A GENETIC REGISTER FOR VONHIPPEL-LINDAU DISEASE

A genetic register for von Hippel-Lindau disease was set up in the nor th west of England in 1990. Population statistics, clinical features, age at onset, and survival of 83 people affected with von Hippel-Linda u (VHL) disease were studied. In addition, the effectiveness of the sc reening programme used and the occurrence of central nervous system ha emangioblastomas in the general population were examined. The diagnost ic point prevalence of heterozygotes in the North Western Region was 1 .18/100 000 (1/85 000) people, with an estimated birth incidence of 2. 20/100 000 (1/45 500) Live births. The mutation rate was estimated dir ectly to be 1.4 x 10(-6)/gene/generation (1/714 200). The mean age at onset of first symptoms was 26.25 years, with cerebellar haemangioblas toma being the most common presenting manifestation (34.9% of cases). The mean age at diagnosis of VHL disease was 30.87 years. Overall, 50 patients (60.2%) developed a cerebellar haemangioblastoma, 34 (41.0%) a retinal angioma, 21 (25.3%) a renal cell carcinoma, 12 (14.5%) a spi nal haemangioblastoma, and 12 (14.5%) a phaeochromocytoma. Mean age at diagnosis of renal cell carcinoma (38.9 years) was significantly high er than that for cerebellar haemangioblastoma (30.0 years) and retinal angioma (21.1 years). Mean age at death was 40.9 years with cerebella r haemangioblastoma being the most common cause (47.7% of deaths). A t otal of 65 VHL manifestations were diagnosed asymptomatically followin g appropriate clinical and radiological screening tests, and failure t o detect manifestations of VHL disease in spite of appropriate screeni ng occurred on only two occasions. The use of DNA linkage analysis and direct mutation testing reduced the personal risk of carrying the VHL gene to below 1% in 14 people. In addition to the 83 clinically affec ted subjects, three obligate carriers who were considered to be lesion fi ee in spite of extensive screening tests were identified. Fourteen percent of all CNS haemangioblastomas on the regionally based Cancer Registry were found to occur as part of VHL disease, but investigation s for VHL in apparently sporadic disease appeared to be limited.