Muscular

Dystrophy
RUDY HANDOYO
REHABILITASI MEDIK
FK UNDIP/RS Dr KARIADI

Introduction
Muscular dystrophies are genetic disorders
characterized by progressive muscle wasting and
weakness that begin with microscopic changes in
the muscle.
As muscles degenerate over time, the person's
muscle strength declines, characterized by rapidly
progressive muscle weakness which starts in the
legs and pelvis and later affects the whole body.
Duchenne muscular dystrophy (DMD) was first
described by the French neurologist Guillaume
Benjamin Amand Duchenne in the 1860s.
Becker muscular dystrophy (BMD) is named after
the German doctor Peter Emil Becker, who first
described this variant of DMD in the 1950s.

Introduction
Although the disease is present from
conception, symptoms usually do not develop
until the child is five or six years old, or even a
year or two later.
By the early teens or even earlier, the boy's
heart and respiratory muscles may also be
affected.
In the late stages of muscular dystrophy, fat and
connective tissue often replace muscle fibers.
The most common muscular dystrophies appear
to be due to a genetic deficiency of the muscle
protein dystrophin.
There's no cure, but medications and therapy
can slow the course of the disease.

CAUSES
The defective gene that causes Duchenne's and
Becker's muscular dystrophies is located on the
X-chromosome.
Women who have the defective gene that causes
these muscular dystrophies are simply carriers
and exhibit no signs or symptoms of the disease.
The disease can "skip" a generation until another
son inherits the defective gene on the Xchromosome.
In some cases of Duchenne's and Becker's
muscular dystrophies, the disease arises from a
new mutation in a gene rather than from an
inherited defective gene.

CAUSES
Myotonic dystrophy is passed along in a pattern
called autosomal dominant inheritance.
If either parent carries the defective gene for
myotonic dystrophy, there's a 50 percent chance
the disorder will be passed along to a child.
Other types of muscular dystrophy can be
passed on from generation to generation and
affect males and females equally.
Still others require a defective gene from both
parents.

CAUSES
Dystrophin is localized to the
sarcolemmal membrane of the muscles
cells and the absence allows increased
permeability of the cell
Because several lytic enzymes within the
muscles cell are activated by calcium, it is
now hypothesized that necrosis may be
due to an uncontrolled rise of calcium
concentration in the cell thereby
activating proteolytic enzymes leading to
cell destruction

X-Linked Recessive Genetic

Defects
Females may get the defective gene either from her
mother's defective X, or, if her father has the disorder, from
her father. In either case, the girl will be a carrier and will
probably pass the defect to her offspring. She will not
manifest the disorder the way a boy would, because she
has 2 X chromosomes, and the dominant X will compensate
for the defect on the recessive X. Only if a female has 2
parents with the defect on their X chromosomes will she
get a milder form of the disorder.
If a woman has the defect on one of her X chromosomes,
and the father's X chromosome is normal, there is a 25%
chance for each pregnancy to produce: an unaffected girl;
a girl who carries the defect; an unaffected boy; or a boy
with the disorder.
Her female children have a fifty percent chance of carrying
the gene, each male child has a fifty percent chance of
having the disease and showing signs of the disorder.

X-Linked Recessive Genetic

Defects

X-Linked Recessive Genetic

Defects - How Boys are
Affected

X-Linked Recessive Genetic

Defects - How Girls are
Affected

X-Linked Recessive Genetic

Defects
A man with DMD or BMD can't pass the
flawed gene to his sons because he gives
a son a Y chromosome, not an X.
But he'll certainly pass it to his
daughters, because each daughter
inherits her father's only X chromosome.
They'll then be carriers, and each of
their sons will have a 50 percent chance
of developing the disease, and so on.

How can a family with no history of

DMD or BMD suddenly produce a son
with the disease?
There are two possible explanations:
The genetic mutation leading to DMD or
BMD may have existed in the females of a
family for some generations without anyone
knowing it. Perhaps no male children were
born with the disease, or, even if a boy in an
earlier generation was affected, relatives
may not have known what disease he had.
The second possibility is that the child with
DMD or BMD has a brand new genetic
mutation that arose during his development
as a fetus.

