title: Genetic testing in pheochromocytoma or functional paraganglioma.
abstract: OBJECTIVE
  To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl).
  
  
  METHODS
  We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria.
  
  
  RESULTS
  We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant.
  
  
  CONCLUSIONS
  Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.
authors.affiliation: Université Paris-Descartes, Faculté de Médecine, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Amar
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.forename: Christiane
authors.initials: C
authors.lastname: Ajzenberg
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bressac-de Paillerets
authors.forename: Olivier
authors.initials: O
authors.lastname: Chabre
authors.forename: Bernard
authors.initials: B
authors.lastname: Chamontin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Delemer
authors.forename: Sophie
authors.initials: S
authors.lastname: Giraud
authors.forename: Arnaud
authors.initials: A
authors.lastname: Murat
authors.forename: Patricia
authors.initials: P
authors.lastname: Niccoli-Sire
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard
authors.forename: Vincent
authors.initials: V
authors.lastname: Rohmer
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Sadoul
authors.forename: Laurence
authors.initials: L
authors.lastname: Strompf
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Xavier
authors.initials: X
authors.lastname: Bertagna
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002648:Child; D005260:Female; D005602:France; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000235:genetics; D010235:Paraganglioma / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C497446:VHL protein, human