Download PDF
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2017; 75(08): 589-599
DOI: 10.1590/0004-282X20170112
CONSENSUS

Brazilian consensus on Duchenne muscular dystrophy. Part 1: diagnosis, steroid therapy and perspectives

Consenso brasileiro sobre distrofia muscular de Duchenne - Parte 1 diagnóstico, corticoterapia e perspectivas
Alexandra P. Q. C. Araujo
1   Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Rio de Janeiro, RJ, Brasil;
,
Alzira A. S. de Carvalho
2   Faculdade de Medicina do ABC, Santo André SP, Brasil;
,
Eduardo B. U. Cavalcanti
3   Rede Sarah de Reabilitação, Ambulatório de Doenças Neuromusculares, Brasília DF, Brasil;
,
Jonas Alex M. Saute
4   Hospital de Clinicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
,
Elmano Carvalho
5   Rede SARAH de Hospitais de Reabilitação, Equipe de Doenças Neuromusculares, Belo Horizonte MG, Brasil;
,
Marcondes C. França Junior
6   Universidade Estadual de Campinas, Departamento de Neurologia, Campinas SP, Brasil;
,
Alberto R. M. Martinez
6   Universidade Estadual de Campinas, Departamento de Neurologia, Campinas SP, Brasil;
,
Monica de M. M. Navarro
5   Rede SARAH de Hospitais de Reabilitação, Equipe de Doenças Neuromusculares, Belo Horizonte MG, Brasil;
,
Anamarli Nucci
6   Universidade Estadual de Campinas, Departamento de Neurologia, Campinas SP, Brasil;
,
Maria Bernadete D. de Resende
7   Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brasil;
,
Marcus Vinicius M. Gonçalves
8   Universidade da Região de Joinville, Joinville SC, Brasil;
,
Juliana Gurgel-Giannetti
9   Universidade Federal de Minas Gerais, Faculdade de Medicina, Belo Horizonte MG, Brasil;
,
Rosana H. Scola
10   Universidade Federal do Paraná, Serviço de Doenças Neuromusculares, Curitiba PR, Brasil;
,
Cláudia F. da R. Sobreira
11   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brasil.
,
Umbertina C. Reed
7   Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brasil;
,
Edmar Zanoteli
7   Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brasil;
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

ABSTRACT

Significant advances in the understanding and management of Duchenne muscular dystrophy (DMD) took place since international guidelines were published in 2010. Our objective was to provide an evidence-based national consensus statement for multidisciplinary care of DMD in Brazil. A combination of the Delphi technique with a systematic review of studies from 2010 to 2016 was employed to classify evidence levels and grade of recommendations. Our recommendations were divided in two parts. We present Part 1 here, where we describe the guideline methodology and overall disease concepts, and also provide recommendations on diagnosis, steroid therapy and new drug treatment perspectives for DMD. The main recommendations: 1) genetic testing in diagnostic suspicious cases should be the first line for diagnostic confirmation; 2) patients diagnosed with DMD should have steroids prescribed; 3) lack of published results for phase 3 clinical trials hinders, for now, the recommendation to use exon skipping or read-through agents.

RESUMO

Avanços na compreensão e no manejo da distrofia muscular de Duchenne (DMD) ocorreram desde a publicação de diretrizes internacionais em 2010. Nosso objetivo foi elaborar um consenso nacional baseado em evidências de cuidado multidisciplinar dos pacientes com DMD no Brasil. Utilizamos a técnica de Delphi combinada com revisão sistemática da literatura de 2010 a 2016 classificando níveis de evidência e graus de recomendação. Nossas recomendações foram divididas em duas partes. Apresentamos aqui a parte 1, descrevendo a metodologia utilizada e conceitos gerais da doença, e fornecemos recomendações sobre diagnóstico, tratamento com corticosteroides e novas perspectivas de tratamentos medicamentosos. As principais recomendações: 1) testes genéticos deveriam ser a primeira linha para confirmação de casos suspeitos; 2) pacientes com diagnóstico de DMD devem receber corticosteroides; 3) por enquanto, a falta de publicações de resultados dos ensaios clínicos de fase 3, dificulta recomendações de uso medicamentos que “saltam exons” ou “passam” por código de parada prematura.

muscular dystrophy, Duchenne - practice guideline - consensus - diagnosis - genetic testing - drug therapy - glucocorticoids - utrophin
distrofia muscular de Duchenne, guia de prática clínica - consenso - diagnóstico - testes genéticos - tratamento farmacológico - glucocorticoides - utrofina

Support:

Genzyme, GSK, PTC, Biomarin, Biogen, Roche. Those do not influence the content of this work.


