Journal of Neurology

, Volume 266, Issue 6, pp 1367–1375 | Cite as

Congenital myopathies are mainly associated with a mild cardiac phenotype

  • Helle PetriEmail author
  • Karim Wahbi
  • Nanna Witting
  • Lars Køber
  • Henning Bundgaard
  • Emna Kamoun
  • Geoffroy Vellieux
  • Tanya Stojkovic
  • Anthony Béhin
  • Pascal Laforet
  • John Vissing
Original Communication



To evaluate the prevalence of cardiac involvement in patients with congenital myopathies and the association to specific genotypes.


We evaluated patients with physical examination, electrocardiogram, echocardiography, and 48-h Holter monitoring. Follow-up was performed for major events.


We included 130 patients, 55 men (42%), with a mean age of 34 ± 17 years. A genetic diagnosis was established in 97 patients (75%). Right bundle branch block was observed in three patients: 2/34 patients with a ryanodine receptor 1 (RYR1) and 1/6 with a tropomyosin two gene (TPM2) gene mutation. Echocardiography showed left-ventricular hypertrophy in five patients: 2/17 and 3/34 patients with a Dynamin 2 (DNM2) and a RYR1 mutation, respectively. One patient with a myosin heavy-chain (MYH7) mutation had dilated cardiomyopathy and heart failure. On Holter monitoring, frequent ventricular premature contractions were observed in one patient with a DNM2 mutation. Two patients with a TPM2 and a RYR1 mutation, respectively, had a single short run of non-sustained ventricular tachycardia. Atrioventricular nodal re-entry tachycardia was observed in a 20-year-old man with an actin 1 gene mutation. During follow-up (median 8.4 years), four patients died, all of non-cardiac causes.


Congenital myopathies are generally associated with a mild cardiac phenotype. Our findings substantiate the literature and indicate that, except for patients with specific genotypes, such as MYH7 and TTN mutations, repeated cardiac assessments can be minimized, given a normal initial cardiac screening at time of diagnosis.


Congenital myopathies Arrhythmia Echocardiography Heart failure 



This work was supported by The Research Foundation of Rigshospitalet, The Danish Heart Foundation, The Lundbeck Foundation, and The Stibo Foundation.

Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


  1. 1.
    Agrawal PB, Pierson CR, Joshi M, Liu X, Ravenscroft G, Moghadaszadeh B, Talabere T, Viola M, Swanson LC, Haliloglu G, Talim B, Yau KS, Allcock RJ, Laing NG, Perrella MA, Beggs AH (2014) SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet 95:218–226CrossRefGoogle Scholar
  2. 2.
    Al-Ruwaishid A, Vajsar J, Tein I, Benson L, Jay V (2003) Centronuclear myopathy and cardiomyopathy requiring heart transplant. Brain Dev 25:62–66CrossRefGoogle Scholar
  3. 3.
    Amburgey K, McNamara N, Bennett LR, McCormick ME, Acsadi G, Dowling JJ (2011) Prevalence of congenital myopathies in a representative pediatric united states population. Ann Neurol 70:662–665CrossRefGoogle Scholar
  4. 4.
    Broendberg AK, Nielsen JC, Bjerre J, Pedersen LN, Kristensen J, Henriksen FL, Bundgaard H, Jensen HK (2017) Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Heart 103:901–909CrossRefGoogle Scholar
  5. 5.
    Bussink BE, Holst AG, Jespersen L, Deckers JW, Jensen GB, Prescott E (2013) Right bundle branch block: prevalence, risk factors, and outcome in the general population: results from the Copenhagen City Heart Study. Eur Heart J 34:138–146CrossRefGoogle Scholar
  6. 6.
    Carmignac V, Salih MA, Quijano-Roy S, Marchand S, Al Rayess MM, Mukhtar MM, Urtizberea JA, Labeit S, Guicheney P, Leturcq F, Gautel M, Fardeau M, Campbell KP, Richard I, Estournet B, Ferreiro A (2007) C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy. Ann Neurol 61:340–351CrossRefGoogle Scholar
  7. 7.
    Cullup T, Lamont PJ, Cirak S, Damian MS, Wallefeld W, Gooding R, Tan SV, Sheehan J, Muntoni F, Abbs S, Sewry CA, Dubowitz V, Laing NG, Jungbluth H (2012) Mutations in MYH7 cause multi-minicore disease (MmD) with variable cardiac involvement. Neuromuscul Disord 22:1096–1104CrossRefGoogle Scholar
  8. 8.
    D’Amico A, Graziano C, Pacileo G, Petrini S, Nowak KJ, Boldrini R, Jacques A, Feng JJ, Porfirio B, Sewry CA, Santorelli FM, Limongelli G, Bertini E, Laing N, Marston SB (2006) Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with ACTA1 K336E mutation. Neuromuscul Disord 16:548–552CrossRefGoogle Scholar
  9. 9.
    Darin N, Tulinius M (2000) Neuromuscular disorders in childhood: a descriptive epidemiological study from western Sweden. Neuromuscul Disord 10:1–9CrossRefGoogle Scholar
  10. 10.
    de VM, de Voogt, la Riviere WG GV (1992) The heart in Becker muscular dystrophy, facioscapulohumeral dystrophy, and Bethlem myopathy. Muscle Nerve 15:591–596CrossRefGoogle Scholar
  11. 11.
    Esposito T, Sampaolo S, Limongelli G, Varone A, Formicola D, Diodato D, Farina O, Napolitano F, Pacileo G, Gianfrancesco F, Di IG (2013) Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy. Orphanet J Rare Dis 8:91CrossRefGoogle Scholar
  12. 12.
    Feingold B, Mahle WT, Auerbach S, Clemens P, Domenighetti AA, Jefferies JL, Judge DP, Lal AK, Markham LW, Parks WJ, Tsuda T, Wang PJ, Yoo SJ (2017) Management of cardiac involvement associated with neuromuscular diseases: a scientific statement from the American Heart Association. Circulation 136:e200–e231CrossRefGoogle Scholar
  13. 13.
