Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-24T14:32:23.430Z Has data issue: false hasContentIssue false
  • English
  • Français

Evaluation of genetic causes of cardiomyopathy in childhood*

Published online by Cambridge University Press:  17 September 2015

Stephanie M. Ware
Stephanie M. Ware*
Affiliation:
Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
*
Correspondence to: S. M. Ware, Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America. Tel: +1-317-274-8938; Fax: +1-317-274-8679; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Cardiomyopathy frequently has a genetic basis. In adults, mutations in genes encoding components of the sarcomere, cytoskeleton, or desmosome are frequent genetic causes of cardiomyopathy. Although children share these causes, ~30% of children have an underlying metabolic, syndromic, or neuromuscular condition causing their cardiomyopathy, making the aetiologies more diverse in children as compared with adults. Although some children present with obvious signs or symptoms of metabolic, syndromic, or neuromuscular disease, other cases may be quite subtle, requiring a high level of suspicion in order to diagnose them. In general, the younger the child, the more extensive the differential. Advantages of identifying the underlying genetic cause of cardiomyopathy in the paediatric population include confirming the diagnosis in ambiguous cases, facilitating appropriate surveillance and management of cardiac and extra-cardiac diseases, providing prognostic information, and establishing the genetic basis in the family, thereby allowing the identification of at-risk relatives and institution of appropriate family screening as indicated. For these reasons, genetic testing is increasingly recognised as standard of care, and guidelines for genetic counselling, testing, and incorporation of family-based risk assessment have been established. Therapies aimed at treating specific genetic aetiologies of cardiomyopathy are emerging and are exciting new developments that require increasingly sophisticated approaches to diagnosis. As genetic testing capabilities continue to expand technically, careful interpretation, knowledgeable clinical utilisation, and appropriate dissemination of genetic information are important and challenging components of clinical care.

Keywords

Mutationgenetic variantgenetic syndromesarcomere
Type
Original Articles
Information
Cardiology in the Young , Volume 25 , Supplement S2: Special Supplement of Cardiology in the Young: Proceedings of the 2015 International Paediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute , August 2015 , pp. 43 - 50
Copyright
© Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Presented at Johns Hopkins All Children’s Heart Institute, International Pediatric Heart Failure Summit, Saint Petersburg, Florida, United States of America, 4–5 February, 2015.

