In the United States, current estimates are 1 in 59 children will receive an autism diagnosis by age 8. Individuals with autism all have difficulty with social communication and interactions, as well as restricted interests or repetitive patterns of behavior. However, the strengths and challenges for these individuals truly is a spectrum that can range from a completely nonverbal kindergartner, to a professor of linguistics.
We’ve known for more than 20 years that the lion’s share of the risk for developing autism is genetic. However, pinpointing specific genetic changes linked to autism has been tremendously challenging. Recently, new breakthroughs in our ability to read our DNA, our genomes, and partnerships between families and researchers have begun to shine a new light on our understanding of autism genetics. Importantly, these efforts are already sparking new actions that will help benefit individuals with autism, and their families, in the years to come.
April is World Autism Awareness Month, and three years ago this week, OHSU and more than 20 other sites across the U.S., helped launch SPARK, the largest genetic study of autism ever. SPARK’s goal is to recruit more than 50,000 families as research partners to accelerate the scientific understanding of autism.
I’m a co-leader of the OHSU SPARK site, now one of just 32 across the country. And, as a human geneticist who has studied autism and related developmental disorders for the past 15 years, I often have conversations with families, self-advocates and primary care clinicians about genetic testing and research. Generally, these conversations can be split into two types: “Why can’t I get genetic testing?” and “What’s the point of genetic testing? It’s‘not actionable.’”
The American Academy of Pediatrics, along with other leading health professional organizations, has long recommended that all individuals with autism receive some type of genetic testing, such as screening for fragile-X syndrome, or what is known as a chromosomal microarray analysis, which can detect large scale deletions and duplications of the genome.
Learn more about how genetic testing positively impacted two SPARK participants: Hope and Alex.
While these techniques were state-of-the-art when I was a graduate student in the late 2000s, recent technological advances within the last decade have allowed us to do so much more. We can now conduct whole-exome sequencing, a process that directly scrutinizes all protein coding regions of the genome, which is approximately 1 to 2 percent of our DNA. This more comprehensive screening can be done clinically for a similar cost as microarrays. For a bit more, individuals can sequence the other 99 percent of their DNA via whole-genome sequencing. These sequencing data allow clinical labs to find changes down to a single DNA base change, many of which we now know can strongly contribute risk for developing autism.
Despite these recommendations and technical advances, many families struggle to even get the basic recommended testing.
A recent survey published in the journal Application of Clinical Genetics shows that roughly two-thirds of individuals with autism have never had any genetic testing. The reasons behind this issue are complex and not well studied. However, from the parents and physicians I’ve spoken with, there is at least one major culprit for families that want genetic testing and have not had it: insurance.
Genetic tests have to be “authorized” by insurance companies prior to the testing. Plus, there still could be significant out-of-pocket-costs for a family. Assuming a test is even covered by your insurance plan, the patient or physician still needs to justify the necessity of the test to the insurance company.
This seems like a simple calculus. Every major medical association in the U.S. recommends genetic testing for individuals with autism. This individual has an autism diagnosis. Ergo, they are “justified” in having genetic testing. But still too often testing is denied.
So why does an insurance company deny even a basic genetic test recommended by everyone? Well, it’s “not actionable.”
When an insurance company or physician says something is not actionable, they mean that finding that result will not change the routine clinical care of the patient. For many of the families I’ve known and have worked with, this argument doesn’t hold any water. For them, just knowing can create actions.
Autism often co-occurs with other challenges. With new research, we are beginning to link specific risk genes to these challenges, including things such as congenital heart defects or seizure subtypes that are actionable. Families and physicians can use this new information to take actions that will improve care.
Importantly, these recent discoveries have also allowed families with similar genetics to find each other, share their stories, form communities and develop non-profit organizations to support further research. Many of these groups are less than 5 years old. Knowing why has empowered these families to take actions that -- with a lot of hard work to come -- will form the basis of targeted interventions in the future. I’d hardly call that “not actionable.”
SPARK is not a substitute for clinical genetic testing, but we are committed to returning meaningful results back to as many individuals with autism and their families as possible. We are currently analyzing data from over 9,000 families from the first two years of SPARK, and we are learning more about the genetic risk factors for autism every day. As our SPARK participants show us, just knowing can create actions that help bring light to our understanding of autism.
Additional information about OHSU and SPARK , as well as enrollment details, can be found at: www.ohsu.edu/SPARK.
Brian J. O’Roak, Ph.D., is an associate professor of molecular and medical genetics in the OHSU School of Medicine.