Imagine, if you will, your child living with unrelenting pain: beset by paralyzing migraines two out of three days, suffering from unpredictable bouts of ataxia (loss of bodily control) and vertigo.
Worse yet, doctors have no idea what is causing the symptoms, and there are few effective treatments to ease the symptoms.
"A mother doesn't like to see her child suffer like this," says Nathalie Corneau, after stoically describing her daughter Marie-Ève's nightmarish odyssey.
"You feel so powerless."
The six-year-old has been poked and prodded and studied by all manner of specialists, from pediatricians to neurogeneticists.
Their best guess – having eliminated every other possibility – is that the little girl is suffering from a rare neurological disorder, one whose genetic cause has not yet been discovered.
Corneau says that, over the years, she and her spouse have "become accustomed to the questioning looks from doctors who just can't figure out what the hell is going on."
But for Marie-Ève and her mom there is now a small glimmer of hope – a new international collaboration called PhenomeCentral that will see scientists and clinicians worldwide share information in a bid to speed the discovery of genes responsible for rare disorders.
Marie-Ève will have her entire genome sequenced (22,000 genes) and entered into a database, along with her clinical data. If another child with a similar constellation of symptoms is discovered, their genomes will be compared in a bid to find the genetic mutation(s) responsible for the disorder.
"If you have a single child with a rare condition, you're powerless to understand the cause," says Dr. Kim Boycott, a geneticist and senior scientist at the Children's Hospital of Eastern Ontario in Ottawa. "But once you have a second or a third to compare, that gives us a chance for a match, for an answer.
"It's essentially a matchmaking service for rare disorders," Boycott says.
Many diseases are rare, but because there are so many possible genetic mutations, a lot of people are affected by them.
Worldwide, about 350 million people suffer from an estimated 7,000 rare diseases, and the genetic causes have yet to be discovered for fewer than half of them. In Canada, 250,000 people have rare disorders, and fewer than half have been diagnosed.
Because the conditions are genetic, they strike early, so much research focuses on children.
A condition such as Marie-Ève's – which is probably due to defective neurons causing electrical problems in the brain – could be a one in a million, or even a one in a billion, occurrence.
Finding the defective gene will not magically make her better.
"But knowing is better than not knowing," Corneau says. "A diagnosis would give us hope."
There are practical benefits too.
"If you have an accurate diagnosis, you get better support and services. That's sad but true," Boycott says.
Identifying a genetic cause creates the possibility for developing drug therapies and, in some cases, can point clinicians to existing therapies and better treatment. (Marie-Ève, for example, takes painkillers and anti-migraine drugs to lessen symptoms, but few of these drugs have been tested in children, so the long-term risks are unknown.)
Identification also allows for testing so prospective parents can know if their other children might be affected too. "Sometimes the best news we can give parents is that it's a genetic condition that's one in a million," Boycott says. "Often, they're very scared."
But to get to that stage where conditions are pinpointed and named, a lot of work has to happen in the lab – the genetics lab and the computer lab. PhenomeCentral is, in fact, a collaboration between clinicians, genetic researchers and computer scientists.
Groups like CARE for RARE in Canada, the National Institutes of Health Undiagnosed Diseases Program in the United States, RD-Connect in Europe and the International Rare Disease Consortium have come together to swap data in the hope they can find answers for thousands of patients with unsolved conditions.
This work is already under way. In Canada – a leader in the rare-diseases field – 60 novel rare-disease genes have been identified in the past two years alone.
But that's the low-hanging fruit. Most of these conditions affected more than one person in a family, making the discovery of genetic anomalies relatively easy.
Cracking genetic mysteries like Marie-Ève's – a family with no history of migraines and with two other children who are unaffected – is far more difficult.
"You hear a lot these days about the power of Big Data," says Dr. Michael Brudno of the Centre for Computational Medicine at the Hospital for Sick Children in Toronto. "In this case, the data isn't just big, it's complex."
Brudno said that the power of sharing data can't be overstated, and he predicted more collaborators will soon join.
"If you're the only person with a telephone, it's not very useful. But when the network grows the power of the data grows exponentially," he said.
While the software and the science are complex, the ultimate goal is straightforward: to improve the quality of life of children with rare conditions and their families, to shed light on the afflictions of kids like Marie-Ève so that they become a little more bearable.
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