The VHL disease gene maps to chromosome 3p25 and was isolated in 1993 (Latif et al. 1993). Germline mutations may be detected in ≥95 % of patients, and genotype-phenotype correlations have been described such that large deletions and protein-truncating mutations are associated with a low risk of pheochromocytoma, and specific missense mutations may produce a high risk of pheochromocytoma (type 2 families). Families with a high frequency of pheochromocytoma (types 2A, 2B, and 2C) usually have a surface missense mutation, whereas type 1 families have mostly germline deletions or truncating mutations. Regular screening of patients affected by VHL disease and of at-risk relatives is important to detect Tumours at an early stage and to establish the carrier status for at-risk individuals.
Molecular genetic analysis enables the screening protocols to be modified according to an individual’s risk so that screening frequency may be reduced or discontinued as appropriate.
Fig. 1 VHL disease: (a) moderate-sized retinal angioma and (b) fluorescein angiogram of the same lesion (Reproduced with permission from Cambridge University Press)