title: Relevance of germline mutation screening in both familial and sporadic head and neck paraganglioma for early diagnosis and clinical management.
abstract: BACKGROUND
  Head and neck paraganglioma (PGL) are benign tumors that can cause important direct or surgery induced morbidity. Almost all familial and 11-29% of sporadic PGL are caused by inactivating germline mutations in succinate dehydrogenase (SDH) genes. Our aim was to screen for such mutations and to evaluate clinical parameters as predictors of germline mutation.
  
  
  METHODS
  Seventy-four PGL patients were analyzed for germline mutations and large deletions in SDH genes, VHL and RET. Results were correlated to clinical characteristics including gender, age, tumor localization and multifocality. The surgical approach was evaluated in terms of tumor origin, sequelae and subsequent evolution.
  
  
  RESULTS
  Mutations in SDHB and SDHD were identified in equal proportion in 13/13 (100%) of familial and in 15/61 (25%) of sporadic cases. Familiarity, age < or =50 years and male gender were predictors of any germline mutation, while multifocality and carotid/vagal localization were indicative of SDHD mutation in particular.
  
  
  CONCLUSIONS
  In contrast to other series, this cohort of Spanish patients showed many SDHB mutations. Sporadic cases with germline mutation are frequent and underline the importance of mutational screening of all PGL patients, allowing the identification of relatives at risk and the early diagnosis of the disease, reducing or avoiding morbidity.
authors.affiliation: Department of Otolaryngology, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Asturias, Spain. mhermsen@hca.es
authors.forename: Mario A
authors.initials: MA
authors.lastname: Hermsen
authors.forename: María A
authors.initials: MA
authors.lastname: Sevilla
authors.forename: José Luis
authors.initials: JL
authors.lastname: Llorente
authors.forename: Marjan M
authors.initials: MM
authors.lastname: Weiss
authors.forename: Anneliese
authors.initials: A
authors.lastname: Grimbergen
authors.forename: Eva
authors.initials: E
authors.lastname: Allonca
authors.forename: Cristina
authors.initials: C
authors.lastname: Garcia-Inclán
authors.forename: Milagros
authors.initials: M
authors.lastname: Balbín
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D004252:DNA Mutational Analysis; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D011237:Predictive Value of Tests; D012737:Sex Factors; D013030:Spain; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase