{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:10:10Z","timestamp":1792098610566,"version":"4.4.0"},"reference-count":95,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T00:00:00Z","timestamp":1433980800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/deed.en_GB"}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>\n                    The paraganglioma (PGL) syndromes types 1\u20135 are autosomal dominant disorders characterized by familial predisposition to PGLs, phaeochromocytomas (PCs), renal cell cancers, gastrointestinal stromal tumours and, rarely, pituitary adenomas. Each syndrome is associated with mutation in a gene encoding a particular subunit (or assembly factor) of succinate dehydrogenase (\n                    <jats:italic>SDHx<\/jats:italic>\n                    ). The clinical manifestations of these syndromes are protean: patients may present with features of catecholamine excess (including the classic triad of headache, sweating and palpitations), or with symptoms from local tumour mass, or increasingly as an incidental finding on imaging performed for some other purpose. As genetic testing for these syndromes becomes more widespread, presymptomatic diagnosis is also possible, although penetrance of disease in these syndromes is highly variable and tumour development does not clearly follow a predetermined pattern. PGL1 syndrome (\n                    <jats:italic>SDHD<\/jats:italic>\n                    ) and PGL2 syndrome (\n                    <jats:italic>SDHAF2<\/jats:italic>\n                    ) are notable for high frequency of multifocal tumour development and for parent-of-origin inheritance: disease is almost only ever manifest in subjects inheriting the defective allele from their father. PGL4 syndrome (\n                    <jats:italic>SDHB<\/jats:italic>\n                    ) is notable for an increased risk of malignant PGL or PC. PGL3 syndrome (\n                    <jats:italic>SDHC<\/jats:italic>\n                    ) and PGL5 syndrome (\n                    <jats:italic>SDHA<\/jats:italic>\n                    ) are less common and appear to be associated with lower penetrance of tumour development. Although these syndromes are all associated with SDH deficiency, few genotype\u2013phenotype relationships have yet been established, and indeed it is remarkable that such divergent phenotypes can arise from disruption of a common molecular pathway. This article reviews the clinical presentations of these syndromes, including their component tumours and underlying genetic basis.\n                  <\/jats:p>","DOI":"10.1530\/erc-15-0268","type":"journal-article","created":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T22:19:40Z","timestamp":1439504380000},"page":"T91-T103","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":182,"title":["15 YEARS OF PARAGANGLIOMA: Clinical manifestations of paraganglioma syndromes types 1\u20135"],"prefix":"10.1530","volume":"22","author":[{"given":"Diana E","family":"Benn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce G","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick J","family":"Clifton-Bligh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2015081319191276000_22.4.T91.1","doi-asserted-by":"crossref","unstructured":"Amar L Eisenhofer G Diagnosing phaeochromocytoma\/paraganglioma in a patient presenting with critical illness: biochemistry versus imaging Clinical Endocrinology 2015 [in press] doi:10.1111\/cen.12745).","DOI":"10.1111\/cen.12745"},{"key":"2015081319191276000_22.4.T91.2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1398"},{"key":"2015081319191276000_22.4.T91.3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0709"},{"key":"2015081319191276000_22.4.T91.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-0969-6"},{"key":"2015081319191276000_22.4.T91.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04378-6"},{"key":"2015081319191276000_22.4.T91.6","doi-asserted-by":"publisher","DOI":"10.1086\/321282"},{"key":"2015081319191276000_22.4.T91.7","doi-asserted-by":"publisher","DOI":"10.1007\/BF00569208"},{"key":"2015081319191276000_22.4.T91.8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-6-39"},{"key":"2015081319191276000_22.4.T91.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5454.848"},{"key":"2015081319191276000_22.4.T91.10","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.3.178"},{"key":"2015081319191276000_22.4.T91.11","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2490-13-22"},{"key":"2015081319191276000_22.4.T91.12","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206300"},{"key":"2015081319191276000_22.4.T91.13","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1862"},{"key":"2015081319191276000_22.4.T91.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03256.x"},{"key":"2015081319191276000_22.4.T91.15","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-144"},{"key":"2015081319191276000_22.4.T91.16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0423"},{"key":"2015081319191276000_22.4.T91.17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2504"},{"key":"2015081319191276000_22.4.T91.18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq206"},{"key":"2015081319191276000_22.4.T91.19","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20283"},{"key":"2015081319191276000_22.4.T91.20","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.054965"},{"key":"2015081319191276000_22.4.T91.21","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2756"},{"key":"2015081319191276000_22.4.T91.22","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700360102"},{"key":"2015081319191276000_22.4.T91.23","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3143"},{"key":"2015081319191276000_22.4.T91.24","doi-asserted-by":"crossref","unstructured":"Dahia PL Ross KN Wright ME Hayashida CY Santagata S Barontini M Kung AL Sanso G Powers JF Tischler AS 2005 A HIF1\u03b1 regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. 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