Pediatric neurologist Genevieve Bernard chats with research assistant Kether Guerrero at the MUHC in Montreal on Monday, Feb. 25, 2019. Bernard joined forces with scientists from the Rady Children’s Institute for Genomic Medicine in San Diego to discover a new genetic mutation responsible for a rare paediatric neurodevelopmental condition known as VARS-related disorder.
Dave Sidaway / Montreal Gazette
Emily Standen’s pregnancy was uneventful, but it was clear as soon as her daughter Mathilde Poliquin was born, in January of 2013 at the McGill University Health Centre‘s Royal Victoria Hospital, a month early, that there was a problem.A pediatrician popped his head into the room and said, “I need to speak to the father.” Gabriel Poliquin remembers being told, “Something is wrong. We don’t know what it is.”The baby was immediately transferred to the neonatal intensive care unit of the Montreal Children’s Hospital. Her head was smaller than normal and her neurological exam was “very abnormal,” recalled MUHC pediatric neurologist Geneviève Bernard, and she had severe epilepsy.A magnetic resonance imaging scan showed that Mathilde’s brain had not developed completely and there was leukoencephalopathy, a disorder of the brain’s white matter. Doctors could not say how long she would live but they were “pretty certain” it would be less than a year, Poliquin said. Palliative care was involved; Mathilde was heavily medicated to try to control her seizures.
Mathilde Poloquin lived for 2 1/2 months after her birth in January of 2013. Five years later, her parents learned that she had been born with a rare genetic disorder — after scientists in Montreal and in San Diego had found the gene that had caused the extremely rare neurodevelopmental disorder she died from, VARS-related disorder.
courtesy Emily Standen
She was brought home in late February. “Our No. 1 concern when she was alive was keeping her comfortable,” Standen said. She died at home in mid-April. What had caused Mathilde’s condition “was a mystery and an unknown,” she said.And then in 2018 they heard from Bernard, isa research scientist as well as a clinician, that Mathilde had died of an extremely rare neuro-developmental condition known as VARS-related disorder and that Bernard and her team at the MUHC Research Institute had found the gene that had caused the condition.“To have Dr. Bernard say ‘It is this and we can screen for it’ was this amazing relief,” said Standen. She and her husband have a healthy daughter who was 2½ when Mathilde was born; they were concerned about the possibility that she would one day have to endure the pain they did.There was a sense of closure, too, “that there is an answer to what caused the problem. And information is always better than the unknown,” said Standen, a scientist herself: She is an assistant professor of biology at the University of Ottawa. Mathilde was born when she was doing a post-doctoral fellowship in Montreal.“t doesn’t change anything with respect to our own suffering or our experience,” said Poliquin, a lawyer. “It does put a conclusion to a narrative arc and there is some relief in that. I would rather that the story had not happened — but it is a story that has a kind of ending, and there is a therapeutic quality to that.”He said he and his wife had given their consent to having their daughter’s blood samples used in Bernard’s study “as a way to help people or the advancement of science — and even just participating providing meaning for Mathilde’s life.”Finding a disease-causing gene is a complex procedure. “For it to be recognized as a disease-causing gene, you need to find several people with the same mutation and a similar clinical presentation,” Bernard explained in an interview on Monday. “That is why it is so important to collaborate with international researchers.”It was because of an international effort led by physician-scientists at Rady Children’s Institute for Genomic Medicine in San Diego in collaboration with Bernard’s team at the MUHC that she was able to confirm Mathilde’s diagnosis. Their findings, published this month in Nature Communications, are a first step into research into potential targeted therapies for the devastating condition.Investigators did advanced genetic tests on blood samples from seven children with neurodevelopmental conditions evaluated by doctors in Montreal, San Diego and Cairo. Mathilde, Bernard said, was the most severely affected.“And you have to prove that the gene causes the disease in lab experiments. So we did studies to prove we had the right gene.”A research article must be peer reviewed before it is accepted for publication — and “only after it is accepted for publication is it a real gene,” she said.In the six years that Bernard’s lab has been in place, her team has discovered six genes. Most labs specialize in a sub-category of disease, she explained. “I am a gene hunter for white-matter abnormalities.”The term rare diseases is in some ways a misnomer., Bernard suggested. Considered individually, every disease is rare: Only about 23 cases of VARS-related disorder have described, although there may be more. But together, rare diseases affect one person in nine or 10.And many “are so severe and terrible that they have a huge impact on families,” she said. “Families feel isolated. I think it is important to show the world they exist so that people understand what these families are going through.”firstname.lastname@example.org