Etiology and Treatment of Neonatal Seizure
Study Details
Study Description
Brief Summary
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.
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Detailed Description
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.
Study Design
Outcome Measures
Primary Outcome Measures
- Mutation rate of common seizure genes [From the oneset of seizure to the genetic sequencing finish, the process may last up to 3 months.]
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.
- Rate of seizure free [From the onset of seizure to 6 months after the onset of seizure]
After the onset of seizure, through clinical management and individualized intervention, we expect to observe the number and proportion of effective seizure treatments.
Eligibility Criteria
Criteria
Inclusion Criteria:
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severe seizures in neonates or generalized epilepsy or intractable epilepsy in infancy with generalized tonic-clonic seizures,
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seizures onset before 1 year of age,
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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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children Hospital of Fudan University | Shanghai | Shanghai | China | 201102 |
Sponsors and Collaborators
- Children's Hospital of Fudan University
Investigators
- Study Chair: Wenhao Zhou, Doctor, Children's Hospital of Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
- EpiPM Consortium. A roadmap for precision medicine in the epilepsies. Lancet Neurol. 2015 Dec;14(12):1219-28. doi: 10.1016/S1474-4422(15)00199-4. Epub 2015 Sep 20. Review. Erratum in: Lancet Neurol. 2016 Mar;15(3):241.
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- Møller RS, Larsen LH, Johannesen KM, Talvik I, Talvik T, Vaher U, Miranda MJ, Farooq M, Nielsen JE, Svendsen LL, Kjelgaard DB, Linnet KM, Hao Q, Uldall P, Frangu M, Tommerup N, Baig SM, Abdullah U, Born AP, Gellert P, Nikanorova M, Olofsson K, Jepsen B, Marjanovic D, Al-Zehhawi LI, Peñalva SJ, Krag-Olsen B, Brusgaard K, Hjalgrim H, Rubboli G, Pal DK, Dahl HA. Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies. Mol Syndromol. 2016 Sep;7(4):210-219. Epub 2016 Aug 20.
- Myers CT, Mefford HC. Advancing epilepsy genetics in the genomic era. Genome Med. 2015 Aug 25;7:91. doi: 10.1186/s13073-015-0214-7. Review.
- Striano P, Vari MS, Mazzocchetti C, Verrotti A, Zara F. Management of genetic epilepsies: From empirical treatment to precision medicine. Pharmacol Res. 2016 May;107:426-429. doi: 10.1016/j.phrs.2016.04.006. Epub 2016 Apr 11.
- Striano P, Zara F. Epilepsy: Common and rare epilepsies share genetic determinants. Nat Rev Neurol. 2017 Apr;13(4):200-201. doi: 10.1038/nrneurol.2017.30. Epub 2017 Mar 10.
- Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010 Sep;38(16):e164. doi: 10.1093/nar/gkq603. Epub 2010 Jul 3.
- CHFudanU_NNICU10