Hereditary Diseases Predisposing to Pheochromocytoma (VHL, NF-1, Paraganglioma Syndromes, and Novel Genes)

Abstract

Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare tumors originating from catecholamine-producing chromaffin cells. They occur approximately in 0.1% of patients affected with hypertonia. Pheo/PGL may manifest itself at any age; in 10% of the patients, the disease is bilateral, and also in 10% it occurs outside of the adrenal medulla. From a genetic aspect, a considerable proportion of these tumors represents a prototype for an autosomal dominantly inherited syndrome with incomplete penetrance. In addition, to date more than 15 genes have been identified representing genetic susceptibility for Pheo/PGL and accounting for 40% of all cases. In general, in familiar cases, the tumor manifests at younger age, and they are often occurring as multiplex tumors. Permanent recovery can be achieved with an early diagnosis and with a successful surgical removal of the tumor tissue. On the other hand, undiagnosed, hormonally active Pheos may lead to severe, or even lethal, consequences. This chapter will summarize our recent knowledge about the genetics of Pheo/PGL, focusing on tumor syndromes where Pheo/PGLs are among the main manifestations.