    Fiorillo C, Astrea G, Savarese M, Cassandrini D, Brisca G, Trucco F, Pedemonte M, Trovato R, Ruggiero L, Vercelli L, D’Amico A, Tasca G, Pane M, Fanin M, Bello L, Broda P, Musumeci O, Rodolico C, Messina S, Vita GL, Sframeli M, Gibertini S, Morandi L, Mora M, Maggi L, Petrucci A, Massa R, Grandis M, Toscano A, Pegoraro E, Mercuri E, Bertini E, Mongini T, Santoro L, Nigro V, Minetti C, Santorelli FM, Bruno C (2016) MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients. Orphanet J Rare Dis 11:91CrossRefGoogle Scholar
  14. 14.
    Gatayama R, Ueno K, Nakamura H, Yanagi S, Ueda H, Yamagishi H, Yasui S (2013) Nemaline myopathy with dilated cardiomyopathy in childhood. Pediatrics 131:e1986–e1990CrossRefGoogle Scholar
  15. 15.
    Hermans MC, Pinto YM, Merkies IS, de Die-Smulders CE, Crijns HJ, Faber CG (2010) Hereditary muscular dystrophies and the heart. Neuromuscul Disord 20:479–492CrossRefGoogle Scholar
  16. 16.
    Homayoun H, Khavandgar S, Hoover JM, Mohsen AW, Vockley J, Lacomis D, Clemens PR (2011) Novel mutation in MYH7 gene associated with distal myopathy and cardiomyopathy. Neuromuscul Disord 21:219–222CrossRefGoogle Scholar
  17. 17.
    Jungbluth H, Treves S, Zorzato F, Sarkozy A, Ochala J, Sewry C, Phadke R, Gautel M, Muntoni F (2018) Congenital myopathies: disorders of excitation-contraction coupling and muscle contraction. Nat Rev Neurol 14:151–167CrossRefGoogle Scholar
  18. 18.
    Kim SY, Park YE, Kim HS, Lee CH, Yang DH, Kim DS (2011) Nemaline myopathy and non-fatal hypertrophic cardiomyopathy caused by a novel ACTA1 E239K mutation. J Neurol Sci 307:171–173CrossRefGoogle Scholar
  19. 19.
    Laitinen PJ, Brown KM, Piippo K, Swan H, Devaney JM, Brahmbhatt B, Donarum EA, Marino M, Tiso N, Viitasalo M, Toivonen L, Stephan DA, Kontula K (2001) Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 103:485–490CrossRefGoogle Scholar
  20. 20.
    Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John SM, Stewart W (2006) Recommendations for chamber quantification. Eur J Echocardiogr 7:79–108CrossRefGoogle Scholar
  21. 21.
    Lund M, Diaz LJ, Ranthe MF, Petri H, Duno M, Juncker I, Eiberg H, Vissing J, Bundgaard H, Wohlfahrt J, Melbye M (2014) Cardiac involvement in myotonic dystrophy: a nationwide cohort study. Eur Heart J 35:2158–2164CrossRefGoogle Scholar
  22. 22.
    Maggi L, Scoto M, Cirak S, Robb SA, Klein A, Lillis S, Cullup T, Feng L, Manzur AY, Sewry CA, Abbs S, Jungbluth H, Muntoni F (2013) Congenital myopathies–clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom. Neuromuscul Disord 23:195–205CrossRefGoogle Scholar
  23. 23.
    Marian AJ, Braunwald E (2017) Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res 121:749–770CrossRefGoogle Scholar
  24. 24.
    Marseglia L, D’Angelo G, Manti S, Salpietro V, Arrigo T, Cavallari V, Gitto E (2015) Sudden cardiac arrest in a child with nemaline myopathy. Ital J Pediatr 41:20CrossRefGoogle Scholar
  25. 25.
    Mavrogeni S, Markousis-Mavrogenis G, Papavasiliou A, Kolovou G (2015) Cardiac involvement in Duchenne and Becker muscular dystrophy. World J Cardiol 7:410–414CrossRefGoogle Scholar
  26. 26.
    Mavrogeni SI, Markousis-Mavrogenis G, Papavasiliou A, Papadopoulos G, Kolovou G (2018) Cardiac involvement in duchenne muscular dystrophy and related dystrophinopathies. Methods Mol Biol 1687:31–42CrossRefGoogle Scholar
  27. 27.
    Mir A, Lemler M, Ramaciotti C, Blalock S, Ikemba C (2012) Hypertrophic cardiomyopathy in a neonate associated with nemaline myopathy. Congenit Heart Dis 7:E37–E41CrossRefGoogle Scholar
  28. 28.
