Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families.

W. J. McKenna, P. Spirito, M. Desnos, O. Dubourg, M. Komajda

Department of Cardiological Sciences, St George's Hospital Medical School, London.

The diagnosis of hypertrophic cardiomyopathy has relied on echocardiographic demonstration of unexplained left ventricular hypertrophy. The prevalence of hypertrophic cardiomyopathy defined in this way has been estimated to be 1:500 and experience indicates that these criteria are relatively specific when other causes of left ventricular hypertrophy are absent. In recent years, however, the systematic evaluation of pedigrees performed in the context of molecular genetic studies revealed that in some families with hypertrophic cardiomyopathy up to 20% of adults who carry a disease causing gene defect do not fulfil conventional echocardiographic criteria. None the less, most of these individuals show symptoms, electrocardiographic alterations, and/or minor echocardiographic abnormalities. Revised diagnostic criteria in members of families with hypertrophic cardiomyopathy are proposed, including major and minor criteria based on symptoms, and electrocardiographic and echocardiographic abnormalities. Given that the chance of inheriting the gene defect is 1:2, the likelihood that symptoms plus electrocardiographic or echocardiographic abnormalities are the expression of a disease causing gene is high.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Corrado, D., Pelliccia, A., Heidbuchel, H., Sharma, S., Link, M., Basso, C., Biffi, A., Buja, G., Delise, P., Gussac, I., Anastasakis, A., Borjesson, M., Bjornstad, H. H., Carre, F., Deligiannis, A., Dugmore, D., Fagard, R., Hoogsteen, J., Mellwig, K. P., Panhuyzen-Goedkoop, N., Solberg, E., Vanhees, L., Drezner, J., Estes, N.A. M. III, Iliceto, S., Maron, B. J., Peidro, R., Schwartz, P. J., Stein, R., Thiene, G., Zeppilli, P., McKenna, W. J., On behalf of the Sections of Sports Cardiology of, (2009). Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 0: ehp473v1-ehp473 [Abstract] [Full Text]  
• Michels, M., Soliman, O. I.I., Phefferkorn, J., Hoedemaekers, Y. M., Kofflard, M. J., Dooijes, D., Majoor-Krakauer, D., Ten Cate, F. J. (2009). Disease penetrance and risk stratification for sudden cardiac death in asymptomatic hypertrophic cardiomyopathy mutation carriers. Eur Heart J 30: 2593-2598 [Abstract] [Full Text]  
• Gimeno, J. R., Tome-Esteban, M., Lofiego, C., Hurtado, J., Pantazis, A., Mist, B., Lambiase, P., McKenna, W. J., Elliott, P. M. (2009). Exercise-induced ventricular arrhythmias and risk of sudden cardiac death in patients with hypertrophic cardiomyopathy. Eur Heart J 30: 2599-2605 [Abstract] [Full Text]  
• Corrado, D, Biffi, A, Basso, C, Pelliccia, A, Thiene, G (2009). 12-lead ECG in the athlete: physiological versus pathological abnormalities. Br. J. Sports. Med. 43: 669-676 [Abstract] [Full Text]  
• Ho, C. Y., Carlsen, C., Thune, J. J., Havndrup, O., Bundgaard, H., Farrohi, F., Rivero, J., Cirino, A. L., Andersen, P. S., Christiansen, M., Maron, B. J., Orav, E. J., Kober, L. (2009). Echocardiographic Strain Imaging to Assess Early and Late Consequences of Sarcomere Mutations in Hypertrophic Cardiomyopathy. Circ Cardiovasc Genet 2: 314-321 [Abstract] [Full Text]  
