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A family with a new elastin gene mutation: broad clinical spectrum, including sudden cardiac death

Published online by Cambridge University Press:  16 November 2010

André Jakob*
Department of Pediatric Cardiology, University Hospital of Freiburg, Mathildenstraße 1, 79106 Freiburg, Germany
Sheila Unger
Department of Human Genetics, University Hospital of Freiburg, Breisacherstraße 33, 79106 Freiburg, Germany
Raoul Arnold
Department of Pediatric Cardiology, University Hospital of Freiburg, Mathildenstraße 1, 79106 Freiburg, Germany
Jochen Grohmann
Department of Pediatric Cardiology, University Hospital of Freiburg, Mathildenstraße 1, 79106 Freiburg, Germany
Cornelia Kraus
Department of Human Genetics, University Hospital of Erlangen, Schwabachanlage 10, 91054 Erlangen, Germany
Christian Schlensak
Department of Cardiac Surgery, University Hospital of Freiburg, Hugstetter Street 55 79106 Freiburg, Germany
Brigitte Stiller
Department of Pediatric Cardiology, University Hospital of Freiburg, Mathildenstraße 1, 79106 Freiburg, Germany
Correspondence to: Dr A. Jakob, Department of Pediatric Cardiology, University Hospital of Freiburg, Mathildenstraße 1, 79106 Freiburg, Germany. Tel: +49(0)761 270 4323; Fax: +49(0)761 270 4468; E-mail:


Supravalvular aortic stenosis is associated with the Williams–Beuren syndrome, but it also occurs in a non-syndromatic congenital form. An elastin gene mutation of chromosome 7q11.23 is responsible in both cases. The vascular features are identical. These patients have a higher risk of sudden death, particularly when undergoing diagnostic or surgical procedures. We report the account of a family with a new mutation in the elastin gene. Screening over three generations revealed eight affected individuals. The cardiac and vascular malformations ranged from mild asymptomatic supravalvular aortic stenosis and isolated dysplastic atrioventricular valves to diffuse arterial hypoplasia. Two infants presented arteries affected at multiple locations, including the left coronary artery. Both died of sudden cardiac death and myocardial ischaemia, one while under general anaesthesia for cardiac catheterisation, and the other perioperatively. We discuss the pathophysiological aspects in these patients that deserve consideration before any general anaesthesia is administered.

