Tumor risks and surveillance outcomes in SDHA variant carriers.

SDHA

Germline pathogenic SDHA variants, which confer a lower tumour risk than other hereditary paraganglioma genes

Germline pathogenic SDHA variants confer a lower paraganglioma risk than other hereditary paraganglioma genes, which has prompted proposals to reduce screening in carriers without a personal or family history, although supporting data remain limited. This single-institution retrospective cohort study reviewed the records of 106 carriers of a pathogenic or likely pathogenic SDHA variant identified between July 2015 and July 2025 in an academic family cancer assessment clinic. Fifteen per cent of carriers had a personal history of an SDHA-associated tumour, and 47% of identified tumours were metastatic or showed malignant behaviour (3 of 3 extra-adrenal paragangliomas, 4 of 5 gastrointestinal stromal tumours, 0 of 7 head and neck paragangliomas). No affected carrier had a known family history of an SDHA-associated tumour and no case of multiple related tumours was observed; 63% of carriers had neither a personal nor a family history, and over ten years of high-risk screening no previously unidentified SDHA-associated tumour was found.

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

Zero previously unknown tumours found over ten years of high-risk screening is a figure with real practical weight: it gives a tangible argument for scaling back a demanding and anxiety-inducing imaging protocol in SDHA carriers without a personal or family history. The counterpoint sits in the same abstract: 47% of tumours occurring in affected carriers were metastatic or behaved malignantly, which makes de-escalation uncomfortable and argues for individualised decisions rather than a blanket rule. A single-centre series of 106 carriers, with neither person-years nor screening intervals stated in the abstract: this is one more argument in an open debate, not yet a recommendation.

Analysis by Dr Thibaut Benquey