Muscle diseases and muscular dystrophy
There are dozens of different types of muscle diseases. They differ according to
their clinical and laboratory characteristics.
- Age of onset of signs of the disease
- in some diseases, the muscle disorder appears immediately after birth or in infancy.
In others it only starts at an older age or even in adulthood.
- Inheritance pattern - in
some of these diseases inheritance is
X-linked, and in others it is autosomal recessive or autosomal dominant.
- Muscles in different parts of the
body are affected in the different types of muscular dystrophies in some,
only the limb girdles are involved, manifesting mainly in difficulties in getting
up from a lying position without the help of the hands. In another, the facial muscles
and/or the limb muscles become weak, and in another all the muscles are affected.
- Severity of the muscle impairment
and the pattern of progression - in some types, the disease progresses rapidly
and causes death by the age of 20, whereas in others it progresses more slowly and
does not cause death.
- Laboratory test findings
- the different diseases can be differentiated by the type of changes in the muscle
that can be seen under the microscope in a muscle biopsy, the type of metabolic
changes (enzymes and proteins that are altered in the muscle and that can be measured
in muscle biopsy), the type of changes visible on electromyography (EMG), and according
to the genes responsible for each type of disease.
The different groups of muscle diseases are listed below
- Muscular dystrophy - this
is a group of varied and common congenital muscle diseases. The common denominator
of all of them is a characteristic picture of progressive muscle destruction visible
under the microscope. It eventually results in gradual loss of function of the muscles
involved in the disease.
A number of common types of muscular dystrophy are listed below - See separate information
sheet on each one:
Duchenne or Becker muscular dystrophy (DMD or BMD).
girdle dystrophy (LGMD).
Facioscapulohumeral muscular dystrophy (FSHD).
Congenital muscular dystrophy (CMD).
Dozens of different genes that are associated with these types of muscular dystrophy
have been identified. Most, but not all, of the proteins produced by these genes
actually constitute a complex surrounding a central protein (known as dystrophin)
and other proteins connected to it. The function of this complex is to attach the
muscle fibers to one another. Each muscle is composed of many fibers that contract
and relax at the same time. When the dystrophin complex is normal, all the muscle
fibers move together without friction. When this complex is impaired, the resulting
friction between the fibers causes progressive destruction of the fibers. The severity
and the distribution of the muscles affected are determined by which of the proteins
in this complex is involved.
- Other muscle diseases there
are many other muscle diseases that are not included in the group of muscular dystrophies.
These diseases are each characterized by properties differing from those mentioned
above, and the defect in them is not associated with the dystrophin complex, but
with other complexes in the muscle.
Muscle diseases not defined as muscular dystrophy are listed below:
- Myotonic dystrophy
apart from muscle weakness, the characteristic difficulty in this disease is the
relaxation of contracted muscles.
- Muscular metabolic disorders arising from defects in the complexes that provide
energy to the muscle. The metabolic defects can be demonstrated by measuring
the activity of the enzymes of the muscle respiratory chain. This is the enzyme
chain that converts oxygen extracted from the air that is breathed into a chemical
substance known as ATP. This provides the energy to the muscle.
- Other problems manifesting as defects
in muscle function that are not diseases of the muscle itself some of these
diseases appear to be disorders of the muscles, but are in fact diseases of the
nerves that conduct the stimuli from the brain to the muscles, or a disorder in
the brain itself. There may also be metabolic disorders of the blood that are associated
with muscular weakness, and other problems. The precise diagnosis of the disorder
must therefore be made by a neurologist. The final tests and the verification of
the diagnosis are carried out by a geneticist whenever possible.
Disorders manifesting as muscle weakness that are not diseases of the muscle itself
are listed below
(see separate information sheet on each):
- Spinal muscular
atrophy: in this condition the muscle weakness is caused by a defect in the
nerves in the spinal column. The disease is therefore not a muscle disease but a
nerve disease. It manifests as generalized muscle weakness and tremor that is present
in the tongue in particular. There are different types of varying severity.
- Cerebral palsy.
