Increased Mortality in but Not in Pathogenic Variant Carriers.

Germline mutations in succinate dehydrogenase subunit B and D ( and ) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nationwide cohort of variant carriers and that of a large cohort of variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 variant carriers and 232 variant carriers were included in this study. The Standard Mortality Ratio (SMR) for mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in variant carriers, especially in those affected by PGL. In variant carriers, the mortality is comparable to that of the general Dutch population, even if they are affected by PGL. This insight emphasizes the significance of DNA-testing in all PGL and PHEO patients, since different clinical risks may warrant gene-specific management strategies.