Cerebral palsy (CP) starts in early childhood, and is a motor impairment that does not progress. CP is caused when children are deprived of oxygen during birth, or because of other factors around that time, such as being born premature. New research has indicated, however, that in as many as one in four CP cases, genetic factors may create a predisposition to the disorder. In some cases, those genetic variants appear when no other cause does. The findings have been reported in the Annals of Clinical and Translational Neurology, and may impact the care plan of some CP patients.
When it comes to CP, "birth injury or asphyxia" is still "the first thing that comes to many physicians’ minds,” noted senior study investigator and neurogenetic disorder specialist Siddharth Srivastava, MD, of Boston Children’s Cerebral Palsy and Spasticity Program. “That idea has become pervasive, in both neurology and orthopedics training and in the general public.” Some parents suffer years of guilt. Srivastava noted that a genetic diagnosis can alleviate some of that stress, as was the case with “one mother of an adult child with CP.”
In this study, the researchers assessed whole genome sequencing data, clinical reports and MRIs from CP patients with an average age of ten. Of this cohort, 24 did not have any known risk factor; 20 had some CP risk factor, like oxygen deprivation, bleeding on the brain, or prematurity; there were also five patients that met the criteria for CP but experienced neurodegeneration. Because the disease had progressed in the last group of five, they are considered "CP masqueraders." The study authors wanted a study cohort that represented patients they see, so all types were included.
The genetic sequencing indicated that a genetic variant that causes CP or is suspected to cause CP was carried by thirteen of the patients or 26 percent of the group. There were variants in thirteen different genes: ACADM, ADAT3, ATL1, COL4A1, ECHS1, GNAO1, PDHX, POLR2A, SATB2, SLC16A2, SPAST, THOC2, and ZMYM2. Three of the five CP masqueraders carried a causative variant, while seven of 24 patients who did not have any known CP risk factor like oxygen deprivation were found to carry a causative variant.
There were, however, genetic risk factors even among CP patients (three of twenty or 15 percent) with another known risk factor.
“These three patients are particularly intriguing,” said co-first study author Maya Chopra, MBBS, FRACP, a clinical geneticist and Director of Translational Genomic Medicine at Boston Children’s. The researchers are interested in whether kids that carry variants like these are predisposed to brain injury.
Knowing more about variants like that could help researchers and clinicians develop better care plans, and learn more about CP.