• Michels, M., Soliman, O. I.I., Kofflard, M. J., Hoedemaekers, Y. M., Dooijes, D., Majoor-Krakauer, D., ten Cate, F. J. (2009). Diastolic abnormalities as the first feature of hypertrophic cardiomyopathy in Dutch myosin-binding protein C founder mutations.. J Am Coll Cardiol Img 2: 58-64 [Abstract] [Full Text]  
• Hess, O. M., McKenna, W., Schultheiss, H.-P. (2009). CHAPTER 18 Myocardial Disease. ESC Textbook of Cardiovascular Medicine 2: med-9780199566990-chapter-med-9780199566990-chapter [Abstract] [Full Text]  
• Corrado, D., Basso, C., Pelliccia, A., Thiene, G. (2009). CHAPTER 32 Sports and Heart Disease. ESC Textbook of Cardiovascular Medicine 2: med-9780199566990-chapter-med-9780199566990-chapter [Abstract] [Full Text]  
• Geier, C., Gehmlich, K., Ehler, E., Hassfeld, S., Perrot, A., Hayess, K., Cardim, N., Wenzel, K., Erdmann, B., Krackhardt, F., Posch, M. G., Bublak, A., Nagele, H., Scheffold, T., Dietz, R., Chien, K. R., Spuler, S., Furst, D. O., Nurnberg, P., Ozcelik, C. (2008). Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy. Hum Mol Genet 17: 2753-2765 [Abstract] [Full Text]  
• Kounas, S., Demetrescu, C., Pantazis, A. A., Keren, A., Lee, P. J., Hughes, D., Mehta, A., Elliott, P. M. (2008). The Binary Endocardial Appearance Is a Poor Discriminator of Anderson-Fabry Disease From Familial Hypertrophic Cardiomyopathy. J Am Coll Cardiol 51: 2058-2061 [Abstract] [Full Text]  
• Monserrat, L., Gimeno-Blanes, J. R., Marin, F., Hermida-Prieto, M., Garcia-Honrubia, A., Perez, I., Fernandez, X., de Nicolas, R., de la Morena, G., Paya, E., Yague, J., Egido, J. (2007). Prevalence of Fabry Disease in a Cohort of 508 Unrelated Patients With Hypertrophic Cardiomyopathy. J Am Coll Cardiol 50: 2399-2403 [Abstract] [Full Text]  
• Corrado, D., McKenna, W. J. (2007). Appropriate interpretation of the athlete's electrocardiogram saves lives as well as money. Eur Heart J 28: 1920-1922 [Full Text]  
• Geier, C., Perrot, A., Ozcelik, C. (2007). Letter by Geier et al Regarding Article, "Hypertrophic Cardiomyopathy Is Predominantly a Disease of Left Ventricular Outflow Tract Obstruction". Circulation 115: e622-e622 [Full Text]  
• Elliott, P. M., Gimeno, J. R., Tome, M. T., Shah, J., Ward, D., Thaman, R., Mogensen, J., McKenna, W. J. (2006). Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J 27: 1933-1941 [Abstract] [Full Text]  
• Elliott, P M, Gimeno, J R, Thaman, R, Shah, J, Ward, D, Dickie, S, Tome Esteban, M T, McKenna, W J (2006). Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy. Heart 92: 785-791 [Abstract] [Full Text]  
• Sipola, P., Lauerma, K., Jaaskelainen, P., Laakso, M., Peuhkurinen, K., Manninen, H., Aronen, H. J., Kuusisto, J. (2005). Cine MR Imaging of Myocardial Contractile Impairment in Patients with Hypertrophic Cardiomyopathy Attributable to Asp175Asn Mutation in the {alpha}-Tropomyosin Gene. Radiology 236: 815-824 [Abstract] [Full Text]  
• Moon, J C, Mogensen, J, Elliott, P M, Smith, G C, Elkington, A G, Prasad, S K, Pennell, D J, McKenna, W J (2005). Myocardial late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by mutations in troponin I. Heart 91: 1036-1040 [Abstract] [Full Text]  
• Thaman, R, Gimeno, J R, Murphy, R T, Kubo, T, Sachdev, B, Mogensen, J, Elliott, P M, McKenna, W J (2005). Prevalence and clinical significance of systolic impairment in hypertrophic cardiomyopathy. Heart 91: 920-925 [Abstract] [Full Text]  
