Differential diagnosis of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a disease with an X-linked recessive type of inheritance, belonging to a group of disorders with primary muscle damage, caused by pathogenic variants in the DMD gene and associated with dysfunction of the dystrophin protein. Since DMD is manifested by the gradual development of progressive, mainly proximal muscle weakness, the differential diagnosis is primarily carried out in the group of diseases with muscle damage - myopathies. Among these diseases, the leading candidates for differential diagnosis are hereditary myopathies (limb-girdle muscular dystrophies, facioscapulohumeral dystrophy, congenital muscular dystrophies, glycogenoses - the most common juvenile form of glycogenosis type II (Pompe disease)) and, much less often, congenital myopathies and other conditions of neuromuscular diseases). When conducting a differential diagnosis in a child with suspected DMD, the age of the onset of the disease, early initial clinical manifestations and the development of symptoms as they grow, genealogical analysis, laboratory tests (the level of creatine kinase, aspartate aminotransferase, alanine aminotransferase in blood serum), instrumental (electromyography, magnetic resonance imaging of the brain and muscles) and molecular genetics (polymerase chain reaction, multiplex ligation-dependent probe amplification, next-generation sequencing, Sanger sequencing, etc.) of studies, and in some cases, muscle biopsy data. Knowledge of the nuances of the differential diagnosis allows establishing a genetic diagnosis of DMD as early as possible, which is extremely important for the formation of the prognosis of the disease and the implementation of all available treatment methods, including pathogenetic therapy, and is also necessary for medical and genetic counselling of families with DMD patients.

1. Birnkrant D.J., Bushby K., Bann C.M., Apkon S.D., Blackwell A., Brumbaugh D., et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018; 17(3): 251–67. https://doi.org/10.1016/S1474-4422(18)30024-3

2. Mah J.K., Korngut L., Dykeman J., Day L., Pringsheim T., Jette N. A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul. Disord. 2014; 24(6): 482–91. https://doi.org/10.1016/j.nmd.2014.03.008

3. Goemans N. An introduction to muscular dystrophies and Duchenne and Becker muscular dystrophies. In: Deconinck N., Goemans N., eds. Neuromuscular Disorders in Children: a Multidisciplinary Approach to Management. London: Mac Keith Press; 2019: 166–86.

4. Mah J.K. Duchenne and Becker muscular dystrophies: underlying genetic and molecular mechanisms. In: Huml R.A., ed. Muscular Dystrophy: a Concise Guide. New York: Springer; 2015: 21–35.

5. Ciafaloni E., Fox D.J., Pandya S., Westfield C.P., Puzhankara S., Romitti P.A., et al. Delayed diagnosis in Duchenne muscular dystrophy: data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). J. Pediatr. 2009; 155(3): 380–5. https://doi.org/10.1016/j.jpeds.2009.02.007

6. Birnkrant D.J., Bushby K., Bann C.M., Alman B.A., Apkon S.D., Blackwell A., et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018; 17(4): 347–61. https://doi.org/10.1016/S1474-4422(18)30025-5

7. Arkhipova E.N. Cardiac involvement in children with neuro-muscular disorders. Nervno-myshechnye bolezni. 2015; 5(4): 10–5. https://doi.org/10.17650/2222-8721-2015-5-4-10-15 (in Russian)

8. van Ruiten H.J.A., Straub V., Bushby K., Guglieri M. Improving recognition of Duchenne muscular dystrophy: a retrospective case note review. Arch. Dis. Child. 2014; 99(12): 1074–7. https://doi.org/10.1136/archdischild-2014-306366

9. Laing N.G., Davis M.R., Bayley K., Fletcher S., Wilton S.D. Molecular diagnosis of Duchenne muscular dystrophy: past, present and future in relation to implementing therapies. Clin. Biochem. Rev. 2011; 32(3): 129–34.

10. Pushkov A., Savostyanov K., Kuzenkova L., Kurenkov A., Podkletnova T., Zhurkova N., et al. Different alterations in DMD gene in 62 Russian children with Duchenne muscular dystrophy as a result of a two-stage molecular genetic analysis. Euro. J. Neurol. 2020; 27(S1): 1154.