References

1. Colan, SD, Lipshultz, SE, Lowe, AM, et al. Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the pediatric cardiomyopathy registry. Circulation 2007; 115: 773–781.Google Scholar
2. Grenier, MA, Osganian, SK, Cox, GF, et al. Design and implementation of the North American Pediatric Cardiomyopathy registry. Am Heart J 2000; 139: S86–S95.CrossRefGoogle ScholarPubMed
3. Towbin, JA, Lowe, AM, Colan, SD, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA 2006; 296: 1867–1876.Google Scholar
4. Wilkinson, JD, Landy, DC, Colan, SD, et al. The Pediatric Cardiomyopathy Registry and heart failure: key results from the first 15 years. Heart Fail Clin 2010; 6: 401–413, vii.Google Scholar
5. Cox, GF, Sleeper, LA, Lowe, AM, et al. Factors associated with establishing a causal diagnosis for children with cardiomyopathy. Pediatrics 2006; 118: 1519–1531.Google Scholar
6. Lipshultz, SE, Orav, EJ, Wilkinson, JD, et al. Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: an analysis of data from the Pediatric Cardiomyopathy Registry. Lancet 2013; 382: 1889–1897.CrossRefGoogle ScholarPubMed
7. Kaski, JP, Syrris, P, Burch, M, et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. Heart 2008; 94: 1478–1484.Google Scholar
8. Kaski, JP, Syrris, P, Esteban, MT, et al. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ Cardiovasc Genet 2009; 2: 436–441.CrossRefGoogle ScholarPubMed
9. Kindel, SJ, Miller, EM, Gupta, R, et al. Pediatric cardiomyopathy: importance of genetic and metabolic evaluation. J Card Fail 2012; 18: 396–403.CrossRefGoogle ScholarPubMed
10. Tariq, M, Ware, SM. Importance of genetic evaluation and testing in pediatric cardiomyopathy. World J Cardiol 2014; 6: 1156–1165.Google Scholar
11. Tandon, A, Jefferies, JL, Villa, CR, et al. Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophies using cardiac magnetic resonance imaging. Am J Cardiol 2015; 115: 967–971.Google Scholar
12. Payne, RM, Wagner, GR. Cardiomyopathy in Friedreich ataxia: clinical findings and research. J Child Neurol 2012; 27: 1179–1186.CrossRefGoogle ScholarPubMed
13. Cox, GF. Diagnostic approaches to pediatric cardiomyopathy of metabolic genetic etiologies and their relation to therapy. Prog Pediatr Cardiol 2007; 24: 15–25.Google Scholar
14. Badertscher, A, Bauersfeld, U, Arbenz, U, Baumgartner, MR, Schinzel, A, Balmer, C. Cardiomyopathy in newborns and infants: a broad spectrum of aetiologies and poor prognosis. Acta Paediatrica 2008; 97: 1523–1528.CrossRefGoogle ScholarPubMed
15. Byers, SL, Ficicioglu, C. Infant with cardiomyopathy: when to suspect inborn errors of metabolism? World J Cardiol 2014; 6: 1149–1155.CrossRefGoogle ScholarPubMed
16. American College of Medical Genetics Newborn Screening Expert G. Newborn screening: toward a uniform screening panel and system – executive summary. Pediatrics 2006; 117: S296–S307.CrossRefGoogle Scholar
17. Therrell, BL Jr., Lloyd-Puryear, MA, Camp, KM, Mann, MY. Inborn errors of metabolism identified via newborn screening: ten-year incidence data and costs of nutritional interventions for research agenda planning. Mol Genet Metab 2014; 113: 14–26.CrossRefGoogle ScholarPubMed
18. Laemmle, A, Balmer, C, Doell, C, Sass, JO, Haberle, J, Baumgartner, MR. Propionic acidemia in a previously healthy adolescent with acute onset of dilated cardiomyopathy. Eur J Pediatr 2014; 173: 971–974.Google Scholar
19. Lee, TM, Addonizio, LJ, Barshop, BA, Chung, WK. Unusual presentation of propionic acidaemia as isolated cardiomyopathy. J Inherit Metab Dis 2009; 32 (Suppl 1): S97–S101.Google Scholar
20. Scaglia, F, Towbin, JA, Craigen, WJ, et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics 2004; 114: 925–931.CrossRefGoogle ScholarPubMed
21. Tartaglia, M, Gelb, BD, Zenker, M. Noonan syndrome and clinically related disorders. Best Prac Res Clin Endocrinol Metab 2011; 25: 161–179.Google Scholar
22. Wilkinson, JD, Lowe, AM, Salbert, BA, et al. Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: a study from the Pediatric Cardiomyopathy Registry. Am Heart J 2012; 164: 442–448.CrossRefGoogle ScholarPubMed
23. Romano, AA, Allanson, JE, Dahlgren, J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics 2010; 126: 746–759.Google Scholar
24. Long, PA, Evans, JM, Olson, TM. Exome sequencing establishes diagnosis of Alstrom syndrome in an infant presenting with non-syndromic dilated cardiomyopathy. Am J Med Genet A 2015; 167A: 886–890.Google Scholar
25. Michaud, JL, Heon, E, Guilbert, F, et al. Natural history of Alstrom syndrome in early childhood: onset with dilated cardiomyopathy. J Pediatr 1996; 128: 225–229.CrossRefGoogle ScholarPubMed
26. Czosek, RJ, Goldenberg, P, Miller, EM, Spicer, R, Towbin, JA, Ware, SM. Cardiac electrical system involvement in Alström syndrome: uncommon causes of dilated cardiomyopathies. Cardiogenetics 2012; 2: 6–10.CrossRefGoogle Scholar
27. Worthley, MI, Zeitz, CJ. Case of Alstrom syndrome with late presentation dilated cardiomyopathy. Intern Med J 2001; 31: 569–570.Google Scholar
28. Hershberger, RE, Lindenfeld, J, Mestroni, L, et al. Genetic evaluation of cardiomyopathy – a heart failure society of America practice guideline. J Card Fail 2009; 15: 83–97.CrossRefGoogle Scholar
29. Ackerman, MJ, Priori, SG, Willems, S, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm 2011; 8: 1308–1339.CrossRefGoogle ScholarPubMed
30. Bos, JM, Towbin, JA, Ackerman, MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol 2009; 54: 201–211.Google Scholar
31. Charron, P, Arad, M, Arbustini, E, et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2010; 31: 2715–2726.Google Scholar
32. Watkins, H, Ashrafian, H, Redwood, C. Inherited cardiomyopathies. N Engl J Med 2011; 364: 1643–1656.CrossRefGoogle ScholarPubMed
33. Van Langen, I, Arens, Y, Baars, H, et al. Genetic diagnostics and genetic counselling in Hypertrophic Cardiomyopathy (HCM). Neth Heart J 2010; 18: 144–159.Google Scholar
34. Miller, EM, Wang, Y, Ware, SM. Uptake of cardiac screening and genetic testing among hypertrophic and dilated cardiomyopathy families. J Genet Couns 2013; 22: 258–267.Google Scholar