Association between CACNA1A and ATP1A2 variants are responsible for severe neurodevelopmental disorder.

ATP1A2 and CACNA1A genes encode proteins forming transmembrane channels, Na+/K+/ATPase transporter and voltage-gated calcium channel, respectively. Pathogenic variants in these genes are associated with hemiplegic migraines, movement disorders and developmental and epileptic encephalopathy.
CASE REPORT: We report a child presenting epileptic encephalopathy with cognitive and behavioral troubles. He carries a likely pathogenic variant in the ATP1A2 gene, inherited from his mother who presents hemiplegic migraines, and a variant of uncertain significance in the CACNA1A gene, inherited from his asymptomatic father and also found in his brother, who presents a milder neurodevelopmental disorder. 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.
CONCLUSION: We illustrate the synergetic impact of ATP1A2 and CACNA1A genes in neurodevelopmental disorders.