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Key Points

  • Disease summary:

    • The term dystrophinopathy encompasses three interrelated diseases: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and DMD-associated dilated cardiomyopathy.

    • DMD has an incidence of approximately 1:4000 live male births and presents in early childhood with progressive proximal muscle weakness leading to loss of ambulation and, cardiomyopathy in the second decade with death in the third decade due to cardiorespiratory compromise. BMD causes later onset of muscle weakness with cardiomyopathy being the most common cause of death in the fourth to fifth decades. DMD-associated dilated cardiomyopathy is common in both phenotypes and may also be present in female carriers of DMD mutations.

    • Dystrophinopathies result from mutations in the DMD gene on Xp21.2 causing a reduced or deficient amount of dystrophin, a membrane-bound protein expressed in skeletal, cardiac, smooth muscle, and neurons. The type of mutation determines the amount of residual protein and the phenotype.

  • Hereditary basis:

    • Deletions, duplications, insertions, and point mutations in the DMD gene, on Xp21.2, cause the dystrophinopathies.

    • Inheritance is X-linked and there is complete penetrance in males who inherit the mutation.

    • Manifestations in female heterozygotes including muscle weakness, myalgias, and cardiomyopathy, are usually due to skewed X-inactivation. In rare circumstances, females can have classic DMD or BMD. In these individuals a structural abnormality of the X chromosome should be ruled out.

    • One-third of mutations are de novo, and are not inherited.

  • Differential diagnosis:

    • When considering the diagnosis of muscular dystrophy, the differential should include facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, Emery-Dreifuss muscular dystrophy, and dilated cardiomyopathy (Table 135-1).

Table 135-1Genetic Differential Diagnosis

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria for Dystrophinopathies

Diagnostic evaluation should include the following

  • Three-generation pedigree to identify affected or at-risk family members

  • Physical examination with particular attention paid to gait, ability to run and jump, proximal muscle weakness, calf hypertrophy, and Gower sign. Fasciculations are absent.

  • Creatine kinase level

    • Elevated to greater than 10× normal in DMD

    • Elevated to greater than 5× normal in BMD

    • Increased in DMD-associated dilated cardiomyopathy

  • DNA testing for deletion, duplication, or mutation of DMD. If no mutation identified, muscle ...

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