2. Introduction
• Defination :
- Myopathies – is abnormality of muscle cell structure and
metabolism leading to various patterns of weakness and
dysfunction.
- Muscular Dystrophy – is a genetic disorder characterized by
progressive weakness and degenration of voluntary and
some involuntary muscles.
3. Classification of Myopathies
- Divided mainly into acquired and inherited.
- Also divided depending on age of onset. Usually early
age onset with longer duration of disease suggests an
inherited myopathy and late age onset with sudden or
subacute onset suggests acquired myopathy.
- Usually present with proximal, symmetric weakness with
preserved reflexes and sensation.
6. Defination :
- DMD – is one of the genetic muscle disease
characterized by progressive myofiber degeneration
and the gradual replacement of muscle by fibrotic
tissue.
• Also called as pseudohypertrophic muscular dystrophy
• Duchenne muscular dystrophy is the most common
muscular dystrophy (1 in 4000 male infants )
• Common genetic disorders (X-linked recessive disorder)
of childhood (early onset )
7. Etiopathogenesis
• It results from a deletion on the short arm of the X
chromosome (at the Xp21 site). This site codes for a protein
called dystrophin.
• Basically this dystrophin protein connects the cytoskeleton
of a muscle fibre( muscle cell ) to the surrounding
extracellular matrix through the cell membrane.
• There are several aberrant intracellular signalling pathways
associated with an influx of calcium ions.
8. • Abnormal gene is located at Xp21 locus on the X-
chromosome, which leads to deficiency of
dystrophin protein in the muscle fibre .
• Where it is deficient there is a breakdown of the calcium
calmodulin complex and an excess of free radicals
ultimately leading to myofibre necrosis.
• The serum creatine phosphokinase (CPK) is markedly
elevated.
9. Clinical Features
Age(yrs) Description
2 Age of onset of condition, Awkward gait
3to 4 Difficulty to walk and run, delayed motor milestones
5.5 Average age of diagnosis, hip girdle muscles weakness, Gowers sign positive
6 Iliotibial band contracture, Lordotic posture, Weakness of shoulder girdle
muscles,
8to 10 Inability to walk, joint contractures and limitations at joint movement, calf
pseudohypertrophy
12 Wheelchair dependent, Contractures become fixed and progressive, Tendon
reflexes diminished, Scoliosis
10to 14 Progressive muscle atrophy and weakness, wheelchair dependent, Mental
retardation
16to 18 Cardiac and pulmonary complication , sever scoliosis and postural deformities
18to 20 Progressive respiratory decline , cardiac dysfunction, aspiration, Death
10.
11. Clinical Features
• Onset is usually before the 3rd or 4th year of life. Although the
average age of diagnosis remains 5.5 years; though becomes
symptomatic much earlier.
• About 2 to 3 years of age, boys develop an awkward gait and an
inability to run properly
• Mild slowness in attaining motor milestones i.e poor head
control during infancy, sitting, standing, walking.
• Progressive weakness in hip and shoulder girdle muscles
beginning by age 5. Difficulty getting up from the floor, the
patient uses his hands to climb up himself (Gowers’ maneuver).
12. • Contractures of the heel cords and iliotibial bands become
apparent by age 6 years, when toe walking is associated
with a lordotic posture.
• Loss of muscle strength is progressive mainly of proximal
limb muscles and the neck flexors; leg involvement is more
severe than arm involvement.
• Weakness of the shoulder muscles may render the child
unable to raise his hands above his head.
• Also includes macrogliosis, absence of incisor teeth.
13. • Between ages 8 and 10 years, walking may require the use
of braces; joint contractures and limitations of hip flexion &
knee, elbow, and wrist extension are made worse by
prolonged sitting.
• There is pseudohypertrophy of the calves because of
replacement of muscle fibres by fat and fibrous tissue.
• Firm calf hypertrophy and mild to moderate proximal leg
weakness with a hyperlordotic, waddling gait.
14. • By age 12 years, most patients are wheelchair dependent.
Contractures become fixed, and progressive.
• Tendon reflexes become progressively diminished and
finally cannot be elicited.
• Scoliosis often develops that may be associated with pain.
The chest deformity with scoliosis impairs pulmonary
function, which is already diminished by muscle weakness.
• Skeletal and postural deformities particularly scoliosis may
later become severe.
15. • The progressive muscle atrophy and weakness means that
they are no longer ambulant(confined to a wheel chair ) by
the age of about 10–14 years.
