Myotonic dystrophy: Diagnosis, management and new therapies

Current Opinion in Neurology

Volumn 27, Issue 5, 2014, Pages 599-606

  Turner, Chris ^a   Hilton Jones, David ^b  

^a NATIONAL HOSPITAL FOR NEUROLOGY AND NEUROSURGERY   (United Kingdom)

^b JOHN RADCLIFFE HOSPITAL   (United Kingdom)

Author keywords

CNBP; Myotonic dystrophy protein kinase; Myotonic dystrophy type 1; Myotonic dystrophy type 2; Proximal myotonic myopathy; Steinert's disease; ZNF9

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; RNA;

CLINICAL FEATURE; DAYTIME SOMNOLENCE; DIGESTIVE SYSTEM FUNCTION DISORDER; ENDOCRINE DISEASE; GENE THERAPY; HEART; HUMAN; MENTAL DISEASE; MOLECULAR DIAGNOSIS; MYOTONIC DYSTROPHY; NEUROLOGIC DISEASE; NONHUMAN; PREGNANCY; RESPIRATORY FUNCTION; REVIEW; SCREENING; SKELETAL MUSCLE; DISEASE MANAGEMENT;

DISEASE MANAGEMENT; HUMANS; MYOTONIC DYSTROPHY;

EID: 84925851628     PISSN: 13507540     EISSN: 14736551     Source Type: Journal    
DOI: 10.1097/WCO.0000000000000128     Document Type: Review

References (82)

