How to Conquer a Chromosome Abnormality, Part 1

I'm thrilled that Dr. Cody has written another post! Today, she discusses how attitudes can make all the difference when it comes to conquering chromosome abnormalities.

When a family is diagnosed with a chromosome 18 change, the next question is, of course, “What do we do? How do we treat it?” All too often, families still hear “There is no treatment. There is nothing that can be done.” How frustrating!! It leads us to wonder if this will always be the case. Will we ever get to the point where a physician says, “Ah! Yes, I’m very familiar with this condition and the recommended treatments. Here is what we need to do,”?

This is already happening for some other chromosome conditions, namely, Down syndrome. What can we learn from the study of Down syndrome? How did the Down syndrome community get to where they are today? What has made a difference in the lives of people with Down syndrome and how was that achieved?

The average life expectancy of someone with Down syndrome has dramatically improved over the last 40 years. The graph below illustrates this point by comparing the average age at death of someone with Down syndrome from 1968 to 1997. During the period of time covered by these data, no specific treatment for Down syndrome was developed. The changes in life expectancy are merely due to a change in attitude within the medical community. Physicians used to withhold treatment for people with Down syndrome. However, as parents and families advocated for their children, the medical community started applying standard medical care as warranted for specific symptoms. Their congenital heart conditions were repaired. They were screened for thyroid problems. If they developed leukemia, they were treated.

**This graph is from the Centers for Disease Control, Mortality and Morbidity Report.

Another major shift has been the change in society’s view towards people with disabilities. Over the course of the past several decades, families with a child with Down syndrome started keeping them at home with the family instead of placing them in institutions. I don’t think anyone will disagree that a family environment is superior and provides a child with better attention their specific health needs, not to mention more varied social interactions and learning opportunities. However, the graph also unfortunately shows that not all families have the same access to healthcare or receive the same respect for their concerns. Clearly, we still have some work to do to make sure that all families have access to the resources to keep their children healthy.

The lessons for us in the chromosome 18 community are two-fold. (1) We can make great progress if we advocate that our special children be treated the same as a child with normal chromosomes who presented with the same health concerns. (2) We need to continue to change society’s views on disabilities. We have come a long way from routine institutionalization, but there is still a long way to go. We need to make sure that all our children have access to all opportunities to lead a fulfilling life. From the opportunity to develop strong relationships with friends and families to the chance to follow a dream career, we need to continue to advocate for them. We could develop the “cure” but it won’t make a difference if we do not work to correct the social and ethical issues that hold our children back from having a full life.

Tea Time!!!

Well, today's the day! Happy Phantom Tea Day!! I hope that you are enjoying a cuppa something or other, wherever you happen to be! Me, I'm sticking with the hot chocolate...


In the interest of full disclosure, this photo was taken last winter--this week-end I managed to spill an entire Diet Coke in my purse, which was holding my camera. Perhaps it is needless to say that I was unable to resuscitate the camera. But, rest assured that I drank a cup of hot chocolate today in honor of the Phantom Tea!

I hope that you all had a lovely day! And also, just because the actual day is almost over, it doesn't mean that we are no longer accepting Phantom Tea donations!! Keep sending your friends and families to the Registry website to make a donation!

The Dynamic Duo

Phantom Tea Practice continues!! Here's Dr. Jannine Cody, founder and director of the Registry and the Clinical Research Center, with her daughter, Liz, the inspiration for it all! If I'm not mistaken, they are sitting in their dining room, which is one floor above the Registry office!


Have you sent out your Phantom Tea invites? Or have you donated? Are you enjoying your cup of tea right now? Me, I'm sipping on some hot chocolate. A few more calories than tea, perhaps, but just as warm! And since it is all in the name of the Registry, those calories don't count anyway, right?!

Phantom Tea Practice...

Hard to believe, but the Phantom Tea is just around the corner!

Of course, the whole point of the Phantom Tea is that you don't really have to DO anything on a particular day...That's why it is the easiest fundraiser around! All you have to do to participate is donate to the Chromosome 18 Registry & Research Society. However, once the donation is made, you are invited to enjoy a cup of tea on December 5th in honor of all those families touched by a chromosome 18 change...

Some members of the Registry's Board of Directors have already started practicing for the big event. Here's a picture of Denise Parker, Treasurer of the Registry, and her daughter, Rebecca, enjoying a cup of hot chocolate in a tea house!


I'd love to get a collection of pictures of people enjoying tea (or other beverages!) in honor of the Phantom Tea...If you think of it, snap a picture of yourself and your tea and send it to me at seboldc@uthscsa.edu. I wonder how many pics I can collect!