Support:

On behalf of the Brazilian Academy of Neurology, Neuromuscular Disease Department




Publication History

Received: 08 March 2017

Accepted: 03 April 2017

Article published online:
05 September 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Emery AE. Population frequencies of inherited neuromuscular diseases: a world survey. Neuromuscul Disord. 1991;1(1):19-29. https://doi.org/10.1016/0960-8966(91)90039-U
  • 2 Quan F, Janas J, Toth-Fejel S, Johnson DB, Wolford JK, Popovich BW. Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy. Am J Hum Genet. 1997;60(1):160-5.
  • 3 Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987;51(6):919-28. https://doi.org/10.1016/0092-8674(87)90579-4
  • 4 Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis and pharmacological and psychosocial management. Lancet Neurol. 2010;9(1):77-93. https://doi.org/10.1016/S1474-4422(09)70271-6
  • 5 Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 2010;9(2):177-89. https://doi.org/10.1016/S1474-4422(09)70272-8
  • 6 Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: corticosteroid treatment of Duchenne muscular dystrophy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;86(5):465-72. https://doi.org/10.1212/WNL.20170112201701122337
  • 7 Topaloglu H, Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: corticosteroid treatment of Duchenne muscular dystrophy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;87(2):238. https://doi.org/10.1212/01.wnl.0000489553.99227.18
  • 8 Hadorn DC, Baker D, Hodges JS, Hicks N. Rating the quality of evidence for clinical practice guidelines. J Clin Epidemiol. 1996;49(7):749-54. https://doi.org/10.1016/0895-4356(96)00019-4
  • 9 Hsu C-C, Sandford BA. The Delphi technique: making sense of consensus. Pract Assess, Res Eval. 2007;12(10):1-8.
  • 10 Bushby KM, Hill A, Steele JG. Failure of early diagnosis in symptomatic Duchenne muscular dystrophy. Lancet. 1999;353(9152):55-78. https://doi.org/10.1016/S0140-6736(98)05279-9
  • 11 Mirski KT, Crawford TO. Motor and cognitive delay in Duchenne muscular dystrophy: implication for early diagnosis. J Pediatr. 2014;165(5):1008-10. https://doi.org/10.1016/j.jpeds.2014.07.006
  • 12 Manjunath M, Kiran P, Preethish-Kumar V, Nalini A, Singh RJ, Gayathri N. A comparative study of mPCR, MLPA, and muscle biopsy results in a cohort of children with Duchenne muscular dystrophy: a first study. Neurol India. 2015;63(1):58-62. https://doi.org/10.4103/0028-3886.152635
  • 13 Cuisset JM, Rivier F. [Central manifestations of dystrophinopathies]. Arch Pediatr. 2015;22(12 Suppl 1):12S58-62. French. https://doi.org/10.1016/S0929-693X(16)30010-0
  • 14 Mendell JR, Shilling C, Leslie ND, Flanigan KM, Dahhak R, Gastier-Foster J et al. Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol. 2012;71(3):304-13. https://doi.org/10.1002/ana.23528
  • 15 McMillan HJ, Gregas M, Darras BT, Kang PB. Serum transaminase levels in boys with Duchenne and Becker muscular dystrophy. Pediatrics. 2011;127(1):e132-6. https://doi.org/10.1542/peds.2010-0929
  • 16 Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K et al. The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat. 2015;36(4):395-402. https://doi.org/10.1002/humu.22758
  • 17 Khordadpoor-Deilamani F, Akbari MT, Nafissi S, Zamani G. Dystrophin gene mutation analysis in Iranian males and females using multiplex polymerase chain reaction and multiplex ligation-dependent probe amplification methods. Genet Test Mol Biomarkers. 2011;15(12):893-9. https://doi.org/10.1089/gtmb.2011.0057
