A 35-year-old woman presents with headaches and ataxia. MRI reveals a cystic lesion in the cerebellum with an enhancing mural nodule. Her father had a similar brain tumor, and she has a history of retinal hemangioblastomas and renal cell carcinoma. The most likely underlying genetic abnormality is a mutation in which gene?

• A NF1 gene on chromosome 17
• B PTEN gene on chromosome 10
• C TSC1 gene on chromosome 9
• D VHL gene on chromosome 3 ✓

Explanation

This describes von Hippel-Lindau (VHL) disease, an autosomal dominant disorder caused by mutation of the VHL tumor suppressor gene on chromosome 3p25. It is associated with hemangioblastomas (CNS and retinal), clear cell renal cell carcinoma, pheochromocytoma, and pancreatic cysts. The cerebellar cystic lesion with enhancing mural nodule is classic hemangioblastoma. NF1 causes neurofibromas. TSC causes cortical tubers. PTEN causes Cowden syndrome.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.