Retinal angiomatosis and von Hippel-Lindau disease

Background: To evaluate the significance of angioma number (single or multi ple) for the presence of von Hippel-Lindau (VHL) disease in patients presen ting with capillary retinal angioma. Methods: Forty-one nonrelated patients presenting with capillary retinal angioma were evaluated. An ophthalmic wo rkup, screening for other organ lesions, and molecular genetic screening fu r a mutation of the VHL gene was performed. The diagnosis of VI-IL was made on the basis of the personal and family history, the presence of other VEI L-associated organ lesions, or the presence of a mutation of the VHL gene. Result: Thirteen patients (32%) presented with a single angioma and 28 pati ents (68%) presented with multiple angiomas. In 81% of all patients, VHL co uld be diagnosed. Diagnosis of VHL could be readily made by the personal or family history in 51% of all patients. In another 27% of all patients, VHL disease was evidenced by screening fur other VHL-associated lesions. In tw o patients (3%) VHL could be diagnosed by molecular genetics only. All pati ents with multiple retinal angiomas had VHL disease and, in 38% of patients with a single angioma, VHL was present. Reasons for a missing family histo ry in patients with VHL disease were the presence of a de novo mutation (15 % of VHL patients) or clinical anticipation of VHL disease (18% of VHL pati ents). Conclusion: The presence of multiple retinal angiomas strongly sugge sts VHL disease, which, however, can be obscured by presence of a de novo m utation or by clinical anticipation of VHL disease in affected families. A single retinal angioma may be sporadic as well as the presenting sign of VH L. Diagnosis and screening for this multitumor syndrome is substantially su pported by molecular genetics.