title: Head and neck paragangliomas in von Hippel-Lindau disease and multiple endocrine neoplasia type 2.
abstract: BACKGROUND
  Head and neck paragangliomas (HNPs) occur as sporadic or familial entities, the latter mostly in association with germline mutations of the SDHB, SDHC, or SDHD (SDHx) genes. Heritable non-SDHx HNP might occur in von Hippel-Lindau disease (VHL, VHL gene), multiple endocrine neoplasia type 2 (MEN2, RET gene), and neurofibromatosis type 1 (NF1, NF1 gene). Reports of non-SDHx HNP presentations are scarce and guidance for genetic testing nonexistent.
  
  
  METHODS
  An international consortium registered patients with HNPs and performed mutation analyses of the SDHx, VHL, and RET genes. Those with SDHx germline mutations were excluded for purposes of this study. Personal and family histories were evaluated for paraganglial tumors, for the major tumor manifestations, and for family history of VHL, MEN2, or NF1.
  
  
  RESULTS
  Twelve patients were found to have hereditary non-SDHx HNPs of a total of 809 HNP and 2084 VHL registrants, 11 in the setting of germline VHL mutations and one of a RET mutation. The prevalence of hereditary HNP is five in 1000 VHL patients and nine in 1000 non-SDHx HNP patients. Comprehensive literature review revealed previous reports of HNPs in five VHL, two MEN2, and one NF1 patient. Overall, 11 here presented HNP cases, and four previously reported VHL-HNPs had lesions characteristic for VHL and/or a positive family history for VHL.
  
  
  CONCLUSIONS
  Our observations provide evidence that molecular genetic testing for VHL or RET germline mutations in patients with HNP should be done only if personal and/or family history shows evidence for one of these syndromes.
authors.affiliation: Department of Otorhinolaryngology, Albert-Ludwigs-University, Freiburg D-79106, Germany.
authors.forename: Carsten C
authors.initials: CC
authors.lastname: Boedeker
authors.forename: Zoran
authors.initials: Z
authors.lastname: Erlic
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard
authors.forename: Udo
authors.initials: U
authors.lastname: Kontny
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: Alberto
authors.initials: A
authors.lastname: Cascon
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robledo
authors.forename: José M
authors.initials: JM
authors.lastname: de Campos
authors.forename: Francien H
authors.initials: FH
authors.lastname: van Nederveen
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.forename: José
authors.initials: J
authors.lastname: Gaal
authors.forename: Martin A
authors.initials: MA
authors.lastname: Walter
authors.forename: Kirsten
authors.initials: K
authors.lastname: Reschke
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiech
authors.forename: Johannes
authors.initials: J
authors.lastname: Weber
authors.forename: Klaus
authors.initials: K
authors.lastname: Rückauer
authors.forename: Pierre Francois
authors.initials: PF
authors.lastname: Plouin
authors.forename: Vincent
authors.initials: V
authors.lastname: Darrouzet
authors.forename: Sophie
authors.initials: S
authors.lastname: Giraud
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Hartmut P H
authors.initials: HP
authors.lastname: Neumann