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.