Von Hippel-Lindau (VHL) disease is an autosomal, dominant inherited tumour syndrome. The disease is named after the German ophthalmologist Eugen von Hippel, who described retinal haemangioblastoma in 1904, and the Swedish pathologist Arvid Lindau who associated retinal and CNS haemangioblastoma with cysts of the kidneys, pancreas and epididymis in 1926. The estimated prevalence of the disease varies between 1:31,000 and 1:53,000 persons. Objectives The main objective of this thesis is to identify patients and families with VHL disease by molecular genetic analysis. Presymptomatic DNA analysis and identification of carriers of VHL germline mutations in families then permits tumour development to be followed from a relative early age, and optimises the time at which treatment is carried out. In addition, we collected clinical and genetic data to identify possible genotype-phenotype correlations and aimed to formulate national guidelines for diagnosis and periodic monitoring of VHL patients. Results and conclusions In order to prevent both patient and doctor delay in the diagnosis of VHL disease, persons at risk for the disease as well as doctors should be provided with clear oral and written information about the clinical and genetic aspects of the disease. In addition, an intercentre co-operation should be established between the medical specialists involved to prevent unnecessary morbidity and mortality in VHL patients. Multidisciplinary teams following national and international guidelines should guarantee the best results in the management of VHL patients. We demonstrate genotype-phenotype correlations for some tumours In VHL disease, but there appears to be no simple relationship between a germline mutation in the VHL gene and the manifestation of VHL-related tumours. For example, there is intrafamilial variability in the age of onset and the manifestation of different types of VHL-related tumours. Furthermore, we provide evidence non-penetrance of certain VHL germline mutations. We estimate that the ...