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Epileptic Encephalopathies—Clinical Syndromes and Pathophysiological Concepts

  • Pediatric Neurology (WE Kaufmann, Section Editor)
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Abstract

Epileptic encephalopathies account for a large proportion of the intractable early-onset epilepsies and are characterized by frequent seizures and poor developmental outcome. The epileptic encephalopathies can be loosely divided into two related groups of named syndromes. The first comprises epilepsies where continuous EEG changes directly result in cognitive and developmental dysfunction. The second includes patients where cognitive impairment is present at seizure onset and is due to the underlying etiology but the epileptic activity may then worsen the cognitive abilities over time. Recent, large-scale exome studies have begun to establish the genetic architecture of the epileptic encephalopathies, resulting in a re-consideration of the boundaries of these named syndromes. The emergence of this genetic architecture has lead to three main pathophysiological concepts to provide a mechanistic framework for these disorders. In this article, we will review the classic syndromes, the most significant genetic findings, and relate both to the pathophysiological understanding of epileptic encephalopathies.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Waaler PE, Blom BH, Skeidsvoll H, Mykletun A. Prevalence, classification, and severity of epilepsy in children in western Norway. Epilepsia. 2000;41:802–10.

    Article  CAS  PubMed  Google Scholar 

  2. Berg AT 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;51:676–85.

    Article  PubMed  Google Scholar 

  3. Howell KB, Harvey AS, Archer JS. Epileptic encephalopathy: use and misuse of a clinically and conceptually important concept. Epilepsia. 2016;57:343–7.

    Article  PubMed  Google Scholar 

  4. Ohtahara S, Ohtsuka Y, Oka E. Epileptic encephalopathies in early infancy. Indian J Pediatr. 1997;64:603–12.

    Article  CAS  PubMed  Google Scholar 

  5. Yamatogi Y, Ohtahara S. Early-infantile epileptic encephalopathy with suppression-bursts, Ohtahara syndrome; its overview referring to our 16 cases. Brain Dev. 2002;24:13–23.

    Article  PubMed  Google Scholar 

  6. Ohtahara S, Yamatogi Y. Ohtahara syndrome: with special reference to its developmental aspects for differentiating from early myoclonic encephalopathy. Epilepsy Res. 2006;70:2–5.

    Article  Google Scholar 

  7. Wilmshurst JM et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia. 2015;56:1185–97.

    Article  PubMed  Google Scholar 

  8. Saitsu H et al. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet. 2008;40:782–8.

    Article  CAS  PubMed  Google Scholar 

  9. Deprez L et al. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology. 2010;75:1159–65.

    Article  CAS  PubMed  Google Scholar 

  10. Saitsu H et al. STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia. 2010;51:2397–405.

    Article  CAS  PubMed  Google Scholar 

  11. Mignot C et al. STXBP1-related encephalopathy presenting as infantile spasms and generalized tremor in three patients. Epilepsia. 2011;52:1820–7.

    Article  CAS  PubMed  Google Scholar 

  12. Milh M et al. Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations. Epilepsia. 2011;52:1828–34.

    Article  PubMed  Google Scholar 

  13. Carvill GL et al. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology. 2014;82:1245–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Stamberger H et al. STXBP1 encephalopathy A neurodevelopmental disorder including epilepsy. Neurology. 2016;86:954–62.

    Article  CAS  PubMed  Google Scholar 

  15. Biervert C. A potassium channel mutation in neonatal human epilepsy. Science. 1998;279:403–6.

    Article  CAS  PubMed  Google Scholar 

  16. Singh N et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat Genet. 1998;18:231–6.

    Article  Google Scholar 

  17. Weckhuysen S et al. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology. 2013;81:1697–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Saitsu H et al. Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome. Ann Neurol. 2012;72:298.

    Article  CAS  PubMed  Google Scholar 

  19. Kato M et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia. 2013;54:1282–7.

    Article  CAS  PubMed  Google Scholar 

  20. Nakamura K et al. Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome. Neurology. 2013;81:992–8.

    Article  CAS  PubMed  Google Scholar 

  21. Heron SE et al. Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet. 2002;360:851–2.

    Article  CAS  PubMed  Google Scholar 

  22. Berkovic SF et al. Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol. 2004;55:550–7.

    Article  CAS  PubMed  Google Scholar 

  23. Aicardi J, Goutieres F. [Neonatal myoclonic encephalopathy (author’s transl)]. Rev Electroencephalogr Neurophysiol Clin. 1978;8:99–101.