11. Hoffman E.P., Arahata K., Minetti C., Bonilla E., Rowland L.P. Dystrophinopathy in isolated cases of myopathy in females. Neuro­logy. 1992; 42(5): 967–75. https://doi.org/10.1212/wnl.42.5.967

12. Hoogerwaard E.M., van der Wouw P.A., Wilde A.A., Bakker E., Ippel P.F., Oosterwijk J.C., et al. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul. Disord. 1999; 9(5): 347–51. https://doi.org/10.1016/s0960-8966(99)00018-8

13. Amato A.A., Brown R.H.Jr. Muscular dystrophies and other muscle diseases. In: Kasper D.L., Fauci A.S., Longo D.L., eds. Harrison’s Principles of Internal Medicine. New York, NY: McGraw-Hill; 2015: 462e-1-462e-20.

14. Goemans N. Limb-girdle muscular dystrophies. In: Deconinck N., Goemans N., eds. Neuromuscular Disorders in Children: a Multidisciplinary Approach to Management. London: Mac Keith Press; 2019.

15. Straub V., Murphy A., Udd B. 229th ENMC international workshop: Limb girdle muscular dystrophies – Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017. Neuromuscul. Disord. 2018; 28(8): 702–10. https://doi.org/10.1016/j.nmd.2018.05.007

16. Straub V., Bushby K. The childhood limb-girdle muscular dystrophies. Semin. Pediatr. Neurol. 2006; 13(2): 104–14. https://doi.org/10.1016/j.spen.2006.06.006

17. Nigro V., Savarese M. Genetic basis of limb-girdle muscular dystrophies: the 2014 update. Acta Myol. 2014; 33(1): 1–12.

18. Domingos J., Sarkozy A., Scoto M., Muntoni F. Dystrophinopathies and limb-girdle muscular dystrophies. Neuropediatrics. 2017; 48(4): 262–72. https://doi.org/10.1055/s-0037-1601860

19. Melacini P., Fanin M., Duggan D.J., Freda M.P., Berardinelli A., Danieli G.A., et al. Heart involvement in muscular dystrophies due to sarcoglycan gene mutations. Muscle Nerve. 1999; 22(4): 473–9. https://doi.org/10.1002/(sici)1097-4598(199904)22:4%3C473::aid-mus8%3E3.0.co;2-5

20. Fanin M., Melacini P., Boito C., Pegoraro E., Angelini C. LGMD2E patients risk developing dilated cardiomyopathy. Neuromuscul. Disord. 2003; 13(4): 303–9. https://doi.org/10.1016/s0960-8966(02)00280-8

21. Duggan D.J., Gorospe J.R., Fanin M., Hoffman E.P., Angelini C. Mutations in the sarcoglycan genes in patients with myopathy. N. Engl. J. Med. 1997; 336(9): 618–24. https://doi.org/10.1056/nejm199702273360904

22. Schwartz M., Hertz J.M., Sveen M.L., Vissing J. LGMD2I presenting with a characteristic Duchenne or Becker muscular dystrophy phenotype. Neurology. 2005; 64(9): 1635–7. https://doi.org/10.1212/01.wnl.0000157654.59374.e5

23. Poppe M., Cree L., Bourke J., Eagle M., Anderson L.V., Birchall D., et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology. 2003; 60(8): 1246–51. https://doi.org/10.1212/01.wnl.0000058902.88181.3d

24. Deenen J.C., Arnts H., van der Maarel S.M., Padberg G.W., Verschuuren J.J., Bakker E., et al. Population-based incidence and prevalence of facioscapulohumeral dystrophy. Neurology. 2014; 83(12): 1056–9. https://doi.org/10.1212/wnl.0000000000000797

25. Deconinck N. Facioscapulohumeral muscular dystrophy. In: Deconinck N., Goemans N., eds. Neuromuscular Disorders in Children: a Multidisciplinary Approach to Management. London: Mac Keith Press; 2019: 214–9.

26. Mul K., Lassche S., Voermans N.C., Padberg G.W., Horlings C.G., van Engelen B.G. What’s in a name? The clinical features of facioscapulohumeral muscular dystrophy. Pract. Neurol. 2016; 16(3): 201–7. https://doi.org/10.1136/practneurol-2015-001353

27. McDonald C.M., Campbell C., Torricelli R.E., Finkel R.S., Flanigan K.M., Goemans N., et al. Clinical Evaluator Training Group, ACT DMD Study Group. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 390(10101): 1489–98. https://doi.org/10.1016/s0140-6736(17)31611-2

28. Mercuri E., Muntoni F., Osorio A.N., Tulinius M., Buccella F., Morgenroth L.P., et al. Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study. J. Comp. Eff. Res. 2020; 9(5): 341–60. https://doi.org/10.2217/cer-2019-0171