When it comes to fetal alcohol syndrome disorder (FASD), the math is clear early diagnosis + early treatment = best possible outcomes. Unfortunately, for many kids with FASD, that’s not quite how the equation adds up. Three per cent of Canadian kids have FASD and most won’t be diagnosed until they are in elementary school, when their behaviour and learning challenges set them apart from their peers – and when therapies start becoming less and less effective.
Researchers at BC Children’s Hospital are leading efforts to change all of that. In a study published in Clinical Epigenetics, Dr. Michael Kobor and his colleagues identified a series of distinctive changes in DNA methylation – a chemical modification to the DNA that can affect how genes are regulated – that seems to be associated with FASD. Pinpointing these unique patterns brings researchers closer to creating a simple test that could help to diagnose FASD faster and earlier in life.
In 2016, Dr. Kobor garnered international attention by leading an initial study of DNA from children with FASD. Dr. Kobor and co-author Dr. Elodie Portales-Casamar, BC Children’s investigator, looked at the epigenetic level—the changes that can happen to our genes as a result of our environments before and after birth. He specifically looked at one epigenetic process called DNA methylation.
“DNA methylation works like a dimmer switch on specific genes,” Dr. Kobor explains. “It turns some down, and it turns some up. In the case of FASD, prenatal exposure to alcohol affects the pattern of DNA methylation in the baby’s cells. It leaves behind distinct patterns that we may be able to test for one day.”
FASD results from exposure to alcohol in the womb and encompasses a range of symptoms including problems with memory, learning behaviour and social skills. If children are identified early – before age three – behavioural interventions are often effective at teaching them skills and strategies to manage their symptoms. Early diagnosis also means better access to support such as counselling and respite care.
Dr. Kobor says this latest study builds off his 2016 study by using a different group of DNA samples to replicate the initial results.
“Our first study was a major leap forward—it was the biggest human study of FASD to date. To be able to replicate those findings, to validate them, is very significant. Very few findings are replicated to this extent, with DNA we had not looked at before.”
In this recent study, Dr. Kobor’s team used a complex statistical analysis program to classify the patterns they observed in these distinct genetic markings. This kind of computer analysis, called machine learning, is most powerful with large data sets.
To date, Dr. Kobor’s team has tested hundreds of DNA samples. The program will be even more effective with thousands.
“Our studies only used samples from Canadian populations. To get results that are more meaningful we need larger and more diverse population groups. Now, researchers around the world are setting out to replicate our findings with their own populations. The hope is to combine all this data and get more precise signatures and one day, a reliable biomarker,” says Dr. Kobor.
Dr. Kobor’s research approach is already being used with US samples. Plans are underway for a similar project in Australia and he will soon share his work with researchers in Europe and South Africa.
“There is a real movement worldwide to embrace the opportunities we have with epigenetics and DNA methylation to better understand FASD,” says Dr. Kobor. “I’m pleased and proud that our team is at the forefront; that our research is the root of next-generation efforts towards a possible breakthrough in this condition.”
For Dr. Kobor, epigenetics holds promise beyond new diagnostic tests. “Epigenetic changes are more complicated to unravel than genetic mutations. There is a lot more malleability – and perhaps more potential for intervention.”
Dr. Kobor says the children he meets motivate his FASD research. “Early interventions show great promise and can make a huge difference. I hope this complex DNA work can one day help kids.”
He is also grateful to the families who generously participate in his studies. “They often go out on a limb for us so it’s really important to keep them in mind when we are working in isolation in the lab. We need to respect their concerns and not stigmatize them; we need to work hard to help them.”
To that end, Dr. Kobor’s Sunny Hill BC Leadership Program is planning follow-up focus groups with families living with FASD, as well as with medical personnel, educators, and other professionals who provide support to families and children with FASD, to talk about the epigenetic research and address any concerns they may have.
Dr. Kobor is also inspired by the late Clyde Hertzman, whose picture sits on Kobor’s desk. Hertzman founded the Human Early Learning Partnership at UBC.
“He was a strong advocate for the rights of children and the first in Canada to think about the continuum from cell to society,” says Dr. Kobor. It’s my hope that if we can provide hard scientific evidence for the impact of early-life experience on our DNA that may push our society to do something for vulnerable children.”
Dr. Michael Kobor is an investigator at BC Children’s Hospital and the Centre for Molecular Medicine and Therapeutics, a professor in the Department of Medical Genetics at the University of British Columbia, the Tier 1 Canada Research Chair in Social Epigenetics and the Sunny Hill BC Leadership Chair in Child Development.
Dr. Elodie Portales-Casamar is an investigator at BC Children’s and a clinical assistant professor in the UBC Department of Pediatrics.
This research is supported by the Kids Brain Health Network, a Canadian Network of Centres for Excellence and BC Children’s Hospital Foundation.