We describe two unrelated patients with ischemic strokes, intractable epilepsy, and developmental delays in the setting of CACNA1A gene mutations.  Our first patient is an 11-year-old girl who presented with seizures at birth and recurrent ischemic stroke at ages 5 years, 7 years, and 11 years. Our second patient is a 9-year-old girl who presented with status epilepticus and a simultaneous ischemic stroke at 17 months old. Whole exome sequencing was performed as part of these patients' diagnostic work-up.

Whole exome sequencing demonstrated de novo pathogenic mutations in the CACNA1A gene in both patients. Patient 1 was found to have a recurrent heterozygous de novo variant, c.2137 G>A (p.A713T), which has not been associated with ischemic stroke to date. Patient 2 was found to have a novel de novo pathogenic gene variant, c.4015 T>C (p.C1369R).

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.