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Von Hippel-Lindau (VHL) Syndrome

People with von Hippel-Lindau (VHL) have a higher risk of developing certain cancers, benign (noncancerous) tumors, and cysts.

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What is von Hippel-Lindau?

VHL is an inherited condition that increases the risk of developing certain cancers, benign tumors, and cysts. Problems related to VHL may start at an early age. VHL is estimated to affect about 1 in 36,000 people.

Most people with VHL develop their first VHL-related tumor in young adulthood. However, some people are diagnosed with their first tumor in childhood or adolescence. Hemangioblastomas and pheochromocytomas tend to occur at younger ages than other types of VHL-related tumors.

Tumors that are more common in people with VHL include:

What causes von Hippel-Lindau?

VHL is caused by a gene change (mutation) in the VHL gene, a tumor suppressor gene. VHL occurs when:

  • A gene change is inherited from one parent
  • A normal gene mutates early in fetal development such that the gene change is present in cells throughout the body

The VHL gene normally makes a protein that controls how cells grow and how the body responds to low oxygen levels. When this protein is missing or does not work the way it should, another protein called HIF-2α (hypoxia-inducible factor-2α) builds up in the body. Too much HIF-2α tells cells and blood vessels to keep growing when they shouldn't. This uncontrolled growth can lead to tumors.

Signs and symptoms of von Hippel-Lindau

Signs and symptoms of VHL depend on whether cysts (fluid-filled sacs) or tumors have developed and where they are located.

VHL can cause cysts in various parts of the body. For example, cysts can grow on the kidneys, pancreas, or reproductive tracts. Cysts often do not cause symptoms and may be found on imaging tests done for some other reason. In some cases, VHL-related tumors like pheochromocytomas and paragangliomas can also be asymptomatic.

VHL can cause several types of tumors. Each may cause different symptoms depending on where it grows.

These tumors have many blood vessels. They tend to form in the back of the brain (cerebellum), upper spinal cord, or retina, though they can grow anywhere in the CNS.

When they occur in the brain, they can cause symptoms like:

  • Trouble walking
  • Poor balance
  • Vomiting
  • Severe headaches

In the spinal cord, they can press on nerves, causing:

  • Pain
  • Numbness
  • Weakness

In the eye (retina), they can cause blindness.

Renal cell carcinoma is a type of cancer that forms in the kidney. It can cause:

  • Blood in the urine
  • Back pain
  • Fever
  • Weight loss

It can cause other problems if it spreads to other parts of the body.

These tumors grow in the adrenal glands, which sit above the kidneys in the belly. Some cause no symptoms. Others release hormones (catecholamines) that can cause:

  • High blood pressure
  • Palpitations
  • Sweating
  • Changes in mood

Pheochromocytoma can cause high blood pressure that is difficult to control with medicine. When the blood pressure is dangerously high, it can cause other symptoms like trouble breathing, chest pain, headaches, or blurry vision.

These tumors grow in the nervous system outside the adrenal glands and can be found in the chest or belly. Most do not make hormones and might cause no symptoms. When they do grow large enough to press on nearby nerves or blood vessels, they can cause pain or other problems. The few that do make hormones can cause symptoms similar to pheochromocytomas.

Pancreatic neuroendocrine tumors grow in the pancreas. They may cause no symptoms, or they might cause symptoms such as weight loss, fatigue, abdominal pain, and jaundice as they grow and press on nearby structures. Most of these tumors do not make hormones. In rare cases, they can make hormones that cause symptoms such as severe diarrhea or low blood sugar.

These tumors grow in the side of the skull near the ear. These tumors can cause:

  • Hearing loss
  • Drooping of one side of the face
  • Tinnitus (ringing in the ears)
  • Balance problems

These tumors can grow in the reproductive tract (epididymis in males or the broad ligament in females). They usually don’t cause any symptoms and are found on imaging tests done for some other reason.

Types of VHL and cancer risk

People with VHL can have different cancer risks, depending on how the VHL gene is affected.

  • Type 1A: These people have a much lower risk of pheochromocytomas, but can develop other VHL-related tumors
  • Type 1B: These people have a lower risk of pheochromocytomas and renal cell carcinoma, but can develop other VHL-related tumors
  • Type 2A: These people have a higher risk of pheochromocytomas and hemangioblastomas, but a lower risk of renal cell carcinoma than other types of VHL
  • Type 2B: These people have a higher risk of pheochromocytomas, hemangioblastomas, pancreatic tumors, cysts, and renal cell carcinoma
  • Type 2C: These people have a higher risk of pheochromocytomas only

How is von Hippel-Lindau diagnosed?

VHL can be diagnosed through genetic testing or based on clinical criteria, after a doctor uses your personal and family medical history to make the diagnosis.

Clinical criteria

Clinical criteria may be used when a person has:

  • A family history of VHL plus at least one VHL-related tumor
  • Two or more VHL-related tumors without a family history
  • Certain VHL-related tumors at a young age

Anyone with these features should be evaluated for VHL gene changes.

Genetic testing for VHL

A blood, saliva, or cheek swab test can find VHL gene changes and confirm the diagnosis in most cases. Sometimes, testing on a tissue sample from a tumor is needed, especially when a person has no family history of VHL and standard testing is not conclusive.

If a family member is found to have a VHL gene change, blood relatives, including children, might be offered testing to find out if they carry the same change.

Visit Genetic Testing for Cancer Risk for more information.

Questions to ask your doctor

If you or a family member has VHL, consider asking your doctor:

  • What is my risk of developing cancer related to VHL?
  • Does my family history mean I need genetic testing?
  • What cancer screening tests should I have? When?
  • What signs or symptoms should I watch for?
  • What can I do to lower my risk of cancer?
  • Should my children or other family members be tested?
  • Are there clinical trials I should know about?

