Muscular dystrophies
Duchenne muscular dystrophy

Topic Completed: 1 December 2017

Minor changes: 28 May 2020

Copyright: 2003-2020,, Inc.

PubMed Search: Duchenne muscular dystrophy [title] humans AND "loattrfree full text"[sb]

Wesley Hiser, M.D.
Jesse L. Kresak, M.D.
Page views in 2019: 6,163
Page views in 2020 to date: 3,423
Cite this page: Hiser W. Duchenne muscular dystrophy. website. Accessed July 4th, 2020.
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)
  • "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 coding
  • 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)
  • 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
  • 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)
  • 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
  • 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:
Missing Image

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

Contributed by Wesley Hiser, M.D.
Missing Image

Myopathic features

Missing Image

Fatty replacement

Missing Image

End stage

Missing Image

Dystrophin protein loss

Missing Image

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 style 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
Back to top