von Hippel-Lindau disease


Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 29 August, 2019 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (26)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

VHL 3p25.3 RCA1, VHL1, pVHL, HRCA1 -VHL and von Hippel-Lindau Disease
HIF1A 14q23.2 HIF1, MOP1, PASD8, HIF-1A, bHLHe78, HIF-1alpha, HIF1-ALPHA, HIF-1-alpha -HIF1A and von Hippel-Lindau Disease
CA9 9p13.3 MN, CAIX -CA9 and von Hippel-Lindau Disease
THRB 3p24.2 GRTH, PRTH, THR1, ERBA2, NR1A2, THRB1, THRB2, C-ERBA-2, C-ERBA-BETA -THRB and von Hippel-Lindau Disease
SDHAF2 11q12.2 PGL2, SDH5, C11orf79 -SDHAF2 and von Hippel-Lindau Disease
TMEM127 2q11.2 -TMEM127 and von Hippel-Lindau Disease
SDHA 5p15.33 FP, PGL5, SDH1, SDH2, SDHF, CMD1GG -SDHA and von Hippel-Lindau Disease
FH 1q43 MCL, FMRD, HsFH, LRCC, HLRCC, MCUL1 -FH and von Hippel-Lindau Disease
EPOR 19p13.2 EPO-R -EPOR and von Hippel-Lindau Disease
ATRX Xq21.1 JMS, XH2, XNP, MRX52, RAD54, RAD54L, ZNF-HX -ATRX and von Hippel-Lindau Disease
MAP2K1 15q22.31 CFC3, MEK1, MKK1, MAPKK1, PRKMK1 -MAP2K1 and von Hippel-Lindau Disease
SKP1 5q31.1 OCP2, p19A, EMC19, SKP1A, OCP-II, TCEB1L -SKP1 and von Hippel-Lindau Disease
DAXX 6p21.32 DAP6, EAP1, BING2 -DAXX and von Hippel-Lindau Disease
CHGA 14q32.12 CGA -CHGA and von Hippel-Lindau Disease
TNFRSF10D 8p21.3 DCR2, CD264, TRUNDD, TRAILR4, TRAIL-R4 -TNFRSF10D and von Hippel-Lindau Disease
CBL 11q23.3 CBL2, NSLL, C-CBL, RNF55, FRA11B -Proto-Oncogene Proteins c-cbl and von Hippel-Lindau Disease
CD70 19p13.3 CD27L, CD27-L, CD27LG, TNFSF7, TNLG8A -CD70 and von Hippel-Lindau Disease
TNFRSF10A 8p21.3 DR4, APO2, CD261, TRAILR1, TRAILR-1 -TNFRSF10A and von Hippel-Lindau Disease
ERCC2 19q13.32 EM9, TTD, XPD, TTD1, COFS2, TFIIH -ERCC2 and von Hippel-Lindau Disease
VIM 10p13 HEL113, CTRCT30 -VIM and von Hippel-Lindau Disease
HNRNPA2B1 7p15.2 RNPA2, HNRPA2, HNRPB1, SNRPB1, HNRNPA2, HNRNPB1, IBMPFD2, HNRPA2B1 -HNRNPA2B1 and von Hippel-Lindau Disease
RBX1 22q13.2 ROC1, RNF75, BA554C12.1 -RBX1 and von Hippel-Lindau Disease
EGLN3 14q13.1 PHD3, HIFPH3, HIFP4H3 -EGLN3 and von Hippel-Lindau Disease
TFEB 6p21.1 TCFEB, BHLHE35, ALPHATFEB -TFEB and von Hippel-Lindau Disease
GNAS 20q13.32 AHO, GSA, GSP, POH, GPSA, NESP, SCG6, SgVI, GNAS1, PITA3, C20orf45 -GNAS and von Hippel-Lindau Disease
ERCC6 10q11.23 CSB, CKN2, COFS, ARMD5, COFS1, POF11, RAD26, UVSS1 -ERCC6 and von Hippel-Lindau Disease

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest publications

Publications about von Hippel-Lindau Disease and cancer

Mishra P, Pal S, Kanaujia V, Sharma K
Retinal capillary hemangioblastoma associated with retinochoroidal coloboma in Von Hippel-Lindau disease.
Indian J Ophthalmol. 2019; 67(5):688-690 [PubMed] Free Access to Full Article Related Publications