1. Brook JD, McCurrach ME, Harley HG, et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3-prime end of a transcript encoding a protein kinase family member. Cell 1992;68:799-808.
2. Martorell L, Monckton DG, Sanchez A, et al. Frequency and stability of the myotonic dystrophy type 1 premutation. Neurology 2001;56:328-335.
3. Addis M I, Serrenti M, Meloni C, et al. Triplet-primed PCR is more sensitive than southern blotting-long PCR for the diagnosis of myotonic dystrophy type1. Genet Test Mol Biomarkers 2012;16:1428-1431.
4. 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;36:59-61.
5. Lavedan C, Hofmann-Radvanyi H, Shelbourne P. Myotonic dystrophy: sizeand sex-dependent dynamics of CTG meiotic instability, and somatic mosaicism. Am J Hum Genet 1993;52:875-883.
6. Morales F, Couto JM, Higham CF, et al. Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity. Hum Mol Genet 2012;16:3558-3567. Estimated progenitor allele size is described as having a strong correlation with age of onset. Age at onset is also described as being modified by the level of somatic instability. This suggests a primary role for somatic instability in myotonic dystrophy type 1 severity and further highlights it as a potential therapeutic target.
7. Pettersson OJ, Aagaard L, Andrejeva D, et al. DDX6 regulates sequestered nuclear CUG-expanded DMPK-mRNA in dystrophia myotonica type 1. Nucleic Acids Res 2014;42:7186-7200.
8. Ravel-Chapuis A, Bélanger G, Yadava RS, et al. The RNA-binding protein Staufen1 is increased in DM1 skeletal muscle and promotes alternative premRNA splicing. J Cell Biol 2012;196:699-712.
9. Mankodi A, Takahashi MP, Jiang H, et al. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel premRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell 2002;10:35-44.
10. Osborne R, Thronton C. RNA-dominant diseases. Hum Mol Genet 2006;15:R162-R169.
11. Machuca-Tzili L, Brook D, Hilton-Jones D. Clinical and molecular aspects of the myotonic dystrophies: a review. Muscle Nerve 2005;32:1-18.
12. Mahadevan MS. Myotonic dystrophy: is a narrow focus obscuring the rest of the field? Curr Opin Neurol 2012;25:609-613. This review is an up-to-date summary of the molecular pathogenesis and potential molecular treatments for myotonic dystrophy type 1.
13. Liquori CL, Ricker K, Moseley ML, et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 2001;293:864-867.
14. Hilton Jones D, Damian MS, Meola G. Somnolence and its management. In: Harper PS, Van Engelen B, Eymard B, Wilcox DE, editors. Myotonic dystrophy: present management, future therapy. Oxford: Oxford University Press; 2004. pp. 135-149.
15. Yotova V, Labuda D, Zietkiewicz E, et al. Anatomy of a founder effect: myotonic dystrophy in Northeastern Quebec. Hum Genet 2005;117:177-187.
16. Turner C, Hilton-Jones D. The myotonic dystrophies: diagnosis and management. J Neurol Neurosurg Psychiatry 2010;81:358-367.
17. Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 2012;11:891-905.
18. Pénisson-Besnier I, Devillers M, Porcher R, et al. Dehydroepiandrosterone for myotonic dystrophy type 1. Neurology 2008;71:407-412.
19. Heatwole CR, Eichinger KJ, Friedman DI, et al. Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1. Arch Neurol 2011;68:37-44.
20. Walter MC, Reilich P, Lochmüller H, et al. Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. J Neurol 2002;249:1717-1722.
21. Tarnopolsky M, Mahoney D, Thompson T, et al. Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Muscle Nerve 2004;29:51-58.
22. Schneider-Gold C, Beck M, Wessig C, et al. Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. Neurology 2003;60:500-502.
23. 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;76:612-620.
24. Logigian EL, Blood CL, Dilek N, et al. Quantitative analysis of the 'warm-up' phenomenon in myotonic dystrophy type 1. Muscle Nerve 2005;32:35-42.
25. Trip J, Drost GG, Van Engelen BGM, Faber CG. Drug treatment for myotonia. Cochrane Database Syst Rev 2007; CD004762.
26. Logigian EL, Martens WB, Moxley RT 4th, et al. Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology 2010;74:1441-1448.
27. Bassez G, Lazarus A, Desguerre I, et al. Severe cardiac arrhythmias in young patients with myotonic dystrophy type 1. Neurology 2004;63:1939-1941.
28. Chebel S, Ben Hamda K, Boughammoura A, et al. Cardiac involvement in Steinert's myotonic dystrophy. Rev Neurol (Paris) 2005;161:932-939.
29. Dello Russo A, Pelargonio G, Parisi Q. Widespread electroanatomic alterations of right cardiac chambers in patients with myotonic dystrophy type 1. J Cardiovasc Electrophysiol 2006;17:34-40.
