title: Succinate dehydrogenase gene mutations are strongly associated with paraganglioma of the organ of Zuckerkandl.
abstract: Organ of Zuckerkandl paragangliomas (PGLs) are rare neuroendocrine tumors that are derived from chromaffin cells located around the origin of the inferior mesenteric artery extending to the level of the aortic bifurcation. Mutations in the genes encoding succinate dehydrogenase subunits (SDH) B, C, and D (SDHx) have been associated with PGLs, but their contribution to PGLs of the organ of Zuckerkandl PGLs is not known. We aimed to describe the clinical presentation of patients with PGLs of the organ of Zuckerkandl and investigate the prevalence of SDHx mutations and other genetic defects among them. The clinical characteristics of 14 patients with PGL of the organ of Zuckerkandl were analyzed retrospectively; their DNA was tested for SDHx mutations and deletions. Eleven out of 14 (79%) patients with PGLs of the organ of Zuckerkandl were found to have mutations in the SDHB (9) or SDHD (2) genes; one patient was found to have the Carney-Stratakis syndrome (CSS), and his PGL was discovered during surgery for gastrointestinal stromal tumor. Our results show that SDHx mutations are prevalent in pediatric and adult PGLs of the organ of Zuckerkandl. Patients with PGLs of the organ of Zuckerkandl should be screened for SDHx mutations and the CSS; in addition, asymptomatic carriers of an SDHx mutation among the relatives of affected patients may benefit from tumor screening for early PGL detection.
authors.affiliation: Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA.
authors.forename: Maya B
authors.initials: MB
authors.lastname: Lodish
authors.forename: Karen T
authors.initials: KT
authors.lastname: Adams
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Huynh
authors.forename: Tamara
authors.initials: T
authors.lastname: Prodanov
authors.forename: Alex
authors.initials: A
authors.lastname: Ling
authors.forename: Clara
authors.initials: C
authors.lastname: Chen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Shusterman
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
authors.forename: Maria
authors.initials: M
authors.lastname: Merino
authors.forename: Marybeth
authors.initials: M
authors.lastname: Hughes
authors.forename: Kendall W
authors.initials: KW
authors.lastname: Cradic
authors.forename: Dragana
authors.initials: D
authors.lastname: Milosevic
authors.forename: Ravinder J
authors.initials: RJ
authors.lastname: Singh
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004701:Endocrine Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010220:Para-Aortic Bodies / Q000473:pathology*; D010236:Paraganglioma, Extra-Adrenal / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D013385:Succinate Dehydrogenase