Banezhad F, Kiamanesh Z, Emami F, Sadeghi R
68Ga DOTATATE PET/CT Versus 18F-FDG PET/CT for Detecting Intramedullary Hemangioblastoma in a Patient With Von Hippel-Lindau Disease.
Clin Nucl Med. 2019; 44(6):e385-e387 [PubMed] Related Publications
Von Hippel-Lindau disease is an inherited syndrome associated with several benign and malignant tumors such as central nervous system (CNS) hemangioblastoma. Herein, we report a known case of A Von Hippel-Lindau patient with a cerebral hemangioblastoma who was referred for further evaluation because of recent paraparesis. F-FDG PET/CT showed no focal uptake in the thoracic spine, which demonstrated increased Ga DOTATATE activity, owing to overexpression of somatostatin receptors, suggesting spinal cord hemangioblastoma. This case report indicates the significant role of Ga-labeled somatostatin receptor analogs in the diagnosis of hemangioblastoma.

Minervini G, Quaglia F, Tabaro F, Tosatto SCE
Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors.
PLoS Comput Biol. 2019; 15(4):e1006478 [PubMed] Free Access to Full Article Related Publications
Familiar cancers represent a privileged point of view for studying the complex cellular events inducing tumor transformation. Von Hippel-Lindau syndrome, a familiar predisposition to develop cancer is a clear example. Here, we present our efforts to decipher the role of von Hippel-Lindau tumor suppressor protein (pVHL) in cancer insurgence. We collected high quality information about both pVHL mutations and interactors to investigate the association between patient phenotypes, mutated protein surface and impaired interactions. Our data suggest that different phenotypes correlate with localized perturbations of the pVHL structure, with specific cell functions associated to different protein surfaces. We propose five different pVHL interfaces to be selectively involved in modulating proteins regulating gene expression, protein homeostasis as well as to address extracellular matrix (ECM) and ciliogenesis associated functions. These data were used to drive molecular docking of pVHL with its interactors and guide Petri net simulations of the most promising alterations. We predict that disruption of pVHL association with certain interactors can trigger tumor transformation, inducing metabolism imbalance and ECM remodeling. Collectively taken, our findings provide novel insights into VHL-associated tumorigenesis. This highly integrated in silico approach may help elucidate novel treatment paradigms for VHL disease.

Palui R, Kamalanathan S, Sahoo J, et al.
Adrenal adenoma in von Hippel-Lindau syndrome: A case report with review of literature.
J Cancer Res Ther. 2019; 15(Supplement):S163-S166 [PubMed] Related Publications
A 29-year-old hypertensive male with von Hippel-Lindau (VHL) syndrome came to the Endocrinology department for evaluation. Contrast-enhanced computed tomography of the abdomen revealed an adrenal mass, bilateral renal cell carcinoma, and multiple pancreatic cysts. The hormonal investigations for adrenal mass were normal. He underwent left-sided adrenalectomy, and the histopathological report was suggestive of an adrenocortical adenoma. Genetic analysis of VHL gene in this patient revealed a heterogeneous 5' splice site variation of intron 1 of the VHL gene that affects splice site of exon 1 (c. 340 + 1G > A). Adrenocortical adenoma is very rare in VHL syndrome. Only two cases of adrenocortical adenoma in VHL have been reported in the literature, and both were associated with pheochromocytoma. This is probably the first reported case of adrenocortical adenoma in VHL syndrome without accompanying pheochromocytoma.

Shell J, Tirosh A, Millo C, et al.
The utility of
Eur J Radiol. 2019; 112:130-135 [PubMed] Related Publications
PURPOSE: Patients with von Hippel-Lindau (VHL) disease may develop various tumors, including neuroendocrine tumors of the pancreas (PNETs) and adrenal, central nervous system and retinal hemangioblastomas, kidney tumors and more.
METHODS: Patients with a diagnosis of VHL were enrolled in a prospective study and underwent surveillance imaging for pancreatic lesions (n = 301). The current analysis includes 73 evaluations with multiple imaging modalities of 36 patients (2.1 ± 0.8 evaluations/patient, range 1-4) for a head-to-head comparison of

