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Von Hippel–Lindau Disease (VHL)

By

M. Cristina Victorio

, MD, Akron Children's Hospital

Last full review/revision Sep 2021| Content last modified Sep 2021
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GET THE QUICK FACTS

Von Hippel-Lindau disease is a rare hereditary disorder that causes noncancerous and/or cancerous tumors to develop in several organs.

  • Von Hippel-Lindau disease is caused by mutations in a gene.

  • Children may have headaches, impaired vision, or high blood pressure and feel dizzy or weak.

  • Doctors suspect the disorder based on the person’s family history and results of a physical examination, then do imaging and other tests to check for tumors and other problems.

  • Tumors are removed surgically, treated with radiation, or destroyed using a laser or application of extreme cold.

Von Hippel-Lindau disease is a neurocutaneous syndrome. A neurocutaneous syndrome causes problems that affect the brain, spine, and nerves (neuro) and the skin (cutaneous).

In Von Hippel-Lindau disease, tumors most commonly develop in the brain and retina of the eyes. These tumors, called angiomas, consist of blood vessels. Other types of tumors develop in other organs and include tumors in the adrenal glands (pheochromocytomas Pheochromocytoma A pheochromocytoma is a tumor that usually originates from the adrenal glands’ chromaffin cells, causing overproduction of catecholamines, powerful hormones that induce high blood pressure and... read more ) and cysts in the kidneys, liver, or pancreas. As people with the disorder age, the risk of developing kidney cancer Kidney Cancer Kidney cancer may cause blood in the urine, pain in the side, or fever. Cancer is most often detected by accident when an imaging test is done for another reason. Diagnosis is by computed tomography... read more increases. By age 60, the risk may be as high as 70%.

The gene that causes von Hippel-Lindau disease has been identified. Only one gene for the disorder—from one parent—is required for the disorder to develop. Each child of an affected parent has a 50% chance of inheriting the disorder. In 20% of people with this disorder, it results from a spontaneous new (not inherited) mutation. This disorder occurs in 1 of 36,000 people.

Symptoms of VHL

Typically, symptoms of von Hippel-Lindau disease appear between ages 10 and 30, but they can appear earlier.

Symptoms depend on the size and location of the tumors. Children may have headaches and feel dizzy or weak. Vision may be impaired, and blood pressure may be high. Coordination may be lost. About 10% of affected children have a tumor of the inner ear, which may impair hearing.

Angiomas in the retina usually cause no symptoms, but if they enlarge, they can cause substantial loss of vision. When these angiomas are present, the retina may become detached, fluid may accumulate on or under the macula (the central part of the retina), and the optic nerve may be damaged by increased pressure within the eye (glaucoma Glaucoma Glaucomas are a group of eye disorders characterized by progressive optic nerve damage (often, but not always, associated with increased eye pressure) that can lead to irreversible loss of vision... read more ).

Without treatment, people may become blind, have brain damage, or die. Death usually results from complications of brain angiomas or kidney cancer.

Diagnosis of VHL

  • Imaging tests

  • Eye examination

  • Genetic testing

Doctors determine whether any family members have von Hippel-Lindau disease and do a physical examination.

If findings suggest the disorder, various tests are done to check for tumors and other abnormalities:

Von Hippel-Lindau disease is diagnosed when one of the following is present:

  • A family history of von Hippel-Lindau disease plus at least one characteristic tumor in the eyes, brain, spine, adrenal glands, kidneys, or pancreas

  • Two or more characteristic von Hippel-Lindau disease tumors in people who have no known family history of von Hippel-Lindau disease

If doctors detect one tumor, they look for others.

If doctors are still unsure of the diagnosis, they do tests that analyze chromosomes (molecular genetic testing) to identify the abnormal VHL gene and confirm the diagnosis.

If the abnormal VHL gene is identified in a person, genetic testing is done to check for the abnormal gene in family members.

Treatment of VHL

  • Surgery or sometimes radiation therapy

  • For angiomas of the retina, laser therapy or application of extreme cold

  • Sometimes the drug belzutifan

Tumors are surgically removed, if possible, before they cause permanent damage. High-dose radiation therapy, focused on the tumor, can sometimes be used instead. People who have tumors in the adrenal glands may also need drugs to control their blood pressure. People who have advanced kidney cancer may be given other drug treatments.

Belzutifan is now available for use in adults who have kidney cancer, tumors in the brain or spine, or tumors in the pancreas that do not need to be immediately surgically removed. This drug shrinks tumors and stops them from progressing. It can be used until the disease worsens or until any side effects become too severe.

Typically, angiomas of the retina are destroyed using laser therapy or application of extreme cold (cryotherapy). These procedures help preserve vision.

Screening for new problems

Because new complications and tumors can develop in von Hippel-Lindau disease, affected people must be closely monitored for the rest of their life.

In people who have been diagnosed with von Hippel-Lindau disease, the following screening examinations and tests are repeated every 1 or 2 years and when symptoms occur:

In people who have not been diagnosed with von Hippel-Lindau disease but who have the abnormal gene or who have not been tested but who have a parent or sibling with von Hippel-Lindau disease, blood pressure monitoring and examinations to look for vision, hearing, and eye problems are done every year.

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