Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Myotonic dystrophy: Etiology, clinical features, and diagnosis

Basil T Darras, MD
David A Chad, MD
Section Editors
Jeremy M Shefner, MD, PhD
Douglas R Nordli, Jr, MD
Deputy Editor
John F Dashe, MD, PhD


Myotonic dystrophy (DM) is a clinically and genetically heterogeneous disorder. There are two major forms:

DM1, for a century known as Steinert's disease

DM2, recognized in 1994 as a milder version of DM1

The prevalence of DM is 1 in 8000 in the general population, but the proportions of myotonic dystrophy caused by DM1 and DM2 are unknown.

These autosomal dominant conditions are among the most common forms of adult-onset muscular dystrophy. However, DM is more than simply a muscular dystrophy per se, since affected individuals may show cataracts, cardiac conduction abnormalities, infertility, and insulin resistance. Furthermore, there is a severe congenital form of DM1 with marked developmental disability.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Mar 29, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Brook JD, McCurrach ME, Harley HG, et al. 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 1992; 69:385.
  2. Buxton J, Shelbourne P, Davies J, et al. Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature 1992; 355:547.
  3. Fu YH, Pizzuti A, Fenwick RG Jr, et al. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 1992; 255:1256.
  4. Harley HG, Brook JD, Rundle SA, et al. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 1992; 355:545.
  5. Mahadevan M, Tsilfidis C, Sabourin L, et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science 1992; 255:1253.
  6. Liquori CL, Ricker K, Moseley ML, et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 2001; 293:864.
  7. Harper PS. Myotonic Dystrophy, 3rd Ed, WB Saunders, London 2001.
  8. Dalton JC, Ranum LPW, Day JW. Myotonic dystrophy type 2. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1466/ (Accessed on October 17, 2016).
  9. Hamshere MG, Harley H, Harper P, et al. Myotonic dystrophy: the correlation of (CTG) repeat length in leucocytes with age at onset is significant only for patients with small expansions. J Med Genet 1999; 36:59.
  10. Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 2012; 11:891.
  11. Puymirat J, Giguère Y, Mathieu J, Bouchard JP. Intergenerational contraction of the CTG repeats in 2 families with myotonic dystrophy type 1. Neurology 2009; 73:2126.
  12. Day JW, Ricker K, Jacobsen JF, et al. Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum. Neurology 2003; 60:657.
  13. Arsenault ME, Prévost C, Lescault A, et al. Clinical characteristics of myotonic dystrophy type 1 patients with small CTG expansions. Neurology 2006; 66:1248.
  14. Cho DH, Tapscott SJ. Myotonic dystrophy: emerging mechanisms for DM1 and DM2. Biochim Biophys Acta 2007; 1772:195.
  15. Lee JE, Cooper TA. Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans 2009; 37:1281.
  16. Kino Y, Washizu C, Oma Y, et al. MBNL and CELF proteins regulate alternative splicing of the skeletal muscle chloride channel CLCN1. Nucleic Acids Res 2009; 37:6477.
  17. Cooper TA. A reversal of misfortune for myotonic dystrophy? N Engl J Med 2006; 355:1825.
  18. Fugier C, Klein AF, Hammer C, et al. Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. Nat Med 2011; 17:720.
  19. Charlet-B N, Savkur RS, Singh G, et al. Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell 2002; 10:45.
  20. Savkur RS, Philips AV, Cooper TA. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 2001; 29:40.
  21. Philips AV, Timchenko LT, Cooper TA. Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. Science 1998; 280:737.
  22. Berg J, Jiang H, Thornton CA, Cannon SC. Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current. Neurology 2004; 63:2371.
  23. Wheeler TM, Lueck JD, Swanson MS, et al. Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy. J Clin Invest 2007; 117:3952.
  24. Yadava RS, Frenzel-McCardell CD, Yu Q, et al. RNA toxicity in myotonic muscular dystrophy induces NKX2-5 expression. Nat Genet 2008; 40:61.
