Von Hippel-Lindau disease is a rare hereditary disorder that causes noncancerous and/or cancerous tumors to develop in several organs.
Von Hippel-Lindau disease is caused by mutations in a gene.
Children may have headaches, impaired vision, or high blood pressure and feel dizzy or weak.
Doctors suspect the disorder based on the person’s family history and results of a physical examination, then do imaging and other tests to check for tumors and other problems.
Tumors are removed surgically, treated with radiation, or destroyed using a laser or extreme cold, and medications such as belzutifan and pazopanib may reduce the size of tumors without surgery.Tumors are removed surgically, treated with radiation, or destroyed using a laser or extreme cold, and medications such as belzutifan and pazopanib may reduce the size of tumors without surgery.
Von Hippel-Lindau disease is a neurocutaneous syndrome. A neurocutaneous syndrome causes problems that affect the brain, spine, and nerves (neuro) and the skin (cutaneous).
The gene that causes von Hippel-Lindau disease has been identified. Only 1 gene for the disorder from 1 parent is required for the disorder to develop. Each child of an affected parent has a 50% chance of inheriting the disorder. Some people inherit the gene, whereas other people develop von Hippel-Lindau disease from a spontaneous and new (not inherited) gene mutation.
In von Hippel-Lindau disease, tumors most commonly develop in the brain (cerebellar hemangioblastomas) and retina of the eyes (retinal angiomas). These tumors consist of blood vessels. Other types of tumors develop in other organs and include tumors in the adrenal glands (pheochromocytomas) and cysts in the genital tract, kidneys, liver, or pancreas.
As people with the disorder age, the risk of developing kidney cancer increases. By age 60, the risk may be as high as 70%.
Symptoms of von Hippel-Lindau Disease
Typically, symptoms of von Hippel-Lindau disease appear between ages 10 and 30, but they can appear earlier.
Symptoms depend on the size and location of the tumors. Children may have headaches and feel dizzy or weak. Vision may be impaired, and blood pressure may be high. Coordination may be lost. Some affected children have a tumor in their inner ear, which may impair hearing.
Retinal angiomas usually cause no symptoms, but if they enlarge, they can cause substantial loss of vision. When these angiomas are present, the retina may become detached, fluid may accumulate on or under the macula (the central part of the retina), and the optic nerve may be damaged by increased pressure within the eye (glaucoma).
Without treatment, people may become blind, have brain damage, or die. Death usually results from complications of brain tumors or kidney cancer.
Diagnosis of von Hippel-Lindau Disease
Imaging tests
Eye examination
Genetic testing
Doctors do a physical examination.
If examination findings suggest von Hippel-Lindau disease, doctors do various tests to check for tumors and other abnormalities:
Computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain and spine
An eye examination including ophthalmoscopy
Ultrasound, CT scan, or MRI of the abdomen
Genetic tests
Hearing tests
Blood or urine tests
Von Hippel-Lindau disease is diagnosed when 1 of the following is present:
A family history of von Hippel-Lindau disease plus at least 1 characteristic tumor in the eyes, brain, spine, adrenal glands, kidneys, or pancreas
Two or more characteristic von Hippel-Lindau disease tumors in people who have no known family history of the disease
If doctors detect one tumor, they look for others.
Doctors also do tests to analyze chromosomes (molecular genetic testing) to identify the abnormal gene and confirm the diagnosis.
If the abnormal gene is identified in a person, genetic testing is done to check for the abnormal gene in family members.
Doctors do a yearly blood or urine test to check for substances called fractionated metanephrines. If the level of these substances is increased, a person may have a pheochromocytoma.
Doctors check for ear tumors and potential hearing loss by performing a thorough hearing exam called audiometry.
Treatment of von Hippel-Lindau Disease
Surgery or sometimes radiation therapy
For angiomas of the retina, laser therapy or application of extreme cold
Sometimes the medication belzutifan or pazopanib
Tumors are surgically removed, if possible, before they cause permanent damage. High-dose radiation therapy, focused on the tumor, can sometimes be used instead. People who have tumors in the adrenal glands (pheochromocytomas) may also need medications to control their blood pressure. People who have advanced kidney cancer may be given other medications.
Belzutifan is a medication that may be used in adults who have kidney cancer, tumors in the brain or spine, or tumors in the pancreas that do not need to be immediately surgically removed. This medication shrinks tumors and stops them from progressing. It can be used until the disease worsens or until any side effects become too severe. Pazopanib is a medication that can be used in adults who have advanced kidney cancer.Belzutifan is a medication that may be used in adults who have kidney cancer, tumors in the brain or spine, or tumors in the pancreas that do not need to be immediately surgically removed. This medication shrinks tumors and stops them from progressing. It can be used until the disease worsens or until any side effects become too severe. Pazopanib is a medication that can be used in adults who have advanced kidney cancer.
Typically, angiomas of the retina are destroyed using laser therapy or application of extreme cold (cryotherapy). These procedures help preserve vision.
Screening for new problems
Because new complications and tumors can develop in von Hippel-Lindau disease, affected people must be regularly monitored for the rest of their life.
In people who have been diagnosed with von Hippel-Lindau disease, the following screening examinations and tests are repeated at various intervals and when symptoms occur:
Physical examination
Eye examination to screen for eye tumors
Blood pressure checks and urine and blood tests to screen for pheochromocytomas
Magnetic resonance imaging (MRI) scans of the brain and spine to screen for tumors
Hearing tests to screen for inner ear tumors
MRI or ultrasound of the abdomen to screen for kidney cancer, pheochromocytomas, and pancreas tumors
In people who have not been diagnosed with von Hippel-Lindau disease but who have the abnormal gene or who have not been tested but who have a parent or sibling with von Hippel-Lindau disease, blood pressure monitoring and examinations to look for vision, hearing, and eye problems are done every year.
