NEW YORK – New research suggests routine genetic testing could have clinical utility for individuals with cerebral palsy (CP), making it possible to uncover unappreciated clinical management or treatment options for a significant subset of patients.
The work appeared in a paper published in JAMA Pediatrics on Monday.
"Our findings suggest that genetic testing could improve quality of life and reduce the overall cost of care," first author Sara Lewis, a postdoctoral researcher affiliated with Phoenix Children's Hospital and the University of Arizona, said in an email. "We hope by demonstrating clinical utility and summarizing the currently available evidence, more physicians and geneticists will recommend genetic testing for their patients."
For their analyses, Lewis and colleagues at Phoenix Children's Hospital, the University of Arizona, and other centers in the US and internationally searched for pathogenic or likely pathogenic variants in 1,841 exome-sequenced individuals with CP who were enrolled in previous clinical or research cohorts, to discern the proportion of cases involving clinically actionable variants or changes to individual genes already targeted by existing treatments.
Although genetic testing is not routinely recommended for cerebral palsy, reflecting a relative dearth of research in the area, the study's authors suspected that sequencing-based tests may unearth clinically informative alterations that could improve precision medicine possibilities for patients, while providing answers for the individuals and their families.
"Previous studies from our lab and others have shown that monogenic etiologies account for about [one in three] cases of CP," senior and corresponding author Michael Kruer, a researcher with the pediatric movement disorders program at Phoenix Children's Hospital, said in an email, noting that the new study "builds on this prior work to address how positive findings from whole-exome sequencing could impact patient care."
All told, the team uncovered pathogenic or likely pathogenic variants in 243 genes across 502 participants, accounting for 27 percent of those sequenced. More than one-quarter of those cases involved variants that were classified as clinically actionable and expected to inform some aspect of a patient's clinical management.
"Changes in care could include avoiding complications, reaching for the best treatments first, or targeting underlying molecular mechanisms," Kruer explained.
Clinically actionable variants turned up in 140 individuals with CP (8 percent of those tested), the researchers reported, with 58 of the pathogenic/likely pathogenic variant-containing genes showing ties to CP disease mechanisms, prevention, or symptom management.
"These findings indicate that asking why a person has cerebral palsy is important, and incorporating genome sequencing into the diagnostic workup for individuals with CP could impact treatment," Kruer said.
He noted that further research is expected to help the investigators untangle the broader consequences of a molecular understanding of CP contributors on patient care, while the growing list of actionable alterations in CP is expected to inform gene knockdown or replacement experiments for developing future therapeutic methods.
"Our findings build on prior work that indicates that identifying specific etiologies of CP may change clinical care," the authors explained, noting that "[e]arly use of genetic sequencing could lead to optimal clinical outcomes by offering therapies tailored to the individual before complications develop, potentially reducing lifetime costs for families, payers, and society, which can be considerable."