title: Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.
abstract: OBJECTIVE
  Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations.
  
  
  METHODS
  Retrospective case-series.
  
  
  METHODS
  Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres.
  
  
  METHODS
  Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management.
  
  
  RESULTS
  Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension.
  
  
  CONCLUSIONS
  SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease.
authors.affiliation: Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK. u.srirangalingam@qmul.ac.uk
authors.forename: Umasuthan
authors.initials: U
authors.lastname: Srirangalingam
authors.forename: Lisa
authors.initials: L
authors.lastname: Walker
authors.forename: Bernard
authors.initials: B
authors.lastname: Khoo
authors.forename: Fiona
authors.initials: F
authors.lastname: MacDonald
authors.forename: Daphne
authors.initials: D
authors.lastname: Gardner
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Wilkin
authors.forename: Robert H
authors.initials: RH
authors.lastname: Skelly
authors.forename: Emad
authors.initials: E
authors.lastname: George
authors.forename: David
authors.initials: D
authors.lastname: Spooner
authors.forename: John P
authors.initials: JP
authors.lastname: Monson
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.forename: Scott A
authors.initials: SA
authors.lastname: Akker
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Pollard
authors.forename: Nick
authors.initials: N
authors.lastname: Plowman
authors.forename: Norbert
authors.initials: N
authors.lastname: Avril
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
authors.forename: Jacky M
authors.initials: JM
authors.lastname: Burrin
authors.forename: Rodney H
authors.initials: RH
authors.lastname: Reznek
authors.forename: V K Ajith
authors.initials: VK
authors.lastname: Kumar
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Shern L
authors.initials: SL
authors.lastname: Chew
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D015897:Comorbidity; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: C108095:SDHB protein, human; D013385:Succinate Dehydrogenase