Muscular Dystrophy
What are muscular dystrophies (MD)?
The muscular dystrophies (MD) are a diverse group of genetically determined
(inherited) disorders primarily affecting the muscles of the body. Most tend to
be progressive, but the rate of disease progression differs based on the
specific type. They typically result from an ongoing breakdown of the muscle due
to an absence of crucial protein (building block) required to maintain the
strength and stability of the muscle. As a result, the muscle is replaced by
fibrous (scar) tissue and fatty tissue. Often, the muscles-- especially the calf
muscles--may appear abnormally large due this fatty replacement of the muscle ("pseudohypertrophy"), but the muscle is weak.
The muscular dystrophies may also involve the heart muscles,
breathing or respiratory muscles, and--less commonly--other body systems such as
brain, eye, gastrointestinal tract, and other organ systems. Scoliosis
(curvature of the spine) often results as a consequence of the spinal muscle
weakness and of a child’s being confined to a wheelchair. Obesity is also often
a problem since children are less active due to their weakness.
Who is affected by MD?
MD can affect people of all ages. Although some forms first become apparent
in infancy or childhood, others may not appear until middle age or later.
Duchenne muscular dystrophy is the most common childhood form, usually affecting
only males, occurring in about 1 in every 3,500 live male births. Myotonic
dystrophy is the most common form MD affecting adults.
What are the types of MD?
The muscular dystrophies are classified based on their clinical features,
pattern of inheritance (see below), and the gene defect (when known). They
include:
- Duchenne/Becker (X linked recessive)
- Emery-Dreifuss (X linked recessive or Autosomal dominant)
- Limb girdle (Autosomal dominant or recessive)
- Myotonic dystrophy (Autosomal dominant)
- Facioscapulohumeral (Autosomal dominant)
- Oculopharyngeal (Autosomal dominant)
- Congenital muscular dystrophy (Autosomal recessive)
- Distal (Autosomal dominant)
What are the clinical features of MD?
The clinical features of muscular dystrophy vary based on the specific form
of MD.
Pain is usually not a feature of MD (except in some cases of
myotonic dystrophy). Symptoms usually relate to motor difficulties and may
include:
- excessive falling or clumsiness
- delayed milestones
- difficulty getting up from the floor
- difficulty climbing stairs
- weakness of legs and/or arms
- toe-walking
Physical signs include:
- large or prominent calf muscles ("pseudohypertrophy")
- toe-walking
- contractures or tightness of tendons-- especially the Achilles tendon
- weakness--usually of the proximal muscles of the legs/pelvis and/or
arms/shoulder girdle
- reduced/diminished reflexes
- Gower sign--a classical clinical finding in which the child with
proximal weakness tries to get up from the floor, first rolling from the
back to stomach, then spreading the legs apart ("tripoding") while pushing
on the knees in order to get upright.
How is MD diagnosed?
After carefully evaluating a patient’s medical history, the doctor will
perform a thorough physical exam to rule out other causes. If MD is suspected,
there is a variety of laboratory tests that can be used to confirm a diagnosis.
These tests may include:
- Blood tests:
- Creatine kinase: When blood tests are performed to test for MD, the
doctors are looking for an enzyme called creatine kinase (CK). This
enzyme is raised in the blood due to the ongoing muscle damage.
Unfortunately, this finding is not specific in determining the type of
MD, but is helpful to confirm the muscle involvement. A normal CK does
not always exclude MD, as some forms of MD may have normal CK levels. In
Duchenne muscular dystrophy, the CK is always elevated very high.
- Genetic tests: These are very specific blood tests done to try and
determine the type of MD. The missing or altered gene is not,
unfortunately, known for all types of MD. To date, over 30 different
genes have been identified as causing MD. A positive gene test can spare
the need for a muscle biopsy (see below).
- Electromyogram (EMG): An EMG is a test that measures the muscle’s
response to stimulation of its nerve supply (nerve conduction study) and the
electrical activity in the muscle (needle electrode examination). This test
will confirm that the muscle weakness is due to a muscle disease, not a
nerve disease. It is not very specific for determining the type of muscle
disease, so is usually only used if there is uncertainty as to whether there
is, in fact, a muscle disease before considering further testing.
- Muscle biopsy: During a muscle biopsy, a small piece of muscle tissue is
removed and then examined under a microscope. If MD is present, destructive
changes in the structure of the muscle cells are seen, confirming it is a
muscular dystrophy rather than some other type of muscle disease. The
changes are not, however, specific enough to determine one type of MD from
another. Special testing on the muscle can be done to detect the presence or
absence of particular proteins.
How is MD inherited?
There are three primary types of inheritance in which the faulty gene that
causes MD can be passed along to offspring:
- X-linked recessive: Diseases such as Duchenne/Becker muscular dystrophy
are X-linked recessive, meaning they are carried on one of the two paired
genes on the X chromosome of the mother. The mother, being female, has two X
chromosomes, one of which will be passed on to an offspring. If the affected
gene on the X chromosome is passed on to a male child, they will develop the
disease. A male needs only one copy of an X linked recessive gene in order
to manifest the trait or disease, since they do not have a second X
chromosome to offset the affected gene, but rather a Y sex chromosome passed
on from their father (XY). If the healthy X chromosome is passed on to a
male child, they will be unaffected. Since one of the two X chromosomes is
passed on to a daughter (the other X coming from the father), any daughter
of a female carrier of the affected X gene has a 50% chance of inheriting
that gene and being a carrier as well. Since they get a healthy X chromosome
from their father, they are usually unaffected clinically (with some rare
exceptions). In Duchenne/Becker muscular dystrophy, one third of all cases
are the result of a new mutation in the child, rather than being passed on
from the mother. One form of Emery-Dreifuss muscular dystrophy is also
X-linked recessive.
