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Clinical Picture
Each person, even people within the same family, may differ
slightly in the severity of FSHD. In severe cases, an infant
may present with very weak muscles. However, FSHD may be so
mild that adults may be unaware they are affected until a family
member with more severe symptoms is diagnosed. This variation
in symptoms is called genetic heterogeneity.
Both males and females are affected equally with FSHD because
the genetic mutation lies on an autosome. (This is the name
given to chromosomes numbered 1 through 22, while the 23rd
pair is called the sex chromosomes. Please see the genetics
review section for a more detailed explanation.) By age
20, nearly all affected individuals experience some level
of muscle weakness due to shrinkage (atrophy) of the muscles.
Most affected individuals first notice facial weakness and
have difficulty with smiling, whistling, closing their eyes,
and certain facial expressions. A phenomenon called scapular
winging also commonly occurs in individuals with FSHD. This
occurs because the shoulder muscles weaken and do not hold
the shoulder blade (scapula) in place, which may cause them
to protrude. This may be visible when you look at the back
of an individual with FSHD. Some people with FSHD have forward
sloping of their shoulders and difficulty raising their arms
over their head because of weakness in the shoulder and upper
arm areas.
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Figure 1: The Muscles Affected
in FSHD
The pectoral muscles of the chest and abdominal muscles
may become weak. Difficulty in walking occurs if the
lower leg and hip muscles weaken. Muscular weakness
is often more noticeable on one side of the body. Approximately
50% of those with the disorder retain the ability to
walk throughout their lives, and only a minority of
individuals require a wheelchair. Muscles involved in
breathing and swallowing are usually not affected.
The progression of this disease is slow, with muscular
weakness increasing over the course of several years.
Sometimes there are rapid spurts of progression that
soon plateau. A minority of patients require a wheelchair
because of difficulty walking. The extent to which muscle
weakness affects a person's ability to function is very
variable and unpredictable.
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Figure 1.
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Other potential symptoms of FSHD may occur. Often, affected
individuals experience high-frequency hearing loss. This type
of hearing loss is usually not noticeable and can only be
detected with an audiogram hearing test. Some develop arrhythmias,
or abnormalities of heart rhythm, which only rarely cause
medical problems. Very rarely, individuals with FSHD develop
abnormalities of the blood vessels of the eye that may cause
vision problems.
Unfortunately, at this time there is no cure or treatment
that can prevent symptoms of FSHD. However, there are medical
management strategies that can help to maintain or improve
muscular function, including orthopedic supports and sometimes
surgery to improve function in the shoulder area.
Ways a person gets FSHD:
There are three main ways that an individual can get this disorder.
- A parent with FSHD can pass on the gene defect to his
or her daughter or son. Often, this defect is a genetic
deletion, or loss of a segment of a gene. Researchers have
discovered that there is an association between the size
of the deleted segment and symptom severity. (The bigger
the deletion, the more severe the FSHD.)
- A deletion may occurr in the sperm or egg that formed
the embryo by chance. This is called a sporadic mutation.
If this occurs, then other family members other than the
affected person's children are not at increased risk to
get FSHD. Children with a parent with FSHD have a 50% chance
of inheriting FSHD.
- A parent may have germline mosaicism, a very rare genetic
phenomenon in which all the cells in a person's body do
not have the same genetic content. Germline refers to the
sex cells that form eggs in women and sperm in men. Mosaicism
is an event that happens when a new mutation (a deletion
in this case) occurs in a single cell early in the pregnancy
when the baby is a tiny embryo. This cell then divides over
and over, with the mutation present in all the cells that
cam from the original cell with the mutation. Consequently,
only some cells in the person's body have the DNA with a
mutation, and the other cells do not. The effect of mosaicism
varies in every person. Some mosaic individuals may show
no signs of the disease, but are at risk to pass on FSHD
to their children if their sex cells contain the deletion.
The exact risk of passing on FSHD is unknown, but can be
as high as 50%. Other mosaic individuals may have a severe
case of FSHD.
It may be that a person is the first in the family to have
FSHD. This can happen if a parent had a mild case of the disorder
that went medically undetected. This can also happen if a
parent had a deletion but never developed symptoms. This is
called genetic penetrance, and refers to the amount of individuals
with a genetic mutation that actually develop the symptoms
of a given disorder. FSHD is 95% penetrant, meaning that about
95% of individuals with a mutation will develop some type
of symptoms during the course of their lifetime. Thus, 5%
of individuals with the mutation that cause FSHD do not develop
symptoms, but can pass on the genetic mutation to their offspring.
Last, a sporadic mutation and germline mosaicism can be the
cause of an individual being the first person with symptoms
of FSHD in a family.
