Transcript Muscular Dystrophies Lhedaven C. Santos R.N.

Muscular Dystrophies
Lhedaven C. Santos R.N.
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:
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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 it’s protein product
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)
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
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)
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
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
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
Gower’s maneuver
• 4 point position
• Hands up to thigh
alternately
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 DTR’s are lost
• Bones are thin and demineralized
• Can have mild mental retardation
• Although smooth muscle is usually spared heart is
usually affected
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
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 Duchenne’s 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
Facioscapulohumeral MD
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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
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
Scapular winging
• Weak (serratus, lower
trapezius, rhomboids)
stabilizers of scapula
cause winging
• Scapular angles can be
seen when facing the
patient
Facioscapulohumeral MD
• Foot drop might be seen
• Early in the disease weakness can be
asymmetrical
• Rare cardiac involvement
• CPK normal or slightly elevated
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
Limb-girdle MD
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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
AD Limb Girdle Dystrophies
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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)
AR Limb Girdle Dystrophies
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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)
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
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
LGMD