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Cardiac manifestations of congenital LMNA-related muscular dystrophy in children: three case reports and recommendations for care

Published online by Cambridge University Press:  12 December 2016

Felice Heller ,
Ivana Dabaj ,
Jean K. Mah ,
Jean Bergounioux ,
Aben Essid ,
Carsten G. Bönnemann ,
Anne Rutkowski ,
Gisèle Bonne ,
Susana Quijano-Roy  and
Karim Wahbi
Felice Heller*
Affiliation:
Department of Pediatrics, University of Connecticut School of Medicine, Connecticut Children’s Medical Center, Hartford, Connecticut, United States of America
Ivana Dabaj
Affiliation:
AP-HP, Pediatric Department, Raymond Poincaré Hospital, University Hospitals of West Paris, Garches, France Referral Center for Neuromuscular Diseases Garches-Necker-Mondor-Hendaye (GNMH), French Network of Neuromuscular Diseases (FILNEMUS), Garches, France
Jean K. Mah
Affiliation:
Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
Jean Bergounioux
Affiliation:
AP-HP, Pediatric Department, Raymond Poincaré Hospital, University Hospitals of West Paris, Garches, France
Aben Essid
Affiliation:
AP-HP, Pediatric Department, Raymond Poincaré Hospital, University Hospitals of West Paris, Garches, France
Carsten G. Bönnemann
Affiliation:
Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America
Anne Rutkowski
Affiliation:
Cure Congenital Muscular Dystrophy and Kaiser SCPMG, Los Angeles, California, United States of America
Gisèle Bonne
Affiliation:
Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS974, CNRS FRE3617, Center for Research in Myology, Paris, France Institut de Myologie, Paris, France
Susana Quijano-Roy
Affiliation:
AP-HP, Pediatric Department, Raymond Poincaré Hospital, University Hospitals of West Paris, Garches, France Referral Center for Neuromuscular Diseases Garches-Necker-Mondor-Hendaye (GNMH), French Network of Neuromuscular Diseases (FILNEMUS), Garches, France Versailles-St Quentin University, U1179 UVSQ – INSERM, Montigny, France
Karim Wahbi
Affiliation:
Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS974, CNRS FRE3617, Center for Research in Myology, Paris, France Institut de Myologie, Paris, France Cardiology Department, AP-HP, Cochin Hospital, Paris Cedex, France AP-HP, Pitié-Salpêtrière Hospital, Referral Center for Muscle Diseases East Paris, Myology Institute, Paris, France Université Paris Descartes-Sorbonne Paris Cité, Paris, France
*
Correspondence to: F. Heller, MD, Division of Pediatric Cardiology, Suite 2B, Connecticut Children’s Medical Center, 282 Washington Street, Hartford, CT 06106, United States of America. Tel: 860 545 9400; Fax: 860 545 9410; E-mail: fheller@connecticutchildrens.org
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Abstract

Skeletal and cardiac muscle laminopathies, caused by mutations in the lamin A/C gene, have a clinical spectrum from congenital LMNA-related muscular dystrophy to later-onset Emery–Dreifuss muscular dystrophy, limb girdle muscular dystrophy, and dilated cardiomyopathy. Although cardiac involvement is observed at all ages, it has only been well described in adults. We present the evolution of cardiac disease in three children with congenital muscular dystrophy presentation of LMNA-related muscular dystrophy. In this series, atrial arrhythmia was the presenting cardiac finding in all three patients. Heart failure developed up to 5 years later. Symptoms of right heart failure, including diarrhoea and peripheral oedema, preceded a rapid decline in left ventricular ejection fraction. Recommendations for cardiac surveillance and management in these patients are made.