    Article  CAS  PubMed  Google Scholar 

  24. Dalla Bernardina B et al. Early myoclonic epileptic encephalopathy (E.M.E.E.). Eur J Pediatr. 1983;140:248–52.

    Article  CAS  PubMed  Google Scholar 

  25. Ohtahara S, Yamatogi Y. Epileptic encephalopathies in early infancy with suppression-burst. J Clin Neurophysiol. 2003;20:398–407.

    Article  PubMed  Google Scholar 

  26. Molinari F et al. Impaired mitochondrial glutamate transport in autosomal recessive neonatal myoclonic epilepsy. Am J Hum Genet. 2005;76:334–9.

    Article  CAS  PubMed  Google Scholar 

  27. Kato M et al. PIGA mutations cause early-onset epileptic encephalopathies and distinctive features. Neurology. 2014;82:1587–96.

    Article  CAS  PubMed  Google Scholar 

  28. Hansen J et al. De novo mutations in SIK1 cause a spectrum of developmental epilepsies. Am J Hum Genet. 2015;96:682–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Eling P, Renier WO, Pomper J, Baram TZ. The mystery of the Doctor’s son, or the riddle of West syndrome. Neurology. 2002;58:953–5.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lux AL et al. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial. Lancet Neurol. 2005;4:712–7.

    Article  CAS  PubMed  Google Scholar 

  31. Osborne JP et al. The underlying etiology of infantile spasms (West syndrome): information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia. 2010;51:2168–74.

    Article  PubMed  Google Scholar 

  32. •• Allen AS et al. De novo mutations in epileptic encephalopathies. Nature. 2013;501:217–21. Collaborative large-scale exome study revealing the signicance of de novo mutations in epileptic encephalopathies.

  33. •• EuroEPINOMICS-RES Consortium, E. P. & Genome Project, E. C. De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. Am J Hum Genet. 2014;95:360–70. Collaborative large-scale exome study revealing the signicance of de novo mutations in epileptic encephalopathies.

  34. Kalscheuer VM et al. Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. Am J Hum Genet. 2003;72:1401–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Klein KM et al. A distinctive seizure type in patients with CDKL5 mutations: hypermotor-tonic-spasms sequence. Neurology. 2011;76:1436–8.

    Article  CAS  PubMed  Google Scholar 

  36. Jähn J 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;28:937–41.

    Article  PubMed  Google Scholar 

  37. Evans JC et al. Early onset seizures and Rett-like features associated with mutations in CDKL5. Eur J Hum Genet. 2005;13:1113–20.

    Article  CAS  PubMed  Google Scholar 

  38. Strømme P et al. Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nat Genet. 2002;30:441–5.

    Article  PubMed  CAS  Google Scholar 

  39. Kato M, Das S, Petras K, Sawaishi Y, Dobyns WB. Polyalanine expansion of ARX associated with cryptogenic West syndrome. Neurology. 2003;61:267–76.

    Article  CAS  PubMed  Google Scholar 

  40. Kato M et al. Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. Hum Mutat. 2004;23:147–59.

    Article  CAS  PubMed  Google Scholar 

  41. Dravet C. The core Dravet syndrome phenotype. Epilepsia. 2011;52:3–9.

    Article  PubMed  Google Scholar 

  42. Bender AC, Morse RP, Scott RC, Holmes GL, Lenck-Santini PP. SCN1A mutations in Dravet syndrome: impact of interneuron dysfunction on neural networks and cognitive outcome. Epilepsy Behav. 2012;23:177–86.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Akiyama M, Kobayashi K, Yoshinaga H, Ohtsuka Y. A long-term follow-up study of Dravet syndrome up to adulthood. 2010;51:1043–52.

  44. Claes L et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet. 2001;68:1327–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sugawara T et al. Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy. Neurology. 2002;58:1122–4.

    Article  CAS  PubMed  Google Scholar 

  46. Djémié T et al. Pitfalls in genetic testing: the story of missed SCN1A mutations. Mol Genet Genomic Med. 2016;1–8. doi:10.1002/mgg3.217.

