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Von Hippel-Lindau syndrome(VHL)

MedGen UID:
42458
Concept ID:
C0019562
Disease or Syndrome
Synonyms: VHL; VHL syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: von Hippel-Lindau syndrome (46659004); VHL - von Hippel-Lindau syndrome (46659004); Lindau's disease (46659004); Von Hippel-Lindau syndrome (46659004); Familial cerebello-retinal angiomatosis (46659004); Lindau' disease (46659004); Cerebroretinal angiomatosis (46659004)
 
Genes (locations): CCND1 (11q13.3); VHL (3p25.3)
OMIM®: 193300
Orphanet: ORPHA892

Disease characteristics

Excerpted from the GeneReview: Von Hippel-Lindau Syndrome
Von Hippel-Lindau (VHL) syndrome is characterized by hemangioblastomas of the brain, spinal cord, and retina; renal cysts and clear cell renal cell carcinoma; pheochromocytoma, pancreatic cysts, and neuroendocrine tumors; endolymphatic sac tumors; and epididymal and broad ligament cysts. Cerebellar hemangioblastomas may be associated with headache, vomiting, gait disturbances, or ataxia. Spinal hemangioblastomas and related syrinx usually present with pain. Sensory and motor loss may develop with cord compression. Retinal hemangioblastomas may be the initial manifestation of VHL syndrome and can cause vision loss. Renal cell carcinoma occurs in about 70% of individuals with VHL and is the leading cause of mortality. Pheochromocytomas can be asymptomatic but may cause sustained or episodic hypertension. Pancreatic lesions often remain asymptomatic and rarely cause endocrine or exocrine insufficiency. Endolymphatic sac tumors can cause hearing loss of varying severity, which can be a presenting symptom. Cystadenomas of the epididymis are relatively common. They rarely cause problems, unless bilateral, in which case they may result in infertility. [from GeneReviews]
Authors:
Rachel S van Leeuwaarde  |  Saya Ahmad  |  Thera P Links, et. al.   view full author information

Additional descriptions

From OMIM
Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors. Neumann and Wiestler (1991) classified VHL as type 1 (without pheochromocytoma) and type 2 (with pheochromocytoma). Brauch et al. (1995) further subdivided VHL type 2 into type 2A (with pheochromocytoma) and type 2B (with pheochromocytoma and renal cell carcinoma). Hoffman et al. (2001) noted that VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. McNeill et al. (2009) proposed that patients with VHL syndrome caused by large VHL deletions that include the HSPC300 gene (C3ORF10; 611183) have a specific subtype of VHL syndrome characterized by protection from renal cell carcinoma, which the authors proposed be named VHL type 1B. Nordstrom-O'Brien et al. (2010) provided a review of the genetics of von Hippel-Lindau disease.  http://www.omim.org/entry/193300
From GHR
Von Hippel-Lindau syndrome is an inherited disorder characterized by the formation of tumors and fluid-filled sacs (cysts) in many different parts of the body. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood; however, the signs and symptoms of von Hippel-Lindau syndrome can occur throughout life.Tumors called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels. Although they are typically noncancerous, they can cause serious or life-threatening complications. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination (ataxia). Hemangioblastomas can also occur in the light-sensitive tissue that lines the back of the eye (the retina). These tumors, which are also called retinal angiomas, may cause vision loss.People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys, pancreas, and genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor.Von Hippel-Lindau syndrome is associated with a type of tumor called a pheochromocytoma, which most commonly occurs in the adrenal glands (small hormone-producing glands located on top of each kidney). Pheochromocytomas are usually noncancerous. They may cause no symptoms, but in some cases they are associated with headaches, panic attacks, excess sweating, or dangerously high blood pressure that may not respond to medication. Pheochromocytomas are particularly dangerous in times of stress or trauma, such as when undergoing surgery or in an accident, or during pregnancy.About 10 percent of people with von Hippel-Lindau syndrome develop endolymphatic sac tumors, which are noncancerous tumors in the inner ear. These growths can cause hearing loss in one or both ears, as well as ringing in the ears (tinnitus) and problems with balance. Without treatment, these tumors can cause sudden profound deafness.Noncancerous tumors may also develop in the liver and lungs in people with von Hippel-Lindau syndrome. These tumors do not appear to cause any signs or symptoms.  https://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome

