Von Hippel–Lindau disease

Von Hippel–Lindau disease is an inherited cancer predisposition syndrome caused by pathogenic variants in the VHL gene. It can lead to tumors and cysts in multiple organs, including the brain, kidneys, pancreas, and eyes.

VHL protein: A tumor-suppressor protein that helps target hypoxia-inducible factors for degradation when oxygen is available. Pathogenic VHL variants impair this protein’s role in controlling hypoxia-inducible factors.
VHL disease surveillance: A program of regular imaging, eye examinations, and other evaluations for people with Von Hippel–Lindau disease. Repeated screening detects tumors early, before they cause irreversible harm.
Autosomal dominant inheritance: A pattern in which one altered gene copy can cause a trait, with each child of an affected parent having a 50% chance of inheriting it. VHL disease is usually inherited this way, though new variants also occur.
Hemangioblastoma: A usually benign, highly vascular tumor that commonly arises in the central nervous system or retina. Multiple central nervous system or retinal hemangioblastomas are characteristic findings in VHL disease.
Hypoxia-inducible factor: A transcription factor that activates genes supporting cellular adaptation to low oxygen. When VHL function is lost, hypoxia-inducible factors can accumulate even when oxygen is plentiful.
Belzutifan: A drug that inhibits hypoxia-inducible factor 2α and is used for selected VHL-associated tumors. It targets a central consequence of VHL loss and can delay or avoid some surgeries.
VHL gene: A gene on chromosome 3 that encodes the VHL tumor-suppressor protein. Pathogenic variants in this gene define the molecular cause of the disorder.
Cerebellar hemangioblastoma: A vascular tumor in the cerebellum that can cause neurological symptoms through growth or pressure. It is a common VHL-associated lesion and may require repeated imaging and treatment.
Ubiquitin-mediated proteolysis: A process that marks proteins with ubiquitin for degradation by the proteasome. The VHL protein complex uses this pathway to remove hypoxia-inducible factors.
Retinal hemangioblastoma: A vascular tumor of the retina that can impair vision and occur in Von Hippel–Lindau disease. Regular retinal examinations can identify these lesions while vision-preserving treatment remains possible.

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Tuberous sclerosisCompared with: Like TSC, it affects multiple organs, but its characteristic lesions and pathway differ.