  • 18 Kerr R, Robinson C, Essop FB, Krause A. Genetic testing for Duchenne/Becker muscular dystrophy in Johannesburg, South Africa. S Afr Med J. 2013;103(12 Suppl 1):999-1004. https://doi.org/10.7196/SAMJ.7274
  • 19 Dastur RS, Kachwala MY, Khadilkar SV, Hegde MR, Gaitonde PS. Identification of deletions and duplications in the Duchenne muscular dystrophy gene and female carrier status in western India using combined methods of multiplex polymerase chain reaction and multiplex ligation-dependent probe amplification. Neurol India. 2011;59(6):803-9. https://doi.org/10.4103/0028-3886.91355
  • 20 Chen C, Ma H, Zhang F, Chen L, Xing X, Wang S et al. Screening of Duchenne muscular dystrophy (DMD) mutations and investigating its mutational mechanism in Chinese patients. PLoS One. 2014;9(9):e108038. https://doi.org/10.1371/journal.pone.0108038
  • 21 Hegde MR, Chin EL, Mulle JG, Okou DT, Warren ST, Zwick ME. Microarray-based mutation detection in the dystrophin gene. Hum Mutat. 2008;29(9):1091-9. https://doi.org/10.1002/humu.20831
  • 22 Ishmukhametova A, Khau Van Kien P, Méchin D, Thorel D, Vincent MC, Rivier F et al. Comprehensive oligonucleotide array-comparative genomic hybridization analysis: new insights into the molecular pathology of the DMD gene. Eur J Hum Genet. 2012;20(10):1096-100. https://doi.org/10.1038/ejhg.2012.51
  • 23 Wang Y, Yang Y, Liu J, Chen XC, Liu X, Wang CZ et al. Whole dystrophin gene analysis by next-generation sequencing: a comprehensive genetic diagnosis of Duchenne and Becker muscular dystrophy. Mol Genet Genomics. 2014;289(5):1013-21. https://doi.org/10.1007/s00438-014-0847-z
  • 24 Wei X, Dai Y, Yu P, Qu N, Lan Z, Hong X et al. Targeted next-generation sequencing as a comprehensive test for patients with and female carriers of DMD/BMD: a multi-population diagnostic study. Eur J Hum Genet. 2014;22(1):110-8. https://doi.org/10.1038/ejhg.2013.82
  • 25 Takeshima Y, Yagi M, Okizuka Y, Awano H, Zhang Z, Yamauchi Y et al. Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. J Hum Genet. 2010;55(6):379-88. https://doi.org/10.1038/jhg.2010.49
  • 26 Percy ME, Andrews DF, Thompson MW. Serum creatine kinase in the detection of Duchenne muscular dystrophy carriers: effects of season and multiple testing. Muscle Nerve. 1982;5(1):58-64. https://doi.org/10.1002/mus.880050111
  • 27 Percy ME, Andrews DF, Brasher PM, Rusk AC, Reyolds JF. Making the most of multiple measurements in estimating carrier probability in Duchenne muscular dystrophy: the Bayesian incorporation of repeated measurements using logistic discrimination. Am J Med Genet. 1987;26(4):851-61. https://doi.org/10.1002/ajmg.1320260412
  • 28 Hoogerwaard EM, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, Leschot NJ et al. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study. Lancet. 1999;353(9170):2116-9. https://doi.org/10.1016/S0140-6736(98)10028-4
  • 29 Malcov M, Ben-Yosef D, Schwartz T, Mey-Raz N, Azem F, Lessing JB et al. Preimplantation genetic diagnosis (PGD) for Duchenne muscular dystrophy (DMD) by triplex-nested PCR. Prenat Diagn. 2005;25(13):1200-5. https://doi.org/10.1002/pd.1317
  • 30 Ye Y, Yu P, Yong J, Zhang T, Wei X, Qi M et al. Preimplantational genetic diagnosis and mutation detection in a family with duplication mutation of DMD gene. Gynecol Obstet Invest. 2014;78(4):272-8. https://doi.org/10.1159/000365083
