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Clinical Picture
Miyoshi myopathy has only been identified and researched for
a few years in the United States. It was first recognized in
Japan in the early 1980’s. The disease typically begins
focally in the distal leg muscles (particularly the calves).
An early sign is difficulty standing on the toes or running.
Over many years, the disease slowly spreads to involve proximal
(close to the trunk of the body) as well as distal (far from
the trunk of the body) muscles. The arms may become involved.
Many patients with Miyoshi myopathy require the use of wheelchairs
after several years. Fortunately, though, despite significant
weakness, these individuals live well into mature adulthood.
Unlike some other neuromuscular disease, patients with Miyoshi
myopathy usually do not have heart or lung problems. However,
it is best to have an examination by a cardiologist and pulmonologist
with experience in treating muscular dystrophy patients to rule
out this remote possibility.
Pain is not a major part of Miyoshi myopathy, but the limited
mobility may lead to muscle soreness and joint pain later in
life. This can be treated with exercises, warm baths, and medications
if necessary.
The brain, intellect and the senses are not affected in individuals
with this myopathy. People with Miyoshi myopathy maintain control
over their bowel and bladder functions and have normal sexual
function.
It is not yet possible to predict the course that Miyoshi myopathy
will take in an individual. But we do know that it is not a
fatal disease. Awareness of the problems associated with the
disorder and the treatment that is available for them can lead
to a longer and higher quality life.
What causes Miyoshi Myopathy
The cause of this disorder is a genetic alteration on a part
of chromosome 2, called the dysferlin gene. This gene codes
for a special protein that helps our muscle cells to work properly.
When there is a genetic change in this gene, the protein may
be abnormal, leading to the symptoms that we see in Miyoshi
myopathy.
Chromosome 2 is one of the autosomes that are the non-sex chromosomes
(chromosomes 1 through 22) that both males and females have
in common. This means that, unlike Duchenne and Becker muscular
dystrophy, both males and females are equally likely to inherit
a genetic alteration that leads to Miyoshi myopathy. Miyoshi
myopathy is an autosomal recessive genetic disorder. This means
that a person needs to inherit an altered gene from both his
mother and his father in order to get the disorder. (Please
visit our Genetics Review
section for a review of important genetic concepts). Therefore,
if a mother and a father carry a genetic alteration in the dysferlin
gene, there is a 25% risk with each pregnancy that the baby
will inherit both copies of the altered gene and thus be affected
with Miyoshi myopathy.
Ways a person gets Miyoshi myopathy:
There are two main ways an individual can get this disorder.
- Inheritance of the genetic alteration from the parents.
In this instance, a mother and a father pass on an altered
dysferlin gene to their son or daughter. The parents are
healthy, but the child who inherits two altered copies of
the dysferlin gene is affected. A son or daughter who inherit
only one altered gene carry the defect but do not show the
disease. An affected Miyoshi patient will pass one of the
two altered dysferlin genes on to every child. However,
that child will not develop Miyoshi myopathy unless the
child also inherits a genetic mutation in the dysferlin
gene from a second parent. This is an unlikely event.
- Development of a new mutation that is not inherited from
a parent. In addition to inheriting an altered dysferlin
gene from a parent, an individual can develop a new mutation
in the second copy of the gene. This typically occurs in
the sperm or egg that formed the embryo from which the individual
developed. This new gene defect is called a sporadic mutation.
If this occurs, then the only family members at risk for
Miyoshi myopathy other than the affected person are that
person’s children. That person’s children would
not be affected with Miyoshi myopathy unless they also inherit
a genetic mutation in the dysferlin gene from a second parent.
As noted above, this is a very unlikely event.
When a person is the first in the family to have Miyoshi
myopathy, this usually reflects the fact that this is the
only family member to inherit two copies of the altered dysferlin
gene (one from each parent). Unaffected siblings may be carriers
of only one defective gene, in which case they will not have
symptoms. It is not unusual for carriers of a rare autosomal
recessive disease not to know they are carriers until some
one in the family develops the rare genetic disease.
Diagnosing Miyoshi Myopathy
The first step in diagnosing muscular myopathy is noticing the
signs of muscular weakness. Next, a visit with a physician will
include a detailed physical examination and detailed questions,
including asking about the patient and the family medical histories.
The doctor or nurse may ask many questions about the patient’s
siblings, parents, aunts and uncles, grandparents and cousins
and construct a family tree, which is called a pedigree. A physical
examination will focus on muscle weakness and the nervous system.
Additional studies such as electrical tests of nerve and muscle
(electromyogram or EMG) may be performed. Together, these studies
determine whether the patient’s weakness is a result of
problems with muscles, nerves, spinal cord or brain. The first
step is a careful patient and family history.
