Blog Maintenance

Hi, everyone!

Just a note that I've added a few more chromosome 18 blogs to the list on the right of this page. When you have a few minutes, I hope that you will make a quick visit to their pages! They are some very talented and honest writers. And, of course, the photos they post on their blogs are simply fantastic.

Step 3: Syndrome Description

So far, we have gathered information about the effects of chromosome changes through (a) a literature review, and (b) a thorough series of clinical assessments. Now, it is time to pull together a syndrome description. This description is a comprehensive collection of all the different things that we’ve found in a group of people with a particular chromosome change. Some things might be quite common, such as strabismus in people with tetrasomy 18p. Other things might be seen in a minority of individuals, such as holoprosencephaly in people with 18p-. Other things might only be reported once, and it is unclear whether it is a consequence of the chromosome change, or perhaps it is completely unrelated to the chromosome change.

Once we’ve got the syndrome description, what do we do with it? Well, the first thing we want to do is share our description with others. We can do this in a couple of different ways. We write scientific papers for publication in medical journals to share information. We make presentations at various scientific conferences. We also share information with patient advocacy groups. In our case, this is mainly through the Chromosome 18 Registry’s website as well as at the annual Registry meeting.

The syndrome description gives families and providers an idea of what kinds of issues and concerns may arise in someone with a particular chromosome change. This gives them an opportunity to screen for problems, prepare for various possible outcomes, and just have a better idea of what kinds of things might pop up as a person ages. However, as most parents will tell you, a syndrome description is useful, but it most certainly is not the end-all, be-all. Although we are able to describe the different features that have been seen in people with chromosome changes, we cannot predict precisely who will get which features. There are still several steps that must be completed before we are able to provide personalized information based on a person’s specific genetic change.

Once we are able to fully describe the range of features that are associated with a condition, we can then start to figure out which ones are associated with different breakpoints. For example, we can ask questions such as, “What is different between people who have a breakpoint in 18q23.1 versus those with a breakpoint in 18q12.3?” In fact, this question leads us directly into the next step on the path to treatment: gene identification.

Step 2: Clinical and Molecular Assessments

Once we have completed the literature review, we can move on to the next step in the process: the clinical and molecular assessments.

Clinical Assessments. Using the information from the literature review, we can design a series of evaluations aimed at clarifying and expanding our understanding of the condition. The ultimate goal of this step is to understand how, precisely, the chromosome change affects a person. How does it affect development? What about bone structure? Does the chromosome change lead to any hormonal issues? How about vision? And hearing?

The information gathered in the literature review is critical in helping us with this step. Because we have been able to identify gaps in knowledge about the conditions, we can design assessments to fill in those gaps! Thanks to the literature review, we also know which features have already been described but still require additional investigations. For example, thanks to the literature review, we recognized that many people with distal 18q- have short stature. This led us to question WHY they have short stature. Is it because of a change in their bones? Is it because they are missing certain growth factors? We developed assessments that would help us answer these questions. We included bone surveys and growth hormone testing. We learned that many people with distal 18q- often have growth hormone deficiency! With that knowledge, we were able to start treating people, which, in many cases, led not only to an improvement in growth, but also an improvement in cognitive ability!

As you might have guessed from the example above, the phrase “clinical assessments” may refer to a pretty wide range of possible evaluations. It might involve an examination by a medical professional, such as a geneticist or an ophthalmologist. It might involve imagine studies, such as x-rays or an MRI. It could involve some blood work to look at different hormones and other substances in the blood. Surveys might be used to determine whether behavior and intelligence are affected by the chromosome change.

In addition to deciding which assessments to complete, it is also important to determine who will perform those assessments. Obviously, we want only highly-qualified professionals performing these evaluations. They should have advanced training in their area of expertise, and they should also have experience in working with people with intellectual or physical challenges. This is where our team of clinical investigators comes in. We have assembled a team of professionals who help us design informative evaluations.

In addition to designing the evaluations, our team of clinical investigators is also responsible for performing those evaluations. It is very important that every person we see is evaluated using the same protocols; ideally, the same professional would perform the evaluation as well! This is important because we want to make sure that any differences that we identify between study patients are not due to different procedures. In other words, by ensuring that every study patient goes through the same evaluation process completed by the same clinical investigator, we ensure that we are collecting the most reliable data!

One last word about our team of clinical investigators. All of our clinical investigators collaborators have one very important quality: the ability to think outside of the box. In addition to performing evaluations and making treatment recommendations, our clinical investigators must also be able to take their findings and move them to the next level. In other words, they need to understand underlying biological and molecular mechanisms and use that knowledge to identify novel treatments. This requires them to keep abreast of all the latest developments and technologies in addition to seeing patients, interpreting complex data, and writing manuscripts! No small feat!

Molecular Assessments.

While our clinical investigators are busy evaluating patients and interpreting clinical data, our laboratory technicians are busy examining the molecular basis of the chromosome 18 conditions. The molecular assessments we complete in the laboratory are focused on chromosome 18 and provide us with more data than tests run in clinical laboratories. This is important for two reasons.

First, we must confirm that everyone in a particular study group has the same chromosome change. We have to make sure, for example, that individuals in the 18p- study group do not also have a duplication or deletion on another chromosome. If there are other non-18 chromosomes involved, it is more difficult to determine the effects of a chromosome 18 change. For example, if a child with a heart defect has both a deletion on chromosome 18 as well as a duplication on chromosome 6, we would not be able to determine whether the heart defect is due to the missing genes on chromosome 18, the extra genes on chromosome 6, or a combination of the two!

