Clinical features and ATP1A3 gene mutations in alternating hemiplegia of childhood patients with epilepsy

Abstract

Objective To analyze the clinical features and the genotype-phenotype correlations of ATP1A3 mutations in alternating hemiplegia of childhood (AHC) patients with epilepsy. Methods The clinical data and peripheral blood of AHC patients in Department of Pediatrics, Peking University First Hospital from August 2005 to November 2015 were collected and analyzed.Mutations in ATP1A3 were screened by Sanger sequencing and PCR amplification. Results A total of 93 AHC patients were recruited.Fourteen patients (15.1%) had concurrent epilepsy.The age of seizure onset ranged from 6 hours to 6 years.Focal seizure was observed in 9 cases, generalized tonic-clonic seizures (GTCS) in 7 cases, and atypical absence was found in 1 case.Three of those patients had 2 types, and 11 patients experienced status epilepticus during the course.Electroencephalography (EEG) was performed in 13 cases.EEG were abnormal in 5 patients.The background activity was slow in 5 cases.Multiple focal or generalized spikes were found in 3 patients and diffused slow waves in 1 patient.Nonconvulsive status epilepticus(atypical absence status epilepticus) was monitored in 1 patient, whose actions were reduced and response slowed in the next 35 min while the EEG monitored 2.0-2.5Hz generalized spike and waves.EEG were normal in 8 cases.ATP1A3 mutations were identified in 14 patients with epilepsy.Four types of missense mutations were found, including mutation E815K in 11 patients.Mutation D801N, L839P, and E277K were detected in one patient, respectively.In 93 AHC patients, 18 patients were found with E815K mutation, and 11 of them (61.1%) had epilepsy. Conclusions The age of seizure onset in AHC patients could happen as early as neonatal period.Focal seizures and GTCS are the two most common types in AHC patients with epilepsy and these patients often experienced status epilepticus.Most of their interictal EEG were normal.AHC patients with epilepsy are more likely to carry ATP1A3 gene E815K mutation. Key words: Alternating hemiplegia of childhood; Epilepsy; Focal seizure; ATP1A3 gene