Von Hippel Lindau disease (VHL) is an inherited mutation of the VHL gene, which causes tumors to form in areas of the body that contain large numbers of blood vessels. According to recent medical studies, one in every 32,000 children is affected by VHL.
Von Hippel Lindau (VHL) disease was first described at the beginning of the 20th century by Eugen von Hippel and Arvid Lindau. A mutation of the VHL gene can affect several organs of the body, and can be expressed differently in every patient and every family. The most common manifestations of VHL include cysts and tumors of the retina, brain, spinal cord, kidney, pancreas and inner ear.
Patients with VHL can present with cerebellar hemangioblastomas, retinal hemangioblastomas, pheochromocytomas, kidney cancer, pancreatic cysts and pancreatic neuroendocrine tumors.
It is very important that patients and families living with VHL have their care coordinated by a team of doctors and counselors with expertise in the various aspects of their care. Proper genetic testing, appropriate screening and appropriately timed therapies are all important factors of any treatment plan for VHL.
The adrenal glands are located on top of each kidney. Each adrenal gland is divided into an outer cortex and an inner medulla. The adrenal cortex is responsible for making several key steroid hormones that are important in maintaining blood pressure and salt balance, among other things. The adrenal medulla is derived from nerve cells and is a source of the catecholamines, epinephrine (adrenaline) and norepinephrine (noradrenaline).
A pheochromocytoma is a tumor that derives from the adrenal medulla and makes excess catecholamines. In VHL syndrome, these tumors tend to make more normetanephrine (a breakdown product of norepinephrine). Occasionally, a catecholamine-producing tumor arises from other nerve cells located outside of the adrenal glands; in these cases, the tumor is called a paraganglioma. For simplification, the term pheochromocytoma will be used to designate catecholamine-producing tumors that arise from both within and outside the adrenal gland.
A pheochromocytoma will be identified in about 10-15% of VHL patients. By definition, it occurs only in individuals with VHL type II; therefore, in families with VHL type II, it can be quite common. Furthermore, pheochromocytomas are more likely to occur in more than one location (e.g. both adrenal glands) in VHL syndrome.
Although a pheochromocytoma is a tumor, it is rarely malignant in VHL syndrome, meaning that it is unlikely to spread to other places. If detected early, pheochromocytomas are not difficult to deal with. However, if not treated, they may be potentially lethal because of the dangerously high blood pressures that can occur with physical stressors such as accidents, surgery or childbirth.
Symptoms of Pheochromocytoma
A pheochromocytoma can present with classic symptoms or it may have no symptoms at all. The symptoms may resemble what one feels in an emergency (“fight or flight”) situation:
- High blood pressure, either persistent or intermittent
- Rapid or irregular heartbeats
- Feelings of anxiety/panic/fear
- Pallor (paleness)
- Dizziness/lightheadedness with standing
- Weight loss
Between 60 to 80% of patients with VHL develop hemangioblastomas, which occur in the cerebellum, the spinal cord and the brainstem.The average age for developing these is 33 years, although cases have been seen in patients as young as nine. Although these are benign tumors, they can cause a large number of problems, with changes in brain or spinal cord function arising out of the size or number of hemangioblastomas, or because of bleeding into the hemangioblastomas.
Symptoms of hemangiolastomas vary depending on their location.
Symptoms of tumors in the cerebellum include:
- Difficulty walking and with muscular coordination
- Double vision
Symptoms of hemangioblastomas in the spinal cord include:
- Decreased sensation in the arms, legs and body
- Difficulty walking
- Difficulties with bowel and bladder function.
Brainstem hemangioblastomas can cause decreased sensation, difficulty walking, difficulties swallowing, headaches and poor coordination.
Kidney Cancer & VHL
Kidney cancer affects up to 40% of patients with VHL and is the most common cause of disease-related death in patients with VHL. Kidney cancer can arise as a single tumor in one kidney or as multiple tumors in both kidneys. The key to treatment is early detection, which can be achieved with CT scanning at regular intervals.
Ocular Manifestations of VHL
Retinal hemangioblastomas can be seen in up to 60% of patients with VHL. The median age of onset is 25 years, although they can occur as early as one year of age. Retinal hemangioblastomas can occur anywhere within the retina (visual portion of the eye). They can occur in both eyes, and in multiple sites within the same eye.
Pancreatic Manifestations of VHL
Pancreatic cysts and serous cystadenomas arise in between 20 to 50% of patients with VHL. The more serious pancreatic neuroendocrine tumors arise in approximately 15% of patients with VHL. The average age pancreatic manifestations are diagnosed is around 35 years of age.
Pancreatic neuroendocrine tumors are generally silent, but can behave like true cancers, and have the potential to spread to other organs in the body. Spread of neuroendocrine tumors usually only occurs if they become larger than three centimeters (slightly more than one inch) in size.
Pancreatic cysts and cystadenomas are completely benign and generally do not cause difficulties for patients with VHL. In certain cases, the cysts can become large, and can press on surrounding pancreatic tissue or other organs in the body, causing blockage of the pancreas, pain or disruption of other organs.