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Polydactyly (Supernumerary Digits)
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Types
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Polydactyly (6, 7 or more digits per limb) can occur in one or more limbs. From
a medical viewpoint, 2 main types are distinguished:
- An extra digit on the little finger/toe side (postaxial).
- An extra digit on the thumb/big toe side (preaxial).
The presence of other defects or abnormal findings and other cases in the family
is important, as will be discussed below.
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Postaxial polydactyly
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Clinical signs
This is the more common type of polydactyly - it is ten times more common than the
preaxial type. The extra digit on the little finger/toe side can be an intact digit
(type A), or only a degenerate vestige of a digit that appears as threadlike thin
tissue that contains no bone and that can easily be removed by ligation with thread
immediately after birth (type B). In the same family there may be some members with
a type A supernumerary digit and others with a type B digit, so the difference is
probably due to variability of expression of the same condition and genetic mutation.
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In the great majority of these cases (about 90%), polydactyly constitutes the only
manifestation of the condition, and affected children have no other abnormalities.
Here, the mutation is in the gene for polydactyly and the likeliest mode of inheritance
is autosomal
dominant.
The presence of additional cases of polydactyly in one of the parents or in other
family members may support this.
Sometimes the existence of other affected family members is only discovered after
a detailed family history has been taken.
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Without questions and an in-depth investigation of the family, it is not always
possible to know this, as some cases are expressed very mildly and the digit may
have been removed immediately after birth without the parents being notified. If
the same condition is found in other family members, including in one of the parents,
and if these people have no additional abnormalities, it can be assumed that this
is isolated (non-syndromic) polydactyly.
Inheritance pattern
Autosomal dominant
Penetrance
Penetrance is not full. The probability that the polydactyly gene will be expressed
in a person who carries it is about 65%. In other words, there may be instances
where members of a family with many cases of polydactyly will be born with a normal
number of digits, but will give birth to children with polydactyly - these family
members carry an abnormal gene for the condition but do not express it. In such
families there may be some children with polydactyly restricted to a single limb,
and others where all four limbs are involved.
Associated features that can be demonstrated by imagery
In a certain percentage of cases, additional problems may occur, in which case the
condition is not isolated polydactyly but a genetic syndrome of which polydactyly
is a part. Some of these syndromes include structural defects that can be identified
by ultrasound examination,
and some, albeit a relatively small proportion, will have functional problems such
as mental retardation, etc., without defects/changes in the body structure that
can be identified by ultrasound.
Hence if a case of polydactyly is discovered, further testing is very important
in order to confirm or rule out the presence of a syndrome involving several systems.
Performing amniocentesis to confirm or rule out a chromosomal problem should also
be considered. It is necessary to carry out a comprehensive and thorough ultrasound
scan in order to ascertain whether there are further defects in the digits such
as fused digits (syndactyly), shortening of other digits, etc., or defects in other
body organs. An ultrasound examination that gives a normal result apart from the
postaxial polydactyly indicates a significantly reduced risk of a genetic syndrome,
but there is still a small risk that is approximately 2% higher than the regular
risk for defects and mental retardation (2 - 4%), although there are
no reliable estimates. Thus there may be syndromes in which the only additional
feature apart from the polydactyly is mental retardation (e.g. Lawrence-Moon-Beadle
syndrome, etc.), but the probability of this is low.
What is the risk of recurrence in a subsequent pregnancy?
- In cases where the affected individual
is the only one in the family: If this is the first case in the family and
it is the isolated (non-syndromic) type of polydactyly, there is a high probability
that the condition in the child/fetus is the result of a new mutation in the gene
for polydactyly - i.e. the hereditary transmission starts with the child/fetus,
and there is a 50% chance in every pregnancy that he or she will transmit the abnormal
gene to his or her offspring. On the other hand, in these cases, the parents and
other family members who are not offspring of the patient apparently have no increased
risk for having another affected child.
- In cases where there are many affected
individuals in the family: The situation is different if there are already
other cases in the family, because here one of the parents of each affected individual
also carries an abnormal gene for polydactyly, and the risk of transmitting this
to the offspring is 50% in every pregnancy, although it may not always be expressed.
Because the gene is not always expressed, one of the parents may carry it without
having polydactyly him- or herself. In such situations, of course, there is a 50%
risk of recurrence in every subsequent pregnancy, and the same risk of recurrence
also applies to more distant relatives who carry this abnormal gene.
When the polydactyly is part of a syndrome, the exact risk for recurrence must be
evaluated. This varies depending on which syndrome the patient has. In some cases
the condition is sporadic and occurs as a result of a new mutation, and in others
it is hereditary, with a recurrence risk of up to 50% for syndromes transmitted
by autosomal dominant inheritance and 25% for syndromes transmitted by autosomal recessive inheritance.
Molecular genetic information
The gene for the disease:
There is genetic heterogeneity, and there are probably a number of genes. In some
cases it has been found that there is a mutation in a gene called GLI3 - a mutation
in this gene can cause the postaxial type, but to compound the problem, it can also
cause mixed cases where one family/person has polydactyly of both postaxial and
preaxial types. There are probably also other genes that have not yet been found.
The location: The GLI3 gene
is situated on chromosome 7p13, and in other families another gene has been linked
to chromosome 13q21-q32. There may also be other genes as well.
Genetic testing
Diagnostic testing: At the
present time there is no simple test for identifying the mutation associated with
the non-syndromic type of polydactyly. In very large families it is possible to
perform linkage analysis (see: Indirect testing for genetic markers in a family that has a number
of patients - when there are a number of genes that can each cause the disease -
not all genes having been located / identified / mapped - autosomal dominant diseases).
Carrier testing: The test
for detecting a carrier of an abnormal gene in an autosomal dominant disease where
the condition is not clinically expressed is in fact the same as a diagnostic test.
Fetal testing: When polydactyly
is detected in pregnancy, where there are no other known cases of polydactyly in
the family, it cannot be determined definitively that this is the non-syndromic
type. An attempt can be made to rule out some of the differential diagnoses, mainly
by ultrasound examination and by ruling out the presence of other defects.
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Preaxial polydactyly
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Clinical signs
This is the less common type of polydactyly. The additional digit is on the thumb/big
toe side, usually having the structure of a separate intact digit or one connected
to the big digit (as a bifid thumb/big toe). Sometimes the second digit is bifid.
Sometimes the polydactyly is complex and features fusion between the digits.
Here too, in most of the cases (approximately 80%), the polydactyly is an isolated
finding and the affected children do not have any other defects. However, in contrast
to postaxial polydactyly, the defects of the digits are often more complex and can
include such abnormalities as fusion between digits, missing parts of digits, etc.
There may also be defects in other organs if the polydactyly is part of a syndrome.
In the cases where the polydactyly is an isolated finding, there is a mutation in
the gene for polydactyly, and in these cases the likeliest mode of inheritance is
autosomal dominant. The presence of additional cases of polydactyly in one of the
parents or in other relatives may support this. Sometimes the existence of other
affected family members is only discovered after a detailed family history has been
taken. Without questions and an in-depth investigation of the family, it is not
always possible to know this, as some cases are expressed very mildly without being
reported to physicians and without the family being aware of them.
If the same condition is found in other family members, including in one of the
parents, and if these people have no additional abnormalities, it can be assumed
that this is isolated (non-syndromic) polydactyly.
Inheritance pattern
Autosomal dominant
Penetrance
The penetrance is incomplete. The probability that the polydactyly gene will be
expressed in a person who carries it is about 50%. In other words, there may be
instances where members of a family with many cases of polydactyly will be born
with a normal number of digits, but will give birth to children with polydactyly
- these family members carry an abnormal gene for the condition but do not express
it. In such families there may be some children with polydactyly restricted to a
single limb, and others where all four limbs are involved.
