History of Emanuel Syndrome and C22C

Introduction

Since our group began, we have found hundreds of children with Emanuel Syndrome and are aware of hundreds of carriers of the balanced t(11;22). Much of the information on this website has been obtained by information collected from our families, previously published medical reports, as well as results from a recent study on children with Emanuel Syndrome and t(11;22) carriers by Dr. Melissa Carter and colleagues.

Our children are amazing! If you have ever read a medical article on Emanuel Syndrome, you will not read that some of our children have some reading ability and can do a bit of math…have learned to skip rope, dribble basketballs and even have earned a yellow belt in Taekwondo! You will not read that some can ski with a bit of assistance, or enjoy horse riding. While not all of our children can do these things, some certainly can! All of our children have special gifts.

Let’s start at the beginning….

Balanced translocations have been estimated to occur in approximately 1 in 500 people; however, it is the t(11;22) translocation that is known to be the most common reciprocal translocation in humans. 

While the translocation itself is considered to be relatively common, there are not many children known in the world with the unbalanced version, known as Emanuel Syndrome. Between published cases and members of our group, we know of about 400+ cases. It is presumed that there are more cases in the world, especially in non-English speaking countries, but we cannot know for sure how many.

History of our group

In 1995, Maia was born to Stephanie and Martin St-Pierre, in Alberta, Canada. Stephanie had 4 previous miscarriage, and no knowledge that she was a t(11;22) carrier. Maia was identified as having unbalanced 11/22 translocation, or as it was then known, the supernumerary der(22) syndrome. Stephanie went on a search for others, and found them. In 1996, a group of 17 families came together who had affected children and created The International 11;22 Translocation Network. The natural evolution of our group came to be inclusive of all chromosome 22 disorders and was renamed to Chromosome 22 Central; however, our organization continues to support many families who have children with Emanuel Syndrome.

Articles on the unbalanced 11/22 translocation a.k.a Supernumerary Der(22) Syndrome date back to the 1970s.  Even earlier reports in the 1960s describe some cases of “trisomy 22,” a distict condition which was confused with Der(22) syndrome in the early days of chromosome analysis. While not able to be conclusive due to the limited technology of the time, these reports likely describe children with unbalanced t(11;22).

Historically, the medical literature has offered many different terms for this disorder. Families found it difficult to connect with each other because of the different names given to their child’s condition. While technically known in the most recent past as the Supernumerary Der(22) Syndrome, it has also been termed partial trisomy 22q, unbalanced 11;22 translocation, erroneously in very early reports as Cat Eye Syndrome,  and even partial trisomy 11q. Many of the clinical symptoms seen in our children are also found in children who have trisomy 11q. It is the effects of the extra genes of chromosome 11 that likely cause the more serious developmental issues that our children have.

While numerous reports have been published about t(11;22) and the unbalanced syndrome, one researcher, a cytogeneticist at the Children’s Hospital of Philadelphia/University of Pennsylvania Medical Centre, has been consistent in her work on the subject. Several of our group members have participated in her studies. She and her colleagues were the first to describe the mechanism by which the chromosomes of a t(11;22) carrier get wrongly sorted into egg and sperm cells so that the extra derivative chromosome ends up causing problems. Dr. Emanuel’s laboratory has studied the DNA sequence of the derivative chromosome and discovered that all individuals have identical pieces of chromosome 22 and chromosome 11 switch places. They also were the first to describe the mechanism of formation of this translocation. Chromosome 22 is particularly prone to rearrangement because of DNA sequences called PATRRs (palindromic AT-rich repeats) found along the q arm.  This area of is also involved in the development of other chromosome 22 disorders, including Cat Eye Syndrome, the more common 22q11.2 Deletion Syndrome, and the 22q11.2 Microduplication Syndrome. It has also been involved in a recurring translocation with chromosome 8.

The name given to the disorder in 2004, Emanuel Syndrome, was chosen by our parent group to reflect the consistent contributions of Dr. Beverly S. Emanuel, a cytogeneticist at the Children’s Hospital of Philadelphia/University of Pennsylvania Medical Centre. Her long-standing dedication to research on t(11;22) dates back to the early 1970s and continues to this day. Her research has been invaluable in helping us understand why this translocation happens. This, along with her support of our efforts to get information on this condition out to the public, made it easy for our group to request her name be given to this relatively rare condition. The term “Emanuel Syndrome” was welcomed as a unifying name for our families, and is slowly being adopted by the medical community.  

Prior to her involvement, this condition did not even exist as an entry in the National Library of Medicine’s database, “Online Mendelian Inheritance in Man” (OMIM), which is a database of human genes and genetic syndromes. At our group’s request, this entry was added in November of 2004, with the ID number 609029. (http://www.ncbi.nlm.nih.gov/omim/609029).  It was our first step in getting this condition not only named, but properly recognized.

In 2007, Dr. Emanuel and colleagues graciously wrote an article for GeneReviews, an expert-authored database of genetic conditions, also through the National Library of Medicine. Emanuel Syndrome did not have an entry prior to this time. The new entry offered families current information on genetic counselling as well as an overview of the condition.  The entry was updated in 2010 after publication of our more recent studies, and can be found here:

http://www.ncbi.nlm.nih.gov/books/NBK1263/

The largest study ever conducted on people with Emanuel Syndrome was done in 2009, titled Phenotypic Delineation of Emanuel Syndrome (Supernumerary Derivative 22 syndrome): Clinical features of 63 individuals, by Melissa T Carter, Stephanie A St. Pierre, Elaine H Zackai, Beverly S Emanuel, and Kym M Boycott. It was published in the August 2009 edition of the American Journal of Medical Genetics. It was a landmark paper that gave current and accurate information about the condition, which was something that had been lacking. This paper was invaluable in getting information to families and their treatment providers.

A follow up paper which studied balanced 11/22 translocation carriers was released in the same journal, in January of 2010. Risk of breast cancer not increased in translocation 11;22 carriers: Analysis of 80 pedigrees; Melissa T. Carter, Nicholas J. Barrowman, Stephanie A. St-Pierre, Beverly S. Emanuel, Kym M. Boycott. There had been previous reports in the literature which suggested that balanced t(11;22) carriers were at an increased risk of breast cancer. We wanted to determine if there was a true risk or not. The study concluded that there was no increased risk in breast cancer compared to the general population

On November 22, 2010, our group held its first Emanuel Syndrome Day Campaign, which helped spread awareness through the cyber world. We will recognize this date, “11/22”, each year as a way to bring continued awareness of the condition.

In between these milestones, we have had opportunities to meet other members in special C22C “family reunions”. We have tried our best to educate each other on a very rare condition.