TREACHER COLLINS SYNDROME:
GENETIC UPDATE
a publication of :
TREACHER COLLINS FOUNDATION
April 1996: Thank you for your interest in the genetics of Treacher
Collins syndrome. The Treacher Collins Syndrome Collaborative Group
(composed of the genetic research teams directed by Dr. Michael Dixon
of the United Kingdom and Dr. John Wasmuth of the University of
California, Irvine) discovered the location of the gene for Treacher
Collins syndrome, Treacle. The information about this discovery
appeared in the following article:
The Treacher Collins Syndrome Collaborative Group (1996). Positional
cloning of a gene involved in the pathogenesis of Treacher Collins
syndrome. Nature Genetics.
The following letter explains what this discovery means; it is
reprinted from correspondence with Dr. Michael Dixon.
Should you need further information or have any questions, feel free
to contact the Treacher Collins Foundation at the above location or
the Alliance of Genetic Support Groups at:
It is with a great deal of excitement that I am writing to you, in
that I am pleased to be able to let you know that a gene that is
"faulty" in Treacher Collins syndrome has finally been identified.
This is a very recent discovery that has arisen from a collaborative
research project between members of both my own laboratory and that
of Professor John Wasmuth at the University of California, Irvine,
USA. I do so hope that despite the time that the research has taken,
you will be pleased about what benefits this will have both in the
short and longer term. Firstly, let me point out that there is, as
always, still a lot of work that remains to be completed before we
have a completely clear picture of how the gene works and what
problems in the gene occur in people with Treacher Collins syndrome.
Nevertheless, this work is on-going and we hope that we will continue
to make progress in the research so that we can help to provide the
best possible care and advice for families with Treacher Collins
syndrome.
In terms of benefits that will result from the discovery, there are a
number of points that I should like to make. Firstly, we will, in the
fullness of time, be able to assess each family to see if the same
gene is faulty in all families with Treacher Collins syndrome.
Secondly, we hope to be able to perform more accurate diagnosis for a
much greater percentage of families (this will apply to both pre- and
post-natal diagnostic predictions.) This is slightly complicated by
the fact that, to date, the fault in the gene is different in every
family with Treacher Collins syndrome. This does not create a problem
for those families where we have identified the fault, but will be
more problematical in families where this remains unidentified, as it
can take quite some time to track down the problem in any single
family. This is one area where we are continuing to work very hard as
we have only been able to identify the problem in a percentage of
families to date. The potential for being able to make diagnostic
predictions is, in my opinion, likely to have the most impact in
confirming the clinical diagnosis in very mildly affected patients,
where the features are very subtle and also in confirming that other
people are unaffected. This will be helpful in providing more
accurate genetic counselling.
Another area where this may well prove to be useful is where two
unaffected parents have produced an affected child, which is thought
to occur in approximately 60% of cases. Why is this important? In
situations where the parents are truly unaffected, the risk of them
having another affected child is very small, however, if one of the
parents is so mildly affected that it is difficult/impossible to make
a clinical diagnosis the risk of having a second affected child would
be much highter (50:50) for each and every pregnancy. Again, genetic
testing may be able to help in providing genetic counselling for
those families who are interested in this option. I think that it is
also extremely important to point out that we still will NOT be able
to make any prediction about the severity of Treacher Collins
syndrome in any individual. We are obviously happy to help out in any
way we can, however, I feel that it is important that any help that
we can give be coupled with similar help from local clinical
geneticists and genetic counsellors, so that you are able to more
fully discuss any concerns that you may have.
In terms of other benefits that may occur in the longer term, we are
now able to investigate other conditions which resemble Treacher
Collins syndrome in some way (e.g., Nager, Miller and "first arch"
syndromes), to see if they result from problems in the same gene.
This is probably a "long-shot", but is certainly worth pursuing. In
addition, research into the function of this gene during development
of the ear and the face will improve our understanding of the
formation of these tissues and will provide important information on
the problems in Treacher Collins syndrome.
I am aware that this discovery does raise a number of ethical
questions, however, I feel that if we work together in a careful and
sensitive way, these issues are by no means insurmountable. There is
still an enormous amount of work to be done before many of these
benefits will be fully realised, nevertheless, this is clearly a very
important and significant breakthrough. I realise that many of you
will have questions/concerns about the discovery of this gene and you
may feel that you would like to discuss things in more detail. I
should be happy to talk with anybody at greater length if they feel
that they would like to phone me on the number below. Early evening
is the best time to reach me as I am more likely to be in my office.
If you would like to talk with somebody other than myself or your
local geneticist/counsellor, Hope Charkins has kindly agreed to act
as a contact person for families from the USA.
Thank you for taking the time to read this letter.
With best wishes.
Yours sincerely,
Michael Dixon
School of Biological Sciences Phone/Fax:
TCF GENETIC UPDATE 3 APRIL 1996
Diagnostic Predictions and the Treacher Collins Syndrome Gene
by Michael J. Dixon, B.D.S., Ph.D.
School of Biological Sciences, University of Manchester (U.K.)
