An Infant With Epilepsy and Recurrent Hemiplegia Due to Compound Heterozygous Variants in ATP1A2

Publication date: Available online 8 June 2017
Source:Pediatric Neurology
Author(s): Colin Wilbur, Sarah E. Buerki, Ilaria Guella, Eric Toyota, Daniel M. Evans, Marna B. Mckenzie, Anita Datta, Aspasia Michoulas, Shelin Adam, Margot Van Allen, Tanya N. Nelson, Matthew J. Farrer, Mary B. Connolly, Michelle Demos
BackgroundPathogenic heterozygous variants in the ATP1A2 gene have most commonly been associated with familial hemiplegic migraine. However, a wide spectrum of phenotypes that include alternating hemiplegia of childhood and epilepsy have been described.Patient DescriptionWe describe a young boy who presented at age 3 months with a complex phenotype that included epilepsy, non-epileptic paroxysmal events, and recurrent hemiplegia. MRI demonstrated unilateral cortical edema during a severe episode of hemiplegia that was followed by a persistent mild hemiparesis. Whole-exome sequencing identified a previously reported ATP1A2 missense variant (p.Arg548Cys) classified as pathogenic and a novel missense variant (p.Arg1008Trp) classified as a variant of uncertain significance. Following this genetic diagnosis, treatment with flunarizine was initiated and no further episodes of hemiplegia have occurred.ConclusionThis is only the second reported case of compound heterozygosity in the ATP1A2 gene. It demonstrates the spectrum of paroxysmal neurologic events that can arise as a result of ATP1A2 variants, with unique features overlapping alternating hemiplegia of childhood, hemiplegic migraine, and epilepsy. This reinforces the diagnostic challenges these disorders can present and the importance of genetic diagnosis in guiding management.



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