Von Hippel-Lindau Syndrome: Clinical Features, Genetics and Surveillance of a Family

Background: Von Hippel-Lindau (VHL) syndrome represents a rare familial condition caused by germline mutations of the tumorsuppressor gene VHL, which is located on the short arm of chromosome 3p25. Only 20% of the cases arise from de novo mutations, most patients having a positive family history with an autosomal dominant transmission. VHL is characterized by the presence of vascular tumors including hemangioblastomas of the cerebellum, spinal cord, brain stem and retina and the appearance of multiple cysts in different organs. Frequently, patients can associate clear cell renal carcinoma (RCC) and pheochromocytomas, or endolymphatic sac tumors. Case reports: We present the cases of two sisters, diagnosed with VHL, with a positive family history (their father was diagnosed with VHL as well). The first patient, a 40 year old female, non-smoker, presented with multiple hemangioblastomas (right cerebellar, brainstem, right optic nerve, spinal cord), bilateral pheochromocytoma and multiple cysts (hepatic, renal and ovary) had a positive genetic analysis (VHL heterozygote mutation p.Arg167Gln) and underwent multiple surgical interventions. The second patient, her sister, 38 year old, presented with multiple emangioblastomas (cerebellar hemangioblastomas, right retinal hemangioblastoma), ovarian and breast cysts. Conclusions: Patients with rare tumors characteristic of VHL (e.g. retinal or cerebellar hemangioblastomas) should be evaluated clinically and molecularly for VHL. This includes reviewing a detailed family history focused on characteristic tumors.