Alternative Names
Angiomatosis retinae; Cerebelloretinal Angiomatosis, Familial; Hippel-Lindau Disease; VHL syndrome; von Hippel-Lindau Disease; VHL Disease
Symptoms & Characteristics
Von Hippel-Lindau syndrome (also known as von Hippel-Lindau disease or VHL disease) is an inherited disorder characterized by the formation of tumors and fluid-filled sacs (cysts) in many different parts of the body. Tumors may be either noncancerous or cancerous and usually appear during young adulthood; however, the signs and symptoms of von Hippel-Lindau syndrome can occur throughout life.
Tumors called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels and are typically noncancerous. 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.
People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys, pancreas, and male genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of noncancerous tumor called a pheochromocytoma. 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 can lead to dangerously high blood pressure.
About 10% of people with von Hippel-Lindau syndrome develop noncancerous tumors (called endolymphatic sac 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.
Von Hippel-Lindau syndrome can be divided into two major types based on the risk of developing pheochromocytomas. Type 1 von Hippel-Lindau syndrome is associated with a low risk of these tumors, and type 2 is characterized by a much higher risk. Type 2 can be further divided into types 2A, 2B, and 2C, depending on the probability of developing renal cell carcinoma and hemangioblastomas.
Treatment
Early diagnosis, routine surveillance and treatment of von Hippel-Lindau syndrome may help to manage some of the symptoms and sometimes prevent related problems.
How Common Is It?
Von Hippel-Lindau syndrome occurs in about 1 in 32,000 individuals.
Genetics & Inheritance
Mutations in the VHL gene cause 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 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 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 in each cell 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% f cases, however, the altered gene is the result of a new mutation that occurred during the formation of reproductive cells (eggs or sperm) or in early fetal development.
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 von Hippel-Lindau syndrome. A mutation in the second copy of the VHL gene occurs during a person's lifetime in 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.
Genetic Testing
Cancer predisposition testing for von Hippel-Lindau syndrome may be available through an in person genetic consultation for people who are considered at risk. Use our find a genetic professional directory to locate a trained genetic professional in your area.
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