Maladie de Von Hippel-Lindau: Progres genetiques recents et prise en charge des patients

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder, predisposing to the development of central nervous system (CNS) and retinal hemangioblastomas, endolymphatic sac tumors, renal cell carcinoma and/or renal cysts, pheochromocytomas, pancreatic cysts and/or tumors. Incidence of the disease is 1/36.000. CNS hemangioblastomas and renal cell carcinoma are the main causes of death. The VHL gene, located on 3p25-26, is a tumor- suppressor gene which plays a major role in regulation of VEGF expression. Germline mutations of the VHL gene are identified in about 70-99 % of the patients. Mutations associated with VHL type 2 (with pheochromocytoma) are mainly, missense mutations with hot-spot at codon 167. Somatic mutations of the VHL gene are found in both sporadic central nervous system hemangioblastomas and sporadic renal cell carcinoma. For endocrinologists search for VHL disease (as for MEN) should be imperative in presence of a patient with pheochromocytoma and neuroendocrine pancreatic tumor.