  25. Nakamori M, Kimura T, Kubota T, et al. Aberrantly spliced alpha-dystrobrevin alters alpha-syntrophin binding in myotonic dystrophy type 1. Neurology 2008; 70:677.
  26. Meola G, Moxley RT 3rd. Myotonic dystrophy type 2 and related myotonic disorders. J Neurol 2004; 251:1173.
  27. Harper, PS. Myotonic Dystrophy, 3rd Ed, WB Saunders, London 2001.
  28. Avaria M, Patterson V. Myotonic dystrophy: relative sensitivity of symptoms signs and abnormal investigations. Ulster Med J 1994; 63:151.
  29. Ricker K, Koch MC, Lehmann-Horn F, et al. Proximal myotonic myopathy: a new dominant disorder with myotonia, muscle weakness, and cataracts. Neurology 1994; 44:1448.
  30. Udd B, Krahe R, Wallgren-Pettersson C, et al. Proximal myotonic dystrophy--a family with autosomal dominant muscular dystrophy, cataracts, hearing loss and hypogonadism: heterogeneity of proximal myotonic syndromes? Neuromuscul Disord 1997; 7:217.
  31. Papadimas GK, Kekou K, Papadopoulos C, et al. Phenotypic variability and molecular genetics in proximal myotonic myopathy. Muscle Nerve 2015; 51:686.
  32. Milone M, Batish SD, Daube JR. Myotonic dystrophy type 2 with focal asymmetric muscle weakness and no electrical myotonia. Muscle Nerve 2009; 39:383.
  33. Machuca-Tzili L, Brook D, Hilton-Jones D. Clinical and molecular aspects of the myotonic dystrophies: a review. Muscle Nerve 2005; 32:1.
  34. Suokas KI, Haanpää M, Kautiainen H, et al. Pain in patients with myotonic dystrophy type 2: a postal survey in Finland. Muscle Nerve 2012; 45:70.
  35. Heatwole C, Johnson N, Bode R, et al. Patient-Reported Impact of Symptoms in Myotonic Dystrophy Type 2 (PRISM-2). Neurology 2015; 85:2136.
  36. George A, Schneider-Gold C, Zier S, et al. Musculoskeletal pain in patients with myotonic dystrophy type 2. Arch Neurol 2004; 61:1938.
  37. Auvinen S, Suominen T, Hannonen P, et al. Myotonic dystrophy type 2 found in two of sixty-three persons diagnosed as having fibromyalgia. Arthritis Rheum 2008; 58:3627.
  38. Rönnblom A, Forsberg H, Danielsson A. Gastrointestinal symptoms in myotonic dystrophy. Scand J Gastroenterol 1996; 31:654.
  39. Bellini M, Biagi S, Stasi C, et al. Gastrointestinal manifestations in myotonic muscular dystrophy. World J Gastroenterol 2006; 12:1821.
  40. Tieleman AA, van Vliet J, Jansen JB, et al. Gastrointestinal involvement is frequent in Myotonic Dystrophy type 2. Neuromuscul Disord 2008; 18:646.
  41. Tieleman AA, Knuijt S, van Vliet J, et al. Dysphagia is present but mild in myotonic dystrophy type 2. Neuromuscul Disord 2009; 19:196.
  42. Lund M, Diaz LJ, Ranthe MF, et al. Cardiac involvement in myotonic dystrophy: a nationwide cohort study. Eur Heart J 2014; 35:2158.
  43. Fragola PV, Luzi M, Calò L, et al. Cardiac involvement in myotonic dystrophy. Am J Cardiol 1994; 74:1070.
  44. Florek RC, Triffon DW, Mann DE, et al. Electrocardiographic abnormalities in patients with myotonic dystrophy. West J Med 1990; 153:24.
  45. Hawley RJ, Milner MR, Gottdiener JS, Cohen A. Myotonic heart disease: a clinical follow-up. Neurology 1991; 41:259.
  46. Melacini P, Buja G, Fasoli G, et al. The natural history of cardiac involvement in myotonic dystrophy: an eight-year follow-up in 17 patients. Clin Cardiol 1988; 11:231.
