‘The right place’: Sisters with rare disorder find help

The first moment she held her daughter Bella, Emily Burkhart knew.

Bella had a noticeably small head that announced what tests would later confirm: Bella was born with a rare genetic disorder.

Emily Burkhart immediately suspected a genetic problem because she’d seen this before – in Bella’s older sister, Anna. And because of that, she knew exactly where to find help: the Fralin Biomedical Research Institute at VTC Neuromotor Research Clinic.

A decade earlier, doctors predicted Anna would never walk, talk, or have a fulfilling life. Today, she is in many mainstream classrooms and made her middle school cheerleading squad.

“If I would not have brought Anna here to Virginia Tech, she would not be where she is today,” Emily Burkhart said. “We're so thankful for the intensive therapy program here, and I think we are proof that it works. When the need and opportunity for her sister, Bella, to come here popped up, it wasn't even a question.”

Seven years after Anna’s visit, the Burkharts brought Bella from Pittsburgh to Roanoke for four weeks of the research clinic’s unique intensive neurorehabilitative therapy.

“We all have challenges in life, and the goal of our research is to help families and children reach all of their potential,” said Stephanie DeLuca, co-director of the Neuromotor Research Clinic. “When we help one individual maximize their potential, ultimately what we do is help everybody learn how to maximize their potential.”

‘It’s go time’

The signs with Anna didn’t emerge immediately. Emily Burkhart was 24 and a first-time mom. To her, nothing seemed unusual about her newborn.

But within a few months, Anna began to miss developmental milestones. She didn’t reach, grab, or roll over when children typically do. Anna was 15 months old before she crawled, and she didn’t walk until she was nearly 3 years old.

Her parents sought answers for Anna’s delays. After years of testing and hospitalizations, Anna was finally diagnosed with a rare mutation of a gene common in many species, called CASK. Doctors knew little about the condition, Emily Burkhart said.

“Basically, she was just going to struggle, and she was probably going to be wheelchair bound and non-verbal,” she said. “I just wasn't going to accept that.”

Through Konark Mukherjee, a CASK mutation expert and assistant professor at the Fralin Biomedical Research Institute, the family learned about biological aspects of the mutation and was introduced to the research institute’s Neuromotor Research Clinic.

Soon, the family was visiting Roanoke so Anna could receive intensive therapy through an experimental research protocol, developed by research institute investigators and supported by the National Institutes of Health. While customary occupational and physical therapy is delivered for only one hour a week, therapists at the Neuromotor Research Clinic work with children three to six hours a day, five days a week, for up to four weeks.

Anna had just turned 5 when she first visited Roanoke.

“She wasn’t really talking, she couldn't calm down enough to figure out how to play with something,” Emily Burkhart recalled.

The research clinic’s team had worked with many children with disabilities that had affected their brain development and function, including those with cerebral palsy. But the team never worked with a child with Anna’s diagnosis before and wasn’t sure what to expect.

"What Anna needed was different than previous kids we’d worked with,” said Dory Wallace, a senior occupational therapist. “It was about helping her learn how to pay better attention, how to use her words, and how to interact and engage with the people in her environment. Once we met her, we completely changed what we thought we were going to do to meet her needs.”

Anna responded right away.

“I love seeing that light switch go on when a child realizes she’s learned something new,” Wallace said, “Because then it's like, ‘It's go time.’”

Two weeks later, the change was already dramatic.

“She was sorting colors and she was sitting still to play with a toy,” Emily Burkhart said. “She was just doing all the things that we were able to want and expect, plus some.”

Learning from each child

Parents like Emily Burkhart might feel like their children’s improvements are a kind of miracle.

But what they’ve benefitted from is a therapy called ACQUIRE, which is rooted in scientific research and has been repeated for dozens of children. Most of the children who come to the Neuromotor Research Clinic are participants in clinical trials designed to research, assess, and improve the therapy they receive, though some children come for therapy on a strictly clinical basis.

