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Eur J Hum Genet. 2017 Feb;25(3):301-307. doi: 10.1038/ejhg.2016.173. Epub 2016 Dec 14.

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

Author information

1
Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
2
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
3
Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark.

Abstract

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.

PMID:
27966541
PMCID:
PMC5315510
DOI:
10.1038/ejhg.2016.173
[Indexed for MEDLINE]
Free PMC Article

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