Duchenne muscular dystrophy (DMD)

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Early diagnosis is crucial, because if DMD is treated in time, its progression may be slowed down.

Duchenne muscular dystrophy (DMD) is a severe progressive and rare genetic childhood muscle-wasting disease, most commonly affecting boys. It is caused by a mutation in the gene that encodes dystrophin, an important component of the muscle cell. The lack of dystrophin leads to muscles damage and their gradual degeneration. Early diagnosis is crucial, because if DMD is treated in time, its progression may be slowed down. 1–4

  • Experts estimate that 250,000 patients worldwide suffer from Duchenne muscular dystrophy. The disease affects 1 in 3,600–6,000 live male births. Current life expectancy for people with DMD is no more than 30 years. The disease progresses fast and the patients lose their ability to move between ages 6 and 13.1–4
  • DMD is characterized by proximal muscles weakness, which ultimately causes respiratory and cardiac failure, leading to death.1–4
  • The treatment goal is to slow down the disease progression and to extend the time when the patient is able to move independently, maintaining quality of the patient's life.3-4
  • On 7 September, we celebrate World Duchenne Awareness Day.
  • Early diagnosis is crucial, treatment as early as possible can improve outcomes and may delay disease progression.10,11

Duchenne muscular dystrophy is caused by a mutation in the gene for the protein called dystrophin2

  • DMD is caused by a mutation of the gene for the protein called dystrophin. The gene is located on the X chromosome.2–6
  • The mutation of the gene for dystrophin causes a lack of dystrophin synthesis, which is responsible for the stabilization of the muscle cell membrane.2,4 
  • The lack of dystrophin causes muscle degeneration and gradual replacement of muscle tissue with fibrous connective tissue or fat tissue.6,7
  • Duchenne muscular dystrophy can be caused by different types of mutations.8,9 

Clinical signs of Duchenne muscular dystrophy2–5

  • Up to age 2
    Delayed motor milestones such as walking, delayed speech 
  • Ages 3–4
    Difficulty running and jumping
  • Ages 5–8
    Characteristic clumsy walk (waddling gait ) and toe walking
  • Up to age 13
    Patients are no longer able to move independently (increasing use of wheelchair)
  • When patients become permanently confined to a wheelchair
    Loss of self-feeding, respiratory, orthopaedic and cardiac complication 

Early diagnosis of Duchenne Muscular Dystrophy is crucial for improving the patient’s life; it is important to:10,11,16

  1. Recognize the signs10
    • Motor and speech developmental delay
    • Difficulty running, jumping and walking up the stairs
    • Walking on toes
    • Pseudohypertrophy of the calf muscles 
    • Characteristic walk: “waddle”
    • Gower’s sign
    • Raised transaminase enzyme levels
  2. Determine creatinine kinase values (CK)11,12
    • High CK levels may indicate muscle damage.11,12 
  3. 3. Refer the patient to a neuropaediatrician to confirm the diagnosis10
    • A clinical evaluation of the neuromuscular status is important10 and
    • To refer patient to genetic testing to establish -the type of mutation in order to determine the appropriate treatment.10,13–16

References:

1. McDonald CM, et al. Muscle Nerve. 2013;48:343–356; 2. Goemans N, et al. Eur Neurol Rev. 2014;9:78–82; 3. Van Ruiten HJ, et al. Arch Dis Child. 2014;99:1074–1077; 4. Bushby K, et al. Lancet Neurol. 2010;9:77–93; 5. Annexstad EJ, et al. Tidsskr Nor Laegeforen. 2014;134:1361–1364; 6. Amato AA and Brown RH Jr. Muscular Dystrophies and other muscle diseases. In: Longo DL, Fauci AS, Kaspar DL, et al., eds., Harrison's Principles of Internal Medicine, 19th ed.; 7. Blake DJ, et al. Physiol Rev. 2002; 82:291–329; 8. Bladen CL, et al. Hum Mutat. 2015;36:395–402; 9. Kalman L, et al. J Mol Diagn. 2011;13:167–174.; 10. Bushby K, et al. Lancet Neurol. 2010;9:77–93; 11. Van Ruiten HJ, et al. Arch Dis Child. 2014;99:1074–1077; 12. National Task Force for Early Identification of Childhood Neuromuscular Disorders. Developmental delay, do a CK. Available at: www.childmuscleweakness.org/index.php/developmentaldelay-do-a-ck [quoted 18.10.2016]; 13. Kalman L, et al. J Mol Diagn. 2011;13:167–174; 14. Dent KM, et al. Am J Med Genet. A 2005;134:295–298; 15. Abbs S, et al. Neuromuscul Disord. 2010;20:422–427; 16. Laing NG, et al. Clin Biochem Rev. 2011;32:129–134