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Muscular dystrophy
1.
2. • Skeletal muscle diseases, or myopathies,
are disorders with structural changes or
functional impairment of muscle
3.
4. Clinical Features
• proximal, symmetric limb weakness (arms or
legs) with preserved reflexes and sensation
• asymmetric and predominantly distal
weakness can be seen in some myopathies
• sensory loss suggests injury to peripheral
nerve or the central nervous system (CNS)
rather than myopathy.
• On occasion, disorders affecting the motor
nerve cell bodies in the spinal cord (anterior
horn cell disease), the NMJ , or peripheral
nerves can mimic findings of myopathy
6. intermittent weakness
• myasthenia gravis
• periodic paralyses (hypokalemic, hyperkalemic,
and paramyotonia congenita)
• metabolic energy deficiencies of glycolysis
(especially myophosphorylase deficiency)
• fatty acid utilization (carnitine
palmitoyltransferase deficiency)
• mitochondrial myopathies.
• The states of energy deficiency cause activity-
related muscle breakdown accompanied by
myoglobinuria
7.
8. persistent weakness
• Muscular dystrophy, Polymyositis and Dermatomyositis,
– the proximal muscles are weaker than the distal and are
symmetrically affected, and the facial muscles are spared, a
pattern referred to as limb-girdle.
• Facioscapulohumeral dystrophy (FSHD).
– Facial weakness (difficulty with eye closure and impaired
smile) and scapular winging
• Myotonic dystrophy type 1.
– Facial and distal limb weakness associated with hand grip
myotonia
• NMJ disorders, oculopharyngeal muscular dystrophy,
mitochondrial myopathies, or some congenital myopathies
– cranial nerve muscles are weak, causing ptosis or extraocular
muscle weakness
9.
10.
11. • Muscular dystrophy refers to a group of
hereditary progressive diseases each
with unique phenotypic and genetic
features
14. Pathogenesis
• Dystrophin-glycoprotein complex confer
stability to the sarcolemma
• deficiency of dystrophin (Duchenne's
dystrophy) may lead to secondary loss of the
sarcoglycans and dystroglycan
• Loss of a single sarcoglycan (LGMD) results in
secondary loss of other sarcoglycans in the
membrane without affecting dystrophin
• Disruption of the dystrophin-glycoprotein
complexes weakens the sarcolemma, causing
membrane tears and a cascade of events
leading to muscle fiber necrosis
16. Duchene’s muscular dystrophy
• Most common muscular dystrophy
• X-linked recessive disorder
• Onset before age 5
Epidemiology
• Incidence : ~30 per 100,000 live-born males
• Age : Present at birth ,Usually becomes apparent
between ages 3 and 5
• Sex : Male
Etiology
• XR
• Deletion mutation of the gene that encodes
dystrophin.
23. Symptoms & Signs
• Onset of symptoms typically begins
before age 5.
• Muscular manifestations
– Progressive loss of muscle strength
– Predilection for proximal limb muscles and
neck flexors (girdle muscles)
– involvement of legs is more marked than
arms.
– Muscle weakness by age 5 is obvious by
muscle testing.
24. – Common early signs and symptoms include:
• Frequent falls
• Difficulty keeping up with friends when playing
• Abnormal running, jumping, and hopping
• Use of hands to climb up (Gowers’ maneuver) when
getting up from the floor
• Contractures of the heel cords and iliotibial bands
• Toe walking associated with a lordotic posture
• Apparent by age 6
– Progressive kyphoscoliosis common
– Use of wheelchair typical by age 12
– Respiratory failure in second or third decade
25.
26.
27. • Gowers' sign
• lordotic posture caused by combined trunk
and hip weakness, frequently exaggerated
by toe walking
• Waddling gait, inability of weak hip muscles
to prevent hip drop or hip dip.
• Hyperextension of the knee (genu
recurvatum or back-kneeing), quadriceps
muscle weakness; and a steppage gait, due
to footdrop, accompanies distal weakness
28. • Extramuscular manifestations
– Cardiomyopathy in almost all patients
• Arrhythmias are rare.
