Von Hippel-Lindau disease: a genetic study.

Maher, Eamonn R.; Iselius, L; Yates, John R.; Littler, M; Benjamin, Caroline; Harris, Rodney; Sampson, Julian R.; Williams, A. Prysor; Ferguson‐Smith, M. A.; Morton, N. E.

doi:10.1136/jmg.28.7.443

Cited by 504 publications

(277 citation statements)

References 19 publications

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“…The patients referred had been evaluated systemically in a single center and almost all patients (98.1%) clinically diagnosed with VHL disease could also be assigned a germline mutation responsible for VHL disease 7 . The comprehensive clinical diagnosis of VHL disease, supported by genotype analysis excludes with certainty patients with sporadic RCHs unrelated to VHL.…”

Section: Discussionmentioning

confidence: 99%

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Clinical Characterization of Retinal Capillary Hemangioblastomas in a Large Population of Patients with von Hippel–Lindau Disease

et al. 2008

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Objective-To report the epidemiology and ocular phenotype of retinal capillary hemangioblastomas associated with von Hippel-Lindau (VHL) disease in a large cohort of patients and to correlate patient and ocular characteristics to visual morbidity in this population. Design-Prospective consecutive case series.Participants-In 220 unrelated pedigrees, 335 patients affected with VHL disease and retinal capillary hemangioblastomas (RCHs) in at least 1 eye.Methods-Demographics of the patient population were recorded and the ocular phenotype of each patient was obtained with a comprehensive ocular examination.Main Outcome Measures-The patient population was characterized and the ocular phenotype described in relationship to tumor location, number, and extent of retinal involvement. Correlations between patient demographics, ocular phenotype, and visual function were analyzed.Results-RCHs were detected unilaterally in 42.1% and bilaterally in 57.9% of patients. No correlation was detected between the age, gender, and laterality of involvement. Eighty-seven (86.6%) percent of involved eyes had tumors that could be individually visualized; of these, tumors were commonly found in the peripheral retina (84.7%) only, and less commonly in the juxtapapillary area (15.3%). The tumor count in the periphery averaged 2.5±1.8 per eye, with 25.2% of eyes having greater than 1 quadrant of retinal involvement. Thirteen (13.4%) percent of involved eyes were enucleated or pre-phthsical; approximately 1 in 5 patients had one or more eyes so affected. Severe visual impairment (visual acuity worse or equal to 20/160) in affected eyes were more likely to be associated with increasing age, the presence of juxtapapillary lesions, and an increasing number and extent of peripheral lesions.Conclusions-This large cohort of VHL patients with RCHs has enabled a systematic and quantitative characterization of the demographics, ocular features, and visual function in VHL disease. Clinical correlations between the visual morbidity and ocular features of the disease were also performed, producing measures that can help clinicians better estimate visual prognoses based on the ocular phenotype of the disease. RCHs in VHL disease are benign tumors that have a characteristic orange-red color, a globular shape, and typically dilated feeding and draining vessels. Histologically, they are comprised of capillary-like vascular channels surrounded by large vacuolated stromal cells, and also smaller "tumorlet" cells that express stem cell markers 3 . RCHs can be highly variable in their number, size, and location. Although often slow-growing in nature and benign in their effect, they can sometimes result in vision loss and structural disruption to the integrity of the globe through exudative and tractional effects on the retina 4 .The diagnosis of VHL disease is often performed clinically, using criteria involving a family history of the disease and the detection and characteristic tumors in various organ systems 5 . Genetic testing for VHL disease is now...

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Section: Discussionmentioning

confidence: 99%

“…Genetic testing for VHL disease is now available and mutations in the VHL gene can be detected and characterized at a very high rate 6 . Owing to the high penetrance of the disease, almost all patients testing positive genetically will develop clinically definite disease with time 7 .…”

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confidence: 99%

Clinical Characterization of Retinal Capillary Hemangioblastomas in a Large Population of Patients with von Hippel–Lindau Disease

et al. 2008

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“…9,10 Prior to the advent of molecular genetic testing VHL disease was estimated to have an incidence of 1/36 000 live births in Eastern England and prevalences of 1/39 000 in South-West Germany and 1/53 000 in Eastern England. 11,12 VHL disease is suggested to account for approximately a third of patients with a CNS haemangioblastoma, 450% of patients with a retinal angioma, 1% of patients with RCC, 50% of patients with apparently isolated familial phaeochromocytoma and 11% of patients with an apparently sporadic phaeochromocytoma 5,8,13 (and unpub- Haemangioblastomas with an associated cyst tend to become symptomatic sooner. 16 Microscopically, haemangioblastomas consist of large polygonal stromal cells enmeshed in a capillary network and stromal cells arise from mesoderm-derived embryologically arrested haemangioblasts.…”

Section: Introductionmentioning

confidence: 99%

von Hippel–Lindau disease: A clinical and scientific review

Neumann²,

2011

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“…Clinical von Hippel-Lindau (VHL) disease (MIM] 193300) is an autosomal dominant disorder affecting 1 in 36,000 individuals worldwide, with similar prevalence in both genders and across all ethnic backgrounds [Maher et al, 1991;Maher, 2004]. The onset of VHL disease occurs at a mean age of 26 years [Maher et al, 1990b].…”

Section: Introductionmentioning

confidence: 99%

“…VHL patients have a 70% risk of developing RCC by 60 years old [Maher et al, 1990b[Maher et al, , 1991Whaley et al, 1994], at an average age of 44 years versus the average age of 62 years, at which sporadic RCC develops in the general population (http:// www.umd.be/VHL/W_VHL/clinic.shtml). Renal cysts are common in VHL patients as well; however, unlike the completely benign cysts in the general population, renal cysts in VHL patients might degenerate into RCC [Kaelin, 2004].…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of von Hippel-Lindau disease

et al. 2010

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Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types as well. Reports of VHL mutations are dispersed throughout original articles and databases that have not been recently updated. We compiled a comprehensive mutation table of 1,548 germline and somatic VHL mutations, derived from this protein of only 213 amino acids. We describe detailed phenotype and gene mutation information for 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). These data represent the most extensive catalog of germline VHL mutations to date. We also review VHL disease, known and theorized pathogenesis of common VHL manifestations, and genotype-phenotype correlations. Analysis of all VHL families, excluding germline mutations resulting in congenital polycythemias, describes the spectrum of mutation types: 52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11% large/complete deletions, and 7% splice mutations. This easy-to-use compilation of VHL mutations is intended to facilitate research and function as a necessary adjunct for physicians when providing patient information. Hum Mutat 31:521-537,

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Von Hippel-Lindau disease: a genetic study.

Cited by 504 publications

References 19 publications

Clinical Characterization of Retinal Capillary Hemangioblastomas in a Large Population of Patients with von Hippel–Lindau Disease

Clinical Characterization of Retinal Capillary Hemangioblastomas in a Large Population of Patients with von Hippel–Lindau Disease

von Hippel–Lindau disease: A clinical and scientific review

Genetic analysis of von Hippel-Lindau disease

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