• Mogensen, J., Murphy, R. T., Kubo, T., Bahl, A., Moon, J. C., Klausen, I. C., Elliott, P. M., McKenna, W. J. (2004). Frequency and clinical expression of cardiac troponin I mutations in 748 consecutive families with hypertrophic cardiomyopathy. J Am Coll Cardiol 44: 2315-2325 [Abstract] [Full Text]  
• Maron, B. J., Seidman, J.G., Seidman, C. E. (2004). Proposal for contemporary screening strategies in families with hypertrophic cardiomyopathy. J Am Coll Cardiol 44: 2125-2132 [Abstract] [Full Text]  
• Mogensen, J, Perrot, A, Andersen, P S, Havndrup, O, Klausen, I C, Christiansen, M, Bross, P, Egeblad, H, Bundgaard, H, Osterziel, K J, Haltern, G, Lapp, H, Reinecke, P, Gregersen, N, Borglum, A D (2004). Clinical and genetic characteristics of {alpha} cardiac actin gene mutations in hypertrophic cardiomyopathy. J. Med. Genet. 41: e10-10 [Full Text]  
• Isobe, S., Izawa, H., Takeichi, Y., Nonokawa, M., Nanasato, M., Ando, A., Kato, K., Ikeda, M., Murohara, T., Yokota, M. (2003). Relationship Between Exercise-Induced Myocardial Ischemia and Reduced Left Ventricular Distensibility in Patients with Nonobstructive Hypertrophic Cardiomyopathy. JNM 44: 1717-1724 [Abstract] [Full Text]  
• Woo, A, Rakowski, H, Liew, J C, Zhao, M-S, Liew, C-C, Parker, T G, Zeller, M, Wigle, E D, Sole, M J (2003). Mutations of the {beta} myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Heart 89: 1179-1185 [Abstract] [Full Text]  
• Monserrat, L., Elliott, P. M., Gimeno, J. R., Sharma, S., Penas-Lado, M., McKenna, W. J. (2003). Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients. J Am Coll Cardiol 42: 873-879 [Abstract] [Full Text]  
• Crilley, J. G., Boehm, E. A., Blair, E., Rajagopalan, B., Blamire, A. M., Styles, P., McKenna, W. J., Ostman-Smith, I., Clarke, K., Watkins, H. (2003). Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J Am Coll Cardiol 41: 1776-1782 [Abstract] [Full Text]  
• Sipola, P., Vanninen, E., Aronen, H. J., Lauerma, K., Simula, S., Jaaskelainen, P., Laakso, M., Peuhkurinen, K., Kuusisto, J., Kuikka, J. T. (2003). Cardiac Adrenergic Activity Is Associated with Left Ventricular Hypertrophy in Genetically Homogeneous Subjects with Hypertrophic Cardiomyopathy. JNM 44: 487-493 [Abstract] [Full Text]  
• Geier, C., Perrot, A., Ozcelik, C., Binner, P., Counsell, D., Hoffmann, K., Pilz, B., Martiniak, Y., Gehmlich, K., van der Ven, P. F.M., Furst, D. O., Vornwald, A., von Hodenberg, E., Nurnberg, P., Scheffold, T., Dietz, R., Osterziel, K. J. (2003). Mutations in the Human Muscle LIM Protein Gene in Families With Hypertrophic Cardiomyopathy. Circulation 107: 1390-1395 [Abstract] [Full Text]  
• Havndrup, O., Bundgaard, H., Skytt Andersen, P., Allan Larsen, L., Vuust, J., Kjeldsen, K., Christiansen, M. (2003). Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac {beta}-myosin gene mutations. Cardiovasc Res 57: 347-357 [Abstract] [Full Text]  
• Olivotto, I., Gistri, R., Petrone, P., Pedemonte, E., Vargiu, D., Cecchi, F. (2003). Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 41: 315-321 [Abstract] [Full Text]  
• Sipola, P., Lauerma, K., Husso-Saastamoinen, M., Kuikka, J. T., Vanninen, E., Laitinen, T., Manninen, H., Niemi, P., Peuhkurinen, K., Jaaskelainen, P., Laakso, M., Kuusisto, J., Aronen, H. J. (2003). First-Pass MR Imaging in the Assessment of Perfusion Impairment in Patients with Hypertrophic Cardiomyopathy and the Asp175Asn Mutation of the {alpha}-Tropomyosin Gene. Radiology 226: 129-137 [Abstract] [Full Text]  
