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Disease Profile

Von Hippel-Lindau disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Childhood

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ICD-10

Q85.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

VHL syndrome; VHL; Von Hippel-Lindau disease;

Categories

Blood Diseases; Congenital and Genetic Diseases; Endocrine Diseases;

Summary

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]

Symptoms

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]

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.

Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Adrenal pheochromocytoma
0006748
Cerebellar hemangioblastoma
0006880
Elevated urinary catecholamines
0011976
Hypertension
0000822
Renal cell carcinoma
Cancer starting in small tubes in kidneys
0005584
Retinal capillary hemangioma
0009711
5%-29% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Abnormal left ventricular function
0005162
Anxiety
Excessive, persistent worry and fear
0000739
Back pain
0003418
Cardiomyopathy
Disease of the heart muscle
0001638
Distal lower limb muscle weakness
0009053
Elevated circulating catecholamine level
0003334
Endolymphatic sac tumor
0030393
Headache
Headaches
0002315
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Hypertensive retinopathy
0001095
Limb pain
0009763
Macular edema
0040049
Multiple renal cysts
Multiple kidney cysts
0005562
Pallor
0000980
Palpitations
Missed heart beat
Skipped heart beat

[ more ]

0001962
Pancreatic cysts
0001737
Pancreatic islet cell adenoma
0008261
Papillary cystadenoma of the epididymis
0009715
Papilledema
0001085
Stroke
0001297
Upper limb muscle weakness
Decreased arm strength
Weak arm

[ more ]

0003484
Vertigo
Dizzy spell
0002321
Visual loss
Loss of vision
Vision loss

[ more ]

0000572
1%-4% of people have these symptoms
Epididymal cyst
0030424
Increased intracranial pressure
Rise in pressure inside skull
0002516
Myocardial infarction
Heart attack
0001658
Myocarditis
Inflammation of heart muscle
0012819
Paraganglioma
0002668
Polycythemia
Increased red blood cells
0001901
Retinal detachment
Detached retina
0000541
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
Neoplasm of the pancreas
Cancer of the pancreas
Pancreatic tumor

[ more ]

0002894
Pheochromocytoma
0002666
Pulmonary capillary hemangiomatosis
0005954
Sensorineural hearing impairment
0000407
Spinal hemangioblastoma
0009713
Tinnitus
Ringing in ears
Ringing in the ears

[ more ]

0000360

Cause

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]

Diagnosis

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]

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

    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]

    Organizations

    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

          Learn more

          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

          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • Genetics Home Reference (GHR) contains information on Von Hippel-Lindau disease. This website is maintained by the National Library of Medicine.
          • 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

                References

                1. Frantzen C, Klasson TD, Links TP, and Giles RH. Von Hippel-Lindau Syndrome. GeneReviews. August 6, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1463/.
                2. Von Hippel-Lindau Syndrome. Genetics Home Reference. July, 2012; https://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.

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