    Muller-Hocker J, Schafer S, Mendel B, Lochmuller H, Pongratz D (2000) Nemaline cardiomyopathy in a young adult: an ultraimmunohistochemical study and review of the literature. Ultrastruct Pathol 24:407–416CrossRefGoogle Scholar
  29. 29.
    Nagata R, Kamimura D, Suzuki Y, Saito T, Toyama H, Dejima T, Inada H, Miwa Y, Uchino K, Umemura S, Shimizu M (2011) A case of nemaline myopathy with associated dilated cardiomyopathy and respiratory failure. Int Heart J 52:401–405CrossRefGoogle Scholar
  30. 30.
    Nakajima M, Shima Y, Kumasaka S, Kuwabara K, Migita M, Fukunaga Y (2008) An infant with congenital nemaline myopathy and hypertrophic cardiomyopathy. J Nippon Med Sch 75:350–353CrossRefGoogle Scholar
  31. 31.
    Nomura S, Funabashi N, Sekiguchi Y, Masuda S, Kuwabara S, Misawa S, Daimon M, Uehara M, Miyaiuchi H, Komuro I, Kobayashi Y (2011) Dilated cardiomyopathy with centronuclear myopathy in a young male. Int J Cardiol 150:213–216CrossRefGoogle Scholar
  32. 32.
    North KN, Wang CH, Clarke N, Jungbluth H, Vainzof M, Dowling JJ, Amburgey K, Quijano-Roy S, Beggs AH, Sewry C, Laing NG, Bonnemann CG (2014) Approach to the diagnosis of congenital myopathies. Neuromuscul Disord 24:97–116CrossRefGoogle Scholar
  33. 33.
    Petri H, Ahtarovski KA, Vejlstrup N, Vissing J, Witting N, Kober L, Bundgaard H (2014) Myocardial fibrosis in patients with myotonic dystrophy type 1: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 16:59CrossRefGoogle Scholar
  34. 34.
    Petri H, Vissing J, Witting N, Bundgaard H, Kober L (2012) Cardiac manifestations of myotonic dystrophy type 1. Int J Cardiol 160:82–88CrossRefGoogle Scholar
  35. 35.
    Petri H, Witting N, Ersboll MK, Sajadieh A, Duno M, Helweg-Larsen S, Vissing J, Kober L, Bundgaard H (2014) High prevalence of cardiac involvement in patients with myotonic dystrophy type 1: a cross-sectional study. Int J Cardiol 174:31–36CrossRefGoogle Scholar
  36. 36.
    Petropoulou E, Soltani M, Firoozabadi AD, Namayandeh SM, Crockford J, Maroofian R, Jamshidi Y (2017) Digenic inheritance of mutations in the cardiac troponin (TNNT2) and cardiac beta myosin heavy chain (MYH7) as the cause of severe dilated cardiomyopathy. Eur J Med Genet 60:485–488CrossRefGoogle Scholar
  37. 37.
    Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino V, Danieli GA (2001) Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103:196–200CrossRefGoogle Scholar
  38. 38.
    Romero NB, Clarke NF (2013) Congenital myopathies. Handb Clin Neurol 113:1321–1336CrossRefGoogle Scholar
  39. 39.
    Ryan MM, Schnell C, Strickland CD, Shield LK, Morgan G, Iannaccone ST, Laing NG, Beggs AH, North KN (2001) Nemaline myopathy: a clinical study of 143 cases. Ann Neurol 50:312–320CrossRefGoogle Scholar
  40. 40.
    Simsek Z, Acar G, Akcakoyun M, Esen O, Emiroglu Y, Esen AM (2012) Left ventricular noncompaction in a patient with multiminicore disease. J Cardiovasc Med (Hagerstown) 13:660–662CrossRefGoogle Scholar
  41. 41.
    Skyllouriotis ML, Marx M, Skyllouriotis P, Bittner R, Wimmer M (1999) Nemaline myopathy and cardiomyopathy. Pediatr Neurol 20:319–321CrossRefGoogle Scholar
  42. 42.
    Taglia A, D’Ambrosio P, Palladino A, Politano L (2012) On a case of respiratory failure due to diaphragmatic paralysis and dilated cardiomyopathy in a patient with nemaline myopathy. Acta Myol 31:201–203Google Scholar
  43. 43.
