Muscle
Muscular dystrophies
Duchenne muscular dystrophy

Author: Wesley Hiser, M.D. (see Authors page)
Editor: Jesse L. Kresak, M.D.

Revised: 13 December 2017, last major update December 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Duchenne muscular dystrophy [title] humans AND "loattrfree full text"[sb]
Cite this page: Hiser, W. Duchenne muscular dystrophy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/muscleduchennemusculardystrophy.html. Accessed July 21st, 2018.
Definition / general
  • Most common muscular dystrophy, caused by mutations of the DMD gene on chromosome Xp21
  • Severe, progressive muscle weakness eventually leads to death in early adulthood as a result of respiratory and cardiac muscle involvement
Essential features
  • X linked recessive disease caused my a mutation in the DMD gene, leading to a deficiency of the structural protein dystrophin
  • Progressive muscle weakness leads to loss of ambulation in the early second decade and death, most commonly in the third decade
  • Histologic findings include variation of myofiber size, fatty replacement of myofibers and nonspecific regenerative changes
  • Named after Guillaume-Benjamin-Amand Duchenne (de Boulogne)
Terminology
  • "Dystrophinopathy" refers to both Duchenne and Becker muscular dystrophies, as the clinical distinction between the diseases can be blurred and is based on the amount of dystrophin produced
ICD-10 coding
Epidemiology
Sites
Pathophysiology
  • Mutations in the DMD result in a deficiency of dystrophin, which serves as a structural protein, which stabilizes the dystroglycan complex of the cell membrane (Int J Hematol 2014;99:184)
Etiology
  • Inherited disease caused by dystrophin DMD gene mutations, most often through an X linked inherited pattern
  • Up to 1 / 3 of cases have spontaneous mutations (Tidsskr Nor Laegeforen 2014;134:1361)
Clinical features
  • Clinical symptoms appear within the first 5 years of life
  • Often present first with delayed motor milestones
  • Waddling gait with lumbar lordosis
  • Inability to jump or hop
  • Difficulty rising up from floor (Gowers’ sign)
  • Achilles tendon contractures result in toe walking
  • Pseudohypertrophy of calf muscles as a result of muscle replacement by fibrous and adipose tissue
  • Intellectual impairment present in up to 1 / 3 of patients
  • Ambulation lost by 12 years of age
  • Respiratory failure occurs late in the second decade
  • Female carriers are most often asymptomatic but may demonstrate mild symptoms and are susceptible to cardiomyopathies
Diagnosis
  • Based on combination of clinical features, creatinine kinase levels and genetic studies
  • Muscle biopsy is infrequently performed but may be utilized to evaluate degree of dystrophin expression (Tidsskr Nor Laegeforen 2014;134:1361)
Laboratory
  • Serum creatinine kinase (CK) is extremely high (50 - 100 times normal level)
  • Serum CK is highest early in the disease course and may drop over time
  • Up to 70% of carriers may have increased CK levels
Prognostic factors
  • Disease is progressive and invariably fatal, with death typically occurring in the third or fourth decade of life
Case reports
Treatment
  • No curative treatment
  • Corticosteroids are the primary therapy and are typically initiated by age 5
  • Corticosteroids improve muscle strength and function and appear to reduce development of respiratory and cardiac complications and scoliosis (Tidsskr Nor Laegeforen 2014;134:1361)
  • Abundant research into curative gene and cellular therapies
Clinical images

Images hosted on other servers:
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Back view of boy with Duchenne muscular dystrophy

Microscopic (histologic) description
  • Marked variation in myofiber size, with small, atrophic fibers admixed with large, rounded, hypertrophic ones
  • Increased internal nuclei
  • Myofiber splitting, necrosis and regeneration
  • Increased endomysial fibrosis and fatty replacement of muscle (more prominent later in disease course)
  • May have inflammation (macrophages, T cells) in association with necrosis
  • Architectural changes (whorled fibers, moth eaten fibers) may be seen
  • Carriers may demonstrate histologic abnormalities as well as a mosaic pattern of dystrophin expression (Yachnis: Neuropathology - A Volume in the High Yield Pathology, 1st Edition, 2014)
Microscopic (histologic) images

Images hosted on Pathout server:

Images contributed by Wesley Hiser, M.D.
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Myopathic features

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Fatty replacement

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End stage

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Dystrophin protein loss

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Spectrin control

Positive stains
Negative stains
  • Staining for dystrophin will show absent to markedly reduced expression in sarcolemma of myofibers
  • May have secondary reduced expression of proteins in the dystrophin associated complex, such as utrophin, myosin, dystroglycan and sarcoglycans to variable degrees
Molecular / cytogenetics description
  • Mutation in dystrophin DMD gene (Xp21)
  • Over 4,700 mutations have been described (Tidsskr Nor Laegeforen 2014;134:1361)
  • Up to 30% of cases are caused by spontaneous mutations (Tidsskr Nor Laegeforen 2014;134:1361)
  • Majority of mutations result in deletions that affect amount of dystrophin produced
  • Disruption of reading frame results in significantly decreased or absent protein expression
Differential diagnosis
  • Becker muscular dystrophy: variable severity, typically later onset
  • Congenital muscular dystrophies
  • Limb girdle muscular dystrophy
  • Spinal muscular atrophy
  • Congenital myopathies
  • Metabolic diseases
Board review question #1
    What type of mutation is most frequently associated with Duchenne muscular dystrophy?

  1. Autosomal dominant
  2. Autosomal recessive
  3. De novo
  4. Mitochondrial
  5. X linked recessive
Board review answer #1
E. X linked recessive