Clinical features

From HPO
Renal cell carcinoma, papillary, 1
MedGen UID:
766
Concept ID:
C0007134
Neoplastic Process
Hereditary papillary renal cell carcinoma is characterized by the development of multiple, bilateral papillary renal tumors (Zbar et al., 1995). The transmission pattern is consistent with autosomal dominant inheritance with incomplete penetrance. Papillary renal cell carcinoma is histologically and genetically distinct from 2 other forms of inherited renal carcinoma, von Hippel Lindau disease (193300), caused by mutation in the VHL gene (608537) on chromosome 3, and a form associated with the chromosome translocation t(3;8), as described by Cohen et al. (1979). Bodmer et al. (2002) reviewed the molecular genetics of familial and nonfamilial cases of renal cell carcinoma, including the roles of VHL, MET, and translocations involving chromosomes 1, 3, and X. For background information and a discussion of genetic heterogeneity of nonpapillary renal cell carcinoma, see RCC (144700). See also a hereditary syndrome of predisposition to uterine leiomyomas and papillary renal cell carcinoma (HLRCC; 150800) caused by germline mutation in the FH gene (136850).
Sensorineural hearing loss
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Hypertension
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
Blood pressure that is abnormally high.
Abnormality of the liver
MedGen UID:
9792
Concept ID:
C0023895
Disease or Syndrome
An abnormality of the liver.
Pancreatic cysts
MedGen UID:
45293
Concept ID:
C0030283
Disease or Syndrome
A cyst of the pancreas that possess a lining of mucous epithelium.
Paraganglioma
MedGen UID:
10571
Concept ID:
C0030421
Neoplastic Process
A benign or malignant neoplasm arising from paraganglia located along the sympathetic or parasympathetic nerves. Infrequently, it may arise outside the usual distribution of the sympathetic and parasympathetic paraganglia. Tumors arising from the adrenal gland medulla are called pheochromocytomas. Morphologically, paragangliomas usually display a nesting (Zellballen) growth pattern. There are no reliable morphologic criteria to distinguish between benign and malignant paragangliomas. The only definitive indicator of malignancy is the presence of regional or distant metastases.
Pheochromocytoma
MedGen UID:
18419
Concept ID:
C0031511
Neoplastic Process
Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues distributed along the paravertebral axis from the base of the skull to the pelvis) and pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas cause catecholamine excess; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base and neck (referred to as head and neck PGL [HNPGL]) and sometimes in the upper mediastinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically lead to catecholamine excess. Symptoms of PGL/PCC result from either mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for developing metastatic disease is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas.
Polycythemia
MedGen UID:
18552
Concept ID:
C0032461
Disease or Syndrome
Abnormally high mass or concentration of red blood cells in the blood, either due to an increase in erythropoiesis or a decrease in plasma volume.
Epididymal cyst
MedGen UID:
20857
Concept ID:
C0037859
Disease or Syndrome
A benign cystic dilatation in the head of the epididymis that contains milky or watery fluid and spermatozoa.
Tinnitus
MedGen UID:
52760
Concept ID:
C0040264
Disease or Syndrome
A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of COCHLEAR DISEASES; VESTIBULOCOCHLEAR NERVE DISEASES; INTRACRANIAL HYPERTENSION; CRANIOCEREBRAL TRAUMA; and other conditions.
Vertigo
MedGen UID:
53006
Concept ID:
C0042571
Sign or Symptom
A feeling of movement, a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). Vertigo is medically distinct from dizziness, lightheadedness, and unsteadiness.
Pulmonary capillary hemangiomatosis
MedGen UID:
87404
Concept ID:
C0340548
Disease or Syndrome
Multiple renal cysts
MedGen UID:
140917
Concept ID:
C0431718
Disease or Syndrome
The presence of many cysts in the kidney.
Cerebellar hemangioblastoma
MedGen UID:
234108
Concept ID:
C1332900
Neoplastic Process
A 'hemangioblastoma of the cerebellum.
Retinal capillary hemangioma
MedGen UID:
271678
Concept ID:
C1514915
Neoplastic Process
A benign vascular tumor of the retina without any neoplastic characteristics.
Neoplasm of the pancreas
MedGen UID:
330845
Concept ID:
C1842408
Finding
Papillary cystadenoma of the epididymis
MedGen UID:
869791
Concept ID:
C4024221
Neoplastic Process
A cystadenoma, an epithelial tumor, that originates within the head of the epididymis.
Spinal hemangioblastoma
MedGen UID:
869793
Concept ID:
C4024223
Neoplastic Process
A 'hemangioblastoma of the spinal cord.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVVon Hippel-Lindau syndrome
Follow this link to review classifications for Von Hippel-Lindau syndrome in Orphanet.