  47. Schoser BG, Ricker K, Schneider-Gold C, et al. Sudden cardiac death in myotonic dystrophy type 2. Neurology 2004; 63:2402.
  48. Phillips MF, Harper PS. Cardiac disease in myotonic dystrophy. Cardiovasc Res 1997; 33:13.
  49. Olofsson BO, Forsberg H, Andersson S, et al. Electrocardiographic findings in myotonic dystrophy. Br Heart J 1988; 59:47.
  50. Griggs RC, Davis RJ, Anderson DC, Dove JT. Cardiac conduction in myotonic dystrophy. Am J Med 1975; 59:37.
  51. Hiromasa S, Ikeda T, Kubota K, et al. Myotonic dystrophy: ambulatory electrocardiogram, electrophysiologic study, and echocardiographic evaluation. Am Heart J 1987; 113:1482.
  52. Motta J, Guilleminault C, Billingham M, et al. Cardiac abnormalities in myotonic dystrophy. Electrophysiologic and histopathologic studies. Am J Med 1979; 67:467.
  53. Nguyen HH, Wolfe JT 3rd, Holmes DR Jr, Edwards WD. Pathology of the cardiac conduction system in myotonic dystrophy: a study of 12 cases. J Am Coll Cardiol 1988; 11:662.
  54. Church SC. The heart in myotonia atrophica. Arch Intern Med 1967; 119:176.
  55. Wahbi K, Meune C, Bécane HM, et al. Left ventricular dysfunction and cardiac arrhythmias are frequent in type 2 myotonic dystrophy: a case control study. Neuromuscul Disord 2009; 19:468.
  56. Bhakta D, Lowe MR, Groh WJ. Prevalence of structural cardiac abnormalities in patients with myotonic dystrophy type I. Am Heart J 2004; 147:224.
  57. 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.
  58. Culebras A. Sleep and neuromuscular disorders. Neurol Clin 2005; 23:1209.
  59. Laberge L, Bégin P, Montplaisir J, Mathieu J. Sleep complaints in patients with myotonic dystrophy. J Sleep Res 2004; 13:95.
  60. Heatwole C, Bode R, Johnson N, et al. Patient-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1). Neurology 2012; 79:348.
  61. Tieleman AA, Knoop H, van de Logt AE, et al. Poor sleep quality and fatigue but no excessive daytime sleepiness in myotonic dystrophy type 2. J Neurol Neurosurg Psychiatry 2010; 81:963.
  62. Gilmartin JJ, Cooper BG, Griffiths CJ, et al. Breathing during sleep in patients with myotonic dystrophy and non-myotonic respiratory muscle weakness. Q J Med 1991; 78:21.
  63. van der Meché FG, Bogaard JM, van der Sluys JC, et al. Daytime sleep in myotonic dystrophy is not caused by sleep apnoea. J Neurol Neurosurg Psychiatry 1994; 57:626.
  64. Gibbs JW 3rd, Ciafaloni E, Radtke RA. Excessive daytime somnolence and increased rapid eye movement pressure in myotonic dystrophy. Sleep 2002; 25:662.
  65. Park JD, Radtke RA. Hypersomnolence in myotonic dystrophy: demonstration of sleep onset REM sleep. J Neurol Neurosurg Psychiatry 1995; 58:512.
  66. Vazquez JA, Pinies JA, Martul P, et al. Hypothalamic-pituitary-testicular function in 70 patients with myotonic dystrophy. J Endocrinol Invest 1990; 13:375.
  67. Tieleman AA, den Broeder AA, van de Logt AE, van Engelen BG. Strong association between myotonic dystrophy type 2 and autoimmune diseases. J Neurol Neurosurg Psychiatry 2009; 80:1293.
  68. Rudnik-Schöneborn S, Zerres K. Outcome in pregnancies complicated by myotonic dystrophy: a study of 31 patients and review of the literature. Eur J Obstet Gynecol Reprod Biol 2004; 114:44.
