Von Hippel-Lindau Syndrome
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[edit] Name of Condition
Von Hippel-Lindau Syndrome [also referred to as Angiomatosis Retinae, VHL Syndrome, von Hippel-Lindau Disease]
[edit] Definition
Von Hipple-Lindau syndrome (VHL) is a genetic condition involving cysts or tumors of the brain, eye, kidneys, adrenal glands, pancreas, and other organs.
[edit] Description, Signs and Symptoms
Von Hippel-Lindau syndrome is a genetic cancer syndrome that can affect people within the same family in different ways. The problems which may be present are: brain and spine tumors (hemangioblastomas), eye tumors (retinal angiomas), kidney cysts and/or tumors (clear cell renal cell carcinoma), adrenal gland cysts and/or tumors (pheochromocytoma) and other problems such as tumors near the ear (endolymphatic sac tumors), or epididymal cysts in males.
[edit] Inheritance
This condition is due a altered gene on a chromosome; each person with the VHL gene has a 50% chance of passing this gene to a child.
The gene for VHL is on chromosome #3, and is transmitted from parents to children in an autosomal dominant inheritance pattern.
Genes come in pairs, one from each parent. A person with VHL has one VHL gene, and one normal gene. Either gene can be passed to children. Therefore offspring will get either the gene for VHL, or the other gene without VHL. The chance is the same with each child (50%), since chance has no memory.
Some people with VHL do not have an affected parent, because of a new alteration in one of their genes at birth (new mutation). They can still pass this gene to children, because once you have the diagnosis of VHL, the chance of passing the gene is the same, whether or not you have an affected parent.
The gene is very variable, so that the problems can be different from person to person, even in the same family, and the age when the symptoms show up can be very different, too.
[edit] Demographics
About one in 36,000 persons are estimated to have VHL. Most individuals with VHL have an affected parent and other family members with VHL, but others are the first in their family. Symptoms can be quite different from person-to-person, even within the same family.
[edit] Diagnosis
The diagnosis is made based on the features in the affected individual, as well as the family. A DNA test can determine if a person has the particular genetic change in the family, even if there are no clinical features.
A person with no known family history of VHL syndrome may be diagnosed because they have two or more features of the condition, such as two brain or eye tumors, or cysts / tumors in kidneys, pancreas, or adrenal gland. The other less common problems in the endolymphatic sac, epididymis (males) or broad ligament (females).
A person with an affected parent, sibling, or other relative may be diagnosed because they have one or more of these same features.
Sometimes tests are needed to determine the diagnosis such as a CT scan or MRI of the brain / spinal cord, or of the abdomen. Or, an ultrasound may show some of the abdominal tumors. High blood pressure, or a urine test (VMA, metanephrine, and total catecholamine) may be used to determine if an adrenal gland tumor (pheochromocytoma) is present.
[edit] Treatment and Management
Management and treatment depends on which features are already present, as well monitoring for those that might occur. If problems are detected early, there are many potential treatments. The following list shows the potential VHL feature and the recommended evaluations (these may vary for some individuals and families):
Retinal hemangioblastoma A yearly eye exam, by an ophthalmologist, to evaluate and monitor risk for eye tumor (retinal angioma).
Renal cell carcinoma, pheochromocytoma, pancreas tumors Yearly abdominal evaluations (ultrasound, CT or MRI) to detect cysts and/or tumors of the kidney, adrenal gland, or pancreas.
Pheochromocytomas Yearly blood pressure monitoring, and 24-hour urine test (catecholamine metabolites) especially in families with a high incidence of pheochromocytoma.
Nervous system hemangioblastoma A neurology evaluation and monitoring for brain tumor (hemangioblastoma) or central nervous system tumors.
Endolymphatic sac tumors An ear evaluation for possible hearing loss associated with endolymphatic sac tumors.
Other Surveillance as needed Individuals with known VHL syndrome, individuals without clinical manifestations but known to have a VHL disease-causing mutation, and at-risk relatives who have not undergone DNA-based testing need regular clinical monitoring by a physician or medical team familiar with the spectrum of VHL syndrome.
[edit] Prognosis
As early diagnostic techniques and management improves, individuals with VHL who have regular monitoring and treatment can have relatively long, productive lives, interrupted by relatively brief periods of hospitalization (for surgery to remove a brain tumor, part of a kidney, or other procedure). While many organ systems are "at risk" and need monitoring, few individuals have all the features of this condition, however most individuals get a few features at some point in their lives. Since it is not possible to predict what features any individual person will get, or at what age it will occur, it is important to continue monitoring for problems throughout a person's life.
[edit] Resources
VHL Family Alliance, www.vhl.org
[edit] References
- von Hippel-Lindau Syndrome, GeneReview on GeneTests.org, http://www.genetests.org/profiles/vhl/index.html
- Schimke, RN and Collins DL, Von Hippel-Lindau Syndrome, chapter in Management of Genetic Syndromes (second edition), edited by Suzanne B Cassidy, M.D. and Judity E. Allanson, M.D., Wiley- Liss Publisher, Hoboken, New Jersey, 2005 [third edition, currently being revised for publication in 2008] [1]
Background information on the individuals whose names are associated with this condition:
