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Duchenne and Becker muscular dystrophy
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Clinical types
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Duchenne muscular dystrophy
- the more severe type.
Becker muscular dystrophy
- the milder type.
There are other similar conditions that mimic these diseases- some are transmitted
by autosomal
recessive inheritance. They can be differentiated by clinical and laboratory
tests after examination by a geneticist.
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Clinical signs
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Both these conditions occur as a result of a mutation in the dystrophin gene. The
mutation is expressed in both conditions in males, although there are always rare
exceptions. The affected children are born normal and early development is normal.
Signs of Duchenne muscular dystrophy appear at the age of 4 - 5 years, manifesting
as difficulty in climbing steps in children previously able to do so without difficulty.
The waist girdle muscles used to lift the body up from a crouching position are
particularly affected. The muscle weakness progresses rapidly and the boys usually
need a wheelchair by the age of 10. Weakness is also present in other body muscles,
causing death at around the age of 20 from cardiac and respiratory failure.
In Becker muscular dystrophy, the signs appear at a later age - around 8 - 10 years.
The clinical course is similar to but slower than that in Duchenne muscular dystrophy.
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Laboratory tests reveal that patients have very high blood levels of creatine phosphokinase
(CPK - an enzyme that originates from muscle and that is secreted into the blood).
High values such as those found in this disease are rare in the healthy population.
The signs shown on electromyography are also characteristic.
Muscle biopsies show characteristic dystrophic changes.
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The most accurate diagnostic test is a muscle biopsy with immunofluorescent staining
for dystrophin. In healthy individuals whose muscles contain this, antibodies bind
with the dystrophin and a fluorescent glow can be seen that is evidence of the presence
of dystrophin in the muscle, whereas in Duchenne muscular dystrophy patients who
lack normal dystrophin there is no binding of the antibody with dystrophin and therefore
no fluorescent glow. In patients with Becker muscular dystrophy there is some binding
but only a small amount. In women who are carriers of Duchenne or Becker muscular
dystrophy there is partial binding, and this enables carriers to be identified.
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Inheritance pattern
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X-linked.
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Penetrance
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Full
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Associated features that can be demonstrated by imagery
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Usually there are no defects that can be identified by ultrasound examination during pregnancy.
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What is the risk of recurrence in a subsequent pregnancy?
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In cases where the affected individual
is the only one in the family: The mother need not necessarily be a carrier.
The mutation could be a new mutation. If the couple has only one child with Becker
or Duchenne muscular dystrophy and he is the only known affected individual in the
family, there is a 66% chance that his mother is a carrier. Therefore in each subsequent
pregnancy with a male fetus, the couple has a 33% chance of having another affected
son. In these cases the risk that a sister or maternal aunt of the patient will
be a carrier is half that of the mother.
In cases where there are many affected
individuals in the family: Women who have given birth to more than one
affected son are considered to be carriers, with a 50% risk in every subsequent
pregnancy that a male fetus will be affected and a female fetus will be a carrier.
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Molecular genetic information
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The gene for the disease
DMD
Location
X chromosome
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Genetic testing
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Diagnostic testing (identification of genetic mutation and proof of disease)
: Regarding diagnosis by non-genetic methods, see above under laboratory tests.
The gene for dystrophin is very long, and most mutations in it are a deletion of
part of the sequence. This deletion can be detected by a relatively simple screening
test at the level of protein production by the gene - this is called protein truncation
testing and it allows the mutation to be demonstrated in approximately 70% of cases.
Another screening test for the deletion identifies only 50% of cases. See: Screening test for identifying defects
(mutations) using various methods such as SSCP - X-linked diseases, and
Screening tests for identifying gene products for
establishing the existence of a disease (methods such as protein truncation) - X-linked
diseases.
Carrier testing
Fifty percent of Duchenne muscular dystrophy carriers have elevated creatine phosphokinase
levels. However, the test that identifies carrier status with a higher level of
accuracy than any of the other tests is a muscle biopsy to detect the presence of
dystrophin (see above under laboratory tests).
Genetic tests for carrier status depend on the family:
In cases where there are many affected
individuals in the family, the defect (mutation) must be identified in
the patients. Testing for carriers in the family starts with the first-rank relatives
of the affected individuals, and initially, the sisters and mothers of the patients
are examined. Based on the results, the carrier tests can then be extended to other
women who are related to the patients and to the carriers detected in the first
round of tests. Each carrier identified can be offered prenatal diagnosis in pregnancy
- during this the sex of the fetus will be determined, and in the case of a male
fetus, whether or not he is affected. All these tests must be carried out through
a genetic institute.
If it is not possible to identify the mutation easily, an indirect test (linkage
analysis) can be performed, but not before it is established with certainty that
the mother, and any other woman in the family wishing to test her status, is a carrier.
In these situations a muscle biopsy to demonstrate the presence of dystrophin (see
above) should be carried out. Only then is it possible to use the indirect tests
in women who have undergone a biopsy and who have been found to be carriers. See:
Indirect testing for genetic markers in a family that has a one or more patients
- when there is only one gene that can cause the disease - X-linked diseases.
In cases where the affected individual
is the only one in the family: In these cases, the patient's mother has
a 2 in 3 probability of being a carrier, and other women in the family are not necessarily
carriers. The mutation must first be identified in the patient and in his mother.
If the defect (mutation) in the patient is present in his mother, she is a carrier.
Testing for carriers in the family starts with the first-rank relatives of the affected
individual, and initially, the sisters and mother of the patient are examined. Based
on the results, the carrier tests can then be extended to other women who are related
to the carriers detected in the first round of tests. Each carrier identified can
be offered prenatal diagnosis in pregnancy - during this the sex of the fetus will
be determined, and in the case of a male fetus, whether or not he is affected. All
these tests must be carried out through a genetic institute.
The indirect test (linkage analysis) cannot be performed before it is established
with certainty that the mother, and any other woman in the family wishing to test
her status, is a carrier. If it is not possible to identify the mutation easily,
then a muscle biopsy to demonstrate the presence of dystrophin (see above) should
be carried out. Only then is it possible to use the indirect tests in women who
have undergone a biopsy and who have been found to be carriers. See: Indirect testing for genetic markers in a family that has one
or more patients - when there is only one gene that can cause the disease - X-linked
diseases.
Fetal testing
After it has been established that the woman (mother, sister, or a more distant
relative of the patient) is a carrier, genetic tests can be used for prenatal testing.
In the case of a male, it is possible to determine whether he has received the mutation
identified in the patients in the family. See: Screening test for identifying
defects (mutations) using various methods such as SSCP - X-linked diseases.
If the defect is not identified, indirect tests may be employed, once again on basis
that the mother is a carrier, because if she is not, the next fetus may be healthy
even if he has received the same allele as the affected child, because the affected
child may have a new mutation which occurred only in the ovum that created him -
see: Indirect testing for genetic markers in
a family that has one or more patients - when there is only one gene that can cause
the disease - X-linked diseases.
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