Von Hippel-Lindau syndrome

von Hippel-Lindau syndrome (VHL) is a multisystem, neoplastic heritable disorder of high penetrance in affected individuals who carry the autosomal dominantly inherited trait. The disorder is also called a cancer syndrome because it includes malignant neoplasms or carcinomas that may arise in the kidneys and pancreas and, more rarely, in association with adrenal pheochromocytomas. Clinical manifestations mainly include hemangioblastomas of the brain and spinal cord, retinal angiomas, endolymphatic sac tumors, clear-cell renal carcinomas, pancreatic neuroendocrine tumors and cysts, and pheochromocytomas. Periodic surveillance for VHL tumors is guided by site-specific screening protocols, often leading to pre-symptomatic and early detection of occult neoplasms. Treatment is multidisciplinary, and although surgery remains the main treatment for VHL tumors, nonsurgical treatment modalities are emerging. VHL arises in individuals with a VHL gene mutation that is found most often in the germline. In 1993, the VHL gene was localized to chromosome region 3p26→p25 and was shown to be a tumor suppressor gene. In later years, improved methods were developed for genetic testing to increase detection rates of the various types of mutations among kindreds and to determine which members within these kindreds carry the trait. The VHL gene (VHL) codes for a protein (pVHL) that is being widely investigated because of its apparent role in oxygen sensing and its link to stimulation of tumor angiogenesis through interaction with hypoxia-inducible factors and other proteins.