How is von Hippel-Lindau managed?

There is no cure for VHL. However, early screening and surveillance tests might catch tumors or cancers early before symptoms occur, when treatment is more likely to be successful.

Certain tests and exams are recommended when VHL is first diagnosed and periodically after diagnosis to catch problems before symptoms develop.

When first diagnosed, your care team will likely recommend:

  • A history and physical exam that includes a neurologic exam (checking nerve, brain, and spinal cord function) and a blood pressure check
  • An MRI of the brain and spinal cord
  • An eye exam by an ophthalmologist, a doctor specialized in diagnosing and treating eye problems
  • An abdominal ultrasound in people 16 and older, looking for any cysts or tumors
  • Blood or urine tests for metanephrines (hormones that can be released by pheochromocytomas) starting at age 5
  • Hearing testing
  • A special thin-cut MRI of the ear canals for people between ages 15 and 20, or earlier if there are symptoms
  • Genetic counseling

Ongoing surveillance and testing for people with VHL who have no symptoms should include:

  • A yearly health exam, including blood pressure monitoring and checking for changes in vision, hearing, or neurologic functioning
  • An annual eye exam by an ophthalmologist
  • Brain and spine MRI imaging every 2 years, beginning at age 11
  • Abdominal MRI every 2 years, starting at age 15
  • Blood or urine tests for metanephrines once a year, starting at age 5
  • Hearing tests every 2 years starting at age 11
  • A one-time MRI of the inner ear canals between ages 15 and 20

MRI is preferred over CT scans for people with VHL. Because VHL is a lifelong condition requiring many scans, avoiding repeated radiation exposure from CT scans is important.

These tests should be continued until age 65. If no signs of VHL-related tumors have been found at that time, those tests can be stopped. However, all people with VHL should continue:

  • A yearly health exam with blood pressure checks by a healthcare professional familiar with VHL
  • Yearly eye exams by an ophthalmologist

Treatment depends on the type, size, and location of the tumor, as well as whether it is causing symptoms. Some tumors are managed the same as they would be in people without VHL. In other cases, VHL-related tumors might be managed differently.

Brain and spinal cord tumors:

  • Small, slow-growing tumors that aren't causing symptoms are usually watched with regular MRI scans rather than treated right away.
  • If a tumor is in an area where surgery would be too risky, your doctor might suggest the targeted drug belzutifan. Starting it early can sometimes help avoid more aggressive treatment later.
  • Tumors that are growing or causing symptoms can be treated with surgery, radiation, targeted therapy, or a combination of these.

Eye tumors (retinal hemangioblastomas):

  • There is no single standard approach for tumors not yet causing symptoms. Some doctors recommend early laser treatment. Others prefer to watch and wait.
  • If you have multiple tumors in the eye or a tumor close to the optic nerve, targeted therapy is usually recommended.

Small, slow-growing tumors are often watched closely with imaging rather than treated right away.

Larger or faster-growing tumors are usually treated with the targeted drug belzutifan or with surgery.

When surgery is needed, doctors try to remove only the tumor and leave as much of the kidney as possible (called nephron-sparing surgery) to protect kidney function over time.

Visit Kidney Cancer Treatment for more information on how renal cell carcinoma can be treated.

Surgery to remove all or part of the adrenal gland is the standard treatment.

Before surgery, your doctor will test whether the tumor is releasing hormones. If it is, you will be given medicine to block those hormones first. This makes surgery safer.

If the cancer has spread to other parts of the body, chemotherapy or targeted therapy may be used.

Surgery is the main treatment when possible.

If the tumor releases hormones, medicine is given beforehand to block their effects.

If a tumor is near the skull or neck where surgery would be too difficult and it is not releasing hormones, radiation therapy is an option.

If the cancer has spread, chemotherapy or targeted therapy might be considered.

Small tumors are often monitored with imaging or treated with targeted therapy.

Tumors larger than 2 to 3 centimeters are usually treated with surgery when possible, depending on their location. Targeted therapies and other treatments may be options if surgery is not possible.

To learn more, visit Pancreatic Neuroendocrine Tumor Treatment.

Surgery is the main treatment.

If the tumor is found before it causes symptoms, some doctors may recommend early removal, while others prefer to wait because surgery carries risks.

Surgery can cure these tumors when the entire tumor can be removed.

These benign tumors usually do not need treatment.

If they are not causing problems, they are watched over time with imaging.

Surgery is rare and only considered if a tumor causes severe symptoms or is thought to be affecting fertility.

Targeted drugs for people with VHL

For certain VHL-related tumors, your cancer care team might consider the use of a targeted drug called belzutifan (Welireg).

Belzutifan blocks HIF-2α, which is an overactive protein in people with VHL and can cause tumor growth. It might be a part of the treatment plan for VHL-related:

  • Renal cell carcinoma that doesn’t need surgery right away, continues to grow, or comes back after other treatments have been tried.
  • Retinal hemangioblastomas, especially those that are close to the main nerve to the eye (optic nerve) or when there are multiple tumors.
  • CNS (brain or spinal cord) hemangioblastomas, especially if they are growing, don’t need surgery immediately, if there are multiple tumors, or if they are located in parts of the brain or spinal cord where surgery would be difficult.
  • Pancreatic neuroendocrine tumors that don’t need immediate surgery.

Researchers are looking at using belzutifan for other VHL-related problems, such as pancreatic cyst lesions.

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The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.

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Last Revised: June 15, 2026

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