Krüger MT, Klingler JH
Resection of a cerebellar hemangioblastoma via a minimally invasive tubular approach.
J Clin Neurosci. 2019; 63:240-243 [PubMed] Related Publications
Hemangioblastomas are rare benign, highly vascularized tumors occurring in the cerebellum and the spinal cord. They often develop tumor-associated cysts multiple times the size of the solid part of the tumor. Patients with von Hippel-Lindau (VHL) disease typically exhibit multiple tumors with the need of repeated surgeries during their lifetime. As multiple surgeries involve an increased risk of access-related morbidity, a minimally invasive approach can be favorable for specific types of tumors in the posterior fossa. We here present the case of a minimally invasive removal of a superficial cerebellar hemangioblastoma with tumor-associated cyst and indicate the potential benefits and limitations of this technique.

De Luise M, Guarnieri V, Ceccarelli C, et al.
A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1
Oxid Med Cell Longev. 2019; 2019:8069583 [PubMed] Free Access to Full Article Related Publications
The Von Hippel-Lindau (VHL) syndrome has been rarely associated with renal oncocytomas, and tumors usually show HIF1

Hopp AC, Collins JM, Nguyen CC, Yang M
Radiopathological correlation of a von Hippel-Lindau syndrome associated pancreatic neuroendocrine tumour with clear cell features.
BMJ Case Rep. 2019; 12(2) [PubMed] Related Publications

Tsang SH, Sharma T
Von Hippel-Lindau Disease.
Adv Exp Med Biol. 2018; 1085:201-203 [PubMed] Related Publications
Phakomatoses (phakoma = birthmark) are a group of diseases or syndromes that have hamartomas (tumorous malformations composed of tissues normally present at the location where they develop) of the skin, brain, and eye (oculoneurocutaneous syndromes).

Trotta AM, Santagata S, Zanotta S, et al.
Mutated Von Hippel-Lindau-renal cell carcinoma (RCC) promotes patients specific natural killer (NK) cytotoxicity.
J Exp Clin Cancer Res. 2018; 37(1):297 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Previous evidence demonstrated that restoration of wild type VHL in human renal cancer cells decreased in vitro NK susceptibility. To investigate on the role of tumoral VHL status versus NK capability in renal cancer patients, 51 RCC patients were characterized for VHL mutational status and NK function.
METHODS: VHL mutational status was determined by direct DNA sequencing on tumor tissue. NK cytotoxicity was measured against specific target cells K562, VHL-wild type (CAKI-1) and VHL-mutated (A498) human renal cancer cells through externalization of CD107a and IFN-γ production. Activating NK receptors, NKp30, NKp44, NKp46, NKG2D, DNAM-1, NCAM-1 and FcγRIIIa were evaluated through quantitative RT-PCR. RCC tumoral Tregs were characterized as CD4
RESULTS: VHL mutations were detected in 26/55 (47%) RCC patients. IL-2 activated whole-blood samples (28 VHL-WT-RCC and 23 VHL-MUT-RCC) were evaluated for NK cytotoxicity toward human renal cancer cells A498, VHL-MUT and CAKI-1, VHL-WT. Efficient NK degranulation and increase in IFN-γ production was detected when IL-2 activated whole-blood from VHL-MUT-RCC patients were tested toward A498 as compared to CAKI-1 cells (CD107a
CONCLUSIONS: VHL tumoral mutations improve NKs effectiveness in RCC patients and need to be considered in the evaluation of immune response. Moreover therapeutic strategies designed to target NK cells could be beneficial in VHL-mutated-RCCs alone or in association with immune checkpoints inhibitors.

Wu X, Chen L, Zhang Y, et al.
A novel mutation in the VHL gene in a Chinese family with von Hippel-Lindau disease.
BMC Med Genet. 2018; 19(1):204 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome, and VHL is identified as a tumor suppressor gene. The main objective of this study was to identify disease-causing mutations in a Chinese family affected with VHL disease.
METHODS: Genomic DNA was extracted from peripheral blood from a Chinese family with VHL. A predicted pathogenic variant was identified by targeted exome capture technology and next-generation sequencing.
RESULTS: A novel heterozygous mutation (c.349 T > A, p.W117R) was detected in affected family members. No mutation was detected in unaffected family members or in the 150 normal controls. The mutation segregated with the disease phenotype throughout three generations. Histopathological examination revealed the characteristics of hemangioblastoma.
CONCLUSIONS: A novel W117R was detected in the VHL gene that caused retinal hemangioblastomas in affected members of a Chinese family.

