von Hippel-Lindau Disease (VHL)

What is von Hippel-Lindau disease?

von Hippel-Lindau disease (VHL) is a rare genetic disorder that significantly increases the chance that you’ll have certain kinds of cancerous (malignant) tumors and noncancerous (benign) tumors and cysts. Healthcare providers may call this condition von Hippel-Lindau syndrome.

The condition happens if you inherit a specific genetic mutation (change). Research shows that by the time they’re 65 years old, 97% of people who carry this genetic mutation will develop tumors and other conditions that VHL causes. Surgery is the most common treatment for conditions that von Hippel-Landau disease may cause.

What cancers are associated with von Hippel-Landau disease?

Having this condition increases the chance you’ll have one or more of the following kinds of cancer:

• Clear cell renal carcinoma (ccRCC): This is the most common form of renal cell carcinoma (kidney cancer). Experts estimate 25% to 60% of people with VHL disease have this cancer. 
• Pancreatic neuroendocrine tumors (pancreatic NETs): These are rare tumors that start in your pancreas’ endocrine cells. Between 9% and 17% of people with von Hipple-Landau disease develop pancreatic NETS.
• Pheochromocytoma: This is a rare but treatable tumor that starts in your adrenal gland. Pheochromocytomas start as noncancerous tumors but can be cancerous. Between 10% and 20% of people with von Hippel-Lindau disease have pheochromocytomas.
• Broad ligament cystadenomas: This condition affects 10% of people assigned female at birth (AFAB) who have von Hippel-Lindau disease. A broad ligament cystadenoma is a tumor that starts near your fallopian tubes.

What noncancerous tumors are associated with VHL?

Hemangioblastomas are the most common noncancerous tumor that may happen if you have von Hippel-Landau disease. A hemangioblastoma is a noncancerous tumor that grows in the blood vessels in your brain, spinal cord or retina.

These tumors don’t spread from where they started (metastasize), but they can grow large enough to affect nearby tissue and cause serious health issues. Hemangioblastomas associated with von Hippel-Landau disease are:

• Retinal hemangioblastoma: This is a type of eye tumor that can cause vision loss. Research shows that 60% of people with von Hippel-Lindau syndrome develop retinal hemangioblastoma.
• Brain stem and cerebellar hemangioblastomas: These are brain tumors that may affect your balance and cause other issues. They may affect 13% to 72% of people with von Hippel Landau disease.
• Spinal cord hemangioblastoma: Between 13% and 50% of people with VHL have this type of hemangioblastoma.

Having von Hippel-Landau disease may also increase your risk of developing the following noncancerous tumors and cysts include:

• Epididymal cystadenomas: These tumors affect people assigned male at birth (AMAB). They develop in your epididymis, the small tube-like structure near your testicles that stores sperm. Between 25% and 60% of people AMAB with von Hippel Lindau disease develop this type of tumor.
• Endolymphatic sac tumors (ELST): This is a very rare tumor that may develop in your inner ear if you have VHL. Between 10% to 25% of people with von Hippel-Lindau disease have this condition.
• Cysts: Cysts are growths filled with fluid. People with VHL may have cysts on or in their kidneys and pancreas.

How common is von Hippel-Lindau disease?

This is a rare disorder that affects 1 in 36,000 people. Most people with VHL develop symptoms in their mid-20s.

What are the symptoms of von Lindau-Hippel disease?

This condition causes tumors throughout your body, which means you may have several different symptoms depending on where tumors develop and the tumors’ sizes. Symptoms may include:

• Headaches.
• Hearing loss or tinnitus.
• High blood pressure.
• Loss of balance.
• Loss of muscle strength or coordination.
• Vision issues.
• Vomiting.

What causes von Hippel-Lindau disease?

von Hippel-Lindau syndrome is an inherited disorder that may happen when one of your biological parents passes on an abnormal version of the VHL gene, a tumor suppressor gene that manages cell growth. 

