A recurrent de novo mutation in ATP1A3 gene in a Mexican patient with alternating hemiplegia of childhood detected by massively parallel sequencing.

Background: Pediatric movement disorders represent a diagnostic challenge for pediatricians and pediatric neurologists due to their high clinical heterogeneity and shared common features. Therefore, specific diagnoses require different approaches including metabolic work-up and specific tests for frequent genetic conditions. Alternating hemiplegia of childhood (AHC) is an ultra-rare pediatric movement disorder, characterized by paroxysmal alternating hemiplegia, dystonia, and seizure-like episodes that can be misleading during the evaluation of a child with a movement disorder. Case report: We present a Mexican patient with abnormal movements referred to the Genetics clinic because of hyperammonemia and a possible organic acidemia. Our assessment did not find clinical features compatible with an inborn error of metabolism. A massively parallel sequencing approach with targeted panel sequencing was used to get a final diagnosis. A missense variant c.2839G>A (p.Gly947Arg) located at exon 21 of ATP1A3 gene was demonstrated. This variant (rs398122887) has been previously reported as de novo producing alternating hemiplegia of childhood (AHC). Conclusions: AHC is an ultra-rare syndrome presented as a movement disorder with seizure-like episodes and a unique facial phenotype. Clinicians should be aware of this combination in order to diagnose this condition in a timely manner. Massive parallel sequencing panels are emerging as the best approach to diagnose rare movement disorders and simultaneously rule out metabolic disorders and common epileptic syndromes. Copyright: