Genetic causes of cerebral palsy uncovered through whole-genome sequencing

Canadian scientists demonstrate that cerebral palsy may be caused by both genetic and environmental factors, informing diagnosis and care for the diverse condition.

Montreal, March 29, 2024 – A Canadian-led study has identified genes that may be partially responsible for the development of cerebral palsy.

Cerebral palsy (CP), a condition that affects the development of motor skills, is the most common childhood-onset physical disability. CP can have different environmental causes, such as infections, injuries or lack of oxygen before or during birth, but the genetic contributors to CP have remained largely unknown.

Novel research led by scientists at the Research Institute of the McGill University Health Centre (RI-MUHC), the Hospital for Sick Children (SickKids) and Holland Bloorview Kids Rehabilitation Hospital provides a more detailed look into the genetic causes of the condition. Their findings, published in Nature Genetics, suggest the existence of many genetic variants contributing to CP, which may inform future diagnosis and treatment.

“Our findings are a step forward in better understanding the complex genetic and environmental risk factors that may determine an individual’s chance of developing this lifelong condition to help individualize future treatment approaches,” says study co-lead Dr. Maryam Oskoui, Senior Clinician Scientist of the Fonds de Recherche du Québec – Santé at the RI-MUHC and Director of the Pediatric Neurology Division at the Montreal Children’s Hospital (MCH). “Our rich dataset offers the best available evidence to shift clinical practice to include genetic testing in all children with CP.”

“Our findings are a step forward in better understanding the complex genetic and environmental risk factors that may determine an individual’s chance of developing this lifelong condition to help individualize future treatment approaches,” says study co-lead Dr. Maryam Oskoui, Scientist in the Child Health and Human Development Program at the RI-MUHC and Director of the Pediatric Neurology Division at the Montreal Children’s Hospital (MCH). “Our rich dataset offers the best available evidence to shift clinical practice to include genetic testing in all children with CP.”

“The Canadian Cerebral Palsy Registry, from which participants in Alberta and Quebec were recruited for this genomic study, was established over a quarter century ago at the MCH at the instigation of affected families and involved clinicians, long before the molecular studies used in this research paper enabled its important findings,” adds Dr. Michael Shevell, co-author of the study and pediatric neurologist at the MCH. “The Registry has facilitated numerous studies over the years, each of which has contributed to furthering our understanding of this disorder and helped to improve care, inform families and enhance outcomes. It truly is an example of the rewards of patience in scientific progress.”

One in ten children with CP have a genetic variant associated with their condition

The scientists conducted whole-genome sequencing (determining all DNA variations) in 327 children with CP, including their biological parents, and compared it to three independent clinical cohorts as well as two pediatric control cohorts to identify whether genetic variants are involved in CP.

The seven-year study found that more than one in ten children (11.3 per cent) had a genetic variant or likely genetic variant for their CP and 17.7 per cent of children had variants of uncertain significance that may be linked with CP after further research. Many of the variants also overlapped with other neurodevelopmental conditions, including autism spectrum disorder (ASD), which is highly prevalent in children with CP.

The findings suggest that CP and its causes may be much more diverse than previously thought and showcases the strength of combining precision medicine programs, a movement to deliver individualized care to each patient.

“For 100 years cerebral palsy was mostly thought to be the result of entirely environmental factors during birth,” says study co-lead Dr. Stephen Scherer, Chief of Research and Senior Scientist in the Genetics & Genome Biology program at SickKids and Director of The Centre for Applied Genomics. “Now that we have a better understanding into the complex relationship between cerebral palsy’s genetic and environmental factors, we hope we can improve care for these children.”

This research was supported by the Canadian Institutes of Health Research, the Cerebral Palsy Alliance Research Foundation, the Cerebral Palsy Integrated Neuroscience Discovery Network, Illumina, the Ontario Brain Institute, the McLaughlin Centre of the University of Toronto, Kids Brain Health Network, AllerGen NCE, Canada Foundation for Innovation, Genome Canada, The Centre for Applied Genomics and CGEn, and SickKids Foundation.

This research would not have been possible without the participation of patients and families across Canada.