Myotonic dystrophy: genetics and clinical polymorphism

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Abstract

Myotonic dystrophy is the most common form of hereditary progressive muscular dystrophy in adults. The disorder is characterized by progressive course, autosomal
dominant inheritance and multisystem involvement (skeletal muscles, myocardium, endocrine system, eyes, etc.). The paper highlights a huge heterogeneity of
clinical manifestations of myotonic type 1 and type 2, and reviews genetic aspects and current approaches to the diagnosis of myotonic dystrophy. We present our
own clinical observation of myotonic dystrophy in a family, which demonstrates a rare combination of a classical form of myotonic dystrophy type 1, syringomyelia
and proximal muscle weakness, and provides an classical example of the phenomenon of anticipation.

About the authors

Ekaterina O. Ivanova

Research Center of Neurology

Author for correspondence.
Email: kate-fileo@mail.ru
Russian Federation, Moscow

Anna N. Moskalenko

Research Center of Neurology

Email: kate-fileo@mail.ru
Russian Federation, Moscow

Ekaterina Yu. Fedotova

Research Center of Neurology

Email: kate-fileo@mail.ru
Russian Federation, Moscow

Sergey A. Kurbatov

Voronezh Regional Clinical Diagnostic Center

Email: kate-fileo@mail.ru
Russian Federation, Voronezh

Sergey N. Illarioshkin

Research Center of Neurology

Email: kate-fileo@mail.ru
Russian Federation, Moscow

References

  1. Harper P.S., Karpati G., Hilton-Jones D., Griggs R.C. (eds.) Myotonic dystrophy. Disorders of Voluntary Muscle. Cambridge: Cambridge University Press, 2001: 541–559.
  2. Meola G., Cardani R. Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochim Biophys Acta 2015; 1852: 594–606. doi: 10.1016/j.bbadis.2014.05.019. PMID: 24882752.
  3. Brook J.D., McCurrach M.E., Harley H.G. 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. PMID: 1568252
  4. Udd B., Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 2012; 11: 891–905. doi: 10.1016/S1474-4422(12)70204-1. PMID: 22995693.
  5. Savić Pavićević D., Miladinović J., Brkušanin M. et al. Molecular genetics and genetic testing in myotonic dystrophy type 1. BioMed Research International 2013; 2013: 391821. doi: 10.1155/2013/391821. PMID: 23586035.
  6. Meola G., Cardani R. Myotonic dystrophy type 2 and modifier genes: an update on clinical and pathomolecular aspects. Neurol Sci 2017; 38: 535–546. doi: 10.1007/s10072-016-2805-5. PMID: 28078562.
  7. Rudenskaya G.E., Polyakov A.V. [Myotonic dystrophy type 2]. Annals of clinical and experiental neurology 2012; 2: 55–60. (In Russ.)
  8. Mankodi A., Takahashi M.P., Jiang H. et al. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell 2002; 10: 35–44. PMID: 12150905.
  9. Machuca-Tzili L., Brook D., Hilton-Jones D. Clinical and molecular aspects of the myotonic dystrophies: a review. Muscle Nerve 2005; 32: 1–18. doi: 10.1002/mus.20301. PMID: 15770660.
  10. Ho G., Cardamone M., Farrar M. Congenital and childhood myotonic dystrophy: Current aspects of disease and future directions. World J Clin Pediatr 2015; 4: 66–80. doi: 10.5409/wjcp.v4.i4.66. PMID: 26566479.
  11. Echenne B., Bassez G. Congenital and infantile myotonic dystrophy. Handb Clin Neurol 2013; 113: 1387–1393. doi: 10.1016/B978-0-444-59565-2.00009-5. PMID: 23622362.
  12. Douniol M., Jacquette A., Cohen D. et al. Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1. Dev Med Child Neurol 2012; 54: 905–911. doi: 10.1111/j.1469-8749.2012.04379.x. PMID: 22861906.
  13. Ho G., Carey K.A., Cardamone M., Farrar M.A. Myotonic dystrophy type 1: clinical manifestations in children and adolescents. Arch Dis Child 2019; 104: 48–52. doi: 10.1136/archdischild-2018-314837. PMID: 29871899.
  14. Montagnese F., Mondello S., Wenninger S. et al. Assessing the influence of age and gender on the phenotype of myotonic dystrophy type 2. J Neurol 2017; 264: 2472–2480. doi: 10.1007/s00415-017-8653-2. PMID: 29086017.
