The 11/22 Translocation
Carriers of the balanced t(11;22) are considered expected to be
to be normal in every respect, except for the challenges they
can face when trying to have a baby. It is not something you (or
your parents) could have prevented. It is usually passed down
through the generations, but may not be identified until a
carrier has difficulties with infertility, repeat miscarriages
or has a child affected by Emanuel Syndrome.
There are many different types of translocations, however the
t(11;22) is known as a reciprocal translocation and is the most
common recurring reciprocal translocation seen in humans. A
reciprocal translocation means that there is a two way exchange
of information between these two chromosomes. Nothing is missing
and nothing is extra, thus making a carrier of this
translocation “balanced” in terms of genetic information.
Translocations are a relatively common occurrence (1 in 500
people are estimated to have one) and there is nothing you did
to make it happen. Translocations can occur between any
chromosomes. It
happens in unrelated families, from various ethnic backgrounds.
It can be found going back several generations in some families.
It also has been found, rarely,
to happen spontaneously in some carriers.
When a carrier is identified and neither of their parents have
the same translocation, it is called a
de novo
occurrence. Dr. Beverly Emanuel and colleagues have done
studies which show that this specific translocation can
sometimes be found in only in the sperm of normal males (no
other cells are affected with the translocation) and thus they
can go on to have children who can be 11/22 carriers, and their
children in turn have a risk of producing a child with Emanuel
Syndrome.
When a
carrier is identified there may be other family members who are
tested and identified as carriers. It is almost always the case
that one of their parents is a carrier of the translocation as
well. It will be important once a carrier is found in the family
to make other family members aware of their own chances of being
a translocation carrier. If a carrier has other children who do
not have Emanuel Syndrome, it will be important information for
them when they reach the age of reproduction, and testing to
determine if they are carriers is recommended.
How does the
balanced translocation happen?
Most people
with this translocation have inherited it from one of their
parents. You may not have known about this being passed down
from generation to generation. It is a completely random event;
there is nothing you can do to stop it from being passed on, and
there is nothing that makes passing it on more likely.
How did it happen in the first place? Many generations
back, likely in a male relative’s sperm, chromosomes 11 and 22
switched q arms. These two chromosomes have something in common;
they both have PATRRs (see above) in their DNA sequence, which
makes them prone to breakage in that area. If a chromosome
breaks, it often latches on to another broken chromosome end
nearby. The two ends fuse together and become a new chromosome –
which we call a “derivative.” The derivative chromosome can be
passed on to future offspring, and it can also cause problems
with how chromosomes segregate – that is, how they are divided
up during the process of making eggs and sperm. This is why some
balanced translocation carriers have trouble conceiving a
pregnancy, and how you can end up with a pregnancy in which the
baby has an unbalanced karyotype.
I have been diagnosed as a t(11;22) balanced carrier. What risks
do I have if I want to get pregnant?
If you are a
female carrier of the t(11;22):
-
you have an approximately 5-6% chance of having a child with Emanuel Syndrome for each pregnancy conceived
-
you have an approximately 55% chance of having a child who carries the balanced translocation for each pregnancy conceived
-
you have a 23-37% chance of having a miscarriage for each pregnancy conceived
If you are a
male carrier of the t(11;22):
-
you have an approximately 2-5% chance of having a child with Emanuel Syndrome for each pregnancy conceived
-
you have an approximately 40% chance of having a child who carries the balanced translocation for each pregnancy conceived
-
you have a 23-37% chance of your partner having a miscarriage for each pregnancy conceived
In our
recent study of t(11;22) carriers who have a child with Emanuel
Syndrome (Carter et al,
2009), we noted the incidence of miscarriage for those families
to be higher. These findings
cannot be considered as
official risks, as there is a bias in how we obtained the
figures (we didn’t survey all carriers, only carriers who have
accessed the website). In order for us to do a more complete
study on true risks for t(11;22) carriers, a scientific study
with a control group would need to be performed. Keeping that in
mind, for the purposes of this booklet we will share the results
of the carriers surveyed.
Our study
counted 66 female carriers and 5 male carriers, all of whom had
at least one child with Emanuel syndrome, with a total of 297
pregnancies. Out of that number:
For Females:
66 female carriers had 277 pregnancies.
Of those 277
pregnancies:
-
57 pregnancies resulted in a liveborn infant with Emanuel Syndrome,
-
138 of the pregnancies were lost to miscarriage or selective abortion; (approximately 50%), and
-
The remaining pregnancies produced a healthy child who had either a normal karyotype or the balanced translocation (30%)
For Males:
5 carriers partners had 20 pregnancies:
-
1 of the children was born with Emanuel Syndrome (5%)
-
10 of those pregnancies were lost to miscarriage or selective abortion (50%)
-
The remaining pregnancies produced a healthy child who had either a normal karyotype or the balanced translocation (45%)
As this was
not a scientific study of carrier pregnancy outcomes, we did not
separate miscarriage and abortion outcomes during the study.
