Hereditary Cancer

von Hippel-Lindau syndrome (VHL gene analysis)

  • Mutation analysis of VHL gene
  • Interrogation for specific mutation (relatives)

Von Hippel-Lindau syndrome (VHL) is a rare genetic disorder characterized by an increased risk of developing the tumors listed below:

  • hemangioblastomas (benign, or noncancerous, tumors made up of nests of blood vessels) of the brain and spine
  • hemangioblastomas of the retina
  • pheochromocytomas (a tumor of the chromaffin cells, which are present in the adrenal gland; usually benign, or noncancerous) within or outside of the adrenal gland
  • renal cell carcinoma (cancerous tumor of the kidney)

Less commonly, some individuals develop endolymphatic sac tumors (ear tumors that can cause deafness if undetected), pancreatic tumors, and cystadenomas of the epididymis or broad ligament. Other manifestations include cysts (pockets of fluid) of the kidney and pancreas.

The VHL gene is a tumor suppressor gene located on chromosome 3, which usually controls cell growth and cell death. Both copies of a tumor suppressor gene must be altered, or mutated, before a person will develop cancer. In VHL, the first mutation is inherited from either the mother or the father and is therefore present in all cells of the body. This is called a germline mutation. Whether a person who has a germline mutation will develop a tumor and where the tumor(s) will develop depends upon where (which cell type) the second mutation occurs. For example, if the second mutation is in the retina, then a retinal hemangioblastoma may develop. If it is in the brain, then a hemangioblastoma may develop there. The process of tumor development actually requires mutations in multiple growth control genes. Loss of both copies VHL is just the first step in the process. What causes these additional mutations to be acquired is unknown. Possible causes include chemical, physical, or biological environmental exposures or chance errors in cell replication.

Some individuals who have inherited a germline VHL mutation never develop cancer because they never get the second mutation necessary to knock out the function of the gene and start the process of tumor formation. This can make the cancer appear to skip generations in a family, when, in reality, the mutation is present. Persons with a mutation, regardless of whether they develop cancer, however, have a 50/50 chance to pass the mutation on to the next generation. About 1 percent to 3 percent of VHL cases are new mutations, not inherited from a parent.

It is also important to remember that the VHL gene is not located on the sex chromosomes. Therefore, mutations can be inherited from either the mother or the father's side of the family.

The American Society of Clinical Oncologists (ASCO) classifies VHL as a “group 1„ disorder, which means that genetic testing (in this case for mutations in the VHL gene) is considered part of the standard management for first-degree relatives (parent, siblings, children) of affected individuals. For persons who are mutation-positive, annual screening to detect tumors before severe complications develop is recommended. Genetic testing of unaffected relatives is only useful if a germline mutation has already been identified in an affected family member.

Genetic analysis

  • A short family history must be taken. Any information regarding the patient's family history is important and quickens the analysis completion.
  • 2 x 3ml of peripheral blood in EDTA anticoagulant are required. The sample is either sent to BioGenomica laboratory on the same day the blood is being drawn, or can be stored for a longer time period in the freezer (-20 °C) until its postage. (Contant us for more information regarding postage details).
  • Genetic reports are handed to the attending physician in less than four (4) calendar weeks.

OMIM* 193300