  47. Mulley JC et al. SCN1A mutations and epilepsy. Hum Mutat. 2005;25:535–42.

    Article  CAS  PubMed  Google Scholar 

  48. Depienne C et al. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet. 2009;46:183–91.

    Article  CAS  PubMed  Google Scholar 

  49. • Meng H et al. The SCN1A mutation database: updating information and analysis of the relationships among genotype, functional alteration, and phenotype. Hum Mutat. 2015;36:573–80. This is the most up-to-date listing and consideration of mutations and phenotypes in SCN1A related epilepsy, which is the most common genetic casue of the EEs.

  50. Harkin LA et al. Truncation of the GABA A-receptor g2 subunit in a family with generalized epilepsy with febrile seizures plus. 2002;530–6.

  51. Depienne C et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet. 2009;5:e1000381.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Suls A et al. De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome. Am J Hum Genet. 2013;93:967–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Nava C et al. De novo mutations in HCN1 cause early infantile epileptic encephalopathy. Nat Genet. 2014;46:640–5.

    Article  CAS  PubMed  Google Scholar 

  54. Hirose S et al. SCN1A testing for epilepsy: application in clinical practice. Epilepsia. 2013;54:946–52.

    Article  CAS  PubMed  Google Scholar 

  55. Gastaut H et al. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as ‘petit-mal variant’) or Lennox syndrome. Epilepsia. 1966;7:85–138.

    Article  CAS  PubMed  Google Scholar 

  56. Arzimanoglou A et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009;8:82–93.

    Article  PubMed  Google Scholar 

  57. Kaminska A et al. Delineation of cryptogenic Lennox-Gastaut syndrome and myoclonic astatic epilepsy using multiple correspondence analysis. Epilepsy Res. 1999;36:15–29.

    Article  CAS  PubMed  Google Scholar 

  58. Filippini M, Boni A, Dazzani G, Guerra A, Gobbi G. Neuropsychological findings: myoclonic astatic epilepsy (MAE) and Lennox-Gastaut syndrome (LGS). Epilepsia. 2006;47:56–9.

    Article  PubMed  Google Scholar 

  59. Hoffmann-Riem M et al. Nonconvulsive status epilepticus—a possible cause of mental retardation in patients with Lennox-Gastaut syndrome. Neuropediatrics. 2000;31:169–74.

    Article  CAS  PubMed  Google Scholar 

  60. Zupanc ML. Clinical evaluation and diagnosis of severe epilepsy syndromes of early childhood. J Child Neurol. 2009;24:6S–14S.

    Article  PubMed  Google Scholar 

  61. Lund C, Brodtkorb E, Øye AM, Røsby O, Selmer KK. CHD2 mutations in Lennox-Gastaut syndrome. Epilepsy Behav. 2014;33:18–21.

    Article  PubMed  Google Scholar 

  62. Jallon P, Loiseau P. Newly diagnosed unprovoked epileptic seizures: presentation at diagnosis in CAROLE Study. 2001;42:464–75.

  63. DeLorenzo RJ et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 1996;46:1029–35.

    Article  CAS  PubMed  Google Scholar 

  64. Wasterlain CG, Fujikawa DG, Penix L, Sankar R. Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia. 1993;34 Suppl 1:S37–53.

    Article  PubMed  Google Scholar 

  65. Walker MC. Diagnosis and treatment of nonconvulsive status epilepticus. CNS Drugs. 2001;15:931–9.

    Article  CAS  PubMed  Google Scholar 

  66. Wallace RH et al. Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet. 2001;28:49–52.

    CAS  PubMed  Google Scholar 

  67. Jouvenceau A et al. Early report human epilepsy associated with dysfunction of the brain P/Q-type calcium channel. Lancet. 2001;358:801–7.

    Article  CAS  PubMed  Google Scholar 

  68. Cossette P et al. Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet. 2002;31:184–9.

    Article  CAS  PubMed  Google Scholar 

  69. Lu J et al. Mutation screen of the GABAA receptor gamma 2 subunit gene in Chinese patients with childhood absence epilepsy. Neurosci Lett. 2002;332:75–8.

    Article  CAS  PubMed  Google Scholar 

  70. Imbrici P et al. Dysfunction of the brain calcium channel Cav2.1 in absence epilepsy and episodic ataxia. Brain. 2004;127:2682–92.

    Article  PubMed  Google Scholar 

  71. Maljevic S et al. A mutation in the GABAA receptor α1-subunit is associated with absence epilepsy. Ann Neurol. 2006;59:983–7.

