DUCHENNE MUSCULAR DYSTROPHY

__________________________________________________

- It is a steadily progressive, X-linked muscular dystrophy resulting from an abnormality at the Xp21 gene loci and is
also a plasma membrane protein dystrophin*** deficiency.



- Genes of pts having this condition occupies 2.5 million base pairs of DNA on the X chromosome, and is about 10
times larger than the next largest gene identified to date (Braddom 2008).

- Most common of the disorders that affects muscles. The onset of this disorder is insidious, usually resulting in Sx
between 2-5 years of age; however, Sx may not be noticed for months or years, and the disease may be misdiagnosed
for years.

- In early years, rapid developmental gains may mask the progression of disease.













PATHOPHYSIOLOGY








EPIDEMIOLOGY
1:3,500 births
M>F
~1/3 of the isolated cases are d/t mutations .


Plasma
membrane
dystrophin
deficiency/
abscence

Abnormalit
y at the
Xp21 gene
loci

Disruption
of
membrane
cyto-
skeleton
2 loss of
cytoskeleton
components.
Membrane
/sarcolemma
l instability
1. susceptibility of
membrane to injury
from mechanical
stresses
2. transient breaches of
the membrane
3. Ca
+
leakage in the
membrane


CHARACTERISTICS OF DMD
progressive muscular weakness (appears during 3
rd
to 4
th
year of life), wasting and contractures
early onset (usually bet. 3-5 years of age)
delay in motor development (particularly walking) abnormal gait (on level surface).
calf mm. HYPERtrophy (in most pt)
Loss of ind. Amb. By 9-12 years of age.
Slowly progressive, generalized weakness during adolescence.
Relentless progression until death from RESPIRATORY TRACT INFECTION or CARDIAC failure.
Dystrophin is ABSENT from the mm. of DMD pt.

mm. cell
NECROSIS
DYSTROPHINit is the 1 protein product of Xp21 gene and is found in the plasma membrane of all myogenic
cells, in certain types of neurons, and in small amounts in other cell types (Braddom 2008).

in 1/3 of all DMD cases, there is high frequency of new gene mutation.(High mutation rate is d/t the
large size of the gene)
65% of pt with DMD (and Becker muscular dystrophy) have gross deletions (absence) of dystrophin
gene.

CLINICAL SIGNS AND Sx
PSEUDOHYPERTROPHY mostly seen on the calf, deltoids and gluteal mm
Progressive muscular weakness and wasting.
Contractures (evident on hip flexors, ITB and calf muscles).
Pain in the muscles (esp. calf muscles)
Enlargement of calves, thighs and upper arms d/t fatty infiltration.
Feet are firm or woody upon palpation.
(+) Gowers sign.

CLINICAL MANIFESTATIONS
Deterioration of mm. strength.
- Relatively SYMMETRICAL and begins PROXIMALLY in the pelvic girdle, shoulder girdle and trunk.
- Hand function is (N) until the later stages of the disease (but is difficult for the child to use his/her
hands without mechanical assist. d/t extreme weakness of the mm. around the shoulder girdle.
Contractures
- Results in progressive mm. weakness, mm. imbalance and the effect of gravity.
- Contractures of the hip flexors, ITB and calf mm. occurs relatively early and result in the typical
posture and gait.
- Once confined to W/, hip and knee flexion contractures and inverted plantarflexed feet
equinovarus deformity may become very marked.
- Elbow contractures >30 (age of 13).
Mild contractures noted in ITB, hip flexors and heel cords (by 6 years of age) LOM (Knee, elbow and wrist
extension) 2 years later.





COMPLICATIONS:
1.) Contractures
2.) Disuse atrophy from
prolong inactivity
3.) Infection
4.) OBESITY
5.) deformity




Weakened respiratory muscles
- Coughing will become ineffective
- Frequently results in pulmonary infections
Scoliosis (strongly related to age)
- 50% of DMD pt acquire scoliosis between ages 12-15 (Braddom 2008).
- d/t weakened trunk muscles + the effect of gravity (in sitting).
- May become extreme interfering the respiratory fnx.
- LORDOTIC posture (of the lumbar spine which is a compensatory change d/t hip extensor
weakness).
- 90 % of older DMD pt have clinical spinal deformity.







frequent falls
- d/t the child tripping or stumbling on a plantar flexed ankle
- the knee buckling or giving way d/t knee extensor weakness
toe walking
- is a compensatory adaptation t knee extensor weakness
profound muscular atrophy occurs in the later stages of the disease.
difficulty climbing steps
Loss of amb. W/C reliance (age related) LE contracture s
- Average w/c use in an UNTREATED DMD pt is 10 years, with a range of 7-13 years.




