Myotonic dystrophy: Prognosis and management
- Basil T Darras, MD
Basil T Darras, MD
- Professor of Neurology
- Harvard Medical School
- David A Chad, MD
David A Chad, MD
- Associate Professor of Neurology
- Harvard Medical School
- Section Editors
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
- Douglas R Nordli, Jr, MD
Douglas R Nordli, Jr, MD
- Section Editor — Pediatric Neurology
- Chief of Neurology
- Children’s Hospital Los Angeles
- Vice Chair of Neurology
- USC Keck School of Medicine
Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are autosomal dominant, multisystem disorders characterized by skeletal muscle weakness and myotonia, cardiac conduction abnormalities, and iridescent cataracts. Immune and endocrine manifestations of myotonic dystrophy include hypogammaglobulinemia, testicular failure, and insulin resistance (insensitivity).
DM1 results from an unstable CTG repeat expansion in the DMPK gene on chromosome 19, and DM2 is caused by the expansion of a CCTG repeat of the ZNF9 gene on chromosome 3; in both diseases, the multisystem features are caused by corresponding CUG (DM1) and CCUG (DM2) expansions expressed at the RNA level .
In general, DM2 is a less severe disease than DM1. There are congenital, juvenile, and adult onset forms of DM1, whereas only an adult onset form of DM2 is recognized. Typically, DM1 patients come to medical attention because of mental retardation or severe muscle weakness and myotonia, whereas in DM2, the chief complaints are usually muscle pain, stiffness, fatigue, or proximal muscle weakness .
There is no disease-modifying therapy available for the treatment of myotonic dystrophy. Thus, treatment is symptomatic. The systemic (non-neuromuscular) manifestations of myotonic dystrophy are the most treatable aspects of the disease. Recommendations regarding management are based more on consensus and clinical experience than on evidence from randomized controlled trials.
The management and prognosis of patients with myotonic dystrophy will be reviewed here. Other aspects of myotonic dystrophy are discussed separately. (See "Myotonic dystrophy: Etiology, clinical features, and diagnosis".)
- Day JW, Ricker K, Jacobsen JF, et al. Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum. Neurology 2003; 60:657.
- Mathieu J, Allard P, Potvin L, et al. A 10-year study of mortality in a cohort of patients with myotonic dystrophy. Neurology 1999; 52:1658.
- de Die-Smulders CE, Höweler CJ, Thijs C, et al. Age and causes of death in adult-onset myotonic dystrophy. Brain 1998; 121 ( Pt 8):1557.
- Groh WJ, Groh MR, Saha C, et al. Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1. N Engl J Med 2008; 358:2688.
- Mörner S, Lindqvist P, Mellberg C, et al. Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1. J Intern Med 2010; 268:59.
- Nazarian S, Wagner KR, Caffo BS, Tomaselli GF. Clinical predictors of conduction disease progression in type I myotonic muscular dystrophy. Pacing Clin Electrophysiol 2011; 34:171.
- Reardon W, Newcombe R, Fenton I, et al. The natural history of congenital myotonic dystrophy: mortality and long term clinical aspects. Arch Dis Child 1993; 68:177.
- Schoser BG, Ricker K, Schneider-Gold C, et al. Sudden cardiac death in myotonic dystrophy type 2. Neurology 2004; 63:2402.
- Groh WJ, Groh MR, Shen C, et al. Survival and CTG repeat expansion in adults with myotonic dystrophy type 1. Muscle Nerve 2011; 43:648.
- Roig M, Balliu PR, Navarro C, et al. Presentation, clinical course, and outcome of the congenital form of myotonic dystrophy. Pediatr Neurol 1994; 11:208.
- Gagnon C, Noreau L, Moxley RT, et al. Towards an integrative approach to the management of myotonic dystrophy type 1. J Neurol Neurosurg Psychiatry 2007; 78:800.
- Mathieu J, Boivin H, Richards CL. Quantitative motor assessment in myotonic dystrophy. Can J Neurol Sci 2003; 30:129.