• Intellectual impairment common
– Average IQ approximately 1 standard
deviation below mean
– Appears to be nonprogressive
– Verbal ability more affected than
performance
29. Laboratory Tests
• Serum CK
– Elevated to between 20 and 100 times normal
– Abnormal at birth but declines late in the
disease because of inactivity and loss of
muscle mass
30. Mutation analysis on peripheral blood
leukocytes
• Identification of a specific mutation in
dystrophin gene
– Allows for unequivocal diagnosis
– Makes possible accurate testing of potential
carriers
– Is useful for prenatal diagnosis
Diagnostic Procedures
• EMG -> Myopathic
31. Muscle biopsy
• Muscle fibers of varying size
• Small groups of necrotic and regenerating fibers
• Connective tissue and fat replace lost muscle
fibers.
• Definitive diagnosis is established on the basis of
dystrophin deficiency.
• Diagnosis can also be made by Western blot
analysis of muscle biopsy
• specimens.
– Abnormalities on the quantity and molecular weight
of dystrophin protein
33. • Immunocytochemical staining of muscle
with dystrophin antibodies
– Can be used to demonstrate absence or
deficiency of dystrophin
– localizing to the sarcolemmal membrane
– Possible mosaic pattern in carriers of the
disease
– Dystrophin analysis of muscle biopsy
specimens for carrier detection not reliable
35. Treatments
Prednisone 0.75 mg/kg per d
– Significantly slows progression for up to 3
years
– Some patients cannot tolerate
glucocorticoid therapy
• Weight gain is significant
– Complications of long-term use often
outweigh the benefits.
36.
37. Katharine Bushby et al; Lancet Neurol 2009; published online Nov 30. DOI:10.1016/S1474-4422(09)70271-6.
38. Katharine Bushby et al; Lancet Neurol 2009; published online Nov 30. DOI:10.1016/S1474-4422(09)70271-6.
39. Exon skipping therapy
• Duchenne's disease may benefit from
novel therapies that either replace the
defective gene or missing protein or
implement downstream corrections (e.g.,
skipping mutated exons or reading
through mutations that introduce stop
codons).
40.
41. Complications
• Tendon and muscle contractures
• Progressive kyphoscoliosis
• Impaired pulmonary function
• Cardiomyopathy
• Intellectual impairment
42. Prognosis
• Between ages 8 and 10
– Walking may require use of braces.
– Joint contractures and limitations of hip flexion,
knee, elbow, and wrist extension are worsened by
prolonged sitting.
• By age 12
– Most patients are wheelchair-dependent.
– Contractures become fixed.
– Progressive scoliosis often develops.
• May be associated with pain
– Chest deformity occurs with scoliosis.
• Impairs pulmonary function, already diminished by muscle
weakness
43. • By age 16–18
– Predisposition to serious pulmonary
infections
• Respiratory failure in second or third
decade
• Causes of death include:
– Pulmonary infections
– Aspiration
– Acute gastric dilation
– A cardiac cause of death is uncommon
44. Becker’s Muscular dystrophy
• Less-severe form of XR muscular dystrophy
• allelic defects of same gene of Duchenne
Epidemiology
• Incidence :
– 3 per 100,000 live-born males
– ~10 times less frequent than Duchenne
• Age :
– Most between ages 5 and 15
– Onset in the third or fourth decade or even later
can occur
• Sex : Male
45.
46.
47.
48. Symptoms & Signs
• Onset of symptoms occurs between ages 5 and
15.
• Muscular manifestations
– Pattern of muscle wasting closely resembles
Duchenne.
– Progressive weakness of girdle muscles, especially
of lower extremities
– Weakness becomes generalized as disease
progresses.
– Hypertrophy, particularly in calves, is an early and
prominent finding.
– By definition, patients walk beyond age 15 (whereas
patients with Duchenne dystrophy are typically in a
wheelchair by the age of 12).
– Significant facial muscle weakness is not a feature.
– Respiratory failure may develop by fourth decade.
49. • Extramuscular manifestations
– Cardiac, may result in heart failure
– Mental retardation may occur, not as
common as in Duchenne
• Other less common presentations
– Asymptomatic hyper-CK-emia
– Myalgias without weakness
– Myoglobinuria
50. Laboratory Tests
• Serum CK
– Closely resembles findings in Duchenne dystrophy
• Mutation analysis on peripheral blood leukocytes
– Deletions or duplications of the dystrophin gene in 65%
of patients (same as in Duchenne's dystrophy)
– 95% of patients, the DNA deletion does not alter the
translational reading frame of mRNA. These "in-frame"
mutations allow for production of some dystrophin,
which accounts for the presence of altered rather than
absent dystrophin on Western blot analysis
• EMG
– Myopathic
51. • Muscle biopsy
– Results closely resemble those in Duchenne
dystrophy.
