Survival and causes of death in patients with von Hippel-Lindau disease

Binderup, Marie Louise Mølgaard; Jensen, Annette Møller; Budtz‐Jørgensen, Esben; Bisgaard, Marie Luise

doi:10.1136/jmedgenet-2016-104058

Cited by 86 publications

(80 citation statements)

References 30 publications

(52 reference statements)

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“…Recently, in line with our results, a national study in Denmark (n=143) showed that the life expectancy improved to 67 years for men and 60 years for women. And they demonstrated that VHL survival was highly dependent on a person’s birth year; the younger the patient is, the longer is the survival 21. In contrast, our study showed that birth year was not an independent risk factor for overall survival (HR 0.99, 95% CI 0.97 to 1.02, P=0.565).…”

Section: Discussioncontrasting

confidence: 73%

“…However, Binderup and his team found that female patients had a mortality hazard that were twice as high as male patients, and the effect was more evident for missense mutation carriers (HR 4.75, P=0.004). They attributed the result to hormonal effects on tumorigenesis, but the mechanisms were not clear 21. The inconsistency between the two cohorts is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Genotype has been confirmed to be related to the risk of tumours in specific sites, but its effect on patients’ survival is yet unclear. Previous studies reported that VHL survival had improved in patients born in later years, and surveillance attendance reduced death rates in truncating mutation carriers 21. However, the influences of other factors such as sex, onset age, family history, birth order and first presenting symptom on overall and VHL-related survival have not been evaluated or verified until now.…”

Section: Introductionmentioning

confidence: 98%

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

Wang

Peng

et al. 2018

J Med Genet

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Section: Discussioncontrasting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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

Wang

Peng

et al. 2018

J Med Genet

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“…Lifelong surveillance is, therefore, mandated given ongoing risks for tumor development and malignant growth with increasing age, and evidence that longitudinal surveillance in vHL limits morbidity and mortality (14)(15)(16). Multiple groups have developed surveillance guidelines (Table 3).…”

Section: Cancer Screening/surveillance Protocolsmentioning

confidence: 99%

“…Historically, substantial mortality was attributable to RCC, pancreatic NET, and CNS hemangioblastoma (11). Fortunately, these risks have been mitigated in recent years by the institution of comprehensive surveillance paradigms, leading to early recognition of tumors and their multidisciplinary management (14)(15)(16).…”

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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Review of the Neurological Implications of von Hippel–Lindau Disease

et al. 2018

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on Hippel-Lindau (VHL) disease is an autosomal dominant neoplasia syndrome caused by a germline mutation of the VHL tumor suppressor gene (NC_000003.12) located on the short arm of chromosome 3. [1][2][3] This disease carries a prevalence of 1 in 36 000 births 4 and is highly penetrant (>90% penetrance by age 65 years). 3 Patients with VHL disease can develop lesions of the viscera and central nervous system (CNS). Visceral lesions include renal cell carcinomas or cysts, pheochromocytomas, pancreatic neuroendocrine tumors or cysts, and benign cystadenomas of the adnexal organs. The CNS-associated lesions include hemangioblastomas of the retina and craniospinal axis as well as endolymphatic sac tumors (ELSTs). [4][5][6] The most frequent cause of VHL diseaseassociated morbidity and mortality is craniospinal hemangioblastoma development and progression. 7 IMPORTANCE von Hippel-Lindau (VHL) disease-associated central nervous system (CNS) lesions include hemangioblastomas and endolymphatic sac tumors (ELSTs), which are associated with significant neurological morbidity and mortality. Recent studies provide critical new biological, diagnostic, and management insights into these tumors.OBSERVATIONS Biological features, natural history, clinical findings, and management strategies of VHL disease-associated CNS tumors are reviewed. The VHL disease results from a germline mutation of the VHL gene (located on the short arm of chromosome 3), a tumor suppressor that encodes for the VHL protein. Whereas VHL disease is associated with visceral manifestations, CNS lesions are the most common source of morbidity and mortality. Craniospinal hemangioblastomas are almost entirely (99%) found in the cerebellum, brainstem, and spinal cord. These tumors arise from multipotent hemangioblasts. Peritumoral cysts frequently underlie the clinical findings associated with hemangioblastomas (>90% of symptomatic tumors). Prospective natural history studies demonstrate that CNS hemangioblastomas typically grow in a saltatory pattern. Due to this unpredictable growth pattern, surgical resection is reserved for symptomatic lesions, as many tumors do not become symptomatic. Recent studies indicate that VHL disease-associated ELSTs cause audiovestibular morbidity (hearing loss, tinnitus, and vertigo) via 3 mechanisms-otic capsule invasion, intralabyrinthine hemorrhage, and endolymphatic hydrops. Specialized magnetic resonance imaging techniques have been defined to elucidate each of these mechanisms, even when a tumor mass is not identified on imaging. Endolymphatic sac tumors cause audiovestibular morbidity unrelated to size or progression, and resection is now recommended at initial discovery of a tumor mass or a tumor-associated mechanism of morbidity.CONCLUSIONS AND RELEVANCE New insights into the development, pathobiological origin, natural history, and long-term outcomes of VHL disease-associated CNS tumors have redefined their management and treatment indications and potentially provide new targeted therapeutic strategies. Resection is rese...

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Survival and causes of death in patients with von Hippel-Lindau disease

Cited by 86 publications

References 30 publications

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

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

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

Review of the Neurological Implications of von Hippel–Lindau Disease

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