{"id":15789,"date":"2026-04-15T16:00:16","date_gmt":"2026-04-15T16:00:16","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=e22088b0529af0ce112eef89e6434168"},"modified":"2026-04-15T16:00:16","modified_gmt":"2026-04-15T16:00:16","slug":"clinical-characteristics-and-prognosis-of-sdhd-pathogenic-variant-carriers-a-systematic-review-and-meta-analysis","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/04\/15\/clinical-characteristics-and-prognosis-of-sdhd-pathogenic-variant-carriers-a-systematic-review-and-meta-analysis\/","title":{"rendered":"Clinical characteristics and prognosis of SDHD pathogenic variant carriers: a systematic review and meta-analysis"},"content":{"rendered":"<sec><st>Background<\/st><p>Germline pathogenic variants (PVs) of succinate dehydrogenase subunit D (<I>SDHD<\/I>) are major genetic causes of pheochromocytomas and paragangliomas. Existing studies have reported inconsistent findings and lack a comprehensive synthesis regarding penetrance, multifocality and metastatic risk in carriers of <I>SDHD<\/I> PVs.<\/p><\/sec><sec><st>Objective<\/st><p>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&ndash;phenotype associations through a systematic review and meta-analysis.<\/p><\/sec><sec><st>Methods<\/st><p>Eligible observational studies were selected from PubMed, MEDLINE and EMBASE that reported age-specific penetrance (in all carriers) and the proportions of multifocality, metastatic disease and mortality among affected carriers (those with tumours). Additionally, data on specific <I>SDHD<\/I> 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.<\/p><\/sec><sec><st>Results<\/st><p>Age-specific penetrance increased from 20% at 20 years of age (95% CI 16% to 25%) to 58% at 40 years (95% CI 48% to 67%) and 82% at 60 years (95% CI 75% to 90%). Among the affected <I>SDHD<\/I> 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.<\/p><\/sec><sec><st>Conclusion<\/st><p><I>SDHD<\/I> PV carriers exhibit increasing age-specific penetrance, with a high proportion of patients having multifocal tumours but low proportions of metastatic disease and mortality, providing partial evidence for the need for lifelong monitoring of <I>SDHD<\/I> PV carriers. However, evidence linking specific variants to these phenotypes is limited and requires further investigation.<\/p><\/sec><sec><st>PROSPERO registration number<\/st><p>CRD420251060752.<\/p><\/sec>","protected":false},"excerpt":{"rendered":"<p>BackgroundGermline pathogenic variants (PVs) of succinate dehydrogenase subunit D (SDHD) are major genetic causes of pheochromocytomas and paragangliomas. Existing studies have reported inconsistent findings and lack a comprehensive synthesis regarding&#8230;<\/p>\n","protected":false},"author":553,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,8,9],"tags":[],"class_list":["post-15789","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg-first","category-open-access"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/15789","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/553"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=15789"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/15789\/revisions"}],"predecessor-version":[{"id":15790,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/15789\/revisions\/15790"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=15789"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=15789"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=15789"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}