Probable genetic vulnerabilities that can account for the pathophysiology of cerebral palsy

PURPOSE:Cerebral palsy (CP) is a nonprogressive brain and movement disorder that manifests as abnormal muscle tone. Despite the increase in cesarean sections, the rates of CP have remained constant. Research has shown that 14% of CP cases of cases have a likely causative single gene mutation and up to 31% have several genetic variations. However, no single gene has been found to explain all the symptoms of CP. The aim of the present study was to use patient’s genetic reports to determine what percentage of patients had a causative/putative gene to explain symptoms and to identify the role of those genes. The pathogenic alleles identified may warrant screenings to assess for secondary risks.

METHODS: Using Invitae CP spectrum disorders panel, we analyzed the positive CP genetic reports of the 31 patients tested from November 2020 and July 2022 from a single pediatric neurology practice. We collected information about patient demographics, pathogenic alleles, and variants of uncertain significance (VUS).

RESULTS: Of the 31 positive genetic reports, 30 patients (97%) had at least one pathogenic allele found; Twenty-nine pathogenic alleles were identified: four (13.8%) with autosomal dominant (AD) diseases, and seven (24.1%) with both AD and recessive (AR) diseases. Some of the pathogenic alleles found were CACNA1A (n=2), CREBBP (n=1), CTNNB1 (n=1), ATM (n=1).

CONCLUSION: Many of the genes identified were associated with a movement disorder that shares features of CP, including spasticity or dystonia. The incidence of genetic findings and the high yield of dominant disorders and potential secondary risks suggest the need for both patient management and family counseling.