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From the Departments of Neurology (K.B.H., M.T.M., V.R.-C., J.L.F., A.S.H., I.E.S.) and Radiology (S.M.), The Royal Children's Hospital, Melbourne; Department of Paediatrics (K.B.H., M.T.M., S.M., A.S.H., I.E.S.), The University of Melbourne; Murdoch Childrens Research Institute (K.B.H., M.T.M., J.L.F., A.S.H.), Melbourne; Epilepsy Research Centre (J.M.M., I.E.S.), Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia; Division of Genetic Medicine (G.L.C., H.C.M.), Department of Paediatrics, University of Washington, Seattle; Epilepsy Genetics Program (D.T., H.E.O., A.P.), Department of Neurology, Harvard Medical School, Boston Children's Hospital, MA; TY Nelson Department of Neurology and Neurosurgery (R.W.), The Children's Hospital at Westmead, Sydney; Department of Neurology (D.C.), Women's and Children's Hospital, Adelaide; Neurosciences Children's Health Queensland (S.C.), Lady Cilento Children's Hospital, Brisbane; and Florey Institute of Neuroscience and Mental Health (S.M., A.S.H., I.E.S.), Melbourne, Australia.
Published: September 2015
AI Article Synopsis
Article 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.
