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Natural history of skeletal muscle involvement in myotonic dystrophy type 1: a retrospective study in 204 cases

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Abstract

Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adult. The aim of this study was to investigate the natural history of skeletal muscle weakness in adults, in a cross-sectional, retrospective study. In a cohort of 204 adult DM1 patients, we quantified muscle impairment, handgrip force and physical disability. Muscle strength was similarly affected in the legs and in the arms, the right and left side, and distally more than proximally in patients. The earliest and the most affected skeletal muscles were the digit flexors, foot dorsiflexors and neck flexors; whereas the elbow and knee extensors and flexors were the least affected muscle groups. The rate of decline of the muscle strength was −0.111 units/year. The handgrip values were lower in DM1 patients than the normative values and the rate of decline in handgrip force per year was −0.24 kg. Limitation in mobility or walking is observed in 84 % of DM1 patients but requirement of wheelchair is infrequent (3 %). The decrease in muscle strength, handgrip force and the increase in physical disability were highly correlated with duration of the disease and the number of CTG repeats in the blood. Significant association was found between decline in muscle strength and the age at onset, physical disability and the age of patients at evaluation, handgrip force and gender. Decline in muscle weakness is very slow and although limitation when walking is a common manifestation of DM1 in patients, the requirement of wheelchair is infrequent.

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References

  1. Andersen G, Ørngreen MC, Preisler N et al (2013) Muscle phenotype in patients with myotonic dystrophy type 1. Muscle Nerve 47:409–415

    Article  CAS  PubMed  Google Scholar 

  2. Antonini G, Giubilei F, Mammarella A et al (2000) Natural history of cardiac involvement in myotonic dystrophy: correlation with CTG repeats. Neurology 55:1207–1209

    Article  CAS  PubMed  Google Scholar 

  3. Arsenault ME, Prévost C, Lescault A, Laberge C, Puymirat J, Mathieu J (2006) Clinical characteristics of myotonic dystrophy type 1 patients with small CTG expansions. Neurology 25:1248–1250

    Article  Google Scholar 

  4. Birouk N, Gouider R, Le Guern E et al (1997) Charcot-Marie-tooth disease type 1A with 17p11.2 duplication. Clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases. Brain 120:813–823

    Article  PubMed  Google Scholar 

  5. Brook JD, McCurrach ME, Harley HG et al (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 68:799–808

    Article  CAS  PubMed  Google Scholar 

  6. Cudia P, Bernasconi P, Chiodelli R et al (2009) Risk of arrhythmia in type I myotonic dystrophy: the role of clinical and genetic variables. J Neurol Neurosurg Psychiatry 80:790–793

    Article  CAS  PubMed  Google Scholar 

  7. de Die-Smulders CE, Howeler CJ, Thijs C et al (1998) Age and causes of death in adult-onset myotonic dystrophy. Brain 121:1557–1563

    Article  PubMed  Google Scholar 

  8. Echenne B, Rideau A, Roubertie A, Sebire G, Rivier F, Lemieux B (1998) Myotonic dystrophy type I in childhood: long-term evolution in patients surviving the neonatal period. Eur J Paediatr Neurol 12:210–223

    Article  Google Scholar 

  9. Facenda-Lorenzo M, Hernandez-Afonso J, Rodrıguez-Esteban M, de Leon-Hernandez JC, Grillo-Perez JJ (2013) Original cardiac manifestations in myotonic dystrophy type 1 patients followed using a standard protocol in a specialized unit. Rev Esp Cardiol 66:193–197

    Article  PubMed  Google Scholar 

  10. Finsterer J, Gharehbaghi-Schnell E, Stöllberger C, Fheodoroff K, Seiser A (2001) Relation of cardiac abnormalities and CTG-repeat size in myotonic dystrophy. Clin Genet 59:350–355

    Article  CAS  PubMed  Google Scholar 

  11. Florence JM, Pandya S, King WM et al (1984) Clinical trials in Duchenne dystrophy: standardization and reliability of evaluation procedures. Phys Ther 64:41–45