American Society of Human Genetics Annual Meeting

Have you ever wondered what goes on at those huge genetic conferences? What happens when you get thousands of genetics nerds together in one conference center? Luckily, Dr. Cody, president of the Registry and director of the Research Center, has the answer! Earlier this month, she attended the American Society of Human Genetics Annual Meeting in Washington DC. Here's her first-hand summary of the conference!

A few weeks ago, I attended the American Society of Human Genetics (ASHG) Annual Meeting in Washington, DC. This is the main scientific meeting for all aspects of human genetics, including the latest in genetic research, clinical genetics and genetics education. I arrived a day early to do some additional business. I met with the Positive Exposure crew to discuss program planning. Our crew included Rick Guidotti (of course), Denise Parker and Liz Grossman. I’ll bet you did not appreciate the chromosome 18 friends were also very involved with Positive Exposure! Every year, ASHG holds a High School Educational Workshop in the city hosting the annual conference. Rick Guidotti has become a regular speaker at the event, and this year was no different! I am certain that Rick’s presentation surprises the students into seeing people in a whole new light and helps them see the humanity and beauty in everyone.

I also met with Victoria Miller (with the Trisomy 18 Foundation) and Dr. John Carey (Medical Advisor to the Support Organization for Trisomy 18 and 13, or SOFT) to discuss Trisomy 18 research strategies. We discussed the priorities for Trisomy 18 research as well as strategies for building a research coalition and raising the necessary funding.

After these two major strategy meetings, the conference finally began! I won’t bore you with the latest advances on copy number variation, exome sequencing for finding new disease genes, or massively parallel sequencing technology. Learning about the latest and greated in genetic technology is the official reason that everyone goes to this meeting. But real reason for attending is to see old friends who share the same type of insanity: a love of genetics and an unquenchable desire to figure out how it all works – even in the face of diminishing funding. Many of my old friends are, like myself, former Genetic Alliance board members. For example, I had the chance to catch up with Donna Appell (President of the Hermansky-Pudlak group), Wendy Uhlman and Ann Smith who are genetic counselors, Mary Ann Wilson (NF Inc.) and Vivian Ota Wong (now at NIH). It is always exciting to hear about the new paths their lives are taking. It is hard to believe that I have been attending this meeting for 20 years and still seeing some people I met at my very first meeting, like Steve Groft from the NIH Office of Rare Diseases and Karen Ball President of the Sturge-Weber Foundation. Many of you know our long time Program Officer from the NIH, Mary Lou Oster-Granite. She was able to attend this year because the meeting was in DC. It is always good to touch base with her. With funding from NIH getting harder and harder to get, an encouraging word from her always keeps me from feeling too downtrodden and inept.

Every year, several thousand scientists present their research in a talk or a poster at the conference. There usually aren’t many people researching the chromosome 18 conditions, and this year was no different. There were only 3 of the more than 3000 posters or talks that were directly relevant to the chromosome 18 conditions. Again I was disappointed. One was about Tetrasomy 18p being a survivable condition based on a single patient – duh! The other two promised new insights into genes on chromosome 18. However, when I talked to each of the presenters, they each had major flaws in their data and incomplete literature reviews making their conclusions erroneous. So, I did not come away with much new information that was specific to our conditions. However, I did learn a lot about the latest technologies and came away with new ideas for experiments and grants.

All in all, it was a great conference, and I am looking forward to using my new connections, knowledge, and ideas to further our understanding of chromosome 18 conditions!

Replacing the "S" Word

In our last post, Dr. Jannine Cody talked about the importance of using the right words when talking about chromosome changes. Specifically, the word "syndrome" is not an accurate description of conditions involving deletions or duplications of chromosome 18. But, the question, then arises, what should we use in its place? In today's post, Dr. Cody talks about this dilemma!

Saying adios to the “s” word is the easy part. I have tried to stop using it for the past 10 years or so. But what do we replace it with? That’s the larger challenge. We may have to take different approaches with the different chromosome 18 conditions as we learn enough to differentiate subtypes of each condition. We embarked on this route last year when we divided 18q- up into proximal 18q- and distal 18q-. This was possible because, while everyone with an 18q deletion has different breakpoints, there is one very small region in the middle of the long arm that has never (so far anyway) been found to be deleted in anyone. This essentially cuts the chromosome arm in half and makes two groups; those with deletions closer to the centromere (proximal deletions) and those with deletions closer to the end of the long arm (distal 18q-). So, now we have broken up the term 18q- into “proximal 18q-“ and “distal 18q-“. The information on our website has been organized in this way.

