Clinical Picture
Typically, there is onset of muscle weakness in the pelvic girdle
which becomes evident in childhood to young adulthood when the
individual with LGMD has difficulty standing from a sitting
position without using arms and when climbing stairs. The individual
may also have a waddling gate. Later there is onset of shoulder
weakness, as shown when individuals have difficulty with tasks
that involve raising their arms, such as reaching and carrying.
In general, after the onset of LGMD in the arms, in the next
20 – 30 years the individual becomes wheelchair dependent.
The muscle deterioration associated with LGMD generally is not
painful, but the limited mobility may lead to muscle soreness
and joint pain. This can be treated with exercises, warm baths,
and medications if necessary. The brain, intellect and the senses
are not affected in individuals with LGMD. Individuals with
a form of LGMD can lead happy, productive lives.
Other Ways LGMD Affect the Body:
Rarely, patients develop cardiomyopathy, conduction abnormalities
(arrhythmias) and weakness of respiratory muscles. Respiratory
function may decline after time, putting the individual at risk
for heart failure. Recent research has suggested that some forms
of LGMD may affect the involuntary muscles responsible for normal
blood vessel contraction and relaxation. This potential involvement
could be a factor in some of the heart problems that occasionally
are seen in patients with LGMD.
LGMD is very heterogeneous and it is not yet possible to predict
the course that LGMD will take in an individual. But we do know
that LGMD is not a fatal disease. Most of the danger comes from
weakening of the heart or respiratory muscles. Awareness of
these problems and the treatment that is available for them
can lead to a longer and higher quality life.
What causes LGMD
Researchers have now identified at least 12 different forms
of LGMD. The types are classified by the genetic alterations
that appear to cause them. Most of these genes lead to the
production of muscle proteins that are altered and therefore
cause LGMD.
Six of the genes that cause LGMD lead to production of proteins
that are normally located in the muscle cell membrane. Some
of the proteins associated with LGMD are not in the cell membrane
area, such as the Calpain-3 protein which is most likely located
in the sarcomere .
Below is a list of the different forms of LGMD that have been
classified, the inheritance pattern they follow, the gene
product affected, and the genetic location responsible for
that form of LGMD. All these mutations occur on the autosomes.
| Inheritance |
Disorder |
Gene Product |
Chromosome Location |
| Autosomal Dominant |
LGMD1A
LGMD1B
LGMD1C
LGMD1D
LGMD1E
LGMD1F
|
Myotilin
Lamin A/C
Caveolin-3
?
?
? |
5q
1q
3p
6q
5q
7q |
| Autosomal Recessive |
LGMD2A
LGMD2B
LGMD2C
LGMD2D
LGMD2E
LGMD2F
LGMD2G
LGMD2H
LGMD2I |
Calpain-3
Dysferlin
Gamma-sarcoglycan
Alpha-sarcoglycan
Beta-sarcoglycan
Delta-sarcoglycan
Telethonin
TRIM32
FKRP |
15q
2p
13q
17q
4q
5q
17q
9q
19q |
Ways a person gets LGMD
- Inheritance of the genetic alteration from the parents,
in an autosomal recessive and an autosomal dominant pattern
- Sporadic Mutations
Because of the numerous forms of LGMD, inheritance risks
for any particular form may be complicated and depend on several
circumstances. It is best to find out more from your Muscular
Dystrophy Association clinic physician or a genetic counselor.
Diagnosing LGMD
- Take a detailed patient and family history (3 generation
pedigree)
- Determine the source of the muscle weakness (nerve or
muscle)
- Detailed exam to look for signs of LGMD: pelvic girdle
weakness
- Schedule a muscle biopsy
- Genetic testing
For more detail on the pathology of the different types of
LGMD, please visit the Neuromuscular
Disease Center.
Genetic Testing
There is genetic testing available for various forms LGMD, some
on a clinical basis and some on a research basis. For information
on testing locations, visit Gene
Tests-Gene Clinics. Or, to find out about the research the
Neuromuscular Disease Project is conducting on LGMD, click here.
Before your patient considers genetic testing either for research
purposes or for diagnostic testing in the future, it is important
to realize that the decision to be genetically tested is a very
important and personal decision. Genetic counseling provides
useful information about the implications of the testing and
emotional support by someone with expertise in the field.
Treatment
Currently there is no medication or cure available for LGMD
and no special dietary restrictions or additions that are known
to help in LGMD. There are, however, several options for individuals
with LGMD to preserve muscle strength.
Support
After your patient is diagnosed with LGMD, he or she is likely
to feel overwhelmed. It may be helpful to let your patient know
that support is available. Contact your local Muscular Dystrophy
Association Clinic for more information, or visit the web site
at www.mdausa.org.
Additionally, visit the Links section
on this Web site to learn more about other support and information.
|