• Mental retardation occurs in about 30% of the cases. One-
third of affected children have learning difficulties.
16. • By age 16–18 years, patients are predisposed to serious,
sometimes fatal pulmonary infections.
• Congestive heart failure seldom occurs except with severe
stress such as pneumonia. Cardiac arrhythmias are rare.
• Heart may fail from involvement of the myocardium.
• Other manifestations include cardiomyopathy, scoliosis,
respiratory decline, and, in some boys, cognitive and
behavioral dysfunction.
17. • Life expectancy is reduced to the late 20yrs of age from
respiratory failure or the associated cardiomyopathy.
• Death is usual during adolescence from intercurrent
respiratory infection, respiratory or cardiac failure.
• Many boys with Duchenne live into adulthood. Most die in
their 20s or early 30s, usually as a result of progressive
respiratory decline or cardiac dysfunction.
• Other causes of death include aspiration of food and acute
gastric dilation.
19. Diagnosis
• Clinically
- Characteristic phenomenon Gower’s sign– is seen when the
child, lying on his back on the floor, is asked to stand up.
- He will roll to one side, flex his knees and hips so that he is on
all fours with both knees and both hands on the ground.
- He then extends his knees and reaches the erect posture by
climbing up his own legs, using his hands to get higher up each
leg in alternate steps.
20.
21. - Pseudohypertrophy of the
calf muscles with
wasting of thigh muscle.
- Tendon reflexes are
diminished and
finally cannot be elicited
- affected areas in DMD
22. • CPK levels (normal up to 150 IU/L) - massive elevations
(20–100 times normal) of serum CPK levels. The levels are
abnormal at birth but decline late in the disease because of
inactivity and loss of muscle mass.
Healthy female carriers often have elevated serum levels of
creatine kinase
• EMG - a myopathic pattern i.e short, small, polyphasic
MUAP’s
• Muscle Biopsy - . with immunohistochemical staining for
dystrophin shows necrotic muscle fibers with regeneration,
phagocytosis, and fatty replacement of muscle
• Peripheral blood - dystrophin deficiency in muscle tissue or
mutation analysis
23. • ECG - increased net RS in lead V1, deep, narrow Q waves in
the precordial leads, tall right precordial R waves in V1
• Antenatal diagnosis is possible using DNA analysis.
• Impairment of intellectual function appears to be
nonprogressive and affects verbal ability more than
performance.
• Definitive diagnosis – dystrophin deficiency in a biopsy of
muscle tissue or mutation analysis on peripheral blood
leukocytes.
24. Problem List
• Delayed motor milestones ( head holding, sitting, standing, waking )
• Weakness in LL > UL & Proximal > Distal.
• Walking difficulties(tip toe walking ) Gait impairements (waddling
gait, reduced step & stride length, reduced cadence, reduced arm
swing, incomplete stance & swing phase), Balance Problems.
• Leg pain, calf hypertrophy.
• Contractures, Stiffening.
• Scoliosis , Kypho-scoliosis, Lordosis , Flexed knee posture.
• Mental retardation.
• Cardiac & pulmonary complications.
25. Medical Management
• Glucocorticoids - prednisone in a dose of 0.75 mg/kg per
day, significantly slow progression of Duchenne’s dystrophy
for up to 3 years.
• Some patients cannot tolerate glucocorticoid therapy;
weight gain and increased risk of fractures.
• Steroids such as deflazacort 0.9 mg/Kg/daymay give short-
term benefit.
• Gene therapy, Exon skipping, Gene repair are under trial.
26. • Respiratory aids, particularly overnight CPAP (continuous
positive airway pressure) or NIPPV (non-invasive positive
pressure ventilation) may be provide to improve the quality
of life.
• Physiotherapy is important to prevent or delay contracture.
• Contractures, particularly at the ankles, should be
prevented by passive stretching and the provision of night
splints
27. • Lightweight calipers and later bracing of the spine
may prolong ambulation
• Walking with provision of orthoses; those which
allow ambulation by leaning from side to side
• Lengthening of the Achilles tendon may be required
to facilitate ambulation.
• Exercise helps to maintain muscle power and
mobility and delays the onset of scoliosis.
28. • Attention to maintaining a good sitting posture helps to
minimise the risk of scoliosis.
• Scoliosis is managed with a truncal brace, a moulded seat
and ultimately surgical insertion of a metal spinal rod.
• Psychological support is needed for the child and the
family. All chronic disabling conditions, parent self-help
groups are a useful.
