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Muscular Dystrophies
Lhedaven C. Santos R.N.
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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
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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 proteinsknown as dystrophin associated proteins (DAP)
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Etiology
Loss of dystrophin leads to disruption of the
dystroglycan-protein complex rendering the
sarcolemma susceptible to breaks duringcontraction
These defects are shown to allow ingress of
EC fluid and calcium which activateproteases and cause protein degradation
Leakage of CK into serum is then seen
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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)
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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
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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
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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
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Gowers maneuver
4 point position
Hands up to thigh
alternately
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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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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 usuallyaffected
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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
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Muscle biopsy
In all dystrophies loss of
muscle fibers, residual fibers of
small and larger size in
haphazard arrangement andincrease 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 disappeardue to exhaustion of regenerative capacity
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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
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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
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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
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Scapular winging
Weak (serratus, lower
trapezius, rhomboids)
stabilizers of scapulacause winging
Scapular angles can be
seen when facing the
patient
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Facioscapulohumeral MD
Foot drop might be seen
Early in the disease weakness can be
asymmetrical
Rare cardiac involvement
CPK normal or slightly elevated
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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
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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
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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)
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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
myofibril+nucleus (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)
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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
sarcoglycan is called adhalin, chr 17q21
sarcoglycan also called hetarosin , chr 4q12
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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
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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/aand a/v conduction defects
Death secondary to cardiac problems although general course is
benign in most
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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
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LGMD