Advertisement

Carotid Body Tumors in Humans Caused by a Mutation in the Gene for Succinate Dehydrogenase D (SDHD)

  • Albert Dahan
  • Peter E. M. Taschner
  • Jeroen C. Jansen
  • Andel van der Mey
  • Luc J. Teppema
  • Cees J. Cornelisse
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 551)

Abstract

Tumors of the carotid bodies (CB) are commonly associated with chronic tissue hypoxia from altitude, cyanotic heart disease and chronic pulmonary disease.1, 2, 3, 4, 5 Here, we describe a hereditary form of carotid body tumors, which is not related to exposure to chronic hypoxia but is related to a missense mutation in the gene that encodes for succinate dehydrogenase D (SDHD). SDHD is a small part of cytochrome b588 of the mitochondrial respiratory chain complex II and an essential enzyme in the Krebs tricarboxylic-acid cycle.6 These carotid body tumors are part of the hereditary paraganglioma type I (PGL1) syndrome.7 The PGL1 syndrome is characterized by slowly growing tumors derived from paraganglia in the head and neck area (see Fig. 1) and (Fig. 2, color insert). Paraganglia are cell-clusters of neuro-ectodermal origin that have a close relationship with the autonomic nervous system and have the ability to synthesize catecholamines (e.g., dopamine). The most common PGL tumor locations are the carotid bodies and the adrenal medulla. Other paraganglia which may be affected are: the vagal bodies at the nodose ganglion of the vagal nerve, the tympanic bodies at the promontory of the middle ear, the jugular bodies at the jugular foramen, the laryngeal bodies in the larynx, and the aortic bodies in the wall of the ascending aorta and aortic arch.

