National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Von Hippel-Lindau disease

Von Hippel-Lindau (VHL) disease is an inherited disorder characterized by the abnormal growth of both benign and cancerous tumors and cysts in many parts of the body. Tumors usually first appear in young adulthood. The types of tumors associated with VHL disease include hemangioblastomas (slow-growing tumors of the central nervous system); kidney cysts and clear cell renal cell carcinoma; pancreatic neuroendocrine tumors; pheochromocytomas (noncancerous tumors of the adrenal glands); and endolymphatic sac tumors. VHL disease is caused by a mutation in the VHL gene and is inherited in an autosomal dominant manner. Early detection and treatment of VHL disease is important, and usually involves surgical removal of tumors.[1][2]
Last updated: 2/2/2016
Symptoms of von Hippel-Lindau (VHL) disease vary among patients and depend on the size and location of tumors.[3][4]

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.

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 they can produce an excess of hormones that cause dangerously high blood pressure.

About 10 percent of people with VHL disease develop endolymphatic sac tumors, which are non-cancerous 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.[1][2]

Individuals with VHL disease are also at a higher risk than normal for certain types of cancer, especially kidney cancer.[949] Renal cell carcinoma occurs in about 70% of individuals with VHL disease by age 60 and is the leading cause of death.[1]

Last updated: 2/2/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 46 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal retinal vascular morphology
Abnormality of retina blood vessels
0008046
Abnormality of the cerebral vasculature
Abnormality of the cerebral blood vessels
0100659
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum
[ more ] 		0007360
Arteriovenous malformation 0100026
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment
[ more ] 		0002167
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Pancreatic cysts 0001737
Renal cell carcinoma
Cancer starting in small tubes in kidneys
0005584
Retinal capillary hemangioma 0009711
Sensorineural hearing impairment 0000407
Visceral angiomatosis 0100761
30%-79% of people have these symptoms
Ataxia 0001251
Capillary hemangioma
Strawberry birthmark
0005306
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches
[ more ] 		0002076
Multicystic kidney dysplasia 0000003
Nausea and vomiting 0002017
Papillary cystadenoma of the epididymis 0009715
Polycystic kidney dysplasia 0000113
Sensory neuropathy
Damage to nerves that sense feeling
0000763
Telangiectasia of the skin 0100585
5%-29% of people have these symptoms
Abnormality of the lymphatic system 0100763
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Glaucoma 0000501
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased
[ more ] 		0000975
Hypertension 0000822
Increased intracranial pressure
Rise in pressure inside skull
0002516
Multiple renal cysts
Multiple kidney cysts
0005562
Neoplasm of the middle ear
Middle ear tumor
0100799
Pheochromocytoma 0002666
Retinal detachment
Detached retina
0000541
Visual loss
Loss of vision
Vision loss
[ more ] 		0000572
Percent of people who have these symptoms is not available through HPO
Abnormality of the liver
Abnormal liver
Liver abnormality
[ more ] 		0001392
Autosomal dominant inheritance 0000006
Cerebellar hemangioblastoma 0006880
Epididymal cyst 0030424
Neoplasm of the pancreas
Cancer of the pancreas
Pancreatic tumor
[ more ] 		0002894
Paraganglioma 0002668
Polycythemia
Increased red blood cells
0001901
Pulmonary capillary hemangiomatosis 0005954
Spinal hemangioblastoma 0009713
Tinnitus
Ringing in ears
Ringing in the ears
[ more ] 		0000360
Vertigo
Dizzy spell
0002321
Showing of 46 |
Last updated: 7/1/2020
Von Hippel-Lindau (VHL) disease is caused by a mutation in the VHL gene. This gene is a tumor suppressor gene, which helps to control cell growth. Mutations in the VHL gene lead to a lack of regulation of cell growth and survival, allowing cells to grow and divide uncontrollably. This contributes to the formation of the tumors associated with VHL disease.[2]
Last updated: 2/2/2016
Mutations in the gene that causes VHL disease (the VHL gene) are inherited in an autosomal dominant manner. This means that having a mutation in only one copy of the VHL gene in each cell is enough to increase a person's risk of developing VHL disease.

In most autosomal dominant conditions, having one mutated copy of the responsible gene is sufficient to cause the condition. However, in VHL disease, a mutation in the other copy of the gene must occur during a person's lifetime to trigger the development of VHL disease. For example, a person may inherit a mutated copy of the gene from a parent, but acquiring a second mutation in the other gene copy in a specific organ may trigger tumor development in that organ. Almost everyone who is born with one VHL mutation will eventually acquire a mutation in the second copy of the gene and develop VHL disease.[2]

In most cases, an affected person inherits the first mutated gene from an affected parent. However, in about 20% of cases, the mutation occurs for the first time in a person with no family history of the condition.[2] This is called a de novo mutation.

When a person with a mutation that can lead to VHL disease has children, each of their children has a 50% (1 in 2) chance to inherit that mutation.
Last updated: 2/2/2016
The diagnosis of von Hippel-Lindau disease can be made based on specific clinical criteria (signs and symptoms), or when molecular genetic testing reveals a change (mutation) in the VHL gene.

Tests that may be used to establish a clinical diagnosis include:
  • MRI of the brain and spinal cord
  • fundoscopy
  • ultrasound examination or MRI of the abdomen
  • blood and urinary catecholamine metabolites.[1]
Last updated: 2/2/2016

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment for Von Hippel-Lindau (VHL) disease depends on the location and size of tumors. In general, the goal is to treat growths when they cause symptoms, but are still small so they don't cause permanent damage. Treatment usually involves surgical removal of tumors. Radiation therapy may be used in some cases. All people with VHL disease should be carefully followed by a physician or medical team familiar with the disorder.[4]
Last updated: 2/2/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include multiple endocrine neoplasia, neurofibromatosis, polycystic kidney disease, tuberous sclerosis, Birt-Hogg-Dube syndrome, and hereditary pheochromocytoma-paraganglioma syndromes (see these terms) associated with succinate dehydrogenase subunit mutations (SDHB, SDHC and SDHD).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Von Hippel-Lindau disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • The VHL Family Alliance has teamed up with the National Disease Research Interchange (NDRI) to create a tissue bank to help scientists find ways of improving diagnosis and treatment of Von Hippel-Lindau syndrome.  To learn more about this tissue bank, click here.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Von Hippel-Lindau disease. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Von Hippel-Lindau disease:
    MyVHL: Patient Natural History Study
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Von Hippel-Lindau disease. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
  • The VHL Alliance provides information about VHL for patients and caregivers.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Von Hippel-Lindau disease. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

  • Click here to read a review article published in the Japanese Journal of Clinical Oncology about Von Hippel-Lindau disease entitled: Von Hippel–Lindau Disease: Molecular Pathological Basis, Clinical Criteria, Genetic Testing, Clinical Features of Tumors and Treatment

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Frantzen C, Klasson TD, Links TP, and Giles RH. Von Hippel-Lindau Syndrome. GeneReviews. August 6, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1463/.
  2. Von Hippel-Lindau Syndrome. Genetics Home Reference. July, 2012; http://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome.
  3. Von Hippel-Lindau Disease. MedlinePlus. 2016; https://medlineplus.gov/vonhippellindaudisease.html.
  4. NINDS Von Hippel-Lindau Disease (VHL) Information Page. NINDS. 2016; https://www.ninds.nih.gov/Disorders/All-Disorders/Von-Hippel-Lindau-Disease-VHL-Information-Page.