  • 31 Drachman DB, Toyka KV, Myer E. Prednisone in Duchenne muscular dystrophy. Lancet 1974;2(7894):1409-12. https://doi.org/10.1016/S0140-6736(74)90071-3
  • 32 Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016;(5):CD003725. https://doi.org/10.1002/14651858.CD003725.pub4
  • 33 Ricotti V, Ridout DA, Scott E, Quinlivan R, Robb SA, Manzur AY et al. Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry. 2013;84(6):698-705. https://doi.org/10.1136/jnnp-2012-303902
  • 34 Parreira SL, Resende MB, Zanoteli E, Carvalho MS, Marie SK, Reed UC. Comparison of motor strength and function in patients with Duchenne muscular dystrophy with or without steroid therapy. Arq Neuropsiquiatr. 2010;68(5):683-8. https://doi.org/10.1590/S0004-282X2010000500002
  • 35 Matthews DJ, James KA, Miller LA, Pandya S, Campbell KA, Ciafaloni E et al. Use of corticosteroids in a population-based cohort of boys with duchenne and becker muscular dystrophy. J Child Neurol. 2010;25(11):1319-24. https://doi.org/10.1177/0883073810362762
  • 36 Silva EC, Machado DL, Resende MB, Silva RF, Zanoteli E, Reed UC. Motor function measure scale, steroid therapy and patients with Duchenne muscular dystrophy. Arq Neuropsiquiatr 2012;70(3):191-5. https://doi.org/10.1590/S0004-282X2012000300007
  • 37 Kim S, Campbell KA, Fox DJ, Matthews DJ, Valdez R. Corticosteroid treatments in males with Duchenne muscular dystrophy: treatment duration and time to loss of ambulation. J Child Neurol. 2015;30(10):1275-80. https://doi.org/10.1177/0883073814558120
  • 38 Moxley RT 3rd, Pandya S, Ciafaloni E, Fox DJ, Campbell K. Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. J Child Neurol. 2010;25(9):1116-29. https://doi.org/10.1177/0883073810371004
  • 39 Lebel DE, Corston JA, McAdam LC, Biggar WD, Alman BA. Glucocorticoid treatment for the prevention of scoliosis in children with Duchenne muscular dystrophy: long-term follow-up. J Bone Joint Surg Am. 2013;95(12):1057-61. https://doi.org/10.2106/JBJS.L.01577
  • 40 Connolly AM, Florence JM, Zaidman CM, Golumbek PT, Mendell JR, Flanigan KM et al. Clinical trial readiness in non-ambulatory boys and men with duchenne muscular dystrophy: MDA-DMD network follow-up. Muscle Nerve. 2016;54(4):681-9. https://doi.org/10.1002/mus.25089
  • 41 Sato Y, Yamauchi A, Urano M, Kondo E, Saito K. Corticosteroid therapy for Duchenne muscular dystrophy: improvement of psychomotor function. Pediatr Neurol. 2014;50(1):31-7. https://doi.org/10.1016/j.pediatrneurol.2013.07.022
  • 42 McDonald CM, Han JJ, Mah JK, Carter GT. Corticosteroids and Duchenne muscular dystrophy: does earlier treatment really matter? Muscle Nerve. 2012;45(6):777-9. https://doi.org/10.1002/mus.23304
  • 43 Merlini L, Gennari M, Malaspina E, Cecconi I, Armaroli A, Gnudi S et al. Early corticosteroyd treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up. Muscle Nerve. 2012;45(6):796-802. https://doi.org/10.1002/mus.23272
  • 44 Hoffman EP, Reeves E, Damsker J, Nagaraju K, McCall JM, Connor EM et al. Novel approaches to corticosteroid treatment in Duchenne muscular dystrophy. Phys Med Rehabil Clin N Am. 2012;23(4):821-8. https://doi.org/10.1016/j.pmr.2012.08.003
  • 45 Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2016;16(4):249-55. https://doi.org/10.1016/j.nmd.2006.01.010