  69. Rudnik-Schöneborn S, Schneider-Gold C, Raabe U, et al. Outcome and effect of pregnancy in myotonic dystrophy type 2. Neurology 2006; 66:579.
  70. Panayiotopoulos CP, Scarpalezos S. Dystrophia myotonica. Peripheral nerve involvement and pathogenetic implications. J Neurol Sci 1976; 27:1.
  71. Logullo F, Censori B, Danni M, et al. Peripheral neuropathy in myotonic dystrophy: electrophysiological and clinical features. Electromyogr Clin Neurophysiol 1992; 32:515.
  72. Olson ND, Jou MF, Quast JE, Nuttall FQ. Peripheral neuropathy in myotonic dystrophy. Relation to glucose intolerance. Arch Neurol 1978; 35:741.
  73. Mondelli M, Rossi A, Malandrini A, et al. Axonal motor and sensory neuropathy in myotonic dystrophy. Acta Neurol Scand 1993; 88:141.
  74. Cros D, Harnden P, Pouget J, et al. Peripheral neuropathy in myotonic dystrophy: a nerve biopsy study. Ann Neurol 1988; 23:470.
  75. Pollock M, Dyck PJ. Peripheral nerve morphometry in myotonic dystrophy. Arch Neurol 1976; 33:33.
  76. Huygen PL, Verhagen WI, Noten JF. Auditory abnormalities, including 'precocious presbyacusis', in myotonic dystrophy. Audiology 1994; 33:73.
  77. Verhagen WI, ter Bruggen JP, Huygen PL. Oculomotor, auditory, and vestibular responses in myotonic dystrophy. Arch Neurol 1992; 49:954.
  78. Wesström G, Bensch J, Schollin J. Congenital myotonic dystrophy. Incidence, clinical aspects and early prognosis. Acta Paediatr Scand 1986; 75:849.
  79. González de Dios J, Martínez Frías ML, Egües Jimeno J, et al. [Epidemiological study of Steinert's congenital myotonic dystrophy: dysmorphological characteristics]. An Esp Pediatr 1999; 51:389.
  80. Darin N, Tulinius M. Neuromuscular disorders in childhood: a descriptive epidemiological study from western Sweden. Neuromuscul Disord 2000; 10:1.
  81. Campbell C, Levin S, Siu VM, et al. Congenital myotonic dystrophy: Canadian population-based surveillance study. J Pediatr 2013; 163:120.
  82. Zaki M, Boyd PA, Impey L, et al. Congenital myotonic dystrophy: prenatal ultrasound findings and pregnancy outcome. Ultrasound Obstet Gynecol 2007; 29:284.
  83. Volpe JJ. Neuromuscular disorders: Muscle involvement and restricted disorders. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadephia 2008. p.801.
  84. Pearse RG, Höweler CJ. Neonatal form of dystrophia myotonica. Five cases in preterm babies and a review of earlier reports. Arch Dis Child 1979; 54:331.
  85. Shore RN, MacLachlan TB. Pregnancy with myotonic dystrophy: course, complications and management. Obstet Gynecol 1971; 38:448.
  86. Dunn LJ, Dierker LI. Recurrent hydramnios in association with myotonia dystrophica. Obstet Gynecol 1973; 42:104.
  87. Moosa A. The feeding difficulty in infantile myotonic dystrophy. Dev Med Child Neurol 1974; 16:824.
  88. Hageman AT, Gabreëls FJ, Liem KD, et al. Congenital myotonic dystrophy; a report on thirteen cases and a review of the literature. J Neurol Sci 1993; 115:95.
  89. Sarnat HB, O'Connor T, Byrne PA. Clinical effects of myotonic dystrophy on pregnancy and the neonate. Arch Neurol 1976; 33:459.
  90. 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.
  91. Modoni A, Silvestri G, Pomponi MG, et al. Characterization of the pattern of cognitive impairment in myotonic dystrophy type 1. Arch Neurol 2004; 61:1943.
  92. Nakagawa M, Yamada H, Higuchi I, et al. A case of paternally inherited congenital myotonic dystrophy. J Med Genet 1994; 31:397.