Peng YC, Chen YB
Recognizing Hereditary Renal Cancers Through the Microscope: A Pathology Update.
Surg Pathol Clin. 2018; 11(4):725-737 [PubMed] Related Publications
A heightened understanding of hereditary renal cancer syndromes and their molecular basis has led to an increased awareness and recognition of these renal neoplasms by pathologists. Because a diagnosis of hereditary renal cell carcinoma has a profound impact on the patient and family members, when and how to raise such a suspicion via pathologic assessment has become an important yet very challenging task. This review discusses key clinicopathologic, immunohistochemical, and genetic characteristics of hereditary renal cancer syndromes, and important differential diagnostic challenges, emphasizing recent pathologic and molecular advances.

Urbieta Anza A, Llarena Ibarguren R, Tomás Zabala Egurrola JA, et al.
[Renal cell carcinoma in von Hippel-Lindau disease. Nephron sparing surgery.]
Arch Esp Urol. 2018; 71(9):757-764 [PubMed] Related Publications
OBJECTIVES: We reviewed the feasibility and safety of nephron sparing surgery for renal cell carcinoma in patients with von Hippel Lindau (VHL) disease.
METHODS: We selected 22 patients with (VHL) disease with a mean age of 43 (range 30-56), from whom 16 underwent radical nephrectomy or nephron sparing surgery at our department between 2000 and 2015.
RESULTS: A total of 33 tumors were treated, by either tumorectomy (n=20), partial nephrectomy (n=5), percutaneous renal radiofrequency ablation (n=3) edaor radical nephrectomy (n=5). All procedures were successfully completed without intraoperative and postoperative complications. The diameter of the tumor ranged from 2.8 to 4.8 cm. The interval between treatments in patients operated more than once was 40 months. Renal function stayed stable with basal creatinine and current creatinine 0.74 ± 0.21 mg/dl and 0.93 ± 0.22 mg/dl respectively. Median follow-up was 72.3 months. Cancer-specific survival was 97%.
CONCLUSIONS: nephron sparing surgery in renal tumors >3 cm is an effective and safe treatment for VHL patients.

Liu WK, Tian XD, Yang YM
[Diagnosis and treatment of pancreatic neuroendocrine neoplasmas in Von Hippel-Lindau syndrome].
Zhonghua Wai Ke Za Zhi. 2018; 56(11):869-872 [PubMed] Related Publications
Von Hippel-Lindau(VHL) syndrome is a rare autosomal dominant hereditary disease, and pancreas is one of the frequently involved intra-abdominal organs, including simple pancreatic cysts, pancreatic serous cystadenomas and neuroendocrine neoplasmas. Most of the VHL-related pancreatic neuroendocrine neoplasmas (VHL-pNEN)were non-functional, but they still have a tendency to be malignant. Treatment options for VHL-pNEN include regular follow-up, surgical resection, and medication therapy. When compared with sporadic pNEN, the malignant degree of VHL-pNEN is lower, with a better prognosis, so the surgical treatment should be carefully considered. The indications of surgery for VHL-pNEN include big primary lesions (≥3 cm), fast tumor doubling time (<500 days), VHL gene mutation on exon 3, malignant manifestations on imaging findings, and functional pNEN lesions. The function-preserving approach should be performed to keep the functional pancreatic parenchyma as much as possible. Even for patients with a late stage malignancy that cannot be radically resected, active medication therapy may still lead to a long-term survival.

