von Hippel-Lindau syndrome

Last reviewed 01/2018

Von Hippel-Lindau (VHL) disease is a heritable multisystem cancer syndrome that is associated with a germline mutation of the VHL tumour suppressor gene on the short arm of chromosome 3.

• the von Hippel-Lindau tumor suppressor gene (VHL) is located on the short arm of chromosome 3 (3p25-26) (1)

Von Hippel-Lindau disease is a hereditary cancer syndrome predisposing carriers to the development of a panel of highly vascularized tumours such as central nervous system and retinal hemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas, pheochromocytomas and pancreatic neuroendocrine tumors. The disease is the foremost cause of inherited renal cell carcinomas, which is induced by germline mutations of the VHL tumor-suppressor gene also inactivated in most sporadic renal cell carcinomas.

This disorder is not rare (2):

• about one in 36000 livebirths
• inherited as a highly penetrant autosomal dominant trait (ie, with a high individual risk of disease) with a high carriage rate of the causative gene in close relatives

Mean age at diagnosis is the mid-20s, often with retinal angioma as the first manifestation (3)

Reference:

• Latif F., Tory K., Gnarra J. et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993;260: 1317-1320
• Lonser RR et al . von Hippel-Lindau disease.Lancet 2003;361(9374):2059-67.
• Maher ER, Yates JR, Harries R, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990;77(283):1151-1163.