FEMALES AND DMD

Why don't girls get DMD or BMD?
When a girl inherits the DMD gene from her mother,
she usually also gets a healthy dystrophin gene from
her father, giving her enough of the protein to protect
her from the disease.
Males who inherit the mutation get the disease because
they have no second dystrophin gene to make up for the
faulty one.
However, although girls don't usually get the full effects
of DMD or BMD, some females with the gene flaw are
somewhat affected.
A minority of females with the mutation are manifesting
carriers, who have a mild form of the disorder.

FEMALES AND DMD

For these women, the dystrophin deficiency may
result in weaker muscles in the back, legs and
arms that fatigue easily.
Manifesting carriers may have heart problems,
which can be manifested as shortness of breath
or inability to do moderate exercise. The heart
problems, if untreated, can be quite serious, even
life-threatening.
It's wise for any potential female carrier of DMD
or BMD to get a full range of diagnostic tests to
find out her status. Then, if she is a carrier,
regular strength evaluations and close cardiac
monitoring can help her manage any symptoms
that may arise.

Type of muscular
dystrophy

The types of muscular dystrophy that are

due to a genetic deficiency of the protein
dystrophin are called dystrophinopathies.
Duchenne's muscular dystrophy is
the most severe form of
dystrophinopathy.
It occurs mostly in young boys and is the
most common form of MD that affects
children.

Type of muscular
dystrophy

Becker's muscular dystrophy

This type of muscular dystrophy is a milder
form of dystrophinopathy.
It generally affects older boys and young
men, and progresses more slowly, usually
over several decades.
Signs and symptoms of Becker's MD are
similar to those of Duchenne's.
The onset of the signs and symptoms is
generally later, from age 2 to 16.
X-linked

Type of muscular
dystrophy

Myotonic dystrophy (Steinert's disease)

Produces stiffness of muscles and an inability to relax muscles at will

(myotonia) and is found only in this type of muscular dystrophy. Muscles
may feel stiff after using them. Progression of this form of MD is slow .
Others signs and symptoms (adult-onset myotonic dystrophy):

Weakening of voluntary muscles, usually beginning with the limb muscles

farthest from the torso the muscles of the feet, hands, lower legs and
forearms.
Weakening of head, neck and face muscles, which may result in the face having
a hollow, drooped appearance.
Weakening of muscles involved in breathing and swallowing. Weaker breathing
muscles may result in less oxygen intake and fatigue. Weaker swallowing
muscles increase the risk of choking.
Fainting or dizziness, which may indicate that the disease is interfering with the
conduction of electrical signals that keep the heart rate normal.
Weakening of muscles of hollow internal organs such as those in the digestive
tract (problems with swallowing as well as constipation and diarrhea) and the
uterus (problems during childbirth.)
Difficulty sleeping well at night and daytime sleepiness, and inability to
concentrate because of the effect of the disease on the brain.
Clouding of the lenses of the eyes (cataracts).
Mild diabetes.

Type of muscular
dystrophy

Rarely, infants have this form of muscular

dystrophy, in which case it's called
congenital myotonic dystrophy.
The infant form is more severe, although
infants with myotonic dystrophy don't
experience myotonia. Signs in infants
include:

Severe muscle weakness

Difficulty suckling and swallowing
Difficulty breathing

Type of muscular
dystrophy

Limb-girdle muscular
dystrophy:

Muscles usually affected first:

Hips Shoulders
This form then progresses to the arms
and legs, though progression is slow.

