Syndactyly (Fusion of Digits)
Syndactyly can occur with or without
polydactyly (supernumerary digits). The fusion can involve the skin between
the digits or the entire digit, including fusion of the bones, which is demonstrable
on X-ray, when the fused digit appears wider than normal. The fusion can occur only
in the proximal parts of the digits involved or along their entire length. The fusion
can include only two digits or all the digits of that limb, and can involve more
than one limb.
The existence of other defects or findings and additional cases in the family, as
specified below, is also important.
Clinical signs and inheritance pattern
The most common type of fusion is between the second and third toes. Usually only
some of the skin between the two toes is fused, and this does not constitute a medical
problem. This is hereditary and is very common.
Medically important genetic syndromes involving syndactyly
- In some cases there is only digital involvement without any associated problems-
the most frequent of these is multi-digit syndactyly. Usually this involves the
third and fourth fingers and the second and third toes. However, there may be other
types featuring involvement of other digits, with or without a supernumerary fourth
digit. In the more severe types, there is involvement of more digits and/or greater
fusion. Altogether, there are at least five types that can be differentiated by
the distribution of fusion of the digits. Essentially, the milder types are transmitted
dominant inheritance. Fusion of the fourth and fifth metacarpal bones in
the hand is transmitted by X-linked
inheritance. The more severe type involving fusion of all the digits is transmitted
- Syndactyly can occur together with polydactyly (supernumerary digits). Apart from
the syndactyly and the polydactyly, there are no other defects, although there may
be variations in the structure of the earlobe. This condition is known as poly-syndactyly
(see information sheet on polydactyly
- supernumerary digits). In these cases, the pattern of inheritance is usually autosomal
dominant. If the same condition is present in one of the parents, or in other relatives,
this supports the autosomal dominant pattern of inheritance. Sometimes it only becomes
apparent that an individual is affected after he or she has undergone a thorough
examination in order to look for the condition. Without asking questions and making
an in-depth investigation of the family, it is not always possible to know this,
as some cases are expressed very mildly and other relatives may not be aware of
them. If the same condition is found in other family members, including in one of
the parents, it can be assumed that this is isolated (non-syndromic) poly-syndactyly
as long as the affected individuals in the family have no other additional problems.
- Syndromic type - there are more than 150 syndromes involving other body systems.
This is a heterogeneous group of disorders, including chromosome disorders and other
syndromes resulting from a mutation in a single gene with varying patterns of inheritance.
These syndromes may involve defects in the eye structure, small head circumference
with mental retardation, cleft palate and lip, etc.
Penetrance is not full. In other words, there may be instances where members of
a family with many cases of syndactyly are born with normal digits, but will give
birth to children with abnormal digits - these family members carry the abnormal
gene for the condition but do not express it. In some families there may be some
children with syndactyly, with or without polydactyly, restricted to a single limb,
and others where all four limbs are involved.
Associated features that can be identified by imagery
In a certain percentage of cases there may be additional problems, and defects in
the eye structure,
small head circumference (usually associated with a relatively high risk
for mental retardation), cleft palate and lip, etc., must be looked for on ultrasound
If other problems are identified, this is not isolated (non-syndromic) syndactyly,
but a genetic syndrome of which the digit anomaly is only a part.
Some syndromes include structural defects detectable by ultrasound examination. Only a relatively
small number of these syndromes feature only functional problems such as mental
retardation, etc. without defects or changes in the body structure that are detectable
by ultrasound examination.
Therefore, when syndactyly is detected, further testing is very important in order
to confirm or rule out the presence of a syndrome, and performing amniocentesis
to confirm or rule out a chromosomal problem should also be considered. It is also
necessary to check for other defects in the digits such as polydactyly, shortening
of other digits, etc., and also in other body organs. An ultrasound examination
that gives a normal result apart from the syndactyly indicates a significantly reduced
risk of a genetic syndrome, but there is still a risk that is slightly higher than
the regular risk for defects and mental retardation (2- 4%). Thus there may be syndromes
in which the only additional feature apart from the syndactyly is mental retardation,
although the likelihood of this is not high.
What is the risk of recurrence in a subsequent pregnancy?
In isolated (non-syndromic) cases
If this is the first case in the family and is mild, with involvement of only some
digits, with or without polydactyly and without other defects, there is a high probability
that the condition in the child/fetus is a result of a new mutation in the gene
for syndactyly- 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. It must always be taken into account that
some cases are transmitted by autosomal recessive or X-linked inheritance, in which case the risk
of recurrence in the parents and in other relatives is relatively high. Therefore
it is important to establish the exact diagnosis and the risks for recurrence within
If 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 the abnormal gene
for syndactyly or poly-syndactyly, and the risk of transmitting this to the offspring
is 50% in every pregnancy, although it may not always be expressed. This risk also
applies to more distant relatives who carry the same abnormal gene. Because the
gene is not always expressed, one of the parents may carry it without having a defect
in his or her digits.
In severe cases of the syndromic type
In these cases, 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 25% in every pregnancy for syndromes transmitted by autosomal recessive
Molecular genetic information
The gene for the disease
Because there is genetic heterogeneity, it is necessary first to establish the exact
For the type involving a fusion of digits 4-5, the gene has been mapped to chromosome
6q22-q24. The gene responsible is the gene causing oculodentodigital syndrome, which
also involves the eyes and teeth.
The gene for the type involving fingers 3-4 and the fifth toe has been mapped to
chromosome 2q31-q32 and is called HOXD13.
The gene for the type involving fusion of the base of fingers 4-5 (not the fingers
themselves), which is transmitted by
X-linked inheritance, has been located, and is called MF4.
There are probably other genes that have not yet been found and that are responsible
for other types.
As stated above by type.
At the present time there is no simple genetic test for diagnosing the mutations
associated with the non-syndromic types of syndactyly. However, when the type is
clinically obvious and the gene has been identified, an attempt can be made to identify
In very large families it is possible to perform linkage analysis (see: indirect testing for
genetic markers in a family with one or more patients in the family - when there
are a number of different genes that can each cause the disease - the gene or most
of the genes have not yet been located / identified / mapped - autosomal dominant
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. In the recessive types, there are a very few syndromes involving syndactyly
where the gene has been found, and carrier status can be tested for in these families.
However, this is not usually necessary.
When syndactyly is detected in pregnancy, where there are no other known cases of
syndactyly 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