Sometimes doctors will order a special blood test that measures
an enzyme in one’s blood called creatine kinase, or CK.
When muscle is damaged, as in the case of muscular dystrophies,
this enzyme leaks out of the muscle cells and gets into the
blood. A high CK blood level, therefore, suggests that the muscles
are likely the cause of the weakness rather than the nerves.
Further studies will be needed , however, to determine the exact
type of muscle disorder. Carrier parents may not have elevated
serum CKs.
Since there are so many types of muscle diseases, the physician
may order a muscle biopsy to determine which is the specific
cause of a particular patient’s weakness. This biopsy
is a minor surgical procedure that involves removal of a small
piece of muscle (usually through a small incision), typically
in the area of the thigh (quadricep) or upper arm (deltoid).
By examining this sample under the microscope, doctors gain
much information about what is happening in the muscle cells.
This may help distinguish one muscle disorder from another.
Often, the muscle is stained with special dyes to look for
the absence or presence of proteins, such as dystrophin. Finding
that a protein is abnormal (either absent or abnormal in size
and quantity) helps define the genes and proteins that are
likely candidates causing the muscle problems. In the case
of Duchenne muscular dystrophy, we often won’t see any
of the dystrophin protein. However, in Becker muscular dystrophy,
we will see some protein, but a decreased amount from what
is present in individuals without these muscle disorders.
Genetic Testing
Genetic testing is not yet available for Miyoshi myopathy
on a routine clinical basis. However, it is usually available
on a research basis. For more information on this testing,
contact the Day
Laboratory for Neuromuscular Research.
Before you would consider genetic testing either for research
purposes or for diagnostic testing in the future, it is important
to realize several things. The decision to be genetically
tested is a very important and personal decision. It may effect
your relationships, family life and family planning, career
and insurance decisions, and psychological and emotional well-being.
It is a decision to be weighed carefully. It can have a very
positive outcome (for example, when a defect is excluded)
but adverse, upsetting outcomes are also encountered (e.g.
after mutation is confirmed). Genetic counselors are available
to review the implications of genetic testing. Genetic counseling
provides useful information about the implications of the
testing and emotional support by someone with training and
expertise in the field. Genetic counselors also provide information
on prenatal testing for muscular dystrophies to see if an
unborn baby has inherited a genetic mutation. This testing
can be done if there is an affected relative in the family
or if the mother is known to be a carrier of a genetic alteration
in an identified gene.
Treatment and Rehabilitation of Miyoshi
Myopathy
Currently there is no medication or cure for Miyoshi myopathy;
there are no special dietary measures that are helpful. There
are, however, several options for treating the symptoms of Miyoshi
myopathy such as assistive devices that can be dramatically
beneficial in daily activities.
At some point, an individual with Miyoshi myopathy may benefit
from or require a wheelchair. Many individuals initially see
the wheelchair as a sign of disability and want to postpone
using it. However, most wheelchair users find they are grateful
for the wheelchair and are actually more mobile, energetic and
independent than when they ambulate exclusively on weak legs.
Exercise therapy is recommended by some doctors for individuals
with neuromuscular disorders. However, we do not know for sure
whether exercise is good or bad for muscle diseases, including
Miyoshi myopathy. The general consensus is that low-intensity
exercise may help overcome some of the muscle shrinkage (atrophy)
that comes from disuse of the muscle. However, it is probable
that high-intensity, strenuous exercise may actually further
damage the muscle by overstressing it. It is important that
exercise therapy be monitored carefully by a clinician who should
look signs of muscle injury.
Support
After one is confirmed to have Miyoshi myopathy, there are several
sources of emotional and informational support the patient or
the family members of the patient can seek. Being diagnosed
with a neuromuscular disorder can be overwhelming. Please use
the link below to see a list of support groups that could benefit
a person with Miyoshi myopathy or a family member of a person
with Miyoshi myopathy.
Research
As more people participate in research for Miyoshi myopathy,
our knowledge of the mechanisms that cause this disorder will
improve. As our understanding of this disorder increases, we
will be better able to treat and manage this condition. There
is research being done on Miyoshi myopathy and related muscular
dystrophies. Please use the links below to find out more about
the research being done and to stay informed about new advances.
Our Research
Links Page
Muscular Dystrophy Association
www.mdausa.org
To find a genetic counselor near you, please visit the National
Society of Genetic Counselors Web site.
Some content adapted from the Muscular
Dystrophy Association. For more detailed information, visit
the MDA web site at www.mdausa.org
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