- Whittaker RG, Ferenczi E, Hilton-Jones D. Myotonic dystrophy: practical issues relating to assessment of strength. J Neurol Neurosurg Psychiatry 2006; 77:1282.
- Wiles CM, Busse ME, Sampson CM, et al. Falls and stumbles in myotonic dystrophy. J Neurol Neurosurg Psychiatry 2006; 77:393.
- Dalton JC, Ranum LPW, Day JW. Myotonic dystrophy type 2. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1466/ (Accessed on May 13, 2015).
- Lindeman E, Leffers P, Spaans F, et al. Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: a randomized clinical trial. Arch Phys Med Rehabil 1995; 76:612.
- Kierkegaard M, Harms-Ringdahl K, Edström L, et al. Feasibility and effects of a physical exercise programme in adults with myotonic dystrophy type 1: a randomized controlled pilot study. J Rehabil Med 2011; 43:695.
- Voet NB, van der Kooi EL, Riphagen II, et al. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev 2013; :CD003907.
- Orngreen MC, Olsen DB, Vissing J. Aerobic training in patients with myotonic dystrophy type 1. Ann Neurol 2005; 57:754.
- Bassez G, Lazarus A, Desguerre I, et al. Severe cardiac arrhythmias in young patients with myotonic dystrophy type 1. Neurology 2004; 63:1939.
- Vladutiu GD, Simmons Z, Isackson PJ, et al. Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve 2006; 34:153.
- Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 2012; 11:891.
- Culebras A. Sleep and neuromuscular disorders. Neurol Clin 2005; 23:1209.
- Bianchi ML, Losurdo A, Di Blasi C, et al. Prevalence and clinical correlates of sleep disordered breathing in myotonic dystrophy types 1 and 2. Sleep Breath 2014; 18:579.
- Lam EM, Shepard PW, St Louis EK, et al. Restless legs syndrome and daytime sleepiness are prominent in myotonic dystrophy type 2. Neurology 2013; 81:157.
- Sartoretti C, Sartoretti S, DeLorenzi D, Buchmann P. Intestinal non-rotation and pseudoobstruction in myotonic dystrophy: case report and review of the literature. Int J Colorectal Dis 1996; 11:10.
- Sjögreen L, Tulinius M, Kiliaridis S, Lohmander A. The effect of lip strengthening exercises in children and adolescents with myotonic dystrophy type 1. Int J Pediatr Otorhinolaryngol 2010; 74:1126.
- Wahbi K, Meune C, Porcher R, et al. Electrophysiological study with prophylactic pacing and survival in adults with myotonic dystrophy and conduction system disease. JAMA 2012; 307:1292.
- Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation 2008; 117:e350.
- Harper PS. Myotonic Dystrophy, 3rd ed, WB Saunders, London 2001.
- Moxley RT 3rd. Carrell-Krusen Symposium Invited Lecture-1997. Myotonic disorders in childhood: diagnosis and treatment. J Child Neurol 1997; 12:116.
- Keller C, Reynolds A, Lee B, Garcia-Prats J. Congenital myotonic dystrophy requiring prolonged endotracheal and noninvasive assisted ventilation: not a uniformly fatal condition. Pediatrics 1998; 101:704.
- Trip J, Drost G, van Engelen BG, Faber CG. Drug treatment for myotonia. Cochrane Database Syst Rev 2006; :CD004762.
- Kurihara T. New classification and treatment for myotonic disorders. Intern Med 2005; 44:1027.
- Logigian EL, Martens WB, Moxley RT 4th, et al. Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology 2010; 74:1441.
- Annane D, Moore DH, Barnes PR, Miller RG. Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic dystrophy. Cochrane Database Syst Rev 2006; :CD003218.
- MacDonald JR, Hill JD, Tarnopolsky MA. Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy. Neurology 2002; 59:1876.
- Talbot K, Stradling J, Crosby J, Hilton-Jones D. Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy. Neuromuscul Disord 2003; 13:357.
