Infantile spasms are a potentially catastrophic form of epilepsy syndrome that are usually associated with substantial developmental delay and commonly occur in children younger than 1 yr. Recent reports on four cases revealed that variants harbored in a novel gene CDK19 were causative for the syndrome. We report a fifth affected individual, a 10-mo-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms. We identified a novel de novo missense variant c.92C > A (p.Thr31Asn) in CDK19 that was classified as a likely pathogenic disease-causing variant. The characterized clinical phenotypes of the proband were similar to the previously reported four patients, but he had few variable features including earlier seizure onset age and earlier occurring developmental abnormality. Protein structure modeling analysis revealed that CDK19 variants may disable its kinase activity, which would further impede the transcriptional regulation, thus leading to detrimental pathologies. Our report expanded CDK19 genotype spectrum and further demonstrated that a CDK19 missense variant was causative of neurodevelopmental disorder clinically marked by infantile spasms.
Keywords: epileptic encephalopathy; infantile spasms; severe global developmental delay.
© 2021 Yang et al.; Published by Cold Spring Harbor Laboratory Press.