TY - JOUR

T1 - Prevalence, birth incidence, and penetrance of von Hippel-Lindau disease (vHL) in Denmark

AU - Binderup, Marie Louise Mølgaard

AU - Galanakis, Michael Carter Bisgaard

AU - Budtz-Jørgensen, Esben

AU - Kosteljanetz, Michael

AU - Luise Bisgaard, Marie

PY - 2017

Y1 - 2017

N2 - Von Hippel-Lindau disease (vHL) is a rare hereditary tumour predisposition with multiorgan involvement that is not always easily recognized. The disease is reported to be almost fully penetrant at age 60 years. Previous estimates of vHL prevalence and incidence are all regional and vary widely. Most are >20 years old and prone to selection bias because of inclusion of only clinically affected vHL patients who were diagnosed before genetic testing was available. In an unselected cohort of all known Danish carriers of a disease-causing VHL variant, we assessed vHL penetrance on a national basis. We further used national health registers to identify individuals who fulfilled the clinical diagnostic vHL criteria based on their registered diagnostic codes, but had not been diagnosed with vHL. We also assessed the medical histories of first-degree relatives to identify familial cases. This study gives the first national estimates of vHL prevalence (1 in 46 900 individuals) and birth incidence (1 in 27 300 live births). vHL has been underdiagnosed in Denmark, and as many as 25% of the overall vHL cohort (diagnosed+undiagnosed patients) have a missed diagnosis in spite of fulfilling the international diagnostic criteria. We found an overall penetrance of 87% at age 60 years. When considering only vHL patients who have not attended surveillance, 20% will still be asymptomatic at age 60 years. This should be considered in the context of genetic counselling, especially when assessing the risk of vHL in asymptomatic adult first-degree relatives who are often not genetically tested.European Journal of Human Genetics advance online publication, 14 December 2016; doi:10.1038/ejhg.2016.173.

AB - Von Hippel-Lindau disease (vHL) is a rare hereditary tumour predisposition with multiorgan involvement that is not always easily recognized. The disease is reported to be almost fully penetrant at age 60 years. Previous estimates of vHL prevalence and incidence are all regional and vary widely. Most are >20 years old and prone to selection bias because of inclusion of only clinically affected vHL patients who were diagnosed before genetic testing was available. In an unselected cohort of all known Danish carriers of a disease-causing VHL variant, we assessed vHL penetrance on a national basis. We further used national health registers to identify individuals who fulfilled the clinical diagnostic vHL criteria based on their registered diagnostic codes, but had not been diagnosed with vHL. We also assessed the medical histories of first-degree relatives to identify familial cases. This study gives the first national estimates of vHL prevalence (1 in 46 900 individuals) and birth incidence (1 in 27 300 live births). vHL has been underdiagnosed in Denmark, and as many as 25% of the overall vHL cohort (diagnosed+undiagnosed patients) have a missed diagnosis in spite of fulfilling the international diagnostic criteria. We found an overall penetrance of 87% at age 60 years. When considering only vHL patients who have not attended surveillance, 20% will still be asymptomatic at age 60 years. This should be considered in the context of genetic counselling, especially when assessing the risk of vHL in asymptomatic adult first-degree relatives who are often not genetically tested.European Journal of Human Genetics advance online publication, 14 December 2016; doi:10.1038/ejhg.2016.173.

U2 - 10.1038/ejhg.2016.173

DO - 10.1038/ejhg.2016.173

M3 - Journal article

C2 - 27966541

VL - 25

SP - 301

EP - 307

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 3

ER -