These genes make special proteins that put the brakes on cell growth that may cause cancer. When tumor suppressor genes mutate (change), it’s as if they switch from pressing on the brakes to hitting the gas pedal, suddenly putting cell growth into overdrive.

This disorder follows an autosomal dominant inheritance pattern. That means if you inherit an abnormal VHL gene from one of your biological parents, there’s a 50% chance that you’ll have von Hippel-Lindau disease. That being said, research shows up to 10% of people with VHL don’t have a family history of the disorder. 

How is von Hippel-Lindau disease diagnosed?

Healthcare providers may suspect you have VHL if you have symptoms of one of the conditions that von Hippel-Lindau disease may cause, like a hemangioblastoma or clear cell renal carcinoma. But genetic testing is the only way to confirm that you have the condition. If anyone in your family has von Hippel-Lindau disease, ask your healthcare provider if genetic testing is right for you. 

What are treatments for von Hippel-Lindau disease?

Treatments vary depending on the type of tumor or cyst that VHL causes. Your healthcare provider will explain your treatment options. Common treatments are:

• Surgery to remove tumors.
• Chemotherapy.
• Radiation therapy.
• Targeted therapy, including peptide receptor radionuclide therapy (PPRT) and tyrosine kinase inhibitors (TKI).
• Immunotherapy.
• Hormone therapy.

Is there a cure for VHL?

von Hippel-Lindau disease doesn’t have a cure. The goal of treatment is to find and remove tumors as early as possible. Your provider may recommend surgery to remove tumors along with other treatments.

Can VHL be prevented?

No, it can’t. von Hippel-Lindau disease occurs when a biological parent passes a genetic mutation onto their child. If you have a family history of VHL, genetic tests will determine whether you’re carrying the mutation.

While you can’t prevent von Hippel-Lindau disease, it’s helpful to know your risk and understand how VHL may affect you. If you know you’re at risk, healthcare providers can watch for signs of VHL-related tumors and move quickly to remove those tumors.

If you carry the VHL gene and plan to have a baby, a genetic counselor can help you understand the risks of passing the gene to your child.

Are there screening tests for von Hippel-Lindau disease-related conditions?

There aren’t any screening guidelines, like the cancer screening tests set by the U.S. Preventive Services Task Force. If genetic tests show you carry an abnormal VHL gene, your healthcare team may recommend that you have specific tests that may detect issues early on. For example, your provider may recommend that you have an abdominal magnetic resonance imaging (MRI) scan every two years to check for VHL-related cancers, like clear cell renal carcinoma.

What can I expect if I have VHL?

If you have this condition, you may have regular tests to monitor for signs of specific kinds of diseases. Finding and treating tumors early on may reduce the impact that von Hippel-Lindau syndrome may have on your life.

How do I take care of myself?​

Living with VHL can mean living with uncertainty. If you inherit the genetic mutation that causes von Hippel-Lindau disease, there’s a 50% chance you’ll have the condition. If you do, there’s a 97% chance you’ll have certain kinds of cancer and other serious illnesses.

But no one can predict exactly how VHL may affect your life. Here are some things you can do that may help you manage those challenges:

• Consider mental health support: One study showed the emotional impact that a VHL diagnosis can have, including anxiety and panic attacks.
• Protect your overall health: Eat a balanced diet of lean protein, whole grains, leafy greens and lots of vegetables. Get some exercise (it may help ease stress) and ask your healthcare team about vaccinations that make sense for you.

When should I seek care?

You should call your healthcare provider if you experience:

• Changes to your vision or hearing.
• Headaches.
• Nausea or vomiting not caused by other illnesses.
• A sharp increase in blood pressure.
• Sudden difficulty with walking, balance or coordination.

What questions should I ask my doctor?

You’ve just learned you have a family history of von Hippel-Lindau disease. Here are some questions you may want to ask your healthcare provider:

• What do the results of my genetic test mean?
• Should other family members have genetic tests?
• How often should I have tests to detect early signs of conditions associated with VHL?