Scientists have identified a strong connection between genetic modifications known to cause cerebral palsy and neurodevelopmental disabilities.
Cerebral palsy influences posture and movement and usually occur together with other neurodevelopmental diseases, such as epilepsy, autism spectrum disorder, and intellectual disability.
Most often, individual cases of cerebral palsy are attributed to birth asphyxia, albeit new studies have suggested that asphyxia is responsible for less than 10% of cases. But according to a growing body of research, cerebral palsy may be induced by genetic variations, as is the case with other neurodevelopmental diseases.
A group of scientists, including researchers from Geisinger and GeneDx Inc.—a wholly-owned subsidiary of BioReference Laboratories Inc., an OPKO Health company and a global leader in genetic diagnostics—analyzed the DNA sequence of a total of 1,526 adults and children with cerebral palsy.
The researchers identified disease-causing modifications in 229 genes, many of which have already been detected in individuals with cerebral palsy and also other neurodevelopmental disorders. They subsequently detected disease-causing genetic changes in 10.5% of a primarily adult group from Geisinger and in 32.7% of a primarily pediatric group of patients from GeneDx.
Finding a genetic cause for cerebral palsy not only provides an answer to the family, but also informs recurrence risk estimates for future children born to the same parents.”
Christa Martin, PhD, Study Senior Co-Author, Professor, and Director, Autism & Developmental Medicine Institute, Geisinger Health System
Martin continued, “Previous studies in families with children with CP have found a risk of recurrence of 1-2%. Identifying a genetic change that causes the CP in a child and is not present in either parent decreases the risk to less than 1% for future children born to the same parents. When the genetic change that causes CP is inherited from one or both of the parents that risk increases to 50% and 25%, respectively.”
At GeneDx, we were able to test three-fourths of patients along with both parents, allowing us to establish the inheritance of the genetic changes. For approximately a third of the families where a causative genetic change was identified, the family recurrence risk increased to 25% to 50%.”
Francisca Millan, MD, Study Co-First Author and Associate Director of Neurogenetics, GeneDx
The researchers wrote that the identification of such genetic variations in numerous patients as well as replication of these results across various settings and cohort types offers strong proof for their role in cerebral palsy. The study results were published in the Journal of the American Medical Association (JAMA).
DNA sequencing is recommended as a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders, which are known to co-occur with cerebral palsy.”
Andres Moreno De Luca, MD, Physician-Scientist and Clinical Neuroradiologist, Geisinger Health System
De Luca, who is also the co-first author of the study, added, “Since cerebral palsy can be identified earlier than other neurodevelopmental disorders, such as intellectual disability and autism spectrum disorder, genetic testing for individuals with cerebral palsy may allow for quicker identification of genetic changes and facilitate early interventions and treatment.”
“This study reiterates the value of genetic testing for neurodevelopmental disorders and highlights the utility of genetic testing for cerebral palsy patients. Increasing utilization of and access to DNA sequencing for these patients will lead to earlier diagnoses and improved care in many cases,” concluded Kyle Retterer, the senior co-author of the study, senior vice president, and chief technology officer at GeneDx.
De Luca, A, M., et al. (2021) Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy. JAMA. doi.org/10.1001/jama.2020.26148.