They are listed together now only to indicate a negative outcome
of the pregnancy. While the outcomes are not definitive risks,
they do show that there can be a significant chance of having a
child with Emanuel Syndrome, or losing a pregnancy to
miscarriage.
There are
t(11;22) carriers in our group who have had more than one
natural child born with Emanuel Syndrome. We also know of a few
pregnancies that resulted in the birth of twins both affected by
Emanuel Syndrome, and one family who has twins where only one of
the children was affected with Emanuel Syndrome.
Most often,
in about 90% of the cases of Emanuel Syndrome, it is determined
that the mother is the carrier of the balanced t(11;22).
Carriers will have some eggs/sperm that will be completely
normal – ie – not affected by either the balanced translocation
or have the extra marker chromosome present, but some of the
eggs/sperm will contain the extra chromosome that results in
Emanuel Syndrome. It is theorized that, for parents of a child
with ES, women are more frequently found to be the carrier
because sperm carrying the extra chromosome may be less able to
fertilize an egg than normal sperm. However, women’s eggs, no
matter if they carry the extra chromosome or not, seem to have
equal chances of being fertilized.
Many members in our group who carry the t(11;22) have had experience with multiple miscarriages, periods of infertility, and some know what it is like to lose a child. No matter what you are going through, there will be someone for you to talk to who understands all of these heartbreaks and frustrations. There are also a lot of success stories and people who can give you the hope.
Are there
any risks to being a balanced carrier beyond fertility
issues?
To date, despite previous studies that referred to a greater
risk of breast cancer for balanced t(11;22) carriers, no medical
risks have been definitively confirmed in carriers. The study by
Dr. Melissa Carter and colleagues in 2010 analyzed 80 pedigrees
and found that the risk of breast cancer was not increased over
the general population.
The study did find a higher incidence of melanoma and
esophageal cancer, but this would have to be investigated
further to prove any true correlation. The number of people in
this study was too small to confirm a statistically significant
correlation, meaning that the findings may have occurred
strictly by chance.
Am I at risk
for complications during pregnancy?
Carter et al (2009)
found that out of 63 female carriers studied, approximately 80%
had no pregnancy complications during the pregnancy with their
child with ES. The reported complications that did occur
included intrauterine
growth restriction (small baby) in 24%, decreased fetal
movement (18%),
oligohydraminos (too little amniotic fluid) in
16%, vaginal bleeding (11%), breech presentation (14.5%) and
prematurity 9.5%). Most mothers though, had completely normal
pregnancies.
I want to
have more children. What are my options?
Many factors
will affect your decision to have more children. Some carriers
make the decision to have a natural pregnancy and rely on
prenatal testing to determine if the unborn child has Emanuel
Syndrome. They can then make the decision to continue the
pregnancy or to terminate. Some carriers know ahead of time that
their child has Emanuel Syndrome, and they were better prepared
before their child’s birth about what to expect.
Others may
choose
preimplantation genetic
diagnosis – a special procedure where the egg or sperm
is taken out of the carrier parent and can be tested to ensure
that it is either balanced or unaffected before being implanted
into the mother. There has been some success with this method of
reproduction. Unfortunately, it is not covered by most health
insurance plans, and is quite expensive.
Carriers may
opt to use donor eggs or sperm implanted through
in vitro fertilization
(IVF). Some health insurance plans will cover this
procedure. Unfortunately, the success rate of achieving a
pregnancy by IVF is lower than we would like.
Other
translocation carriers may decide to adopt.
There are
many carriers in our support group who have used all of these
ways to have more children.
Whatever option you choose will be right for your family,
and will based on your own personal and/or religious views.
Talking to other carriers as well as your genetic counselor or
family physician will help you and your partner decide which
route is best for you.
What testing
is required to diagnose a fetus when pregnant?
When you are
between 10 and 12 weeks gestation, you can have
chorionic villus sampling
(CVS) or
amniocentesis
when you are between 15 to 18 weeks pregnant. These procedures
take either a piece of the placenta or some cells from the
amniotic fluid surrounding the baby, and a chromosome analysis
is performed on these cells in the lab. Based on these results,
you will know whether or not the baby has the extra chromosome
that causes Emanuel syndrome.
Some people
who are already facing fertility issues are reluctant to have
one of these procedures, because they slightly increase the risk
of having a miscarriage. It is possible to get hints about
whether or not the baby has ES based on ultrasound, but it is
not nearly as accurate. Also, by the time the ultrasound shows
abnormalities (if at all – most pregnancies will have normal
ultrasounds), it may be too late to have a pregnancy
termination, if that is your wish.
Pregnancy
termination (also called abortion) is not an option that
everyone will consider. However, if you choose to have prenatal
testing by CVS or amniocentesis, and the baby is affected, you
will be offered termination if it is legal in your area. If you
wish to have a pregnancy termination and it is not legal in your
area, you can ask your doctor to refer you to another state or
country for the procedure.
In
I have other
healthy children. What are the chances that they carry the
balanced translocation?
Siblings of children with Emanuel Syndrome have a 50% chance of inheriting the balanced translocation from the carrier parent, and 50% chance of having normal chromosomes.