Von Hippel-Lindau syndrome

Von Hippel-Lindau syndrome is an inherited disorder characterized by tumors and fluid-filled sacs called cysts that can develop in many different parts of the body. Tumors may be either benign (noncancerous) or malignant (cancerous) and occur from early childhood to late adulthood.

Tumors called hemangioblastomas or angiomas can develop in the brain and spinal cord, the kidneys, and the back of the eye (retina). These tumors are made up of newly formed blood vessels and are typically noncancerous. Other types of tumors, which may be cancerous, often occur in the kidneys, the adrenal glands (hormone-producing glands located above each kidney), the pancreas, certain reproductive organs, and the inner ear.

Von Hippel-Lindau syndrome is sometimes divided into two types. Type 1 von Hippel-Lindau syndrome is associated with a high frequency of pheochromocytoma. This type of tumor, which is usually noncancerous, develops in the adrenal gland and can cause dangerously high blood pressure. Type 2 von Hippel-Lindau syndrome tends to involve fewer pheochromocytomas, but is associated with an increased risk of developing kidney cancer.

This syndrome occurs in about 1 in 32,000 births.

Variations of the VHL gene increase the risk of developing von Hippel-Lindau syndrome.

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 the VHL gene prevent any protein from being made or lead to the production of an abnormal protein. If the VHL protein cannot function properly, cells are unable to effectively control cell growth and division. As a result, cells grow and divide uncontrollably to form the tumors and cysts that are characteristic of von Hippel-Lindau syndrome.

Mutations in the VHL gene are inherited in an autosomal dominant pattern, which means that one copy of the altered gene is sufficient to increase the risk of developing tumors and cysts. Most people with von Hippel-Lindau syndrome inherit an altered copy of the gene from one 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 early in fetal development.

As long as one copy of the VHL gene is producing functional VHL protein in each cell, tumors do not form. If a mutation occurs in the second copy of the VHL gene during a person's lifetime, the cell will have no working copies of the gene and will produce no functional VHL protein. A lack of this protein allows tumors characteristic of von Hippel-Lindau syndrome to develop.

You may find the following resources about von Hippel-Lindau syndrome helpful.

• NIH Publications - National Institutes of Health (3 links)
• MedlinePlus - Health Information (3 links)
• Genes and Disease - Genetic disorder summaries
• Educational resources - Information pages (2 links)
• Patient support - For patients and families (3 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• OMIM - Genetic disorder catalog

See How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

• What does it mean if a disorder seems to run in my family?
• What are the different ways in which a genetic condition can be inherited?
• If a genetic disorder runs in my family, what are the chances that my children will have the condition?
• Why are some genetic conditions more common in particular ethnic groups?

These links provide additional genetics resources that may be useful.

• Genetics and health
• Resources for Patients and Families
• Resources for Health Professionals

adrenal glands ; angioma ; autosomal ; autosomal dominant ; benign ; cancer ; cysts ; familial ; gene ; hemangioblastoma ; hormone ; mutation ; new mutation ; pheochromocytoma ; protein ; retina ; tumor ; tumor suppressor gene

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.