Risk of new tumors in von Hippel–Lindau patients depends on age and genotype

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

doi:10.1038/gim.2015.44

Cited by 21 publications

(18 citation statements)

References 34 publications

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“…The differences in surveillance benefit according to genotype is most likely due to surveillance-facilitated decreased RCC mortality in truncating mutation carriers, who are known to have a higher RCC risk compared with missense mutation carriers 30–32. Further, truncating mutation carriers have more CNS tumours and develop new tumours at higher rates than missense mutation carriers 8 14. Our failure to demonstrate a surveillance effect for missense mutation carriers' survival could in part be because many patients did not initiate surveillance before adulthood.…”

Section: Discussionmentioning

confidence: 79%

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

et al. 2016

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Section: Discussionmentioning

confidence: 79%

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

et al. 2016

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“…The VHL mutations were evaluated using the in silico programme Alamut Visual version 2.6 (Interactive Biosoftware, Rouen, France), and categorized as either truncating (i.e., mutations that produce a truncated protein) or missense mutations. Parts of the Danish cohort have previously been described in (Binderup et al, ; Binderup, Galanakis, et al, ; Binderup, Jensen, et al, ; Poulsen et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Some tumors, such as RCC and CNS hemangioblastomas, are typically not removed until they have reached a certain size or have become symptomatic, while retinal hemangioblastomas are mostly removed at diagnosis (Ammerman, Lonser, Dambrosia, Butman, & Oldfield, ; Toy, Agron, Nigam, Chew, & Wong, ). Some reports of vHL patients have described that most VHL mutation‐carriers are not clinically affected until their twenties (Aufforth et al, ; Binderup et al, ; Binderup, Budtz‐Jorgensen, & Bisgaard, ). But the phenotype is variable and the extent of vHL affection in childhood and adolescence is unclear as very few have studied this matter.…”

Section: Introductionmentioning

confidence: 99%

von Hippel‐Lindau development in children and adolescents

Launbjerg

Bache

Galanakis

et al. 2017

American J of Med Genetics Pt A

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The autosomal dominant von Hippel-Lindau disease (vHL) is associated with a lifelong risk of tumor development, especially retinal and CNS hemangioblastomas, pheochromocytoma, and renal cell carcinoma. Knowledge of paediatric vHL development is limited, and current surveillance guidelines are based on expert opinions. We aimed to describe the course of vHL development in children and adolescents, focusing on age at first manifestation, manifestation frequencies, and types. The prevalence of vHL diagnosis as well as manifestations in childhood were evaluated based on 99 patients, who had started surveillance before 18 years: 37 Danish patients from the national vHL research database and 62 international patients reported in 15 articles. Overall, 70% (69 of 99) developed manifestations before 18 years (median age at first manifestation: 12 years (range: 6-17 years)). Thirty per cent (30 of 99) had developed more than one manifestation type; the most frequent were retinal (34%) and CNS (30%) hemangioblastomas. Among the 37 Danish patients, 85% (97 of 116) of their tumors were asymptomatic. Vision outcome is significantly improved in hemangioblastomas that are treated while still asymptomatic. We agree with current guidelines that retinal surveillance be performed from birth. The patients had their first CNS hemangioblastomas at the median ages of 13-14 years (range: 6-17 years). Further, 11% (4 of 37) of the Danish patients had CNS surgery in their teenage years. Although the cohort is too small to make definite conclusions about specific initiation ages, regular CNS surveillance from vHL patients' teenage years seems clinically relevant.

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“…The risk for RCC and hemangioblastoma in affected individuals may reflect the ability of the variant protein to regulate the hypoxia-inducible factor (HIF) pathway (19,20). Higher HIF expression appears to result in lower risk of RCC and hemangioblastoma.…”

Section: Molecular Genetics Of Vhlmentioning

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

224

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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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Risk of new tumors in von Hippel–Lindau patients depends on age and genotype

Cited by 21 publications

References 34 publications

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

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

von Hippel‐Lindau development in children and adolescents

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

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