Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

Abstract

Germline mutations in succinate dehydrogenase subunit B and D (<i>SDHB</i> and <i>SDHD</i>) 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 <i>SDHB</i> variant carriers and that of a large cohort of <i>SDHD</i> variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 <i>SDHB</i> variant carriers and 232 <i>SDHD</i> variant carriers were included in this study. The Standard Mortality Ratio (SMR) for <i>SDHB</i> mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For <i>SDHD</i> variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in <i>SDHB</i> variant carriers, especially in those affected by PGL. In <i>SDHD</i> 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.