Frequently Asked Questions about von Hippel-Lindau (VHL) Syndrome

What is von Hippel-Lindau syndrome?

Von Hippel-Lindau, or VHL, is a syndrome in which tumors and cysts develop in many parts of the body. The term “syndrome” refers to a group of features that often occur together. The tumors may be either benign (noncancerous) or cancerous.

People with VHL syndrome have an increased risk of developing benign tumors of the blood vessels (hemangioblastomas) in the brain, spinal cord, or eyes and benign tumors of the adrenal gland (pheochromocytomas). People with VHL syndrome can also develop a specific type of kidney cancer called clear cell renal cancer. Some people with VHL syndrome develop many cysts in the kidneys and pancreas, as well as tumors in certain reproductive organs. However, the symptoms of VHL syndrome can vary among members of the same family with VHL syndrome.

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How common is VHL syndrome?

VHL syndrome is rare. It occurs in about 1 in 36,000 births. Both women and men can have it. Most cases of VHL syndrome are inherited (passed down) from an affected parent, but about 1 in 5 people with VHL syndrome are the first members of their family to have the syndrome.

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What causes VHL syndrome?

VHL is a gene that is involved in preventing tumors from growing in the body. A mutated (changed) VHL gene can increase the chance that certain tumors will develop and cause VHL syndrome.

Mutations in the VHL gene can be found through genetic testing.

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What does a negative VHL test result mean?

A negative test result means that no VHL mutation was found. This can happen for several reasons:

  • You could have a mutation in the VHL gene that is not detectable by the testing method used.
  • You may have a mutation in a different gene that causes VHL syndrome. However, at the moment, we only know that the VHL gene is associated with VHL syndrome.
  • You could have a different syndrome. Other syndromes share some similar features with VHL syndrome. Other hereditary syndromes that can cause pheochromocytomas are neurofibromatosis type 1 (NF1) or multiple endocrine neoplasia type 2 (MEN2). Other hereditary syndromes that can cause kidney cancer are hereditary leiomyomatosis renal cell cancer (HLRCC), and Birt-Hogg-Dubé (BHD) syndrome. Your genetic counselor may recommend testing for other syndromes.
  • The feature that prompted VHL genetic testing have occurred by chance. Cysts, kidney cancer, and other tumors seen in people with VHL syndrome can occur by chance or as a part of another, nonhereditary condition.
  • There is a VHL mutation in your family, but you did not inherit it.
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What does a “variant of uncertain significance” (or ambiguous) test result mean?

Genes are written in chemical “letters” called bases. We call the wrong spelling of a gene a “mutation,” and a mutation can cause an increased risk of cancer. However, some spelling changes in genes do not cause disease. We are still learning which spellings are normal (harmless) and which may cause disease. These kinds of uncertain changes are called “variants of uncertain significance.”

If you have a variant of uncertain significance in your VHL gene, we may not be able to tell you whether or not you are at increased risk for cancer. Your genetic counselor will make cancer screening recommendations based on your family history. Your counselor may also suggest testing certain relatives to learn more about the variant, but this information will probably not be helpful in predicting cancer risks for your relatives. Future research may make it clearer whether a variant of uncertain significance leads to increased risks of cancer.

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What does a positive VHL test result mean?

A positive result means that a mutation in the VHL gene was found. This means that you have an increased risk for developing certain features associated with VHL syndrome. The exact risks for VHL syndrome-related tumors are not yet known and may vary from person to person. Most people with VHL develop a tumor, or more than one tumor, by the age of 65.

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How should people with a VHL mutation manage their risks for cancer?

The goal of cancer screening for people with VHL mutations is to try to detect cancer at an early stage if it develops. The best screening for people with VHL syndrome is not yet established. Screening should be ordered by a specialist who knows about the condition and include:

  • Annual physical exams starting at age 1. This should include:
    • Blood pressure measurement lying down and standing.
    • Looking for VHL syndrome-related symptoms, such as neurologic, hearing, and vision problems.
    • Anyone who has vision or hearing problems, such as ringing in the ear or vertigo, should tell his or her doctor. A person should also tell their doctor about any unexplained symptoms such as frequent headaches, sweating, heart palpitations, or severe anxiety.
  • An eye exam by an ophthalmologist every year, starting at age 1.
  • Routine hearing tests by an audiologist for newborns. Starting at age 5, hearing tests should be performed every 2 or 3 years.
  • Beginning at age 5, blood or urine testing every year for the catecholamine hormones. Catecholamines are often called stress or “fight-or-flight” hormones and include adrenaline.
  • An ultrasound examination of the abdomen, including the kidneys, every 1 to 2 years, starting between the ages of 8 to 12, until there is a solid kidney mass over 2 cm in size. At that time, yearly magnetic resonance imaging (MRI) or computed tomography (CT) is recommended.
  • A baseline MRI of the kidneys, pancreas, and adrenal glands should begin at 16 to 18 years of age.
  • An MRI of the brain and spine should be done every 2 years beginning at age 16.
  • Before a surgery or pregnancy, pheochromocytomas should be ruled out since they can trigger a hypertensive crisis (when a person’s blood pressure is dangerously high).

If there are any abnormal findings in any of the above tests, follow-up tests will be advised. Other tests may also be appropriate, depending on personal and family history. When tumors are found, they are usually monitored or removed depending on their size and behavior.

People with VHL syndrome should avoid smoking and using other tobacco products and harmful industrial chemicals.

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If I have a VHL mutation, what are the risks to my children?

If you have a VHL mutation, each of your children will have a 50% (1 in 2) chance of inheriting it. A child who inherits the mutated VHL gene would inherit the risks associated with it. However, the same mutation may cause different problems, or not cause any problems, in different family members.

In this condition, cancer screening starts at an early age. For this reason, it is a good idea for your children to have genetic counseling and consider genetic testing at an early age.

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If I have a VHL mutation, what are my options for having children?

If you have a VHL mutation, you may want to learn about options for family planning (starting a family or having more children). For example, embryos can be tested for the family’s genetic mutation before they are even implanted in a woman’s uterus. This process is called preimplantation genetic diagnosis (PGD). PGD is performed in combination with in vitro fertilization (IVF), and may be an option for families who wish to have children without the hereditary cancer risk. To learn more, ask for a referral to an PGD-IVF specialist before attempting pregnancy.

Other possible family planning options include having children with the assistance of donor eggs or donor sperm or through adoption.

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What if I have questions?

If you have any questions or concerns, please contact the MSK Clinical Genetics Service at 646-888-4050.

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