title: Is genetic screening indicated in apparently sporadic pheochromocytomas and paragangliomas?
abstract: BACKGROUND
  Pheochromocytoma (Pheo) is usually considered a sporadic disease. Recently, an increasing rate of genetically based tumors has been reported. However, the need for systematic screening of unsuspected germline mutations in apparently sporadic forms is still debated. This study aimed to assess the effective rate of germline mutations causing Pheo and Paraganglioma (PGL), and the role of systematic genetic screening.
  
  
  METHODS
  Demographics, clinical, and genetic evaluation were performed in a series of 71 patients with Pheo and/or PGL.
  
  
  RESULTS
  Twelve patients had evident inherited/familial disease at presentation: NF1 (n = 4); MEN2 (n = 4), and familial Pheo/PGL (n = 4). Among 59 patients with apparently sporadic disease, unsuspected germline mutations occurred in 8 cases: TMEM127 (n = 4), SDHB (n = 2), VHL (n = 1), SDHC (n = 1). No differences were found between hereditary and sporadic disease concerning age, sex, and tumor size; bilateral Pheo and/or PGL and recurrences occurred most often in hereditary disease.
  
  
  CONCLUSIONS
  Hereditary Pheo and/or PGL are frequent (28.2%). Inheritance is evident at presentation only in 16.9% of cases; 13.6% of apparently sporadic variants are genetically determined. Despite increased costs, systematic genetic screening might be useful because it might lead to a stricter follow-up, early diagnosis of recurrences in index cases and presymptomatic detection of disease in relatives.
authors.affiliation: Endocrine Surgery Unit, University of Padua, Padua, Italy. maurizio.iacobone@unipd.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Iacobone
authors.forename: Francesca
authors.initials: F
authors.lastname: Schiavi
authors.forename: Marzia
authors.initials: M
authors.lastname: Bottussi
authors.forename: Elisa
authors.initials: E
authors.lastname: Taschin
authors.forename: Sara
authors.initials: S
authors.lastname: Bobisse
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Opocher
authors.forename: Gennaro
authors.initials: G
authors.lastname: Favia
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C108096:SDHC protein, human; C548370:TMEM127 protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human