European Archives of Oto-Rhino-Laryngology

, Volume 265, Issue 5, pp 557–563 | Cite as

Cervical paragangliomas: is SDH genetic analysis systematically required?

  • Nicolas Fakhry
  • Patricia Niccoli-Sire
  • Anne Barlier-Seti
  • Roch Giorgi
  • Antoine Giovanni
  • Michel Zanaret
Head and Neck


To evaluate the prevalence of succinate dehydrogenase (SDH) B, C, and D germline mutations in a surgical series of cervical paragangliomas and to precise the characteristics of patients presenting with familial form. Among 29 patients operated on cervical paragangliomas (carotid or vagal body) at our institution between 1994 and 2007, 23 could be asked for a genetic analysis and a familial study. Clinical characteristics of patients harboring a germline SDH mutation were studied and compared with those presenting without mutation. Mutations were found in 8/23 (35%) patients, mostly in SDHD gene (6 cases), and in SDHB and SDHC gene, respectively, in one case each. Mean age at onset was significantly lower for patients with mutation (34 vs. 51.5 years, P = 0.01). In patients presenting with a mutation, 50% had a family history of paraganglioma compared with 0% for others (P = 0.008) and 87.5% had a multifocal form of paragangliomas versus 0% for others (P = 0.001). No difference was found concerning malignant forms between the two groups (12.5 vs. 13.3%). In the 16 patients who had an apparently sporadic paraganglioma, 6% had mutations in the SDH gene. A positive family history of paraganglioma and/or the presence of bilateral or multiple paragangliomas and/or an early age of onset are the main parameters associated with SDH mutations. Genetic testing should be considered for all patients with a cervical paraganglioma, even for those presenting with an apparently sporadic tumor as familial form may be such identified in 6% of cases.


Hereditary paraganglioma Sporadic paraganglioma Head and neck tumor Succinate dehydrogenase Genetic 


