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Neonatal epilepsy syndromes

Author
Renee Shellhaas, MD, MS
Section Editors
Douglas R Nordli, Jr, MD
Joseph A Garcia-Prats, MD
Deputy Editor
April F Eichler, MD, MPH

INTRODUCTION

Identifying the etiology of seizures is a primary clinical objective in the management of neonatal seizures. Accurate determination of the cause can lead to etiology-specific therapy and may limit central nervous system (CNS) dysfunction that would otherwise occur if left untreated. In addition, etiology-specific therapy may be necessary to control the seizures themselves.

While there has been much discussion of the potential adverse effect of seizures on the immature brain, the overriding factor that affects long-term outcome is the etiology of the seizures and the degree and distribution of brain injury caused by the underlying disturbance.

Most neonatal seizures are due to acute symptomatic causes. However, there is increasing recognition of neonatal-onset epilepsy syndromes. This topic review will discuss recognized neonatal epilepsy syndromes. Acute symptomatic neonatal seizures are discussed separately. (See "Etiology and prognosis of neonatal seizures".)

The characterization of various types of neonatal seizures, with an emphasis upon clinical features and electrodiagnosis, is discussed elsewhere. Treatment is also discussed separately. (See "Clinical features, evaluation, and diagnosis of neonatal seizures" and "Treatment of neonatal seizures".)

OVERVIEW

Although the majority of neonatal seizures occur as acute reactive events in response to identifiable etiologic factors (table 1), additional rare but distinct neonatal epilepsy syndromes are well recognized. These include:

                      