– Diagnosis requires Western blot analysis of
muscle biopsy samples demonstrating a
reduced amount or abnormal size of
dystrophin.
52. Treatments
• Use of glucocorticoids has not been
adequately studied
• Endurance training may be helpful
53. Limb-Girdle muscular dystrophy
• Represents more than 1 genetic disorder
• Systematic classification is based on
inheritance pattern
– Autosomal dominant (LGMD1)
– Autosomal recessive (LGMD2)
– Classification employs a sequential alphabetical
lettering system (LGMD1A, LGMD2A, etc.)
• Highly variable range of onset across
disorders, although most present in first 3
decades of life
58. Epidemiology
• Incidence
– Data have not been systematically gathered for
any large heterogeneous population.
– Less common than dystrophinopathies
• Age
– Onset ranging from late in the first decade to
the fourth decade
• Sex
– Affects both male and female
59. Etiology
• Autosomal dominant (LGMD1)
– Presently there are 5 autosomal dominant
disorders identified.
• Autosomal recessive (LGMD2)
– Presently there are 12 autosomal recessive
disorders identified
60. Symptoms & Signs
• Onset of symptoms varies widely across this
group of diseases, usually in first three
decades of life.
• Muscular manifestations
– Slow, progressive weakness of pelvic and
shoulder girdle musculature
– Respiratory insufficiency from weakness of the
diaphragm may occur.
• Extramuscular manifestations
– Cardiomyopathy may occur.
– Intellectual function is unaffected.
61. Laboratory Tests
• Serum CK
– As the syndrome represents multiple
disorders, CK levels are highly variable.
• EMG
– Myopathic, with mixed
myopathy/neuropathy in LGMD1A
62. Treatment
• Supportive care, including ambulatory
aids if necessary, should be offered for
neuromuscular disability.
• Stretching of contractures is difficult
• Management of cardiomyopathy and
arrhythmias can save lives.
63. Complications
• Complications (e.g., cardiac, respiratory)
vary with the specific subtype of disease
64. Emery-Driefuss muscular dystrophy
Epidemiology
• Age
– Early childhood and teenage years
Etiology
• There are 2 genetically distinct forms.
– X-linked :
• Emerin mutations most common
• FHL1 mutation also simila phenotype
– AD
• Mutations LMNA gene for lamin A/C( LGMD1B) , but
clinical symptoms are closely related
69. Symptoms & Signs
• Onset of symptoms occurs in early
childhood or teenage years.
• Muscular manifestations
– Muscle weakness
• Affects humeral and peroneal muscles first
• Later spreads to a limb-girdle distribution
• Prominent contractures in early childhood
and teenage years
– Often precede muscle weakness
– Most commonly occur at the elbow and neck
– Persist throughout course of disease
70. • Extramuscular manifestations
– Cardiomyopathy
• Potentially life threatening, may result in sudden
cardiac death
• Likely related to a spectrum of abnormal atrial
rhythms and conduction defects (includes atrial
fibrillation and atrioventricular heart block)
• Some patients have a dilated cardiomyopathy
• Female carriers of the X-linked variant may have
cardiac manifestations that become clinically
significant.
71. Laboratory Tests
• Serum CK
– May be elevated 2- to 10-fold
• EMG
– Myopathic
• Muscle biopsy
– Nonspecific dystrophic features
– Immunohistochemistry reveals absent emerin
staining of myonuclei in X-linked Emery-
Dreifuss.
• EKG
– Atrial and atrioventricular rhythm disturbances
72. Treatment
• Supportive care, including ambulatory
aids if necessary, should be offered for
neuromuscular disability
• Stretching of contractures is difficult
• Management of cardiomyopathy and
arrhythmias can save lives
73. Complication
• Contractures
• Cardiomyopathy
• A spectrum of atrial rhythm and
conduction defects
• Includes atrial fibrillation and paralysis
and atrioventricular heart block
• Sudden death
74. Congenital Muscular Dystrophy (CMD)
• A group of autosomal recessive disorders
• Symptoms present at birth or within first
few months
• Merosin deficiency
• Fukutin-related protein deficiency
• Fukuyama congenital muscular dystrophy
(FCMD)
• Muscle-eye-brain (MEB) disease
• Walker-Warburg syndrome (WWS)
– the most severe, causing death by 1 year of age.
