Von Hippel–Lindau disease

Chittiboina, Prashant; Lonser, Russell R.

doi:10.1016/b978-0-444-62702-5.00010-x

Cited by 158 publications

(212 citation statements)

References 150 publications

(284 reference statements)

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“…Individuals were identified as patients with VHL disease if they carried a germline VHL gene mutation (n=244) or fulfilled the clinical criteria (n=131) 10. All the 131 patients diagnosed with clinical symptoms had at least one affected relative identified by VHL mutation test, so that their genotype could be predicted.…”

Section: Methodsmentioning

confidence: 99%

Risk factors for survival in patients with von Hippel-Lindau disease

Wang

Peng

et al. 2018

J Med Genet

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Section: Methodsmentioning

confidence: 99%

Risk factors for survival in patients with von Hippel-Lindau disease

Wang

Peng

et al. 2018

J Med Genet

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“…Up to 80% of patients with VHL develop central nervous system (CNS) hemangioblastomas (HBs) in the infratentorial regions, including the cerebellum and spinal cord, due to somatic ‘second hits’ at the VHL locus34. Approximately half of the VHL associated HBs (VHL-HBs) will grow over time and lead to mass effect-related neurological symptoms5.…”

mentioning

confidence: 99%

Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target

Sizdahkhani

Feldman

Piazza

et al. 2017

Sci Rep

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Von Hippel-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the central nervous system (CNS), and are a leading cause of morbidity and mortality in VHL disease. Currently, surgical resection is the most effective way to manage symptomatic VHL-HBs. Surgically unresectable VHLHBs or those in frail patients are challenging problems. Therapies targeting oncologic and vascular endothelial growth factor (VEGF) pathways have failed to demonstrate tumor control. Our experience and previous reports on VHL-HB avidity to somatostatin analogues suggested somatostatin receptor (SSTR) expression in VHL-HBs, offering an alternative therapeutic strategy. We explored this possibility by demonstrating consistent histologic expression of SSTR1, 2a, 4, and 5 in VHL-HBs. We found that somatostatin analogue octreotide induces apoptosis in VHL-HB stromal cells in a dose-dependent fashion by BAX -caspase-3 pathway unrelated to canonical VHL pathway. When administered to a patient with unresectable symptomatic suprasellar hemangioblastoma, octreotide resulted in tumor volume reduction, symptom stabilization, and tumor cytopenia on repeat 68 Ga-DOTA-TATE positron emission tomography (PET) within 6 months, suggesting tumor infarction. We conclude that VHL-HBs harbor multiple SSTR subtypes that offer actionable chemo-therapeutic strategy for management of symptomatic, unresectable tumors by somatostatin analogue therapy.Von Hippel-Lindau disease (VHL) is an autosomal-dominant tumor disorder affecting 1 in 36,000 live births 1 due to mutations in the tumor suppressor VHL gene 2 . Up to 80% of patients with VHL develop central nervous system (CNS) hemangioblastomas (HBs) in the infratentorial regions, including the cerebellum and spinal cord, due to somatic 'second hits' at the VHL locus 3,4 . Approximately half of the VHL associated HBs (VHL-HBs) will grow over time and lead to mass effect-related neurological symptoms 5 . Surgical resection of symptomatic VHL-HBs remains the standard-of-care, but even with optimal management VHL-HBs remain a leading cause of death in VHL patients 3,4 . In some cases, surgical resection of symptomatic VHL-HBs is not an option due to unresectable locations or due to extensive co-morbidities. Development of chemotherapy and anti-angiogenic therapy for such patients remains underdeveloped due to the indolent nature of VHL disease [6][7][8][9][10] . Due to relatively long life expectancy of VHL patients 11 , treatment with toxic chemotherapeutic agents is not feasible for extended periods of time. Alternative strategies for long term management of unresectable VHL-HBs may arise from observations that VHL-HBs originate from hematopoietic precursors 12,13 , and that hematopoietic stem cells are known to express somatostatin receptors 14 . Our experience with DOTA-TATE positron emission tomography (PET) imaging of VHL patients confirms previous reports of VHL-HB avidity to somatostatin analogues (Fig. 1A-D) [15][16][17] . However, the therapeutic

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“…Von Hippel-Lindau disease (vHL; OMIM #193300) is a multisystemic tumor predisposition syndrome characterized by benign and malignant tumors, including central nervous system (CNS) and retinal hemangioblastomas, clear cell renal cell carcinoma (RCC), pheochromocytoma (PHEO), pancreatic neuroendocrine tumors (pancreatic NET), endolymphatic sac tumor (ELST), and epididymal and broad ligament cystadenoma, as well as visceral (renal and pancreatic) cysts (1). Originally described in 1936 in the context of familial retinal angiomatosis by von Hippel (2) and CNS hemangioblastomas by Lindau (3), the incidence of vHL is estimated at approximately one in 36,000 (based on data preceding the advent of molecular genetic testing), and the lifetime penetrance approaches 100% by age 75 (4).…”

Section: Introductionmentioning

confidence: 99%

Von Hippel–Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood

Rednam

Erez

Druker

et al. 2017

Clinical Cancer Research

214

157

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Von Hippel-Lindau disease (vHL) is a hereditary tumor predisposition syndrome that places affected individuals at risk for multiple tumors, which are predominantly benign and generally occur in the central nervous system or abdomen. Although the majority of tumors occur in adults, children and adolescents with the condition develop a significant proportion of vHL manifestations and are vulnerable to delayed tumor detection and their sequelae. Although multiple tumor screening paradigms are currently being utilized for patients with vHL, surveillance should be reassessed as the available relevant clinical information continues to expand. We propose a new vHL screening paradigm similar to existing approaches, with important modifications for some tumor types, placing an emphasis on risks in childhood. This includes advancement in the timing of surveillance initiation and increased frequency of screening evaluations. Another neuroendocrine-related familial condition is the rapidly expanding hereditary paraganglioma and pheochromocytoma syndrome (HPP). The tumor spectrum for patients with HPP syndrome includes paragangliomas, pheochromocytomas, renal cancer, and gastrointestinal stromal tumors. The majority of patients with HPP syndrome harbor an underlying variant in one of the SHDx genes (SDHA, SDHB, SDHC, SDHD, SDHA, and SDHAF2), although other genes also have been described (MAX and TMEM127). Annual screening for elevated plasma or urine markers along with complete blood count and biennial whole-body MRI accompanied by focal neck MRI is recommended for older children and adults with HPP syndrome to detect tumors early and to decrease morbidity and mortality from HPP-related tumors.

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Von Hippel–Lindau disease

Cited by 158 publications

References 150 publications

Risk factors for survival in patients with von Hippel-Lindau disease

Risk factors for survival in patients with von Hippel-Lindau disease

Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target

Von Hippel–Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood

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