- Antonini G, Morino S, Fiorelli M, et al. Selegiline in the treatment of hypersomnolence in myotonic dystrophy: a pilot study. J Neurol Sci 1997; 147:167.
- Mudge BJ, Taylor PB, Vanderspek AF. Perioperative hazards in myotonic dystrophy. Anaesthesia 1980; 35:492.
- Aldridge LM. Anaesthetic problems in myotonic dystrophy. A case report and review of the Aberdeen experience comprising 48 general anaesthetics in a further 16 patients. Br J Anaesth 1985; 57:1119.
- Moore JK, Moore AP. Postoperative complications of dystrophia myotonica. Anaesthesia 1987; 42:529.
- Anderson BJ, Brown TC. Congenital myotonic dystrophy in children--a review of ten years' experience. Anaesth Intensive Care 1989; 17:320.
- Mathieu J, Allard P, Gobeil G, et al. Anesthetic and surgical complications in 219 cases of myotonic dystrophy. Neurology 1997; 49:1646.
- Rosenbaum HK, Miller JD. Malignant hyperthermia and myotonic disorders. Anesthesiol Clin North America 2002; 20:623.
- Imison AR. Anaesthesia and myotonia--an Australian experience. Anaesth Intensive Care 2001; 29:34.
- Klompe L, Lancé M, van der Woerd D, et al. Anaesthesiological and ventilatory precautions during cardiac surgery in Steinert's disease. J Card Surg 2007; 22:74.
- Aquilina A, Groves J. A combined technique utilising regional anaesthesia and target-controlled sedation in a patient with myotonic dystrophy. Anaesthesia 2002; 57:385.
- SAIDMAN LJ, HAVARD ES, EGER EI 2nd. HYPERTHERMIA DURING ANESTHESIA. JAMA 1964; 190:1029.
- Moulds RF, Denborough MA. Letter: Myopathies and malignant hyperpyrexia. Br Med J 1974; 3:520.
- Lehmann-Horn F, Iaizzo PA. Are myotonias and periodic paralyses associated with susceptibility to malignant hyperthermia? Br J Anaesth 1990; 65:692.
- Bird TD. Myotonic dystrophy type 1. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1165/ (Accessed on May 12, 2015).
- Martorell L, Cobo AM, Baiget M, et al. Prenatal diagnosis in myotonic dystrophy type 1. Thirteen years of experience: implications for reproductive counselling in DM1 families. Prenat Diagn 2007; 27:68.
- Salehi LB, Bonifazi E, Stasio ED, et al. Risk prediction for clinical phenotype in myotonic dystrophy type 1: data from 2,650 patients. Genet Test 2007; 11:84.
- Gharehbaghi-Schnell EB, Finsterer J, Korschineck I, et al. Genotype-phenotype correlation in myotonic dystrophy. Clin Genet 1998; 53:20.
- New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1). The International Myotonic Dystrophy Consortium (IDMC). Neurology 2000; 54:1218.
- Harper PS. Major Problems in Neurology: Myotonic Dystrophy, WB Saunders, London 2001.
- Moxley RT, Meola G. The myotonic dystrophies. In: The Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Rosenberg RN, DiMauro S, Paulson HL, et al. (Eds), Wolters Kluwer, Philadelphia 2008. p.532-41.
- Redman JB, Fenwick RG Jr, Fu YH, et al. Relationship between parental trinucleotide GCT repeat length and severity of myotonic dystrophy in offspring. JAMA 1993; 269:1960.
- DM2 prognosis
- MUSCLE WEAKNESS
- Muscle pain
- Exercise training
- Risk of statins
- RESPIRATORY FUNCTION AND SLEEP
- CARDIAC CONDUCTION DISTURBANCES
- OTHER ISSUES
- Congenital myotonic dystrophy
- Excessive daytime sleepiness
- Risk of anesthesia
- Genetic counseling
- - Genetic testing
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS