Emanuel Syndrome

and the 11/22 Translocation

Emanuel Syndrome

The 11/22 Translocation

Learn more about The 11q;22q Translocation

  • Carrier & Prenatal Testing
  • Pregnancy, Miscarriage, Infertility
  • Reproductive Options
  • 11/22 and Cancer Risks

Carriers of the balanced 11/22 Translocation, also known as t(11;22), are considered 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 diagnosed with Emanuel Syndrome.

Stephanie and Julia visiting together in England – both t(11;22) carriers who met because of their children.

Reciprocal Translocation

There are different types of translocations, however, the t(11;22) is known as a reciprocal translocation. It 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. Including:
  • In unrelated families and from various ethnic backgrounds.
  • It can be found going back several generations in some families.
  • Also it has been found, rarely, to happen spontaneously in some carriers.

When a carrier is identified and neither of their parents has the same translocation, it is called a de novo occurrence. Dr. Beverly Emanuel and colleagues have done studies that show that this specific translocation can sometimes be found only in the sperm of normal males (no other cells are affected by 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 having a child with Emanuel syndrome.

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.
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 (Graphic provided by Dr. Beverly Emanuel)

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 (palindromic AT-ric repeats) 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.

Dr. Beverly Emanuel

In November 2021, Dr. Emanuel did a virtual talk about the history of the t(11;22) and her work. View this on our YouTube channel.

The t(11;22) – Carrier and Prenatal Testing

When one carrier of the t(11;22) 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.

Picture – Cousins with Emanuel Syndrome – both their mothers, who are sisters, carry the 11/22 Translocation, also referred as t(11;22).

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.

What test is used to diagnose the 11;22 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.

Testing to identify Emanuel Syndrome is also done using fluorescence in situ hybridization (FISH) and chromosomal microarray analysis.

Learn about genetic testing from the Children’s Hospital of Philadelphia.

New and novel approaches such as Next Generation Phenotyping (NGP – Face2Gene) using computer-aided facial dysmorphology analysis are starting to show promise, especially for patients living where there is limited access to newer genetic approaches, but are not yet in common use (Liehr et. al., 2017)

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 at least  15 weeks pregnant. These procedures take a piece of the placenta (for CVS) or some cells from the amniotic fluid surrounding the baby (for amniocentesis), 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.

Individuals 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 Emanuel Syndrome 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.

Carter et. al., (2009) found in a study of 63 cases, that less than 20% of congenital anomalies are found by ultrasound before birth, suggesting that a normal prenatal ultrasound cannot exclude a diagnosis of ES.

Reference

Carter, M. T., St Pierre, S. A., Zackai, E. H., Emanuel, B. S., & Boycott, K. M. (2009). Phenotypic delineation of Emanuel syndrome (supernumerary derivative 22 syndrome): Clinical features of 63 individuals. American Journal of Medical Genetics. Part A, 149A(8), 1712–1721. https://doi.org/10.1002/ajmg.a.32957 

The 11/22 Translocation – Pregnancy, Miscarriage and Infertility

Am I at risk for complications during pregnancy?

Carter et. al. (2009) found that out of 63 female carriers studied, approximately 80% had no 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%), oligohydramnios (too little amniotic fluid) in 16%, vaginal bleeding (11%), breech presentation (14.5%) and prematurity 9.5%). Most mothers did have completely normal pregnancies.

What risks do I have if I become pregnant?

FEMALE CARRIERS

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
MALE CARRIERS:
  • 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 2009 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 website 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.

Multiple Children with the 11/22 Translocation

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 as well as one instance of twins where only one of the children was affected with Emanuel syndrome.

Twins with the 11/22 translocation

Most often, in about 90% of the cases of Emanuel syndrome, it is determined that the mother is the carrier of the balanced 11/22 translocation. Carriers will have some eggs/sperm that will be completely normal – ie – not affected by either the balanced translocation or have the extra derivative 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 Emanuel Syndrome, 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.

Sisters who both have Emanuel Syndrome

Many members in our group who carry the 11/22 translocation have had experience with multiple miscarriages, periods of infertility, and some know what it is like to lose a child. There are even families who have had more than one child born with Emanuel syndrome. 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 hope as you build your family.

Support for miscarriage

References

Carter, M. T., St Pierre, S. A., Zackai, E. H., Emanuel, B. S., & Boycott, K. M. (2009). Phenotypic delineation of Emanuel syndrome (supernumerary derivative 22 syndrome): Clinical features of 63 individuals. American Journal of Medical Genetics. Part A, 149A(8), 1712–1721. https://doi.org/10.1002/ajmg.a.32957 

11/22 Translocation & Reproductive Options

If you are a carrier of a balanced 11/22 translocation, you may experience reproductive challenges. Women or men can carry the 11/22 translocation, either in their eggs, or sperm. You will want to ask yourself (and your partner) many questions about what being a carrier will mean as you plan to have children and you will want to talk to your doctor or genetics counsellor to ensure you have a complete understanding of your options. Are you prepared for the possibility of raising a child with disabilities? Are there ways you can ensure you have a child who is not affected by Emanuel syndrome? There are many things to think about. If you are newly diagnosed, this can be a very overwhelming thing to learn.

