Table 2

Summary of recommendations

Report germline likely pathogenic/pathogenic variant in diagnostic settingSurveillance* for affected probandOffer predictive testingOffer surveillance* if positive predictive test
Individual with SDHA-associated tumour (wtGIST, paraganglioma, phaeochromocytoma), renal cancer, neuroblastoma and pituitary adenoma with immunohistochemical evidence of SDH deficiency, see table 1)YesYes
Offer follow-up for initial tumour and surveillance for metachronous tumours (see recommendation 4)
Recommend for FDR, following detailed discussionOffer surveillance (see recommendation 6) following detailed discussion regarding current knowledge and limitations
Individual with non-SDHA-associated tumourYes, recommend reporting is coupled with a recommendation that SDH IHC is performed and the finding is considered to be a non-actionable secondary finding unless there is immunohistochemical evidence of SDHB/SDHA loss in the tumour or a family history of SDHA-associated tumours†No†No†N/A
  • *Surveillance: annual symptom review, blood pressure monitoring, biochemistry with plasma metanephrines and 3–5 yearly imaging of neck, thorax, abdomen and pelvis, preferably with MRI from age 15.

  • †For individuals with non-SDHA-associated tumours identified to have a PGV in SDHA, we would consider these a non-clinically actionable finding, unless the tumour is demonstrated to show SDHB/SDHA loss or there is a family history of SDHA-associated tumours. If either IHC loss or family history is confirmed, then recommendations should shift to that for an individual with an SDHA-associated tumour.

  • FDR, first-degree relative; IHC, immunohistochemical; PGV, pathogenic germline variant; wtGIST, wild-type gastrointestinal stromal tumour.