Genetic testing can change the care, and the lives, of some people with autism.
When Matt was diagnosed with autism spectrum disorder, 16 years ago, it helped explain some of the things that had been troubling his parents for much of his young life.
“He was hitting milestones up until 10 months,” his mother, Bianca Rossi, recalls. (We have changed their names to protect their privacy.) But several months later, Matt was still nonverbal, and at his infant-toddler program “he did a lot of things alone, and didn’t play like the other toddlers did or with them,” she says.
The Rossis were able to get school- and home-based therapies and early intervention services for Matt to help address his developmental delays. They also got him tested for fragile X syndrome, a common genetic cause of autism. At that time, “that was the only testing that I could seek,” Bianca says.
But it came back negative. She went back to wondering what might have caused it: “There were times where I’d be like, was it because I ate tuna fish five days in a row?” Bianca considered the since-disproved idea that vaccines cause autism, but quickly dismissed it. Even as she and her husband focused on getting Matt the care he needed, questions lingered. He had gastrointestinal issues, ADHD, and some skeletal deformities; was it a coincidence, or was it all connected?
Finally, in 2018, the Rossis got answers. Matt, now 20, began seeing a doctor at Bradley Hospital, in East Providence, who told the family about the hospital’s new Genetic Psychiatry Consultation Service. Genetic testing has come a long way since Matt was a toddler, and can pinpoint specific genetic changes with known links to autism. About one-third of autism cases have a clear genetic connection.
The family immediately agreed to the new test. They learned that Matt has an extra copy of a piece of chromosome 15, known as duplication 15q syndrome, which is associated with autism and certain developmental and physical differences.
“It’s like this aha moment,” Bianca says. “To have it connected back to something tangible … you can’t make this up.” An earlier diagnosis may have helped her get more therapeutic services for her son, like physical therapy.
That’s why she wants to spread the word about genetic testing for people with autism. “If more parents knew about this opportunity, they could have an answer that could better prepare them to advocate for additional services for their children,” she says.
Daniel Moreno De Luca, MD, MSc, is a child and adolescent psychiatrist and neuroscientist who evaluates patients like Matt at Bradley’s Verrecchia Clinic for Children with Autism and Developmental Disabilities. He has a background in psychiatric genetics and neurogenetics; when he was a medical resident at Yale he helped develop an autism genetics program and inpatient unit in Connecticut.
Autism spectrum disorder has no single cause. Hundreds if not thousands of genes may be involved, Moreno De Luca says, but only some of them are known; genetic changes may be inherited, or may happen spontaneously. Environmental factors, like viral infections, and pregnancy complications may also play a role.
Thus there is no genetic test for autism: it’s diagnosed clinically, during routine pediatrician visits that check for developmental delays. If it’s warranted, the doctor may refer the family to a specialist for more comprehensive, observational screening. After the diagnosis, the child begins seeing specialists for behavioral and sometimes medical treatments.
Treatment may be further refined if patients have one of the identifiable genetic changes linked to autism. That’s why “genetic testing is the standard of care and is the recommendation of many professional societies, including the American Academy of Pediatrics,” says Moreno De Luca, an assistant professor of psychiatry and human behavior at the Warren Alpert Medical School, and it’s his goal to make sure every single patient with autism is asked if they want to be screened. “But over two-thirds of people have never even been offered genetic testing or discussed that with their physicians,” he says.
Yet the results of such tests may significantly change a patient’s care, he says. For example, if someone has a genetic change known as 17q12 deletion, they are at increased risk for kidney problems and diabetes. So their doctor would “stay away from [medications]that would impact the kidney function or the endocrine function, or use them carefully,” Moreno De Luca says.
“The information does not pertain only to medication choice,” he adds. “We could have a better idea of the strengths and challenges that people have.” Patients with a genetic condition called Phelan-McDermid syndrome have a very hard time talking, for instance. “But they can communicate in other ways,” Moreno De Luca says. Using assistive technology to help them communicate would be much more fruitful than, say, speech therapy. “Building on the strengths,” he says, “can also be a very strong approach that can be informed by genetics.”
Bianca Rossi says Moreno De Luca recommended that Matt get a more specific genetic test after his initial evaluation found duplication 15q syndrome. “Kids that have [this condition]and have a seizure disorder tend to pass away in their sleep, which is extremely frightening,” she says. Though they’ve never observed Matt having a seizure, they want to rule out the possibility.
