Download PDF
Journal of Pediatric Epilepsy 2018; 07(04): 148-151
DOI: 10.1055/s-0039-1691826
Case Report
Georg Thieme Verlag KG Stuttgart · New York

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

Fahad A. Bashiri 
1   College of Medicine, King Saud University, Riyadh, Saudi Arabia
2   Division of Pediatric Neurology, Department of Pediatrics, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
,
Abrar Hudairi
2   Division of Pediatric Neurology, Department of Pediatrics, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
,
Malak Al Ghamdi
1   College of Medicine, King Saud University, Riyadh, Saudi Arabia
3   Division of Medical Genetics, Department of Pediatrics, College of Medicine, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
,
Adel A. Mahmoud
4   Department of Pediatric Neurology, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia
› Author Affiliations Funding This work was funded by the College of Medicine Research Center, Deanship of Scientific Research, King Saud University, Saudi Arabia.
Further Information

Publication History

24 January 2019

09 April 2019

Publication Date:
28 May 2019 (online)

Also available at
    Permissions and Reprints

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.

Keywords

epileptic encephalopathy - ketogenic diet - neonatal seizure - SCN2A
 

  • References

  • 1 Scheffer IE, Berkovic S, Capovilla G. , et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58 (04) 512-521
    CrossrefPubMedGoogle Scholar
  • 2 Ogiwara I, Ito K, Sawaishi Y. , et al. De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies. Neurology 2009; 73 (13) 1046-1053
    CrossrefPubMedGoogle Scholar
  • 3 Yokoi T, Enomoto Y, Tsurusaki Y, Naruto T, Kurosawa K. Nonsyndromic intellectual disability with novel heterozygous SCN2A mutation and epilepsy. Hum Genome Var 2018; 5: 20
    CrossrefPubMedGoogle Scholar
  • 4 Zeng Q, Zhang YH, Yang XL. , et al. Phenotype study of SCN2A gene related epilepsy [in Chinese]. Zhonghua Er Ke Za Zhi 2018; 56 (07) 518-523
    PubMedGoogle Scholar
  • 5 Lakhan R, Kumari R, Misra UK, Kalita J, Pradhan S, Mittal B. Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population. Br J Clin Pharmacol 2009; 68 (02) 214-220
    CrossrefPubMedGoogle Scholar
  • 6 Shi X, Yasumoto S, Kurahashi H. , et al. Clinical spectrum of SCN2A mutations. Brain Dev 2012; 34 (07) 541-545
    CrossrefPubMedGoogle Scholar
  • 7 Sanders SJ, Campbell AJ, Cottrell JR. , et al. Progress in understanding and treating SCN2A-mediated disorders. Trends Neurosci 2018; 41 (07) 442-456
    CrossrefPubMedGoogle Scholar
  • 8 Matalon D, Goldberg E, Medne L, Marsh ED. Confirming an expanded spectrum of SCN2A mutations: a case series. Epileptic Disord 2014; 16 (01) 13-18
    CrossrefPubMedGoogle Scholar
  • 9 Dilena R, Striano P, Gennaro E. , et al. Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy. Brain Dev 2017; 39 (04) 345-348
    CrossrefPubMedGoogle Scholar
  • 10 Foster LA, Johnson MR, MacDonald JT. , et al. Infantile epileptic encephalopathy associated with SCN2A mutation responsive to oral mexiletine. Pediatr Neurol 2017; 66: 108-111
    CrossrefPubMedGoogle Scholar
  • 11 Baasch AL, Hüning I, Gilissen C. , et al. Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities. Epilepsia 2014; 55 (04) e25-e29
    CrossrefPubMedGoogle Scholar
  • 12 Ko A, Jung DE, Kim SH. , et al. The efficacy of ketogenic diet for specific genetic mutation in developmental and epileptic encephalopathy. Front Neurol 2018; 9 (530) 530
    CrossrefPubMedGoogle Scholar
  • 13 Cullingford TE. The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. Prostaglandins Leukot Essent Fatty Acids 2004; 70 (03) 253-264
    CrossrefPubMedGoogle Scholar
  • 14 Wong VC, Fung CW, Kwong AK. SCN2A mutation in a Chinese boy with infantile spasm - response to Modified Atkins Diet. Brain Dev 2015; 37 (07) 729-732
    CrossrefPubMedGoogle Scholar
  • 15 Su DJ, Lu JF, Lin LJ, Liang JS, Hung KL. SCN2A mutation in an infant presenting with migrating focal seizures and infantile spasm responsive to a ketogenic diet. Brain Dev 2018; 40 (08) 724-727
    CrossrefPubMedGoogle Scholar
  • 16 Turkdogan D, Thomas G, Demirel B. Ketogenic diet as a successful early treatment modality for SCN2A mutation. Brain Dev 2019; 41 (04) 389-391
    CrossrefPubMedGoogle Scholar