What is Von Hippel-Lindau Syndrome (VHL)?

On a recent episode of House, a female Air Force pilot comes to Dr. House complaining of a whole slew of odd symptoms. Most notably, she claims that she is having instances where she is hearing with her eyes. Dr. House takes on the case and, of course, there is a myriad of misdiagnoses before House finally realizes the correct diagnosis: Von Hippel-Lindau Syndrome. So what is Von Hippel-Lindau Syndrome?

Von Hippel-Lindau Syndrome (VHL), or Von Hippel-Lindau disease as it is sometimes called, is a rare genetic disorder. VHL was first discovered by German ophthalmologist Eugen von Hippel in 1904. The Swedish pathologist Arvid Lindau made further associations of VHL in 1926. VHL causes tumors and cysts to grow in various parts of the body. They most commonly grow in the brain and spinal cord, eyes, pancreas, and kidneys. However, they can occur in other parts of the body as well. The tumors can be either benign or cancerous.

VHL is a genetic disease affecting approximately one in 32,000 individuals. Inheritance follows an autosomal dominant pattern. VHL occurs as a result of a mutation of the Von-Hippel tumor suppressor gene which is located on the third chromosome. When there is a mutation of the gene, it causes the protein to not suppress tumors. Thus, the development of tumors associated with VHL. Although VHL is genetic, about twenty percent of cases are the result of a new mutation that occurred during early fetal development. VHL is always present at birth, however, it may not present itself until later in life. Cells have two copies of the VHL gene. In most cases, a child inherits one mutated VHL gene. As long as the other VHL gene is producing normal VHL protein, there is no problem. However, if the second VHL gene produces a mutation, then the tumors characteristic of VHL will begin to be produced. Because of this mechanism, there is a wide variation in the age of onset of VHL and the symptoms present. The average age of diagnosis is twenty-six.

Symptoms of VHL can vary greatly depending on the size, type, and number of tumors present. Symptoms can include headaches, problems with balance and walking, dizziness, vomiting, weakness of the limbs, vision problems or loss, hearing problems or loss, and high blood pressure. There are many characteristic signs of VHL. These include hemangioblastomas (benign blood vessel tumors of the brain and spinal cord), angiomas (hemangioblastomas that occur in the eye), kidney cysts, kidney carcinoma, pheochromocytomas (a benign tumor of the adrenal glands), endolymphatic sac tumors (benign tumors of the inner ear), pancreatic tumors, as well as other tumors or cysts.

Early diagnosis is crucial with VHL. Diagnosis can be quite difficult (as was exhibited on House). It is usually made by observing one or more of the characteristic features of VHL. Imaging tests help in detecting these features. The only way to confirm diagnosis is through genetic testing. Once the diagnosis is confirmed, prompt treatment is important. Treatment varies depending on the symptoms present and the type of VHL present. The type of VHL is determined by various factors including the number and type of tumors present. VHL is a progressive disease, so treatment and prevention of new symptoms are key. Patients undergo regular check-ups to evaluate the status of VHL. Prognosis of VHL depends on the severity of the disease. The average life expectancy of individuals with VHL is 49 years. The reason it is so low is because of the high incidence of renal carcinoma. If patients follow their doctors orders and get their regular check-ups, their risk of death is much lower.

VHL is a rare genetic disease. It affects everyone differently. Although the disease can be quite serious, people can expect to live relatively normal lives assuming the disease is detected and treated early.

Sources

Wikipedia

VHL Family Alliance