77. Laboratory Tests
Serum CK
• Markedly elevated
• Merosin deficiency: 5–35 times normal
• Fukutin-related protein deficiency: 10–50 times
normal
• FCMD: 10–50 times normal
• MEB disease: 5–20 times normal
• WWS: 5–20 times normal
EMG
• Myopathic
79. • Muscle biopsy
– Nonspecific dystrophic features
– In merosin deficiency, merosin, or laminin
α2 chain (a basal lamina protein), is deficient
surrounding muscle fibers.
– In other disorders (fukutin-related protein
deficiency, FCMD, MEB disease, WWS),
abnormal dystroglycan staining in muscle.
80. Treatment
• No specific treatment is available
• Proper wheelchair seating is important
• Management of epilepsy and cardiac
manifestations is necessary for some
patients
81. Complications
• Contractures
• Respiratory failure
• Central nervous system is affected in
some forms
– Mental retardation
– Seizures
– Ocular abnormalities impairing vision
82. Myotonic dystrophy
• Also called dystrophia myotonica (DM)
• Two autosomal dominant forms have
been identified: DM1 and DM2.
• unlike other muscular dystrophies
because it is a multi-system disorder that
presents in a large variety of ways
83. Epidemiology
• Prevalence
– 1 in 8,000
• Age
– Usually second decade
– May be infancy if mother affected (DM1 only)
Etiology
• At least 2 clinical disorders with overlapping
phenotype.
– DM1: AD
– DM2 [also called proximal myotonic myopathy
(PROMM)]: AD
84. Patogenesis
• DM1 is transmitted by an intronic mutation
consisting of an unstable expansion of a CTG
trinucleotide repeat in a serine-threonine protein
kinase gene (named DMPK) on chromosome
19q13.3.
• The repeat CTG occurs up to 35 times in unaffected
individuals. In patients with myotonic dystrophy, the
number of repeats is greater than 50.
• An increase in the severity of the disease phenotype
upon increase in the number of trinucleotide repeats
• The unstable triplet repeat in myotonic dystrophy
can be used for prenatal diagnosis.
85. • Congenital disease occurs almost exclusively
in infants born to affected mothers
• DM2 is caused by a DNA expansion
mutation consisting of a CCTG repeat in
intron 1 of the ZNF9 gene located at
chromosome 3q13.3-q24.
• The gene is believed to encode an RNA-
binding protein expressed in many different
tissues, including skeletal and cardiac
muscle.
94. Symptoms & Signs
Muscular manifestations
• Slowly progressive weakness of face, neck, shoulder girdle,
and distal extremities (hands and feet)
– Face and neck
• Temporalis, masseter, and facial muscle atrophy and weakness
– Result in typical "hatchet-faced" appearance
– Less consistent in DM2
• Frontal baldness characteristic in men
– Less consistent in DM2
– Palatal, pharyngeal, and tongue involvement
• Produces dysarthric speech, nasal voice, and difficulty swallowing
– Neck muscles, including flexors and sternocleidomastoids,
involved early
– Distal extremities
• Weakness of wrist extensors, finger extensors, and intrinsic hand
muscles impairs function.
• Ankle dorsiflexor weakness may cause footdrop.
95. • Proximal muscles remain stronger throughout the course.
– Preferential atrophy and weakness of quadriceps may occur.
– DM2, or PROMM, has a distinct pattern of muscle weakness
affecting mainly proximal muscles.
• Some patients have diaphragm and intercostal muscle
weakness.
– Results in respiratory insufficiency
• Myotonia usually appears by age 5.
– percussion of the thenar eminence, tongue, and wrist
extensor muscles
– Causes a slow relaxation of hand grip after a forced voluntary
closure
– Advanced muscle wasting makes myotonia more difficult to
detect
96. Extramuscular manifestations
• Non-neuromuscular
– Daytime Hypersomnia
– Nocturnal hypoventilation
• GI symptom
– delayed gastric emptying
– smooth muscle and sphincter dysfunction
– bile acid malabsorption
– small bowel bacterial overgrowth
• Endocrine complications
– Insulin resistance diabetes mellitus (4 times)
– Gonadal atrophy
• Respiratory complications
– Reduced central drive and respiratory muscle
weakness contribute to nocturnal hypoventilation.
97. • Cardiac involvement
– common in DM1
– sudden death 10–30% of patients
– Not correlate with the degree weakness or size of repeat expansion
– Conduction abnormalities (atrioventricular common CHB)
– arrhythmias (atrial more common)
– cardiomyopathy is rare
– CHF occurs infrequently but may result from cor pulmonale
secondary to respiratory failure.
