Advances in genetic testing result in more effective diagnoses
By Bruce Korf, M.D., Ph.D.
UAB Professor and Chair, Department of Genetics
Birmingham pediatricians now have expanded options for easily accessing genetic expertise and testing, with the recent opening of a genetics clinic at Children’s of Alabama.
For physicians, it’s important to consider when to refer a patient for genetic evaluation, especially for those patients who were unsuccessfully evaluated in the past.
Most pediatricians have experience in recognizing children with congenital malformations, intellectual disability or developmental delay that may have a genetic component. When those patients receive a diagnosis, parents have at least a minimum understanding of what is happening with their child, how best to manage that child, and whether it may occur in their other children.
Unfortunately, in the past a large percentage of patients went undiagnosed, even with an evaluation, putting the parents of young children on a seemingly endless quest to decide how best to manage their child’s medical conditions.
A great deal has changed relatively recently, however, and new tools, including microarray and genome sequencing, are available, which means we have the ability to achieve diagnoses that were not available to us before. So if you have been following a patient with medical issues that you suspect are genetic in origin, and that patient has not had genomic sequencing, it is likely time to refer them to a clinic for retesting.
One of the new tools available to us is microarray testing, which gives us the ability to make a definitive diagnosis at much higher rates than we could expect just a few years ago. Older tools would enable us to see the big picture, much like a satellite picture of the earth. Today’s tools are more like the Google Earth app, allowing us to zoom down to street level, so we can see detail on the genome that was previously impossible.
Genome sequencing is another tool that has improved our ability to diagnose. The cost for the test is dropping dramatically. Once costing $100 million per run, the test and analysis are now in the $6,000 to $7,000 range. While that is still a lot of money, compared to the cost of other medical tests it is actually fairly reasonable.
Microarray can be expected to pick up the genetic cause of 15 to 20 percent of autism spectrum disorder cases. Genome sequencing can pinpoint a diagnosis in about 30 percent of cases of children with intellectual disability, autism spectrum disorder, or congenital anomalies. Putting the two tests together means we can expect a definitive diagnosis in 50 percent of the cases presented to us. Considering that even five years ago we could only expect to diagnose about 5 percent, that’s a tremendous step forward in a very short time.
At one time, a genetic diagnosis relied on the physician’s ability to predetermine the underlying problem in order to test for that particular disorder. Today, we are able to diagnose based on the tests, even finding conditions so rare that no physician would have considered testing for them in the past.
And when a diagnosis still eludes us initially, we can now share results and experience with other geneticists around the world, enabling us to establish a diagnosis we may not have been able to make alone.
In short, the tools we have at our disposal now have never been more powerful, so if you are a pediatrician following a patient and have been unsuccessful getting a diagnosis in the past, it is worth taking a second look now.
Of course, putting a name to a disorder is only part of the battle. The next step is knowing how to treat a patient’s condition, and we have made progress in that area as well. Certainly, we can’t say we are able to treat every condition we see, but once we figure out which gene underlies the condition, we then begin to ask why the change in the gene causes the problems it does. And we are gradually figuring that out and identifying drugs that improve quality of life.
With such dramatic and rapid developments in the field of genetics, there are many implications to be considered as we move forward. There is increasing discussion that perhaps everyone should have their genome sequenced, as the cost goes down and the feasibility of the testing goes up. This emerging area will have to be addressed carefully. Between 1 to 3 percent of people whose genes are sequenced will discover a condition they did not realize they had or were at risk for, and virtually everyone can learn how their body manages specific medications or can become aware of risk factors for common diseases. But there are also questions about what options exist to manage these risks once they are known. We will have to proceed carefully in light of our increasing technological abilities.
For patients with known medical problems that can be addressed with genetic evaluation, however, there are ample reasons to make referrals and try to determine a diagnosis that can improve quality of life for the patient and their family.
We have a new clinic integrated into Children’s, with access to parking and other specialists, making genetic evaluation more convenient for parents than ever before. In addition to our Children’s clinic, we have a prenatal diagnosis program through ob/gyn and maternal fetal medicine at UAB, and our newest clinic at Kirklin Clinic for adults.
If you have questions about referring a patient to one of our Birmingham area clinics, please call (205) 934-4983 to discuss.