Professional guidelines

PubMed

Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee.
Genet Med 2015 Jan;17(1):70-87. Epub 2014 Nov 13 doi: 10.1038/gim.2014.147. PMID: 25394175
ACMG Board of Directors.
Genet Med 2015 Jan;17(1):68-9. Epub 2014 Nov 13 doi: 10.1038/gim.2014.151. PMID: 25356965
Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society.
J Clin Endocrinol Metab 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498. PMID: 24893135
Reaume MN, Graham GE, Tomiak E, Kamel-Reid S, Jewett MA, Bjarnason GA, Blais N, Care M, Drachenberg D, Gedye C, Grant R, Heng DY, Kapoor A, Kollmannsberger C, Lattouf JB, Maher ER, Pause A, Ruether D, Soulieres D, Tanguay S, Turcotte S, Violette PD, Wood L, Basiuk J, Pautler SE; Kidney Cancer Research Network of Canada.
Can Urol Assoc J 2013 Sep-Oct;7(9-10):319-23. doi: 10.5489/cuaj.1496. PMID: 24319509Free PMC Article
Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics.
Genet Med 2013 Jul;15(7):565-74. Epub 2013 Jun 20 doi: 10.1038/gim.2013.73. PMID: 23788249Free PMC Article
Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K; North American Neuroendocrine Tumor Society (NANETS).
Pancreas 2010 Aug;39(6):775-83. doi: 10.1097/MPA.0b013e3181ebb4f0. PMID: 20664475Free PMC Article
Trepanier A, Ahrens M, McKinnon W, Peters J, Stopfer J, Grumet SC, Manley S, Culver JO, Acton R, Larsen-Haidle J, Correia LA, Bennett R, Pettersen B, Ferlita TD, Costalas JW, Hunt K, Donlon S, Skrzynia C, Farrell C, Callif-Daley F, Vockley CW; National Society of Genetic Counselors.
J Genet Couns 2004 Apr;13(2):83-114. doi: 10.1023/B:JOGC.0000018821.48330.77. PMID: 15604628

External

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

Recent clinical studies

Etiology

Prokopienko M, Kunert P, Podgórska A, Marchel A
Neurol Neurochir Pol 2016;50(5):349-55. Epub 2016 Jun 23 doi: 10.1016/j.pjnns.2016.06.003. PMID: 27591060
Wong M, Chu YH, Tan HL, Bessho H, Ngeow J, Tang T, Tan MH
Chin J Cancer 2016 Aug 15;35(1):79. doi: 10.1186/s40880-016-0141-z. PMID: 27527340Free PMC Article
Vikkath N, Valiyaveedan S, Nampoothiri S, Radhakrishnan N, Pillai GS, Nair V, Pooleri GK, Mathew G, Menon KN, Ariyannur PS, Pillai AB
Fam Cancer 2015 Dec;14(4):585-94. doi: 10.1007/s10689-015-9806-z. PMID: 25952756
Weisbrod AB, Kitano M, Thomas F, Williams D, Gulati N, Gesuwan K, Liu Y, Venzon D, Turkbey I, Choyke P, Yao J, Libutti SK, Nilubol N, Linehan WM, Kebebew E
J Am Coll Surg 2014 Feb;218(2):163-9. Epub 2013 Nov 12 doi: 10.1016/j.jamcollsurg.2013.10.025. PMID: 24440063Free PMC Article
Benhammou JN, Boris RS, Pacak K, Pinto PA, Linehan WM, Bratslavsky G
J Urol 2010 Nov;184(5):1855-9. Epub 2010 Sep 17 doi: 10.1016/j.juro.2010.06.102. PMID: 20846682Free PMC Article

Diagnosis

Ma X, Jing Y, Liu Y, Yu L
J Int Med Res 2019 Feb;47(2):973-981. Epub 2018 Sep 4 doi: 10.1177/0300060518792368. PMID: 30178691Free PMC Article
Glushkova M, Dimova P, Yordanova I, Todorov T, Tourtourikov I, Mitev V, Todorova A
Int J Neurosci 2018 Feb;128(2):117-124. Epub 2017 Sep 13 doi: 10.1080/00207454.2017.1372436. PMID: 28849724
Vikkath N, Valiyaveedan S, Nampoothiri S, Radhakrishnan N, Pillai GS, Nair V, Pooleri GK, Mathew G, Menon KN, Ariyannur PS, Pillai AB
Fam Cancer 2015 Dec;14(4):585-94. doi: 10.1007/s10689-015-9806-z. PMID: 25952756
Dessauvagie BF, Wong G, Robbins PD
J Clin Neurosci 2015 Jan;22(1):215-8. Epub 2014 Jul 23 doi: 10.1016/j.jocn.2014.04.024. PMID: 25088480
Takahashi T, Nogimura H, Kuriki K, Kobayashi R
World J Surg Oncol 2014 Mar 29;12:74. doi: 10.1186/1477-7819-12-74. PMID: 24678933Free PMC Article

