Reply to: A genomic cause of cerebral palsy should not change the clinical classification

Dear Editor, We thank MacLennan et al. for their letter pertaining to our article on the interpretation that our patients with pathogenic variants are “masquerading as cerebral palsy.” We entirely agree with their comments that cerebral palsy is an umbrella diagnosis of nonprogressive disorders of the control of movement and posture, encompassing a heterogeneous group of etiologies, which infer no specific causation. In addition, we agree that if patients with genetic causes of clinically diagnosed cerebral palsy are eliminated, an artificial reduction will occur in the incidence of cerebral palsy. Moreover, removing genomic causes could disenfranchise patients and families from the support. At present, not all healthcare providers accurately comprehend the definition of cerebral palsy. In fact, in the draft and review process, some experts opined that our cohort did not fit into the cerebral palsy group because our cases neither exhibited “typical” nor “classical” cerebral palsy. Hence, for broader acceptance, we changed the expression from “cerebral palsy with pathogenic variants” to “masqueraders of cerebral palsy.” Because it has been revealed that several patients with cerebral palsy have more than anticipated genetic abnormalities (i.e., monogenic causative genes, susceptibility genes, and copy number variations), we believe that it is crucial to retain the umbrella clinical diagnosis of cerebral palsy with subclassifications by possible or likely cause, including neonatal asphyxia, infarction, and genetic abnormality, for the reasons suggested by them. We hope that their international cohort and subsequent analysis results in the elucidation of the underlying mechanisms of cerebral palsy and the optimization of therapeutic interventions.