Clinical characteristics and prognosis of <i>SDHD</i> pathogenic variant carriers: a systematic review and meta-analysis

BACKGROUND: PVs. OBJECTIVE: To systematically assess age-specific penetrance (in all carriers) and the proportions of multifocality, metastatic disease and mortality among affected carriers, and explore potential genotype-phenotype associations through a systematic review and meta-analysis. METHODS: variants associated with tumour multifocality or metastatic behaviour were collected. Following independent data extraction and quality assessment by two reviewers, these proportions were meta-analysed using random-effects models or fixed-effect model to generate pooled estimates with 95% CIs and prediction intervals. RESULTS: PV carriers, the pooled proportions were 75% (95% CI 72% to 79%) for multifocal tumours, 3% (95% CI 2% to 4%) for metastatic disease and 1% (95% CI 1% to 2%) for mortality. CONCLUSION: PV carriers. However, evidence linking specific variants to these phenotypes is limited and requires further investigation. PROSPERO REGISTRATION NUMBER: CRD420251060752.