Long-Term Outcome of Neonatal Seizure with PACS2 Mutation: Case Series and Literature Review

Abstract

Phosphofurin Acidic Cluster Sorting Protein 2 (PACS2)-related early infantile developmental and epileptic encephalopathy (EIDEE) is a rare neurodevelopmental disorder. EIDEE is characterized by seizures that begin during the first three months of life and are accompanied by developmental impairment over time. In this article, we present three patients with EIDEE who experienced neonatal-onset seizures that developed into intractable seizures during infancy. Whole exome sequencing revealed a de novo heterozygous missense variant in all three patients in the p.Glu209Lys variant of the PACS2 gene. We conducted a literature review and found 29 cases to characterize the seizure patterns, neuroimaging features, the usage of anticonvulsants, and the clinical neurodevelopmental outcomes of PACS2-related EIDEE. The seizures were characterized by brief, recurring tonic seizures in the upper limbs, sometimes accompanied by autonomic features. Neuroimaging abnormalities were observed in the posterior fossa region, including mega cisterna magna, cerebellar dysplasia, and vermian hypoplasia. The long-term prognosis ranges from low–average intelligence to severe developmental retardation, emphasizing the importance of early recognition and accurate diagnosis by pediatric neurologists to provide personalized patient management.