Michael Kruer, MD explains genetic testing and cerebral palsy

A recent meta-analysis, co-authored by Michael C. Kruer, MD, pediatric neurologist and human geneticist at Phoenix Children's Hospital, sheds new light on the genetic underpinnings of cerebral palsy (CP) and the implications for diagnosis and treatment.

Kruer and his team have been investigating the genetic basis of CP for over a decade.

“This study really has kind of built upon the work that my laboratory has been doing for the last 10 years or so,” he explained. Initially, their research aimed to answer a fundamental question: Can cerebral palsy sometimes have a genetic basis?

“I think we now know that the answer to that question is a firm yes,” said Kruer. “We know, in fact, that about around 25 to 35% of individuals with cerebral palsy will have a genetic cause for their symptoms at this point in time that we can detect."

The study, published in JAMA Pediatrics in December of 2024, systematically reviewed genetic findings in CP cases. Among 1,841 patients who underwent exome sequencing, 27% had pathogenic or likely pathogenic variants related to their CP phenotype. Additionally, 8% of individuals had genetic findings classified as actionable, meaning the results could lead to changes in clinical management, such as targeted therapies or preventative strategies.

Kruer emphasized that understanding the genetic origins of CP is crucial for affected families and medical professionals alike.

“So, what difference does that make to families and individuals with CP? What difference does that make to the clinicians, the therapists, the physicians that care for them?” he asked. “We now know that we can reliably diagnose CP in at-risk infants as early as 6 months of age, or in the right context, even 3 to 4 months of age,” Kruer noted. This early detection can facilitate timely interventions, potentially improving long-term outcomes.

Advancements in genetic testing technology have made it more accessible and less invasive.

“We now have the ability to do whole exome or whole genome sequencing… instead of looking at one of the 20,000 or so genes in the human body at a time, [this] looks at at least the coding regions of all of those genes all at once,” said Kruer.

Notably, genetic testing can now be performed using a simple blood test or even a painless mouth swab, making it more feasible for routine clinical use.

“The interpretation of the test is actually becoming increasingly complicated,” he said. “So there may be some general pediatricians that are comfortable with that, but I think increasingly they’re relying on their sub-specialist colleagues.”

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