For most of her 12 years of life, Anna Boileau has been a medical mystery.
As an infant, her oxygen levels were low and she failed to gain weight. She spent the second six months of her life in hospital.
While her fine motor skills are good and she learned to talk early, she didn’t walk until she was two. She doesn’t have the reflex to protect herself from falls by putting out her arms, so she has suffered broken bones and sustained concussions. She has shortness of breath and needs a breathing machine at night to ensure that she keeps breathing.
Over the years, Anna saw hundreds of doctors. There were dozens of tests, from muscle biopsies and metabolic testing to at least five different genetic tests.
“Sometimes she had so many stitches and surgeries, she looked like Frankenstein. And they couldn’t figure out what she had,” said Anna’s mother, Mallory Boileau.
Then, about month ago, the results of Anna’s genome-wide sequencing concluded that she has an ultra-rare genetic condition because of two variants affecting a gene called SELENON. She inherited one variant from her mother and one from her father.
While there is no cure, the knowledge has provided her family with a roadmap for treatment, based on other cases from around the world.
“I keep picturing a family with a new baby. If I knew then what I know now, it would have been a game-changer,” said Boileau.
There are thousands of rare diseases. Added together, they affect millions of people. About 930,000 Ontario residents have a rare disease. About a third of these don’t have a genetic diagnosis.
CHEO and the Hospital for Sick Children in Toronto are part of Genome-wide Sequencing Ontario (GSO), a pilot project aimed at ensuring children with rare diseases in Ontario get diagnosed as early as possible.
Under the two-year project, about 2,000 families will get exome sequencing and genome sequencing.
Exome sequencing examines the very important one to two per cent of the genome that codes for proteins. Genome sequencing examines the patient’s entire genome.
Genome-wide sequencing can search all known genes for variants that could cause disease. It provides a much more comprehensive analysis of a patient’s genetic data. In Anna’s case, her condition would not have been identified with exome sequencing.
The GSO project started about a year ago. So far, the DNA of more than 1,800 patients and family members has been sequenced.
It’s a time-consuming process, but the project aims to return results within 12 weeks, said Dr. Kym Boycott, a medical geneticist at CHEO and a senior scientist at the CHEO Research Institute. About 300 to 500 patients a year at CHEO would be candidates.
So far, GSO has been able to provide a diagnosis for 32 per cent of participating families, in line with worldwide diagnostic rates reported for this technology.
Conventional genetic testing involves testing subsets of genes. This can lead to multiple tests and investigations, which can be time-consuming and costly without a diagnosis. Boileau recalls one of Anna’s samples was sent first to Toronto, then Boston, then Europe — but there were still no answers.
Although exome sequencing was already available through labs outside Canada, the pilot project will determine whether it’s feasible to provide increased access to genome-wide sequencing with faster results.
The GSO project will also help track how many cases were diagnosed and the impact on the health-care system. It may be more efficient if the sequencing is done at the beginning of the patient’s diagnostic journey, saving time and money on other diagnostics, said Boycott.
For families, having a name for a mystery illness is a relief. Anna’s diagnosis was the first time in 12 years that her family could put a name to her condition, said Boileau.
“It would be great for families to get this type of answer at the beginning of their journey,” she said.
A diagnosis can also be the first step to targeted care. Other children with Anna’s genetic condition, for example, have been at risk of developing scoliosis — curvature of the spine — and heart conditions.
Only about 30 children have been reported with Anna’s condition in medical literature, but there are likely more who have not been identified.
“We have databases for many rare diseases and identifying families to share their experience is an important part in understanding what this disease means for kids and how best to manage it,” said Boycott.
There is currently a clinical trial recruiting to study Anna’s condition and it is looking to find 20 children to participate to understand more about the condition itself. “This is a really important next step for all rare diseases,” she said.
Anna has missed a lot of school because of her appointments and hospitalizations, but she is resilient and gets straight As at school, said her mother. While she will never be an athlete, she’s an avid reader who loves art and wants to be a teacher some day.
Anna hopes her 12-year journey will be helpful to others.
“I’m hoping I can help other kids.”