This issue was really brought to a head with the recent identification of TCF4 as the first gene on chromosome 18 to be definitively defined as dosage sensitive. In other words, one copy of this particular gene is responsible for specific outcomes. Of all the genes on chromosome 18, we only expect that about 5-10% of genes will cause problems when present in one copy instead of two. So TCF4 is one of the key genes we have been trying to identify. To make this all the more important, those with one copy of this gene have a very different developmental progression and medical characteristics than most others with 18q deletions. So it is not only important to distinguish between proximal and distal 18q-, but also between those with and without TCF4 deletions.

Truly, these refinements in the nomenclature of 18q- are ground-breaking, and since we are treading where no geneticist has gone before, we need a new naming convention. Using the nomenclature proposed for single gene disorders as a starting point, I came up with a new naming convention:

Proximal 18q- for someone with a deletion of a region between the centromere 44 Mb.

Distal 18q- (TCF4 +/+) for someone with a deletion somewhere between 45 Mb and the 18q teleomere that does not include the TCF4 gene.

Distal 18q- (TCF4 +/-) for someone with a deletion somewhere between 45 Mb and the 18q teleomere that does include the TCF4 gene.

The +/+ symbol indicates that there are two copies of the TCF4 gene, and the +/- symbol indicates that there is only one copy of the gene.

We have now replaced the single term (18q-) with 3 new terms. And this is just the beginning. As we figure out which other genes are responsible for the features of 18q-, the list within the parentheses will get longer. But, at the same time, this means that our understanding of these conditions is growing as well. I don’t envision one day having a list of 30 genes as a part of someone’s formal genotype, but maybe only 5 or so key genes that will be informative about the prognosis.

I know some of the families whose children have 1 copy of the TCF4 gene as a result of a larger deletion refer to their child as having Pitt Hopkins, which they sort of do. But they may also have additional issues that are not related to the absence of the TCF4 genesuch as delayed myelination or hearing impairment based on the other genes they are missing. So between us, when people use the term Pitt Hopkins, we know what that means and does not mean, and that is just kind of a shorthand term. But just remember that your medical team is not as “in the know” about the nuances of this terminology and you may mislead them by using the term Pitt Hopkins when they actually have distal 18q- (TCF4 +/-). You may also mislead them by using the word syndrome. Without them even realizing it, they are programmed to expect that all kids with the same syndrome are pretty much alike. They may have expectations and biases regarding prognoses or treatments that are inaccurate. So, be knowledgeable and accurate about the terms you use.

The same issues will apply to 18p- and Ring 18 as we learn more about these conditions as well. Right now we are appreciating that about half of the people with 18p deletions have breakpoints very near the centromere. So this makes for two major groups 18p- (cen) and 18p-. Stay tuned for more information about how these are different. With regard to Tetrasomy 18p and full Trisomy 18, the majority of individuals have the same genetic abnormality, but they are still not syndromes because there are many different genes involved. For example, the features associated with trisomy 18 are caused not by the extra chromosome itself, but by the extra copy of the genes ON chromosome 18. So, in this way, there are actually 300 different causes for the features associated with trisomy 18!

When I was defending my PhD dissertation, John Opitz (a towering figure in human genetics – figuratively and literally) asked me if 18q- was a syndrome. As I explained my answer, I realized that I had better stop using that word. I asked him what term he would suggest and he said, “the phenotype associated with a deletion of 18q.” That is kind of a mouthful. So when forced I use the term “condition” when talking about the outward presentation (phenotype) and the word “abnormality” when talking about the genetic component (genotype). But I still find it hard after all these years to completely jettison the “s word”.

What's in a Name?

Today's post is the first in a two-part series about the importance of the terms we use. It was written by Dr. Jannine Cody, president of the Registry and director of the Chromosome 18 Clinical Research Center!

I once read an article in a medical journal in which the author made the comment that Trisomy 21 was the leading cause of Down syndrome. My first thought was, “Well, duh!” I wondered what else he thought could cause Down syndrome...Maybe bad karma? But I have come to appreciate that there are fundamentally different approaches to describing a condition. In the case of Down syndrome and trisomy 21, the two terms seem synonymous and are often used interchangeably. But, in our world, where each individual has a slightly different chromosome change, the terms “trisomy 21” and “Down syndrome” are significantly different. The term “trisomy 21” describes a genetic change, namely, an extra copy of chromosome 21. The term “Down syndrome” describes the collection of medical and developmental issues that are caused by the extra chromosome. We need to understand the difference and be sure we use the correct terms. If we don’t, then we inadvertently send the wrong message to the medical community.