Usually begins in the teen or early

adult years.
Autosomal recessive

Type of muscular
dystrophy
Facioscapulohumeral muscular dystrophy

Also known as Landouzy-Dejerine disease, this form

involves progressive muscle weakness, usually in this
order:

Face
Shoulders
Abdomen
Feet
Upper arms
Pelvic area
Lower arms

When someone with facioscapulohumeral MD raises his or

her arms, the shoulder blades may stick out like wings.
Progression of this form is slow, with some spurts of
rapidly increasing weakness.
Onset usually occurs during the teen to early adult years.
Autosomal dominant

Type of muscular
dystrophy

Congenital muscular dystrophy

Signs of congenital MD may include:
General muscle weakness
Joint deformities
This form is apparent at birth and
progresses slowly.
A more severe form of congenital MD
called Fukuyama type congenital muscular
dystrophy, may involve severe mental and
speech problems as well as seizures
Autosomal recessive

Type of muscular
dystrophy

Oculopharyngeal muscular dystrophy

The first sign of this type of muscular
dystrophy is usually drooping of the eyelids,
followed by weakness of the muscles of the
eye, face and throat, resulting in difficulty
swallowing.
Progression is slow.
Signs and symptoms first appear in
adulthood, usually in a person's 40s, 50s or
60s.
Autosomal dominant

Type of muscular
dystrophy

Distal muscular dystrophy

This group involves the muscles farthest
away from the center of the body those of
the hands, forearms, feet and lower legs.
The severity is generally less than for other
forms of MD, and this form tends to progress
slowly.
Distal MD generally begins in adulthood
between the ages of 40 and 60.
Autosomal dominant

Type of muscular
dystrophy

Emery-Dreifuss muscular dystrophy

This rare form of muscular dystrophy
usually begins in the muscles of the:

Shoulders
Upper arms
Shins

Emery-Dreifuss MD usually begins in the

childhood to early teen years and
progresses slowly.
X-linked

SYMPTOMS & SIGNS

Muscle weakness

Rapidly progressive
Frequent falls
Difficulty with motor skills (running, hopping, jumping)
Difficulty standing up
Difficulty climbing stairs
Difficulty descending stairs

Progressive difficulty walking

Ability to walk may be lost by age 12

Fatigue
Intellectual retardation/handicap (possible)
Skeletal deformities
Chest and back (scoliosis)

SYMPTOMS & SIGNS

Waddling gait
Muscle deformities
Contractures of heels, legs. Later development
indicates a tendency to stand and walk on the forward
part of the foot with the heels off the ground.
Pseudo hypertrophy of calf muscles

Hyperlordosis
To try to keep his balance.

Apparent lack of coordination

Progressive crippling, resulting in fixation of the
muscles around the joints (contractures) and loss
of mobility

SYMPTOMS & SIGNS

Because of weakened leg muscles,
boys with DMD have a distinctive
way of rising from the floor, called
the Gowers' maneuver. They first get
on hands and knees, then elevate the
posterior, then "walk" their hands up
the legs to raise their upper body.

SYMPTOMS & SIGNS

SYMPTOMS & SIGNS

DIAGNOSIS & TESTS

Usually begins by taking a patient and family
history and performing a physical examination.
Unless a boy with DMD is known to be at risk
because of his family history, he is unlikely to be
diagnosed before the age of 2 or 3 years or
older.
It's important to get a formal diagnosis because
other diseases have some of the same symptoms
as DMD and BMD. Becker MD has often been
overlooked or misdiagnosed as limb-girdle
muscular dystrophy or spinal muscular atrophy.

DIAGNOSIS & TESTS

Muscle wasting (atrophy) begins in the legs and pelvis,
then progresses to the muscles of the shoulders and
neck, followed by loss of arm muscles and respiratory
muscles.
Calf muscle enlargement (pseudohypertrophy) is quite
obvious.
Cardiomyopathy is commonly present, but signs of
congestive heart failure or arrhythmias (irregular
heartbeats) are rare.
Respiratory disorders are common during the later
stages, including pneumonia and aspiration of food or
fluid into the lungs
A neurologic exam demonstrates weakness and lack of
coordination or balance.

DIAGNOSIS & TESTS

Blood tests.

