Abstract
Tumors of the carotid bodies (CB) are commonly associated with chronic tissue hypoxia from altitude, cyanotic heart disease and chronic pulmonary disease.1–5 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
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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
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).
M.J. Nissenblatt. Cyanotic heart disease: “low altitude” risk for carotid body tumor? Johns Hopkins Med. J. 142, 18–21 (1978).
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).
H. Gruber and R. Metson. Carotid body paraganglioma regression with relief of hypoxemia. Ann. Int. Med. 92, 800–802 (1980).
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).
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).
J.C. Jansen. Paragangliomas of the head and neck: Clinical implications of growth rate and genetics (PhD thesis, Leiden University, Leiden, 2001).
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).
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).
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).
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).
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).
W. Reik and J. Walter. Genomic imprinting: parental influence on the genome. Nat. Rev. Genet. 2, 21–32 (2001).
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).
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).
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).
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).
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.
S. Niemann and U. Muller. Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat. Genet. 26, 268–270 (2000).
J. Arias-Stella and J. Valcarcel. The human carotid body at high altitudes. Pathol. Microbiol. (Basel) 39, 292–297 (1973).
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).
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).
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).
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).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Kluwer Academic/Plenum Publishers, New York
About this paper
Cite this paper
Dahan, A., Taschner, P.E.M., Jansen, J.C., van der Mey, A., Teppema, L.J., Cornelisse, C.J. (2004). Carotid Body Tumors in Humans Caused by a Mutation in the Gene for Succinate Dehydrogenase D (SDHD). In: Champagnat, J., Denavit-Saubié, M., Fortin, G., Foutz, A.S., Thoby-Brisson, M. (eds) Post-Genomic Perspectives in Modeling and Control of Breathing. Advances in Experimental Medicine and Biology, vol 551. Springer, Boston, MA. https://doi.org/10.1007/0-387-27023-X_12
Download citation
DOI: https://doi.org/10.1007/0-387-27023-X_12
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-306-48507-7
Online ISBN: 978-0-387-27023-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)