Von-Hippel Lindau Disease Essay, Research Paper

Von Hippel-Lindau syndrome is one of over 7000 known inherited diseases. It is an autosomal dominant disease that affects about 10% of the population.1 The history of VHL reaches back to 1864 when scattered reports of knots of blood vessels known as hemangioblastomas on the retina surfaced and were written up by opthamolagists. Eugene Von Hippel, a German opthamologist is credited with discovering the familial nature of the disease, however Swedish pathologist Arvid Lindau was the one who suggested that these hemangioblastomas are part of a larger “angiomatus [involving knots of blood vessels] lesion of the central nervous system.” Additional reports of affected small families confermed Lindau’s theory. In 1964, Melmon and Rosen summarized all knowlege of the disease and coined the name “Von Hippel-Lindau.” The invention of ultrasound aided detection in the late 1970’s, and by the mid 1980’s, MRI was commonly used for detection of angiomas on the spine. In 1993, the VHL gene was located by researchers at the National Cancer Institute.

Patients with VHL suffer tumors known as angiomas (they are referred to as hemangioblastomas when discussing the retina, brain, or spinal chord and pheochromocytomas when discussing the adrenal glands) consisting of tiny knots of blood vessels. These angiomas can occur in the brain, spinal cord, retina, adrenal glands, kidney, pancreas, and very rarely in the epididymis is men and the fallopian tubes in women. Based on these manifestations, scientists have identified two types of VHL: 1) without pheochromocytoma 2) with pheochromocytoma. VHL type 2 has further been divided into two subcatagories: 2a) without pancreatic cysts 2b) with pancreatic cysts. VHL type 1 is the most common form of the disease. Scientists have also identified trends in race associated with manifestations of VHL: French families are most likely to have pancreatic cysts, German families are most likely to have pheochromocytomas, and Japanese families are more likely to have kidney tumors2.

When hemangioblastomas form in the retina, they start out very small and difficult to detect. They tend to grow around the equator of the retina (See Fig 1), far from the area of central vision. A very indepth opthamological examination is required to detect hemangioblastomastomas of the retina. Once discovered, there are two main options for treatment: laser surgery or cryotherapy (freezing). The goal of these treatments is to keep the hemangioblastomas from growing.

Hemangioblastomas in the brain and spinal cord can be a bit more dangerous. Early signs of a growth in these areas may include back pain, headaches, numbness, dizziness, and weakness or pain in the arms or legs. The danger of these hemangioblastomas is the pressure they exert on brain tissue or nerves on the spine. This can result in blockage of spinal fluid. Surgery in these areas carries many risks since these areas are so delicate.

Perhaps the most dangerous of the manifestations of this rare disease are angiomas in the kidney, pancreas, and adrenal glands. Detected early, pheochromocytomas (or “pheos” for short) can be very easy to handle, but they can be lethal if not detected in the early stages. Pheos release nonadrenaline and adrenaline, the so-called “stress hormones” that the body uses to gain speed and strength in an emergency. Symptoms experienced when pheos secrete excess stress hormones into the blood stream include high blood pressure (which can cause heart attack or stroke), headache, irregular or rapid heartbeat, increased cold perspiration, or what feels like a panic attack, fear, and sometimes rage. New tests show that pheos are 4 times more common than previously conceived. Since traditional blood and urine tests are usually inadequate in finding pheos, MRI is the most common procedure for detecting them.

VHL in the kidney and pancreas are the two most dangerous types of VHL. VHL can instigate tumors known as hypernephromas or renal cell carcinomas (RCC) in the kidney which are cancerous and can also cause pancreatitis in the pancreas which is an extremely serious condition. The pancreas can also fill with small cysts and thus become non-functional. Symptoms include fatty stools and diarrhea. In very rare cases this may cause diabetes. If cysts block the delecate ducts surrounding the pancreas, jaundice (yellowing of skin and urine), pain, inflammation, or infection may result. Pancreatits can be treated with enzyme replacement therapy. Normal cancer precautions are taken in the case of hypernephroma of RCC.

VHL is an autosomal dominant disease which means that a parent with the VHL gene has a 50% chance of passing it on to their offspring. (See Fig. 2) The VHL gene is on chromosome 3 (See Fig. 3) and is a tumor-suppressor gene. When both copies of the gene are idle due to mutation or loss, cell growth not supressed. Mutations could mean nucleotide substitution, or nucleotide insertions3. (See Fig. 4)

VHL is an extremely rare disease in that there is not any common symptom or one common area of the body affected. Families with a history of VHL are encouraged to have frequent MRIs and opthamology examinations to prevent late detection of angiomas.