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Literature review current through: Nov 2016. | This topic last updated: Mon Aug 22 00:00:00 GMT+00:00 2016.
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References
Top
  1. Proposal for classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1985; 26:268.
  2. Wolfe P. International classification of the epilepsies. In: Epilepsy: A Comprehensive Textbook, Engel J Jr, Pedley TA. (Eds), Lippincott-Raven, Philadelphia 1997. p.773.
  3. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989; 30:389.
  4. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010; 51:676.
  5. Goldberg HJ, Sheehy EM. Fifth day fits: an acute zinc deficiency syndrome? Arch Dis Child 1982; 57:633.
  6. Herrmann B, Lawrenz-Wolf B, Seewald C, et al. [5th day convulsions of the newborn infant in rotavirus infections]. Monatsschr Kinderheilkd 1993; 141:120.
  7. Ishii A, Fukuma G, Uehara A, et al. A de novo KCNQ2 mutation detected in non-familial benign neonatal convulsions. Brain Dev 2009; 31:27.
  8. Dehan M, Quillerou D, Navelet Y, et al. [Convulsions in the fifth day of life: a new syndrome?]. Arch Fr Pediatr 1977; 34:730.
  9. Okumura A, Watanabe K, Negoro T, et al. Long-term follow-up of patients with benign partial epilepsy in infancy. Epilepsia 2006; 47:181.
  10. Auvin S, Pandit F, De Bellecize J, et al. Benign myoclonic epilepsy in infants: electroclinical features and long-term follow-up of 34 patients. Epilepsia 2006; 47:387.
  11. Plouin P, Anderson VE. Benign familial and non-familial neonatal seizures. In: Epileptic Syndromes in Infancy, Childhood and Adolescence, Roger J, Bureau M, Dravet CH, et al. (Eds), John Libbey & Company, 2005. p.3.
  12. Quattlebaum TG. Benign familial convulsions in the neonatal period and early infancy. J Pediatr 1979; 95:257.
  13. Ronen GM, Penney S, Andrews W. The epidemiology of clinical neonatal seizures in Newfoundland: a population-based study. J Pediatr 1999; 134:71.
  14. Noebels JL. Ion Channelopathies and Heritable Epilepsy. News Physiol Sci 1998; 13:255.
  15. Noebels JL. Modeling human epilepsies in mice. Epilepsia 2001; 42 Suppl 5:11.
  16. Leppert M, Singh N. Benign familial neonatal epilepsy with mutations in two potassium channel genes. Curr Opin Neurol 1999; 12:143.
  17. Leppert M. Novel K+ channel genes in benign familial neonatal convulsions. Epilepsia 2000; 41:1066.
  18. Cunniff C, Wiedlin N, Jones KL. Autosomal dominant benign neonatal seizures. Am J Med Genet 1988; 30:963.
  19. Grinton BE, Heron SE, Pelekanos JT, et al. Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome. Epilepsia 2015; 56:1071.
  20. Howell KB, McMahon JM, Carvill GL, et al. SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures. Neurology 2015; 85:958.
  21. Leppert M, Anderson VE, Quattlebaum T, et al. Benign familial neonatal convulsions linked to genetic markers on chromosome 20. Nature 1989; 337:647.
  22. Singh NA, Charlier C, Stauffer D, et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat Genet 1998; 18:25.
  23. Claes LR, Ceulemans B, Audenaert D, et al. De novo KCNQ2 mutations in patients with benign neonatal seizures. Neurology 2004; 63:2155.
  24. Zara F, Specchio N, Striano P, et al. Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance. Epilepsia 2013; 54:425.
  25. Biervert C, Schroeder BC, Kubisch C, et al. A potassium channel mutation in neonatal human epilepsy. Science 1998; 279:403.
  26. Ryan SG, Wiznitzer M, Hollman C, et al. Benign familial neonatal convulsions: evidence for clinical and genetic heterogeneity. Ann Neurol 1991; 29:469.
  27. Charlier C, Singh NA, Ryan SG, et al. A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet 1998; 18:53.
  28. Ottman R, Hirose S, Jain S, et al. Genetic testing in the epilepsies--report of the ILAE Genetics Commission. Epilepsia 2010; 51:655.
  29. Ronen GM, Rosales TO, Connolly M, et al. Seizure characteristics in chromosome 20 benign familial neonatal convulsions. Neurology 1993; 43:1355.
  30. Aicardi J, Goutieres F. [Neonatal myoclonic encephalopathy (author's transl)]. Rev Electroencephalogr Neurophysiol Clin 1978; 8:99.
  31. Ohtahara, S. Clinico-electrical delineation of epileptic encephalopathies in childhood. Asian Med J 1978; 21:499.
  32. Beal JC, Cherian K, Moshe SL. Early-onset epileptic encephalopathies: Ohtahara syndrome and early myoclonic encephalopathy. Pediatr Neurol 2012; 47:317.
  33. Numis AL, Angriman M, Sullivan JE, et al. KCNQ2 encephalopathy: delineation of the electroclinical phenotype and treatment response. Neurology 2014; 82:368.
  34. Weckhuysen S, Mandelstam S, Suls A, et al. KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 2012; 71:15.
  35. Saitsu H, Kato M, Mizuguchi T, et al. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet 2008; 40:782.
  36. Mei D, Marini C, Novara F, et al. Xp22.3 genomic deletions involving the CDKL5 gene in girls with early onset epileptic encephalopathy. Epilepsia 2010; 51:647.
  37. Guerrini R, Moro F, Kato M, et al. Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus. Neurology 2007; 69:427.
  38. Bahi-Buisson N, Girard B, Gautier A, et al. Epileptic encephalopathy in a girl with an interstitial deletion of Xp22 comprising promoter and exon 1 of the CDKL5 gene. Am J Med Genet B Neuropsychiatr Genet 2010; 153B:202.
  39. Kato M, Saitoh S, Kamei A, et al. A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome). Am J Hum Genet 2007; 81:361.
  40. Saitsu H, Kato M, Okada I, et al. STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia 2010; 51:2397.
  41. Pavone P, Spalice A, Polizzi A, et al. Ohtahara syndrome with emphasis on recent genetic discovery. Brain Dev 2012; 34:459.
  42. Kato M, Yamagata T, Kubota M, et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia 2013; 54:1282.
  43. Weckhuysen S, Ivanovic V, Hendrickx R, et al. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology 2013; 81:1697.
  44. Mizrahi EM, Milh M. Early severe neonatal and infantile epileptic encephalopathies. In: Epileptic Syndromes in Infancy, Childhood and Adolescence, 5th, Bureau M, Genton P, Dravet C. (Eds), Libbey Eurotex, 2012.
  45. Jähn J, Caliebe A, von Spiczak S, et al. CDKL5 mutations as a cause of severe epilepsy in infancy: clinical and electroencephalographic long-term course in 4 patients. J Child Neurol 2013; 28:937.
  46. Ngoh A, McTague A, Wentzensen IM, et al. Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum. Dev Med Child Neurol 2014; 56:1124.
  47. Shen J, Gilmore EC, Marshall CA, et al. Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nat Genet 2010; 42:245.
  48. Malik SI, Galliani CA, Hernandez AW, Donahue DJ. Epilepsy surgery for early infantile epileptic encephalopathy (ohtahara syndrome). J Child Neurol 2013; 28:1607.
  49. Yamatogi Y, Ohtahara S. Severe epilepsy with multiple independent spike foci. J Clin Neurophysiol 2003; 20:442.
  50. Orhan G, Bock M, Schepers D, et al. Dominant-negative effects of KCNQ2 mutations are associated with epileptic encephalopathy. Ann Neurol 2014; 75:382.
  51. Pisano T, Numis AL, Heavin SB, et al. Early and effective treatment of KCNQ2 encephalopathy. Epilepsia 2015; 56:685.
  52. Hattersley AT, Ashcroft FM. Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes 2005; 54:2503.
  53. Shimomura K, Hörster F, de Wet H, et al. A novel mutation causing DEND syndrome: a treatable channelopathy of pancreas and brain. Neurology 2007; 69:1342.
  54. Pearson ER, Flechtner I, Njølstad PR, et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med 2006; 355:467.
  55. Landau Z, Wainstein J, Hanukoglu A, et al. Sulfonylurea-responsive diabetes in childhood. J Pediatr 2007; 150:553.