    Uro-Coste E, Arne-Bes MC, Pellissier JF, Richard P, Levade T, Heitz F, Figarella-Branger D, Delisle MB (2009) Striking phenotypic variability in two familial cases of myosin storage myopathy with a MYH7 Leu1793pro mutation. Neuromuscul Disord 19:163–166CrossRefGoogle Scholar
  44. 44.
    van der Kooi AJ, de Voogt WG, Bertini E, Merlini L, Talim FB, Ben YR, Urtziberea A de VM (2006) Cardiac and pulmonary investigations in Bethlem myopathy. Arch Neurol 63:1617–1621CrossRefGoogle Scholar
  45. 45.
    van der Linde IHM, Hiemstra YL, Bokenkamp R, van Mil AM, Breuning MH, Ruivenkamp C, Ten Broeke SW, Veldkamp RF, van Waning JI, van Slegtenhorst MA, van Spaendonck-Zwarts KY, Lekanne Deprez RH, Herkert JC, Boven L, van der Zwaag PA, Jongbloed JDH, Bootsma M, Barge-Schaapveld DQCM (2017) A Dutch MYH7 founder mutation, p.(Asn1918Lys), is associated with early onset cardiomyopathy and congenital heart defects. Neth Heart J 25:675–681CrossRefGoogle Scholar
  46. 46.
    Walsh R, Rutland C, Thomas R, Loughna S (2010) Cardiomyopathy: a systematic review of disease-causing mutations in myosin heavy chain 7 and their phenotypic manifestations. Cardiology 115:49–60CrossRefGoogle Scholar
  47. 47.
    Wang J, Wan K, Sun J, Li W, Liu H, Han Y, Chen Y (2018) Phenotypic diversity identified by cardiac magnetic resonance in a large hypertrophic cardiomyopathy family with a single MYH7 mutation. Sci Rep 8:973CrossRefGoogle Scholar
  48. 48.
    Witting N, Werlauff U, Duno M, Vissing J (2017) Phenotypes, genotypes, and prevalence of congenital myopathies older than 5 years in Denmark. Neurol Genet 3:e140CrossRefGoogle Scholar
  49. 49.
    Yuceyar N, Ayhan O, Karasoy H, Tolun A (2015) Homozygous MYH7 R1820W mutation results in recessive myosin storage myopathy: scapuloperoneal and respiratory weakness with dilated cardiomyopathy. Neuromuscul Disord 25:340–344CrossRefGoogle Scholar
  50. 50.
    Zaharieva IT, Thor MG, Oates EC, van KC, Hendson, Blom G, Witting E, Rasmussen N, Gabbett M, Ravenscroft MT, Sframeli G, Suetterlin M, Sarkozy K, D’Argenzio A, Hartley L, Matthews L, Pitt E, Vissing M, Ballegaard J, Krarup M, Slordahl C, Halvorsen A, Ye H, Zhang XC, Lokken LH, Werlauff N, Abdelsayed U, Davis M, Feng MR, Phadke L, Sewry R, Morgan CA, Laing JE, Vallance NG, Ruben H, Hanna P, Lewis MG, Kamsteeg S, Mannikko EJ, Muntoni R F (2016) Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or ‘classical’ congenital myopathy. Brain 139:674–691CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Helle Petri
    • 1
    Email author
  • Karim Wahbi
    • 2
  • Nanna Witting
    • 3
  • Lars Køber
    • 1
  • Henning Bundgaard
    • 1
  • Emna Kamoun
    • 4
  • Geoffroy Vellieux
    • 4
  • Tanya Stojkovic
    • 4
  • Anthony Béhin
    • 4
  • Pascal Laforet
    • 5
    • 6
  • John Vissing
    • 3
  1. 1.Department of CardiologyCopenhagen University Hospital RigshospitaletCopenhagenDenmark
  2. 2.APHP, Cochin Hospital, Cardiology Department, Centre de Référence de Pathologie, Neuromusculaire Nord/Est/Ile de France, Paris-DescartesSorbonne Paris Cité UniversityParisFrance
  3. 3.Department of NeurologyCopenhagen University HospitalCopenhagenDenmark
  4. 4.Myology Institute, Nord/Est/Ile de France Neuromuscular CenterPitié-Salpêtière hospital, APHPParisFrance
  5. 5.Neurology Department, Nord/Est/Ile de France Neuromuscular CenterRaymond Poincaré Teaching Hospital, APHPGarchesFrance
  6. 6.END-ICAPINSERM U1179, Université Versailles Saint-Quentin-en-YvelinesMontigny-le-BretonneuxFrance

Personalised recommendations