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Muscular Dystrophies

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Title: Muscular Dystrohies Author: Brenda Deliz MD Keywords: 2009, Neuromuscular, Muscular Dystrophy Last modified by: Dannewille Leonne Created Date – PowerPoint PPT presentation

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Title: Muscular Dystrophies


1
Muscular Dystrophies
  • Lhedaven C. Santos R.N.

2
Muscular Dystrophies
  • Progressive hereditary degenerative diseases of
    the skeletal muscle
  • Intact spinal motor neurons, muscular nerves, and
    nerve endings in the presence of severe
    degenerative changes in muscle fibers
  • General features
  • symmetrical distribution of weakness and atrophy
  • intact sensation
  • preservation of reflexes
  • heredofamilial
  • Classified by clinical types, pattern of
    inheritance and by the abnormal gene or its
    protein product

3
Etiology
  • The abnormal gene and the gene product for
    Duchenne and Becker identified by Kunkel in 1986
  • Dystrophin is the protein encoded by the affected
    gene
  • Dystrophin absent in Duchenne and structurally
    abnormal in Becker
  • Dystrophin in normal skeletal and cardiac muscle
    is localized in the sarcolemma (cytoplasmic site)
    and interacts with F-actin of the cytoskeleton
    (reinforcing structure of muscle cell)
  • Dystrophin also bound to a complex of sarcolemmal
    proteins known as dystrophin associated proteins
    (DAP)

4
Etiology
  • Loss of dystrophin leads to disruption of the
    dystroglycan-protein complex rendering the
    sarcolemma susceptible to breaks during
    contraction
  • These defects are shown to allow ingress of EC
    fluid and calcium which activate proteases and
    cause protein degradation
  • Leakage of CK into serum is then seen

5
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6
Duchenne MD
  • Incidence rate 13-33 per 100,000 male births
    annually
  • X-linked recessive
  • 30 of cases represent new mutations
  • Females can present disease if only one
    chromosome is present (Turner) or due to
    inactivation of the normal paternal X chromosome
    in large proportion of embryonic cells (decreased
    expression of the normal dystrophin allele)

7
Clinical findings
  • Recognized usually in third year of life due to
    delay in motor milestones or due to frequent
    falls
  • Latter sway back and waddling gait (weak gluteus
    medius) as well as climbing stairs become more
    affected
  • Elevated CK may be the first clue

8
Clinical findings
  • Muscles mostly affected
  • early illiopsoas, quadriceps, gluteal
  • latter pretibial, pectoral girdle (serratus,
    pectorals, latissimus) and upper limbs (biceps,
    brachioradialis)
  • Muscles pseudo-hypertrophied
  • gastronemius, lateral vastus and deltoid
  • have rubbery feel and are less strong and
    hypotonic than normals

9
Clinical findings
  • Weakness of abdominal and paravertebral muscles -
    lordotic posture and protuberant abdomen when
    standing and rounded back when sitting
  • Weak extensors of the knee and hip - difficult to
    climb stairs or from a chair
  • Use of hands to compensate for weakness when
    rising from sitting position or from floor

10
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11
Gowers maneuver
  • 4 point position
  • Hands up to thigh alternately

12
Clinical Findings
  • Ocular, facial and bulbar and hand muscles are
    usually spared
  • Limbs later become flaccid but as disability
    progresses fibrous contractures appear due to
    immobility
  • Early in the disease there is equinovarus due to
    weak pretibial and peroneal muscles later knee
    contractures appear due to weak quadriceps
  • Pelvic tilt also seen later due to contracture of
    hip flexors this is compensated with lordosis
    when standing

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14
Clinical Findings
  • Contractures contribute to eventual loss of
    ambulation
  • Scoliosis appears due to unequal weakening of
    paravertebral muscles usually after walking is
    not possible
  • As muscle atrophy progresses DTRs are lost
  • Bones are thin and demineralized
  • Can have mild mental retardation
  • Although smooth muscle is usually spared heart is
    usually affected

15
Clinical Findings
  • Cardiac problems
  • Arrhythmias
  • prominent R waves in right precordial leads and
    deep Q waves in left precordial and limb leads as
    result of replacement fibrosis of the basal part
    of the left ventricular wall
  • Death is usually 2dary to pulmonary infection and
    respiratory failure or in some due to cardiac
    decompensation
  • No more than 25 of patients survive beyond 25
    years

16
Muscle biopsy
  • In all dystrophies loss of muscle fibers,
    residual fibers of small and larger size in
    haphazard arrangement and increase in lipocytes
    and fibrosis
  • Duchenne -Early segmental degeneration,
    phagocytosis and evidence of regenerative
    activity
  • basophilia of sarcoplasm
  • hyperplasia and nucleolation of sarcolemmal
    nuclei
  • myotubes and myocytes
  • Necrotic sarcoplasm and sarcolemma removed by
    mononuclear cells
  • Hyalinization of the sarcoplasm of muscle fibers
    as marker of irritability of m fiber
  • Fibers eventually degenerate and disappear due to
    exhaustion of regenerative capacity

