Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder characterized by progressive muscle degeneration and weakness. It is caused by the absence of the protein dystrophin due to mutations in the DMD gene. Symptoms usually begin between ages 2-6 and include difficulty walking, climbing stairs, and rising from the floor. Affected individuals lose the ability to walk by age 12 and often die in their 20s from respiratory or cardiac failure. Diagnosis involves testing for elevated creatine kinase levels and detecting dystrophin abnormalities through muscle biopsy or genetic testing. Currently there is no cure, but treatment focuses on symptom management through bracing, steroids, respiratory support, and physical therapy

2. 
The disease was first described by the Neapolitan physician
Giovanni Semmola in 1834 and Gaetano Conte in 1836

DMD is named after the French neurologist Guillaume
Benjamin Amand Duchenne

In an 1868 publication, Duchenne established the
diagnostic criteria that are still used

Gowers was the first to deduce the genetic basis for the
disease

In 1986, Kunkel provided molecular genetic confirmation of
the X-linked inheritance pattern

3. The muscular dystrophies are a group of genetically
determined, progressive diseases of skeletal muscle
They are non-inflammatory and have no neurological
cause
Duchenne muscular dystrophy (DMD) is the most
common muscular dystrophy affecting 1 in 3500 boys
born worldwide.
Seen in males only
(expect in females with TURNER’S SYNDROME)

4. DMD is inherited in an X-linked
recessive pattern(defect at Xp21
locus)
Females will typically be
carriers for the disease while
males will be affected
The son of a carrier mother has a
50% chance of inheriting the
defective gene from his mother.
The daughter of a carrier mother
has a 50% chance of being a
carrier or having two normal
copies of the gene.

5. The disorder is caused by a mutation in
the dystrophin gene, the largest gene
located on the human X
chromosome which codes for
the protein dystrophin
Without dystrophin, muscles are
susceptible to mechanical injury and
undergo repeated cycles of necrosis
and regeneration.
Ultimately, regenerative capabilities are
exhausted or inactivated

6. Dystrophin is responsible for
connecting the cytoskeleton of each
muscle fiber to the underlying basal
lamina
The absence of dystrophin permits
excess calcium to penetrate
the sarcolemma leading to
mitochondrial dysfunction
mitochondrial dysfunction gives rise
to an amplification of stress-induced
cytosolic calcium signals and an
amplification of stressinduced reactive-oxygen species
(ROS) production.

7. Increased oxidative stress within the cell damages
the sarcolemma and eventually results in the death of the
cell.
Muscle fibers undergo necrosis and are ultimately replaced
with adipose and connective tissue

8. age of onset is between 2-6 years of age
Stage 1 – Presymptomatic
Creatine kinase usually elevated
Positive family history

9. Stage 2- Early ambulatory
clumsy & Waddling gait, manifesting in children aged 2-6 years;
secondary to hip girdle muscle weakness
Inexorable progressive weakness in the proximal
musculature, initially in the lower extremities, but later involving
the neck flexors, shoulders, and arms
Meryon’s sign
child slips through examiner’s grasp when lifted under arms
Possible toe-walking
Can climb stairs

10. Gower's sign
-'climbing up legs' using the hands when rising from the
floor

11. Stage 3- Late ambulatory
More difficulty walking
Around age 8 years, most patients notice difficulty with
ascending stairs and respiratory muscle strength begins a
slow but steady decline
Cannot arise from the floor
The forced vital capacity begins to gradually wane, leading to
symptoms of nocturnal hypoxemia such as lethargy and early
morning headaches

12. Stage 4 – Early nonambulatory
Can self-propel for some time
Able to maintain posture
Possible development of scoliosis
Stage 5 – Late nonambulatory
Scoliosis may progress, especially when more wheelchair
dependent
If wheelchair bound and profoundly weak, patients develop
terminal respiratory or cardiac failure, usually by the early 30s
poor nutritional intake can also be a serious complication in
individuals with severe end-stage DMD
Contractures may develop

13. Generally, neck flexors, wrist extensors,
quadriceps, tibialis anterior, biceps, and triceps
muscles are affected more.
Deep tendon reflexes, which tend to parallel muscle
fiber loss, slowly diminish and ultimately disappear
Calf muscle enlargement (pseudo hypertrophy)
contractures of the iliotibial bands, hip flexors, and
heel cords
Equinovarus deformity of ankle is universal
Asymmetric weakening of the paraspinal muscles
leads to kyphoscoliosis, which in turn further
compromises pulmonary and gastrointestinal
function.

14. 


most are unable to ambulate independently by age 10
most are wheelchair dependent by age 15
most die of cardio respiratory problems by age 25-30

15. Similar traits to
Duchenne's
Distinguishing traits from
Duchenne's
Becker's
Calf pseudo
hypertrophy
• markedly
elevated CPK
• x-linked
transmission
Becker's has slower progression of
weakness with diagnosis made later
(~8 yrs)
• cardiac involvement is frequent
Spinal muscular
atrophy
proximal
weakness
onset of weakness is earlier in
childhood
• absent deep tendon reflexes and
fasciculations
• CPK levels are normal
• pseudo hypertrophy is absent
Emery-Dreifuss
dystrophy
similar clinical
picture
• no calf pseudo hypertrophy
• CPK levels near normal
• elbow and ankle contractures develop
early
Limb girdle
dystrophy
• progressive
motor weakness
•no calf pseudohypertrophy
• CPK levels are only mildly elevated

16.  Serum
Creatine phosphokinase
 Electromyography
 Nerve Conduction Velocity Study
 Molecular diagnosis
 Muscle biopsy
 Imaging Studies
 Electrocardiogram and echocardiogram

17. 
It is elevated in patients with muscle disease and is not specific
to the muscular dystrophies

As the muscle cell degenerates, CK is released and levels can
be elevated 20 to 200 times above normal


It is elevated in the Presymptomatic phase,
falls as the disease worsens,
and approaches near-normal levels in end-stage disease
useful for carrier screening
Muscle provocation test- After strenuous exercise,cpk
levels rise more in carrier females than non carriers.

