Authors' recommendations: Von Hippel-Lindau (VHL) syndrome is a heritable disorder characterized by formation of cysts and tumors in the central nervous system (CNS) and viscera. Symptoms may manifest throughout life but typically become evident in young adulthood. Approximately 1 in 36,000 individuals across all populations are affected with VHL syndrome worldwide. The most common VHL syndrome–associated tumors are vascular growths of the CNS and retina. Renal cell carcinoma (RCC), pancreatic tumors and cysts, and pheochromocytoma are also common. Symptoms and morbidity associated with VHL syndrome depend upon the organ system involved and may include vision loss, sensory and motor skill loss, hypertension, endocrine or exocrine insufficiency, infertility, vomiting, and headaches. The most common causes of death in VHL syndrome patients are metastasizing RCC and neurological damage resulting from CNS tumors. VHL disease is associated with heritable variants in the von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase (VHL) gene. The normal VHL gene product is a multifunctional tumor suppressor. Variants in the VHL gene lead to uncontrolled cell growth in susceptible body tissues. VHL syndrome is inherited in an autosomal dominant fashion (i.e., presence of 1 abnormal copy of VHL is sufficient to cause disease in an individual). Parents, children, and full siblings of VHL syndrome patients have a 50% risk of carrying a VHL variant. Individuals carrying the same VHL variant may exhibit different symptoms and disease severity. VHL syndrome is virtually 100% penetrant (i.e., nearly all people with VHL variants develop VHL syndrome in their lifetime). Patients can be diagnosed with VHL syndrome by evaluating their clinical characteristics or by genetic testing for VHL variants. If a VHL variant is discovered in a VHL patient, that information may be used to test relatives of the patient who are at risk of developing VHL syndrome, and for prenatal or preimplantation genetic diagnosis. Some correlations have been reported between certain types of VHL variants and certain symptoms. Once a patient has been diagnosed with VHL syndrome and the extent of current manifestations has been established through evaluation and imaging of potentially affected body tissues, an ongoing surveillance program is typically adopted. At-risk relatives who have been determined through genetic testing to carry VHL variants are also candidates for ongoing surveillance. Surveillance contributes to better disease outcomes through early detection and treatment of disease manifestations. Without surveillance and treatment, median life expectancy of VHL syndrome patients is between 41 and 49 years. Regular surveillance and treatment protocols have increased life expectancy for VHL syndrome patients by approximately 16 years.

Project Status: Completed

Year Published: 2014

URL for published report: The report may be purchased from: http://www.hayesinc.com/hayes/crd/?crd=16371

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

Contact Name: saleinfo@hayesinc.com

Contact Email: saleinfo@hayesinc.com

Copyright: 2014 Winifred S. Hayes, Inc