title: Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes.
abstract: BACKGROUND
  The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations.
  
  
  OBJECTIVE
  Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations.
  
  
  METHODS
  The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland.
  
  
  METHODS
  Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, pathology, and disease progression. Clinical features were evaluated for evidence of genotype-phenotype associations, and penetrance was determined.
  
  
  RESULTS
  SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereas SDHD mutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43 SDHB and 19 SDHD mutation carriers in the time to first diagnosis (34 vs. 28 yr, respectively; P = 0.3). However, when all mutation carriers were included (n = 112), the estimated age-related penetrance was different for SDHB vs. SDHD mutation carriers (P = 0.008).
  
  
  CONCLUSIONS
  For clinical follow-up, features of SDHB mutation-associated disease include a later age of onset, extraadrenal (abdominal or thoracic) tumors, and a higher rate of malignancy. In contrast, SDHD mutation carriers, in addition to head and neck paragangliomas, should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma.
authors.affiliation: Department of Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Benn
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Reilly
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: John
authors.initials: J
authors.lastname: Burgess
authors.forename: Karen
authors.initials: K
authors.lastname: Byth
authors.forename: Michael
authors.initials: M
authors.lastname: Croxson
authors.forename: Patricia L M
authors.initials: PL
authors.lastname: Dahia
authors.forename: Marianne
authors.initials: M
authors.lastname: Elston
authors.forename: Oliver
authors.initials: O
authors.lastname: Gimm
authors.forename: David
authors.initials: D
authors.lastname: Henley
authors.forename: Philippe
authors.initials: P
authors.lastname: Herman
authors.forename: Victoria
authors.initials: V
authors.lastname: Murday
authors.forename: Patricia
authors.initials: P
authors.lastname: Niccoli-Sire
authors.forename: Janice L
authors.initials: JL
authors.lastname: Pasieka
authors.forename: Vincent
authors.initials: V
authors.lastname: Rohmer
authors.forename: Kathy
authors.initials: K
authors.lastname: Tucker
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D002648:Child; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000235:genetics*; D010641:Phenotype; D010673:Pheochromocytoma / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: D007506:Iron-Sulfur Proteins; D021122:Protein Subunits; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase