Risk of multisystem disease in isolated ocular angioma (haemangioblastoma)

Risk of multisystem disease in isolated ocular angioma (haemangioblastoma) EDITOR—Ocular angioma (haemangioblastoma) is the most common presenting feature of the multisystem famil-ial cancer syndrome von Hippel-Lindau disease (VHL). 1 Recognition of VHL is important because of the opportunity to reduce morbidity and mortality by early diagnosis of renal cell carcinoma, phaeochromocytoma, and cerebellar, spinal, and ocular haemangioblastomas. Although the finding of typical and multiple ocular lesions indicates VHL, the risk of multisystem disease in those presenting with a single ocular lesion has not been determined. That such risk exists is shown by the presence of patients with solitary angiomas in families with VHL, and the identification of mutations in the VHL gene in aVected subjects without a family history of disease owing to non-penetrance for VHL manifestations in relatives and a significant new mutation rate. Consequently, the management of patients with a solitary ocular lesion may be inappropriate, such that patients with VHL may be falsely reassured, and others without symptoms may be subjected to unnecessary surveillance. On the basis of previous estimates, we have used a Baysian approach to calculate approximate risks for VHL disease in a patient presenting with a single ocular angioma in the context of other clinical and molecular information available. The proportion of VHL patients who have a solitary ocular angioma after ophthalmic examination has been calculated in previous work on a cohort of VHL gene carriers, 2 and this proportion, like all the following proportions , can be used as an estimate of a corresponding conditional probability. However, calculation of the reverse conditional probability, that is, the probability of VHL given a diagnosis of solitary ocular angioma, requires the use of Bayes' theorem, as shown below: Here Pr(VHL) s) represents the probability of VHL disease in a patient presenting with a single ocular angioma. Pr(s * VHL) represents the probability of a solitary angioma given a diagnosis of VHL disease, which has been estimated in a recent survey of VHL gene carriers 2 as 0.20. Pr(VHL) represents the population prevalence of VHL disease, which is taken as 18.9 × 10-6. 3 Pr(s * VHL) represents the prevalence of patients who harbour a solitary ocular lesion, but who do not have underlying VHL disease. The existence of non-VHL ocular angioma has been confirmed recently in a British population using a joint molecular genetic and clinical approach, and its prevalence estimated as 9.0 × 10-6. 4 …