De novo SCN1A mutations in migrating partial seizures of infancy
- 26 July 2011
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 77 (4), 380-383
- https://doi.org/10.1212/wnl.0b013e318227046d
Abstract
Objective: To determine the genetic etiology of the severe early infantile onset syndrome of malignant migrating partial seizures of infancy (MPSI). Methods: Fifteen unrelated children with MPSI were screened for mutations in genes associated with infantile epileptic encephalopathies: SCN1A, CDKL5, STXBP1, PCDH19, and POLG. Microarray studies were performed to identify copy number variations. Results: One patient had a de novo SCN1A missense mutation p.R862G that affects the voltage sensor segment of SCN1A. A second patient had a de novo 11.06 Mb deletion of chromosome 2q24.2q31.1 encompassing more than 40 genes that included SCN1A. Screening of CDKL5 (13/15 patients), STXBP1 (13/15), PCDH19 (9/11 females), and the 3 common European mutations of POLG (11/15) was negative. Pathogenic copy number variations were not detected in 11/12 cases. Conclusion: Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. MPSI is now the most severe SCN1A phenotype described to date. While not a common cause of MPSI, SCN1A screening should now be considered in patients with this devastating epileptic encephalopathy.This publication has 10 references indexed in Scilit:
- Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutationsNeurology, 2010
- Deletion of the SCN gene cluster on 2q24.4 is associated with severe epilepsy: An array-based genotype–phenotype correlation and a comprehensive review of previously published casesEpilepsy Research, 2008
- Epilepsy and electroencephalographic anomalies in chromosome 2 aberrations: A reviewEpilepsy Research, 2008
- Migrating Focal Seizures in Infancy: Analysis of the Electroclinical Patterns in 17 PatientsJournal of Child Neurology, 2008
- Abundance of the POLG disease mutations in Europe, Australia, New Zealand, and the United States explained by single ancient European foundersEuropean Journal of Human Genetics, 2007
- The spectrum of SCN1A-related infantile epileptic encephalopathiesBrain, 2007
- Maternal origin of a novel C‐terminal truncation mutation in CDKL5 causing a severe atypical form of Rett syndromeClinical Genetics, 2006
- Mutational scanning of potassium, sodium and chloride ion channels in malignant migrating partial seizures in infancyBrain & Development, 2006
- Migrating Partial Seizures in Infancy: Expanding the Phenotype of a Rare Seizure SyndromeEpilepsia, 2005
- Migrating Partial Seizures in Infancy: A Malignant Disorder with Developmental ArrestEpilepsia, 1995