Taking the Reins: A Family’s Decision Pays Off
Date Published: December 20, 2019
When Jodie Zeyer thinks about her daughter Mackenzie as an infant, she recalls a happy baby. Mackenzie had some speech delay. But doctors thought this stemmed from hearing issues related to frequent ear infections. They assured Jodie that the problem would resolve with time.
But at 3 years old, Mackenzie still wasn’t talking. Her temperament had also changed — she became easily angry or frustrated. “I felt like my happy baby disappeared,” Jody says.
By age 4, the Zeyer’s pediatrician had also become concerned, particularly about throat issues, and referred the family to Primary Children’s Hospital in Salt Lake City. Testing revealed that Mackenzie had a cleft larynx — she was missing the part of the throat that stops food from getting into the lungs.
“That was a red flag,” Jodie says. “Those things don’t usually show up alone.” Mackenzie also had low muscle tone, which made it difficult for her to write. “In preschool, they realized that she was using her entire arm to write a letter,” Jodie says.
A year later when the family moved to Texas, Mackenzie was finally able to see a pediatric neurologist. Within 15 minutes, Jodie recalls, he confirmed that something was wrong. He told the Zeyers that the different parts of Mackenzie’s brain were working, but they weren’t working together. That meeting spurred appointments with a series of specialists, including a gastroenterologist, because Mackenzie often complained of an upset stomach, and a geneticist.
The geneticist recommended a test known as a microarray, which looks for changes to the structure of chromosomes, the long threads that contain our genes. But the test was not covered by their insurance. Wanting to figure out the source of Mackenzie’s issues, the Zeyers decided to pay for the test themselves.
Taking the Reins
That decision paid off. Testing revealed that Mackenzie had a change in the PHIP gene. The condition is extremely rare — at the time, only 10 to 15 people had been diagnosed. These people shared similar traits, including developmental delay, obesity, and unusual facial features.
The diagnosis was in many ways a huge relief for the family. “For years, I wondered if I was making it up,” Jodie says. “I was overjoyed to have the diagnosis because it validated all my concerns that there was something different about Mackenzie.”
Mackenzie maintained her sweet demeanor around other people, for example, but often acted out at home. “She would have meltdowns and tantrums,” Jodie says. “I thought something was wrong, but I also questioned myself.”
Dr. Wendy Chung, director of clinical research at the Simons Foundation Autism Research Initiative, is one of the world’s experts on PHIP and autism and one of the first people to study the condition. In 2016, Chung’s team was the first to describe two children, including Mackenzie, who had changes in the PHIP gene and developmental delay.
To better understand how changes in PHIP affect people’s health, Chung visited families around the country searching for other people who had changes in the gene. They published results from their follow-up study in 2019.
Studying more people who have the condition has improved our understanding of PHIP-related syndrome. Some children, for example, have weight issues. But it’s become clear that this isn’t the case for everyone. “That’s helpful for families to know,” Chung says.
Chung notes that PHIP-related syndrome is a bit different from some of the other autism-related genetic syndromes they have studied. “The kids are higher functioning and have the ability to do more things,” Chung says. “But they also have some challenges.” These include intellectual disability, developmental delay, and low muscle tone.
Getting Involved in Research
The Zeyer family found out about SPARK, which is funded by the Simons Foundation, through their geneticist. One of SPARK’s goals is to find genes linked to autism risk and to better understand the genes that are already linked to autism. For a full list, see SPARK’s gene list. This type of research could eventually help to develop new treatments for autism.
SPARK offers free genetic analysis to participants. It also connects participants with researchers who study autism, a program called research matching. “We joined SPARK to help with research,” Jodie says. “If McKenzie can help others behind her, then why not.”
The Zeyers enrolled in a research match study at Baylor College of Medicine, run by Dora Angelaki, a neuroscientist at New York University who is also funded by the Simons Foundation. Angelaki’s team is trying to understand how people who have autism process sensory information, such as sights and sounds.
“Our brains create a mental estimate of the outside world based on sensory information,” Angelaki says. But sometimes that information is incomplete, and the brain has to fill in the missing details. In the study, Angelaki’s team showed people sights or sounds that were easy or hard to interpret and looked for differences between those who have autism and those who do not.
Because the symptoms of autism can be so variable, Angelaki and collaborators wanted to study as large a group as possible. Over the last two to three years, they have recruited about 40 families through SPARK’s research matching program, and some of these families have participated in several experiments. “We wouldn’t be able to do this without this collection of families,” Angelaki says. “We are grateful to everyone who participated.”
Both Mackenzie and her 13-year-old brother Paul, who does not have autism or PHIP-related syndrome, participated in the study. They went into a simulator room where they were surrounded by virtual fireflies that looked like flashing green arrows. They had to use a joystick to navigate to a spot where a firefly had flashed. “Mackenzie loved it,” Jodie says. “It was really fascinating for her.”
The research has not yet been published, but Angelaki says preliminary findings suggest that the two groups process sensory information differently. Research like this may aid in the development of new therapies to address issues with sensory processing.
Mackenzie, now 11, loves playing with her brothers and enjoys puzzles and games. “That’s the biggest way we bond,” Jodie says. Mackenzie is overweight, a trend in some people who have PHIP-related syndrome. Last year, her parents got her a puppy to help encourage Mackenzie to go for walks. “It’s been a huge blessing,” Jodie says. “She wants to play with him and train him.”
Mackenzie’s parents have been very open with her about her autism and genetic diagnosis. “I don’t ever want her to use autism as an excuse for not trying her best,” Jodie says. “If Cs are her best and she tried her hardest, then we are happy with Cs.”
“Sometimes she comes home from school and says ‘I hate autism, why don’t my muscles work like everyone else’s,” Jody says. “But by being open about it, she can talk about it and tell us how frustrated she feels.”
Mackenzie still has developmental delays, particularly in terms of her social skills. “She has lots of problems with other kids,” Jodie says. “She comes home upset almost every day.” Jodie wishes they had received the diagnosis when Mackenzie was younger. “Therapy would have been so much more helpful at a younger age,” She says. “Now it’s hard to change her handwriting and other things.”
Fortunately, the school situation is starting to improve. Mackenzie is now in fifth grade, and for the first time, she loves going to school. “She has three amazing teachers who love her and make her feel like she’s their favorite,” Jodie says.
Resources and References
Simons Searchlight PHIP Facebook Group: www.facebook.com/groups/436264670311297/
Webster E. et al. Cold. Spring. Harb. Mol. Case. Stud. 2, a001172 (2016) PubMed
Craddock K.E. et al. Cold. Spring. Harb. Mol. Case. Stud. 5, a004200 (2019) PubMed