Von Hippel-Lindau Syndrome

Approved by the Lineagotica Editorial Board, 12/2016

What is von Hippel-Lindau syndrome?

Von Hippel-Lindau syndrome (VHL) is a hereditary condition associated with tumors arising in multiple organs. The tumors in VHL include hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and eye. The eye tumors are also called retinal angiomas. People with VHL also have an increased risk of developing clear cell renal cell carcinoma, which is a specific type of kidney cancer; pheochromocytoma, which is a tumor of the adrenal gland; and a type of pancreatic tumor known as pancreatic neuroendocrine tumor. Other features of VHL include: kidney cysts, which are closed sacs usually filled with fluid; pancreatic cysts, epididymal cystadenomas, which are tumors near a man’s testicles; and endolymphatic sac tumors, which are tumors of the ear that may cause hearing loss.

What causes VHL?

VHL is a genetic condition. This means that the risk of developing cancer and other features of VHL can be passed from generation to generation in a family. The gene associated with VHL is also called VHL. A mutation, meaning alteration, in the VHL gene gives a person an increased risk of developing kidney cancer and other symptoms of VHL. Nearly everyone who has VHL syndrome has an identifiable VHL genetic mutation.

How is VHL inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. VHL follows an autosomal dominant inheritance pattern, in which a mutation happens in only 1 copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.

Options exist for people interested in having a child when they know that 1 of them carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos that do not have the mutation. PGD has been in use for over a decade, and more recently has been used for several hereditary cancer predisposition syndromes.  However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is VHL?

It is estimated that about 1 in 30,000 people has VHL. About 20% of people with VHL do not have any family history of the condition. They have a de novo mutation, meaning a new mutation in the VHL gene.

How is VHL diagnosed?

VHL is suspected when a person has:

  • Multiple hemangioblastomas of the brain, spinal cord, or eye, or

  • 1 hemangioblastoma and clear cell kidney cancer, pancreatic cysts, pheochromocytoma, endolymphatic sac tumor, or epididymal cyst

  • In young patients, VHL is also suspected with multiple bilateral clear cell renal cell carcinoma.

If a person has a family history of VHL, he or she is suspected of also having VHL if the person has any one symptom, such as hemangioblastoma, kidney or pancreatic cysts, pheochromocytoma, or kidney cancer. Genetic testing for mutations in the VHL gene is available for people suspected to have VHL. Nearly all people with VHL will be found to have the genetic mutation once tested.

What are the estimated cancer risks associated with VHL?

The risk of kidney cancer in families with VHL is estimated to be about 40%.

Would the treatment of kidney cancer change if I have VHL?

In general, treatment for kidney cancer is similar regardless of whether a patient has VHL. However, there is some evidence about specific VHL considerations regarding  surgery. For a person with VHL and kidney cancer, surgery for a kidney tumor is generally considered when a tumor reaches 3 centimeters (cm) in size. Preserving renal function with the intent of preventing or delaying dialysis is an important part of the current surgical approach to VHL, and surgeons generally try to remove kidney tumors while trying to leave as much normal kidney behind as possible (called nephron sparing surgery or partial nephrectomy).Similarly, the main treatment for tumors arising in other organs is also surgery, which is done when the tumor reaches a specific size or causes symptoms.

What are the screening options for VHL?

It is important to discuss with your doctor the following screening options, as each individual is different:

  • Yearly eye examination to look for retinal tumors, beginning around age 2

  • Yearly physical examination

  • Yearly 24-hour urine test to screen for elevated catecholamines, beginning around age 2

  • Yearly abdominal ultrasound to look at the kidneys, pancreas, and adrenal glands beginning in the teenage years; change screening to abdominal computed tomography (CT or CAT) scan or MRI in adulthood

  • Magnetic resonance imaging (MRI) of the brain and spine every 2 years beginning in the teenage years

  • Depending on the growth rate of tumors or the presence of symptoms, the time duration between scans may be adjusted by your doctor.

For more detailed screening recommendations by age group, see the National Cancer Institute screening protocol for VHL.

Screening options may change over time as new technologies are developed and more is learned about VHL. It is important to talk with your doctor about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans.

Questions to ask the doctor

If you are concerned about your risk for developing cancer, talk with your doctor. Consider asking the following questions of your doctor:

  • What is my risk of developing kidney cancer?

  • What is my risk of developing other types of cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

  • When is surgery needed to remove kidney tumors?

If you are concerned about your family history and think your family may have VHL, consider asking the following questions:

  • Does my family history increase my risk of developing kidney cancer?

  • Does it suggest the need for a cancer risk assessment?

  • Will you refer me to a genetic counselor or other genetics specialist?

  • Should I consider genetic testing?

More Information

The Genetics of Cancer

Genetic Testing

What to Expect When You Meet With a Genetic Counselor

Collecting Your Family Cancer History

Sharing Genetic Test Results with Your Family

Additional Resources

VHL Family Alliance

www.vhl.org

National Cancer Institute

www.cancer.gov  

American Cancer Society
www.cancer.org  

CancerCare 
www.cancercare.org

To find a genetic counselor in your area, ask your doctor or visit the following websites:      

National Society of Genetic Counselors                    

www.nsgc.org

National Cancer Institute: Cancer Genetics Services Directory

www.cancer.gov/cancertopics/genetics/directory