null 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.

Study co-lead Dr. Maryam Oskoui is a 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.
Study co-lead Dr. Maryam Oskoui is a 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.

“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.

About the study

The study Comprehensive Whole-Genome Sequence Analyses Provide Insights into the Genomic Architecture of Cerebral Palsy was conducted by Darcy L. Fehlings, Mehdi Zarrei, Worrawat Engchuan, Neal Sondheimer, Bhooma Thiruvahindrapuram, Jeffrey R. MacDonald, Edward J. Higginbotham, Ritesh Thapa, Tarannum Behlim, Sabrina Aimola, Lauren Switzer, Pamela Ng, John Wei, Prakroothi S. Danthi, Giovanna Pellecchia, Sylvia Lamoureux, Karen Ho, Sergio L. Pereira, Jill de Rijke, Wilson W.L. Sung, Alireza Mowjoodi, Jennifer L. Howe, Thomas Nalpathamkalam, Roozbeh Manshaei, Siavash Ghaffari, Joseph Whitney, Rohan V. Patel, Omar Hamdan, Rulan Shaath, Brett Trost, Shannon Knights, Dawa Samdup, Anna McCormick, Carolyn Hunt, Adam Kirton, Anne Kawamura, Ronit Mesterman, Jan Willem Gorter, Nomazulu Dlamini, Daniele Merico, Murto Hilali, Kyle Hirschfeld, Kritika Grover, Nelson X. Bautista, Kara Han, Christian R. Marshall, Ryan K. C. Yuen, Padmaja Subbarao, Meghan B. Azad, Stuart E. Turvey, Piush Mandhane, Theo J. Moraes, Elinor Simons, George Maxwell, Michael Shevell, Gregory Costain, Jacques L. Michaud, Fadi F. Hamdan, Julie Gauthier, Kevin Uguen, Dimitri J. Stavropoulos, Richard F. Wintle, Maryam Oskoui and Stephen W. Scherer.

DOI 10.1038/s41588-024-01686-x

About the Research Institute of the MUHC

The Research Institute of the McGill University Health Centre (RI-MUHC) is a world-renowned biomedical and healthcare research centre. The Institute, which is affiliated with the Faculty of Medicine of McGill University, is the research arm of the McGill University Health Centre (MUHC) – an academic health centre located in Montreal, Canada, that has a mandate to focus on complex care within its community. The RI-MUHC supports over 420 researchers and close to 1,200 research trainees devoted to a broad spectrum of fundamental, clinical and health outcomes research at the Glen and the Montreal General Hospital sites of the MUHC. Its research facilities offer a dynamic multidisciplinary environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan. The RI-MUHC is supported in part by the Fonds de recherche du Québec – Santé (FRQS).

About the Montreal Children’s Hospital

Established in 1904, the Montreal Children's Hospital (MCH) is Quebec’s oldest children’s hospital and the pediatric hospital of the McGill University Health Centre (MUHC). A tertiary and quaternary care teaching and research facility, treating newborns, children and adolescents up to age 18, it serves 63 per cent of the geographic population of Quebec.

With its pediatric care and research facilities adjacent to the adult facility on the Glen site, the Children’s is in a unique position to offer services and research across the lifespan. The Centre for Innovative Medicine - the only clinical research centre in a hospital setting in North America – allows its researchers to conduct clinical trials on the hospital site.

The Children's is a leader in providing a broad spectrum of highly specialized care to young patients and families from all across Quebec. The hospital is a provincially designated trauma centre and is recognized for its wealth of expertise in cardiology and cardiac surgery, emergency care, neurology and neurosurgery.

Media contact

Christine Bouthillier
Communications Agent, Montreal Children’s Hospital