Germline Pathogenic Variants in Succinate Dehydrogenase Genes: Implications from a Single Institution Study.

SDHB, SDHA, SDHD

Constitutional pathogenic variants in succinate dehydrogenase genes (SDHx), with gene-specific patterns of ascertainment

This single-centre natural history study describes 156 patients carrying a pathogenic variant in a succinate dehydrogenase gene (SDHx), collected over 10 years at an academic medical centre. SDHB variants were the most common; among probands tested for tumours other than pheochromocytoma-paraganglioma (PPGL), SDHA variants predominated, whereas no SDHD variant was ever detected this way. Some carriers also had a variant in a second cancer-associated gene. Among carriers without a tumour at initial presentation, the rate of tumour development was below 5%. The authors suggest that SDHx variants may be more common than expected and that surveillance guidelines may warrant reconsideration.

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

The low rate of new tumours in carriers without an initial tumour is an interesting signal, but the abstract reports neither follow-up duration nor breakdown by gene, even though the study itself describes gene-specific patterns. The most useful point is the detection of SDHA variants through cancer predisposition testing, outside a PPGL context: the level of surveillance to offer these carriers remains to be defined. Revising surveillance would require multicentre data stratified by gene.

Analysis by Dr Thibaut Benquey