    CAS  PubMed  Google Scholar 

  12. Foff EP, Mahadevan MS (2011) Therapeutics development in myotonic dystrophy type 1. Muscle Nerve 44:160–169

    Article  PubMed Central  PubMed  Google Scholar 

  13. Fu YH, Pizzuti A, Fenwick RG Jr et al (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255:1256–1258

    Article  CAS  PubMed  Google Scholar 

  14. Gharehbaghi-Schnell EB, Finsterer J, Korschineck I, Mamoli B, Binder BR (1998) Genotype-phenotype correlation in myotonic dystrophy. Clin Genet 53:20–26

    Article  CAS  PubMed  Google Scholar 

  15. Harper PS (2001) Myotonic dystrophy, 3rd edn. Saunders WB, London

    Google Scholar 

  16. Heatwhole C, Bode R, Johnson N et al (2012) Patients-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1). Neurology 79:348–357

    Article  Google Scholar 

  17. Hébert LJ, Remec JF, Saulnier J, Vial C, Puymirat J (2010) The use of muscle strength assessed with handheld dynamometers as a non-invasive biological marker in myotonic dystrophy type 1 patients: a multicenter study. BMC Musculoskelet Disord 11:72–80

    Article  PubMed Central  PubMed  Google Scholar 

  18. Johnson ER, Abresch RT, Carter GT et al (1995) Profile of neuromuscular diseases: myotonic dystrophy. Am J Phys Rehabil 74(suppl 5):S104–S116

    CAS  Google Scholar 

  19. Kaminsky P, Poussel M, Pruna L, Deibener J, Chenuel B, Brembilla-Perrot B (2011) Organ dysfunction and muscular disability in myotonic dystrophy type 1. Medicine 90:262–268

    Article  PubMed  Google Scholar 

  20. Khoshbakht R, Soltanzadeh A, Zamani B et al (2014) Correlation between distribution of muscle weakness, electrophysiological findings and CTG expansion in myotonic dystrophy. J Clin Neurosci 21:1123–1126

    Article  PubMed  Google Scholar 

  21. Kierkegaard M, Harms-Ringdahl K, Widén Holmqvist L, Tollbäck A (2009) Perceived functioning and disability in adults with myotonic Dystrophy type 1: a survey according to the international classification of functioning, disability and health. J Rehabil Med 41:512–520

    Article  PubMed  Google Scholar 

  22. Kole R, Krainer AR, Altman S (2012) RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat Rev Drug Discov 11:125–140

    CAS  PubMed  Google Scholar 

  23. Kroksmark AK, Ekström AB, Björck E, Tulinius M (2005) Myotonic dystrophy: muscle involvement in relation to disease type and size of expanded CTG-repeat sequence. Dev Med Child Neurol 47:478–485

    Article  PubMed  Google Scholar 

  24. Laberge L, Veillette S, Mathieu J, Auclair J, Perron M (2007) The correlation of CTG repeat length with material and social deprivation in myotonic dystrophy. Clin Genet 71:59–66

    Article  CAS  PubMed  Google Scholar 

  25. Magaña JJ, Cisneros B (2011) Perspectives on gene therapy in myotonic dystrophy type 1. J Neurosci Res 89:275–285

    Article  PubMed  Google Scholar 

  26. Mahadevan M, Tsilfidis C, Sabourin L et al (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255:1253–1255

    Article  CAS  PubMed  Google Scholar 

  27. Marchini C, Lonigro R, Verriello L, Pellizzari L, Bergonzi P, Damante G (2000) Correlations between individual clinical manifestations and CTG repeat amplification in myotonic dystrophy. Clin Genet 57:74–82

    Article  CAS  PubMed  Google Scholar 

  28. Mathieu J, DeBraekeleer M, Prevost C (1990) Genealogical reconstruction of myotonic dystrophy in the Saguenay-Lac-Saint-Jean area (Quebec, Canada). Neurology 40:839–842

    Article  CAS  PubMed  Google Scholar 

  29. Mathieu J, Allard P, Potvin L, Prevost C, Begin P (1999) A 10-year study of mortality in a cohort of patients with myotonic dystrophy. Neurology 52:1658–1662

    Article  CAS  PubMed  Google Scholar 

  30. Mathieu J, Boivin H, Meunier D, Gaudreault M, Begin P (2001) Assessment of a disease-specific muscular impairment rating scale in myotonic dystrophy. Neurology 56:336–340

    Article  CAS  PubMed  Google Scholar 

  31. Mathieu J, Boivin H, Richards CL (2003) Quantitative motor assesment in myotonic dystrophy. Can J Neurol Sci 30:129–136

