von Hippel-Lindau (VHL) disease: recent progress in genetics and patient management

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder predispos ing to the development of central nervous system (CNS) and retinal hemangio blastomas, endolymphatic sac tumors, renal cell carcinoma and/or renal cyst s, pheochromocytomas, pancreatic cysts and/or tumors. Incidence of the dise ase is 1/36.000. CNS hemangioblastomas and renal cell carcinoma are the mai n 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 mu tations of the VHL gene are identified irt about 70-99% of the patients. Mu tations associated with VHL type 2 (with pheochromocytoma) are mainly misse nse mutations with hot-spot at codon 167. Somatic mutations of the VHL gene are found in both sporadic central nervous system hemangioblastomas and sp oradic renal cell carcinoma. For endocrinologists search for VHL disease (a s Sor MEN) should be imperative in presence of a patient with pheochromocyt oma and neuroendocrine pancreatic tumor.