The recent discovery of the gene that causes Treacher Collins
syndrome has made possible more accurate diagnosis for a much greater
percentage of families with a history of Treacher Collins syndrome
(this will apply to both pre- and post-natal diagnostic predictions.)
Prenatal testing
Parents who are thinking about having additional children are often
interested in prenatal testing for a variety of reasons - not least
of which is allowing for improved medical care at delivery if another
child with Treacher Collins syndrome is born. If you are concerned
that future children might have Treacher Collins syndrome, prenatal
testing may be available. In this regard, the Manchester team is
happy to help out in any way that we possibly can, however, we feel
that it is essential that any help we can provide be coupled with
similar help from clinical geneticists and genetic counsellors. This
will ensure that you are able to more fully discuss any concerns that
you may have and will also ensure that ethical standards are
maintained. For those families who are thinking about prenatal
testing it would be advisable to consult a clinical geneticist prior
to becoming pregnant. The information that follows is an outline of
what is becoming available.
Prenatal testing is a possibility for families with a history of
Treacher Collins syndrome and would ideally be achieved from a
chorionic villus sample (CVS.) Information on the timing of CVS is
best obtained from your clinical geneticist/counsellor. While the
discovery of the Treacher Collins syndrome gene will make this test
more accurate than ever before, diagnosis is complicated by the fact
that, to date, the disruption in the gene is different in every
family with Treacher Collins syndrome that we have examined. This
does not create a problem for those families where the disruption has
been identified, but will be more problematical in families where
this remains unidentified. This is because the disruption in the gene
has to be located before it is possible to undertake prenatal
diagnosis and it may take quite some time to track down the problem
in any single family. The ideal thing from our own point of view
would be to analyse samples from parents who were interested in
genetic diagnosis well in advance of a potential pregnancy. This way
time would work for, rather than against, us.
It is also extremely important to stress that it will still NOT be
possible to make any prediction about how mildly or severely affected
a child might be. In this regard, high resolution ultrasonography can
also detect features of Treacher Collins syndrome prenatally, but
usually not before twenty weeks of pregnancy. You should consult a
radiologist who is experienced in visualizing the eyes, jaws, chin,
ears, etc. Ultrasonography, however, is not a definitive diagnostic
procedure and a fetus with mild features might not be detected. The
way to proceed might be to use the two tests in conjunction with one
another and this is another area in which it is advisable to seek
advice.
Postnatal diagnosis
The potential for being able to make diagnostic predictions is also
likely to have a large impact in confirming the clinical diagnosis in
very mildly affected patients, where the features are very subtle and
also in confirming that other people are unaffected. This will be
helpful in providing more accurate genetic counselling. Another area
where this may well prove to be useful is where two unaffected
parents have
produced an affected child, which is thought to occur in
approximately 60% of cases. Why is this important? In situations
where the parents are truly unaffected, the risk of them having
another affected
child is very small, however, if one of the parents is so mildly
affected that it is difficult/impossible to make
a clinical diagnosis, the risk of having a second affected child
would be much higher (50:50) for each and every pregnancy. Again,
genetic testing may be able to help in providing genetic counselling
for those families who are interested in this option.
TREACHER COLLINS FOUNDATION:
POSITION STATEMENT ON GENETIC DISCOVERIES
IN TREACHER COLLINS SYNDROME
The gene for Treacher Collins syndrome, Treacle, was discovered in
1995 by The Treacher Collins Syndrome Collaborative Group, composed
of the genetic research teams of Dr. Michael Dixon of the University
of Manchester, United Kingdom, and Dr. John Wasmuth of the University
of California, Irvine, U.S.A. Treacher Collins syndrome is a
craniofacial anomaly. It is caused by a gene mutation that is, so
far, different in every family. The mutation occurs before conception
affecting one out of every 10,000 live births.
With the discovery of this gene, accurate diagnosis of Treacher
Collins syndrome in a person is now possible with a blood test.
Reliable pre-natal testing can also be performed at the time when the
Chorionic Villus Sampling (CVS) can be performed. A genetic
professional can offer guidelines about the timing of the CVS.
Pre-natal testing can only indicate whether the fetus carries the
gene; it cannot determine how mildly or severely affected the fetus
might be. For those families who are thinking about pre-natal
testing, it would be advisable to consult a clinical geneticist prior
to becoming pregnant.
As with many genetic discoveries, scientific recognition of the gene
for Treacher Collins syndrome, brings ethical, legal and social
implications to the forefront. The Treacher Collins Foundation will
facilitate discussion about these issues and continue to be a
clearinghouse to individuals, families, professionals and the public
for information and support regarding Treacher Collins syndrome.
While the Treacher Collins Foundation will offer referrals to the
genetic research groups studying Treacher Collins syndrome and
genetic professionals local to the inquirer, it is not our intent to
offer genetic counseling or serve as a replacement for genetic
counseling.
The Treacher Collins Foundation thanks Susan Hayflick, M.D. at Oregon
Health Sciences University, professional advisor to TCF, for
reviewing this document, "TCF Genetic Update."