title: Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations.
abstract: OBJECTIVE
  To present data on the high rate of SDHB mutations in patients with metastatic pheochromocytoma/paraganglioma whose initial tumor presentation began in childhood or adolescence.
  
  
  METHODS
  From 2000 to 2010, 263 patients with pheochromocytoma/paraganglioma were evaluated through the National Institutes of Health (NIH), Bethesda, MD. Of the 263 patients, 125 patients were found to have metastatic disease; of these 125 patients, 32 patients presented with a tumor before 20 years of age. An additional 17 patients presented with a tumor before 20 years of age but demonstrated no development of metastatic disease. Genetic testing for mutations in the VHL, MEN, and SDHB/C/D genes was performed on patients without previously identified genetic mutations.
  
  
  RESULTS
  Of the 32 patients who presented with metastatic disease and had their primary tumor in childhood or adolescence, sequence analysis of germline DNA showed SDHB mutations in 23 patients (71.9%), SDHD mutations in three patients (9.4%), VHL mutations in two patients (6.3%), and an absence of a known mutation in four patients (12.5%). The majority of these 32 patients (78.1%) presented with primary tumors in an extra-adrenal location.
  
  
  CONCLUSIONS
  The majority of patients with metastatic pheochromocytoma/paraganglioma who presented with a primary tumor in childhood/adolescence had primary extra-adrenal tumors and harbored SDHB mutations. Except for primary tumors located in the head and neck where SDHD genetic testing is advised, we recommend that patients who present with metastatic pheochromocytoma/paraganglioma with primary tumor development in childhood or adolescence undergo SDHB genetic testing before they undergo testing for other gene mutations, unless clinical presentation or family history suggests a different mutation.
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1109, USA.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: King
authors.forename: Tamara
authors.initials: T
authors.lastname: Prodanov
authors.forename: Vitaly
authors.initials: V
authors.lastname: Kantorovich
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Hewitt
authors.forename: Margaret
authors.initials: M
authors.lastname: Zacharin
authors.forename: Robert
authors.initials: R
authors.lastname: Wesley
authors.forename: Maya
authors.initials: M
authors.lastname: Lodish
authors.forename: Margarita
authors.initials: M
authors.lastname: Raygada
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: Shana
authors.initials: S
authors.lastname: McCormack
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: Dragana
authors.initials: D
authors.lastname: Milosevic
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics* / Q000556:secondary; D010673:Pheochromocytoma / Q000235:genetics* / Q000556:secondary; D011237:Predictive Value of Tests; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C108096:SDHC protein, human; C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase