A new study has identified genes which may be partially responsible for the development of cerebral palsy, adding a new dimension to understanding its risk factors and causes.
Cerebral palsy (CP), a condition that affects the development of motor skills in children, is the most common childhood-onset physical disability with more than 46,000 people impacted in Ontario alone. CP can have different causes, such as infections, injuries, or lack of oxygen before or during birth, but until now, the genetic contributors to CP have remained largely unknown.
Recent research published in Nature Genetics, from a multi-site Canadian project with the involvement of Dr. Darcy Fehlings, Dr. Stephen Sherer, and Dr. Richard Wintle of the Childhood Cerebral Palsy Integrated Neuroscience Discovery Network (CP-NET), an Ontario Brain Institute Integrated Discovery Program, provides a more detailed look into the genetic causes of the condition. Findings from the study suggest the existence of many genetic variants contributing to CP.
In fact, the seven-year study – which included more than 200 participants from CP-NET plus their biological parents in addition to the participants from Canadian CP Registry – found that more than one in ten children (11.3 per cent) had a genetic variant or likely genetic variant for their CP, and almost 18 per cent of children had variants of uncertain significance that may be linked with the condition after further research.
Dr. Wintle, the governance chair for the International CP Genomics Consortium and the executive director of HPC4Health, explained that the collaborative research team looked at both the children and parents to see which genes may have been inherited but were also able to identify those in the children that weren’t. He said that these differences may be attributed to ‘de novo changes’ in the genetic makeup of a person – a change in the DNA sequence of a gene that is seen for the first time in a person and has not appeared in previous generations – which can sometimes point to genes that may be involved in CP or some of the other health conditions that people with CP can have.
“We discovered some genes that might not have previously been appreciated as being involved in CP, so especially in the 18 per cent [of variants of uncertain significance], there is still a lot of work to be done to fully understand how they may be involved and contributing to CP in terms of nervous system development and function,” he noted.
Dr. Fehlings, a senior clinician scientist at the Holland Bloorview Kids Rehabilitation Hospital, said that the results of this study highlight an opportunity for precision health for children where clinicians can look at a person’s individual genetic variation to understand how it contributes to the whole picture a child has with cerebral palsy. Moreover, she noted, it may inform future diagnosis and treatment, impacting how interventions are designed for each child.
"Many of the children we see come through our doors have genetic variations that are associated with their cerebral palsy. This opportunity for precision medicine is of utmost importance to accurately diagnose etiology across all children with CP, improve family counselling, and choose medical and rehabilitation interventions best suited for the child.”
- Dr. Darcy Fehlings, CP-NET program lead
Jessica Geboers, a member of CP-NET’s Stakeholder Advisory Group and someone who lives with CP, feels encouraged by the results of this ground-breaking research but understands that more research into the potential genetic causes of this childhood disorder is needed before patients see a change in their lives.
“New information from this study could be helpful for families looking for answers about the root of cerebral palsy but it’s early days and work needs to be done to translate these results into everyday language,” she said. “For instance, ‘genetic’ doesn’t necessarily mean ‘hereditary’. And moving forward, I think it will be important for people with CP to understand exactly how genetic causes may affect treatment and care.”
As part of her work with CP-NET, Ms. Geboers has collaborated with researchers like Drs. Fehlings and Wintle to embed patient priorities into scientific studies as well as help describe findings in lay terms.
The data collected through this study are the first whole-genome sequencing data – the process of determining the entirety of a person’s DNA sequence at a single time – to be made available in Brain-CODE, OBI’s neuroinformatics and analytics platform, in an effort to improve access to genome sequencing data for scientists around the world.
Ultimately, Drs. Fehlings and Wintle, along with their research teams at the Holland Bloorview Kids Rehabilitation Hospital and SickKids, acknowledge that more research is needed into the genetic causes of cerebral palsy, and hope the data can also help other scientists identify new genes and pathways that are involved in CP.
Read this groundbreaking CP-NET paper.
Visit the CP-NET website.
