TY - JOUR

T1 - von Hippel-Lindau disease

T2 - Updated guideline for diagnosis and surveillance

AU - Louise M Binderup, Marie

AU - Smerdel, Maja

AU - Borgwadt, Line

AU - Beck Nielsen, Signe Sparre

AU - Madsen, Mia Gebauer

AU - Møller, Hans Ulrik

AU - Kiilgaard, Jens Folke

AU - Friis-Hansen, Lennart

AU - Harbud, Vibeke

AU - Cortnum, Søren

AU - Owen, Hanne

AU - Gimsing, Steen

AU - Friis Juhl, Henning Anker

AU - Munthe, Sune

AU - Geilswijk, Marianne

AU - Rasmussen, Åse Krogh

AU - Møldrup, Ulla

AU - Graumann, Ole

AU - Donskov, Frede

AU - Grønbæk, Henning

AU - Stausbøl-Grøn, Brian

AU - Schaffalitzky de Muckadell, Ove

AU - Knigge, Ulrich

AU - Dam, Gitte

AU - Wadt, Karin AW

AU - Bøgeskov, Lars

AU - Bagi, Per

AU - Lund, Lars

AU - Stochholm, Kirstine

AU - Ousager, Lilian Bomme

AU - Sunde, Lone

N1 - Funding Information: This work was not financially supported by external sources. Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families. This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations. Recommendations: vHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.

AB - von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families. This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations. Recommendations: vHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.

KW - Guideline

KW - Hemangioblastoma

KW - Pheochromocytoma

KW - Renal cell carcinoma

KW - Surveillance

KW - von Hippel-Lindau disease

U2 - 10.1016/j.ejmg.2022.104538

DO - 10.1016/j.ejmg.2022.104538

M3 - Journal article

C2 - 35709961

AN - SCOPUS:85132511144

VL - 65

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

SN - 1769-7212

IS - 8

M1 - 104538

ER -