Immobilization
- Can lead to a marked and often precipitous decline in the mm. power and ambulatory ability of a
child with DMD.


difficulty getting up from the floor
- Usually progressive.
Respiratory Failure
- Insidious in its onset, and results in respiratory muscle weakness and fatigue, alteration in
respiratory system mechanics and impairment of the central control of respiration.


o Amb. Past the age of 14 is probably caused by MILDER form of muscular dystrophies (such us Becker muscular
dystrophy OR Limb girdle muscular dystrophy)
o Amb. Beyond 16 years was previously noted as an exclusion criterion for DMD.
o A fall resulting to fracture leading to immobilization and loss of ambulatory ability is not an uncommon occurrence.
o NO cause and effect relationship has been established between the onset of W/C reliance and the occurrence of
scoliosis.
o (B) W/C reliance and spinal deformity can be significantly related to other factors.
Age, adolescent growth spurt, progressive weakness of the trunk musculature.
o Ambulation becomes impossible by 12 years of age.
o Facial, oropharyngeal and respiratory muscles are spared until the terminal stages of the disease.


- Absolute FVC volumes in pt with DMD during the first decade, and plateau during the early part
of the second decade linear decline between ages 10-20.
- Pt with severe DMD: maximal FVC reached a plateau >1200 mL- 1700 mL. (d/t inability to walk and
severe progressive scoliosis).
Cardiac abnormalities
- Can be detected by clinical exam., electrocardiography, echocardiogram and Holter monitoring.
- In pt with DMD, cardiac exam. Note a point of maximal impulse palpable at the (L) sterna border d/t
marked reduction in AP chest dimension.
- (+) loud pulmonic component of 2
nd
heart sound suggests pulmonary htn in pt with restrictive
pulmonary compromise.
- All pt over age of 13 shows abnormal ECG. (first abnormality to appear: Q waves in the lateral leads.
- (+) cardiac conduction disturbances, premature ventricular contraction and sinus tachycardia.
- Ventricular ectopy is a known complication of cardiomyopathy after age 10 in DMD pt. (may lead to
sudden death).





INTELLECTUAL FUNCTIONING
- Decrease IQ scores (mean score: 1.0-1.5).
- (+) mild global deficits.
- Some studies also shows relative deficits in verbal IQ.

DIAGNOSTIC EVALUATION
SERUM CK LEVEL
- In pt with DMD, serum CK level is extremely high in the first 2years of life before onset of clinical weakness
and is diagnosed by the ff:
1.) Serum enzyme measurement
2.) Mm. biopsy
3.) EMG
- (N) serum CK level: <160 UI/L.
- It is 50-200 times the (N) serum CK levels (~ 15,000 35,000 IU/L).
ASPARTATE AMINOTRANSFERASE LEVELS
- Maybe mildly elevated before mm. weakness is noted (Roland 2000).



MM. BIOPSY
- Reveals degeneration of mm. fibers, with fibrosis and fatty tissue replacement.
- It is usually perform to confirm Dx and shows degenerating and regenerating fibers, inflammatory infiltrates,
which can be compared to (N) mm.
EMG
- EMG readings show a in amplitude and duration of motor unit potentials.
IMMUNOHISTOLOGIC STAINING
- Staining of the tissue reveals the absence of dystrophin along the mm. cell membranes.




- (B) serum CK and aspartate aminotransferase levels diminish with mm. deterioration but do not
reach (N) levels until severe mm. wasting and incapacitation have occurred.
Poor prognosticating factors in DMD:
o Development of cardiomyopathy
o Onset of systolic dysfnx.
MYOCARDIAL IMPAIRMENTS remains clinically silent until late in the course of the disease.

GENETIC TESTING
- Use for more specific Dx of the type of mutation present in DMD (and in Becker muscular dystrophy) to
provide information for possible Tx in the future.