“We’re learning from each child while we’re simultaneously trying to help that child,” DeLuca said. The result is a therapy with a defined protocol that can be taught to other therapists. “We provide very specific guidelines for how therapists should deliver the interactions of therapy to help the child progress and maximize their development.”

DeLuca, Neuromotor Research Clinic Co-Director Sharon Ramey, and Karen Echols developed the foundations of the ACQUIRE therapy protocol when they were colleagues at the University of Alabama at Birmingham.

DeLuca saw a void in evidence-based therapy for children, although similar protocols had been developed for adults who had suffered strokes. The trio developed an intensive, high-dosage, play-based therapy in which children work with a therapist, not once a week for an hour, but multiple hours a day, every day, for several weeks, following a process with specific therapeutic guidelines.

The therapy relies on the brain’s plasticity – its capacity to change in response to intensive training.

Most children the Neuromotor Research Clinic works with have cerebral palsy or hemiparesis – a weakness or loss of ability in one side of the body caused by some type of damage to an area on one side of the brain that contributes to motor control. Such injuries may occur when a baby suffers a stroke in utero, at birth, or soon after. One version of ACQUIRE therapy is called ACQUIREc therapy for children with hemiparesis, which often involves constraining the functioning limb to compel the child to rely on the affected limb.

A study by scientists at the Fralin Biomedical Research Institute, Virginia Tech, UVa Children’s, the Ohio State University, and Nationwide Children’s Hospital found that 60 hours of constraint-induced movement therapy over four weeks was significantly more beneficial to children than customary forms of therapy.

“We've now been able to expand use of our therapy into other diagnoses,” DeLuca said. They are finding that children with many different types of issues that affect brain development and function respond to high-dose therapy.

CASK genetic mutations are exceedingly rare, with just 130 cases documented as of 2020, according to the National Institutes of Health.

Anna was the first child to come to the clinic because of a CASK genetic mutation. Since then, there have been others, but no one suspected there would be another in Anna’s own family. 

‘We’re in the right place’

Emily’s pregnancy with Bella was unremarkable, but when she was born, her small head alarmed her mother immediately. She knew microencephaly was an indicator of a genetic mutation that could impair her development.

After months of testing, the confirmation came.

“You start thinking about the stuff you could miss out on,” said Charlie Burkhart, Bella’s father and Anna’s stepfather. “Am I going to be able to dance with my daughter at her wedding?”

Soon the Burkharts were scheduling time for Bella at the Neuromotor Research Clinic and planning long visits to Roanoke.

“Bella was struggling,” Charlie Burkhart recalled. “You're just going, ‘All right, she's this many months old. She should be trying to roll over, right?’”

Bella was 14 months old when she started therapy.

“Dory had her doing things the first day that we hadn’t seen Bella be able to do,” Emily Burkhart said. “I started to cry because it was like, ‘OK, we're in the right place.’”

Charlie Burkhart was mesmerized.

“I’ve never seen Bella work so hard. I videotaped a lot so I can replicate it at home,” he said. “To be able to come down here for a month and get this blueprint and get her going, there's no words to describe how appreciative I am.”

The Burkharts have high hopes for Bella, because they’ve seen how big sister Anna has progressed. Anna continues to use some of the therapeutic program the family learned at the clinic years ago.

“Anna’s living a pretty independent life,” Emily Burkhart said. “She takes the bus by herself to school. She's like a like a normal, typical 12-year-old. She’s on TikTok and she wants to dye her hair and she's just into all the things that you think that she would be into.”

News of Anna’s progress is what keeps DeLuca and the clinic staff going.

“Research is tough. Science is tough,” DeLuca said. “I keep doing it because I hear stories like Anna’s and Bella’s and other children that we’ve seen through the years, knowing we played some small part in maximizing their development. It gives me the strength to go back and say, ‘OK, there’s one more question we need to answer so that we can get what we do out there to more and more children.’”