Original Articles
Copyright © Cambridge University Press 2010

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1. Curran, ME, Atkinson, DL, Ewart, AK, Morris, CA, Leppert, MF, Keating, MT. The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis. Cell 1993; 73: 159168.CrossRefGoogle ScholarPubMed
2. Ewart, AK, Morris, CA, Ensing, GJ, et al. A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7. Proc Natl Acad Sci U S A 1993; 90: 32263230.CrossRefGoogle ScholarPubMed
3. Rodriguez-Revenga, L, Badenas, C, Carrio, A, Mila, M. Elastin mutation screening in a group of patients affected by vascular abnormalities. Pediatr Cardiol 2005; 26: 827831.CrossRefGoogle Scholar
4. Morris, CA. Genetic aspects of supravalvular aortic stenosis. Curr Opin Cardiol 1998; 13: 214219.Google ScholarPubMed
5. Metcalfe, K, Rucka, AK, Smoot, L, et al. Elastin: mutational spectrum in supravalvular aortic stenosis. Eur J Hum Genet 2000; 8: 955963.CrossRefGoogle ScholarPubMed
6. Ewart, AK, Jin, W, Atkinson, D, Morris, CA, Keating, MT. Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene. J Clin Invest 1994; 93: 10711077.CrossRefGoogle ScholarPubMed
7. Wu, YQ, Sutton, VR, Nickerson, E, et al. Delineation of the common critical region in Williams syndrome and clinical correlation of growth, heart defects, ethnicity, and parental origin. Am J Med Genet 1998; 78: 8289.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
8. Boeckel, T, Dierks, A, Vergopoulos, A, et al. A new mutation in the elastin gene causing supravalvular aortic stenosis. Am J Cardiol 1999; 83: 11411143; A9–A10.CrossRefGoogle ScholarPubMed
9. Dedic, J, Weiss, AS, Katahira, J, Yu, B, Trent, RJ, Urban, Z. A novel elastin gene mutation (1281delC) in a family with supravalvular aortic stenosis: a mutation cluster within exon 20. Hum Mutat 2001; 17: 81.3.0.CO;2-X>CrossRefGoogle Scholar
10. Li, DY, Toland, AE, Boak, BB, et al. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis. Hum Mol Genet 1997; 6: 10211028.CrossRefGoogle ScholarPubMed
11. Tassabehji, M, Metcalfe, K, Donnai, D, et al. Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis. Hum Mol Genet 1997; 6: 10291036.CrossRefGoogle ScholarPubMed
12. Urban, Z, Michels, VV, Thibodeau, SN, Donis-Keller, H, Csiszar, K, Boyd, CD. Supravalvular aortic stenosis: a splice site mutation within the elastin gene results in reduced expression of two aberrantly spliced transcripts. Hum Genet 1999; 104: 135142.Google ScholarPubMed
13. von Dadelszen, P, Chitayat, D, Winsor, EJ, et al. De novo 46,XX,t(6;7)(q27;q11;23) associated with severe cardiovascular manifestations characteristic of supravalvular aortic stenosis and Williams syndrome. Am J Med Genet 2000; 90: 270275.3.0.CO;2-R>CrossRefGoogle Scholar
14. Olson, TM, Michels, VV, Urban, Z, et al. A 30 kb deletion within the elastin gene results in familial supravalvular aortic stenosis. Hum Mol Genet 1995; 4: 16771679.CrossRefGoogle ScholarPubMed
15. Tassabehji, M, Metcalfe, K, Fergusson, WD, et al. LIM-kinase deleted in Williams syndrome. Nat Genet 1996; 13: 272273.CrossRefGoogle ScholarPubMed
16. Frangiskakis, JM, Ewart, AK, Morris, CA, et al. LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell 1996; 86: 5969.CrossRefGoogle ScholarPubMed
17. Bird, LM, Billman, GF, Lacro, RV, et al. Sudden death in Williams syndrome: report of ten cases. J Pediatr 1996; 129: 926931.CrossRefGoogle ScholarPubMed
18. Conway, EE Jr, Noonan, J, Marion, RW, Steeg, CN. Myocardial infarction leading to sudden death in the Williams syndrome: report of three cases. J Pediatr 1990; 117: 593595.CrossRefGoogle ScholarPubMed
19. Wessel, A, Gravenhorst, V, Buchhorn, R, Gosch, A, Partsch, CJ, Pankau, R. Risk of sudden death in the Williams–Beuren syndrome. Am J Med Genet A 2004; 127A: 234237.CrossRefGoogle ScholarPubMed
20. Pham, PP, Moller, JH, Hills, C, Larson, V, Pyles, L. Cardiac catheterization and operative outcomes from a multicenter consortium for children with Williams syndrome. Pediatr Cardiol 2009; 30: 914.CrossRefGoogle Scholar
21. Hirano, E, Knutsen, RH, Sugitani, H, Ciliberto, CH, Mecham, RP. Functional rescue of elastin insufficiency in mice by the human elastin gene: implications for mouse models of human disease. Circ Res 2007; 101: 523531.CrossRefGoogle ScholarPubMed
22. van Son, JA, Edwards, WD, Danielson, GK. Pathology of coronary arteries, myocardium, and great arteries in supravalvular aortic stenosis. Report of five cases with implications for surgical treatment. J Thorac Cardiovasc Surg 1994; 108: 2128.CrossRefGoogle ScholarPubMed
23. Stamm, C, Li, J, Ho, SY, Redington, AN, Anderson, RH. The aortic root in supravalvular aortic stenosis: the potential surgical relevance of morphologic findings. J Thorac Cardiovasc Surg 1997; 114: 1624.CrossRefGoogle ScholarPubMed
24. Vaideeswar, P, Shankar, V, Deshpande, JR, Sivaraman, A, Jain, N. Pathology of the diffuse variant of supravalvar aortic stenosis. Cardiovasc Pathol 2001; 10: 3337.CrossRefGoogle ScholarPubMed
25. Eronen, M, Peippo, M, Hiippala, A, et al. Cardiovascular manifestations in 75 patients with Williams syndrome. J Med Genet 2002; 39: 554558.CrossRefGoogle ScholarPubMed
26. Stamm, C, Friehs, I, Ho, SY, Moran, AM, Jonas, RA, del Nido, PJ. Congenital supravalvar aortic stenosis: a simple lesion? Eur J Cardiothorac Surg 2001; 19: 195202.CrossRefGoogle ScholarPubMed
27. Matsuda, H, Miyamoto, Y, Takahashi, T, Kadoba, K, Nakano, S, Sano, T. Extended aortic and left main coronary angioplasty with a single pericardial patch in a patient with Williams syndrome. Ann Thorac Surg 1991; 52: 13311333.CrossRefGoogle Scholar
28. Terhune, PE, Buchino, JJ, Rees, AH. Myocardial infarction associated with supravalvular aortic stenosis. J Pediatr 1985; 106: 251254.CrossRefGoogle ScholarPubMed
29. van Pelt, NC, Wilson, NJ, Lear, G. Severe coronary artery disease in the absence of supravalvular stenosis in a patient with Williams syndrome. Pediatr Cardiol 2005; 26: 665667.CrossRefGoogle Scholar
30. Bonnet, D, Cormier, V, Villain, E, Bonhoeffer, P, Kachaner, J. Progressive left main coronary artery obstruction leading to myocardial infarction in a child with Williams syndrome. Eur J Pediatr 1997; 156: 751753.CrossRefGoogle Scholar
31. Geggel, RL, Gauvreau, K, Lock, JE. Balloon dilation angioplasty of peripheral pulmonary stenosis associated with Williams syndrome. Circulation 2001; 103: 21652170.CrossRefGoogle ScholarPubMed
32. Izzo, JL Jr. Arterial stiffness and the systolic hypertension syndrome. Curr Opin Cardiol 2004; 19: 341352.CrossRefGoogle ScholarPubMed
33. Horowitz, PE, Akhtar, S, Wulff, JA, Al Fadley, F, Al Halees, Z. Coronary artery disease and anesthesia-related death in children with Williams syndrome. J Cardiothorac Vasc Anesth 2002; 16: 739741.CrossRefGoogle ScholarPubMed
34. Bragg, K, Fedel, GM, DiProsperis, A. Cardiac arrest under anesthesia in a pediatric patient with Williams syndrome: a case report. AANA J 2005; 73: 287293.Google Scholar
35. Monfared, A, Messner, A. Death following tonsillectomy in a child with Williams syndrome. Int J Pediatr Otorhinolaryngol 2006; 70: 11331135.CrossRefGoogle Scholar
36. Park, JH, Kim, HS, Jin, GY, Joo, CU, Ko, JK. Demonstration of peripheral pulmonary stenosis and supravalvular aortic stenosis by different cardiac imaging modalities in a patient with Williams syndrome usefulness of noninvasive imaging studies. Int J Cardiol 2008; 128: e95e97.CrossRefGoogle Scholar