TY - CHAP M1 - Book, Section TI - von Hippel-Lindau Syndrome A1 - Shuch, Brian A1 - Linehan, W. Marston A2 - Murray, Michael F. A2 - Babyatsky, Mark W. A2 - Giovanni, Monica A. A2 - Alkuraya, Fowzan S. A2 - Stewart, Douglas R. PY - 2014 T2 - Clinical Genomics: Practical Applications in Adult Patient Care AB - Disease summary:Manifestations of von Hippel-Lindau (VHL) disease were first observed in the early 20th century by Drs. von Hippel (retinal angiomas) and Lindau (cerebellar hemangioblastomas).The disease is characterized by the development of multiple tumors including retinal angiomas, central nervous system (CNS) hemangioblastomas, pancreatic cysts and neuroendocrine tumors, renal cell carcinomas (RCC), pheochromocytomas, and epididymal cystadenomas.Prior to comprehensive screening and early intervention, median survival of those with VHL was less than 50 years due to complications of RCC and hemangioblastomas.VHL has an incidence of 1:35,000 and the majority of affected individuals have a family history of the disease.Patients can have a germline missense, nonsense, or partial/complete deletion of the VHL gene. Most tumors generally have a second hit in the wild-type allele, which results from loss of heterozygosity, hypermethylation, and occasionally a second mutation.Hereditary basis:VHL is a highly penetrant autosomal dominant disease due to a germline mutation in the VHL gene. Children of affected individuals have a 50% chance of inheriting the affected allele. In kindreds with VHL, up to a quarter have no family history and have been considered as founder mutations. However in cases of apparently de novo mutations, these actually may represent a nontraditional transmission of the VHL mutation. Detailed testing of parents of affected individuals can demonstrate genetic mosaicism in VHL.Differential diagnosis:It is important to distinguish VHL from other multiorgan syndromes that have overlapping tumor types. Syndromes that feature pheochromocytomas include multiple endocrine neoplasia (MEN2a/b), neurofibromatosis type 1, and succinate dehydrogenase deficiency (SDH). Other kidney cancer syndromes associated with multiple tumor types include Birt-Hogg-Dubé (BHD), hereditary leiomyomatosis and renal cell carcinoma (HLRCC), SDH B and C deficiency, and Cowden syndrome. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102705191 ER -