NeuroDevNet study documents strong role of genetics in cerebral palsy

Août 3, 2015

New evidence arising from collaboration between NeuroDevNet’s cerebral palsy and autism researchers has uncovered surprisingly strong evidence for genetic causes for CP.

Stroke, oxygen deprivation and infections in newborns have long been considered causes of cerebral palsy, the most common cause of physical disability in children. CP is occurs in two out of every thousand births in Canada. “Clinically Relevant Copy Number Variants Detected in Cerebral Palsy,” published online today in Nature Communications has the potential to reboot understanding of the condition, as well as approaches to counseling, prevention and treatment of children with cerebral palsy.  

“Our research suggests that there is a much stronger genetic component to cerebral palsy than previously suspected,” says lead study author Dr. Maryam Oskoui, Pediatric neurologist at the Montreal Children’s Hospital, and co-director of the Canadian Cerebral Palsy Registry, a confidential, trans-national collection of information about people with cerebral palsy whose data served as the basis of the new study.

Clinical geneticists floored by findings

Just how the genetic factors identified – copy number variants (CNVs), or genetic changes that involve duplication, deletion or reorganization of segments of DNA in a person’s genetic code – interplay with other established risk factors remains to be fully understood. “Two newborns exposed to the same environmental stressors will often have very different outcomes,” said Oskoui. “Our research suggests that our genes impart resilience, or conversely, a susceptibility to injury [that underlies CP].”
Children with cerebral palsy have difficulty with motor skills development in early life, and often have learning, speech, hearing and visual impairments, as well as other disabilities, such as epilepsy or autism. The condition has a very diverse profile: some children are mildly affected, while others are unable to walk on their own or communicate.
Genetic testing is not routinely performed or recommended, and is only resorted to when other causes for CP cannot be found, according to Oskoui. In the study, researchers tested genetic samples from 115 children with CP drawn from the Registry. They found that 10 percent of the children have CNVs affecting genes that are deemed clinically relevant. CNVs are found in less than one percent of the general population.
“When we made the CNV findings I was surprised at the high rate of de novo, or new mutations,” said Dr. Stephen Scherer, principal investigator of the study, and co-lead of NeuroDevNet’s Autism Research Group. “When I showed the results to our clinical geneticists at the Centre for Applied Genomics at SickKids, they were floored. In light of the findings, we suggest that genomic analyses be integrated into the standard of practice for diagnostic assessment of cerebral palsy, as is already the case with autism and other developmental disorders.”

The Tip of the Iceberg

The study also indicates there are many genes involved in cerebral palsy. “It’s a lot like autism, in that many different CNVs affecting different genes are involved, which could possibly explain why the clinical presentations of both of these conditions are so diverse, added Scherer, who is also the director of the University of Toronto McLaughlin Centre. “Interestingly, the frequency of new CNVs identified in these children with cerebral palsy is even more significant than some of the major CNV autism research from the last ten years. We’ve opened many doors for new research into cerebral palsy.”
Those doors were opened, in large part, due to NeuroDevNet, a national Network of Centres of Excellence focusing on early diagnosis, early intervention and treatment, and support for families, according to Scientific Director Dr. Daniel Goldowitz. “These findings are what NeuroDevNet is all about - and validate its coming of age - catalyzing efforts between multiple disciplines and researchers that would likely not have otherwise occurred. The Network brought together the world-leading genetics of Dr. Scherer, with the passionate clinical leads of the NeuroDevNet-funded Canadian Cerebral Palsy Registry, Dr. Oskoui and Dr. Michael Shevell – to produce a landmark finding that lays the groundwork for the adoption of best practices in the care of children with cerebral palsy.

“These findings embody what NeuroDevNet is all about,” added Goldowitz. “As we gather more data in the registry, and align the cases of CP with genomic, and soon, epigenomic findings – modifications to DNA that do not change the DNA sequence but can affect a gene’s activity – there will be knowledge obtained that will make the current report seem as the tip of the iceberg.” 

Implications for Families - and for Clinical Practice

"Parents want to know why their child has particular challenges," said Dr. Michael Shevell, co-director of the Canadian CP Registry and Chair of the Department of Pediatrics at the MCH-MUHC. "Finding a particular reason opens up multiple vistas related to understanding, specific treatment, prevention and rehabilitation. This study will provide the impetus to make genetic testing a standard part of the comprehensive assessment of the child with cerebral palsy."

Having accompanied a number of families through the process of diagnosis, Dr. Oskoui believes the findings will help resolve some - but not all - of the inevitable questions that arise about pregnancy and delivery when a child is born with CP. "Families want to know why," she said, "but sometimes, we will never know that answer."

Clinically Relevant Copy Number Variations Detected in Cerebral Palsy
was supported by NeuroDevNet, the Canadian Institutes of Health (CIHR), Genome Canada, The University of Toronto McLaughlin Centre, and SickKids Foundation. Currently supported by NeuroDevNet, the Canadian Cerebral Palsy Registry was initially funded by the Réseau de recherche sur le développement, la santé et le bien-être de l'enfant (RSDE) des Fonds de Recherche en Santé du Québec (FRSQ). Dr. Maryam Oskoui is a FRSQ Chercheur-Boursier Clinicien Junior 1.