- Autosomal recessive: For this type of inheritance, both parents must
carry an affected gene on one of their paired chromosomes and pass on the
faulty gene unknowingly to their offspring. The child has to inherit both
copies of the affected ("bad") gene in order to manifest the trait or
disease. Neither parent shows any symptoms as they have a healthy,
unaffected gene on the other chromosome. Each of their offspring, regardless
of gender, will have a 25 percent chance of developing the disease and a 50%
chance of inheriting one of the affected genes (i.e. being a carrier
themselves). Some forms of Limb-girdle muscular dystrophy (type 2 forms) and
congenital muscular dystrophies are autosomal recessive.
- Autosomal dominant: In the case of autosomal dominant inheritance, a
person that carries one affected gene will manifest the trait or disease.
Since it is dominant, the gene on the opposite paired chromosome is unable
to mitigate the effect of the affected ("bad") gene. This faulty gene can
come from either parent, and it can affect either sex equally. Each child of
an affected parent will have a 50 percent chance of inheriting the affected
gene and therefore developing MD. For this type of inheritance, the severity
of MD can vary greatly. It can be so mild that it is often not recognized in
the affected parent. In other instances, the affected parent is aware they
have symptoms. Examples of dominantly inherited MD include some forms of
Emery-Dreifuss, Limb-girdle (type 1 forms), Myotonic dystrophy,
facioscapulohumeral dystrophy (FSHD), and oculopharyngeal muscular dystrophy
(OPMD).
How is MD treated?
There is currently no cure for any of the muscular dystrophies, although a
lot of active research is being carried out in the field. Despite this, there
are treatments aimed at preventing complications due to the effects of weakness,
decreased mobility, contractures, scoliosis, heart defects, and respiratory
weakness. Treatments also are meant to maximize functional ability.
- Medication: The only drug that has proven to be of some benefit
in helping to prolong ambulation in children with Duchenne muscular
dystrophy is oral steroids. This may prolong ambulation by up to 3 years in
some cases. The timing of starting steroids is still uncertain. Steroids
also carry potential risks and adverse effects such as weight gain (possibly
making weakness worse), growth impairment, and osteopenia (decrease in bone
mass), among others. Heart failure, if present, is treated with a variety of
cardiac medications.
- Physical therapy: Physical therapy, especially regular
stretching, is important in helping to maintain the range of motion for
affected muscles and to prevent or delay contractures. Strengthening other
muscles to compensate for weakness in affected muscles may be of benefit
also, especially in earlier stages of milder MD. Regular exercise is
important in maintaining good overall health, but strenuous exercise may
damage muscles further and should be avoided. For patients whose leg muscles
are affected, braces may help lengthen the period of time that they can walk
independently.
- Surgery: If a patient’s muscle contractures (shortening) have
become more pronounced, surgery may be used to relieve the tension by
cutting the tendon of the affected muscle, then maintaining a normal
position with the help of bracing. Metal rods for rigid fixation of the
spine is sometimes necessary to prevent the progression of scoliosis
(curvature of the spine) and help to protect the lung volumes and assist
with positioning and sitting.
- Occupational therapy: Occupational therapy involves employing
methods and tools to compensate for a patient’s loss of strength and
mobility. This may include modifications at home, dressing aids, wheelchair
accessories, and communication aids.
- Nutrition: Nutrition has not been shown to treat any conditions
of MD, but it is essential to maintaining good health. It is important to
avoid obesity.
- Cardiac care: Arrhythmias and cardiomyopathy (enlarged hearts)
may be associated with the muscular dystrophies. Arrhythmias may need to be
treated with special drugs or occasionally artificial pacemakers.
Cardiomyopathies result in heart failure and are treated medially for the
most part. In some selected cases of MD, heart transplantation may be an
option. Regular cardiac screening and follow-up is important for most forms
of MD.
- Respiratory care: When the muscles of the diaphragm and other
respiratory muscles become too weak to function on their own, a patient may
require a ventilator to continue breathing deeply enough, especially at
night during sleep. Air may also be administered through a tube or
mouthpiece. Therefore, it is very important to maintain healthy lungs to
reduce the risk of respiratory complications. Prolonging the ability to walk
and stand is important in this regard, as is avoiding or treating scoliosis
(curvature of the spine).
Resources
Education about muscular dystrophy is the most important tool with which to
manage and prevent complications. The following organizations can provide more
information about muscular dystrophy:
The Muscular Dystrophy Association
National Headquarters
3300 E. Sunrise Drive
Tucson, AZ 85718
1-800-572-1717
www.mda.org
Muscular Dystrophy Family Foundation
3951 N. Meridian Street, Suite 100
Indianapolis, Indiana 46208
Toll Free: (800) 544-1213
www.mdff.org
Parent Project Muscular Dystrophy
1012 North University Boulevard
Middletown OH 45042
Phone: 800-714-5437; 513-424-0696
Fax: 513-425-9907
Email: pat@parentprojectmd.org
www.parentprojectmd.org
European Neuromuscular Centre (ENMC)
Lt. Gen. van Heutszlaan 6
3743 JN Baarn
Netherlands
Phone: 035 54 80 481
Fax: 035 54 80 499
Email: info@enmc.org
www.enmc.org
©
Copyright 1995-2008 The Cleveland Clinic Foundation. All rights reserved
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