– MVP is common.
– Conduction defects are less common in DM2
• CNS and eyes
– Intellectual impairment
– reduced drive and reduced ability to sustain interest in activities
– Posterior subcapsular cataracts
98. • Pregnancy and delivery risks
– involvement of uterine smooth muscle
– impaired fetal swallowing and movement
– risk of placenta praevia, polyhydramnios,
preterm birth, and postpartum
haemorrhage
99. Laboratory test
• Serum CK
– May be normal or mildly elevated
• EMG
– Evidence of myotonia is present in most
cases of DM1 but may be more patchy in
DM2.
100. Muscle biopsy
• Muscle atrophy
– Selectively involves type 1 fibers in 50% of cases
– Ringed fibers in DM1 but not in DM2
• Typically, numerous internalized nuclei can
be seen in individual muscle fibers as well as
atrophic fibers with pyknotic nuclear clumps
in both DM1 and DM2.
• Necrosis of muscle fibers and increased
connective tissue not common
101. • atrophy of type 1 fibers, a profusion of central nuclei
(normally myonuclei are under the sarcolemma),
and ring fibers.
102. • EKG
– Abnormalities include first-degree heart
block and more extensive conduction
system involvement.
103. Complications
• increased risk of complications of general
anaesthesia, such as hypotension,
pulmonary aspiration, and respiratory
depression
104. Treatments
• Myotonia in DM1 rarely warrants treatment.
• Some patients with DM2 experience significant
discomfort related to the associated muscle stiffness.
– Phenytoin and mexiletine are preferred agents for the
occasional patient who requires an anti-myotonia drug.
• Other agents, particularly quinine and procainamide, may
worsen cardiac conduction.
• Cardiac pacemaker insertion should be considered
for patients with:
– Unexplained syncope
– Advanced conduction system abnormalities with
evidence of second-degree heart block
– Trifascicular conduction disturbances with marked
prolongation of the PR interval
105. • Molded ankle-foot orthoses
– Help prevent footdrop in patients with distal
lower extremity weakness
• Excessive daytime somnolence with or
without sleep apnea: not uncommon,
and patient may benefit from:
– Sleep studies
– Noninvasive respiratory support (BiPAP)
– Modafinil
106.
107. Genetic counselling in myotonic dystrophy
• The smallest expansions of 50 to 60 repeats are
found in older, unaffected, or mildly affected
individuals, in topmost generations of the family
• repeat size rises in the mutation next generation.
• Relatives of patient are risk
– symptomatic DNAbased diagnostic test
– asymptomatic discuss the genetic of family
history, options such as DNA-based presymptomatic
or prenatal testing
• symptomatic mother higher chance that infant
who inherits the mutation has congenital disease
• females have a congenitally affected child, next
children inheriting the mutation are always
congenitally affected.
108. • Symptomatic children are assessed by a
paediatrician or neurologist
• Genetic testing of the asymptomatic child is
not recommended
• Anxious parents request testing of their
healthy children but after detailed
discussion, it is usually postponed until the
child is mature and can make informed
decision.
• For couples who avoid affected pregnancy,
in vitro fertilisation techniques and pre-
implantation genetic diagnosis
109. Figure 2 Nuclear RNA retention in DM1 causes alteration of the function of MBNL1 and
CUGBP1 proteins and subsequent downstream RNA mis-splicing
Biology of the Cell 2010 102, 515-523 - Nikolas P. Mastroyiannopoulos, Christos Shammas and Leonidas A. Phylactou
www.biolcell.org
112. Facioscapulohumoral (FSH)
muscular dystrophy
Epidemiology
• Prevalence
– ~5 in 100,000
• Age
– Childhood or young adulthood
• Etiology
• Autosomal dominant with almost complete penetrance
• Each family member should be examined for presence of
disease, because ~30% of those affected are unaware of
involvement.
• Caused by deletions of distal 4q
– Mutation permits carrier detection and prenatal diagnosis.
– Most sporadic cases represent new mutations.
113.
114. Symptoms & Signs
• Onset of symptoms occurs in childhood or early
adulthood.
• Muscular manifestations
– Slowly progressive weakness of face, shoulder
girdle, and foot dorsiflexion
– Facial weakness is typically the initial manifestation.