17
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19
Becker Muscular Dystrophy
  • Incidence estimated to be 3-6 per 100,000 male
    births
  • X-linked disorder
  • Later onset than Duchenne (mean age 12 years but
    range 5-45 y/o)
  • Affects same muscles as Duchennes MD
  • Patient non-ambulatory at 25-30 y/o
  • Death in 5th decade in most
  • Less frequent cardiac involvement
  • Serum CK 25-200 times normal
  • EMG fibrillations, positive waves, low amplitude
    polyphasic MUP

20
Facioscapulohumeral MD
  • Slowly progressive or nearly complete arrest
  • Usually autosomal dominant 4 q35
  • Subvariety w/o facial weakness
  • Onset usually 6-20 y/o
  • Difficulty raising arms above head and winging of
    the scapulae first manifestations
  • Invariably weakness of lower trapezius and
    sternal part of pectoralis
  • Deltoids unusually large and strong
  • Weak orbicularis oculi and oris, zygomaticus

21
Facioscapulohumeral MD
  • Eventually atrophy involves sternomastoid,
    serratus, rhomboid, erector spinae, latissimus
    and deltoids
  • Winged and elevated scapulae, prominent clavicles
  • Popeye arm upper arm thinner than forearm
  • Pelvic muscles involved later and milder
  • Can be asymmetrical
  • CPK can be normal or mildly elevated
  • Rare cardiac involvement

22
Scapular winging
  • Weak (serratus, lower trapezius, rhomboids)
    stabilizers of scapula cause winging
  • Scapular angles can be seen when facing the
    patient

23
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24
Facioscapulohumeral MD
  • Foot drop might be seen
  • Early in the disease weakness can be asymmetrical
  • Rare cardiac involvement
  • CPK normal or slightly elevated

25
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27
Scapuloperoneal MD
  • Autosomal dominant, Chromosome 12
  • Typically involves muscles of the neck, shoulder,
    upper arms, anterior tibial and peroneal groups
  • Onset usually in early or middle adulthood
  • Walking becomes difficult due to foot drop
  • Symptoms in arms and shoulders usually seen later
  • Progression slow in most cases

28
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29
Limb-girdle MD
  • Heterogeneous group
  • Children of both sexes affected
  • No hypertrophy (besides SCARMD)
  • Adults can have weakness in either pelvic or
    shoulder girdle or both, if later onset more
    benign course
  • Most commonly heredited as autosomal recessive
    (2A-2J),
  • Also AD (1A-1E) forms, AD good prognosis
  • EMG myopathic, CK normal or only moderately
    elevated, cardiac involvement infrequent

30
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31
AD Limb Girdle Dystrophies
  • LGMD 1
  • Onset is varied from 4-38 years
  • CPK is slightly or moderately increased
  • Can have flexion contractures of elbows, ankles,
    and IPJ but non-disabling
  • Slow progression with long periods of arrest
  • Normal longevity
  • Some with facial and cardiac involvement
  • Includes defects in proteins located in
    myofibril, cell membrane and EC (collagen
    proteins)

32
AR Limb Girdle Dystrophies
  • LGMD 2
  • Affects males and females equally
  • Shoulder and pelvic girdles affected
  • Defects in proteins located on cell membranes but
    also on myofibrilnucleus (calpain 3)
  • SCARMD (2C-2F)- clinically similar to DMB, from
    3-12 y/o onset, CPK 10-100 times normal,
    hypertrophy and joint contractures, rare cardio
    involvement
  • Some have involvement of distal lower extremities
    (dysferlinopathy)

33
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35
Severe Childhood AR Muscular Dystrophy (SCARMD)
  • LGMD 2C -2E
  • Calf hypertrophy
  • Cardiac involvement
  • marked elevations of CPK early
  • Defect is in one of the 3 dystrophin associated
    glycoproteins
  • ? sarcoglycan, chr 13q
  • a sarcoglycan is called adhalin, chr 17q21
  • ß sarcoglycan also called hetarosin , chr 4q12

36
AD Limb-Girdle Dystrophy with cardiac conduction
involvement
  • Mild proximal limb/girdle dystrophy
  • In half cases cardiac conduction disorders being
    the major threat to life
  • Begins in Lext then shoulders
  • CK normal or moderately elevated
  • All patients retain ambulation
  • Mild contratures infrequent
  • Pacemaker required in some old patients

37
Emery- Dreifuss Muscular Dystrophy
  • X-linked, chromosome Xq28 -emerin
  • Age of onset childhood- adulthood
  • Weakness first upper arm and pectoral girdle
    later pelvic girdle and distal muscles in Lexts
  • Early appearance of contractures in elbow
    flexors, extensors of the neck and posterior calf
    muscles
  • No pseudohypertrophy
  • Usually accompanied by severe cardiomyopathy with
    variable s/a and a/v conduction defects
  • Death secondary to cardiac problems although
    general course is benign in most

38
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39
Oculopharyngeal Dystrophy
  • Autosomal dominant chr 14q11.2-14q13
  • Usually late onset (after 45th y/o)
  • Bilateral ptosis and dysphagia noticed as
    progressive difficulty in swallowing and change
    in voice, can progress to cachexia
  • External ocular muscles, shoulder and pelvic
    muscles can later become weak
  • CK and aldolase might be normal
  • EMG only altered in the affected muscle

40
LGMD
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