Therapy

Ma X, Jing Y, Liu Y, Yu L
J Int Med Res 2019 Feb;47(2):973-981. Epub 2018 Sep 4 doi: 10.1177/0300060518792368. PMID: 30178691Free PMC Article
Chen Y, Liu H, Zhang K, Gao L
Photodiagnosis Photodyn Ther 2014 Jun;11(2):250-3. Epub 2014 Mar 13 doi: 10.1016/j.pdpdt.2014.02.013. PMID: 24632330
Volkin D, Yerram N, Ahmed F, Lankford D, Baccala A, Gupta GN, Hoang A, Nix J, Metwalli AR, Lang DM, Bratslavsky G, Linehan WM, Pinto PA
J Pediatr Surg 2012 Nov;47(11):2077-82. doi: 10.1016/j.jpedsurg.2012.07.003. PMID: 23164001Free PMC Article
Aiello LP, George DJ, Cahill MT, Wong JS, Cavallerano J, Hannah AL, Kaelin WG Jr
Ophthalmology 2002 Sep;109(9):1745-51. PMID: 12208726
Bender BU, Gutsche M, Gläsker S, Müller B, Kirste G, Eng C, Neumann HP
J Clin Endocrinol Metab 2000 Dec;85(12):4568-74. doi: 10.1210/jcem.85.12.7015. PMID: 11134110

Prognosis

Ma X, Jing Y, Liu Y, Yu L
J Int Med Res 2019 Feb;47(2):973-981. Epub 2018 Sep 4 doi: 10.1177/0300060518792368. PMID: 30178691Free PMC Article
Prokopienko M, Kunert P, Podgórska A, Marchel A
Neurol Neurochir Pol 2016;50(5):349-55. Epub 2016 Jun 23 doi: 10.1016/j.pjnns.2016.06.003. PMID: 27591060
Vikkath N, Valiyaveedan S, Nampoothiri S, Radhakrishnan N, Pillai GS, Nair V, Pooleri GK, Mathew G, Menon KN, Ariyannur PS, Pillai AB
Fam Cancer 2015 Dec;14(4):585-94. doi: 10.1007/s10689-015-9806-z. PMID: 25952756
Dessauvagie BF, Wong G, Robbins PD
J Clin Neurosci 2015 Jan;22(1):215-8. Epub 2014 Jul 23 doi: 10.1016/j.jocn.2014.04.024. PMID: 25088480
Takahashi T, Nogimura H, Kuriki K, Kobayashi R
World J Surg Oncol 2014 Mar 29;12:74. doi: 10.1186/1477-7819-12-74. PMID: 24678933Free PMC Article

Clinical prediction guides

Ma X, Jing Y, Liu Y, Yu L
J Int Med Res 2019 Feb;47(2):973-981. Epub 2018 Sep 4 doi: 10.1177/0300060518792368. PMID: 30178691Free PMC Article
Wong M, Chu YH, Tan HL, Bessho H, Ngeow J, Tang T, Tan MH
Chin J Cancer 2016 Aug 15;35(1):79. doi: 10.1186/s40880-016-0141-z. PMID: 27527340Free PMC Article
Kozaczuk S, Ben-Skowronek I
Ital J Pediatr 2015 Aug 13;41:56. doi: 10.1186/s13052-015-0158-y. PMID: 26268347Free PMC Article
Volkin D, Yerram N, Ahmed F, Lankford D, Baccala A, Gupta GN, Hoang A, Nix J, Metwalli AR, Lang DM, Bratslavsky G, Linehan WM, Pinto PA
J Pediatr Surg 2012 Nov;47(11):2077-82. doi: 10.1016/j.jpedsurg.2012.07.003. PMID: 23164001Free PMC Article
Benhammou JN, Boris RS, Pacak K, Pinto PA, Linehan WM, Bratslavsky G
J Urol 2010 Nov;184(5):1855-9. Epub 2010 Sep 17 doi: 10.1016/j.juro.2010.06.102. PMID: 20846682Free PMC Article

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