30. Mathieu J, Allard P, Potvin L, et al. A 10-year study of mortality in a cohort of patients with myotonic dystrophy. Neurology 1999;52:1658-1662.
31. Groh WJ, Groh MR, Saha C. Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1. N Engl J Med 2008;358:2688-2697.
32. Lazarus A, Varin J, Ounnoughene Z, et al. Relationships among electrophysiological findings and clinical status, heart function, and extent of DNA mutation in myotonic dystrophy. Circulation 1999;99:1041-1046.
33. Wahbi K, Meune C, Porcher R, et al. Electrophysiological study with pro-phylactic pacing and survival in adults with myotonic dystrophy and conduction system disease. J Am Med Assoc 2012;307:1292-1301. This article provided evidence that an invasive strategy to cardiac monitoring may help reduce cardiac mortality in myotonic dystrophy type 1.
34. Hanostia P, Frenz D. Hypersomonia associated with alveolar hypoventilation in myotonic dystrophy. Neurology 1981;31:1336-1337.
35. Bogaard JM, Van Der Meché FG, Hendriks I, Ververs C. Pulmonary function and resting breathing pattern in myotonic dystrophy. Lung 1992;170:143-153.
36. Mathieu J, Allard P, Gobeil G, et al. Anesthetic and surgical complications in 219 cases of myotonic dystrophy. Neurology 1997;49:1646-1650.
37. Rubinsztein JS, Rubinsztein DC, Goodburn S, Holland AJ. Apathy and hypersomnia are common features of myotonic dystrophy. JNeurol Neurosurg Psychiatry 1998;64:510-515.
38. Ono S, Takahashi K, Jinnai K, et al. Loss of serotonin-containing neurons in the raphe of patients with myotonic dystrophy: a quantitative immunohistochemical study and relation to hypersomnia. Neurology 1998;50:535-538.
39. Giubilei F, Antonini G, Bastianello S, et al. Excessive daytime sleepiness in myotonic dystrophy. J Neurol Sci 1999;164:60-63.
40. Van Der Werf S, Kalkman J, Bleijenberg G, et al. The relation between daytime sleepiness, fatigue, and reduced motivation in patients with adult onset myotonic dystrophy. J Neurol Neurosurg Psychiatry 2003;74:138-139.
41. MacDonald JR, Hill JD, Tarnopolsky MA. Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy. Neurology 2002;59:1876-1880.
42. Talbot K, Stradling J, Crosby J, Hilton-Jones D. Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy. Neuromuscul Disord 2003;13:357-364.
43. Wintzen AR, Lammers GJ, Van Dijk JG. Does modafinil enhance activity of patients with myotonic dystrophy? A double-blind placebo-controlled crossover study. J Neurol 2007;254:26-28.
44. Damian MS, Gerlach A, Schmidt F, et al. Modafinil for excessive daytime sleepiness in myotonic dystrophy. Neurology 2001;56:794-796.
45. Annane D, Moore DH, Barnes PRJ, Miller RG. Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic dystrophy. Cochrane Database Syst Rev 2006; CD003218.
46. Hilton-Jones D, Bowler M, Lochmüeller H, et al. Modafinil for excessive daytime sleepiness in myotonic dystrophy type 1: the patients' perspective. Neuromuscul Disord 2012;22:597-603. After all the controversy over the use of modafinil in myotonic dystrophy type 1, this article studies the patient's perspective which is strongly positive - proving this in a randomized controlled trial will be difficult logistically.
47. Turnpenny P, Clark C, Kelly K. Intelligence quotient profile in myotonic dystrophy, intergenerational deficit, and correlation with CTG amplification. J Med Genet 1994;31:300-305.
48. Modoni A, Silvestri G, Pomponi MG, et al. Characterization of the pattern of cognitive impairment in myotonic dystrophy type 1. Arch Neurol 2004;61:1943-1947.
49. 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;67:350-352.
50. Winblad S, Lindberg C, Hansen S. Cognitive deficits and CTG repeat expansion size in classical myotonic dystrophy type 1 (DM1). Behav Brain Func 2006;2:16.
51. Delaporte C. Personality patterns in patients with myotonic dystrophy. Arch Neurol 1998;55:635-640.
52. Winblad S, Lindberg C, Hansen S. Temperament and character in patients with classical myotonic dystrophy type 1 (DM-1). Neuromuscul Disord 2005;15:287-292.
53. Sistiaga A, Urreta I, Jodar M, et al. Cognitive/personality pattern and triplet expansion size in adult myotonic dystrophy type 1 (DM1): CTG repeats, cognition and personality in DM1. Psychol Med 2010;40:487-495.
54. Winblad S, Hellström P, Lindberg C, Hansen S. Facial emotion recognition in myotonic dystrophy type 1 correlates with CTG repeat expansion. J Neurol Neurosurg Psychiatry 2006;77:219-223.
55. Weber YG, Roebling R, Kassubek J, et al. Comparative analysis of brain structure, metabolism, and cognition in myotonic dystrophy 1 and 2. Neurology 2010;74:1108-1117.
