One in four people with cerebral palsy have an underlying genetic condition, according to new research that has the potential to change the overall approach to their care.

The study published in Annals of Clinical and Translational Neurology sequenced the DNA of 50 patients with cerebral palsy through the Boston Hospital's Children’s Rare Disease Cohorts (CRDC) genomics initiative. Sequencing identified a causative or likely causative genetic variant in 13 patients (26%).

Cerebral palsy is a non-progressing motor impairment that begins in early childhood that has widely been viewed as the result of oxygen deprivation during birth or other birth-related factors such as prematurity. It is not a learning disability, but some people with cerebral palsy might have a learning disability.

In the study, patients whose average age was 10, had clinical exams and brain MRIs. They fell into three groups: 20 had a known risk factor for cerebral palsy, such as prematurity, a brain bleed, or oxygen deprivation; 24 had no known risk factors; and five were “cerebral palsy masqueraders” — meeting most criteria for cerebral palsy but experiencing deterioration of their condition over time.

Senior investigator Siddharth Srivastava, a neurologist in Boston Children’s Cerebral Palsy and Spasticity Program who specialises in neurogenetic disorders, said: “In cerebral palsy, the first thing that comes to many physicians’ minds is birth injury or asphyxia. That idea has become pervasive, in both neurology and orthopedics training and in the general public.

“One mother of an adult child with cerebral palsy told us that his genetic diagnosis absolved her of more than three decades of guilt. Many families felt they finally had a sense of closure.”

Implications of a genetic diagnosis in cerebral palsy

The researchers said that in some cases, the genetic findings led to changes in the patient’s care plan. One child, for example, turned out to have a gene linked to a metabolic disorder and was referred the metabolism clinic; an adult was referred for ocular and kidney evaluations based on his mutation; and an adolescent diagnosed with cerebral palsy all his life turned out to have a genetic mutation linked to a progressive neurological disorder, alerting his care team to watch for worsening of his condition.   

Based on their results, the researchers urge parents and clinicians to consider a genetic cause for any child that has cerebral palsy without known risk factors, or has cerebral palsy-like features but whose condition is worsening, and to investigate or refer accordingly.

They also suggest considering genetic testing in children with established risk factors for cerebral palsy if they have features suggestive of a genetic condition, such as congenital anomalies or other affected family members. Finally, they suggest that children with cerebral palsy be reevaluated periodically to make sure other aspects of their condition haven’t been missed, or to see if new features have emerged over time.

Benjamin Shore, MD, MPH, co-director of the Cerebral Palsy and Spasticity Center, said: “This work is groundbreaking and very exciting. Historically, the diagnosis of cerebral palsy has been assigned to many children who have elements of muscle tightness and developmental delay without really understanding the cause. We can now investigate these causes with much more detail. I hope in the future we can provide genetic diagnoses for many more children, particularly cerebral palsy masqueraders.”