Musculoskeletal System ORGAN SYSTEMS


Dystrophinopathies are a group of disorders resulting from mutations in the dystrophin gene (located on the short arm of X chromosome in the Xp21 region)


Muscular dystrophy is where the muscles weaken and lose muscle mass; in this case, both Duchenne and Becker muscular dystrophy are caused by a genetic mutation in the dystrophin gene.

Dystrophinopathies are a group of disorders resulting from mutations in the dystrophin gene (located on the short arm of X chromosome in the Xp21 region)

  • Muscular dystrophies are diseases of muscle membrane or supporting proteins which are generally characterized by pathological evidence of ongoing muscle degeneration and regeneration.
  • X-linked recessive inheritance
  • M/C hereditary neuromuscular disease



  • Duchenne (pseudomhypertrophic) muscular dystrophy (DMD)
    • M/C muscle dystrophy & dystrophinopathy
    • Due to absent dystrophin gene; more severe
  • Becker muscular dystrophy (BMD)
    • Due to defective dystrophin gene; less severe


Dystrophin gene (DMD)
(Largest protein-coding human gene)

↑ chance of spontaneous mutation

Loss of dystrophin


Dystrophin protein:

Anchors muscle fibres
  • Primarily found in skeletal & cardiac muscle
  • Connects the intracellular cytoskeleton (actin) to the transmembrane proteins α- and β-dystroglycan, which are connected to the extracellular matrix (ECM).
The Calgary Guide |

Clinical features

Begins before 5 years age and worsens quickly: Weakness begins in pelvic girdle muscles and progresses superiorly.

Classical presentation:

  • Trendelenburg/waddling gait
  • Gower sign: Patient uses upper extremities to help stand up
    • Also seen in other muscular dystrophies (eg. polymyositis)
  • Calf muscle pseudohypertrophy: Due to fibrofatty replacement of muscle
Gowers’ sign | William Richard Gowers (1845–1915) – Gowers WR. Clinical lecture on pseudohypertrophic muscular paralysis. Lancet 1879;ii,73-5., Public Domain,


  • Wheelchair-confinement
  • Respiratory failure: Weak diaphragm and respiratory muscles
  • Skeletal deformities: Scoliosis, lordosis
  • Cardiac manifestations: Dilated cardiomyopathy, arrhythmias
  • Intellectual disability (less common in BMD than it is in DMD)
A 13 year-old-boy wheelchair bound for 2 years with Duchenne muscular dystrophy. (A, B) Preoperative antero-posterior and lateral radiographs showing left sided scoliosis with 40。curvature. (C, D) Two year post-operative antero-posterior and lateral radiographs showing instrumentation with pedicle screws. | (2018). Papers citing Spinal Deformity Correction in Duchenne Muscular Dystrophy (DMD): Comparing the Outcome of Two Instrumentation Techniques – Semantic Scholar. [online] Available at: [Accessed 8 Jun. 2018].


  • ↑ Creatine kinase (CK) & ↑ Aldolase
    • Due to death of muscle cells

Gene testing (CONFIRMATORY):

  • Multiplex PCR
  • Multiplex ligation-dependent probe amplification (MLPA)


  • Features of muscular dystrophy:
    • Necrosis and attempted regeneration of individual muscle fibres
    • ↑ variability of muscle fibre diameter
      • With both hypertrophic and small fibres
    • Central nuclei
  • End-stage biopsy:
    • Almost the entire muscle is replaced by fibrofatty tissue
  • Immunohistochemical analysis (CONFIRMATORY)
    • Dystrophin (1, 2 and 3) staining
      • Absent: Duchenne muscular dystrophy
      • Sparse: Becker muscular dystrophy


  • Corticosteroids:
    • Prednisone
    • Deflazacort
  • Supportive management:
    • Pulmonary and cardiac care
    • Nutrition
    • Calcium homeostasis
    • Appropriate immunization
    • Orthopaedic care
A leg brace worn on the left foot with ankle hinge | Daniel Lewis – CC0,

Novel threapies:

  • Viltolarsen: For confirmed DMD mutation
  • Casimersen: Confimed mutation amenable to exon 45 skipping

Leave a Reply