18.  not
diagnostic but
excludes primarily
neurogenic processes.
 Myopathic
pattern
• decreased amplitude,
short duration,
polyphasic motor

19.  In
a neuropathy, nerve conduction
velocities usually are slowed

In a myopathy, nerve conduction velocities
usually are normal

20.  PCR
amplification
to examine
deletion "hotspots
Absence of a DNA abnormality does not exclude them as
carriers

21. 
used for quantifying the amount of muscle dystrophin as well as
for detecting asymptomatic female carriers

the ideal muscle to biopsy is one that is easily accessible and
exhibits moderate weakness (i.e., has 80% strength)

Gastrocnemius are involved early and are a poor site to obtain
material for a biopsy

Quadriceps (esp. vastus lateralis at midthigh) & rectus
abdominis usually are the most reliable.

General anesthesia carries the known risk of anesthetic
complications, such as malignant hyperthermia. Regional
anesthesia may be used

22. 
The typical muscle biopsy sample consists of 2
specimens: fresh and fixed.

A second sample of muscle tissue should be taken at the
time of biopsy and sent for dystrophin analysis

Electrocautery should not be used while obtaining a
specimen for muscle biopsy

A fresh specimen is used for histochemical studies in all
patients and for immunofluorescence in selected patients

23. It should measure approximately 0.5 X 0.5 cm in crosssection, or 0.5 cm in diameter, and 1 cm in length along the
longitudinal axis of the muscle fibers.
The sample can be sent to the laboratory on salinemoistened gauze in a sealed container on ice. This technique
keeps the specimen cold but does not cause it to freeze
A fixed specimen is used for routine microscopy and possible
electron microscopy
The preferred fixative is liquid nitrogen for light microscopy
and for electron microscopy 3% glutaraldehyde be used.

24. 



increased fibrosis in and between muscle spindles with
necrosis of the fibers
deposition of fat within the fibers accompanied by hyaline
and granular degeneration of the fibers
Special histochemical stains that can show muscle fiber
type show a preponderance of type I fibers
will show absent dystrophin with immunostaining

25. 
Radiographs of the spine are important for screening and
evaluating the degree of scoliotic deformity

As the disease progresses and dyspnea becomes a
complaint, chest radiography is also likely to become a
part of the evaluation

Dual energy x-ray absorptiometry
- Individuals with dystrophinopathies can have
accelerated osteopenia/osteoporosis/fracture risk

26. 
sinus arrhythmias and also may demonstrate deep Q waves
and elevated right precordial R waves.

Transthoracic echocardiography often reveals small
ventricles with prolonged diastolic relaxation.

27. 
Carrier detection is an important aspect of the care and
evaluation of patients with DMD and their family members

For many years, CPK testing was the best method for carrier
detection; however, it is elevated in only two thirds of female
carriers

If affected male in family has a known deletion or
duplication of the dystrophin gene, testing for carrier status
is performed accurately by testing possible carriers for the
same deletion or duplication

28. 
Absence of a DNA abnormality does not exclude them as
carriers

In families in which the affected male has no detectable
deletion or duplication, muscle immunofluorescence for
dystrophin used
- Carrier females should exhibit a mosaic
pattern, with some myofibers being normal and some being
abnormal

29. 
corticosteroid therapy (prednisone 0.75 mg/kg/day)

acutely improves strength, slows progressive
weakening, prevents scoliosis formation, and prolongs
ambulation
 delays deterioration of pulmonary function
• side effects
 osteonecrosis
 weight gain
 cushingoid appearance
 GI symptoms
 short stature
pulmonary care with nightly ventilation

30. 



physiotherapy for range of motion
exercises
adaptive equipment
power wheelchairs
KAFO bracing
The purpose of this is to keep the foot
from pointing downward and sustain the
stretch of the Achilles tendon
also used for walking or for standing and can
be used to prolong ambulation or help delay
the onset of lower limb contractures

31. The goal of orthopaedic treatment is to maintain functional
ambulation as long as possible

32. For surgical correction of lower extremity contractures,
three approaches have been used, as follows
Ambulatory approach:
goal - to correct any contractures in the
lower extremity while the patient is still ambulatory.
Rideau indications:
• first appearance of contractures in lower extremities
• a plateau in muscle strength
•difficulty in maintaining upright posture with the feet
together.
• surgery be performed before deterioration of the Gower
maneuver time

33. Rehabilitative approach:
Surgery is performed after the patient has lost the ability to
walk but with the intention that walking will resume.
Surgery during this stage usually allows for only minimal
ambulation with braces.
Palliative approach:
Treats only contractures that interfere with shoe
wear(equinovarus) and comfortable positioning in a
wheelchair.

34. Percutaneous release of
Hip flexion and
abduction contractures
and Achilles tendon
contracture
Rideau technique
a similar technique, but with an
open procedure to release the
hip flexor contractures and
lateral thigh contractures.
They also excised the iliotibial
band and the lateral
inter
muscular septum