Outcomes of SDHB Pathogenic Variant Carriers

Area of Science:

• Genetics and Oncology
• Endocrinology
• Cancer Risk Assessment

Background:

• Germline pathogenic variants (PVs) in succinate dehydrogenase type B (SDHB) are associated with an elevated risk of developing pheochromocytomas and paragangliomas (PPGLs).
• Understanding the clinical outcomes for SDHB PV carriers is crucial for refining risk assessment and early detection strategies.

Purpose of the Study:

• To conduct a systematic review and meta-analysis to evaluate key outcomes in individuals carrying SDHB PVs.
• The study focused on age-specific tumor development risk, metastatic progression, secondary primary tumor incidence, and overall mortality.

Main Methods:

• A comprehensive search of PubMed, MEDLINE, and EMBASE databases was performed.
• Sixteen studies were included and categorized by outcome: age-specific penetrance, metastatic disease, risk of second tumor, and mortality.
• A random-effects model was employed for meta-analysis to assess heterogeneity across studies.

Main Results:

• PPGL penetrance in SDHB PV carriers increases with age, reaching 35% by age 80.
• The lifetime risk of metastatic disease for affected nonproband/nonindex carriers is 9%.
• The risk of a second primary tumor is 24%, and the 5-year all-cause mortality is 18% for affected carriers.

Conclusions:

• Penetrance of PPGLs in SDHB PV carriers demonstrates a linear increase with age.
• Affected carriers face significant risks of metastatic disease, secondary tumors, and mortality.
• Continuous, lifelong surveillance is warranted for individuals with SDHB PVs.