Duchenne Muscular Dystrophy: Clinical Characteristics, Molecular Mechanisms and Management

Ceren Alavanda (Author)

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The dystrophinopathies encompass a range of X-linked muscle disorders varying from mild to severe, including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and DMD-associated dilated cardiomyopathy (DCM). DMD typically manifests in early childhood and progresses rapidly, with affected children becoming wheelchair-dependent by the age of 12. Increased serum CK levels are detected in almost [...]

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    Work TypeBook Chapter
    Published inMolecular Approaches in Medicine
    First Page171
    Last Page189
    DOIhttps://doi.org/10.69860/nobel.9786053359524.9
    Page Count19
    Copyright HolderNobel Tıp Kitabevleri
    Licensehttps://nobelpub.com/publish-with-us/copyright-and-licensing

    The dystrophinopathies encompass a range of X-linked muscle disorders varying from mild to severe, including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and DMD-associated dilated cardiomyopathy (DCM). DMD typically manifests in early childhood and progresses rapidly, with affected children becoming wheelchair-dependent by the age of 12. Increased serum CK levels are detected in almost all DMD patients. Pathogenic variants in the DMD gene affect dystrophin expression, leading to DMD. More than four thousand pathogenic variants have been identified in the DMD gene. deletions of one or more exons are the most common variants in the DMD gene and are found in 60%-70% of patients. With current genetic methods, it is possible to elucidate the molecular etiology in approximately 95% of patients. Penetrance of DMD is complete in males. The penetrance varies in heterozygous carrier females and may depend, partly, X-chromosome inactivation (XCI) patterns. Since DMD has X-linked inheritance pattern, carrier screening should always be considered for mothers of boys with DMD. There are two important points to remember in genetic counseling for DMD. One is that 33% of DMD cases are sporadic (de novo), and the other is that the probability of germline mosaicism for DMD is 15%-20%. Sarcoglycanopathies, Emery-Dreifuss muscular dystrophy, and Barth syndrome are diseases that are included in the differential diagnosis of DMD. Since multiple systems can be affected in DMD patients, management ideally should be provided within a multidisciplinary care setting. Although corticosteroids have been shown to increase muscle strength in DMD patients and are frequently used, they are not a curative treatment. In recent years, antisense oligonucleotides and nonsense suppression therapies have emerged as variant-specific treatments. Also, several new and promising therapies have entered clinical trials or are on the horizon. In this chapter, in addition to this summary about DMD, more comprehensive information is provided.

    Ceren Alavanda (Author)
    MD, Doctor, Van Training and Research Hospital
    https://orcid.org/0000-0002-7327-3849
    3Dr. Ceren Alavanda has been providing routine clinical services and conducting research in human genetics for the past six years. Her primary areas of study are rare genetic diseases and cancer. During this period, she has published over 30 scientific articles and has an h-index of 5. She has received awards for both oral presentations and posters at national conferences. Dr. Alavanda is currently working in the Department of Medical Genetics at Van Education and Research Hospital

    • Aartsma-Rus, A., Fokkema, I., Verschuuren, J., et al. (2009). Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Human mutation, 30(3), 293–299.

    • Banihani, R., Smile, S., Yoon, G., et al. (2015). Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy. Journal of child neurology, 30(11), 1472–1482.

    • Battini, R., Chieffo, D., Bulgheroni, S., et al. (2018). Cognitive profile in Duchenne muscular dystrophy boys without intellectual disability: The role of executive functions. Neuromuscular disorders : NMD, 28(2), 122–128.

    • Beggs, A. H., Koenig, M., Boyce, F. M., Kunkel, L. M. (1990). Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Human genetics, 86(1), 45–48.

    • Connuck, D. M., Sleeper, L. A., Colan, S. D. et al. (2008). Characteristics and outcomes of cardiomyopathy in children with Duchenne or Becker muscular dystrophy: a comparative study from the Pediatric Cardiomyopathy Registry. American heart journal, 155(6), 998–1005.

    • Cotton, S. M., Voudouris, N. J., Greenwood, K. M. (2005). Association between intellectual functioning and age in children and young adults with Duchenne muscular dystrophy: further results from a meta-analysis. Developmental medicine and child neurology, 47(4), 257–265.

    • Crisafulli, S., Sultana, J., Fontana, A., et al. (2020). Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet journal of rare diseases, 15(1), 141.

    • Darras, B. T., Urion, D. K., Ghosh, P. S. In M. P. Adam (Eds.) et. al (2000), Dystrophinopathies. GeneReviews®. University of Washington, Seattle.

    • Datta, N., Ghosh, P. S. (2020). Update on Muscular Dystrophies with Focus on Novel Treatments and Biomarkers. Current neurology and neuroscience reports, 20(6), 14.

    • Den Dunnen, J. T., Grootscholten, P. M., Bakker, E., et al. (1989). Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. American journal of human genetics, 45(6), 835–847.

    • Drousiotou, A., Ioannou, P., Georgiou, T., et al. (1998). Neonatal screening for Duchenne muscular dystrophy: a novel semiquantitative application of the bioluminescence test for creatine kinase in a pilot national program in Cyprus. Genetic testing, 2(1), 55–60.