• Inability to smile, whistle, or fully close the eyes
– Weakness of shoulder girdles usually brings patient
to medical attention.
• Loss of scapular stabilizer muscles makes arm elevation
difficult.
• Scapular winging is apparent with attempts at abduction
and forward movement of the arms.
115. • Biceps and triceps muscles may be severely
affected.
– Relative sparing of the deltoid muscles
• Weakness is worse for wrist extension than
for wrist flexion.
• Weakness of the anterior compartment
muscles of the legs may lead to footdrop.
• In 20% of patients, weakness progresses to
involve pelvic girdle muscles.
– Results in severe functional impairment and
possible wheelchair dependency
116. • Extramuscular manifestations
– Characteristically, patients do not have
involvement of other organ systems.
• Labile hypertension common
• Increased incidence of nerve deafness
• Coats’ disease, a disorder consisting of
telangiectasia, exudation, and retinal
detachment
117. Laboratory tests
• Serum CK
– May be normal or mildly elevated
• EMG
– Usually indicates a myopathic pattern
• Muscle Biopsy
– Nonspecific features of a myopathy
– A prominent inflammatory infiltrate present
in some biopsy samples Often multifocal in
distribution
118. treatment
• No specific treatment is available.
• Ankle-foot orthoses are helpful for
footdrop.
• Scapular stabilization procedures
– Improve scapular winging but may not
improve function
119. Oculopharyngeal dystrophy
Epidemiology
• Age
– Onset in fifth and sixth decades
• Geographic and ethnic distribution
– Incidence is high in French-Canadians and in
Spanish-American families of the
southwestern U.S.
– Large kindreds of Italian and of eastern
European Jewish descent have been
reported.
120. • AD with complete penetrance
• Molecular defect is a subtle expansion of
a modest polyamine repeat tract
• in a poly-RNA binding protein (PABP2) in
muscle.
123. Symptoms & Signs
• Onset of symptoms occurs in fifth and sixth decades of life.
• Slowly progressive weakness of:
– Extraocular muscles
– Pharyngeal muscles
– Limb muscles
• Progressive external ophthalmoplegia
– Slowly progressive ptosis
– Limitation of eye movements
– Sparing of pupillary reactions for light and accommodation
– Patients usually do not complain of diplopia.
• Dysphagia
– May become debilitating
– May result in pooling of secretions and repeated episodes of
aspiration
• Mild weakness of neck and extremities may also occur.
124. Laboratory test
• Serum CK
– May be 2–3 times normal
• EMG
– Myopathic
• Muscle biopsy
– Muscle fibers contain vacuoles.
– Electron microscopy shows membranous
whorls, accumulation of glycogen, and other
nonspecific debris related to lysosomes.
– A distinct feature is the presence of tubular
filaments, 8.5 nm in diameter, in muscle cell
nuclei.
125. Treatment
• Cricopharyngeal myotomy
– May improve swallowing
– Does not prevent aspiration
• Eyelid crutches
– Can improve vision when ptosis obstructs
vision
– Candidates for ptosis surgery must be
carefully selected.
– Those with severe facial weakness are
usually not suitable.
127. Distal Myopathies
• A group of muscle diseases, the distal
myopathies, are notable for their
preferential distal distribution of muscle
weakness in contrast to most Muscular
Dystrophies and Other Muscle Diseases
muscle conditions associated with
proximal weakness.
130. Laboratory test
• Serum CK
– Miyoshi's myopathy is very elevated
– In the other conditions, serum CK is only slightly increased.
• EMGs
– myopathic.
– MFMs, myotonic or pseudomyotonic discharges are common.
• Muscle biopsy
– Often show nonspecific dystrophic features rimmed vacuoles.
– MFM is associated with the accumulation of dense inclusions,
as well as amorphous material best seen on Gomori's
trichrome and myofibrillar disruption on electron microscopy.
– MFM Immune staining sometimes demonstrates
accumulation of desmin and other proteins
– Laing's myopathy large deposits of myosin heavy chain in
the subsarcolemmal region of type 1 muscle fibers
– Miyoshi's myopathy reduced or absent dysferlin
131. Treatment
• Occupational therapy is offered for loss
of hand function
• ankle-foot orthoses can support distal
lower limb muscles
132. Complication
• The MFMs can be associated with
cardiomyopathy (congestive heart failure
or arrhythmias) and respiratory failure
• Laing's-type distal myopathy can also be
associated with a cardiomyopathy
