Succinate dehydrogenase (SDHB, SDHC, SDHD) gene variants significantly modify clinical outcomes in paraganglioma-pheochromocytoma but have a limited impact on head and neck paraganglioma.

SDHB, SDHC, SDHD

SDHB, SDHC and SDHD variants (missense or protein-truncating) whose type differentially influences the risk of thoracic-abdominal paraganglioma-pheochromocytoma and head and neck paraganglioma

SDH gene variant types differentially influence the risk of thoracic-abdominal paraganglioma-pheochromocytoma (PPGL) and head and neck paraganglioma (HNPGL), but quantitative correlations were lacking. This genotype-phenotype study analysed 2706 patients carrying SDHB, SDHC or SDHD variants from 57 centres worldwide. Variant type (missense versus protein-truncating) had a major impact on PPGL but little effect on HNPGL, and combined PPGL and HNPGL was more common with SDHD, especially for truncating variants. Patients with SDHB variants were diagnosed with PPGL significantly earlier than HNPGL, and paediatric HNPGL cases had an elevated risk of metastasis; an elevated risk of combined PPGL and HNPGL was also observed in males.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

With 2706 carriers, this work provides a quantitative basis for what genetic counselling could only outline: variant type weighs on PPGL risk, much less on HNPGL risk, which could justify surveillance tailored to the gene and variant type. The abstract, however, reports no quantified relative risk or hazard ratio, and the recruitment mode of the 57 centres is not specified: these correlations should be read in the full article before being applied in consultation.

Analysis by Dr Thibaut Benquey