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Diastrophic dysplasia
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Clinical signs
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Diastrophic dysplasia is a hereditary disease that mainly affects bone growth. Patients
with this condition have scoliosis, a form of bilateral
clubfoot, malformed pinnae with calcification of the cartilage, premature
calcification of the costal cartilages, and cleft palate in some cases. Particularly
characteristic is the 'hitchhiker' thumb due to deformity of the first metacarpal.
Median adult height is 136 cm for males and 129 cm for females. Growth failure is
progressive, partly because of an absent or weak pubertal growth spurt. The severity
of the growth failure varies greatly, even among siblings. The final height does
not correlate with midparental height, but does correlate well with height at age
1 year and 5 years. The relative weight is normal in childhood but increases before
puberty, and more than a quarter of the adults are overweight. Head circumference
is normal.
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Inheritance pattern
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Autosomal
recessive.
When both parents are carriers, the child will only be affected if he or she inherits
two abnormal genes - one from the mother and one from the father.
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Penetrance
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Penetrance is complete, but the severity of the growth failure varies greatly, even
among affected siblings.
The disease is relatively frequent in Finland, where at least 160 affected patients
have been reported. The carrier rate among individuals of Finnish ancestry with
no family history is 1 in 25.
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Associated features that can be demonstrated in tests performed during pregnancy
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In a significant number of cases of classical Diastrophic dysplasia, abnormally
short limbs and lateral projection of the thumbs can be detected on ultrasound examination
at 16 weeks of gestation.
These abnormalities should be checked for in subsequent pregnancies after the birth
of an affected child. DNA tests can confirm the
diagnosis.
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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- For a couple who has already had an affected child, the risk is 25% in every subsequent
pregnancy. When only one parent carries the abnormal gene, there is no risk that
any of their offspring will have the disease; however, in such families there is
a 50% chance that the infant will be a carrier, but he himself will be healthy,
like the carrier parent.
- The risk for more distant relatives depends on the degree of relationship between
the relatives and the affected individuals, the ethnic groups of their partners,
affected relatives of partners, consanguinity
between the parents, if present, etc., and is established within genetic counseling.
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Molecular genetic information
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The gene for the disease:
SLC26A2
Location
Chromosome 5q32-33.
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Genetic testing
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Diagnostic testing
In Finland, a direct test can be performed to identify the mutation in the gene
by testing for the common mutations. See: Testing the disease-causing
gene for mutations that are common in a specific ethnic group - autosomal recessive
diseases.
Carrier testing
- The mutation C26+2T→C in the gene causing Diastrophic dysplasia is the one that
is common in the Finnish population. The carrier rate varies between 1:20 in the
healthy population of Finland and 1:100 in people from other ethnic origins.
- In view of this, it is very important to ascertain the ethnic origins of the couple,
and it is advisable to examine (carrier DNA testing) those couples where both partners
are fully or even partially of Finnish origin.
See also: "Introduction to population
DNA screening for autosomal recessive diseases such as Cystic fibrosis and others".
Carrier status testing in relatives of Diastrophic dysplasia patients
It is important that relatives of Diastrophic dysplasia patients clarify which mutations
are present in the patient or parents in their family in order to ascertain that
they are included in the battery of mutations routinely tested for - otherwise it
will be necessary to expand the list of mutations tested for and/or examine the
partner. This will be discussed in genetic counseling.
Fetal testing
Same as the diagnostic test.
Prenatal diagnosis can also be offered to each couple who has had an affected child.
The best way is after identifying the mutations in the parents, but if these are
not found, indirect linkage analysis can be performed. 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 - autosomal recessive diseases.
Preimplantation diagnosis
(before the embryonic cells implant in the uterine wall) can also be offered for
this disease - this is performed in special centers, and in special cases this can
be considered within genetic counseling.
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