Two Children with Early-Onset Strokes and Intractable Epilepsy, Both with CACNA1A Mutations

Abstract

Background: Mutations in the CACNA1A gene have been associated phenotypically with Familial Hemiplegic Migraine Type 1, Episodic Ataxia Type 2, Idiopathic Generalized Epilepsy, and Developmental and Epileptic Encephalopathy 42. Only six cases have linked ischemic strokes to mutations in the CACNA1A gene. Summary of Cases: We describe two unrelated patients who were found to have different mutations of the CACNA1A gene, one being a novel mutation, as shown by whole exome sequencing. One presented with seizures at birth and the other with seizures at 17 months old, both eventually exhibiting intractable epilepsy, ischemic stroke, and developmental delays. Results: Whole exome sequencing demonstrated de novo pathogenic mutations in the CACNA1A gene, which both caused similar phenotypes in unrelated patients. Conclusion: Pediatric patients who present with ischemic stroke and a history of seizures should be evaluated for CACNA1A mutations, as prompt recognition can help providers facilitate appropriate medical management.

Keywords: epilepsy; genetics; magnetic resonance imaging; mutation; refractory; seizures; status epilepticus; stroke.