Extremely Rare Condition Linked to Autism
Date Published: January 23, 2020
Travis King spoke his first words when he was 4 years old and under duress. He was in the hospital for surgery for what’s known as a dermoid cyst on the end of his nose. With restraints on his arms to stop him from pulling out his oxygen tubes, Travis looked at his mother and said ‘Mommy, it hurts.’ “That’s when we found out he could talk,” says his mother, Threasa King.
The former volunteer firefighter knew very little about autism at the time. Her older son had been slow to speak, so King wasn’t concerned about Travis’s lack of communication. As a baby, Travis never cried, which seemed like a good thing. “People said, you have the most amazing baby,” King recalls. “But that’s a red flag. Crying babies are communicating. We didn’t know that’s part of the communication process.”
In the course of his care after surgery, a doctor suggested that Travis be evaluated for developmental delay. “I was still in the denial stage,” King says. “I didn’t know anything about autism.” She now recognizes that Travis had been showing classic autism behaviors, such as lining up his crayons.
After waiting for a year and a half, the Kings finally got an evaluation at their local autism center. The day before Travis’s sixth birthday, the family got the phone call. Travis had autism.
The Kings were told that Travis was not communicating or reading at a typical level for his age. But they received little other information about the condition. “The staff were still learning how to explain autism to parents,” King says.
Over the next eight years, King would become an autism expert. She watched how behavioral therapists worked with Travis and continued that work at home. She attended autism training conferences, even paying to bring one of Travis’s aides. She learned about the laws governing autism and education, including the individualized education plans that children who have autism may be entitled to.
She now uses that knowledge to help other families who have just received an autism diagnosis. “I feel that if I can teach one or two parents then they can also help new parents who have gone through what they have gone through,” King says.
King first learned about SPARK, the largest study of autism, through a story on the local news. “We saw it and said, we want to be a part of this,” King says. The family wanted to know what caused Travis’s autism. If it was genetic, what would that mean for Travis’s older brother? Would his future children be at risk?
To date, scientists have identified almost 200 genes and larger genetic changes that can increase the risk of autism. And they estimate that there are hundreds more. SPARK, which is funded by the Simons Foundation Autism Research Initiative, also called SFARI, aims to find these additional genes and to better understand the genes that are already linked to autism. This type of research could eventually help to develop new treatments for autism.
King enrolled in SPARK online and received saliva kits through the mail. Participants send in saliva samples to be analyzed for genetic changes linked to autism.
A year and a half after sending off their saliva, King received word that researchers had found something in Travis’s genes. The family gathered around the phone in their living room to talk to Dr. Wendy Chung, a clinical geneticist who runs SPARK. “Travis sat there listening,” King says. “I never know how much he understands, but I wanted him to be a part of it.”
They learned that Travis had a change in a gene called CUL3. The change was de novo, or new, meaning that he did not inherit it from King or her husband Darren. Tyler, Travis’s brother, also does not have it. “It was such a relief to me,” King says. “Parents feel so much guilt, thinking that this is my fault.”
Changes in the CUL3 gene have been linked to different conditions, including hypertension or high blood pressure, schizophrenia, and autism. The types of symptoms a person has depends on where in the gene the change happens. Cases like Travis’s are extremely rare.
King shared the diagnosis with Travis’s doctor and everyone else who works with Travis. No specific treatments exist yet for CUL3 gene changes and autism. But the diagnosis has influenced Travis’s medical care in other ways. Travis was taking a medication for aggression that requires regular blood pressure monitoring. But because CUL3 is linked to hypertension, they decided to switch medicines. “Now his docs are all on board,” she says.
CUL3 in the Brain
Scientists know very little about how changes in the CUL3 gene affect the brain, but it has clear effects on behavior. Zhen Yan, a scientist at the State University of New York at Buffalo, is trying to better understand the role of CUL3 by studying the gene in mice. Like most genes, CUL3 makes a protein that does important jobs in the cell. Yan’s team has found that mice that are missing the CUL3 protein show changes in social and repetitive behaviors, both of which are common in autism.
CUL3 affects many other genes that are important in the brain and body. Yan’s team also found that changing one of these genes can improve social behaviors. The findings may one day inspire the development of new treatments, but scientists caution that is still a long way off.
Yan’s team also studies other autism genes, such as SHANK3, and sometimes works with doctors who treat people with changes in these genes. But for CUL3, the gene change is so rare, she hasn’t found anyone to work with.
As genetic testing becomes more common, particularly among people who have developmental disorders, more people are likely to be diagnosed with CUL3 gene changes and autism. Yan and others hope that this will bring more attention to the condition.
King eventually hopes to meet other families with children who have CUL3 changes. “I want to know if they talk alike and act alike,” she says. “We are going through puberty now; no one knows how to help this child.”
King is a natural advocate. When a child in her hometown of Wapato, Washington is newly diagnosed with autism, the family is likely to be put in touch with her. “Say autism in this town, and the first number they get is mine,” she says. “I will do whatever it takes to help them.” King is often on the phone until late in the night, helping to advise families with kids having meltdowns or worse, who have gone missing.
King’s expertise is hard won. Travis was 6 years old when the family moved to a 10-acre farm home. On their first morning there, Travis disappeared. Half an hour of frantic searching found him playing in a deep irrigation ditch, chest deep in water and mud and totally unaware of his parents’ terror.
The King’s experience is not unusual. Wandering off — also called elopement — is a common behavior in children who have autism. About 50 percent of families report wandering by a child who has autism, and parents often rank this as one of their top stressors.
Water provides a particular danger for these children. Drowning is a top cause of death in children who have autism and are under 14 years old. The vast majority of wandering fatalities in children who have autism are related to drowning. “91 percent of children with autism under age 14 that die, die of water-related injuries,” King says. “Nothing was being done about it. There was no awareness.”
King and her husband resolved to change that. They spent the last four years working to pass a law in Washington state, called the Travis Alert law, that teaches first responders how to interact with people who have disabilities. A second part of the law, which they are still working on, alerts first responders when someone calling 911 has an emergency concerning a person who has certain conditions, such as autism, Alzheimer’s disease, or Down syndrome.
She’s also worked hard to help the local school system be more autism-aware. She advocates for parents to get individualized education plans for their children and makes sure that teachers have autism training and the help they need to work with children who have autism.
Travis, who is now 15, started high school this year, where he attends a mix of mainstream classes and self-contained, or special education, classes. He knows all the states and their capitals, as well as the flags of each country. He loves languages and watches communication videos in different languages, including Spanish, German, Swahili, and sign language. “He craves communication so much, he learns it on his iPad,” King says. Threasa often communicates with Travis using sign language and teaches sign language at the high school as a volunteer. After graduation, he dreams of going to Disneyland and opening a hot dog stand.
She hopes that her efforts, and projects like SPARK, will help broaden our understanding of autism and get people the help they need as soon as possible. “I was completely unaware of autism until I had Travis,” King says. “If it doesn’t happen in your family, you have no idea. Let’s help them be successful in life instead of waiting until they’re 6.”
Rapanelli M. et al. Mol Psychiatry. Epub ahead of print (2019) PubMed