  • 46 Griggs RC, Herr BE, Reha A, Elfring G, Atkinson L, Cwik V et al. Corticosteroids in Duchenne muscular dystrophy: major variations in practice. Muscle Nerve. 2013;48(1):27-31. https://doi.org/10.1002/mus.23831
  • 47 Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2002;12(10):917-25. https://doi.org/10.1016/S0960-8966(02)00180-3
  • 48 Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V et al. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011;77(5):444-52. https://doi.org/10.1212/WNL.0b013e318227b164
  • 49 Beytía ML, Vry J, Kirschner J. Drug treatment of Duchenne muscular dystrophy: available evidence and perspectives. Acta Myol. 2012;3(1)1:4-8.
  • 50 Pane M, Fanelli L, Mazzone ES, Olivieri G, D’Amico A, Messina S et al. Benefits of glucocorticoids in non-ambulant boys/men with Duchenne muscular dystrophy: a multicentric longitudinal study using the performance of upper limb test. Neuromuscul Disord. 2015;25(10):749-53. https://doi.org/10.1016/j.nmd.2015.07.009
  • 51 Barber BJ, Andrews JG, Lu Z, West NA, Meaney FJ, Price ET et al. Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy. J Pedriatr. 2013;163(4):1080-4.e1. https://doi.org/10.1016/j.jpeds.2013.05.060
  • 52 Voit T, Topaloglu H, Straub V, Muntoni F, Deconinck N, Campion G et al. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014;13(10):987-96. https://doi.org/10.1016/S1474-4422(14)70195-4
  • 53 Drugs.com. Kyndrisa approval status. 2017 [cited 2017 May 15]. Available from: https://www.drugs.com/history/kyndrisa.html
  • 54 European Medicines Agency. Science Medicines Health. Withdrawal of the marketing authorisation application for Kyndrisa (drisapersen). 2016 [cited 2017 May 15]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2016/06/WC500209339.pdf
  • 55 Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016;79(2):257-71. https://doi.org/10.1002/ana.24555
  • 56 Drugs.com. Exondys 51 approval history. 2017 [cited 2017 May 15]. Available from: https://www.drugs.com/history/exondys-51.html
  • 57 Kesselheim AS, Avorn J. Approving a problematic muscular dystrophy drug: implications for FDA policy. JAMA. 2016;316(22):2357-8. https://doi.org/10.1001/jama.2016.16437
  • 58 European Medicines Agency. Science Medicines Health. EMEA-001722-PIP01-14-M01: Etepilrsen. 2016 [cited 2017 May 15]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001722-PIP01-14-M01/pip_001413.jsp&mid=WC0b01ac058001d129
  • 59 Bushby K, Finkel R, Wong B, Barohn R, Campbell C, Comi GP et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve. 2014;50(4):477-87. https://doi.org/10.1002/mus.24332
  • 60 European Medicines Agency. Science Medicines Health. Translarna: ataluren. 2017 [cited 2017 May 15]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002720/human_med_001742.jsp&mid=WC0b01ac058001d124
  • 61 Drugs.com. Translarna approval status. 2017 [cited 2017 May 15]. Available from: https://www.drugs.com/history/translarna.html
  • 62 McDonald CM, Meier T, Voit T, Schara U, Straathof CS, D’Angelo MG et al. Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy. Neuromuscul Disord. 2016;26(8):473-80. https://doi.org/10.1016/j.nmd.2016.05.008
  • 63 Drugs.com. Idebenone approval status. 2017 [cited 2017 May 15]. Available from: https://www.drugs.com/history/idebenone.html
  • 64 European Medicines Agency. Science Medicines Health. Raxone: idebenone. 2017 [cited 2017 May 15]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003834/human_med_001900.jsp&mid=WC0b01ac058001d124