title: Testing for germline mutations in sporadic pheochromocytoma/paraganglioma: a systematic review.
abstract: BACKGROUND
  The presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown.
  
  
  OBJECTIVE
  To describe the frequency of germline mutations in SPPs and to determine the value of testing index patients and their family members for these mutations.
  
  
  METHODS
  We searched databases through June 2012 for observational studies of patients with SPPs who underwent germline genetic testing. The criteria used to define sporadic tumours were (i) the absence of a family history of PCC/PG, (ii) the absence of syndromic features, (iii) the absence of bilateral disease and (iv) the absence of metastatic disease.
  
  
  RESULTS
  We included 31 studies including 5031 patients (mean age 44). These patients received tests for any of these ten mutations: SDHAF2, RET, SDHD, SDHB, SDHC, VHL, TMEM127, MAX, Isocitrate Dehydrogenase Mutation (IDH) and NF1. The overall frequency of germline mutation in SPP was 551 of 5031 or 11%; when studies with patients fulfilling four criteria for sporadic tumours were used, the frequency was 171 of 1332 or 13%. The most common germline mutation was SDHB 167 of 3611 (4·6%). Little outcome data were available to assess the benefits of genetic testing in index cases and family members.
  
  
  CONCLUSIONS
  The frequency of germline mutations in SPPs is approximately 11-13% and the most common mutations affect less than 1 in 20 patients. The value of testing for germline mutations in patients with SPPs and their family members is unknown, as the balance of potential benefits and harms remains unclear.
authors: Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA; Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA.
authors: Juan P
authors: JP
authors: Brito
authors: Noor
authors: N
authors: Asi
authors: Irina
authors: I
authors: Bancos
authors: Michael R
authors: MR
authors: Gionfriddo
authors: Claudia L
authors: CL
authors: Zeballos-Palacios
authors: Aaron L
authors: AL
authors: Leppin
authors: Chaitanya
authors: C
authors: Undavalli
authors: Zhen
authors: Z
authors: Wang
authors: Juan P
authors: JP
authors: Domecq
authors: Gabriela
authors: G
authors: Prustsky
authors: Tarig A
authors: TA
authors: Elraiyah
authors: Larry J
authors: LJ
authors: Prokop
authors: Victor M
authors: VM
authors: Montori
authors: Mohammad H
authors: MH
authors: Murad
mesh_terms: D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / 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: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C543341:SDHAF2 protein, human; C108096:SDHC protein, human; C491545:SDHD protein, human; C548370:TMEM127 protein, human; D007521:Isocitrate Dehydrogenase; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; C497446:VHL protein, human