Cerebral palsy can be genetic rather than acquired at birth, new research has revealed.
The motor impairment is widely viewed as the result of oxygen deprivation during birth or other birth-related factors such as prematurity.
While this is true for many children, new research from Boston Children’s Hospital finds that as many as one in four have an underlying genetic condition with potential to change the overall approach to their care.
“In cerebral palsy, the first thing that comes to many physicians’ minds is birth injury or asphyxia,” says senior investigator Dr Siddharth Srivastava, MD, a neurologist in Boston Children’s Cerebral Palsy and Spasticity Program who specialises in neurogenetic disorders.
“That idea has become pervasive, in both neurology and orthopaedics training and in the general public.”
The research team sequenced the DNA of 50 patients with cerebral palsy (CP) through the hospital’s Children’s Rare Disease Cohorts (CRDC) genomics initiative.
The patients, whose average age was ten, had clinical exams and brain MRIs.
They fell into three groups: 20 had a known risk factor for CP, such as prematurity, a brain bleed, or oxygen deprivation; 24 had no known risk factors; and five were “CP masqueraders” — meeting most criteria for CP but experiencing deterioration of their condition over time (by definition, CP is a non-progressing disease).
“We wanted to include these three groups to reflect the breadth of patients we see,” explains Dr Srivastava.
Overall, sequencing identified a causative or likely causative genetic variant in 13 patients (26 per cent). These variants involved 13 different genes.
The likelihood of a genetic diagnosis was highest for the CP masqueraders: a cause was identified in three of five patients with progressing CP-like disease (60 per cent). Next were patients with CP and no known risk factors: a genetic cause was found for seven of 24 (29 per cent).
Surprisingly, even some patients with a known risk factor for CP, such as asphyxia around the time of birth, had a genetic mutation identified (three of 20 patients, or 15 per cent).
The concept that cerebral palsy is acquired is something that often sees families blaming themselves, believing that something that happened during pregnancy caused their child’s condition.
“One mother of an adult child with CP told us that his genetic diagnosis absolved her of more than three decades of guilt,” says Dr Srivastava. “Many families felt they finally had a sense of closure.”
Based on their results, the researchers urge parents and clinicians to consider a genetic cause for any child that has CP without known risk factors, or has CP-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 CP if they have features suggestive of a genetic condition, such as congenital anomalies or other affected family members.
Finally, they suggest that children with CP be re-evaluated periodically to make sure other aspects of their condition haven’t been missed, or to see if new features have emerged over time.
“This work is groundbreaking and very exciting,” says Dr Benjamin Shore, co-director of the Cerebral Palsy and Spasticity Center.
“Historically, the diagnosis of CP 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 CP masqueraders.”