Nguyen TH, Pham T, Strickland T, et al.
Von Hippel-Lindau with early onset of hemangioblastoma and multiple drop-metastases like spinal lesions: A case report.
Medicine (Baltimore). 2018; 97(39):e12477 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Hemangioblastoma is a rare tumor of the central nervous system (CNS). It is usually observed in patients with von-Hippel Lindau (VHL). The peak age for hemangioblastoma is between 20 and 50 years of age with very few cases over 65 or below 18 years of age.
PATIENT CONCERNS: We report a female with a rare VHL mutation (c.337C>T) who was diagnosed with multifocal CNS hemangioblastoma at a very young age.
DIAGNOSIS: At 17-years of age, she presented with obstructive hydrocephalus due to large cystic cerebellar mass. Imaging showed multiple lesions resembling drop metastases throughout her spinal cord. Immunohistochemistry of the resected tumor confirmed the pathological diagnosis of hemangioblastoma (World Health Organization Grade 1).
INTERVENTIONS AND OUTCOME: She was treated with multi-stage resection of her primary and drop- metastasis like disease. She presented six months later with retinal hemangioblastoma while her other lesions were stable. She presented with multiple CNS and eye hemangioblastomas after failing to follow up for 2 years. Subsequently, Everolimus was started to treat her systemic disease.
LESSONS: The unique feature of our case is the presence of multiple drop-metastases like spinal lesions, which has not been reported in the literature to be associated with hemangioblastoma.

Shmueli MD, Levy-Kanfo L, Haj E, et al.
Arginine refolds, stabilizes, and restores function of mutant pVHL proteins in animal model of the VHL cancer syndrome.
Oncogene. 2019; 38(7):1038-1049 [PubMed] Related Publications
The von Hippel-Lindau (VHL) syndrome is a rare inherited cancer, caused by mutations in the VHL gene, many of which render the VHL protein (pVHL) unstable. pVHL is a tumor-suppressor protein implicated in a variety of cellular processes, most notably in response to changes in oxygen availability, due to its role as part of an E3-ligase complex which targets the hypoxia-inducible factor (HIF) for degradation. Previously we reported, using in silico and in vitro analyses, that common oncogenic VHL mutations render pVHL less stable than the wild-type protein, distort its core domain and as a result reduce the ability of the protein to bind its target HIF-1α. Among various chemical chaperones tested, arginine was the most effective in refolding mutant of pVHL. Here we examined the consequences of administering L- or D-arginine to a Drosophila VHL model and to human renal carcinoma cells, both expressing misfolded versions of human pVHL. Arginine treatment increased pVHL solubility in both models and increased the half-life of the mutant pVHL proteins in the cell culture. In both models, L- as well as D-arginine enhanced the ability of wild-type pVHL and certain misfolded mutant versions of pVHL to bind ODD, the HIF-derived target peptide, reflecting restoration of pVHL function. Moreover, continuous feeding of Drosophila expressing misfolded versions of pVHL either L- or D-arginine rich diet rescued their lethal phenotype. Collectively, these in vivo results suggest that arginine supplementation should be examined as a potential novel treatment for VHL cancer syndrome.

Minnella AM, Pagliei V, Maceroni M, et al.
Effect of intravitreal dexamethasone on macular edema in von Hippel-Lindau disease assessed using swept-source optical coherence tomography: a case report.
J Med Case Rep. 2018; 12(1):248 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Von Hippel-Lindau disease is a rare hereditary syndrome caused by germinal mutations in a von Hippel-Lindau tumor-suppressing gene. Retinal hemangioblastoma is the ocular hallmark lesion of von Hippel-Lindau disease.
CASE PRESENTATION: A 20-year-old Caucasian woman presented to our institution with painless visual impairment in the right eye. A fundus ophthalmoscopic evaluation and swept-source optical coherence tomographic examination revealed a retinal hemangioblastoma associated with cystoid macular edema. On the basis of the clinical ocular findings and genetic analysis, von Hippel-Lindau disease was diagnosed. Following an intravitreal injection of ranibizumab, off-label administration of intravitreal dexamethasone was considered to reduce the edema. An almost complete resolution of the edema in the macular area was observed 1 week after the injection. Finally, laser photocoagulation and transconjunctival cryotherapy were performed; the patient developed "ablatio fugax" after cryotherapy.
CONCLUSIONS: In our experience, intravitreal dexamethasone administration has proven to be a useful tool for reducing retinal hemangioblastoma-related macular edema in von Hippel-Lindau disease and may be considered a potentially valuable treatment that can be used in combination with other therapies.

