Introduction ATP1A3 gene was identified as the causative gene of Alternating hemiplegia of childhood (AHC). Our research is aimed to summarize the correlations between genotypes and phenotypes of AHC patients.

Methods The clinical data and peripheral blood DNA of AHC patients were collected, and the ATP1A3 gene mutations were screened by Sanger sequencing or next generation sequencing.

Results 119 AHC patients were recruited and ATP1A3 gene mutations were detected in 113 (95%) patients. All of the patients had hemiplegic episodes. Paroxysmal eye movements were observed in 109 (91.6%, 109/119) cases,  dystonic episodes in 104 (87.4%, 104/119) cases, and epileptic seizures in 31 (26.1%, 31/119) cases. 117 patients (98.3%) had long-term developmental delay. In 113 patients with ATP1A3 gene mutations, 111 (98.2%, 111/113)were de novo mutation. The three hotspot mutations were D801N（30.1%）, E815K（17.7%） and G947R（11.5%）. The age of onset and first hemiplegic events of D801N and E815K were earlier than G947R. A greater proportion of patients with E815K mutations presented epilepsy than D801N and G947R. Patients with E815K mutations also presented the greater motor and intellectual disability than the patients with D801N and G947R mutations.

Conclusion ATP1A3 gene was the main causative gene of AHC. Hotspot mutation E815K was associated with the most severe phenotype, which presented an earlier age at the time of the first paroxysmal manifestation and first hemiplegic event, severer developmental delay and a greater proportion of epilepsy.