Tumor detection rates in screening of individuals withSDHx-related hereditary paraganglioma-pheochromocytoma syndrome

Purpose Minimal data exist regarding the efficacy of screening protocols for individuals withSDHxgermline pathogenic variants with hereditary paraganglioma-pheochromocytoma syndrome. This study aimed to evaluate theSDHx-related tumor detection rate in individuals undergoing clinical screening protocols. Methods A multicenter retrospective longitudinal observational study was conducted. Individuals with germlineSDHxpathogenic variants underwent clinical whole-body imaging and biochemical testing. Results Two hundred sixty-three individuals withSDHxgermline pathogenic variants completed 491 imaging screens. Individuals withSDHBgermline pathogenic variants were most common (n = 188/263, 72%), followed bySDHD(n = 35/263, 13%) andSDHC(n = 28/263, 11%).SDHx-related tumors were found in 17% (n = 45/263) of the cohort. MostSDHx-related tumors were identified on baseline imaging screen (n = 39/46, 85%). Individuals withSDHDpathogenic variants had the highest tumor detection rate (n = 14/35, 40%). Of imaging screens identifyingSDHx-related paraganglioma/pheochromocytoma, 29% (n = 12/41) had negative biochemical testing. Secondary actionable findings were identified in 15% (n = 75/491) of imaging screens. Conclusion CurrentSDHxscreening protocols are effective at identifyingSDHx-related tumors. Tumor detection rates vary bySDHxgene and screening has the potential to uncover actionable secondary findings. Imaging is an essential part of the screening process as biochemical testing alone does not detect all disease.