Etiology and Treatment of Neonatal Seizure

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Gene Profiling and Individualized Treatment of Neonatal Seizure in China

Conditions
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Seizures, Seizure Disorder, Seizure Newborn, Seizure Generalized

Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mutation rate of common seizure genes | We'll get the genetic profiles of all neonates who had seizures during this period. The mutation rate of common variant gene was calculated by gene spectrum. | From the oneset of seizure to the genetic sequencing finish, the process may last up to 3 months. | 
| Rate of seizure free | After the onset of seizure, through clinical management and individualized intervention, we expect to observe the number and proportion of effective seizure treatments. | From the onset of seizure to 6 months after the onset of seizure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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seizure