Researchers unlock answers in children with genetic mapping

KANSAS CITY, Mo. – For Angela and Earl McWilliams, it had been a mystery from her birth why their daughter, Millie, kept running into one medical calamity after another.

She was born with diabetes. She had trouble eating. She needed surgery after the bones of her skull fused prematurely. She couldn't walk, and she quickly lost what little speech she had. Doctors said she was autistic.

But after years of brain scans and endless blood work, doctors couldn't identify the cause of 9-year-old Millie's condition.

Then researchers at Children's Mercy Hospital in Kansas City mapped Millie's entire exome, the 1 to 2 percent of the human genome responsible for most genetic disorders. It revealed an exceedingly rare gene mutation, found in less than one in a million births. While there isn't a treatment for it, at least it now has a name: Bainbridge-Ropers syndrome.

"It's like you're in a dark room and a light, at least a dim light, starts to go on and you can see things," Earl McWilliams said. "This is a beginning. I like to call it a unique beginning."

The researchers recently published their groundbreaking findings on Millie McWilliams and 118 other children with neurological and developmental disorders, showing that mapping a child's complete genetic information can quickly identify rare disorders that otherwise might go years without a diagnosis.

In some cases, the tests were able to change the course of a child's treatment for the better, the researchers found. They could have cut short years of inconclusive testing that ran into tens of thousands of dollars. And they gave parents answers where before there was only doubt.

"We were able to understand more of why [Millie] was going through the things she was that had appeared to be random," Angela McWilliams said.

Soden said the Children's Mercy researchers conducted the study to see how useful genomic sequencing would be in a broad array of children with neurological disorders.

More than 2,400 genetic neurological disorders already have been identified, and that number is growing. That makes it increasingly impractical to test patients for one genetic disorder at a time, particularly as the cost of genome and exome sequencing continues to decline, the researchers concluded. "We're in an era of a lot of new genetic disorders being discovered all the time," Soden said. "A lot of conditions we found [in patients] were just discovered as we were doing the research."

The researchers ran genetic tests on children with a variety of disorders such as intellectual disabilities, seizures, autism, developmental delays or poor muscle tone. They included 85 families with children who were, on average, about 7 years old and had never received a clear diagnosis, as well as 15 families of infants who were born with symptoms and were in intensive care. Some of the families had more than one child enrolled.

For each of the older children, their whole exome was mapped. The infants had their whole genome mapped using technology developed at Children's Mercy and that is unique to the hospital. The technology, called STAT-Seq, can sequence an entire genome in about 50 hours.