Association between CACNA1A and ATP1A2 Variants are Responsible for Severe Neurodevelopmental Disorder

<i>ATP1A2</i> and <i>CACNA1A</i> genes encode proteins forming transmembrane channels, Na⁺/K⁺/ATPase transporter, and voltage-gated calcium channels, respectively. Pathogenic variants in these genes are associated with hemiplegic migraines, movement disorders, and developmental and epileptic encephalopathy.We report a child presenting epileptic encephalopathy with cognitive and behavioral troubles. He carries a likely pathogenic variant in the <i>ATP1A2</i> gene, inherited from his mother who presents hemiplegic migraines, and a variant of uncertain significance in the <i>CACNA1A</i> gene, inherited from his asymptomatic father and also found in his brother, who presents a milder neurodevelopmental disorder (NDD). No other significant copy number or single nucleotide variations were identified after an in-depth genetic study including whole exome sequencing, array comparative genomic hybridization, and screening for Fragile X and Prader-Willi/Angelman syndromes.We illustrate the synergetic impact of <i>ATP1A2</i> and <i>CACNA1A</i> genes in NDDs.