Outcomes of SDHB Pathogenic Variant Carriers.

CONTEXT: Carriers of germline pathogenic variants (PVs) in succinate dehydrogenase type B (SDHB) are at increased risk of developing pheochromocytomas and paragangliomas (PPGLs). Understanding their outcomes can guide recommendations for risk assessment and early detection.

OBJECTIVE

We performed a systematic review and meta-analysis of the following outcomes in SDHB PV carriers: age-specific risk of developing tumors, metastatic progression, second primary tumor development, and mortality.

METHODS

PubMed, MEDLINE, and EMBASE were searched. Sixteen studies met the inclusion criteria and were sorted into 4 outcome categories: age-specific penetrance, metastatic disease, risk of second tumor, and mortality. We assessed heterogeneity and performed a meta-analysis across studies using a random-effects model with the DerSimonian and Laird method.

RESULTS

Penetrance of PPGLs for nonproband/nonindex SDHB PV carriers by age 20 was 4% (95% CI, 3%-6%), 11% (95% CI, 8%-15%) by age 40, 24% (95% CI, 19%-31%) by age 60%, and 35% (95% CI, 25%-47%) by age 80. The overall risk of metastatic disease for nonproband/nonindex carriers with PPGLs was 9% (95%, CI 5%-16%) per lifetime. In all affected cases (combining both proband/index and nonproband/nonindex carriers with tumors), the risk of a second tumor was 24% (95% CI, 18%-31%) and all-cause 5-year mortality was 18% (95% CI, 6%-40%).

CONCLUSION

Penetrance for PPGLs in SDHB PV carriers increases linearly with age. Affected carriers are at risk of developing and dying of metastatic disease, or of developing second tumors. Lifelong surveillance is appropriate.