DIFFERENTIATING DMD FROM OTHER MUSCULAR DYSTROPHIES
Muscular
Dystrophies
Inheritance
pattern
Age of onset Initial
manifestations
progression therapy
DMD
(pseudohypertrophic)
X-linked recessive Early childhood
age
(3-5 y/o)
Lordosis
Waddling gait
Frequent falls
Toe walking
Difficulty in rising
from floor and
climbing stairs
Fat deposits
replace wasted
gastrocnemius
mm.

Rapid
Ultimately
involves ALL
voluntary mm.
Death usually
occurs bet. Ages
15-30 y/o.
PT to prevent
disuse atrophy of
unaffected mm.
Becker muscular
dystrophy
(BMD)
X-linked
recessive,
sporadic
>7 years of age (same as DMD) Much slower
progression than
DMD
(same as DMD)
Limb girdle muscular
dystrophy
(LGMD)
Autosomal
recessive
(usually)
Late childhood or
adolescence
(>8 y/o)
Weakness of prox.
Mm. of (B) pelvic
and shoulder
girdles
Variable but
usually slow
Most become
incapacitated
with in 20 yrs. Of
onset; in some,
disability may
remain slight
Supportive
PT to prevent
disuse atrophy of
unaffected mm.
Facioscapulojumeral
dystrophy
Autosomal
dominant
Early adolescence
(>8 y/o)
Lack of facial
mobility
Difficulty in raising
arms over head
Forward slope of
shoulders
Very slow
Maybe intervals
with no
progression
Considerable
disability in time,
but life span
unaffected
supportive

MALE family membersscreened for the disorder
o FEMALE family membersscreened for their carrier status.

(from ALEXANDER)

MANAGEMENT
- Although definitive tx is lacking, proper mx can prolong the maximum functional ability of the child.
- The program of mx begins once the dx is established, and it is initiated concurrently with parental counselling
in an attempt to reduce the gulit, hostility, fer, depression, hopelessness and numerous other emotions
commonly experienced by parents.
- Tx should mean giving support to the parents and as well as to the child giving both practical assistance and
emotional support when they are needed
PHARMACOLOGICAL Mx:
- There is no pharmacological tx that will cure DMD, but several stusies have confirmed an initial report that
glucocorticosteroids (prednisone and deflazacort) increased strength and improve function from 6 months to
up to 2 years in pt with DMD.
1.) Prednisone (administered for 6 months)
-keeps those affected DMD pt stronger for longer.
- (+) strength and functional benefits as well as pulmonary function.
- the progression of weakness.
- side effects : excessive weight gain, cushingoid appearance, behavioural abnormalities and excessive
hair growth.
2.) Deflazacort
- may result in less weight gain and has the same functional and strength benefits.




3.) oral albuterol (taken for 12 weeks)
- in mm. strength.
4.) creatine monohydrate (for 1-4 weeks)
- a naturally occuribng substance that is sometimes recommended for boys with DMD.
5.) aminoglycosides (including gentamicin)
- found to increase dystrophin expression in the cell membrane and provided protection against muscular
injury.

ORTHOPEDIC (SURGICAL) TREATMENT
1.) Spinal fixation/surgery
- Generally recommended for boys with DMD once the scoliosis begins to progress rapidly and the spinal curve
becomes >30 (usually once boys are W/C).
Indications of spinal surgery:
- Increasing pelvic obliquity
- Difficulty with bracing
- Skin breakdown
- Discomfort and decrease tolerance to sitting
- Difficulty using proper extremities 2 to lack of trunk stability requiring propping on arms.
Goals of spinal surgery
- Providing a stable spine
- Maximally correcting scoliosis
- Correcting pelvis obliquity
- Providing sagittal plane alignment for improved comfort and function.





2.) Myoblast transplant
- Used in replacing the missing protein dystrophin.
3.) Achilles tendon lengthening
4.) To increase ROM for prolongation of amb.:
- Yount fasciotomies
- Tibialis posterior transpositions
- Percutaneous tenotomise

PREVENTIVE TREATMENT
1.) Prevention of respiratory illness
Breathing exercises ( about 5 mins. Daily)
.. attempting to obtain good expansion of the lings
Pool exercises
to increase and maintain ventilator fnx
Nocturnal ventilation
.. to address nocturnal hypoxaemia
Postural drainage
.. for cough (~5 mins x 3-4 times per day)
Ventilator assist.
.. used day and night for DMD pt with advanced respiratory failure.
Nasal ventilation
.. to assist breathing patterns.
2.) Prevention of soft tissue contracture and deformity
Full ROM possible + maintenance of an erect posture for as long as possible during the day will delay
the development of mm length changes and deformity.
Movements involve active contractions of antagonist mm with emphasis on EXTENSION.
Night splints for calf mm. (thermo-plastic/plaster of Paris)
Self stretching (calf)
Manual stretching (ITB and hamstring) by parents.