  93. Ohya K, Tachi N, Chiba S, et al. Congenital myotonic dystrophy transmitted from an asymptomatic father with a DM-specific gene. Neurology 1994; 44:1958.
  94. Tachi N, Ohya K, Yamagata H, et al. Haplotype analysis of congenital myotonic dystrophy patients from asymptomatic DM father. Pediatr Neurol 1997; 16:315.
  95. de Die-Smulders CE, Smeets HJ, Loots W, et al. Paternal transmission of congenital myotonic dystrophy. J Med Genet 1997; 34:930.
  96. Tanaka Y, Suzuki Y, Shimozawa N, et al. Congenital myotonic dystrophy: report of paternal transmission. Brain Dev 2000; 22:132.
  97. Harley HG, Rundle SA, MacMillan JC, et al. Size of the unstable CTG repeat sequence in relation to phenotype and parental transmission in myotonic dystrophy. Am J Hum Genet 1993; 52:1164.
  98. Zeesman S, Carson N, Whelan DT. Paternal transmission of the congenital form of myotonic dystrophy type 1: a new case and review of the literature. Am J Med Genet 2002; 107:222.
  99. Bassez G, Lazarus A, Desguerre I, et al. Severe cardiac arrhythmias in young patients with myotonic dystrophy type 1. Neurology 2004; 63:1939.
  100. Igarashi H, Momoi MY, Yamagata T, et al. Hypertrophic cardiomyopathy in congenital myotonic dystrophy. Pediatr Neurol 1998; 18:366.
  101. Moxley, RT III, Meola, G. Myotonic dystrophy. In: Neuromuscular Diseases: From Basic Mechanisms to Clinical Management, Deymeer, F (Ed), S Karger AG, Basel 2000. p.61.
  102. D'Angelo MG, Bresolin N. Cognitive impairment in neuromuscular disorders. Muscle Nerve 2006; 34:16.
  103. Meola G, Sansone V, Perani D, et al. Reduced cerebral blood flow and impaired visual-spatial function in proximal myotonic myopathy. Neurology 1999; 53:1042.
  104. Meola G, Sansone V, Perani D, et al. Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy (PROMM/DM-2). Neuromuscul Disord 2003; 13:813.
  105. Gaul C, Schmidt T, Windisch G, et al. Subtle cognitive dysfunction in adult onset myotonic dystrophy type 1 (DM1) and type 2 (DM2). Neurology 2006; 67:350.
  106. Sansone V, Gandossini S, Cotelli M, et al. Cognitive impairment in adult myotonic dystrophies: a longitudinal study. Neurol Sci 2007; 28:9.
  107. Gadalla SM, Lund M, Pfeiffer RM, et al. Cancer risk among patients with myotonic muscular dystrophy. JAMA 2011; 306:2480.
  108. Mueller CM, Hilbert JE, Martens W, et al. Hypothesis: neoplasms in myotonic dystrophy. Cancer Causes Control 2009; 20:2009.
  109. Meola G, Sansone V. Cerebral involvement in myotonic dystrophies. Muscle Nerve 2007; 36:294.
  110. Minnerop M, Luders E, Specht K, et al. Grey and white matter loss along cerebral midline structures in myotonic dystrophy type 2. J Neurol 2008; 255:1904.
  111. Merlini L, Sabatelli P, Columbaro M, et al. Hyper-CK-emia as the sole manifestation of myotonic dystrophy type 2. Muscle Nerve 2005; 31:764.
  112. Logigian EL, Ciafaloni E, Quinn LC, et al. Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy. Muscle Nerve 2007; 35:479.
  113. Young NP, Daube JR, Sorenson EJ, Milone M. Absent, unrecognized, and minimal myotonic discharges in myotonic dystrophy type 2. Muscle Nerve 2010; 41:758.
  114. Miller TM. Differential diagnosis of myotonic disorders. Muscle Nerve 2008; 37:293.
  115. Lieberman AP, Fischbeck KH. Triplet repeat expansion in neuromuscular disease. Muscle Nerve 2000; 23:843.