title: Neurologic manifestations of von Hippel-Lindau disease.
abstract: von Hippel-Lindau disease (VHL) is an autosomal-dominant neoplasia syndrome that is the result of a germline mutation of the VHL tumor suppressor gene on the short arm of chromosome 3. Patients with VHL are predisposed to develop lesions of the central nervous system and viscera. Central nervous system lesions include hemangioblastomas (the most common tumor in VHL) and endolymphatic sac tumors (ELSTs). Visceral manifestations include renal carcinomas and cysts, pancreatic neuroendocrine tumors and cysts, pheochromocytomas, and cystadenomas of the reproductive adnexal organs. Despite their benign pathology, hemangioblastomas and ELSTs are a frequent cause of morbidity and mortality in patients with VHL. Recent molecular biologic investigations into these VHL-associated central nervous system lesions provide new insight into their origin and development. Emerging data from serial imaging and clinical surveillance protocols provide insight into the natural history of these lesions. Because of the dissimilar pathobiology and clinical course between hemangioblastomas and ELSTs, the optimal management strategies for these neurologic manifestations of VHL are very different.
authors.affiliation: Diagnostic Radiology Department, The Clinical Center of the National Institutes of Health, Bethesda, Maryland 20892-1414, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Butman
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Russell R
authors.initials: RR
authors.lastname: Lonser
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000209:etiology / Q000601:surgery; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery; D018450:Disease Progression; D004428:Ear Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery; D004712:Endolymphatic Sac; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000209:etiology; D018325:Hemangioblastoma / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000601:surgery; D010181:Pancreatic Cyst / Q000175:diagnosis / Q000209:etiology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D006623:von Hippel-Lindau Disease / Q000150:complications* / Q000175:diagnosis*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
references.citation: Hum Mutat. 1998;12(6):417-23
references.pmid: 9829911
references.citation: J Neurosurg. 2008 Apr;108(4):751-6
references.pmid: 18377255
references.citation: J Med Genet. 1991 Jul;28(7):443-7
references.pmid: 1895313
references.citation: Ann Neurol. 2004 Feb;55(2):236-40
references.pmid: 14755727
references.citation: Otol Neurotol. 2004 Jul;25(4):599-603
references.pmid: 15241241
references.citation: J Neurosurg. 2003 Jan;98(1):95-105
references.pmid: 12546357
references.citation: N Engl J Med. 2004 Jun 10;350(24):2481-6
references.pmid: 15190140
references.citation: J Neurosurg Spine. 2006 May;4(5):426
references.pmid: 16703915
references.citation: Am J Med. 1964 Apr;36:595-617
references.pmid: 14142412
references.citation: Nature. 1998 Jul 30;394(6692):485-90
references.pmid: 9697772
references.citation: J Neurosurg. 2004 Mar;100(3):480-7
references.pmid: 15035284
references.citation: Nature. 1999 May 20;399(6733):271-5
references.pmid: 10353251
references.citation: Neuroradiology. 2000 Sep;42(9):639-42
references.pmid: 11071434
references.citation: Lancet. 2003 Jun 14;361(9374):2059-67
references.pmid: 12814730
references.citation: J Neurosurg. 2003 Jan;98(1):82-94
references.pmid: 12546356
references.citation: Radiology. 1995 Mar;194(3):629-42
references.pmid: 7862955
references.citation: Surgery. 2007 Dec;142(6):814-8; discussion 818.e1-2
references.pmid: 18063061
references.citation: Science. 1993 May 28;260(5112):1317-20
references.pmid: 8493574
references.citation: J Neurosurg. 2006 Aug;105(2):256-63
references.pmid: 17219831
references.citation: Neurology. 2000 Aug 8;55(3):460
references.pmid: 10932304
references.citation: Nature. 1988 Mar 17;332(6161):268-9
references.pmid: 2894613
references.citation: Am J Hum Genet. 1972 Sep;24(5):514-32
references.pmid: 4340974
references.citation: J Neurosurg. 2008 Feb;108(2):210-22
references.pmid: 18240914
references.citation: J Neurosurg. 2005 Mar;102(3):503-12
references.pmid: 15796386
references.citation: PLoS Med. 2007 Feb;4(2):e60
references.pmid: 17298169
references.citation: Medicine (Baltimore). 1989 Jan;68(1):1-29
references.pmid: 2642584
references.citation: JAMA. 2007 Jul 4;298(1):41-8
references.pmid: 17609489
references.citation: Hum Pathol. 1997 May;28(5):540-3
references.pmid: 9158701
references.citation: Development. 1998 Feb;125(4):725-32
references.pmid: 9435292
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10589-94
references.pmid: 8855222
references.citation: J Intern Med. 1998 Jun;243(6):547-53
references.pmid: 9681857
references.citation: Cancer. 1989 Dec 1;64(11):2292-302
references.pmid: 2804921
references.citation: Int J Radiat Oncol Biol Phys. 1996 Jun 1;35(3):493-9
references.pmid: 8655372
references.citation: Nature. 2004 Dec 2;432(7017):625-30
references.pmid: 15577911
references.citation: Ophthalmology. 2002 Sep;109(9):1745-51
references.pmid: 12208726
references.citation: J Neurosurg. 2006 Aug;105(2):248-55
references.pmid: 17219830
references.citation: Am J Ophthalmol. 2003 Jul;136(1):194-6
references.pmid: 12834696
references.citation: Am J Hum Genet. 2000 Jan;66(1):84-91
references.pmid: 10631138
references.citation: Am J Pathol. 1995 Aug;147(2):245-50
references.pmid: 7639324
references.citation: Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2156-61
references.pmid: 9122164
references.citation: J Urol. 1999 Sep;162(3 Pt 1):659-64
references.pmid: 10458336
references.citation: Lancet. 1991 May 4;337(8749):1052-4
references.pmid: 1673491
references.citation: Cancer Res. 2005 Dec 1;65(23):10847-53
references.pmid: 16322231
references.citation: Brain. 2007 Mar;130(Pt 3):836-42
references.pmid: 17264095
references.citation: Arch Neurol. 1976 Jun;33(6):435-41
references.pmid: 945725
references.citation: J Neurosurg. 1996 Oct;85(4):591-6
references.pmid: 8814161
references.citation: JAMA. 1997 May 14;277(18):1461-6
references.pmid: 9145719
references.citation: J Urol. 1999 May;161(5):1475-9
references.pmid: 10210376
references.citation: Mol Cell. 1998 Jun;1(7):959-68
references.pmid: 9651579
references.citation: Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6459-63
references.pmid: 7604013
references.citation: J Neurosurg. 2003 Jan;98(1):106-16
references.pmid: 12546358
references.citation: Cancer Res. 2006 Apr 15;66(8):4167-72
references.pmid: 16618738
references.citation: Nat Rev Cancer. 2002 Sep;2(9):673-82
references.pmid: 12209156
references.citation: Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):993-8
references.pmid: 9448273
references.citation: Otol Neurotol. 2002 May;23(3):378-87
references.pmid: 11981399