“It’s our ethical duty to use as much information as we can to help our patients,” Moreno De Luca says. His genetics work is a key project within the Autism Initiative of the Hassenfeld Child Health Innovation Institute, a collaboration between the Warren Alpert Medical School and the Brown University School of Public Health. He says that while genetic testing has limitations, its potential to reveal something that could improve a patient’s care is real. “We’re just not doing what we could be doing right now,” he says.
And patients want that information. Moreno De Luca says that, in general, only 3 percent of people with autism spectrum disorders have had the recommended genetic testing, yet the vast majority said they would have done it if offered. This is even with the knowledge that, in many cases, the tests will not reveal a genetic abnormality linked to autism. Besides helping more patients now, widespread testing would give researchers more data to develop and improve diagnosis and treatments for patients in the future, especially for people from diverse ethnic backgrounds, who have been classically underrepresented in genetic studies.
“It’s frustrating to not have answers,” says Molly Goldman, MS, a genetic counselor at Bradley who works closely with the Genetic Psychiatry Consultation Service and is crunching the numbers for a survey assessing Rhode Island autism patient and family opinions about genetic testing.
Goldman adds that even if a patient’s test doesn’t find a genetic abnormality that explains the autism, “I think that overall people are happy about pursuing their genetic testing.”
Both positive and negative test results can help advance the science. As technology progresses and researchers gather more data from more patients, they may find new links between clinical symptoms and genetic changes, expanding our understanding of autism and improving patient care.
So if most patients say they want genetic testing, why aren’t they getting it? “That’s what we want to know,” Goldman says. “The connection between the patients and the physicians is probably the biggest gap right now.”
“We know that one of the factors that affects physicians,” Moreno De Luca says, “is how comfortable they feel with their genetics knowledge. The field is moving so quickly that sometimes it’s difficult to keep up with what’s going on.” Unfortunately even when some patients request genetic testing, he adds, “their physician may have the misperception that the results may not be clinically useful.”
The Genetic Psychiatry Consultation Service aims to close those gaps, so that physicians view it as a partner in guiding patient care. In addition, Moreno De Luca and his team have completed a quality improvement project to ensure doctors at Bradley who want to order genetic testing can do so swiftly. “We’ve got your back,” Moreno De Luca says. “We won’t let things fall through the cracks.” The team gets insurance preauthorization (“We haven’t had a single denial,” he says, though copays vary and are a worry for some people) so physicians can order the relevant tests; fragile X and chromosomal microarray (which looks for missing or extra pieces of DNA) are recommended for all patients with autism.
When the results come back, the consultation service coordinates with the referring doctors to recommend treatments or further screening, Moreno De Luca says, while simultaneously showing them how genetic information can make a difference in their practice: “It’s a stealth education tool.”
He has more overt education tools, too: he has taught genetics to students and medical trainees at Brown, and he’s helped create exercises that have been completed by hundreds of psychiatrists and trainees across the country, “to maximize the knowledge that our already small workforce has,” he says.
“We already know that there aren’t enough psychiatrists in general for the population of the US,” Moreno De Luca says. “There’s a severe shortage of child and adolescent psychiatrists. And then there’s an even more severe shortage of people doing genetic testing.” As more doctors and medical students learn about the utility of genetic testing, they can bring that knowledge with them wherever they practice.
Genetic testing “is not going to be a cure for everything,” Moreno De Luca cautions; it’s important to be aware of its limitations. But “we’re just not doing what we could be doing right now.”
It’s impossible to know how an earlier genetic diagnosis might have changed Matt’s life. Bianca Rossi describes her son as developmentally delayed, but high functioning—he graduated from high school and gets vocational training through the state. He’s witty, compassionate, and sensitive, his mom says, yet “he is a complete puzzle, still.”
When they found out he has duplication 15q syndrome, “I jumped into being proactive and [asking], what services can I get?” Bianca says. “What can we do to make it better?” Just putting a name to her son’s condition, finding out there are other people—not that many, but some—who have it too, has made things a little better.
“This journey has been really isolating,” Bianca says. But now they know: “There are all these other kids and families out there.”