Mindy Brayman of Pewaukee was already pregnant with her second child when her son Jack, who was less than a year old, started to worry her. He wasn’t hitting his milestones; he wasn’t crawling, walking or vocalizing like a normal baby-turning-toddler should be.
She and her husband, Scott, took Jack to the pediatrician. That was the first trip of dozens of visits to various specialists, and nine years later, doctors are still trying to diagnose exactly what is wrong not only with Jack, but also with Todd, his 8-year-old brother.
The boys are more than brothers. The one-year age gap makes them best friends who share nearly everything, including a disease that affects everything in their lives.
“They have pretty global delays,” Mindy said. “They are both in wheelchairs, and are fed by tubes. They have communication challenges, and they’re both working with iPads to learn how to talk to other people."
Mindy said the way she explains the boys' condition to friends is "like their brain is a remote control that the batteries have gotten low, the signal just doesn’t get through to the rest of their body."
No known cause, no known treatment
The Brayman boys both have a pediatric neurotransmitter disorder, or PND, which is an umbrella term for a genetic disorder that affects neurotransmitters in children.
Neurotransmitters are chemical messengers in the brain that either excite nerve function or inhibit it. Common neurotransmitters include dopamine, adrenalin and serotonin. While some pediatric neurotransmitter disorders can be treated, others remain a mystery, and there are no known treatments.
Jack and Todd fall into the latter category. Not only does their particular disease not fit a typical PND, but there are no medications or therapies that improve their symptoms.
All the Braymans can do is care for their sons, provide nursing care and education, and make the most of each day as a family. But always at the back of Mindy’s mind is the burning question, “What else can I be doing for them?”
“We want to provide the best life possible for our kids. We love them and want to do everything we can for them, and for other families going through this same journey with their children” Mindy said.
Dr. William Rhead, a genetics specialist at Children’s Hospital and the in Wauwatosa has treated the Brayman boys for years. So when a new diagnostic test became available for the first time, he and genetic counselor Amy White talked about it with the Braymans.
The big question: Did the family want to explore whole genome sequencing?
Looking at a unique set of human blueprints
Whole genome sequencing is basically a way to decode the language of life. From a blood sample, every sequence of DNA is determined and recorded. From that human blueprint, scientists begin the painstaking process of poring through the data, looking at variants, or differences, in the DNA from the “reference” DNA.
A whole genome contains more than three billion letters – about 22,000 gene “chapters” located within 23 chromosome volumes. Every human being has more than a million variants.
So what could whole genome sequencing potentially mean for the Braymans?
“First, we have to examine all the variants to determine whether it could be possibly contributing to the disease process. There’s no guarantee we will find anything.
"But there’s a chance we can find the gene responsible for the boys’ neurotransmitter disorder," Rhead said. "And if that happens, there is a chance that we could potentially identify a treatment."
The potential to help the boys – and others
Children’s Hospital and the Medical College established the first clinical whole genome sequencing program in the country. Cases are selected by a panel of physicians and scientists. The Braymans were recently selected for whole genome sequencing, and decided to explore that option.
“There was a lot to think about,” Mindy said. “Amy White, our genetic counselor, was very thorough. She brought up so many things we hadn’t thought of – do we put the boys’ gene out there publicly? What do we want to know from the sequencing process? Do we want to learn about the potential for other diseases?"
But the bottom line, the family decided, was that they would go through the process in the hopes it would end their diagnostic odyssey, and that the information learned would help not only their family, but others.
“I don’t want other families to have to start from scratch like us, if we can help other children by learning more about this and pushing for more research, we have done something not only for our children, but for the greater community,” Mindy said.
Whole genome sequencing and evaluating the data is not an inexpensive process, but the price continues to drop. The Braymans were helped by a grant from the Pediatric Neurotransmitter Disease Association.
Now, the family is hosting its own fundraiser to contribute to research and whole genome sequencing.
On May 21, Scott and Mindy will host a golf fundraiser at The Legend at Brandybrook in Wales. Proceeds will go to the Human and Molecular Genetics Center at the Medical College of Wisconsin, which is a co-founder of the clinical whole genome sequencing program – and where scientists are working on multiple research projects using whole genome sequencing, trying to identify unknown causes of disease.
“There is great potential in whole genome sequencing not only in children with active disease process, but also in children who are going to get sick, and we don’t know it yet,” said Howard Jacob, Ph.D., director of the Human and Molecular Genetics Center.
“Imagine knowing there is a chance your child is going to get cancer, or another illness, in advance, and being able to screen for that disease, find it immediately, and begin treatment if available.
"That’s the future potential role of whole genome sequencing.”
Gene sequencing is a record for the future
The Braymans pray whole genome sequencing sheds some light on their boys’ futures.
“We may not find out what’s causing them to have this disorder… but we might,” said Mindy. “There is a chance we can identify a treatment to help them. There is a chance that other children with neurotransmitter disorders learn from our journey.”
Even if nothing is learned, right now, from whole genome sequencing, that doesn’t mean the Braymans’ diagnostic odyssey is over. The genomics team at the Medical College and Children’s Hospital will revisit every genome, every year, to take a fresh look at the data.
“Think of it like television in the 1960’s,” said Jacob. “Watching the moonwalk was amazing. But 20 years later, we had 500 channels of color TV on cable, and now there are thousands of digital, high-definition programs on demand, streaming to order.
"We expect whole genome sequencing knowledge and technology to grow just as exponentially over the next few years.”
The whole-genome sequencing program was launched in late 2010 by a collaborative team of scientists and physicians at the Medical College and Children’s Hospital.
The team’s first success, in which a Monona boy had a large part of his DNA sequenced, and as a result of findings was successfully treated for his previously unknown disease, was the focus of the Pulitzer Prize-winning series “One in a Billion,” by the Milwaukee Journal Sentinel.
After that case made national and international news, producers of "NOVA," public broadcasting’s long-running science series, produced the documentary film “Cracking Your Genetic Code,” profiling families across the country who are undergoing DNA sequencing to answer questions about their medical conditions.
For more information about the golf fundraiser for the Human and Molecular Genetics Center at the Medical College of Wisconsin, visit www.friendsforresearch.com.
The fundraiser is May 21, 2012 at the Legend at Brandybrook in the town of Wales. For $175, participants will have lunch, play 18 holes of golf, enjoy happy hour after the round, and stay for a buffet dinner and evening event. For non-golfers, sponsorship opportunities and evening event-only packages are also available.