The VHL gene is associated with von Hippel–Lindau (VHL) syndrome, an inherited condition that increases the risk of developing a range of benign and malignant tumors, most commonly hemangioblastomas of the brain, spine, and retina, clear cell renal cell carcinoma, pheochromocytomas (benign adrenal tumors), pancreatic neuroendocrine tumors, endolymphatic sac (ear) tumors, and multiple cysts in various organs. Management of VHL involves lifelong, structured surveillance, including regular MRI imaging of the brain, spine, and abdomen, annual ophthalmologic exams, biochemical screening for catecholamine-secreting tumors, and timely surgical or medical intervention when tumors become symptomatic or reach defined size thresholds. VHL is not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in VHL exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