Damaged muscles release enzymes such as creatine

kinase (CK) into the blood, an enzyme that leaks out of
damaged muscle.
When elevated CK levels are found in a blood sample,
it usually means muscle is being destroyed by some
abnormal process, such as a muscular dystrophy or an
inflammation.
Therefore, a high CK level suggests that the muscles
themselves are the likely cause of the weakness, but it
doesn't tell exactly what the muscle disorder might be.

Electromyography.

The distribution of the disease can be determined by

testing different muscles. EMG shows that weakness
is caused by destruction of muscle tissue rather than
nerve damage.

DIAGNOSIS & TESTS

Muscle biopsy.
The analysis distinguishes muscular
dystrophies from other muscle diseases.
Other tests on the biopsy sample can
provide information about which muscle
proteins are present in the muscle cells,
and whether they're present in the normal
amounts and in the right locations.
This can determine whether the disease is
DMD (with no dystrophin) or BMD (with
some inadequate dystrophin).

DIAGNOSIS & TESTS

Genetic testing.

In the past, certain blood tests that are used to

analyze DNA allowed some forms of muscular
dystrophy to be diagnosed by identifying a particular
mutation of the dystrophin gene.
A new DNA test, called single condition
amplification/ internal primer (SCAIP) sequencing,
allows us to look at the entire dystrophin gene to find
multiple variations, providing more than just one
type of diagnosis.
The availability of DNA diagnostic tests, using either
blood cells or muscle cells to get precise genetic
information, is expanding rapidly.
Sisters of people with DMD or BMD can also be
tested to find out whether they're carriers of the
disease, meaning they could have children with the
disorder.

DIAGNOSIS & TESTS

Often, the diagnosis of Becker muscular dystrophy
isn't made until adolescence or even adulthood,
possibly when a young man finds he can't keep up in
physical education classes or military training. To
compensate for his weakening muscles, the young
man begins walking with a waddling gait, walking on
his toes or sticking out his abdomen.
As with Duchenne, the pattern of muscle loss in BMD
usually begins with the hips and pelvic area, the
thighs and the shoulders. But in BMD, the rate of
muscle degeneration varies a great deal from one
person to another. Some men require wheelchairs by
their 30s or later, while some manage for many years
with minor aids, such as canes.

Vignos Functional Rating

Scale for Duchenne
1. Walks and climbs stairs without assistance
Muscular Dystrophy
2. Walks and climbs stairs with aid of railing
3.

Walks and climbs stairs slowly with aid of railing (over

25 seconds for eight standard steps)
4. Walk, but cannot climb stairs
5. Walks assisted, but cannot climb stairs or get out of
chair
6. Walk only with assistance or with brace
7. In wheelchair, sits erect and can roll chair and perform
bed and wheelchair ADL
8. In wheelchair, sits erect and can roll chair and is unable
to perform bed and wheelchair ADL without assistance
9. In wheelchair, sits erect only with support and is able to
do only minimal AFL
10. In bed: can do no ADL without assistance

TREATMENT
There's currently no cure for any form
of muscular dystrophy. Treatment is
aimed at control of symptoms to
maximize the quality of life.
Current treatment is designed to
help prevent or reduce deformities
in the joints and the spine and to
allow people with MD to remain
mobile as long as possible.

TREATMENT
Activity is encouraged.
Inactivity (such as bed rest) can
worsen the muscle disease.
Regular (daily) physical therapy
sessions may be helpful to maintain
muscle strength and function.