Chao CC, Tsai YS, Chen LW
Teaching NeuroImages: CNS hemangioblastomas in von Hippel-Lindau disease with exon 3 deletion.
Neurology. 2018; 91(6):e601-e602 [PubMed] Related Publications

Gattolliat CH, Couvé S, Meurice G, et al.
Integrative analysis of dysregulated microRNAs and mRNAs in multiple recurrent synchronized renal tumors from patients with von Hippel-Lindau disease.
Int J Oncol. 2018; 53(4):1455-1468 [PubMed] Free Access to Full Article Related Publications
Von Hippel-Lindau (VHL) disease is a rare autosomal dominant syndrome that is the main cause of inherited clear-cell renal cell carcinoma (ccRCC), which generally occurs in the form of multiple recurrent synchronized tumors. Affected patients are carriers of a germline mutation in the VHL tumor suppressor gene. Somatic mutations of this gene are also found in sporadic ccRCC and numerous pan-genomic studies have reported a dysregulation of microRNA (miRNA) expression in these sporadic tumors. In order to investigate the molecular mechanisms underlying the pathogenesis of VHL-associated ccRCC, particularly in the context of multiple tumors, the present study characterized the mRNA and miRNA transcriptome through an integrative analysis compared with sporadic renal tumors. In the present study, two series of ccRCC samples were used. The first set consisted of several samples from different tumors occurring in the same patient, for two independent patients affected with VHL disease. The second set consisted of 12 VHL-associated tumors and 22 sporadic ccRCC tumors compared with a pool of normal renal tissue. For each sample series, an expression analysis of miRNAs and mRNAs was conducted using microarrays. The results indicated that multiple tumors within the kidney of a patient with VHL disease featured a similar pattern of miRNA and gene expression. In addition, the expression levels of miRNA were able to distinguish VHL-associated tumors from sporadic ccRCC, and it was identified that 103 miRNAs and 2,474 genes were differentially expressed in the ccRCC series compared with in normal renal tissue. The majority of dysregulated genes were implicated in 'immunity' and 'metabolism' pathways. Taken together, these results allow a better understanding of the occurrence of ccRCC in patients with VHL disease, by providing insights into dysregulated miRNA and mRNA. In the set of patients with VHL disease, there were few differences in miRNA and mRNA expression, thus indicating a similar molecular evolution of these synchronous tumors and suggesting that the same molecular mechanisms underlie the pathogenesis of these hereditary tumors.

Sivaskandarajah GA, Arnason TG
Unsuspected Von Hippel-Lindau syndrome in acute-onset resistant hypertension.
BMJ Case Rep. 2018; 2018 [PubMed] Related Publications
The discovery of adrenal lesions during routine testing for hypertension requires focused consideration for adrenal overproduction of cortisol, aldosterone or metanephrines. An otherwise healthy 25-year-old woman presented with headaches, diaphoresis and hot flushes with grossly elevated urine catecholamines, normetanephrines and norepinephrine levels, yet normal metanephrines, epinephrine/epinephrine, cortisol and aldosterone levels. Subsequent functional uptake studies and scans identified bilateral adrenal adenomas consistent with phaeochromocytomas. There was no family history of phaeochromocytomas or familial syndromes; however, a targeted genetic analysis for causes of familial phaeochromocytomas identified a heterozygous germline mutation in the

Yilmaz U
[CNS manifestations of neurocutaneous syndromes].
Radiologe. 2018; 58(7):664-667 [PubMed] Related Publications
CLINICAL/METHODICAL ISSUE: Phakomatoses refer to a heterogeneous and inconsistently defined group of neurocutaneous disorders. Tuberous sclerosis, neurofibromatosis types 1 and 2, Sturge-Weber syndrome and von Hippel-Lindau disease are entities with typical findings in neuroimaging studies STANDARD RADIOLOGICAL METHODS: These findings are usually easily depicted on magnetic resonance imaging (MRI) studies, thus, making diagnosis easier.

Yamashima M, Ozawa E, Ohnita K, et al.
Hepatobiliary and Pancreatic: Pancreatic mixed serous neuroendocrine neoplasm in von Hippel-Lindau disease.
J Gastroenterol Hepatol. 2018; 33(11):1821 [PubMed] Related Publications