- Charcot Marie Tooth (CMT): This is a disease of the peripheral
nerves that mainly affects the legs. The onset is in adulthood between the ages
of 20 and 40. The legs are thin and have a characteristic shape caused by atrophy
of the gastrocnemius muscles in the leg. This disease is transmitted by autosomal
dominant inheritance and is slowly progressive. 70% of the patients have a genetic
mutation that is demonstrable relatively easily this is a duplication of part of
the gene known as 1CMT on chromosome 17. For other patients the diagnosis is difficult,
time-consuming, and it involves considerable laboratory effort.
As noted, there are dozens of different types of muscle diseases and muscular dystrophies
causing progressive weakness of the muscles involved in the degenerative process.
The diseases differ in the characteristics described above under types.
The exact type can be diagnosed at a genetic institute.
Based on the exact type, the inheritance pattern is determined, along with the risk
of recurrence, tests available, diagnosis, and preventive measures.
With reference to the above, the following must be remembered: A precise diagnosis
is important, and this is not always made.
It must always be ensured that the diagnosis at a genetic institute is made by examining
the patient, or at least by reviewing documents, the results of the neurologists
examination, laboratory and/or EMG results, and other data. Even though we know
a lot about the inheritance patterns, the risk of recurrence, pathogenesis, etc.,
most of these diseases have exceptions, and each case/family must be examined individually
in a genetic institute.
All types of inheritance occur. Each case must be examined individually based on
the specific disease and the distribution of cases in the family.
Depends on the specific disease.
Associated features that can be demonstrated in tests performed during pregnancy
In diseases in which the genetic mutation has been accurately and precisely identified,
a reliable genetic test can be performed in the fetus if there is a high risk that
he or she may be affected. These diseases cannot be detected by ultrasound examination in pregnancy. It is
important to bring to genetic
counseling all available data including the results of any additional tests
carried out during the pregnancy such as alpha-fetoprotein, nuchal translucency,
What is the risk of recurrence in a subsequent pregnancy?
This depends on which specific disease the patient has, the inheritance pattern,
and the relationship to the patient. The risk for more distant relatives depends
on the number of affected individuals in the family, the relationship of each to
the patients, consanguinity
between the parents, if any, etc. The exact risk is ascertained within genetic counseling.
Molecular genetic information
The gene for the disease:
Depends on the specific disease.
Location: Depends on the
Diagnostic testing: Depends
on the specific disease.
Carrier testing: In families
in whom the specific mutation in the gene responsible for the disease has been found,
other carriers and patients in the family can be examined. Tests to identify carrier
status in the healthy population are currently not recommended.
Fetal testing: Usually the
same as diagnostic testing.
What should be done before genetic counseling?
In order to be able to recommend the specific investigations that are most appropriate
for you, and in order for you to know whether you are in a risk group, it is necessary
to ascertain a number of details about the patient. Below are some examples showing
how different details can help to establish the diagnosis of muscular dystrophy.
After obtaining answers to all these questions, it is important that you come to
a genetic institute in order to determine the diagnosis and to evaluate your level
of risk, if present. You will also be offered recommendations for testing for you
and/or the fetus and for pregnancy monitoring.
- Is an exact diagnosis known?
If so, it will be relatively easy to give you an explanation and an evaluation of
your risk level. It will also be possible to consider appropriate tests.
- Are the affected family members
male only, and does the disease start in early childhood? If so, there are
a number of possibilities of which the main ones are Duchenne muscular
dystrophy or Becker muscular dystrophy. As noted, there are also other types
of childhood muscular dystrophy. With the data you have, you can assist in the diagnostic
process at the genetic institute during your counseling.
- Are the patients of both sexes and
do they have muscular dystrophy dating from birth, or did the signs only appear
at a few weeks of age? If so, there are a number of possibilities, such as
myotonic dystrophy or SMA type 1.
- Did the disease begin in the second
decade of life or later? If so, there are a number of other possibilities,
such as CMT, myotonic dystrophy, etc.
- Is there evidence of hereditary
transmission between parents and children? If so, this suggests autosomal
- Do you know whether the muscle or
the nerves are affected? This is important for establishing the group of
- Did the weakness start in the upper
or lower body? This is important for establishing the group of diseases.
Muscular Dystrophy: The Mysterious Disease