New research has found that as many as 1 in 4 children with cerebral palsy have an underlying genetic condition.
Cerebral palsy is the most common childhood-onset motor disability. In the US alone, it affects over 700,000 individuals. It is defined as a group of developmental disorders that impact movement and posture. These disorders are attributed to nonprogressive disturbances that occur in the developing foetal or infant brain. Several risk factors for cerebral palsy have been established including prematurity, periventricular/intraventricular haemorrhage, perinatal asphyxia, perinatal stroke and infection.
Around 20% of individuals with cerebral palsy have no clear aetiology. These individuals are classified as having cryptogenic cerebral palsy. In the past, there has been an accumulation of evidence that suggests some of these cases may be associated with chromosomal copy number variants and single gene disorders. However, the current evidence regarding genetic causes of cerebral palsy is limited. This is mostly due to the fact that cerebral palsy is considered to be predominantly acquired.
Whole-exome sequencing in CP
In a recent study, published in Annals of Clinical and Translational Neurology, researchers performed a whole-exome sequencing (WES) analysis in a cohort of cerebral palsy patients to further explore the genetic landscape of the condition. They specifically investigated 24 cryptogenic individuals (no risk factors), 20 non-cryptogenic (at least one risk factor) and 5 masqueraders (could be diagnosed with condition, but have regression/progressive symptoms). One proband had an unknown classification.
Overall, WES identified a causative or likely causative genetic variant in 26% of patients. These variants involved 13 different genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, and ATL1).
The likelihood of a genetic diagnosis was greatest in masqueraders – a cause was identified in 60% of patients. Meanwhile, a genetic cause was found in 29% of cryptogenic patients and interestingly 15% of patients with non-cryptogenic cerebral palsy.
In some of these cases, the genetic finding resulted in a change to the patient’s care plan. For example, one child had a variant linked to a metabolic disorder and was referred to the metabolism clinic.
Altogether, these results have demonstrated a significant prevalence of Mendelian disorders in individuals with cerebral palsy, even in individuals with other known risk factors.
Annapurna Poduri, co-senior author on the paper, said:
“We now have the scientific knowledge to pursue a precise diagnosis for children with cerebral palsy that is not just descriptive, but that provides answers and may open a door to treating some of the underlying conditions we uncover.
With precision diagnosis will come precision treatments for more and more children with cerebral palsy, epilepsy, and other neurodevelopmental disorders.”
Image credit: canva