    Article  CAS  PubMed  Google Scholar 

  72. Suls A et al. Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1. Ann Neurol. 2009;66:415–9.

    Article  CAS  PubMed  Google Scholar 

  73. Arsov T et al. Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency. Epilepsia. 2012;53:e204–7.

    Article  PubMed  Google Scholar 

  74. Muhle H et al. The role of SLC2A1 in early onset and childhood absence epilepsies. Epilepsy Res. 2013;105:229–33.

    Article  CAS  PubMed  Google Scholar 

  75. Mullen SA et al. Glucose transporter 1 deficiency as a treatable cause of myoclonic astatic epilepsy. Arch Neurol. 2011;68:1152–5.

    Article  PubMed  Google Scholar 

  76. Larsen J et al. The role of SLC2A1 mutations in myoclonic astatic epilepsy and absence epilepsy, and the estimated frequency of GLUT1 deficiency syndrome. Epilepsia. 2015;56:e203–8.

    Article  CAS  PubMed  Google Scholar 

  77. Helbig I et al. 15Q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet. 2009;41:160–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Dibbens LM et al. Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance. Hum Mol Genet. 2009;18:3626–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. de Kovel CGF et al. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain. 2010;133:23–32.

    Article  PubMed  Google Scholar 

  80. Mullen SA et al. Copy number variants are frequent in genetic generalized epilepsy with intellectual disability. Neurology. 2013;81:1507–14.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Helbig I et al. Structural genomic variation in childhood epilepsies with complex phenotypes. Eur J Hum Genet. 2014;22:896–901.

    Article  CAS  PubMed  Google Scholar 

  82. Patry G, Lyagoubi S, Tassinari CA. Subclinical ‘electrical status epilepticus’ induced by sleep in children. Arch Neurol. 1971;24:242–52.

    Article  CAS  PubMed  Google Scholar 

  83. Doose H, Neubauer B, Carlson G. Children with benign focal sharp waves. Neuropdatrics. 1996;227–41.

  84. Landau WM, Kleffner FR. Syndrome of acquired aphasia with convulsive disorder in children. Neurology. 1957;7:8–1241.

    Article  Google Scholar 

  85. •• Lemke JR et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet. 2013;45:1067–72. One of three studies published in the same issue of Nature Genetics highlighting the importance of mutations in GRIN2A as gene for epilepsy-aphasia syndromes.

  86. •• Carvill GL et al. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nat Genet. 2013;45:1073–6. One of three studies published in the same issue of Nature Genetics highlighting the importance of mutations in GRIN2A as gene for epilepsy-aphasia syndromes.

  87. •• Lesca G et al. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction. Nat Genet. 2013;45:1061–6. One of three studies published in the same issue of Nature Genetics highlighting the importance of mutations in GRIN2A as gene for epilepsy-aphasia syndromes.

    Article  CAS  PubMed  Google Scholar 

  88. Ptáček LJ et al. Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell. 1991;67:1021–7.

    Article  PubMed  Google Scholar 

  89. Ptáček LJ. Channelopathies: ion channel disorders of muscle as a paradigm for paroxysmal disorders of the nervous system. Neuromuscul Disord. 1997;7:250–5.

    Article  PubMed  Google Scholar 

  90. Yu FH et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci. 2006;9:1142–9.

    Article  CAS  PubMed  Google Scholar 

  91. Catterall WA, Kalume F, Oakley JC. NaV1.1 channels and epilepsy. J Physiol. 2010;588:1849–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Liu Y et al. Dravet syndrome patient-derived neurons suggest a novel epilepsy mechanism. Ann Neurol. 2013;74:128–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Swanson DA, Steel JM, Valle D. Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release. Genomics. 1998;48:373–6.

    Article  CAS  PubMed  Google Scholar 

  94. Verhage M et al. Synaptic assembly of the brain in the absence of neurotransmitter secretion. 2000;287:864–9.

  95. Weimer RM et al. Defects in synaptic vesicle docking in unc-18 mutants. Nat Neurosci. 2003;6:1023–30.

    Article  CAS  PubMed  Google Scholar 

  96. Chen Y et al. Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol. 2003;54:239–43.

    Article  CAS  PubMed  Google Scholar 

  97. Ferguson SM et al. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis. Science. 2007;316:570–4.

    Article  CAS  PubMed  Google Scholar 

  98. Hayashi et al. Cell- and stimulus-dependent heterogeneity of synaptic vesicle endocytic recycling mechanisms revealed by studies of dynamin 1-null neurons. Proc Natl Acad Sci U S A. 2008;105:2175–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. • Dhindsa RS et al. Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis. Neurol Genet. 2015;1:1–9. This is a nice recent example of how to determine the underlying pathophysiological deficiencies in specific genetic EEs.