TREATMENT
Assistive devices:
Braces or splints on the legs, particularly at night.
Braces extending from shoes to thighs to facilitate
standing and walking. The braces, fitted with
hinges at the knees, can be worn even while the
child is sitting. They are comfortable and
relatively light in weight.
A walker may be used in combination with the
braces to allow for independent mobility.
Wheelchair

Medication
Surgery

Physical Therapy
As muscular dystrophy progresses and muscles weaken,
contractures can develop in joints. Tendons can
shorten, restricting the flexibility and mobility of joints.
Contractures are uncomfortable and may affect the
joints of the hands, feet, elbows, knees and hips.
The primary goals of physical therapy are to allow
greater motion in the joints and to prevent contractures
and scoliosis.
Exercise can help build skeletal muscle, keep the
cardiovascular system healthy, and contribute to feeling
better. But in muscular dystrophy, too much

exercise could damage muscle. A person

with DMD or BMD can exercise moderately
but shouldn't go to the point of exhaustion.

Physical Therapy
Some experts recommend swimming and
water exercises (aquatic therapy) as a good
way to keep muscles as toned as possible
without causing undue stress on them. The
buoyancy of the water helps protect
against certain kinds of muscle strain and
injury. Before undertaking any exercise
program, make sure a cardiac evaluation.
Using hot baths also can help maintain
range of motion in joints.

Occupational Therapy
Occupational therapy focuses more on
specific activities and functions, while
physical therapy emphasizes mobility
and, where possible, strengthening of
large muscle groups.
OT can help with tasks related to work,
recreation or daily living, such as
driving, dressing or using a computer.

ENVIRONMENTAL
ADAPTATIONS
Various types of environmental
adaptations may be necessary to
help the child remain independent in
daily activities, including raised
toilet seats, special desk tops, ramps
instead of steps, handrails, and
others.

Braces, Standing Frames

and Wheelchairs
Braces support the ankle and
foot or extend over the knee.
Ankle-foot orthoses are
sometimes prescribed for
night wear to keep the foot
from pointing downward
while the child is sleeping.
Standing for a few hours
each day, even with minimal
weight bearing, promotes
better circulation, healthier
bones and a straight spine. A
standing walker or standing
frame can assist people with
DMD and BMD to stand.
Some wheelchairs will tilt
into a standing position

Braces, Standing Frames

and Wheelchairs
Sooner or later, all boys with DMD need
wheelchairs.
Many at first use wheelchairs at school or
the mall, continuing to walk some at home.
In Duchenne, it's typical for a child to be
using a wheelchair full-time by about age 12.
Although the child and parents may dread
the wheelchair as a symbol of disability, most
users find they are actually more mobile,
energetic and independent than when trying
to walk on very weak legs.

MEDICATIONS
Steroids may have a significant benefit in DMD. The
best known of these drugs is prednisone; it's been
shown to slow the loss of muscle function or even to
increase strength in DMD. With these drugs, someone
with DMD may be able to walk and have stronger arms
and legs for several months or even a couple of years
longer than would have been possible without them.
But prednisone also has many potentially damaging
side effects, which can be severe over a prolonged
period. These include significant weight gain, loss of
bone and (paradoxically) muscle tissue, thinning of the
skin, raised blood pressure and blood sugar, and
serious psychological distress, including difficulty
thinking, sleeping and controlling behavior, and even
severe depression. Each of these side effects can
actually worsen the impact of muscular dystrophy.

MEDICATIONS
For myotonic dystrophy.
The medications phenytoin, quinine
and procainamide may be used to
treat the delayed muscle relaxation
that occurs in myotonic dystrophy.

SURGERY
To release the contractures that may
develop and that can position joints
in painful ways, it can be performed
a tendon release surgery.
This may be done to relieve tendons
of the hip, knee and Achilles tendon.

COMPLICATIONS

Deformities: scoliosis, kyphosis

Contractures
Permanent, progressive disability
Decreased mobility
Decreased ability for self-care

Mental impairment (varies, usually minimal)

Pneumonia or other respiratory infections
Respiratory failure
Cardiomyopathy
Congestive heart failure (rare)
Heart arrhythmias (rare)

Pain and Sensation

Since muscular dystrophy doesn't affect nerves
directly, those who have the disorders retain
normal sensations of touch and other senses.
They also usually have control over the smooth,
or involuntary, muscles of the bladder and
bowel, and have normal sexual functions
The muscle deterioration in Duchenne and
Becker usually is not painful in itself.
Some people report muscle cramps at times;
these can usually be treated with over-thecounter pain relievers.

