Von Hippel-Lindau disease (VHL) manifests by angiomas of the retina and hemangioblastomas of the cerebelum. Hemangioblastomas can also occur elsewhere (see image below).
The VHL gene was mapped to the short arm of Cr3 in 1988 by Seizinger et al (Nature 1988:332:268-269), and isolated in 1993 by Latif (Science 1993:260:1317-1320). Life time risk for renal clear cell carcinoma is 70% and this is the most frequent cause of death. Pheochromocytomas affect 7-20% of cases and can be bilateral or malignant. Non-secretory pancreatic cell tumors also occur.
The genetic defect is in the VHL gene which is a tumor supressor gene. VHL is inherited in an autosomal dominant fashion, but two copies of the mutation are needed to cause the disorder. A second mutation can occur during a person's lifetime in a particular cell, which allows tumors and cysts to develop.
Endolymphatic sac tumors affect about 10% of cases, and VHL should be considered in persons with bilateral endolymphatic sac tumors.