ConditionCancer
Von Hippel-Lindau Disease (VHL)
Von Hippel-Lindau (VHL) disease is a rare inherited condition that causes tumors and cysts to grow in several parts of the body, including blood-vessel tumors (hemangioblastomas) in the brain, spinal cord and retina, kidney cancer, adrenal tumors (pheochromocytomas) and pancreatic cysts and tumors. It is caused by a change in the VHL tumor suppressor gene and affects about 1 in 36,000 people. Lifelong screening from childhood finds tumors early, when they are easier to treat, and has greatly improved life expectancy.
Also called: VHL, von Hippel-Lindau syndrome, VHL syndrome, familial cerebelloretinal angiomatosis
At a glance
- What it is
- An inherited tumor syndrome caused by a faulty VHL gene.
- Inheritance
- Autosomal dominant; each child of an affected parent has a 50 percent chance; about 1 in 5 cases are new.
- Main tumors
- Hemangioblastomas (brain, spinal cord, retina), clear cell kidney cancer, pheochromocytoma, pancreatic cysts and neuroendocrine tumors, inner ear tumors.
- Symptoms
- Depend on tumor site: vision changes, headache, balance problems, high blood pressure, hearing loss; often none early.
- Diagnosis
- Clinical criteria and genetic testing.
- Care
- Regular surveillance scans and exams, surgery or ablation, and belzutifan, a targeted medicine.
When to get help
Call 911 or go to the ER
- Sudden severe headache, vomiting, loss of balance, confusion or drowsiness (possible bleeding or pressure from a brain tumor): call 911 or your local emergency number
- Sudden weakness or numbness in the legs, or loss of bladder or bowel control (possible spinal tumor)
- Very high blood pressure with pounding headache, sweating and palpitations, especially during surgery, pregnancy or labor (possible pheochromocytoma crisis)
See a doctor within a day or two
- Sudden vision loss, floaters or distortion in one eye
- Blood in the urine or new flank pain
- Sudden hearing loss, ringing or dizziness on one side
Book a routine appointment
- A parent, sibling or child with VHL, to arrange genetic testing
- A hemangioblastoma, early or bilateral kidney cancer, or pheochromocytoma at a young age, to consider VHL testing
- Keeping to your VHL surveillance schedule
- Planning a pregnancy or surgery with VHL
What causes VHL
The VHL gene normally acts as a tumor suppressor, helping cells break down proteins called hypoxia-inducible factors (HIFs). When both copies of the gene in a cell stop working, HIFs build up and switch on genes for blood vessel growth and cell growth, leading to tumors rich in blood vessels.
People with VHL inherit one faulty copy in every cell. A second change in a specific tissue triggers a tumor there. That is why tumors develop at various times and places throughout life.
Tumors and their effects
| Site | Tumor or cyst | Possible symptoms |
|---|---|---|
| Retina | Retinal hemangioblastoma | Often none early; blurred vision, floaters, vision loss from leakage or detachment |
| Brain (cerebellum) and brainstem | Hemangioblastoma | Headache, vomiting, unsteadiness, dizziness |
| Spinal cord | Hemangioblastoma, cysts | Back pain, numbness, weakness, bladder problems |
| Kidneys | Cysts and clear cell kidney cancer | Often none; blood in urine, flank pain |
| Adrenal glands | Pheochromocytoma | High blood pressure, headaches, sweating, palpitations |
| Pancreas | Cysts, neuroendocrine tumors | Usually none; rarely pain or diabetes |
| Inner ear | Endolymphatic sac tumor | Hearing loss, ringing, dizziness |
| Epididymis (men) or broad ligament (women) | Cystadenoma | Usually harmless lumps |
Tumors often start in childhood or young adulthood. Retinal tumors can appear in young children, and kidney cancer usually after age 20.
Diagnosis
VHL is diagnosed when someone has:
- a VHL gene variant on genetic testing, or
- a family history of VHL plus one characteristic tumor, or
- no family history but two or more characteristic tumors (for example, two hemangioblastomas, or a hemangioblastoma and a kidney cancer or pheochromocytoma)
Genetic testing is recommended for anyone with features suggestive of VHL and for relatives of a person with a known VHL variant, starting in early childhood so surveillance can begin. See genetic counseling.
Surveillance
The VHL Alliance and other expert groups recommend regular screening from early childhood, typically including:
- eye exams with dilation, starting in infancy and continuing at least yearly
- blood pressure checks yearly
- blood or urine metanephrines for pheochromocytoma, starting in childhood
- MRI of the abdomen (kidneys, adrenals, pancreas), usually every 2 years from the teenage years
- MRI of the brain and spine every 2 years from adolescence
- hearing tests and inner ear MRI if symptoms occur
Pregnant women with VHL need closer monitoring.
Treatment
- Retinal tumors: laser or freezing treatment early to protect vision.
- Brain and spine hemangioblastomas: surgery or targeted radiation for growing or symptomatic tumors.
- Kidney tumors: monitored until they reach about 3 cm, then removed with kidney-sparing surgery or ablation, to preserve kidney function over a lifetime.
- Pheochromocytoma: blood pressure control with alpha-blockers, then surgery, often preserving part of the adrenal gland.
- Pancreatic neuroendocrine tumors: surveillance or surgery depending on size and growth.
- Belzutifan: an oral HIF-2 alpha inhibitor approved for adults with VHL who need treatment for kidney cancer, CNS hemangioblastomas or pancreatic neuroendocrine tumors not requiring immediate surgery; it can shrink tumors and delay surgery.
Outlook
With regular surveillance and timely treatment, many people with VHL live long, active lives. Kidney cancer and brain hemangioblastomas were historically the main causes of death; earlier detection and new treatments have improved outcomes. Care at a VHL clinical care center coordinates the many specialists involved.
Frequently asked questions
What is von Hippel-Lindau disease?
VHL is a rare inherited condition caused by a change in the VHL gene. It makes people prone to tumors and cysts in the brain, spinal cord, eyes, kidneys, adrenal glands, pancreas and inner ear. Some tumors are benign; kidney tumors can be cancerous.
How is VHL inherited?
VHL is inherited in an autosomal dominant pattern, so a person with VHL has a 50 percent chance of passing it to each child. About 1 in 5 people with VHL are the first in their family, with a new gene change.
What are the first signs of VHL?
Often there are no symptoms at first, and tumors are found on screening. When symptoms appear, they may include vision changes from retinal tumors, headaches and unsteadiness from brain tumors, high blood pressure from pheochromocytoma, or blood in the urine from kidney tumors.
What is the life expectancy with VHL?
Life expectancy has improved substantially with regular screening and early treatment. Many people with VHL now live into older age. Following a lifelong surveillance schedule and being cared for at a specialized center are the most important factors.
Sources
This guide was written from current patient and clinical guidance, including:
- National Cancer Institute: Von Hippel-Lindau disease
- VHL Alliance: Active surveillance guidelines
- MedlinePlus Genetics: Von Hippel-Lindau syndrome
- National Organization for Rare Disorders (NORD): Von Hippel-Lindau disease
- US Food and Drug Administration: Belzutifan approval for VHL-associated tumors