A syndrome is a group of characteristics that often occur together and therefore are presumed to have the same underlying cause. So, syndromes are defined by the physical characteristics or medical findings (what I usually call the “phenotype”). In many cases, the cause is unknown – or, at least, the cause was unknown at the time that someone recognizes and names a group of characteristics that co-occur in more than one person. An example is Pitt Hopkins syndrome. This is a group of characteristics that includes a broad mouth with full lips, breathing abnormalities, and severe intellectual disability. People who fit this clinical description were said to have Pitt Hopkins syndrome. Now we know that the syndrome has 3 possible causes. In other words, abnormalities in one of three different genes can cause Pitt Hopkins syndrome. So now they are renamed Pitt Hopkins-like I, Pitt Hopkins-like II etc. This renaming aligns the genetic cause (genotype) with the clinical presentation (phenotype).

However, many chromosome abnormalities, like 18p-, 18q-, Ring 18, Tetrasomy 18p and Trisomy 18 are defined by the genetic abnormality rather than the physical characteristics. In the 1960s, chromosome analysis was just starting to be performed on babies with severe developmental problems and multiple malformations in the hopes that it would provide answers about the cause of their problems. Indeed, these and other chromosome abnormalities were found in some of these children. The next step was to define the characteristics of people with each of these “syndromes.”

Hopefully, you have noticed the inconsistency here. The term syndrome should not have been applied here. These conditions were not defined by their physical characteristics but by their underlying genetic change. However, some reverse thinking was applied. Researchers looked for a consistent set of features that would co-occur with each chromosome abnormality. Rather than starting from the physical characteristics (or syndrome) and looking for the genetic change, they started from the genetic change and looked for the physical characteristics. As if each chromosome abnormality was a single entity.

There is another reason that the word “syndrome” is not appropriate to use for chromosome abnormalities. On the molecular level, chromosome abnormalities are very different.

18q- is an excellent illustration of this point. First, we must ask the question, “What is 18q-?” The answer might seem straightforward at first…It is a deletion of a part of chromosome 18q. But what part? You will notice that there is no medical problem, no phenotype associated with this definition. 18q- (and the other chromosome 18 abnormalities) are defined by the genotype. But which genotype? I could easily find 5 people, all with 18q-, with deletions do not overlap with each other. So, at the molecular level they all have unique causes for their condition, but yet they all have 18q-. At some level, people who do not really want to think about it too hard will want to lump them all together for simplicity sake. But for parents who are trying to find other families with children like theirs, who are trying to learn about specific prognoses and treatments, the finer we can define the condition the better. So we better stop using the word syndrome because it implies things to the medical community that are not accurate about our conditions.

So, this leads to our next question...What term should we use instead of the word "syndrome"? That will be the topic of our next post!

The Easiest Fundraiser Ever!

For many of us Registry-types, the arrival of fall means more than finding a Halloween costume, sending out greeting cards, and throwing the idea of "healthy eating" out the window.

For us, it marks the season of the Registry's annual Phantom Tea!

2010 is the 16th year that we have held this fundraiser, if you can believe it! I think that the thing that makes this fundraiser such a great success is the fact that it is simply so stinkin' easy! It isn't like, say, a gala, where you have to buy a dress or rent a tux or arrange for a taxi and a babysitter, all of which costs a pretty penny. And those pretty pennies don't actually go to helping the organization!

For those who don't know, the beauty of the Phantom Tea is that you don't actually have to DO anything, other than make a donation, in order to attend the event! We do invite you to enjoy a cup of tea on December 5th in honor of the individuals with chromosome 18 conditions and their families. But, if you're too busy or forget or simply don't like tea, we're just as happy with a simple donation!

Are you interested in participating? Head over here to read our invitation and follow the link to the donation page!

Are you interested in inviting others to participate? Even better!! There are a few ways to do that! You can...

1. Send them to the Registry homepage, where they can follow the links to the donation page.
2. Copy and paste the invitation into the body of an email and link to the donation page.
3. Contact the Registry office and request invitations to send to your friends and families
4. Invite your friends via Facebook! We have a page set up, and once you've RSVP'd, you can let your friends know about the event by inviting them to "attend" as well!

As for me, I'm already set for December 5th. I'm looking forward to enjoying a cup of hot raspberry tea...Mmmmm.

