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. PATIENTS AND 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.
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-SDHxHNP 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-SDHxHNP presentations are scarce and guidance for genetic testing nonexistent. PATIENTS AND 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 VHLpatients and nine in 1000 non-SDHxHNPpatients. Comprehensive literature review revealed previous reports of HNPs in five VHL, two MEN2, and one NF1patient. 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.
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Authors: D Astuti; F Latif; A Dallol; P L Dahia; F Douglas; E George; F Sköldberg; E S Husebye; C Eng; E R Maher Journal: Am J Hum Genet Date: 2001-06-12 Impact factor: 11.025
Authors: Hartmut P H Neumann; Birke Bausch; Sarah R McWhinney; Bernhard U Bender; Oliver Gimm; Gerlind Franke; Joerg Schipper; Joachim Klisch; Carsten Altehoefer; Klaus Zerres; Andrzej Januszewicz; Charis Eng; Wendy M Smith; Robin Munk; Tanja Manz; Sven Glaesker; Thomas W Apel; Markus Treier; Martin Reineke; Martin K Walz; Cuong Hoang-Vu; Michael Brauckhoff; Andreas Klein-Franke; Peter Klose; Heinrich Schmidt; Margarete Maier-Woelfle; Mariola Peçzkowska; Cesary Szmigielski; Charis Eng Journal: N Engl J Med Date: 2002-05-09 Impact factor: 91.245
Authors: Hartmut P H Neumann; Christian Pawlu; Mariola Peczkowska; Birke Bausch; Sarah R McWhinney; Mihaela Muresan; Mary Buchta; Gerlind Franke; Joachim Klisch; Thorsten A Bley; Stefan Hoegerle; Carsten C Boedeker; Giuseppe Opocher; Jörg Schipper; Andrzej Januszewicz; Charis Eng Journal: JAMA Date: 2004-08-25 Impact factor: 56.272
Authors: Hartmut P H Neumann; Zoran Erlic; Carsten C Boedeker; Lisa A Rybicki; Mercedes Robledo; Mario Hermsen; Francesca Schiavi; Maurizio Falcioni; Pingling Kwok; Catherine Bauters; Karen Lampe; Markus Fischer; Emily Edelman; Diana E Benn; Bruce G Robinson; Stefanie Wiegand; Gerd Rasp; Boris A Stuck; Michael M Hoffmann; Maren Sullivan; Maria A Sevilla; Marjan M Weiss; Mariola Peczkowska; Agata Kubaszek; Pascal Pigny; Robyn L Ward; Diana Learoyd; Michael Croxson; Dmitry Zabolotny; Svetlana Yaremchuk; Wolfgang Draf; Mihaela Muresan; Robert R Lorenz; Stephan Knipping; Michael Strohm; Gerhard Dyckhoff; Christoph Matthias; Nicole Reisch; Simon F Preuss; Dirk Esser; Martin A Walter; Holger Kaftan; Timo Stöver; Christian Fottner; Harald Gorgulla; Mahdi Malekpour; Masoud Motasaddi Zarandy; Jörg Schipper; Christoph Brase; Alexander Glien; Matthias Kühnemund; Sven Koscielny; Peter Schwerdtfeger; Matti Välimäki; Witold Szyfter; Ulrich Finckh; Klaus Zerres; Alberto Cascon; Giuseppe Opocher; Gerd J Ridder; Andrzej Januszewicz; Carlos Suarez; Charis Eng Journal: Cancer Res Date: 2009-04-07 Impact factor: 12.701
Authors: Jodi K Maranchie; Anoushka Afonso; Paul S Albert; Sivaram Kalyandrug; John L Phillips; Shubo Zhou; James Peterson; Bijan M Ghadimi; Katheen Hurley; Joseph Riss; James R Vasselli; Thomas Ried; Berton Zbar; Peter Choyke; McClellan M Walther; Richard D Klausner; W Marston Linehan Journal: Hum Mutat Date: 2004-01 Impact factor: 4.878
Authors: Shankar K Sridhara; Murat Yener; Ehab Y Hanna; Thereasa Rich; Camilo Jimenez; Michael E Kupferman Journal: J Neurol Surg B Skull Base Date: 2013-04-12