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| DiseaseID |
HGD46 |
| Genetic
Disorder |
VON HIPPEL-LINDAU SYNDROME
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| Gene
Name |
VHL gene |
| Description |
Von Hippel-Lindau syndrome 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 percent 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.
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| Symptoms |
Symptoms of VHL vary and depend on the size and location of the tumors.
They may include:
headaches,
problems with balance and walking,
dizziness,
weakness of the limbs,
vision problems and
high blood pressure.
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| Causes |
Von Hippel-Lindau is caused by an alteration in one of your two copies of a gene referred to as the VHL gene. This altered gene may be transmitted genetically, following a dominant pattern of inheritance. Each child receives one gene of each pair from each parent. If one parent has an alteration (mutation) in a dominant gene, each child has a fifty-fifty chance of inheriting that gene. One copy of the altered gene is sufficient to produce the disease. VHL is sometimes referred to as an autosomal dominant trait, meaning that it is not limited to one sex, but may occur in both men and women.Anyone with a parent with VHL and most people with a brother, or sister with VHL are at 50 percent risk of having VHL. Anyone with an aunt, uncle, cousin, or grandparent with VHL may also be at risk. The only way to determine for sure that someone does not have the VHL gene is through DNA testing. Even in people who have an alteration in the VHL gene, however, there is a wide variation in the age at which angiomas and other VHL tumors begin to grow, the organ system in which they grow, and the severity of the involvement. Every person is different. |
| Diagnosis |
The clinical diagnosis of von Hippel-Lindau syndrome (VHL syndrome) is established in:
A simplex case (i.e., an individual with no known family history of VHL syndrome) presenting with two or more characteristic lesions (e.g., two or more hemangioblastomas of the retina or brain or a single hemangioblastoma in association with a visceral manifestation such as kidney or pancreatic cysts; renal cell carcinoma; adrenal or extra-adrenal pheochromocytomas, and, less commonly, endolymphatic sac tumors, papillary cystadenomas of the epididymis or broad ligament, or neuroendocrine tumors of the pancreas);
An individual with a positive family history of VHL syndrome in whom one or more of the following disease manifestations is present: retinal angioma, spinal or cerebellar hemangioblastoma, pheochromocytoma, multiple pancreatic cysts, epididymal or broad ligament cystadenomas, multiple renal cysts, or renal cell carcinoma before age 60 years.
The following tests are used to establish the diagnosis and determine the extent of clinical manifestations:
CT scan or MRI to establish the presence of:
CNS tumors
Pheochromocytomas that exhibit high signal intensity on T2-weighted MRI, which may help differentiate them from adrenal cortical nodules
Endolymphatic sac tumors identified with high signal intensity with T1 imaging on MRI as a mass on the posterior wall of the petrous part of the temporal bone
Ultrasound examination for evaluation of the epididymis and broad ligament, and for less expensive screening of the kidneys
Radioiodine-labeled MIBG for the evaluation of suspected extra-adrenal tumors
18F DOPA whole-body PET, which shows promise as a sensitive and specific method for detection of pheochromocytomas [Hoegerle et al 2002]
Measurement of urinary catecholamine metabolites (VMA, metanephrine, and total catecholamine) to detect elevations that may suggest pheochromocytoma even in the absence of hypertension
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| Treatment |
Treatment usually involves surgery or sometimes radiation therapy. The goal is to treat growths while they are small and before they do permanent damage. |
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