Succinate dehydrogenase gene mutations are strongly associated with paraganglioma of the organ of Zuckerkandl.
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.
Lodish
Maya B
MB
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.
Adams
Karen T
KT
Huynh
Thanh T
TT
Prodanov
Tamara
T
Ling
Alex
A
Chen
Clara
C
Shusterman
Suzanne
S
Jimenez
Camilo
C
Merino
Maria
M
Hughes
Marybeth
M
Cradic
Kendall W
KW
Milosevic
Dragana
D
Singh
Ravinder J
RJ
Stratakis
Constantine A
CA
Pacak
Karel
K
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*
D013385:Succinate Dehydrogenase