Although it is one of the most common childhood-onset physical disabilities, the exact causes of cerebral palsy (CP) are not always clear. The potential causes and risk factors include damage to the brain’s white matter, infections during pregnancy, injury to the unborn baby’s head, premature birth, and low birth weight. Furthermore, the genetic contributors to CP have remained largely unknown to date. 

However, new research from scientists at the Hospital for Sick Children (SickKids), McGill University Health Center, and elsewhere identifies genes that may be at least partially responsible for the development of CP. Full details of the study are published in a paper in Nature Genetics titled, “Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.”

Their findings point to many possible CP-associated genetic variants which could be new treatment targets or improve disease diagnosis. The findings also broaden scientists’ understanding of the factors involved in CP’s development. Historically, “cerebral palsy was mostly thought to be the result of entirely environmental factors during birth,” said study co-lead Stephen Scherer, PhD, chief of research and senior scientist in SickKids’ genetics & genome biology program and director of SickKid’s 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 is the culmination of a seven-year multi-site study that collected whole-genome sequencing data from 327 children with CP and their biological parents. The scientists compared it to data from three independent clinical cohorts and two pediatric control cohorts. About 11% of children had a genetic variant or likely genetic variant for CP, and nearly 18% of children had variants of unknown significance that could be linked to CP. Many of the variants identified also overlapped with other neurodevelopmental disorders including autism spectrum disorder. 

The datasets collected through this study are the first whole-genome sequencing datasets to be made available in the Brain-CODE analytics and informatics platform, which is managed by the Ontario Brain Institute. The platform manages the acquisition and storage of multidimensional datasets including neuroimaging, genomics, proteomics, and genomics data that are collected from participants with various brain disorders. Besides CP, the platform also collects data from patients with epilepsy, neurodegeneration, depression, and neurodevelopmental disorders. 

Identifying genes that are potentially involved in CP is “a step forward in better understanding the complex genetic and environmental risk factors that may determine an individual’s chance of developing this complex condition to help individualize future treatment approaches,” noted study co-lead Maryam Oskoui, MD, MSc, senior clinician scientist at the McGill University Health Centre and director of the neurology division at Montreal Children’s Hospital. “Our rich dataset of deeply genotyped and phenotyped trios offers the best available evidence to shift clinical practice to include genetic testing in all children with CP.” 

The team’s hope is that scientists will build on their work to identify new genes and pathways involved in CP as well as to study how genetic variants affect the brain in children with CP and whether these could be targets for new treatments. 

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