• Hamid, M. S., Norman, M., Quraishi, A., Firoozi, S., Thaman, R., Gimeno, J. R., Sachdev, B., Rowland, E., Elliott, P. M., McKenna, W. J. (2002). Prospective evaluation of relatives for familial arrhythmogenic right ventricular cardiomyopathy/dysplasia reveals a need to broaden diagnostic criteria. J Am Coll Cardiol 40: 1445-1450 [Abstract] [Full Text]  
• Osterziel, K.J., Bit-Avragim, N., Bunse, M. (2002). Cardiac hypertrophy in Friedreich's ataxia. Cardiovasc Res 54: 694-694 [Full Text]  
• Lodi, R., Rajagopalan, B., Crilley, J.G., Cooper, J.M., Styles, P., Schapira, A.H.V. (2002). Reply to Letter to the Editor. Cardiovasc Res 54: 695-696 [Full Text]  
• Ortlepp, J R, Vosberg, H P, Reith, S, Ohme, F, Mahon, N G, Schroder, D, Klues, H G, Hanrath, P, McKenna, W J (2002). Genetic polymorphisms in the renin-angiotensin-aldosterone system associated with expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a study of five polymorphic genes in a family with a disease causing mutation in the myosin binding protein C gene. Heart 87: 270-275 [Abstract] [Full Text]  
• Andersen, P. S., Havndrup, O., Bundgaard, H., Moolman-Smook, J. C., Larsen, L. A., Mogensen, J., Brink, P. A., Borglum, A. D., Corfield, V. A., Kjeldsen, K., Vuust, J., Christiansen, M. (2001). Myosin light chain mutations in familial hypertrophic cardiomyopathy: phenotypic presentation and frequency in Danish and South African populations. J. Med. Genet. 38 : e43-e43 [Full Text]  
• Watkins, H. (2001). Hypertrophic cardiomyopathy: from molecular and genetic mechanisms to clinical management. Eur Heart J Suppl 3: L43-L50 [Abstract]  
• Varnava, A. M., Elliott, P. M., Baboonian, C., Davison, F., Davies, M. J., McKenna, W. J. (2001). Hypertrophic Cardiomyopathy: Histopathological Features of Sudden Death in Cardiac Troponin T Disease. Circulation 104: 1380-1384 [Abstract] [Full Text]  
• Elliott, P. M., Poloniecki, J., Dickie, S., Sharma, S., Monserrat, L., Varnava, A., Mahon, N. G., McKenna, W. J. (2000). Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 36: 2212-2218 [Abstract] [Full Text]  
• D'CRUZ, L. G, BABOONIAN, C., PHILLIMORE, H. E, TAYLOR, R., ELLIOTT, P. M, VARNAVA, A., DAVISON, F., MCKENNA, W. J, CARTER, N. D (2000). Cytosine methylation confers instability on the cardiac troponin T gene in hypertrophic cardiomyopathy. J. Med. Genet. 37: 18e-18 [Full Text]  
• Moolman, J. A., Reith, S., Uhl, K., Bailey, S., Gautel, M., Jeschke, B., Fischer, C., Ochs, J., McKenna, W. J., Klues, H., Vosberg, H.-P. (2000). A Newly Created Splice Donor Site in Exon 25 of the MyBP-C Gene Is Responsible for Inherited Hypertrophic Cardiomyopathy With Incomplete Disease Penetrance. Circulation 101: 1396-1402 [Abstract] [Full Text]  
• Crispell, K. A., Wray, A., Ni, H., Nauman, D. J., Hershberger, R. E. (1999). Clinical profiles of four large pedigrees with familial dilated cardiomyopathy: Preliminary recommendations for clinical practice. J Am Coll Cardiol 34: 837-847 [Abstract] [Full Text]  
• Feetham, S. L. (1999). The Future in Family Nursing Is Genetics and It Is Now. Journal of Family Nursing 5: 3-9  
• Jaaskelainen, P., Soranta, M., Miettinen, R., Saarinen, L., Pihlajamaki, J., Silvennoinen, K., Tikanoja, T., Laakso, M., Kuusisto, J. (1998). The cardiac {beta}-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population. J Am Coll Cardiol 32: 1709-1716 [Abstract] [Full Text]