceeding the classical 'rule of 10' estimate of 10% familial. The most commonly mutated genes include SDHB, SDHD (succinate dehydrogenase subunits B and D), VHL, RET (MEN2), NF1, MAX, TMEM127, and SDHA. SDHx mutations are most frequent in malignant or extra-adrenal cases. This high germline rate justifies genetic testing for all patients with pheochromocytoma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.