A Case of Neonatal Epileptic Encephalopathy due to SCN2A Mutation Responsive to a Ketogenic Diet

Abstract

Neonatal seizures may have multiple causes including metabolic and genetic etiologies. If a genetic diagnosis is known, it can guide the physician to choose the most appropriate treatment modality. SCN2A mutation is a rare cause of epileptic encephalopathy in the neonatal age group. It has a wide phenotypic variation, ranging from benign familial epilepsy to a malignant form of epilepsy. This mutation has been associated with Ohtahara syndrome, migrating focal seizures of infancy, West syndrome, Lennox–Gastaut syndrome, and generalized epilepsy with febrile seizures plus. We present the case of a newborn girl who presented with multiple types of seizures, starting at the age of 3 days. Our initial investigations were not able to identify the etiology of her intractable seizures. Whole exome sequencing confirmed an SCN2A mutation. Various antiepileptic drugs (AEDs), including phenobarbitone, phenytoin, levetiracetam, topiramate, vigabatrin, carbamazepine, clonazepam, and mexiletine, were tried. However, none provided an optimal response. She ultimately showed a dramatic response to the ketogenic diet (KD). This report highlights the effectiveness of the KD as a treatment modality for SCN2A mutation-related epileptic encephalopathy, particularly when seizures are intractable and unresponsive to conventional AEDs.

Genotype–Phenotype Analysis of Children with Epilepsy Referred for Whole-Exome Sequencing at a Tertiary Care University Hospital

“…Similarly, sodium channel, neuronal type 2, alpha subunit (SCN2A) mutation, which is known to be associated with a broad spectrum of infant/childhood epilepsy [ 15 ], was detected in two patients in the current study, with mild presentation that started in the first three months of life. SCN2A mutation has been reported in two Saudi girls who presented with early infantile epileptic encephalopathy starting in the first few days of life [ 24 , 31 ]. Additionally, DENND5A mutation was reported in the current study in three patients from the same family who presented with Niemann–Pick syndrome.…”