    CAS  PubMed  Google Scholar 

  32. Mendell JR, Csimma C, McDonald CM et al (2007) Challenges in drug development for muscle disease: a stakeholders’ meeting. Muscle Nerve 35:8–16

    Article  PubMed  Google Scholar 

  33. Peric S, Rakocevic Stojanovic V, Basta I, Peric M, Milicev M, Pavlovic, Lavrnic D (2013) Influence of multisystemic affection on health-related quality of life in patients with myotonic dystrophy type 1. Clin Neurol Neurosurg 115:270–275

    Article  CAS  PubMed  Google Scholar 

  34. Personius KE, Pandya S, King WM, Tawil R, McDermott MP, the FSH DY group (1994) Facioscapulohumeral dystrophy natural history study: standardization of testing procedures and reliability of measurements. Phys Ther 74:253–263

    CAS  PubMed  Google Scholar 

  35. Reardon W, Newcombe R, Fenton I, Sibert J, Harper PS (1993) The natural history of congenital myotonic dystrophy: mortality and long term clinical aspects. Arch Dis Child 68:177–181

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Shy ME, Blake J, Krajewski K et al (2005) Reliability and validity of the CMT neuropathy score as a measure of disability. Neurology 64:1209–1221

    Article  CAS  PubMed  Google Scholar 

  37. Thompson R, Schoser B, Monckton DG, Blonsky K, Locmüller H (2009) Patients registries and trial readiness in myotonic dystrophy- Treat-NMD/Marigold International Workshop Report. Neuromuscul Disord 19:860–866

    Article  PubMed  Google Scholar 

  38. Wang W, Liu Q, Wang ZX, Zhang W, Yuan Y (2013) Correlation of muscular impairment rating scale with myopathological changes in myotonic dystrophy type 1. Zhonghua Zhonghua Yi Xue Za ZHI 93:508–511

    CAS  PubMed  Google Scholar 

  39. Werle S, Goldhahn J, Drerup S, Simmen BR, Sprott H, Herren DB (2009) Age- and gender-specific normative data of grip and pinch strength in a healthy adult Swiss population. J Hand Surg 1:76–84

    Article  Google Scholar 

  40. Wheeler TM, Thornton CA (2007) Myotonic dystrophy: RNA-mediated muscle disease. Curr Opin Neurol 20:572–576

    Article  CAS  PubMed  Google Scholar 

  41. Whittaker RG, Ferenczi E, Hilton-Jones D (2006) Myotonic dystrophy: practical issues relating to assessment of strength. J Neurol Neurosurg Psychiatry 77:1282–1283

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank the patients for participating. They also thank Sun Makosso-Kallyth from the department of Biostatistics of the CHU de Québec for his very valuable statistical advice. The French muscular association against myopathies (AFM) and the “Réseau de Médecine Génétique Appliquée du FRSQ” (RMGA) provided funding for this study. Integrity of Research and reporting.

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standard

All patients gave an informed consent to participate to the registry, which was approved by the local medical ethics committee. This study has been performed in accordance with the ethical standards laid down in the 1965 Declaration of Helsinski and its later amendments.

Author information

Authors and Affiliations

  1. Department of Neurological Sciences, CHU de Quebec, Enfant-Jesus Hospital, Quebec, Canada

    Jean-Pierre Bouchard

  2. Unit of Human Genetics, CRCHU de Quebec, University of Laval, 2705 Bd Laurier, Quebec, G1V4G2, Canada

    Louise Cossette & Jack Puymirat

  3. Neuromuscular Reference Center, CHU Henri Mondor, AP-HP, Créteil, France

    Guillaume Bassez

  4. INSERM U955, UPEC University, 94010, Créteil, France

    Guillaume Bassez

Authors
  1. Jean-Pierre Bouchard
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  2. Louise Cossette
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  3. Guillaume Bassez
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  4. Jack Puymirat
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Correspondence to Jack Puymirat.

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Bouchard, JP., Cossette, L., Bassez, G. et al. Natural history of skeletal muscle involvement in myotonic dystrophy type 1: a retrospective study in 204 cases. J Neurol 262, 285–293 (2015). https://doi.org/10.1007/s00415-014-7570-x

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  • DOI: https://doi.org/10.1007/s00415-014-7570-x

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