Keywords

Lamin A/C LMNAcongenital muscular dystrophycardiomyopathyarrhythmiaautomatic implantable cardiac defibrillator
Type
Original Articles
Information
Cardiology in the Young , Volume 27 , Issue 6 , August 2017 , pp. 1076 - 1082
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Copyright
© Cambridge University Press 2016 

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References

1. Sparks, S, Quijano-Roy, S, Harper, A, et al. Congenital muscular dystrophy overview. GeneReviews™, University of Washington, Seattle Washington, 1993-2013.Google Scholar
2. Graziano, A, Bianco, F, D’Amico, A, et al. Prevalence of congenital muscular dystrophy in Italy: a population study. Neurology 2015; 84: 904–911.CrossRefGoogle ScholarPubMed
3. Quijano-Roy, S, Mbieleu, B, Bönnemann, CG, et al. De novo LMNA mutations cause a new form of congenital muscular dystrophy. Ann Neurol 2008; 64: 177–186.Google Scholar
4. Bönnemann, CG, Wang, CH, Quijano-Roy, S, et al. Diagnostic approach to the congenital muscular dystrophies. Neuromuscul Disord 2014; 24: 289–311.CrossRefGoogle Scholar
5. Meune, C, Van Berlo, JH, Anselme, F, Bonne, G, Pinto, YM, Duboc, D. Primary prevention of sudden death in patients with lamin A/C gene mutations. N Engl J Med 2006; 354: 209–210.CrossRefGoogle ScholarPubMed
6. van Rijsingen, IA, Arbustini, E, Elliott, PM, et al. Risk factors for malignant ventricular arrhythmias in lamin A/C mutation carriers a European cohort study. J Am Coll Cardiol 2012; 59: 493–500.CrossRefGoogle ScholarPubMed
7. Niebauer, J, Volk, HD, Kemp, M, Dominguez, M, Schumann, RR, Rauchhaus, M, Poole-Wilson, PA, Coats, AJ, Anker, SD. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 1999; 353: 1838–1842.CrossRefGoogle ScholarPubMed
8. Krack, A, Richartz, BM, Gastmann, A, Greim, K, Lotze, U, Anker, SD, Figulla, HR. Studies on intragastric pCO2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure. Eur J Heart Fail 2004; 6: 403–407.CrossRefGoogle ScholarPubMed
9. Raja, K, Kochhar, R, Sethy, PK, Dutta, U, Bali, HK, Varma, JS. An endoscopic study of upper-GI mucosal changes in patients with congestive heart failure. Gastrointest Endosc 2004; 60: 887–893.Google Scholar
10. Sandek, A, Anker, SD, von Haehling, S. The gut and intestinal bacteria in chronic heart failure. Curr Drug Metab 2009; 10: 22–28.Google Scholar
11. Anselme, F, Moubarak, G, Savouré, A, et al. Implantable cardioverter-defibrillators in lamin A/C mutation carriers with cardiac conduction disorders. Heart Rhythm 2013; 10: 1492–1498.CrossRefGoogle ScholarPubMed
12. Maggi, L, D’Amico, A, Pini, A, et al. LMNA-associated myopathies: the Italian experience in a large cohort of patients. Neurology 2014; 83: 1634–1644.CrossRefGoogle Scholar
13. Wang, CH, Bonnemann, CG, Rutkowski, A, et al. Consensus statement on standard of care for congenital muscular dystrophies. J Child Neurol 2010; 25: 1559–1581.CrossRefGoogle ScholarPubMed
14. Choi, JC, Muchir, A, Wu, W, et al. Temsirolimus activates autophagy and ameliorates cardiomyopathy caused by lamin A/C gene mutation. Sci Transl Med 2012; 4: ra102.Google Scholar
15. Ramos, FJ, Chen, SC, Garelick, MG, et al. Rapamycin reverses elevated mTORC1 signaling in lamin A/C – deficient mice, rescues cardiac and skeletal muscle function, and extends survival. Sci Transl Med 2012; 4: 144ra103.CrossRefGoogle ScholarPubMed
16. Azibani, F, Bertrand, AT. Gene therapy for LMNA-related congenital muscular dystrophy (L-CMD) by trans-splicing. Orphanet J Rare Dis 2015; 10 (Suppl 2): O11.Google Scholar