Many of our carriers have healthy children – some naturally, some by the use of reproductive technically (preimplantation genetic diagnosis with invitro fertilization). While some have chosen to adopt. 

I want to have more children. What are my options?

Many factors will affect your decision to have more children, some are:

  • Have a natural pregnancy and rely on prenatal testing to determine if the unborn child has Emanuel syndrome.
  • Continue the pregnancy or to terminate.
  • Knowing ahead of time that your child has Emanuel syndrome may help you better plan and prepare for what to expect.
  • Preimplantation genetic diagnosis. This is a special procedure where the egg or sperm is taken out of the carrier parent and 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.
  • IVF or in vitro fertilzation. This procedure is where carries may opt to use donor eggs or sperm and implanted through 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. 

Many carriers in our support group who have tried all of these ways to have more children and have tried naturally as well. Whatever option you choose will be right for your family, and will be based on your own personal views. Talking to other carriers as well as your genetic counsellor or family physician will help you decide which route is best for you.

Learn more about In vitro fertilization from the Mayo Clinic website

Support: Fertilitymatters.ca

Learn more about Preimplantation Genetic Diagnosis from the University of Utah 

Learn more about Adoption

Raising the Goddess of Spring and Chromosome 22 Central

The book Raising the Goddess of Spring contains stories of people who have experienced the challenges of being a carrier of a chromosome translocation. Learn about some families who have pursued alternative ways to grow their families, in the chapter Reproductive Considerations.

You can talk to other members of our group about their experiences. Please join us on Facebook.

If you are not ready to share with others yet, send us a message. C22C’s founder and the current president both have first-hand experience with the 11/22 translocation. 

Founder of C22C, Stephanie, carrier of a balanced 11/22 translocation, experienced several miscarriages and chose adoption. This is her story. The Adoption Option, excerpt from her book Raising the Goddess of Spring.

Whatever choice you make, there is likely someone in our group who has walked that path and will be able to talk with you.

Balanced 11q;22q Translocation & Cancer Risk

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.

Those of you who have been a part of our group for a period of time will be aware of past articles which have suggested a link between breast cancer and being a carrier of the 11/22 translocation. Below are references regarding this. While our own study with Dr. Melissa Carter in 2010 showed there was no increased risk, breast cancer is common enough and women should be aware of this risk and perform regular self-screening and mammograms as suggested by their physicians. A 2019 study did find there was an increased risk for breast cancer and suggested increased breast cancer surveillance for female carriers.

A link between the 11/22 translocation and the risk of developing cancer has been suggested in other papers, but more research is needed to confirm any definitive connection.

References

Carter, M. T., Barrowman, N. J., St Pierre, S. A., Emanuel, B. S., & Boycott, K. M. (2010). Risk of breast cancer not increased in translocation 11;22 carriers: analysis of 80 pedigrees. American Journal of Medical Genetics. Part A, 152A(1), 212–214. https://doi.org/10.1002/ajmg.a.33166 

Doyen, J., Carpentier, X., Haudebourg, J., Hoch, B., Karmous-Benailly, H., Ambrosetti, D., Fabas, T., Amiel, J., Lambert, J. C., & Pedeutour, F. (2012). Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and review of the potential link between the constitutional t(11;22) and cancer. Cancer Genetics, 205(11), 603–607. https://doi.org/10.1016/j.cancergen.2012.09.006 

Jobanputra, V., Chung, W. K., Hacker, A. M., Emanuel, B. S., & Warburton, D. (2005). A unique case of der(11)t(11;22),-22 arising from 3:1 segregation of a maternal t(11;22) in a family with co-segregation of the translocation and breast cancer. Prenatal Diagnosis, 25(8), 683–686. https://doi.org/10.1002/pd.1196 

Lindblom, A., Sandelin, K., Iselius, L., Dumanski, J., White, I., Nordenskjöld, M., & Larsson, C. (1994). Predisposition for breast cancer in carriers of constitutional translocation 11q;22q. American Journal of Human Genetics, 54(5), 871–876. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1918254/ 

Schoemaker, M. J., Jones, M. E., Higgins, C. D., Wright, A. F., UK Clinical Cytogenetics Group, & Swerdlow, A. J. (2019). Mortality and cancer incidence in carriers of constitutional t(11;22)(q23;q11) translocations: A prospective study. International Journal of Cancer, 145(6), 1493–1498. https://doi.org/10.1002/ijc.32031 

Wieland, I., Muschke, P., Volleth, M., Röpke, A., Pelz, A. F., Stumm, M., & Wieacker, P. (2006). High incidence of familial breast cancer segregates with constitutional t(11;22)(q23;q11). Genes, Chromosomes & Cancer, 45(10), 945–949. https://doi.org/10.1002/gcc.20358 

More Resources: What is Emanuel Syndrome? And be sure to download our free Emanuel Syndrome Guide for Families & Caregivers