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EMANUELSYNDROME.ORG

Information on the 11/22 translocation and
Emanuel Syndrome
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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.

1122What test is used to diagnose the translocation and Emanuel Syndrome?

 A test called a chromosomal analysis (or G-banded karyotype) will reveal the balanced translocation and the extra derivative chromosome. Essentially, it is a picture of the chromosomes in a single cell of an individual. To get this test, your doctor orders a blood sample to be sent to a special laboratory called a Cytogenetics lab.

 

I have been diagnosed as a t(11;22) balanced carrier. What risks do I have if I want to get pregnant?

 Most of the literature we have seen up to now, gives the following statistics for carriers;

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 Canada, most major hospitals offer termination of pregnancy up to 22 weeks.

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.