SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures

Abstract

Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. Results: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1–4 in 8, week 2–6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile–onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control. (PsycINFO Database Record (c) 2016 APA, all rights reserved)Department of Neurology, Royal Children’s Hospital, Melbourne, VIC, Australia. Release Date: 20151026. Publication Type: Journal (0100), Peer Reviewed Journal (0110). Format Covered: Electronic. Document Type: Journal Article. Language: EnglishGrant Information: Howell, Katherine B. Major Descriptor: Encephalopathies; Epilepsy; Sodium Channel. Minor Descriptor: Cluster Analysis; Seizures. Classification: Neurological Disorders & Brain Damage (3297). Population: Human (10); Male (30); Female (40). Age Group: Childhood (birth-12 yrs) (100); Infancy (2-23 mo) (140); Preschool Age (2-5 yrs) (160); School Age (6-12 yrs) (180); Adolescence (13-17 yrs) (200); Adulthood (18 yrs & older) (300); Young Adulthood (18-29 yrs) (320). Methodology: Empirical Study; Quantitative Study. References Available: Y. Page Count: 9. Issue Publication Date: Sep 15, 2015. Publication History: Accepted Date: May 15, 2015; First Submitted Date: Dec 16, 2014. Copyright Statement: Unauthorized reproduction of this article is prohibited. American Academy of Neurology. 2015.Sponsor: National Health and Medical Research Council, Australia. Other Details: Gustav Nossal Postgraduate Scholarship and the Clifford PhD Scholarship, Program Grant and Practitioner Fellowship. Recipients: Howell, Katherine B.; Scheffer, Ingrid E. <br />Sponsor: National Institute of Neurological Disorders and Stroke, US. Recipients: Poduri, Annapurna <br />Sponsor: Burroughs Wellcome Fund. Other Details: Career Award for Medical Scientists. Recipients: Mefford, Heather C. <br />Sponsor: National Institutes of Health, National Institute of Neurological Disorders and Stroke, US. Recipients: Mefford, Heather C. <br />