Background: Pathogenic variants in genes encoding Succinate Dehydrogenase subunits B and D (SDHB/SDHD) predispose to Phaeochromocytoma and Paraganglioma (PPGL). Cascade genetic screening identifies relatives at risk and allows surveillance screening to enable early detection of PPGLs.
Methods: Retrospective analysis of genetic databases and hospital records between January 2000 and December 2018 identified relatives carrying SDHB and SDHD pathogenic variants. Surveillance screening included annual plasma metanephrine measurements and whole-body MRI with contrast every 35 years. 53 SDHB patients and 10 SDHD patients with no prior history of PPGL underwent surveillance screening. The median age at first screen was 34.5 years (range 874), with a median screening duration of 3 years (range 115).
Results: In SDHB group, PPGLs were detected in 9 (17%) non-index cases, of which 44% were sympathetic PGLs, 44% head/neck PGLs and 12% PCC. The youngest diagnosed with PPGL was aged 20 years. 89% of tumours were detected by MRI, while only 1 (11%) was detected following elevated plasma normetadrenaline level and interval functional imaging. No multifocal or metastatic disease was detected. In SDHD group, 6 (60%) of patients were diagnosed with PPGL at initial screening. 33% patients were diagnosed with multifocal disease, 50% of tumours located in the head/neck, and 50% along the sympathetic chain. All tumours were visualised on MRI, with 2 sympathetic PGLs also having raised normetanephrine levels. Penetrance of PPGL in non-index cases at age 50 and 70 respectively were 16.0% and 52% in SDHB and 72% and 82% in SDHD.
Conclusion: Screening enabled the detection of PPGLs in 24% of carriers at first screen of family members affected by either SDHB or SDHD mutations, with SDHD associated with higher incidence of multifocal disease. Penetrance estimates, similar to literature, demonstrated that tumour burden continues with age therefore confirming the need for lifelong screening.