Travis King, 15, and his family gathered around the telephone in the living room of their Washington state farmhouse. They were about to get a call from Wendy Chung, the principal investigator of SPARK (Simons Foundation Powering Autism Research for Knowledge). Chung had important news for them: SPARK had found a genetic cause for Travis’ autism.
“Travis sat there listening,” says his mother, Threasa King. “I never know how much he understands, but I wanted him to be a part of it.”
The Simons Foundation Autism Research Initiative launched SPARK four years ago with the goal of analyzing the genomes of 50,000 people with autism and their biological parents (and sometimes siblings). Different rare genetic changes in hundreds of genes are believed to underlie autism, and with a cohort of 50,000 families, SPARK’s researchers hope to uncover most of these.
To date, SPARK has enrolled about 230,000 individuals with autism and family members. More than 22,000 complete families (consisting of an individual with autism and their parents) have submitted their genetic material in the form of mail-in saliva kits. SPARK and its collaborators have sequenced the genomes of more than 45,000 people, with another 23,000 currently in the works. The study now maintains a list of more than 175 genes and segments of chromosomes where a change is known to contribute to autism. SPARK’s sequencing studies have already identified dozens of other statistically significant autism risk genes that will likely be added to this list in the future.
When SPARK finds that a participant has a genetic change linked to autism, it offers the family the option to receive this information through a genetic counselor or medical doctor. In 2019, SPARK provided a genetic diagnosis to nearly 200 people, including Travis — a dramatic increase over previous years. In 2020, the study expects to inform a further 300 participants.
SPARK researchers estimate that 8 to 10 percent of study participants with autism will be diagnosed with one of the genetic changes that have already been identified. The study continues to find more autism risk genes as it sequences more families, so that percentage could gradually rise. Not everyone will receive a diagnosis, however, since a majority of individuals will have autism that is caused by changes to multiple genes rather than by a single genetic change.
Many parents choose to receive their child’s genetic diagnosis in the hope that it will enable them to better manage their child’s care. “We are giving them the tools and information to help them help their child, and also help science,” says Pamela Feliciano, SPARK’s scientific director.
While there are no specific treatments yet for CUL3 genetic changes related to autism, the diagnosis has nevertheless influenced Travis’ medical care. For instance, he had been taking a medication for aggression that requires regular blood pressure monitoring. But because CUL3 is linked to high blood pressure, the family asked his doctors to reexamine this choice of medicine. “Now his doctors are all on board,” King says.
For some families, receiving a genetic diagnosis from SPARK confirms a long-held suspicion.
Years ago, Cindy and Patrick Badon’s doctor had suspected a genetic cause for their son Reagan’s autism. But Reagan’s symptoms did not fit neatly into any known syndrome, and genetic tests found nothing significant. The doctor said that pinpointing the gene involved would be like “finding a needle in a haystack,” Cindy Badon recalls.
Then SPARK provided the tools needed to comb through Reagan’s haystack. In 2016, the Badons and their sons, Reagan and Chance, joined the study. “I thought maybe SPARK could find what doctors had not been able to [find] so far,” Cindy Badon says.
Even so, she was floored when SPARK told her three years later that Reagan had an alteration in a high-confidence autism risk gene called MED13. Like Travis King, Reagan, now 13, is one of very few people worldwide who have been diagnosed with this particular genetic change, which he did not inherit from his parents.
With “disbelief, shock and excitement,” Cindy Badon shared the news with her husband. “It’s a little unnerving sometimes because there’s not a lot of information out there about MED13 yet,” she says. “But the more I read, the more I feel like this is exactly the piece of the puzzle we’ve been missing.”
In a 2018 article in Human Genetics, researchers described the rare developmental disorder connected to changes in MED13. Of the 13 people they studied, all had intellectual disability or developmental delays. Many could understand more language than they could speak, as is the case with Reagan. Eight had vision or eye problems, and seven had delays in developing motor skills. Five had autism, and two had heart abnormalities, among other issues.
The genetic diagnosis provides a fresh lens through which to view some of Reagan’s more puzzling symptoms. For instance, he has trouble buttoning a shirt if he has to look down to see the buttons. And he needs to eat frequent, high-protein meals to maintain his energy level. “A lot of the things that we now think are genetic were [previously] written off as being ‘just autism,’” Cindy Badon says.
The genetic diagnosis has given the Badons a path to follow. It confirms their decision to stick with scientifically proven behavioral therapies for autism rather than newer ones that don’t apply to Reagan, says Patrick Badon. The family also plans to ask doctors to check Reagan for the kinds of heart, eye and other problems that have been found in people with a MED13 change.
To help expand scientists’ knowledge base about MED13-related syndrome, the Badons have joined a SFARI program called Simons Searchlight that forms communities of families who have a shared genetic diagnosis. Searchlight participants can share information about symptoms and treatments with each other and take part in additional research studies.
“We would like to see research on what we can do to keep [Reagan] healthy and happy and help him deal with the potential health problems in his future,” Patrick Badon says.
Many of the genetic changes thought to cause autism are almost vanishingly rare, so everyone who joins SPARK and Simons Searchlight increases the likelihood that researchers will discover something new. “Literally every person and every family matters,” Feliciano says.