Contributor: Gordon K. Klintworth
von Hippel-Lindau disease (cerebroretinal angiomatosis, von Hippel-Lindau syndrome, OMIM #193300) is an inherited autosomal dominant syndrome. In 1904 von Hippel first described the angioma in the retina and Lindau latter drew attention its presence in the cerebellum in 1926. Ophthalmic manifestations include hemangioblastomas of the retina and much less frequently in the optic nerve. Edema of the optic nerve head [edema - optic disc] may follow increased intracranial pressure from a cerebellar hemangioblastoma. Affected persons develop several tumors [pheochromocytoma, endolymphatic sac tumor, carcinoma - clear cell, neuroendocrine tumor, cystadenoma - epididymis, cystadenoma - broad ligament] and cysts [cyst - kidney, cyst - pancreas] in different organs. This multisystem neoplastic syndrome is due to a deletion or mutation in the VHL gene, which encodes for the VHL protein. A loss of VHL protein function interfers with the formation of the VHL protein complex and induces an upregulation of HIF signally pathways that lead to an overexpression of VEGF, PDGF, and erythropoietin. von Hippel-Lindau disease has been divided into two types: von Hippel-Lindau disease type 1 and von Hippel-Lindau disease type 2.