Duchenne Muscular Dystrophy

Key Points:

  • Progressive skeletal and cardiac muscle myopathy with onset in early childhood.
  • History and physical, chronicity of symptoms, and CPK levels are often diagnostic.  Muscle biopsy is usually not necessary.
  • Aggressive PT and brace management may improve function
  • Corticosteroid therapy may prolong life and delay loss of ambulation
  • Surgical treatment has a role in scoliosis and for joint contractures
  • Needs to be distinguished from other types of muscular dystrophy and neurologic disorders 

Description:

An X linked genetic disorder (1:3500 children, almost all males) in which there is progressive myocyte destruction due to instability of the muscle cell membrane.  This leads to a progressive weakening from early childhood with progressive loss of function and pulmonary capacity that leads to premature death, often in the 3rd decade of life

Natural history

Weakness is noted from early childhood with delay in walking, and difficulties with balance.  Almost all children will achieve ambulation (average age 2 years).  Many children will present as new onset toe walkers as they compensate for quadriceps weakness. Weakness progresses throughout the first decade of life.  Gluteus maximus weakens first resulting in a lordotic gait. Most children lose the ability to ambulate early in the 2nd decade of life.   Upper extremity function will decline as well with loss of shoulder elevation and hand to mouth activity occurring in many by the middle of the second decade.  Pulmonary function exhibits a slow and steady decline.  Cardiomyopathy is often evident.  Most patients expire in the early third decade of life often due to pulmonary insufficiency or cardiomyopathy.

Etiology

DMD is caused by a mutation in the dystrophin gene (Xp21.2) which codes for a muscle cell membrane protein.   The dystrophin protein is usually absent or present at very low levels.  Most mutations are deletions in the coding or promoter regions (60-70% of clinical cases) that cause frame shift mutations resulting in nonsense proteins.   The exact function of dystrophin is not known but it is thought to stabilize the cell membrane against tensile forces of repetitive contraction.   Dystrophin is also present in cardiac and smooth muscle and is implicated in the development of cardiomyopathy.  Dystrophin is also present in the central nervous system and its deficiency leads to cognitive and learning disabilities common in patients with DMD.   
    
The lack of dystrophin function leads to muscle cell breakdown with resultant inflammation and fibrosis.  Progressive loss of muscle function due to weakness (loss of muscle mass) and fibrosis (inflammatory response to muscle breakdown) leads to progressive loss of skeletal and respiratory muscle power with some but not all muscles developing contracture due to scarring.  Becker’s muscular dystrophy is caused by less significant mutations in the same dystrophin gene with higher levels of functioning dystrophin found in myocytes; this leads to a less severe phenotype and more protracted progression of the disease.

Epidemiology:

Clinical Findings:

Physical Examination Affected children will show progressive weakness in the proximal muscles of the shoulder and hip girdle.  They will have a Gower’s sign, using their hands on their thighs to push themselves upright.  As the disease progresses, they will lose the ability to walk and maintain trunk and head support.  
All joints should be evaluated for progressive contracture, especially knee, ankle, and hip.  Patients should be assessed for scoliosis and sitting balance.

Laboratory evaluation will show elevated CPK (100X normal value, usually higher than other muscular dystrophies).  Blood test (Leukocyte DNA) can identify 60-70% of deletions.  Muscle biopsy for diagnosis may be required if blood test / DNA tests are inconclusive. Muscle biopsy will typically show extensive fibrosis.  Electrodiagnostic nerve studies are usually normal.

Differential Diagnosis
Other forms of muscular dystrophy-distinguished by onset and muscles affected:
Myotonic Dystrophy, Becker’s muscular dystrophy, fascioscapulohumeral       dystrophy, limb girdle muscular dystrophy
Spinal muscular atrophy – will have abnormal EMG and normal CPK

Etiology:

Treatment:

Medical Therapy

There is some evidence that corticosteroid therapy may prolong ambulation, prevent/delay scoliosis development and progression, and prolong life expectancy.  The mechanism by which corticosteroids delay functional decline is unknown but it is thought to involve inhibition of the inflammation and scarring associated with the breakdown of muscle tissue.  Corticosteroid regimens vary by region and national regulation of specific types of corticosteroids for human therapy.

Non operative orthopaedic treatment

Physical Therapy has a positive role in maintaining strength and slowing the development of contractures. 

Orthotic Management Lower Extremity
FOs and later locking KAFOs will support and may prolong ambulation.  Spinal orthosis or molded wheelchair seats may delay progression of scoliosis but fusion is usually indicated in progressive curves.

Surgical Treatment

Progressive contractures may be improved with tendon lengthening but recurrence rates may be high. Scoliosis should be addressed early with posterior spinal instrumentation and fusion, often recommended when the Cobb angle reaches 20-30 degrees. Earlier fusion is recommended to avoid pulmonary functional decline and risks associated with more advanced cardiomyopathy.  Caution should be used in aggressively correcting kyphosis since the child may use kyphosis to their advantage to get weak hands to their mouth.

Complications:

Treatment related complications are common in more advanced stages of the disease.   Physical therapy can lead to pathologic fracture due to progressive worsening of osteopenia.  Surgical treatment of scoliosis or joint contracture can be complicated by pneumonia, respiratory failure, or heart failure.  Patients with an ejection fraction of less than 20% are at significantly increased risk for morbidity and mortality.  Implant migration can occur due to osteopenia.  

References:

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  2. Dubowitz V. The muscular dystrophies--clarity or chaos? [editorial; comment]. New England Journal of Medicine 1997; 336( 9): 650-1.
  3. Emery AE. The muscular dystrophies. Bmj 1998; 317( 7164): 991-5.
  4. Lebel DE, Corston JA, McAdam LC, et al. Glucocorticoid treatment for the prevention of scoliosis in children with Duchenne muscular dystrophy: long-term follow-up. J Bone Joint Surg Am. 2013;95:1057–1061. 
  5. Leitch KK, Raza N, Biggar D, Stephen D, Wright JG, Alman B. Should foot surgery be performed for children with Duchenne muscular dystrophy?J Pediatr Orthop. 2005 Jan-Feb;25(1):95-7.
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  7. Rahimov F, Kunkel LM. The cell biology of disease: cellular and molecular mechanisms underlying muscular dystrophy. J Cell Biol. 2013;201:499–510.
  8. Sussman M. Duchenne Muscular DystrophyJ Am Acad Orthop Surg March/April 2002; 10:138-151.
  9. Vignos PJ, Wagner MB, Karlinchak B, Katirji B. Evaluation of a program for long-term treatment of Duchenne muscular dystrophy. Experience at the University Hospitals of Cleveland. Journal of Bone & Joint Surgery -American Volume 1996; 78( 12): 1844-52.

Top Contributors:

Tom McPartland MD