“In some cases, that meant that we could actually go after the primary pathology or the primary cause of the condition in a way that we never would have thought of before."
Cerebral palsy (CP) has long been viewed primarily as a condition arising from environmental factors such as birth complications or infections. However, emerging research underscores the significant role of genetics in CP cases, leading to shifts in both diagnosis and treatment approaches. Michael C. Kruer, MD, a pediatric neurologist and human geneticist at Phoenix Children’s Hospital, emphasized the evolving understanding of CP genetics and its implications for clinical care.
“Pediatricians, you know, inevitably find themselves to be the primary advocates for the kids they look after. They're really the gatekeepers for access to specialists,” Kruer explained. With growing evidence supporting the genetic origins of CP, he urges primary care providers to consider genetic evaluations. “CP can, but often has a genetic cause,” he stated, stressing that recognizing this fact is essential for patient advocacy and informed medical decision-making.
A recent study co-authored by Kruer and published in JAMA Pediatrics analyzed multiple published cohorts to reassess the genetic basis of CP. The findings were striking:
“In our study, about 27% of the nearly 2,000 CP patients who underwent exome sequencing had an identifiable genetic cause for their CP” . This result aligns with previous research indicating that approximately 1 in 4 individuals with CP have a genetic explanation for their condition.
The study also explored the clinical impact of these findings.
“Now the follow-up question was, 'well, does this change anything for that person's care,' not, 'you know, some point in the future, but right now,'” Kruer remarked.
“We found that roughly about 1 in 4 individuals that had an identified genetic cause for their CP, or those folks, it actually prompted a change in their care” .
These changes in care manifested in several ways.
“In some cases, that meant that we could actually go after the primary pathology or the primary cause of the condition in a way that we never would have thought of before,” Kruer explained. “As we know, for CP care and a lot of medicine, it's still very much a guess-and-check world,” he added.
Genetic findings, however, are now helping clinicians tailor treatments more effectively: “The genetic findings would help that clinician to reach for the best treatment first."
The study found that among 1841 patients with CP who underwent exome sequencing, 502 (27%) had pathogenic or likely pathogenic variants. Furthermore, 8% had genetic findings classified as actionable, meaning they could lead to immediate changes in clinical management.
Actionable findings were categorized into 3 groups: interventions targeting the primary disease mechanism, prevention strategies, and symptom management, with 71% of potential interventions deemed to have moderate-to-high safety and practicality.
As research continues to illuminate the genetic underpinnings of CP, genetic testing is poised to become a critical component of CP diagnosis and management, offering tangible benefits for both patients and providers.
Reference:
Lewis SA, Chopra M, Cohen JS, et al. Clinical actionability of genetic findings in cerebral palsy: a systematic review and meta-analysis. JAMA Pediatr. 2025;179(2):137-144. doi:10.1001/jamapediatrics.2024.5059