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.

The genotype–phenotype correlations of the CACNA1A-related neurodevelopmental disorders: a small case series and literature reviews

“…There were 83 variants reported to relate to epilepsy ( Imbrici et al, 2004 ; Kors et al, 2004 ; Rajakulendran et al, 2010 ; Zangaladze et al, 2010 ; Yamazaki et al, 2011 ; Damaj et al, 2015 ; Byers et al, 2016 ; Reinson et al, 2016 ; Du et al, 2017 ; Lv et al, 2017 ; Epperson et al, 2018 ; Hayashida et al, 2018 ; Kothur et al, 2018 ; Lee et al, 2018 ; Angelini et al, 2019 ; Jiang et al, 2019 ; Yamamoto et al, 2019 ; Gauquelin et al, 2020 ; Gudenkauf et al, 2020 ; Mitta et al, 2020 ; Stendel et al, 2020 ; Zhang et al, 2020 ; Ho et al, 2021 ; Le Roux et al, 2021 ; Stubberud et al, 2021 ; Verriello et al, 2021 ; Alehabib et al, 2022 ; Bolte et al, 2022 ; Hommersom et al, 2022 ; Krygier et al, 2022 ; Li et al, 2022 ; Lipman et al, 2022 ; Niu X. et al, 2022 ; Niu Y. et al, 2022 ) as shown in Supplementary Table 2 . The majority of the variants were missense (77.20%) followed by nonsense (8.80%) as shown in Figure 1A .…”