Genetic diagnosis for neonates suffering from epilepsy has important implications for treatment, prognosis, and development of precision medicine strategies. Investigator performed exome sequencing (ES) or targeted sequencing on neonates with seizure onset within the first month of life. Investigator subgrouped our patients based on the onset age of seizure into neonatal and before 1 year (1-12 months), to compare the clinical and genetic features and treatment strategies.

Seizure is one of the most common neurological conditions in neonates, and has substantial impact on patients'quality of life and social integration. Epileptic encephalopathy is characterized by refractory seizures, cognitive dysfunction, and poor prognosis. Despite the recent progress in technology, molecular diagnosis of neonates suffering from possible epileptic seizures can be challenging, due to genetic and phenotypic heterogeneities. A large number of specific pathogenic variations have been related to various forms of epilepsies. Next-generation sequencing (NGS) has significantly improved the molecular diagnosis for rare diseases. NGS focusing on genes known to be associated with human diseases is a practical approach as a first-tier assessment for patients with heterogeneous genetic background. In addition, currently medical therapy for seizure is not based on the etiology, but the clinical manifestations, and the main purpose is not to rescue the underlying diseases process, but just to reduce the likelihood of seizures occurrence. In this study, Investigator performed NGS on neonates with seizure onset before 1 year of age, to detect and quantify genetic variants, and assess existing therapeutic effects. Our findings will have important implications for the development of precision medicine strategies.

Inclusion Criteria:

• severe seizures in neonates or generalized epilepsy or intractable epilepsy in infancy with generalized tonic-clonic seizures,
• seizures onset before 1 year of age,
• epileptic syndromes/epileptic-encephalopathies with unknown etiology.

Exclusion Criteria:

• Patients were excluded if they had traumas, central nervous system infections, hypoxic-ischemic encephalopathy, vascular events, systemic infections, and diagnosed metabolic disorders, and pathogenic copy-number variants were identified using array-based comparative genomic hybridization (CGH).

The subjects were treated in the Department of Neonatology of Children Hospital of Fudan University. All samples in this study were collected with appropriate informed consent and approval of the ethics committee of Children's Hospital, Fudan University. The methods used in this study were carried out in accordance with the approved guidelines.