    Article  CAS  Google Scholar 

  100. Kato M, Dobyns WB. X-linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: proposal for a new term, ‘interneuronopathy’. J Child Neurol. 2005;20:392–7.

    Article  PubMed  Google Scholar 

  101. Anderson SA, Eisenstat DD, Shi L, Rubenstein JL. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science. 1997;278:474–6.

    Article  CAS  PubMed  Google Scholar 

  102. Kitamura K et al. Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet. 2002;32:359–69.

    Article  CAS  PubMed  Google Scholar 

  103. Kato M, Dobyns WB. Lissencephaly and the molecular basis of neuronal migration. Hum Mol Genet. 2003;12 Spec No:R89–96.

    Article  CAS  Google Scholar 

  104. Bonneau D et al. X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. Ann Neurol. 2002;51:340–9.

    Article  PubMed  Google Scholar 

  105. McKenzie O et al. Aristaless-related homeobox gene, the gene responsible for West syndrome and related disorders, is a Groucho/transducin-like enhancer of split dependent transcriptional repressor. Neuroscience. 2007;146:236–47.

    Article  CAS  PubMed  Google Scholar 

  106. Fulp CT et al. Identification of Arx transcriptional targets in the developing basal forebrain. Hum Mol Genet. 2008;17:3740–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Colasante G et al. ARX regulates cortical intermediate progenitor cell expansion and upper layer neuron formation through repression of Cdkn1c. Cereb Cortex. 2015;25:322–35.

    Article  PubMed  Google Scholar 

  108. Sherr EH. The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): one gene leads to many phenotypes. Curr Opin Pediatr. 2003;15:567–71.

    Article  PubMed  Google Scholar 

  109. Friocourt. Mutations in ARX result in several defects involving GABAergic neurons. Front Cell Neurosci. 2010;4:1–11.

    Google Scholar 

  110. Nasrallah MP et al. Differential effects of a polyalanine tract expansion in Arx on neural development and gene expression. Hum Mol Genet. 2012;21:1090–8.

    Article  CAS  PubMed  Google Scholar 

  111. Helbig KL et al. Genetic risk perception and reproductive decision making among people with epilepsy. Epilepsia. 2010;51:1874–7.

    Article  PubMed  Google Scholar 

  112. Lemke JR et al. Targeted next generation sequencing as a diagnostic tool in epileptic disorders. Epilepsia. 2012;53:1387–98.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Markus von Deimling was supported by funds of the Stiftung zur Förderung der medizinischen Forschung of the University of Kiel and by a grant from the German Research Foundation (DFG, HE5415/5-1, HE5415/6-1). Ingo Helbig was supported by intramural funds of the University of Kiel, by a grant from the German Research Foundation (HE5415/3-1) within the EuroEPINOMICS framework of the European Science Foundation, and additional grants of the German Research Foundation (DFG, HE5415/5-1, HE 5415/6-1), German Ministry for Education and Research (01DH12033, MAR 10/012), and grant by the German chapter of the International League against Epilepsy (DGfE).

Eric D. Marsh was supported by NIH/NINDS - R01 NS082761-01. Dr. Marsh has also received a grant from GW Pharma, advisory board fees from Stanley Brothers Social Enterprises, and support from Neuren Pharmaceuticals.

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  1. Division of Neurology, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA, 19104, USA

    Markus von Deimling, Ingo Helbig & Eric D. Marsh

  2. Department of Neuropediatrics, University Medical Center Schleswig-Holstein (UKSH), Christian-Albrechts-University of Kiel, Arnold-Heller-Straße 3, Building 9, 24105, Kiel, Germany

    Markus von Deimling & Ingo Helbig

  3. Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, 34th St and Civic Center Blvd, Philadelphia, PA, 19104, USA

    Eric D. Marsh

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Correspondence to Eric D. Marsh.

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von Deimling, M., Helbig, I. & Marsh, E.D. Epileptic Encephalopathies—Clinical Syndromes and Pathophysiological Concepts. Curr Neurol Neurosci Rep 17, 10 (2017). https://doi.org/10.1007/s11910-017-0720-7

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