The big question I'm having is which teacup to use. You see, I collect teacups. I get one whenever I travel. I'm thinking that, in honor of the Phantom Tea, I'm going to bust out the fancy cups from St. Petersburg, Russia...


Now the main question is which cup! Or maybe I should just drink four cups of tea!

Ten Things To Bring to a School Meeting

I've linked to this blog before, but I happen to think that a recent entry on this page deserves some linky goodness as well. It comes to us from stark.raving.mad.mommy, who has several children with special needs.

I've heard a lot of parents talk about the challenges of the school meeting. The blog authoress has provided a few useful tips for a successful school meeting. Enjoy!

In the Name of Love

As I posted a couple of weeks ago, I just recently had my first baby. He was born at 38 weeks, a healthy 7 pounds, 12 ounces. According to his discharge papers, the pregnancy and delivery were “uneventful”. Even as I read that now, I have to giggle a little. Uneventful? Really? Is that what you call 9 months of discomfort, stretch marks, and worry, followed by 24 hours of intense pain, ending with the arrival of a totally helpless little baby who depends on you to meet his every need? To me, that seems pretty eventful.

Even though the pregnancy and delivery were uneventful, we did have one small “event” at his first pediatrician’s appointment. He was diagnosed with jaundice. His bilirubin levels were significantly elevated, but not enough to warrant intervention. At his 8 week appointment, he still looked a little yellow, but his bilirubin levels were only mildly elevated. Nothing to worry about. At least, that’s what the pediatrician says. As his mother, though, I’m holding him up in every different kind of light, staring at the whites of his eyes, asking, “Does he look yellower to you? Is that a sunbeam? Please excuse me while I go set my baby down in it!” My cat is starting to get jealous because the baby is stealing all of his sunbeams!

This has all gotten me thinking…If my experiences with pregnancy and delivery were uneventful, what would an EVENTFUL one be like? If I’m worrying this much over jaundice, a relatively common issue in newborns, what would it be like to have an UNCOMMON issue identified in my son?

Over the course of my ten years in the field of genetic counseling, I’ve taken hundreds of pregnancy and medical histories. So many of the families I’ve met have experienced those “eventful” pregnancies and those “uncommon” medical issues. They were seen in the high risk pregnancy clinics, and their children see specialists and therapists in addition to their pediatrician. Of course, I always knew that these families face unique and difficult challenges. I’m starting to realize, however, that I didn’t fully understand or appreciate the stories that these families share with me. Let me explain.

Parents of children with special needs are forces to be reckoned with. They advocate tirelessly for their children. They fight for better services in the school system. They seek out second (or third or fourth) opinions on how to best care for their child. They become the experts, teaching their child’s providers about their child’s condition. They reach out to other families in similar positions, searching for new ideas and support. Before I was a parent, I wondered at the depths of parental love. The lengths that parents would go to on behalf of their child astonished me. Now that I’m a parent, I understand the words “love” and “devotion” so much better. I cannot think of anything I would not do for this little guy, if/when the need arises. I would step in front of a bus for him without a second thought.

With this deeper understanding, though, comes an even greater awe of the families of children with special needs. In the moment it takes a doctor to utter a diagnosis, reality shifts for those parents. Suddenly, challenges such as sleeping through the night and potty training become secondary to more pressing concerns. “Will my child need surgery? Where can I get an apnea monitor? How can I get more therapy? Will our insurance cover this? Am I making the right decisions for him? Is there anyone else out there dealing with this?” Those dilemmas make routine parenting issues seem minor.

As a new mom, I’m sometimes overwhelmed by my new responsibilities. Feeding, changing, bathing, and soothing the baby alone seems to be a full-time job. And then there’s the household chores, the errands, the part-time job, and the occasional social outing. As I put the baby to bed, I always ask myself the same question, “Where did today go, and why couldn’t I get everything done?”

Parents of special needs children have all of those “typical” things on their plate, but they also have to make and keep all their doctor and therapy appointments, deal with insurance companies, attend IEP meetings, do research on their child’s condition, and more. And some parents go even further, and start raising funds for research, volunteering to organize events, keep blogs, etc. and so forth. Amazing. I’m not sure how they do it, but they do, and I am in awe of them.

So, in summary, having a baby of my own has given me a deeper understanding and appreciation for the parents of children with special needs. They go above and beyond, and all in the name of love.

And, well, because I’m a proud momma, I can’t help posting two pictures of my little boy, who is teaching me new things every single day.