Which genetic syndromes are associated with pheochromocytoma?

• A. MEN1, Wilson disease, and Marfan syndrome.
• B. MEN2, von Hippel-Lindau disease, and neurofibromatosis type 1.
• C. Klinefelter syndrome, Down syndrome, and Turner syndrome.
• D. No genetic associations.

Answer: (B)

Pheochromocytoma is a tumor of the adrenal medulla that often appears as part of inherited genetic syndromes. The best match includes conditions known to predispose to adrenal medullary tumors: MEN2, von Hippel-Lindau disease, and neurofibromatosis type 1. In MEN2, activating mutations in RET drive medullary thyroid carcinoma but pheochromocytoma is a common accompanying feature. Von Hippel-Lindau disease, caused by VHL gene mutations, includes pheochromocytoma among its characteristic tumors along with hemangioblastomas and renal cell carcinoma. Neurofibromatosis type 1, due to NF1 mutations, also carries a risk of pheochromocytoma, though less frequent than in the other two conditions, among its neurocutaneous manifestations.

Other options don’t have a recognized, typical association with pheochromocytoma: MEN1 is classically linked to parathyroid, pituitary, and pancreatic neuroendocrine tumors; the listed chromosomal conditions and Wilson disease or Marfan syndrome are not established adapters for adrenal medullary tumors. Saying there are no genetic associations would miss these well-described syndromic links.