Duchenne/Becker Muscular Dystrophy Deletion/Duplication With Reflex to Sequencing

Last Literature Review: January 2019 Last Update:
  • Most comprehensive DMD gene test for DMD or BMD
  • Deletion/duplication analysis is performed first
    • If no large deletions or duplications are detected and/or results do not explain the clinical scenario, sequencing of the DMD gene is performed
  • Deletion/duplication and sequencing components are also orderable separately, see below

If a familial sequence variant has been previously identified, targeted sequencing for that variant may be appropriate. Refer to the Laboratory Test Directory for additional test options.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked degenerative muscle disorders caused by pathogenic variants in the DMD gene. Testing for DMD variants can be used to confirm a diagnosis of DMD/BMD in symptomatic individuals or to determine carrier status for females with a family history of DMD/BMD or dilated cardiomyopathy (DCM). Prenatal testing for familial DMD variants is also available.

Disease Overview


  • DMD
    • Delayed childhood milestones (eg, sitting, standing, walking, climbing) due to progressive symmetrical muscular weakness
    • Cardiomyopathy onset: approximately 14 years
      • 95% have cardiovascular involvement
    • Wheelchair dependence: typically by 12 years
    • Laboratory findings
      • No observable dystrophin expression
      • Serum CK levels: significantly increased
  • BMD
    • Later-onset muscle weakness
    • Cardiomyopathy onset: approximately 15 years 
    • Wheelchair dependence: 20s-30s
    • Laboratory findings
      • Dystrophin expression: 20-100%
      • Serum CK levels: increased
  • DMD-Associated Dilated Cardiomyopathy (DCM)
    • Rapidly progressive disease course in the absence of skeletal myopathy
    • Male age of onset: teens and 20s
    • Female age of onset – 30s and 40s


  • DMD: 1/3,500 male births worldwide
  • BMD: 1/19,000 male births worldwide


Gene: DMD

Inheritance: X-linked


  • Males: 100%
  • Females: varies with X-chromosome inactivation

De novo variants: approximately 1/3 cases

Typical Diagnostic Testing Strategy

  • Initial testing for DMD/BMD
    • Serum creatine kinase (CK) concentration
    • Muscle biopsy with dystrophin studies
  • Molecular testing
    • Deletion/duplication analysis
    • Sequencing analysis

Typical Carrier Testing Strategy

  • For a known familial DMD variant, targeted testing is recommended.
  • If there is a family history of DMD/BMD but the causative familial variant is unknown, test an affected relative then perform targeted testing for the identified variant in at-risk relatives.
  • If an affected relative cannot be tested, at-risk relatives should be tested by deletion/duplication analysis first because most DMD variants are large deletions and duplications.
    • If negative, consider DMD sequencing.

Recommended Follow-Up Testing

Cardiac evaluation for affected individuals and carriers

Test Description

Clinical Sensitivity

  • DMD
    • Deletion/duplication: 55-75%
    • Sequencing: 20-35%
  • BMD
    • Deletion/duplication: 75-90%
    • Sequencing: 10-20%


  • Positive
    • One pathogenic variant detected in DMD gene
      • Causative for DMD/BMD in males
      • Female carriers are variably affected
  • Negative
    • No pathogenic variants identified
      • Risk for being affected with, or a carrier of, DMD/BMD, is reduced but not excluded.
  • Inconclusive
    • Variants of uncertain clinical significance detected
    • Whether variants are benign or pathogenic is unknown


  • A negative result does not exclude a heritable form of muscular dystrophy.
  • Diagnostic errors can occur due to rare sequence variations.
  • Interpretation of this test result may be impacted if the individual has had an allogeneic stem cell transplantation.
  • The following will not be evaluated:
    • Variants outside the coding regions and intron-exon boundaries of the targeted gene(s)
    • Regulatory region variants and deep intronic variants
    • Breakpoints of large deletions/duplications
    • Noncoding transcripts
  • The following may not be detected:
    • Deletions/duplications/insertions of any size by massively parallel sequencing
    • Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions
    • Low-level somatic variants

Analytic Sensitivity

  • For MLPA: greater than 99%
  • For massively parallel sequencing:
  • Variant ClassAnalytic Sensitivity (PPA) Estimatea (%)Analytic Sensitivity (PPA) 95% Credibility Regiona (%)
    Deletions 1-10 bp93.884.3-98.2
    Deletions 11-44 bp10087.8-100
    Insertions 1-10 bp94.886.8-98.5
    Insertions 11-23 bp10062.1-100

    DMD gene is a subset of a larger methods-based validation from which the PPA values are derived.

    bp, base pairs; PPA, positive percent agreement; SNVs, single nucleotide variants