Step 1: Literature Review
Step 2: Clinical and Molecular Assessments
Step 3: Syndrome Description
Step 4: Gene Identification
I also just realized that I have not posted a link that may help with the visualization of the whole process! Here's a diagram that shows the steps, in order, as well as where we are with the various chromosome 18 conditions. I'll also post a copy of the image below.
You might want to click on the image to enlarge. Or, visit this link, which will take you to a PDF that has brief descriptions of each step.
And with that introduction, I will start discussing the next step in the process: a "Syndrome Management Plan"!
Once we have identified the genes that are responsible for different features, we can start to create a management plan that is tailored to an individual’s specific chromosome change.
Right now, most chromosome 18 changes are diagnosed by a routine chromosome analysis. You can read more about how chromosome 18 changes are diagnosed here. The chromosome analysis can identify the chromosome change and the general location of that change, but it cannot determine exactly which genes were involved. So, even though we know that different genes are involved in different people’s deletions or duplications, the chromosome analysis does not give us enough information to know exactly which genes are different. Therefore, we cannot give people specific information about what to expect based on the results of the chromosome analysis. Instead, we must rely on a general description of the chromosome change to give families an idea of what types of things to expect.
However, microarray analysis has changed all this. Microarray analysis is a new technology that can give us precise information about the location of a breakpoint, as well as the specific genes that are involved in a chromosome change. It can also detect much smaller chromosome changes. Now, when the diagnosis of a chromosome 18 change is made on a chromosome analysis, clinicians can perform a microarray analysis and learn which of genes are involved in the deletion or duplication. That information, combined with our knowledge of the roles that various genes play in causing medical and developmental concerns, will one day allow us to create personalized medical management guides for individuals with a chromosome 18 change.
This is probably best explained with an example. In the future, we will be able to say something like this: “Gene A is responsible for foot abnormalities, Gene B causes growth hormone deficiency, and Gene C leads to kidney problems.” Then, when a routine chromosome analysis identifies a deletion of the tip of chromosome 18, we will perform microarray analysis to get additional information about exactly which genes are involved in the deletion. Microarray results for this newly diagnosed individual may tell us that Gene A and Gene B are deleted, but Gene C is not deleted. Using this information, we can be sure that the family has a thorough orthopedic evaluation to detect any problems and start necessary treatments as soon as possible. We will also be able to tell the family that there is a high probability the child will develop growth hormone deficiency. We therefore will need to closely monitor growth and refer to endocrinology at the first sign of a problem. We can also tell them that a renal ultrasound is not necessary, because the gene for kidney abnormalities is not deleted, and therefore they are at no greater risk for kidney problems than any other children.
In this way, we can create individualized management guides that are specifically tailored to a person’s chromosome change.
While this is a step in the right direction, an individualized management guide is not the same thing as a treatment. From this point onwards, our efforts will be focused on identifying treatments that are specific to each chromosome change.
