title: Von Hippel-Lindau disease.
abstract: von Hippel-Lindau (VHL) disease is an inheritable condition with an incidence of 1 in 36000 live births. Individuals with VHL develop benign and malignant tumors including retinal and central nervous system hemangioblastomas, clear cell renal cell carcinomas (RCC), pheochromocytomas, pancreatic neuroendocrine tumors and endolymphatic sac tumors (ELSTs). VHL is caused by germline loss of function of the VHL gene on one allele at chromosome 3p25-26. A somatic "second hit" event leads to the loss of the other allele and tumor formation. Loss of VHL function in cells leads to increased expression and stabilization of hypoxia inducible factor (HIF). VHL protein/HIF pathway has been implicated in tumorigenesis for hemangioblastomas, RCC and other VHL tumors. Clinical examination, imaging, and genetic testing for VHL mutations confirm VHL disease. Management of VHL disease largely consists of surgical resection of symptomatic tumors (hemangioblastomas), tumors prone to metastasize (RCC larger than 3cm), or tumors causing hormonal symptoms (pheochromocytomas). Despite advances in early diagnosis and management of VHL disease, life expectancy for VHL patients remains low at 40-52 years. Secondary effects from VHL manifestations are mitigated by routine surveillance and early detection. In this chapter, we summarize the current state of knowledge in VHL disease.
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: prashant.chittiboina@nih.gov.
authors.forename: Prashant
authors.initials: P
authors.lastname: Chittiboina
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurological Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Lonser
mesh_terms: D018325:Hemangioblastoma; D006801:Humans; D006623:von Hippel-Lindau Disease / Q000453:epidemiology / Q000235:genetics
keywords: ELST; VHL; clear cell renal cell carcinoma; endolymphatic sac tumor; hemangioblastoma; pVHL; second hit; von Hippel Lindau disease