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Multiple epiphyseal dysplasia (MED)
a disorder of development of the ends of the long bones
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Types
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There are a number of types, described below, of multiple epiphyseal dysplasia.
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Clinical signs
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This is a relatively common type of short stature. A significant number of patients
have a stature that is not very short, and they are diagnosed as having a congenital
skeletal disease.
Affected individuals have a proportional, relatively short stature; however, exact
measurements will show it to be not completely normal. The fingers, especially their
distal parts, and sometimes the whole hand, are characteristically small. In adults,
there is a common complaint of pain in the area of the femoral head - this is due
to abrasion of the cartilage at the head of the femur, which is vulnerable to this.
X-rays can only assist in diagnosis if they are carried out before adolescence.
The characteristic feature of the bones is that the bone ends, known as epiphyses,
are undeveloped, small and irregular. The external border of the epiphyses, which
should be round with smooth margins, is not smooth and is irregular. The changes
can be prominent in the femoral heads and/or knees. There are no changes in other
parts of the bones.
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A precise diagnosis is important, and a diagnosis made in the past may not always
have been made according to today-s standards and methods and is not always accurate
by today-s standards.
Because of this, the diagnosis must always be confirmed in a genetic institute by
examining the patient, or at least by looking at the clinical picture, photographs,
X-rays and other data.
Even though we know a lot about the inheritance patterns, the risk of recurrence,
the mechanism of the manifestations of the disease, etc., most of these diseases
have exceptions, and each case/family must be examined individually in a genetic
institute.
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Inheritance pattern
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The vast majority of the cases are transmitted by autosomal dominant inheritance.
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Penetrance
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Incomplete
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Associated features that can be demonstrated in tests performed during pregnancy
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This condition cannot usually be detected by ultrasound examination in pregnancy since
usually the shortening of the bones only appears after birth or even after the age
of two years.
In all these cases it is important to refer the couple for genetic counseling, to which they should bring
all data, including the results of other tests performed during the pregnancy such
as alpha fetoprotein,
nuchal translucency, etc.
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What is the risk of recurrence in a subsequent pregnancy?
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Usually one of the parents of a child with MED has the same condition in a more
or less severe form, and in this case the risk of recurrence is 50% in every subsequent
pregnancy. Relatives who do not have all the bone changes are also at risk for having
a child with the same condition - this risk is not high, but is not negligible either,
because these patients may not always be recognized, even in the same family. This
must be established at a genetic institute.
The risk for more distant relatives depends on the number of affected individuals
in the family, the degree of relationship between the relatives and the affected
individuals, consanguinity
between the parents, if present, etc. This risk is established within genetic counseling.
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Molecular genetic information
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The gene for the disease
There are at least four genes: three constitute collagen 9 and another is known
as COMP. Apparently, there is a correlation between the genes and the manifestation
of the disease as shown on X-ray. In cases in which the disease affects mainly the
femur, i.e. the epiphyseal damage is more severe in the femurs, the gene responsible
is usually COMP. If the most prominent changes are mainly in the knees, a collagen
9 defect is usually responsible.
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Genetic testing
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Diagnostic testing
This is a complex test that requires the testing of a number of genes. See: Indirect
testing for genetic markers in a family with a number of patients in the family
- when there are a number of different genes that can each cause the disease - all
of the genes having been located / identified / mapped - autosomal dominant disease.
Carrier testing
In families in whom the mutation in the gene responsible for the disease has been
found, other relatives may be tested both for signs of the disease itself and for
carrier status. There are no carrier tests for the healthy population.
Fetal testing
As for diagnostic testing.
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