The Heart
By the teen years, the damage done by DMD to the
heart and the muscles involved in operating the
lungs can become life-threatening.
People with DMD and BMD often develop
cardiomyopathy because of a deficiency of
dystrophin. Myocardium of the heart deteriorates,
just as the skeletal muscles do, putting the person
at risk of fatal heart failure.
Major symptoms of cardiomyopathy are shortness
of breath, fluid in the lungs or swelling in the feet
and lower legs caused by fluid retention. The
effects can be diminished with a low-sodium diet,
mild exercise, mechanical ventilation or
medications.
Some people with BMD have mild skeletal muscle
involvement but severe cardiac problems. In BMD,
the heart should be checked regularly and treated
if necessary.

Respiratory
Function

After a boy with DMD is about 10 years old, the

diaphragm and other muscles that operate the lungs
may weaken, making them less effective in moving air
in and out. Problems that may indicate poor respiratory
function include headaches, mental dullness, difficulty
concentrating or staying awake, and nightmares.
Anyone with a weakened respiratory system is also
subject to more infections and difficulty in coughing. A
simple cold can quickly progress to pneumonia in this
person. As breathing ability declines, the family can
learn procedures to assist with coughing and keep the
bronchial system free from secretions.
Sometimes a respirator is needed. When it's needed
more often, a tracheostomy may be performed and a
tube inserted directly into the trachea (airway) to
deliver air to the lungs.

Intellectual Effects
About a third of boys with DMD have
some degree of learning disability,
although few are seriously retarded.
Dystrophin abnormalities in the brain may
cause cognitive and behavioral deficits.
The learning problems seen in some
people with DMD and BMD occur in three
general areas: attention focusing, verbal
learning and memory, and emotional
interaction.

DIETS

Many people, when they hear the words "lack of a

protein," logically ask, "Should I eat more protein? "
Unfortunately, eating more protein has no effect on
any of the proteins missing in muscular dystrophy.
No special dietary restrictions or additions are known
to help in DMD or BMD. Most doctors recommend a
diet similar to that for any growing boy, but with a
few modifications. A combination of immobility and
weak abdominal muscles can lead to severe
constipation, so the diet should be high in fluid and
fiber, with fresh fruits and vegetables dominant.
For boys who use power wheelchairs, take prednisone
or who aren't very active, caloric intake should
probably be somewhat restricted to keep weight
down. Obesity puts greater stress on already
weakened skeletal muscles and the heart. Low-calorie
diet doesn't have any harmful effect on the muscles.
Those on prednisone and those with heart problems
also may need a sodium-restricted diet.

HOW DO FAMILIES AND CHILDREN

ADJUST TO DMD OR BMD?
For the Child
Answer children's questions about the disease when
they arise, with honesty and in language they
understand.
Always view the child as an individual, with the
disease only one aspect of his life.
Emphasize what the child can do and let him find
ways to do things he wants. Children often find
creative ways to participate in sports and other
hobbies.
Treat him as any other child, providing discipline,
responsibility, hope and love. Don't overprotect him,
and do help him become independent.
Undertake normal family activities, including
vacations and recreation.

HOW DO FAMILIES AND CHILDREN

ADJUST TO DMD OR BMD?
For the Family
Respect each other's
emotions and stress
levels; be kind and
patient.
Coping with the
illness involves a
major commitment of
physical, emotional
and financial effort.
The disease presents
challenges in the
classroom, in the
home and in all
aspects of life.

PREVENTION
Genetic counseling is advised if
there is a family history of the
disorder. Duchenne muscular
dystrophy can be detected with
about 95% accuracy by genetic
studies performed during pregnancy.

PROGNOSIS
Duchenne muscular dystrophy
results in rapidly progressive
disability. Death usually occurs by
age 25, typically from respiratory
(lung) disorders.