Testing for and Diagnosing FSHD
The first step in diagnosing FSHD is noticing the signs of muscular
weakness. 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. 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 to determine the exact type of muscle disorder. If
FSHD is suspected, a physician may perform inflammation studies
because some cells of the immune system may attack the muscle
in individuals with FSHD.
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.
Genetic Testing:
There is genetic testing available for FSHD, which takes
on average 2 to 6 weeks for results. Test results may be negative
(no mutation is found), positive (mutation is found), or uncertain
(scientists may be uncertain of the clinical significance
of a certain alteration in a patient's DNA). The cost of the
testing depends on who is doing the testing. Usually the cost
is covered, at least in part, by insurance companies. Genetic
testing is done by drawing a small amount of blood (two or
three tablespoons) from the patient, or by taking a small
sample of tissue. From the blood, DNA is isolated and scientists
can measure the size of the region of DNA that is deleted
in persons with FSHD. When the DNA is deleted, a gene in this
region of the DNA may be missing completely or in part and
may not function properly. This leads to muscle weakness.
About 95% of people who have been diagnosed with FSHD have
a deletion. The severity and age of onset of symptoms seems
to correlate with the amount of genetic material that is missing
in the DNA. Therefore, the larger the amount of missing DNA,
the earlier the symptoms will appear and the more severe the
case of FSHD. It is important to caution that the size of
the deletion cannot be used to predict the age when a person
will develop symptoms or the severity of the disease!
The decision to be genetically tested is a very important
and personal decision. It may effect your family life and
planning, relationships, career and insurance decisions, and
psychological and emotional well-being. It is a decision to
be carefully made and it can have a very positive or a less
positive outcome. Genetic counselors are available to individuals
who are considering 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 FSHD to see if an unborn baby has inherited
a genetic mutation. This testing can be done if a parent has
tested positive for a mutation that causes FSHD.
Genetic counselors can also provide information on preimplantation
diagnosis (PGD). This complex technique was not previously
available to families with FSHD, and it may not ever be 100%
effective for this disorder due to the complexity of the genetic
alteration. However, a recent report (Spring 2003)at the Fifth
International Symposium on Preimplantation Genetics announced
that PGD may be available for FSHD in the future. (Abstract
by: J. Marshall, D. Leigh, S McArthur, K de Boer. Sydney IVF,
Sydney Australia.) PGD is a technique whereby eggs are obtained
from the mother that are then fertilized by the father's sperm
in a laboratory. Genetic testing is then done on the embryos
to test for a given genetic disorder. Only those embryos that
have not inherited the mutation for the given disorder are
implanted into the mother's womb. Prenatal testing and PGD
are complex issues and are not covered in depth in this site.
For more information, speak with a physician, a genetic
counselor, or contact Reproductive
Genetics Institute.
Treatment of FSHD
There is no cure for FSHD at this point in time, and the treatment
options that are available are limited to those that target
some of the symptoms. In some cases, surgery and assistive devices
are used to correct for muscle weakness. Consulting with a physical
therapist to discuss braces and supports that are available
may be helpful. Some physical therapists recommend an exercise
regimen which may be helpful, while others are more hesitant
to suggest exercise because we are uncertain of the long term
consequences of muscle exertion. Speak with a qualified neuromuscular
specialist about the options that are currently available.
Research
A small number of people genetically tested for FSHD do not
have a deletion. Because of this, researchers think that there
is more than one genetic cause for FSHD. They are still looking
for other genes that may be a cause of FSHD, which emphasizes
the importance of research. For this small subset of individuals,
genetic testing is not useful in diagnosing FSHD and there is
no other definitive testing to offer them. As more people participate
in research for FSHD, our knowledge of the mechanisms that cause
FSHD 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 FSHD and related muscular dystrophies.
To learn more about our research, click here.
Support
After one is confirmed to have FSHD, one may experience overwhelming
thoughts and emotions. There are several sources of support
the patient or the family members of the patient can seek. Please
use the links below to view support group and educational information
that could benefit a person with muscular dystrophy or a family
member of a person with muscular dystrophy.
The FSH Society (link below) is the only organization whose
sole function is to help people with FSHD. The Society encourages
patients and families to visit their web site for more information
on FSHD and for more information on the organization.
Links
Facioscapulohumeral (FSH) Society, Inc.
www.fshsociety.org
Muscular Dystrophy Association
www.mdausa.org
Some content adapted from the Muscular Dystrophy
Association. For more detailed information, visit the MDA
web site at www.mdausa.org
Figure 1: Graphic used with permission of the
Muscular Dystrophy Association.
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