3.) Prevention of inactivity and immobility (B) mental and physical
Pool games (swimming)
..to encourage mobility, endurance and respiratory control.


Timing of surgery is critical as the risk of surgery become greater as the disease progresses.
1 goal of Mx:
- Maintaining optimum fnx in all mm.
for as long as possible.
2 goal of Mx:
- Prevention of contractures


Sandmill climbing
..to promote endurance
Strengthening (using a pulley system)
..to exercise abdominal, trunk extensor and LE extensor muscles.
Wrestling and punching
..do develop balance in sitting and standing
Activities that promotes dexterity
..tying knots with guidance of a scout manual.
Developing computing skills
..through watching educational TV shows and mind games.
Engagement in W/C sports.
4.) FOR CARDIAC PROBLEMS
Regular echocardiogram aand electrocardiogram monitoring is necessary.
Cardiac meds. For arrhythmias
Heart transplant (for pt with dilated cardiomyopathy).






PT MANAGEMENT
In discussing examination and treatment of the chikd with DMD,it is helpful to categorized the
disease into three general stages:
1.) Early/ ambulatory Stage
2.) Transitional phase during the loss of ambulation
3.) Later (W/C) stae when the child or young adult is W/C bound and dependent for most of his functional
activities.
The ff. should be including during the Hx taking :
1.) Family Hx
2.) Developmental Hx
Review of systems
1.) Pulmonary system
Test and measures
1.) Functional ability
.. transfer activities (supine standing/sitting standing)
..running activities (~30 feet)
..climbing up four steps
2.) MMT
.. a valid approached in assessing the progression of the disease in DMD pt because it is reliable and
sensitive to changes in their strength.
3.) Dynamometry (handheld)
..attempts to better quatify muscle strength in boys with DMD>
4.) ROM
.. done periodically.
..measurement of the popliteal angle is useful in monitoring hamstring flexibility.
5.) Special test
.. THOMAS and OBER test in monitoring hip flexor and ITB tightness.
PT INTERVENTION:
.. PT manage the pt and the problems not the disease.
** 1 problems encountered by DMD pt:
1.) Weakness
2.) Decrease active and passive ROM
3.) Loss of amb.
4.) Decrease fxnl ability
5.) Decrease pulmonary fnx
6.) Emotional trauma- individual and family
7.) Progressive scoliosis
8.) Pain
** major goals of management
1.) Prevent deformity
2.) Prolong fnxl capacity
Part of each day at least 30 mins. Should set aside at home ar at school for vigorous games and activities
(as tolerated by pt) to encouraged strength, mobility and respiratory function.
3.) Improve pulmo. Fnx.



4.) Facilitate the development and assist. Of family support and support of others
5.) Control pain (if necessary)

** home program
.. essential for pt and family as well as it is convenient and cheap.
.. it can be improved by giving simple instructions, requesting a limited number of exercise repetitions each
day and offering extensive feedback and positive reinforcement to people in the support system.
.. periodic re-evaluation, retraining and motivation sessions for parents (recommended).

** Preventing deformity
.. minimizing spinal deformity
**activity level and/ active exercise
.. strengthening exercises
.. weight control
.. Facilitating sleep
** prolonging amb. And W/C use.
** ADL training
.. may request OT for consultation.
**facilitating family support
** pain mx
.. to minimized the discomfort.























Prepared by:
Ferrer, Dionah
Navarro, Casey
NO treatment programme, surgery or bracing will reverse the progression of DMD. But, it has
been shown that regular mm. stretching as well as providing regular periods of walking with long
leg callipers at the appropriate time will delay the loss of amb. And reliance on W/C.
Tx is therefore partly preventive and partly supportive.it should be kept in mind that it is probably
impossible to prevent either respiratory illness or deformity in the later and terminal stages of the
disease. The term preventive is used to indicate the importance of preventing such 2
complications from occurring in the younger child, causing him distress and making him immobile
before he need.