Associated features that can be demonstrated by imagery
As mentioned, in a significant percentage of cases, additional problems may occur,
in which case the condition is not isolated polydactyly but a genetic syndrome of
which polydactyly is a part. Some of these syndromes include structural defects
that can be identified by ultrasound examination, and some, albeit a relatively
small proportion, will have functional problems such as mental retardation, etc.,
without defects/changes in the body structure that can be identified by ultrasound.
Hence if a case of polydactyly is discovered, further testing is very important
in order to confirm or rule out the presence of a syndrome involving several systems.
Performing amniocentesis
to confirm or rule out a chromosomal problem should also be considered. It is necessary
to carry out a comprehensive and thorough
ultrasound scan in order to ascertain whether there are further defects
in the digits such as fused digits (syndactyly), shortening of other digits, etc.,
or defects in other body organs. An ultrasound examination that gives a normal result
apart from preaxial polydactyly indicates a significantly reduced risk of a genetic
syndrome, but there is still a small risk that is approximately 2% higher than the
regular risk for defects and mental retardation (2 - 4%), although there are no
reliable estimates. Thus there may be syndromes in which the only additional feature
apart from the polydactyly is mental retardation (e.g. Lawrence-Moon-Beadle syndrome,
etc,), but the probability of this is low.
What is the risk of recurrence in a subsequent pregnancy?
If this is the first case in the family and it is the isolated (non-syndromic) type
of polydactyly, there is a high probability that the condition in the child/fetus
is the result of a new mutation in the gene for polydactyly - i.e. the hereditary
transmission starts with the child/fetus, and there is a 50% chance in every pregnancy
that he or she will transmit the abnormal gene to his or her offspring. On the other
hand, in these cases, the parents and other family members who are not offspring
of the patient apparently have no increased risk for having another affected child.
The situation is different if there are already other cases in the family, because
here one of the parents of each affected individual also carries an abnormal gene
for polydactyly, and the risk of transmitting this to the offspring is 50% in every
pregnancy, although it may not always be expressed. Because the gene is not always
expressed, one of the parents may carry it without having polydactyly him- or herself.
In such situations, of course, there is a 50% risk of recurrence in every subsequent
pregnancy, and the same risk of recurrence also applies to more distant relatives
who carry this abnormal gene.
When the polydactyly is part of a syndrome, the exact risk for recurrence must be
evaluated. This varies depending on which syndrome the patient has. In some cases
the condition is sporadic and occurs as a result of a new mutation, and in others
it is hereditary, with a recurrence risk of up to 50% for syndromes transmitted
by autosomal dominant inheritance and 25% for syndromes transmitted by autosomal recessive inheritance.
Molecular genetic information
The gene for the disease:
There is genetic heterogeneity, and there are probably a number of genes. In some
cases it has been found that there is a mutation in a gene called GLI3 - a mutation
in this gene can cause the postaxial type, but to compound the problem, it can also
cause mixed cases where one family/person has polydactyly of both postaxial and
preaxial types. There are probably also other genes that have not yet been found.
The location: The location
of the GLI3 gene is on chromosome 7p13, and there may also be other genes as well.
Genetic testing
Diagnostic testing: At the
present time there is no simple test for identifying the mutation associated with
the non-syndromic type of polydactyly. In very large families it is possible to
perform linkage analysis (see: Indirect testing for genetic markers in a family that has a number
of patients - when there are a number of genes that can each cause the disease -
not all genes having been located / identified / mapped - autosomal dominant diseases).
Carrier testing: The test
for detecting a carrier of an abnormal gene in an autosomal dominant disease where
the condition is not clinically expressed is in fact the same as a diagnostic test.
Fetal testing: When polydactyly
is detected in pregnancy, where there are no other known cases of polydactyly in
the family, it cannot be determined definitively that this is the non-syndromic
type. An attempt can be made to rule out some of the differential diagnoses, mainly
by ultrasound examination and by ruling out the presence of other defects.
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