Molecular genetic aspects of Von Hippel-Lindau (VHL) disease and criteria for DNA analysis in subjects at risk

Von Hippel-Lindau (VHL) disease is an autosomal, dominantly inherited tumou r syndrome. Carriers of a germline mutation in the VHL tumour suppressor ge ne tumours are predisposed to develop tumours that are multicentric or bila teral, and manifest at a younger age than in situations without a VHL germl ine mutation. The mutation spectrum is heterogeneous, with mutations scatte red throughout most of the VHL gene. Although some recurrent mutations have been reported, most families have their own unique germline mutation. Test ed individuals are no longer uncertain regarding their risk for developing the disease and family members who are non-carriers are relieved of the bur den of repeated clinical monitoring. VHL germline mutations are identified in virtually all families and sporadic patients with classic VHL disease, b ut also in patients who do not meet clinical diagnostic criteria. The chanc e of finding a VHL germline mutation in (apparently) sporadic patients not fulfilling the criteria increases with: young age at diagnosis, the presenc e of multi-centric or bilateral tumours, involvement of multiple organs and a positive family history of VHL associated tumours. (C) 2001 Elsevier Sci ence B.V. All rights reserved.