  15. Jiménez-Moreno A.C., Raaphorst J., Babačić H. et al. Falls and resulting fractures in myotonic dystrophy: results from a multinational retrospective survey. Neuromuscul Disord 2018; 28: 229–235. doi: 10.1016/j.nmd.2017.12.010. PMID: 29361394.
  16. Wenninger S., Montagnese F., Schoser B. Core clinical phenotypes in myotonic dystrophies. Front Neurol 2018; 9: 303. doi: 10.3389/fneur.2018.00303. PMID: 29770119.
  17. Boentert M., Wenninger S., Sansone V.A. Respiratory involvement in neuromuscular disorders. Curr Opin Neurol 2017; 30: 529–537. doi: 10.1097/WCO.0000000000000470. PMID: 28562381.
  18. Kornblum C., Lutterbey G., Bogdanow M. et al. Distinct neuromuscular phenotypes in myotonic dystrophy types 1 and 2. J Neurol 2006; 253: 753–761. doi: 10.1007/s00415-006-0111-5. PMID: 16511650.
  19. Colding-Jorgensen E. Electromyography and diagnosis of muscular diseases. Ugeskr Laeger 2005; 167: 3070. PMID: 16109264.
  20. Suokas K.I., Haanpää M., Kautiainen H. et al. Pain in patients with myotonic dystrophy type 2: A postal survey in Finland. Muscle Nerve 2011; 45: 70–74. doi: 10.1002/mus.22249. PMID: 22190310.
  21. Pelargonio G., Dello Russo A., Sanna T. et al. Myotonic dystrophy and the heart. Heart 2002; 88: 665–670. PMID: 12433913.
  22. Groh W.J., Groh M.R., Groh W.J. et al. Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1. N Engl J Med 2008; 358: 2688–2697. doi: 10.1056/NEJMoa062800. PMID: 18565861.
  23. Duboc D., Wahbi K. What is the best way to detect infra-Hisian conduction abnormalities and prevent sudden cardiac death in myotonic dystrophy? Heart 2012; 98: 433–434. doi: 10.1136/heartjnl-2011-301407. PMID: 22350028.
  24. Meola G., Moxley R.T. Myotonic dystrophy type 2 and related myotonic disorders. J Neurol 2004; 251: 1173–1182. doi: 10.1007/s00415-004-0590-1. PMID: 15503094.
  25. Schneider-Gold C., Beer M., Kostler H. et al. Cardiac and skeletal muscle involvement in myotonic dystrophy type 2 (DM2): a quantitative 31P-MRS and MRI study. Muscle Nerve 2004; 30: 636–644. doi: 10.1002/mus.20156. PMID: 15452841.
  26. Thornton C.A. Myotonic dystrophy. Neurol Clin 2014; 32: 705–719. doi: 10.1016/j.ncl.2014.04.011. PMID: 25037086.
  27. Orngreen M.C., Arlien-Soborg P., Duno M. et al. Endocrine function in 97 patients with myotonic dystrophy type 1. J Neurol 2012; 259: 912– 920. doi: 10.1007/s00415-011-6277-5. PMID: 22349862.
  28. Turner C., Hilton-Jones D. The myotonic dystrophies: diagnosis and management. J Neurol Neurosurg Psychiatry 2010; 81: 358–367. doi: 10.1136/jnnp.2008.158261. PMID: 20176601.
  29. Savkur R.S., Philips A.V., Cooper T.A. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 2001; 29: 40–47. doi: 10.1038/ng704. PMID: 11528389.
  30. Passeri E., Bugiardini E., Sansone V.A. et al. Vitamin D, parathyroid hormone and muscle impairment in myotonic dystrophies. J Neurol Sci 2013; 331: 132–135. doi: 10.1016/j.jns.2013.06.008. PMID: 23809192.
  31. Angeard N., Jacquette A., Gargiulo M. et al. A new window on neurocognitive dysfunction in the childhood form of Myotonic Dystrophy Type 1 (DM1). Neuromuscul Disord 2011; 21: 468–476. doi: 10.1016/j.nmd.2011.04.009. PMID: 21592796.
  32. Ekström A.B., Hakenäs-Plate L., Tulinius M., Wentz E. Cognition and adaptive skills in myotonic dystrophy type 1: a study of 55 individuals with congenital and childhood forms. Dev Med Child Neurol 2009; 51: 982–990. doi: 10.1111/j.1469-8749.2009.03300.x. PMID: 19459914.
  33. Douniol M., Jacquette A., Cohen D. et al. Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1. Dev Med Child Neurol 2012; 54: 905–911. doi: 10.1111/j.1469-8749.2012.04379.x. PMID: 22861906.
  34. Douniol M., Jacquette A., Guilé J.M. et al. Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy. Eur Child Adolesc Psychiatry 2009; 18: 705–715. doi: 10.1007/s00787-009-0037-4. PMID: 19543792.
