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Genetic and Rare Diseases Information Center (GARD)

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Von Hippel-Lindau disease

Other Names for this Disease
  • VHL
  • VHL syndrome
  • Von Hippel-Lindau disease
  • Von Hippel-Lindau syndrome
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I am looking for information about Von-Hippel Lindau syndrome, including how it might be treated.

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What is Von Hippel-Lindau (VHL) disease?

Von Hippel-Lindau (VHL) disease is a genetic multi-system disorder characterized by the abnormal growth of tumors in certain parts of the body (angiomatosis). The specific tumors that are associated with VHL disease include hemangioblastomas (tumors comprised of a nest of blood vessels) of the brain, spinal cord, and retina; kidney cysts and clear cell kidney cell carcinoma; pheochromocytoma (a type of noncancerous tumor that affects the adrenal glands, which are the small hormone-producing glands located on top of each kidney); and endolymphatic sac tumors (a type of tumor of the inner ear area called the endolymphatic sac).[1][2] Mutations in the VHL gene cause VHL disease. These mutations are  inherited in an autosomal dominant pattern.[2] Detecting and treating VHL early is important. Treatment usually involves surgery or sometimes radiation therapy. The goal is to treat growths while they are small and before they do permanent damage.[3]
Last updated: 5/20/2013

What are the signs and symptoms of Von Hippel-Lindau (VHL) disease?

Symptoms of Von Hippel-Lindau (VHL) disease vary among patients and depend on the size and location of the tumors.[3][4] Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination (ataxia). Hemangioblastomas can also occur in the light-sensitive tissue that lines the back of the eye (the retina). These tumors, which are also called retinal angiomas, may cause vision loss. Pheochromocytomas affect the adrenal glands, which are small hormone-producing glands located on top of each kidney. These tumors often cause no symptoms, but in some cases they can produce an excess of hormones that cause dangerously high blood pressure. About 10 percent of people with VHL disease develop endolymphatic sac tumors, which are noncancerous tumors in the inner ear. These growths can cause hearing loss in one or both ears, as well as ringing in the ears (tinnitus) and problems with balance.[1][2] Individuals with VHL disease are also at a higher risk than normal for certain types of cancer, especially kidney cancer.[4] Renal cell carcinoma occurs in about 40% of individuals with VHL disease and is the leading cause of mortality.[1]

Last updated: 5/20/2013

What causes Von Hippel-Lindau disease?

VHL disease is caused by a mutation (alteration) in the VHL gene.[2] 

The VHL gene is a tumor suppressor gene, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way.  Mutations in this gene prevent production of the VHL protein or lead to the production of an abnormal version of the protein.   An altered or missing VHL protein cannot effectively regulate cell survival and division.  As a result, cells grow and divide uncontrollably to form the tumors and cysts that are characteristic of VHL disease.[1][2]
Last updated: 5/20/2013

Is Von Hippel-Lindau (VHL) disease inherited?

Mutations in the VHL gene are inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and cysts. Most people with VHL disease inherit an altered copy of the gene from an affected parent. In about 20 percent of cases, however, the altered gene is the result of a new mutation that occurred during the formation of reproductive cells (eggs or sperm) or very early in development.[2]

Unlike most autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the VHL gene must be altered to trigger tumor and cyst formation in VHL disease. A mutation in the second copy of the VHL gene occurs during a person's lifetime in certain cells within organs such as the brain, retina, and kidneys. Cells with two altered copies of this gene make no functional VHL protein, which allows tumors and cysts to develop. Almost everyone who inherits one VHL mutation will eventually acquire a mutation in the second copy of the gene in some cells, leading to the features of VHL disease.[2]

Last updated: 5/20/2013

How is Von Hippel-Lindau (VHL) disease diagnosed?

The diagnosis of Von Hippel-Lindau (VHL) disease is suspected in individuals with characteristic lesions with hemangioblastomas, renal cysts, and renal cell carcinoma, pheochromocytoma, and endolymphatic sac tumors.  VHL is the only gene known to be associated with VHL disease.  Molecular genetic testing of the VHL gene detects mutations in nearly 100% of individuals with the disease.  Such testing is clinically available.[1]
Last updated: 5/20/2013

How might Von Hippel-Lindau (VHL) disease be treated?

Treatment for Von Hippel-Lindau (VHL) disease varies according to the location and size of the tumor and its associated cyst. In general, the objective of treatment is to treat the growths when they are causing symptoms but while they are still small so that they do not cause permanent problems by putting pressure on the brain or spine, blocking the flow of cerebrospinal fluid in the nervous system, or impairing vision. Treatment of most cases of VHL disease usually involves surgery to remove the tumors before they become harmful. Certain tumors can be treated with focused high-dose irradiation. Individuals with VHL disease need careful monitoring by a physician and/or medical team familiar with the disorder.[4]

You can access more detailed information about the treatment of VHL disease at the following web pages:
Last updated: 5/20/2013