    • Emery, A. E. H. (2002). “The muscular dystrophies,” in Lancet (Elsevier Limited), 687–695.

    • Ervasti, J. M. (2013). “Structure and function of the dystrophin-glycoprotein complex,” in Madame curie bioscience database. [Internet] (Landes Bioscience).

    • Finkel R. S. (2010). Read-through strategies for suppression of nonsense mutations in Duchenne/ Becker muscular dystrophy: aminoglycosides and ataluren (PTC124). Journal of child neurology, 25(9), 1158–1164.

    • Flanigan K. M. (2014). Duchenne and Becker muscular dystrophies. Neurologic clinics, 32(3), 671–viii.

    • Flanigan, K. M., Dunn, D. M., von Niederhausern, A., et al. (2011). Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene. Human mutation, 32(3), 299–308.

    • Flanigan, K. M., Dunn, D. M., von Niederhausern, A., et al. (2009). Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort. Human mutation, 30(12), 1657–1666.

    • Gao, Q., and McNally, E. (2015). The dystrophin complex: Structure, function, and implications for therapy. Compr. Physiol. 5, 1223–1239.

    • Grimm, T., Müller, B., Müller, C. R. et al. (1990). Theoretical considerations on germline mosaicism in Duchenne muscular dystrophy. Journal of medical genetics, 27(11), 683–687.

    • Hoffman, E. P., Fischbeck, K. H., Brown, R. H., et al. (1988). Characterization of dystrophin in muscle-biopsy specimensfrom patients with Duchenne’s or Becker’s muscular dystrophy. The New England journal of medicine, 318(21), 1363–1368.

    • Hoogerwaard, E. M., van der Wouw, P. A., Wilde, A. A., et al. (1999). Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscular disorders: NMD, 9(5), 347–351.

    • King, W. M., Ruttencutter, R., Nagaraja, H. N., et al. (2007). Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology, 68(19), 1607–1613.

    • Long, C., Amoasii, L., Mireault, A. A., et al. (2016). Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science (New York, N.Y.), 351(6271), 400–403.

    • Mendell, J. R., Campbell, K., Rodino-Klapac, L., et al. (2010). Dystrophin immunity in Duchenne’s muscular dystrophy. The New England journal of medicine, 363(15), 1429–1437.

    • Monaco, A. P., Bertelson, C. J., Liechti-Gallati, S., et al. (1988). An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics, 2(1), 90–95.

    • Nigro, G., Comi, L. I., Politano, L., Bain, R. J. (1990). The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. International journal of cardiology, 26(3), 271–277.

    • Nortitz, G.H., Murphy, N.A. (2013) NEUROMOTOR SCREENING EXPERT PANEL. Motor Delays: Early Identification and Evaluation. Pediatrics. 131(6). Available at: www.pediatrics.org/cgi/content/full/131/6/e2016. (2017). Pediatrics, 140(3), e20172081.

    • Passamano, L., Taglia, A., Palladino, et al. (2012). Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients. Acta myologica: myopathies and cardiomyopathies : Official journal of the Mediterranean Society of Myology, 31(2), 121–125.

    • Pegoraro, E., Schimke, R. N., Garcia, C., et al. (1995). Genetic and biochemical normalization in female carriers of Duchenne muscular dystrophy: evidence for failure of dystrophin production in dystrophin-competent myonuclei. Neurology, 45(4), 677–690.

    • Prior, T. W., & Bridgeman, S. J. (2005). Experience and strategy for the molecular testing of Duchenne muscular dystrophy. The Journal of molecular diagnostics: JMD, 7(3), 317–326.

    • Schwartz, M., Dunø, M. (2004). Improved molecular diagnosis of dystrophin gene mutations using the multiplex ligation-dependent probe amplification method. Genetic testing, 8(4), 361–367.

    • Schwartz, M., Hertz, J. M., Sveen, M. L., et al. (2005). LGMD2I presenting with a characteristic Duchenne or Becker muscular dystrophy phenotype. Neurology, 64(9), 1635–1637.

    • Sumita, D. R., Vainzof, M., Campiotto, S., et al. (1998). Absence of correlation between skewed X inactivation in blood and serum creatine- kinase levels in Duchenne/Becker female carriers. American journal of medical genetics, 80(4), 356–361.

    • Takeshima, Y., Yagi, M., Okizuka, Y., et al. (2010). Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. Journal of human genetics, 55(6), 379–388.

    • Tuffery-Giraud, S., Béroud, C., Leturcq, F., et al. (2009). Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. Human mutation, 30(6), 934–945.

    • White, S. J., Aartsma-Rus, A., Flanigan, K. M., et al. (2006). Duplications in the DMD gene. Human mutation, 27(9), 938–945.

    • Zatz, M., Rapaport, D Vainzof, M., et al. (1991). Serum creatine-kinase (CK) and pyruvate- kinase (PK) activities in Duchenne (DMD) as compared with Becker (BMD) muscular dystrophy. Journal of the neurological sciences, 102(2), 190–196.

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