RT Journal Article
SR Electronic
T1 <em>SCN2A</em> encephalopathy
JF Neurology
JO Neurology
FD Lippincott Williams &amp; Wilkins
SP 958
OP 966
DO 10.1212/WNL.0000000000001926
VO 85
IS 11
A1 Howell, Katherine B.
A1 McMahon, Jacinta M.
A1 Carvill, Gemma L.
A1 Tambunan, Dimira
A1 Mackay, Mark T.
A1 Rodriguez-Casero, Victoria
A1 Webster, Richard
A1 Clark, Damian
A1 Freeman, Jeremy L.
A1 Calvert, Sophie
A1 Olson, Heather E.
A1 Mandelstam, Simone
A1 Poduri, Annapurna
A1 Mefford, Heather C.
A1 Harvey, A. Simon
A1 Scheffer, Ingrid E.
YR 2015
UL http://n.neurology.org/content/85/11/958.abstract
AB 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.BFNIS=benign familial neonatal infantile seizures; EE=epileptic encephalopathy; EIMFS=epilepsy of infancy with migrating focal seizures; MIP=molecular inversion probe; SUDEP=sudden unexpected death in epilepsy; WES=whole-exome sequencing