  1. 1.
    Baysal BE, Farr JE, Rubinstein WS, Galus RA, Johnson KA, Aston CE, Myers EN, Johnson JT, Carrau R, Kirkpatrick SJ, Myssiorek D, Singh D, Saha S, Gollin SM, Evans GA, James MR, Richard CW 3rd (1997) Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23. Am J Hum Genet 60:121–132PubMedGoogle Scholar
  2. 2.
    Jimenez C, Cote G, Arnold A, Gagel RF (2006) Review: should patients with apparently sporadic pheochromocytomas or paragangliomas be screened for hereditary syndromes? J Clin Endocrinol Metab 91:2851–2858PubMedCrossRefGoogle Scholar
  3. 3.
    Paris J, Facon F, Thomassin JM, Zanaret M (2006) Cervical paragangliomas: neurovascular surgical risk and therapeutic management. Eur Arch Otorhinolaryngol 263:860–865PubMedCrossRefGoogle Scholar
  4. 4.
    Marchesi M, Biffoni M, Jaus MO, Nobili Benedetti R, Tromba L, Berni A, Campana FP (1999) Surgical treatment of paragangliomas of the carotid body and other rare localisations. J Cardiovasc Surg (Torino) 40:691–694Google Scholar
  5. 5.
    Mendenhall WM, Million RR, Parsons JT, Isaacs JH Jr, Cassisi NJ (1986) Chemodectoma of the carotid body and ganglion nodosum treated with radiation therapy. Int J Radiat Oncol Biol Phys 12:2175–2178PubMedGoogle Scholar
  6. 6.
    Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M, Buchta M, Franke G, Klisch J, Bley TA, Hoegerle S, Boedeker CC, Opocher G, Schipper J, Januszewicz A, Eng C (2004) Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 292:943–951PubMedCrossRefGoogle Scholar
  7. 7.
    Pawlu C, Bausch B, Neumann HP (2005) Mutations of the SDHB and SDHD genes. Fam Cancer 4:49–54PubMedCrossRefGoogle Scholar
  8. 8.
    Baysal BE, Willett-Brozick JE, Lawrence EC, Drovdlic CM, Savul SA, McLeod DR, Yee HA, Brackmann DE, Slattery WH 3rd, Myers EN, Ferrell RE, Rubinstein WS (2002) Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. J Med Genet 39:178–183PubMedCrossRefGoogle Scholar
  9. 9.
    Lee SC, Chionh SB, Chong SM, Taschner PE (2003) Hereditary paraganglioma due to the SDHD M1I mutation in a second Chinese family: a founder effect? Laryngoscope 113:1055–1058PubMedCrossRefGoogle Scholar
  10. 10.
    Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peczkowska M, Szmigielski C (2002) Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346:1459–1466PubMedCrossRefGoogle Scholar
  11. 11.
    Dannenberg H, Dinjens WN, Abbou M, Van Urk H, Pauw BK, Mouwen D, Mooi WJ, de Krijger RR (2002) Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma. Clin Cancer Res 8:2061–2066PubMedGoogle Scholar
  12. 12.
    Drovdlic CM, Myers EN, Peters JA, Baysal BE, Brackmann DE, Slattery WH 3rd, Rubinstein WS (2001) Proportion of heritable paraganglioma cases and associated clinical characteristics. Laryngoscope 111:1822–1827PubMedCrossRefGoogle Scholar
  13. 13.
    Benn DE, Gimenez-Roqueplo AP, Reilly JR, Bertherat J, Burgess J, Byth K, Croxson M, Dahia PL, Elston M, Gimm O, Henley D, Herman P, Murday V, Niccoli-Sire P, Pasieka JL, Rohmer V, Tucker K, Jeunemaitre X, Marsh DJ, Plouin PF, Robinson BG (2006) Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab 91:827–836PubMedCrossRefGoogle Scholar
  14. 14.
    Benn DE, Robinson BG (2006) Genetic basis of phaeochromocytoma and paraganglioma. Best Pract Res Clin Endocrinol Metab 20:435–450PubMedCrossRefGoogle Scholar
  15. 15.
    Favier J, Briere JJ, Strompf L, Amar L, Filali M, Jeunemaitre X, Rustin P, Gimenez-Roqueplo AP (2005) Hereditary paraganglioma/pheochromocytoma and inherited succinate dehydrogenase deficiency. Horm Res 63:171–179PubMedCrossRefGoogle Scholar
  16. 16.
    Schiavi F, Boedeker CC, Bausch B, Peczkowska M, Gomez CF, Strassburg T, Pawlu C, Buchta M, Salzmann M, Hoffmann MM, Berlis A, Brink I, Cybulla M, Muresan M, Walter MA, Forrer F, Valimaki M, Kawecki A, Szutkowski Z, Schipper J, Walz MK, Pigny P, Bauters C, Willet-Brozick JE, Baysal BE, Januszewicz A, Eng C, Opocher G, Neumann HP (2005) Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. JAMA 294:2057–2063PubMedCrossRefGoogle Scholar
  17. 17.
    Timmers HJLM, Kozupa A, Eisenhofer G, Raygada M, Adams KT, Solis D, Lenders JWM, Pacak K (2007) Clinical presentations, biochemical phenotypes, and genotype–phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 92:779–785PubMedCrossRefGoogle Scholar
  18. 18.
    Amar L, Bertherat J, Baudin E, Ajzenberg C, Bressac de Paiilerets B, Chabre O, Chamontin B, Delemmer B (2005) Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 23:8812–8818PubMedCrossRefGoogle Scholar
  19. 19.
    Mhatre AN, Li Y, Feng L, Gasperin A, Lalwani AK (2004) SDHB, SDHC, and SDHD mutation screen in sporadic and familial head and neck paragangliomas. Clin Genet 66:461–466PubMedCrossRefGoogle Scholar
  20. 20.
    Renard L, Godfraind C, Boon LM, Vikkula M (2003) A novel mutation in the SDHD gene in a family with inherited paragangliomas-implications of genetic diagnosis for follow up and treatment. Head Neck 25:146–151PubMedCrossRefGoogle Scholar
  21. 21.
    Havekes B, Corssmit EPM, Jansen JC, Van der Mey AGL, Vriends AHJT, Romijn JA (2007) Malignant paragangliomas associated mutations in the succinate dehydrogenase D gene. J Clin Endocrinol Metab 92:1245–1248PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Nicolas Fakhry
    • 1
  • Patricia Niccoli-Sire
    • 2
    • 3
  • Anne Barlier-Seti
    • 4
  • Roch Giorgi
    • 5
  • Antoine Giovanni
    • 1
  • Michel Zanaret
    • 1
  1. 1.Service ORL et Chirurgie Cervico-FacialeCentre Hospitalier Universitaire (CHU) la TimoneMarseille Cedex 05France
  2. 2.Service d’Endocrinologie et de Maladies MétaboliquesCentre Hospitalier Universitaire (CHU) la TimoneMarseilleFrance
  3. 3.Groupe d’étude des Tumeurs Endocrines, networkParisFrance
  4. 4.Service de Biologie MoléculaireCentre Hospitalier Universitaire (CHU) la ConceptionMarseilleFrance
  5. 5.Service de Statistiques et d’Information Médicale (LERTIM)Centre Hospitalier Universitaire (CHU) la TimoneMarseilleFrance

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