The second reason that a molecular assessment is so important is that it allows us to determine which genes are involved in the chromosome 18 change. We use the latest technology to identify the precise locations of the breakpoints involved in a deletion or duplication. This is a critical step in understanding which genes lead to a medical or developmental problem. This in turn will tell us about the underlying biology of those problems, which will hopefully lead us to treatment and prevention options.

Once we have thoroughly assessed and evaluated many people with the same condition, it is time to pull all of our data together to create a syndrome description. This is the next step along the pathway to treatment.

Step 1: Literature Review

In order to plot out our research course for the future, we have to know where we’ve already been. What has already been studied? What questions have already been answered? What remains unknown? We answer these questions by completing a review of the medical literature.

Sounds easy enough, doesn’t it? We just need to do a quick search on PubMed (which catalogs all the manuscripts published in most academic journals). Then, we just read them all and VOILA! Literature review complete!

Unfortunately, this is not the way it works.

The first step in performing a quality literature search is the search itself. We often have to use multiple different search terms and weed through the results to find the articles that are relevant to our research questions. This is often easier said than done. For example, let’s say we want to look for all the articles ever published about 18q-. We would have to use multiple search terms, including “18q-“, “deletion 18q”, “de Grouchy syndrome”, and several others in order to capture all the articles that have been written about this condition.

Once we’ve created the list of articles we wish to review, we actually have to track down those articles! This is pretty straightforward, but it can be time-consuming! Some articles are available online, but many (especially the ones published several years ago) have to be manually located and copied. Or, if the library does not subscribe to a particular journal, the article must be ordered from another institution.

Usually, the stack of articles is at least several inches thick, if not more. Now the REAL work can begin! We read each article carefully and thoroughly, looking for information that is relevant to our research questions. We’re looking not only for information about the clinical features of the condition, but also information about the molecular nature of the genetic change. It is important to read all manuscripts with a critical eye and ask the question, “Does this relate to the questions we’re asking? Did the authors use appropriate methods to get their data? What are the conclusions of this paper? What impact does this paper have for the direction of our research?”

Of course, the literature review is not something that is every truly completed. Hundreds of articles are published every month, so we must repeat our original searches every so often to make sure that we catch any new information that is out there.

Once we have a good idea of what is already out there, we can move on to the next step in the research process: the Clinical Assessments.

Path to Treatments

When a child is diagnosed with a chromosome change, families often go through many questions in a very short amount of time. “How did this happen?” “What does it mean?” “What is the treatment? What is the cure?”

Our goal at the Chromosome 18 Clinical Research Center is to answer these questions. We want to be able to tell families exactly what to expect and how to deal with complications if/when they happen. Eventually, we want to be able to prevent complications from ever happening in the first place!

However, research is a time-consuming process. If we want reliable data and solid, publishable conclusions, we have to go about it the right way. Since families are an integral part of this process, it is important that they understand how things progress. In a series of posts, we’re going to discuss the various steps on the path towards treatment.

Supporting Rick Guidotti

Many of us know Rick Guidotti, the man behind Positive Exposure. Rick takes photos of people with various genetic conditions. His photos capture the breathtaking beauty of his subjects. We have had the privilege of having him at our annual conference many times and many of our families have been photographed by him. In fact, the beautiful rotating images on the Registry's website are all Rick Guidotti's.

So, I am sure that many will be interested to know about the documentary about Rick, entitled "On Beauty"! Here is a trailer for the film, which features video footage taken from the 2009 conference in Las Vegas! (Rated PG13 for language!)



The producers of the documentary are looking for funding to finish up the film, so there is not a definite release date yet. But, you can follow the latest on their facebook page, visit their official page, or even make a donation to the film here.

Once again, thank you, Rick, for all you do!

New Year's Resolutions

Holy moly!! I did not realize that it had been so long since I have posted on this here blog! Goodness gracious! Apologies!

It is so hard to believe, but that time of year has come again. Time to make those New Year's resolutions. There are so many possible resolutions to choose from, and at some point in my life, I am pretty sure that I’ve made every resolution out there. I resolve to lost weight! I resolve to save money! I resolve to respond to emails in a timely fashion! I resolve to start a garden! I resolve to learn how to cook! I resolve to keep my resolutions!!

Well, most of the time, these resolutions are forgotten until, say, December, when I look back at the year and wonder what happened to all of my good intentions. Then the guilt sets in and I promise myself that, next year, I’ll do better.

This year, it finally dawned on me that, maybe my dedication is not the issue. Maybe I’m just setting the bar too high for myself! I spent the last week of 2010 wondering what kind of resolution I could make that would still be attainable. Then, this morning, I finally came up with my resolution!!

On the whole, I think I'm a fairly positive person. But I don’t always share my positive thoughts with people when I have them. So, here's my resolution: I am just going to be a more publicly positive person. That is to say, when I think something or someone is the bee’s knees, I’m going to be sure I tell them. Starting right here.

Today, I am grateful for the Chromosome 18 Clinical Research Center. I am thankful for the opportunity to work with a wonderful team of professionals. I am thankful for the recent developments in technology that are enabling us to move forward in the research. I love that so many families out there are willing to open up and share their lives and stories and information with us.

And while I’m on the topic, I am grateful for the Chromosome 18 Registry & Research Society. I think the administrative staff and coordinators do a great job of keeping the families up-to-speed and connected. I L-O-V-E when parents contact me with questions (even when I don’t have the answers!) I love seeing the conversations on the Facebook page. I particularly love seeing the photos there!!

As I re-read what I just wrote, it strikes me as kind of cheesy. But, I think I will post it anyway. Because, after all, who doesn’t love a little cheese now and then?!

Happy New Year, everyone! May you have a fantastic 2011!!!