Bright Futures

Cerebral palsy (CP), a major neurodevelopmental disorder, has no cure. It affects around 1 in 323 children and is long-believed to be the result of premature birth, low birth weight, brain injury, in utero infections and a lack of oxygen during delivery.

However, around one in three children diagnosed with CP do not experience any of these environmental risk factors, which leads doctors to believe there’s a genetic basis for the disease.

Michael Kruer, MD, is one of those physicians. A pediatric neurologist who directs the Cerebral Palsy and Pediatric Movement Disorders Programs at Barrow Neurological Institute at Phoenix Children's Hospital, he is the co-senior author of groundbreaking new research published last week in Nature Genetics, which confirms that a significant number of CP cases can be linked to rare genetic mutations.

The findings have been featured by HealthDay, UPI and numerous other national and international media outlets and science publications.

This research has long been an area of passion for Dr. Kruer, who also serves as associate professor of Child Health, Neurology and Cellular and Molecular Medicine at the University of Arizona College of Medicine. “My interest began with a single amazing family that I cared for,” he said. “They had four children with cerebral palsy. This didn’t fit what I had been taught during my training about the disease and led me to start thinking about it in a different way.”

This work— funded by a $3 million grant from National Institutes of Health— represents the largest genetic study of CP ever conducted. The researchers searched for spontaneous mutations in the genes of 250 families from the U.S., China, and Australia through a collaboration made possible by the International Cerebral Palsy Genomics Consortium.

"In the families, most of the children had CP for unclear reasons. We adopted an approach where we compared the genetic code of the healthy mothers and fathers to that of their child with CP. This allowed us to detect mutations that led to CP," said Dr. Kruer. 

First Conclusive Statistical Evidence

The results of the study show the first firm evidence of a strong genetic basis for many cases of cerebral palsy. About 14% of CP cases were linked to mutations in specific brain-wiring genes – which include genes inherited from carrier parents and spontaneous mutations – that altered early brain connections.

The mutations are usually not in a single gene but appear to be in one of hundreds of different genes. However, certain genes seem more likely to have mutations that affect brain development in children.

The research team is interested in determining the ways in which mutations disrupt early brain development and lead to CP.  

Better Diagnosis and Treatments

As a multidisciplinary center, Barrow Neurological Institute at Phoenix Children’s specializes in care and research for cerebral palsy, epilepsy, autism and other neurodevelopmental disorders. Not only does this ease the burden on patients by creating a single place for them to receive care, but it also gives patients greater access to resources and improves health outcomes.

By understanding the genetic basis of CP, the potential for new therapies increases. The results of the study are already helping change treatment pathways for three children with cerebral palsy. In the future, the study may also help improve the diagnosis process for CP and help children start receiving treatment faster.