The phone call came at 2 a.m. It was a neonatologist calling about Kimberly Aldinger and Scott Houghtaling’s son, Grayson. Kimberly had given birth to premature twins a month earlier and both babies were in the neonatal intensive care unit (NICU) at Swedish Hospital. The new parents had returned home to get a much-needed night of sleep when the doctor left a message on their voicemail.
“I’m really worried about Grayson,” the doctor said. “He’s having a massive seizure. You need to come down here.”
Scott immediately feared the worst. “I thought, the only reason they’d call in the middle of the night was if they were preparing for the worst outcome — Grayson not surviving.”
Thankfully, the medical team was able to stop Grayson’s seizure that night, but it was just the beginning of Kimberly and Scott’s journey to understand the severity of their son’s brain damage and how it would shape all their lives.
Roots in research
Kimberly and Scott are both research scientists at Seattle Children’s Research Institute. In fact, they first met at a meeting between their two research centers.
Kimberly is a senior research scientist in the Center for Integrative Brain Research. Her work is focused on studying genes that are important to healthy brain development and discovering how the brain is affected when something is wrong with that gene.
Scott is the research lab supervisor in Dr. David Beier’s lab within the Center for Developmental Biology and Regenerative Medicine. He manages a team of scientists currently focusing on the development of embryos and birth defects — identifying genes that are important for organ development.
The couple learned they were expecting twins in the fall of 2015; Grayson and Chloe were born at 33 weeks gestation in March 2016. When they were 24 days old, Kimberly noticed something unusual with Grayson.
“I was holding him against my chest and he started to push himself up — that is not normal for such a young baby, especially one in the NICU,” Kimberly said.
Kimberly recognized Grayson was having tonic-clonic (or Grand Mal) seizures, which make a person’s muscles stiffen and twitch or jerk.
That night Grayson had his first massive seizure, which led to the 2 a.m. phone call. After running several tests, providers confirmed he had epilepsy.
“It was my worst fear come to fruition,” Kimberly said.
The reality took Scott longer to process. “He was just a small baby; I didn’t fully appreciate the changes that were going to affect his life and ours,” Scott said. “I was still holding out hope that I would be able to take photos of my boy playing soccer when he was 10.”
Searching for a cause
Grayson’s first massive seizure required so much medication to stop it that he was put on a ventilator to breathe. When the neurologists reviewed his magnetic resonance imaging (MRI) scan, they found his brain was undergoing active injury and some of his brain cells were dying.
To find the cause of Grayson’s epilepsy, he was admitted to Seattle Children’s for genetic testing. If tests revealed a mutation in one of his genes, it might point providers to a treatment that could stop his seizures.
Unfortunately, the tests didn’t reveal any mutations known to cause epilepsy. Still, because of their experience in genetic research, Kimberly and
Scott asked for a copy of the raw data.
“Something I had to do”
That data remained — untouched — on Kimberly’s computer for the next three years while she and Scott were busy managing Grayson’s clinical care. For two years, they struggled to find a medication that could control his seizures. They also had to coordinate with Grayson’s many specialists and care for his sister Chloe, who has limited vision related to her prematurity.
Meanwhile, Grayson’s seizures continued. Eventually, providers found a more effective seizure medication for Grayson and an MRI at age 4 suggested his brain had stabilized. Grayson was still having multiple, small focal dyscognitive seizures each day and more harmful seizures every three to four months. Nonetheless, the family’s daily life started to stabilize.
Kimberly, who felt like she was finally emerging from a fog that had hung over her since giving birth, began to think about Grayson’s genetic data again. While she knew her son’s genes had not changed, scientists’ understanding of genetics had grown rapidly since his test results were first reviewed. She and Scott requested they be analyzed again.
While they waited for the geneticist’s report, Kimberly began investigating the data herself.
“I remember Kimberly was sitting on the couch one morning,” Scott said. “And I had just gotten out of the shower and poured a cup of coffee when she said, ‘I think I found Grayson’s gene.’”
Kimberly found an irregularity in Grayson’s MAST4 gene, which belonged to a family of genes in which some are known to cause epilepsy. Still, little was known about MAST4 specifically. It wasn’t clear whether the change in this gene would influence brain function.
“As soon as she identified the change in Grayson’s gene, I immediately
started investigating it,” Scott said. “There was no other choice for me. It was something I had to do.”
Not just any other research project
Meanwhile, Kimberly began searching for other children with epilepsy who had the same irregular gene expression as Grayson. She identified six other patients, making it even more likely this genetic mutation was responsible for Grayson’s epilepsy.
But Kimberly and Scott still had questions about MAST4, like: What is its function? Why do children develop epilepsy when the gene is changed? And how can the gene be manipulated to change the effects of the disease?
Searching for answers, Kimberly and Scott designed a research study in which they collected skin cells from patients with epilepsy and tested them for the MAST4 gene mutation. One of those skin samples came from Grayson.
“I actively inserted him into the research because of his ongoing seizures, but it was a challenging position to be in,” Kimberly said, “I needed to treat it like any other research project, but it was deeply personal.”
Kimberly was recently awarded a research grant from the American Epilepsy Society to fund Grayson’s MAST4 research study. It will allow her, and Scott, to study how the mutation in MAST4 affects brain cell function.
“We know our research is unlikely to impact Grayson’s clinical care or presentation, but we might uncover something helpful for other children with epilepsy who are diagnosed at an earlier point in their development,” Kimberly said.
His own path
Unfortunately, he continues to have seizures. He has cerebral palsy in four limbs and hypotonia in his torso, which prevents him from sitting up by himself. He also requires assistance with all activities of daily life due to his severe intellectual disability, caused by changes in his developing brain. He loves to stand and walk but needs help to do so. He has a feeding tube and cannot walk without assistance.
But Kimberly and Scott don’t focus on Grayson’s limitations; they celebrate his accomplishments.
“The journey to understanding how therapy can help Grayson continues,” Scott said. “But we’ve also realized he’s happy. I can make him laugh. He has emotions and needs and wants; We love him and it’s obvious he loves us too. He’s on his own path and we’re on it with him.”