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Duchenne Muscular Dystrophy: The Diagnostic Process


Duchenne Muscular Dystrophy: The Diagnostic Process Care at Diagnosis Aim: provide accurate diagnosis as quickly as possible when DMD is suspected Allow the doctor ... – PowerPoint PPT presentation

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Title: Duchenne Muscular Dystrophy: The Diagnostic Process

Duchenne Muscular DystrophyThe Diagnostic
Care at Diagnosis
  • Aim provide accurate diagnosis as quickly as
    possible when DMD is suspected
  • Allow the doctor and family to plan for care
  • Inform family about course of disease and
    treatment options
  • Provide family with appropriate care, including
    genetic counselling, ongoing support and education

Care at Diagnosis 2
  • Ideally performed by specialist neuromuscular
  • Able to provide clinical assessment, and
    initiate/interpret further investigations
  • Post-diagnosis family follow up and support often
    supplemented by genetic counsellors
  • Families should be offered genetic counselling
  • Contact with support/advocacy group can be helpful

When to suspect DMD
  • Without family history of DMD, suspicions raised
  • Problems with muscle function
  • High levels of Creatine Kinase (CK)
  • High levels of transanimases AST/ALT

Problems with muscle function
  • Often noticed by family
  • Symptoms include
  • Late walking
  • Trouble running, jumping or climbing stairs
  • Falls easily
  • Enlarged calf muscles (hypertrophy)
  • May have a tendency to walk on their toes
  • May have a speech delay
  • Gowers manoeuvre

Calf hypertrophy
  • Image

  • Image and/or video

Gowers Manouvre
  • Video

High levels of CK in blood test
  • Levels typically gt 10-100 times normal range
  • Should prompt an urgent referral to a
    neuromuscular specialist
  • Not alone sufficient to confirm DMD
  • Also seen in other muscle conditions, e.g.
    various forms of limb-girdle muscular dystrophy
  • High CK, dont delay

High levels of AST/ALT
  • High levels of liver enzymes in blood tests
  • Aspartate aminotransferase (AST)
  • Alanine aminotransferase (ALT)
  • May be detected on routine blood screening
  • Often associated with liver disease, but can be
    caused by muscular dystrophies
  • Should raise suspicion of high CK and thus
    muscular dystrophy
  • Liver biopsy is not recommended until CK checked
    unless overt liver disease is present

Confirming the Diagnosis
  • DMD caused by dystrophin mutation at Xp21
  • Diagnosis should be confirmed by genetic testing
  • Other tests sometimes performed as well, most
    notably muscle biopsies

Genetic Testing
  • Genetic testing always necessary even if DMD
    first suggested by muscle biopsy
  • Gives specific, detailed information on mutation
  • Helps determine mutation-specific trial
  • Assists family with decisions on carrier status,
    pre-natal diagnosis and further pregnancies
  • Full characterisation (deletion endpoints, exact
    position of point-mutations) is also required
  • Allows correlation the predicted effect of the
    mutation on the reading frame of the gene
  • Major determinant of phenotypic variability

Types of Genetic Test
  • Multiplex PCR
  • Widely available, least expensive
  • Only detects deletion, doesnt cover whole gene
  • Multiplex ligation-dependent probe amplification
  • Now in common use covers whole gene, detects
    deletions and duplications and allows carrier
  • Others
  • Amplifiable probe hybridisation
  • Single-condition amplification/internal primer
  • Detects deletions and provides sequence data

Importance of Carrier Testing
  • If mother is a carrier, other children could be
    at risk of developing DMD
  • Additional possibility of germline mosaicism
  • Carrier status important for female family on
    mothers side, who should also be offered testing
  • Small risk to carriers of developing weak heart
    or leg weakness in later life. Knowledge of
    carrier status allows appropriate monitoring.

Muscle Biopsy Analysis
  • Analyses amount of dystrophin in muscle cells
  • If diagnosis already confirmed by genetic
    testing, may be unnecessary
  • If diagnosis is made by biopsy, genetic testing
    still essential to determine specific mutation
  • Types of biopsy
  • Open muscle biopsy if DMD is not the only
    possible diagnosis
  • Needle biopsy appropriate if testing is only
    for DMD, or clinician skilled in taking multiple
    cores of tissue from paediatric patients
  • Conchotome technique preferred where available
  • Two tests necessary immunocytochemistry and
    immunoblotting for dystrophin. Should be
    performed by an experienced neuromuscular

  • Staining performed on muscle biopsy sections
  • More likely to be available in some areas than
    immunoblotting for dystrophin
  • Images showing normal/DMD cases from muscle

  • Blotting of homogenised tissue sample
  • Less likely to be available than
    immunocytochemistry in some areas
  • Images showing normal/DMD cases from blotting

Other Tests
  • Previously, other tests were used in diagnosis
  • Electromyography (EMG)
  • Nerve conduction
  • These are not appropriate nor necessary for the
    evaluation of DMD
  • Electron microscopy is not required to confirm DMD

References Resources
  • The Diagnosis and Management of Duchenne Muscular
    Dystrophy, Bushby K et al, Lancet Neurology 2010
    9 (1) 77-93 Lancet Neurology 2010 9 (2) 177-189
  • Particularly references, p186-188
  • Best Practice Guidelines on molecular diagnostics
    in Duchenne/Becker muscular dystrophies, Abbs S
    et al, Neuromuscular Disorders 20 (2010) 422-427
  • The Diagnosis and Management of Duchenne Muscular
    Dystrophy A Guide for Families
  • TREAT-NMD website www.treat-nmd.eu
  • CARE-NMD website www.care-nmd.eu
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