Keywords

Carotid Body Uterine Fibroid Glomus Tumor Fumarate Hydratase Nodose Ganglion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    L. Pacheco-Ojeda, D. Enrique, C. Rodriguez and N. Vivar. Carotid body tumors at high altitude: Quito, Equador, 1987. World J. Surg. 12, 856–860 (1988).CrossRefPubMedGoogle Scholar
  2. 2.
    M.J. Nissenblatt. Cyanotic heart disease: “low altitude” risk for carotid body tumor? Johns Hopkins Med. J. 142, 18–21 (1978).PubMedGoogle Scholar
  3. 3.
    J.H. Hirsch, F.C. Killien and R.H. Troupin. Bilateral carotid body tumors and cyanotic heart disease. Am. J. Radiol. 134, 1073–1075 (1980).Google Scholar
  4. 4.
    H. Gruber and R. Metson. Carotid body paraganglioma regression with relief of hypoxemia. Ann. Int. Med. 92, 800–802 (1980).PubMedGoogle Scholar
  5. 5.
    J. Herget, C.A. Brown, S. Kutilek, G.R. Barer and F. Palacek. Enlargement of carotid bodies in rats with lung emphysema or silicosis. Bull. europ. Physiopath. resp. 18, 75–79 (1982).Google Scholar
  6. 6.
    B.E. Baysal, R. Ferrell, J. Willet-Brozik, E. Lawrence, D. Myssiorek, A. Bosch, A. van der Mey, P. Taschner, W. Rubinstein, E. Myers, C. Richard, C.J. Cornelisse, P. Devilee and B. Devlin. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 297, 848–851 (2000).CrossRefGoogle Scholar
  7. 7.
    J.C. Jansen. Paragangliomas of the head and neck: Clinical implications of growth rate and genetics (PhD thesis, Leiden University, Leiden, 2001).Google Scholar
  8. 8.
    A. Dahan, J. DeGoede, A. Berkenbosch and I. Olievier. The influence of oxygen on the ventilatory response to carbon dioxide in man. J. Physiol. (Lond.) 428, 485–499 (1990).Google Scholar
  9. 9.
    L.J. Teppema, D. Nieuwenhuijs, E. Sarton, R. Romberg. C.N. Olievier, D.S. Ward and A. Dahan. Antioxidants prevent depression of the acute hypoxic ventilatory response by subanaesthetic halothane in men. J. Physiol. (Lond.) 544, 931–938 (2002).CrossRefGoogle Scholar
  10. 10.
    C. Eng, M. Kiuru, M.J. Fernandez and L.A. Aaltonen. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat. Rev. Cancer 3, 193–202 (2003).CrossRefPubMedGoogle Scholar
  11. 11.
    F.M. van Baars, C.W. Cremers, P. vanden Broek and J.E. Veldman. Familiar non-chromaffinic paragangliomas (glomus tumors). Clinical and genetic aspects. Acta Otolaryngol. 91, 589–593 (1981).CrossRefPubMedGoogle Scholar
  12. 12.
    A. van der Mey, P. Maaswinkel-Mooy, C. Cornelisse, P. Schmidt and J. vande Kamp. Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory. Lancet 2.8675, 1291–1294 (1989).PubMedGoogle Scholar
  13. 13.
    W. Reik and J. Walter. Genomic imprinting: parental influence on the genome. Nat. Rev. Genet. 2, 21–32 (2001).CrossRefPubMedGoogle Scholar
  14. 14.
    P. Heutink, A.G. van der Mey, L.A. Sandkuijl, A.P. van Gils, A. Bardoel, G.J. Breedveld, M. van Vliet, G.J. van Ommen, C.J. Cornelisse and Oostra BA. A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter. Hum. Mol. Genet. 1, 7–10 (1992).CrossRefPubMedGoogle Scholar
  15. 15.
    E.C. Mariman, S.E. van Beersum, C.W. Cremers, P.M. Struycken and H.H. Ropers. Fine mapping of a putatively imprinted gene for familial non-chromaffin paragangliomas to chromosome 11q13.1: evidence for genetic heterogeneity. Hum. Genet. 95, 56–62 (1995).CrossRefPubMedGoogle Scholar
  16. 16.
    E.M. van Schothorst, M. Beekman, P. Torremans, N.J. Kuipers-Dijkshoom, H.W. Wessels, A.F. Bardoel, A.G. van der Mey, M.J. van der Vijver, G.J. van Ommen, P. Devilee and C.J. Cornelisse. Paragangliomas of the head and neck region show complete loss of heterozygosity at 11q22–q23 in chief cells and the flow-sorted DNA aneuploid fraction. Hum. Pathol. 29, 1045–49 (1998).CrossRefPubMedGoogle Scholar
  17. 17.
    P.E. Taschner, J. Jansen, B.E. Baysal, A. Bosch, E.H. Rosenberg, A.H. Brocker-Vriends, A.G. vander Mey, G. van Ommen, C.J. Cornelisse and P. Devilee. Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene. Gen. Chrom. Canc. 31, 274–281 (2001).CrossRefGoogle Scholar
  18. 18.
    D. Astuti, F. Latif, A. Dallol, P.L. Dahia, F. Douglas, E. George, F. Skoldberg, E.S. Husebye, C. Eng and E.R. Maher. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am.J. Hum Genet. 69(1): 49–54, 2001.CrossRefPubMedGoogle Scholar
  19. 19.
    S. Niemann and U. Muller. Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat. Genet. 26, 268–270 (2000).CrossRefPubMedGoogle Scholar
  20. 20.
    J. Arias-Stella and J. Valcarcel. The human carotid body at high altitudes. Pathol. Microbiol. (Basel) 39, 292–297 (1973).Google Scholar
  21. 21.
    K. Astrom, J. Cohen, J. Willett, C. Aston and B. Baysal. Altitude is a phenotypic modifier in hereditary paraganglioma type 1: evidence for an oxygen-sensing defect. Hum. Genet. 113, 228–237 (2003).CrossRefPubMedGoogle Scholar
  22. 22.
    A.P. Gimenez-Roqueplo and the COMETE Network. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res. 63, 5615–5621 (2003).Google Scholar
  23. 23.
    I.P. Tomlinson and the Multiple Leiomyoma Consortium. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet. 30, 406–410 (2002).CrossRefGoogle Scholar
  24. 24.
    N.H. Edelman, S. Lahiri, L. Braudo, N.S. Cherniack and A.P. Fishman. The blunted ventilatory response to hypoxia in cyanotic congenital heart disease. N. Eng. J. Med. 282, 405–411 (1970).Google Scholar

Copyright information

© Kluwer Academic/Plenum Publishers, New York 2004

Authors and Affiliations

  • Albert Dahan
    • 1
  • Peter E. M. Taschner
    • 2
  • Jeroen C. Jansen
    • 3
  • Andel van der Mey
    • 3
  • Luc J. Teppema
    • 1
  • Cees J. Cornelisse
    • 4
  1. 1.Department of AnesthesiologyLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of Human GeneticsLeiden University Medical CenterLeidenThe Netherlands
  3. 3.Department of OtorhinolaryngologyLeiden University Medical CenterLeidenThe Netherlands
  4. 4.Department of PathologyLeiden University Medical CenterLeidenThe Netherlands

Personalised recommendations