56. Romeo V, Pegoraro E, Ferrati C, et al. Brain involvement in myotonic dystrophies: neuroimaging and neuropsychological comparative study in DM1 and DM2. J Neurol 2010;257:1246-1255.
57. Minnerop M, Weber B, Schoene-Bake JC, et al. The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease. Brain 2011;134:3530-3546.
58. Maurage CA, Udd B, Ruchoux MM, et al. Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease. Neurology 2005;65:1636-1638.
59. Oyamada R, Hayashi M, Katoh Y, et al. Neurofibrillary tangles and deposition of oxidative products in the brain in cases of myotonic dystrophy. Neuropathology 2006;26:107-114.
60. Sergeant N, Sablonnière B, Schraen-Maschke S, et al. Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1. Hum Mol Genet 2001;10:2143-2155.
61. Seznec H, Agbulut O, Sergeant N. Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities. Hum Mol Genet 2001;10:2717-2726.
62. Ronnblom A, Forsberg H, Danielsson A. Gastrointestinal symptoms in myotonic dystrophy. Scand J Gastroenterol 1996;31:654-657.
63. Ronnblom A, Andersson S, Hellstrom PM, Danielsson A. Gastric emptying in myotonic dystrophy. Eur J Clin Invest 2002;32:570-574.
64. Heatwole CR, Miller J, Martens B, Moxley RT III. Laboratory abnormalities in ambulatory patients with myotonic dystrophy type 1. Arch Neurol 2006;63:1149-1153.
65. Ørngreen MC, Arlien-Søborg P, Duno M, et al. Endocrine function in 97 patients with myotonic dystrophy type 1. J Neurol 2012;259:912-920.
66. Garcia De Andoin N, Echeverria J, et al. A neonatal form of Steinert's myotonic dystrophy in twins after in vitro fertilization. Fertil Steril 2005;84:756.
67. Barbosa J, Nuttall FQ, Kennedy W, Goetz F. Plasma insulin in patients with myotonic dystrophy and their relatives. Medicine 1974;53:307.
68. Jakase S, Okita N, Sakuma H, et al. Endocrinological abnormalities in myotonic dystrophy: consecutive studies of eight tolerance tests in 26 patients. Tohoku J Exp Med 1987;153:355-374.
69. Savkur RS, Philips AV, Cooper TA. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 2001;29:40-47.
70. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Abbreviated Report of a WHO Consultation. Report No. WHO/NMH/CHP/CPM/11.1.
71. Sarnat HB, O'Connor T, Byrne PA. Clinical effects of myotonic dystrophy on pregnancy and the neonate. Arch Neurol 1976;33:459-465.
72. Webb D, Muir I, Faulkner J, Johnson G. Myotonia dystrophica: obstetric complications. Am J Obstet Gynecol 1978;132:265-270.
73. Marjan De Rademaeker, Willem Verpoest, Martine De Rycke, et al. Preimplantation genetic diagnosis for myotonic dystrophy type 1: upon request to child. Eur J Hum Genet 2009;17:1403-1410.
74. Meola G, Sansone V, Radice S, et al. A family with an unusual myotonic and myopathic phenotype and no CTG expansion (proximal myotonic myopathy syndrome): a challenge for future molecular studies. Neuromuscul Disord 1996;6:143-150.
75. 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;7:217-228.
76. Day JW, Roelofs R, Leroy B, et al. Clinical and genetic characteristics of a fivegeneration family with a novel form of myotonic dystrophy (DM2). Neuromuscul Disord 1999;9:19-27.
77. Day JW, Ricker K, Jacobsen JF, et al. Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum. Neurology 2003;60:657-664.
78. Turner C, Hilton-Jones D, Lochmüller H, Hanna MG. MRC Centre for Neuromuscular Diseases 1st (1st December 2010), and 2nd (2nd May 2012) myotonic dystrophy workshops, London, UK and the myotonic dystrophy standards of care and national registry meeting, Newcastle, UK July 2011. Neuromuscul Disord 2013;23:1069-1080.
79. Gagnon C, Chouinard MC, Laberge L, et al. Health supervision and anticipatory guidance in adult myotonic dystrophy type 1. Neuromuscul Disord 2010;20:847-851.
80. Magaña JJ, Cisneros B. Perspectives on gene therapy in myotonic dystrophy type 1. J Neurosci Res 2011;89:275-285.
81. Wheeler TM, Leger AJ, Pandey SK, et al. Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature 2012;488:111-115. This is an exciting study demonstrating prolonged pathological and clinical benefit of antisense treatment in a mouse model of myotonic dystrophy type 1.
82. Nakamori M 1, Sobczak K, Puwanant A, et al. Splicing biomarkers of disease severity in myotonic dystrophy. Ann Neurol 2013;74:862-872. This study is one of the first studies to apply our knowledge of splicing dysregulation in myotonic dystrophy type 1 and to correlate it with clinical phenotype for potential use a biomarker for therapeutics.