A novel CACNA1A variant in a child with early stroke and intractable epilepsy

Abstract

Background: CACNA1A variants have been described in several disorders that encompass a wide range of neurologic phenotypes, including hemiplegic migraine, ataxia, cognitive delay, and epilepsy. To date, ischemic stroke caused by a CACNA1A variant has only been reported once in the literature. Methods: We describe a 4-year-old female with recurrent ischemic strokes beginning at 6 weeks of age, intractable epilepsy, and significant global developmental delay. Exome sequencing (ES) was completed for her evaluation. Results: We found a novel de novo, likely pathogenic variant, p.Leu1692Gln in CACNA1A by ES. The substitution affects a leucine residue that is highly conserved in species from fish to primates. Conclusion: We present the second case of recurrent ischemic strokes in a patient with CACNA1A mutation. Our findings expand the phenotypic heterogeneity related to Cav2.1 (P/Q-type) calcium channel dysfunction and suggest consideration of CACNA1A disorder in evaluation of pediatric strokes.