What is Von Hippel-Lindau (VHL) Disease?
- Von Hippel-Lindau (VHL) disease is a rare genetic condition that can cause one or many cysts or tumors to form in many organs throughout the body. These tumors can be cancerous or benign (noncancerous).
- The disease is caused by a mutation of the VHL gene, which is a tumor suppressor gene. People who have a parent with VHL have a 50 percent chance of inheriting the disease.
- Symptoms of VHL can occur at any time. It is impossible to predict exactly how the disease will present or progress for any particular person, which makes regular surveillance exceedingly important for people living with VHL.
Von Hippel-Lindau Disease (VHL) is a genetic condition characterized by tumors, either cancerous or noncancerous, and cysts arising in various parts of the body. Some patients with von Hippel-Lindau syndrome have many tumors, and others just have a few. The number and location of tumors vary greatly between patients. It is a rare, incurable condition, only occurring about once in every 36,000 people.
How Does Von Hippel-Lindau Syndrome Occur?Read More
Almost all people who have a mutated version of the VHL gene that was passed down from their family will develop von Hippel-Lindau disease, according to Dr. Craig Rogers, Chair of Urology, Henry Ford Health. Approximately 97% of people with the mutation will experience complications related to the disease by the time they are 65 years old. However, approximately 20% of VHL patients are the first in their families to have VHL. This means that the mutation was not inherited. Rather, it occurred in the germ cell or embryo before they were born. This is referred to as a de novo mutation. In this case, the mutation is random, as there are no known factors or environmental causes that are connected to VHL. All patients with VHL either inherited the disease from a parent or had a random, de novo mutation when their genetic makeup was first determined.
What Kind of Tumors Does Von Hippel-Lindau Disease Cause?
The location, number, and type of tumors von Hippel-Lindau disease causes can vary. Some patients may only experience a couple of tumors, while others have many, occurring in several different sites in the body. The location of the tumors is impossible to anticipate, meaning regular surveillance is critical. They can be either cancerous or noncancerous (benign). Although most tumors in VHL disease are benign, it is important to remember that these benign tumors can also cause complications for the patient and may need to be ultimately removed. For example, the benign tumor may be in a location that causes pressure on the surrounding tissue, such as the brain. VHL tumors are known to occur in ten different locations:
- Adrenal glands
- Inner ear
- Reproductive organs
Symptoms of VHL
The average age for VHL to first present itself is 26 years of age. Because the location and extent of the tumor(s) can differ, there is not a specific set of symptoms experienced by most patients. The symptom burden will vary between individuals. Some families may see a predominant tumor type; however, this is not always the case. Even though the inherited mutation is the same, the manifestation of the condition can be different between family members. One person in the family may even have manifestations that do not harm anything and just need to be monitored, while another has a malignant disease. Since there are no specific symptoms to monitor, patients with VHL should continually have routine surveillance to check for new tumor growth. Some examples of symptoms include the following:
- Balance issues when walking or muscle weakness from brain tumors
- Blindness from eye tumors
- Hemangioblastomas are the most common tumor type. They occur in the eyes, brain, and spinal cord. Although noncancerous because of their location, treatment may be needed because pressure in the brain, spinal cord, or eyes can lead to significant complications, including blindness or balance difficulties.
- Blood in the urine from cancerous kidney tumors
- This is typically indicative of renal cell carcinoma, which most likely will need surgically removed when the tumor reaches a certain size to prevent the tumor from metastasizing.
- Most clinicians wait until the tumor is 3 cm before removing it surgically.
- Hearing or balance issues from inner ear tumors
- These tumors, called endolymphatic sac tumors, are usually benign.
- High blood pressure, heart palpitations, sweating and turning pale from adrenal gland tumors.
- These tumors, which may feel like a panic attack, are called pheochromocytoma, and they arise from neuroendocrine cells. These hormone-secreting tumors are characteristic of VHL.
- Pain in the abdominal region from pancreas tumors
- These tumors may start as benign but develop into cancer that can spread to other parts of the body.
How is VHL Diagnosed?
DNA testing of a blood sample is the only definitive way to diagnose VHL. Since it is very rare, routine testing is not recommended for the general public. Most patients who have VHL have a family member with the disease, so they would know to have their DNA tested. If the disease is inherited, the DNA testing is a little simpler because it will be the same mutation in the VHL gene, and their DNA can be compared to their family members.
However, for patients who are in the 20% of people with de novo VHL mutations, DNA testing most likely would not be performed until they have manifested some symptoms. If there is an extensive family history of multiple tumors in different organ sites, VHL may be suspected. For these patients, their DNA sample would be compared to a database of patients with and without VHL to see if it matches up with any other patient’s DNA sequence with the disease.
Dr. Tobias Else, endocrinologist, University of Michigan Health Rogel Cancer Center, also recommends these patient groups undergo DNA testing as these complications can be characteristic of VHL:
- Patients with a pheochromocytoma adrenal gland tumor
- Patients with an extensive family history of kidney cancer
- Patients with a hemangioblastoma in the eye or brain
Screening Guidelines for VHL
For patients who have a family history of VHL and undergo genetic testing, a screening plan will be started early in life. This surveillance may include imaging, bloodwork, and functional assessments of certain organs. It is recommended that screening begins before the age of one if VHL mutation is known. This early screening would include an eye exam, hearing test, neurologic tests, and blood pressure evaluation. The Active Surveillance Guidelines, developed by the VHL Alliance, detail the recommendations for screening.
History and physical exam, eye assessments, blood pressure, pulse, and adrenal gland evaluation are recommended at least once a year. An MRI of the brain, spinal cord, abdomen, and an audiogram is recommended every 2 years, starting at different points throughout childhood. An MRI of the internal auditory canal is recommended once at age 15. Once a patient reaches age 65, most routine scans are stopped. The Active Surveillance Guidelines provide more information and specific ages at which each of these assessments are recommended to become part of routine surveillance.
Typically, tumors that develop in the lung or liver are not an issue. Reproductive organ tumors may cause fertility concerns but are otherwise non-problematic as well. For this reason, assessment of these organs is not included in routine surveillance recommendations.
Hope for VHL Patients
Although von Hippel-Lindau disease is considered incurable, treatment options and the way VHL is managed continue to advance. Patients with the disease are being identified and frequently screened for new tumor growth so such tumors can be removed or treated early in disease progression. With appropriate surveillance and treatment, the prognosis of VHL can be better than many other common cancer types. The new drug approval of belzutifan (Welireg®) also gives hope to patients with certain VHL tumor types. Clinical trials for this genetic condition are ongoing.
As is the case with most rare genetic diseases, patients with VHL have been shown to have higher levels of stress and anxiety than the general population. The VHL Alliance provides a list of different types of support groups that could help alleviate some of the mental and emotional stress caused by the disease. The VHL Handbook is available to patients as well. It provides practical information for patients with this condition. Due to rigorous surveillance, patients with VHL have hope for the future.
Moving Forward – Questions to Ask Your Doctor
- What type of surveillance plan will I need for my VHL?
- Which treatments are available for VHL?
- Are there any lifestyle adjustments I can make to avoid the progression of my disease?