  35. Schneider-Gold C., Bellenberg B., Prehn C. et al. Cortical and subcortical grey and white matter atrophy in myotonic dystrophies type 1 and 2 is associated with cognitive impairment, depression and daytime sleepiness. PLoS One 2015; 10: e0130352. doi: 10.1371/journal.pone.0130352. PMID: 26114298.
  36. Peric S., Stojanovic V.R., Nikolic A. et al. Peripheral neuropathy in patients with myotonic dystrophy type 1. Neurol Res 2013; 35: 331–335. doi: 10.1179/1743132812Y.0000000144. PMID: 23336676.
  37. Leonardis L. Peripheral neuropathy in patients with myotonic dystrophy type 2. Acta Neurol Scand 2016; 135: 568–575. doi: 10.1111/ane.12635. PMID: 27401721.
  38. Ronnblom A., Andersson S., Hellstrom P.M., Danielsson A. Gastric emptying in myotonic dystrophy. Eur J Clin Invest 2002; 32: 570–574. PMID: 12190956.
  39. Turner C., Hilton-Jones D. Myotonic dystrophy: diagnosis, management and new therapies. Curr Opin Neurol 2014; 27: 599–606. doi: 10.1097/WCO.0000000000000128. PMID: 25121518.
  40. Zampetti A., Silvestri G., Manco S. et al. Dysplastic nevi, cutaneous melanoma, and other skin neoplasms in patients with myotonic dystrophy type 1: a cross-sectional study. J Am Acad Dermatol 2015; 72: 85–91. doi: 10.1016/j.jaad.2014.09.038. PMID: 25440959.
  41. Campanati A., Giannoni M., Buratti L. et al. Skin features in myotonic dystrophy type 1: an observational study. Neuromusc Disord 2015; 25: 409–413. doi: 10.1016/j.nmd.2015.02.013. PMID: 25813338.
  42. Win A.K., Perattur P.G., Pulido J.S. et al. Increased cancer risks in myotonic dystrophy. Mayo Clin Proc 2012; 87: 130–135. doi: 10.1016/j.mayocp.2011.09.005. PMID: 22237010.
  43. Gadalla S.M., Lund M., Pfeiffer R.M. et al. Cancer risk among patients with myotonic muscular dystrophy. JAMA 2011; 306: 2480–2486. doi: 10.1001/jama.2011.1796. PMID: 22166607.
  44. Van Vliet J., Tieleman A.A., van Engelen B.G.M. et al. Hearing impairment in patients with myotonic dystrophy type 2. Neurology 2018; 90: e615–е622.10.1212. doi: 10.1212/WNL.0000000000004963. PMID: 29343467.
  45. Fedotov V.P., Kurbatov S.A., Ivanova E.A., et al. [Clinical and electromyographic criteria for the diagnosis of hereditary myotonic syndromes]. Nervno-myshechnyye bolezni 2012; (3): 55–66. (In Russ.)
  46. Logigian E.L., Ciafaloni E., Quinn L.C. et al. Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy. Muscle Nerve 2007; 35: 479–485. doi: 10.1002/mus.20722. PMID: 17230537.
  47. Okkersen K., Monckton D.G., Le N. et al. Brain imaging in myotonic dystrophy type 1: A systematic review. Neurology 2017; 89: 960–969. doi: 10.1212/WNL.0000000000004300. PMID: 28768849.
  48. Kornblum C., Reul J., Kress W. et al. Cranial magnetic resonance imaging in genetically proven myotonic dystrophy type 1 and 2. J Neurol 2004; 251: 710–714. doi: 10.1007/s00415-004-0408-1. PMID: 15311347.
  49. Wattjes M.P., Kley R.A., Fischer D. Neuromuscular imaging in inherited muscle diseases. Eur Radiol 2010; 20: 2447–2460. doi: 10.1007/s00330-010-1799-2. PMID: 20422195.
  50. Vihola A., Bassez G., Meola G. et al. Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2. Neurology 2003; 60: 1854–1857. PMID: 12796551.
  51. Levisky R.B., Vianna-Morgante A.M., Frota-Pessoa O. et al. Myotonic dystrophy, syringomyelia, and 2/13 translocation in the same family. J Med Genet 1977; 14: 51–53. PMID: 839501.
  52. Mascalchi M., Padovani R., Taiuti R., Quilici N. Syringomyelia in myotonic dystrophy due to spinal hemangioblastoma. Surg Neurol 1998; 50: 446–448. PMID: 9842869.
  53. Yu X.L., Jia R.Z., Shan P.Y. et al. Myotonic dystrophy type 1 with syringomyelia in a young patient. Chin Med J (Engl) 2016; 129: 487–489. doi: 10.4103/0366-6999.176070. PMID: 26879026.

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Copyright (c) 2019 Ivanova E.O., Moskalenko A.N., Fedotova E.Y., Kurbatov S.A., Illarioshkin S.N.

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