doi:10.1684/epd.2014.0641 Epileptic Disord, Vol. 16, No. 1, March 2014 13 Correspondence: Eric D. Marsh Division of Child Neurology, Children’s Hospital of Philadelphia, Abramson Research Building- Room 502E, 3615 Civic Center Boulevard, Philadelphia PA 19014, USA <marshe@email.chop.edu> Original article Epileptic Disord 2014; 16 (1): 13-8 Confirming an expanded spectrum of SCN2A mutations: a case series Dena Matalon, Ethan Goldberg, Livija Medne, Eric D. Marsh Division of Child Neurology, Departments of Pediatrics and Neurology, Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA Received August 1, 2013; Accepted January 20, 2014 ABSTRACT – Mutations in sodium channel genes are highly associated with epilepsy. Mutation of SCN1A, the gene encoding the voltage gated sodium channel (VGSC) alpha subunit type 1 (Nav1.1), causes Dravet syn- drome spectrum disorders. Mutations in SCN2A have been identified in patients with benign familial neonatal-infantile epilepsy (BFNIE), gene- ralised epilepsy with febrile seizures plus (GEFS+), and a small number of reported cases of other infantile-onset severe intractable epilepsy. Here, we report three patients with infantile-onset severe intractable epilepsy found to have de novo mutations in SCN2A. While a causal role for these muta- tions cannot be directly established, these findings contribute to growing evidence that mutation of SCN2A is associated with a range of epilepsy phenotypes including severe infantile-onset epilepsy. Key words: SCN2A, early epileptic encephalopathy, channelopathy Voltage-gated sodium channels (VGSCs) exist as macromolecular complexes composed of one alpha (pore-forming) subunit and one or more beta subunits (Brackenbury and Isom, 2011). There are 10 alpha subunit genes, 4 of which (SCN1A, 2A, 3A, and 8A) are known to be highly expressed in the central nervous system (Catterall, 2000). Mutations of these sodium channel genes have been identified in mul- tiple epilepsy syndromes (Meisler et al., 2010). Mutations in SCN1A cause generalised epilepsy with febrile seizures plus (GEFS+) (Escayg et al., 2000) and Dravet syndrome (Claes et al., 2001; Harkin et al., 2007). Mutations in SCN2A, which encodes Nav1.2, were first identi- fied in patients with benign familial neonatal-infantile epilepsy (BFNIE) (Heron et al., 2002), an epilepsy syn- drome with onset of focal seizures in the neonatal or infantile period and characterised by a benign course with remission typically in the first or second year of life (Berkovic et al., 2004). However, mutations in SCN2A have also been found in patients with GEFS+ and Dravet-like syndrome, and in a small number of patients with severe intractable infantile-onset epilepsy and infan- tile epileptic encephalopathies (Kamiya et al., 2004; Ogiwara, 2009; Shi et al., 2012). Homozygous disrup- tion of SCN2A in mice is perinatal lethal but heterozygosity for SCN2A did not lead to a clear phenotype