Von Hippel-Lindau disease: a single gene, several hereditary tumors

The Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the predisposition for multiple tumors caused by germline mutations in the tumor suppressor gene VHL. This disease is associated with a high morbidity and mortality and presents a variable expression, with different phenotypes from family to family, affecting different organs during the lifetime. The main manifestations of VHL are hemangioblastomas of the central nervous system and retina, renal carcinomas and cysts, bilateral pheochromocytomas, cystic and solid tumors of the pancreas, cystadenomas of the epididymis, and endolymphatic sac tumors. The discovery of any of the syndrome components should raise suspicion of this disease and other stigmas must then be investigated. Due to the complexities associated with management of the various VHL manifestation, the diagnosis and the follow-up of this syndrome is a challenge in the clinical practice and a multidisciplinary approach is needed. The particular relevance to endocrinologists is the detection of pheochromocytomas in 35% and islet cell tumors in 17% of VHL patients, which can be associated with hypertension, hypoglycemia, cardiac arrhythmias, and carcinoid syndrome. The purpose of this review is to define the Von Hippel-Lindau syndrome addressing its clinical aspects and classification, the importance of genetic counseling and to propose a protocol for clinical follow-up.