Figlus M, Kaczorowska B, Jaskólski DJ, Kępczyński Ł
[Von Hippel-Lindau syndrome - a case report].
Pol Merkur Lekarski. 2018; 44(263):248-252 [PubMed] Related Publications
Von Hippel-Lindau disease (vHL, familial cerebello-retinal angiomatosis) is a rare genetic autosomal dominant disorder associated with predisposition to vascular tumors. Mutations of VHL tumor suppressor gene, located on chromosome 3p25-26, are responsible for clinical manifestation of the disease. The VHL gene product encodes VHL protein, which is responsible for HIF-1 (hypoxia-inducible factor-1) dependent cell cycle regulation and cellular pathways mediated by VEGF, PDGF, TGF-α, EPO. The mechanism substantiates the hypoxia dependent vascular tumor growth caused by loss of wild-type VHL protein. The clinical spectrum of vHL syndrome includes multiple tumors of various localization and low histologic grade, often bilateral. The most typical for the syndrome are: hemangioblastoma of central nervous system (typically posterior fossa or medulla), retinal hemangioblastoma, renal cell carcinoma and pheochromocytoma. The aim of the case report is to remind the typical clinical manifestation of von Hippel- Lindau syndrome, update the diagnostic criteria, recommended diagnostic and follow up methods.

Vikkath N, Ariyannur P, Menon KN, et al.
Exploring the role of defective fibronectin matrix assembly in the VHL-associated CNS hemangioblastoma.
Drug Metab Pers Ther. 2018; 33(3):127-134 [PubMed] Related Publications

Neumann HP, Young WF, Krauss T, et al.
65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma.
Endocr Relat Cancer. 2018; 25(8):T201-T219 [PubMed] Related Publications
Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic

O'Toole SM, Sahdev A, Bhattacharya S, et al.
Paediatric pancreatic neuroendocrine tumours in von Hippel-Lindau disease.
Endocr Relat Cancer. 2018; 25(9):L43-L47 [PubMed] Related Publications

Krauss T, Ferrara AM, Links TP, et al.
Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.
Endocr Relat Cancer. 2018; 25(9):783-793 [PubMed] Related Publications
Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm;

Miscia ME, Di Renzo D, Persico A, et al.
Unilateral Papillary Cystadenoma of the Epididymis as a First Presentation of Von Hippel-Lindau Disease.
Urology. 2018; 118:189-191 [PubMed] Related Publications
Association between papillary cystadenoma of the epididymis (PCE) and Von Hippel-Lindau Disease (VHLD) is well known and stronger for bilateral tumors. Unilateral PCE occurs either as a sporadic tumor without evidence of VHLD or in the context of a known diagnosis of VHLD, indeed it has never been reported as the first manifestation of VHLD. In contrast, we report the case of a boy with an apparently isolated, unilateral PCE that resulted to be the first manifestation of an unknown VHLD. Thus, we recommend screening for VHLD in patients with a new diagnosis of unilateral PCE, especially if the patients are young.

Wang Y, Chen D, Chen M, et al.
A Comprehensive Procedure to Evaluate the In Vitro Performance of the Putative Hemangioblastoma Neovascularization Using the Spheroid Sprouting Assay.
J Vis Exp. 2018; (134) [PubMed] Article available free on PMC after 12/04/2020 Related Publications
The inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene plays a crucial role in the development of hemangioblastomas (HBs) within the human central nervous system (CNS). However, both the cytological origin and the evolutionary process of HBs (including neovascularization) remain controversial, and anti-angiogenesis for VHL-HBs, based on classic HB angiogenesis, have produced disappointing results in clinical trials. One major obstacle to the successful clinical translation of anti-vascular treatment is the lack of a thorough understanding of neovascularization in this vascular tumor. In this article, we present a comprehensive procedure to evaluate in vitro whether classic tumor angiogenesis exists in HBs, as well as its role in HBs. With this procedure, researchers can accurately understand the complexity of HB neovascularization and identify the function of this common form of angiogenesis in HBs. These protocols can be used to evaluate the most promising anti-vascular therapy for tumors, which has high translational potential either for tumors treatment or for aiding in the optimization of the anti-angiogenic treatment for HBs in future translations. The results highlight the complexity of HB neovascularization and suggest that this common form angiogenesis is only a complementary mechanism in HB neovascularization.

Holmen IC, Oakey Z, Altaweel MM
Von Hippel-Lindau Incidentally Diagnosed in Evaluation of Sporadic Aniridia.
Ophthalmology. 2018; 125(5):663 [PubMed] Related Publications

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. von Hippel-Lindau disease, Cancer Genetics Web: http://www.cancer-genetics.org/von_hippel_lindau.html Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 29 August, 2019     Cancer Genetics Web, Established 1999