Diagnostic Approach to Genetic Causes of Early-Onset Epileptic Encephalopathy

Journal of Child Neurology

Volumn 31, Issue 4, 2016, Pages 523-532

  Gürsoy, Semra ^a   Erçal, Derya ^a  

^a DOKUZ EYLUL UNIVERSITY   (Turkey)

Author keywords

Dravet syndrome; early myoclonic encephalopathy; early onset epileptic encephalopathy; infantile spasm; Ohtahara syndrome

Indexed keywords

ARX GENE; BENIGN CHILDHOOD EPILEPSY; CDKL5 GENE; CN1A GENE; CONSANGUINITY; DIAGNOSTIC APPROACH ROUTE; DISEASE ASSOCIATION; EARLY MYOCLONIC ENCEPHALOPATHY; EARLY ONSET EPILEPTIC ENCEPHALOPATHY; EPILEPSY; FOCAL EPILEPSY; GENE; GENE IDENTIFICATION; GENE MUTATION; HUMAN; INFANTILE SPASM; INHERITANCE; KCNQ2 GENE; OHTAHARA SYNDROME; PCDH19 GENE; PHENOTYPE; PRIORITY JOURNAL; RECURRENT DISEASE; REVIEW; SEVERE MYOCLONIC EPILEPSY IN INFANCY; SLC25A22 GENE; TXBP1 GENE; GENETICS; INFANT; NEWBORN; ONSET AGE; SPASMS, INFANTILE;

AGE OF ONSET; HUMANS; INFANT; INFANT, NEWBORN; SPASMS, INFANTILE;

EID: 84957942171     PISSN: 08830738     EISSN: 17088283     Source Type: Journal    
DOI: 10.1177/0883073815599262     Document Type: Review

References (98)

1. 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: 676-685.
2. Khan S, Al Baradie R,. Epileptic encephalopathies: an overview. Epilepsy Res Treat. 2012; 2012: 403592.
3. Sharma S, Prasad AN,. Genetic testing of epileptic encephalopathies of infancy: an approach. Can J Neurol Sci. 2013; 40: 10-16.
4. Donat JF,. The age-dependent epileptic encephalopathies. J Child Neurol. 1992; 7: 7-21.
5. Lemke JR, Riesch E, Scheurenbrand T, et al. Targeted next generation sequencing as a diagnostic tool in epileptic disorders. Epilepsia. 2012; 53: 1387-1398.
6. Kang HJ, Kawasawa YI, Cheng F, et al. Spatio-temporal transcriptome of the human brain. Nature. 2011; 478: 483-489.
7. Beal JC, Cherian K, Moshe SL,. Early-onset epileptic encephalopathies: Ohtahara syndrome and early myoclonic encephalopathy. Pediatr Neurol. 2012; 47: 317-323.
8. Ohtahara S, Yamatogi Y,. Epileptic encephalopathies in early infancy with suppression-burst. J Clin Neurophysiol. 2003; 20: 398-407.
9. Mastrangelo M, Leuzzi V,. Genes of early-onset epileptic encephalopathies: from genotype to phenotype. Pediatr Neurol. 2012; 46: 24-31.
10. 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.
11. 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; 782-788.
12. 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: 361-366.
13. Molinari F, Kaminska A, Fiermonte G, et al. Mutations in the mitochondrial glutamate carrier SLC25A22 in neonatal epileptic encephalopathy with suppression bursts. Clin Genet. 2009; 76: 188-194.
14. Weckhuysen S, Mandelstam S, Suls A, et al. KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol. 2012; 71: 15-25.
15. Mastrangelo M, Celato A, Leuzzi V,. Diagnostic algorithm for the evaluation of early onset genetic-metabolic epileptic encephalopathies. Eur J Paediatr Neurol. 2012; 16: 179-191.
16. Aicardi J, Ohtahara S,. Severe neonatal epilepsies with suppression-burst pattern. In: Roger J, Bureau M, Dravet Ch, eds. Epileptic Syndromes in Infancy, Childhood and Adolescencce. 3rd ed. Eastleigh: John Libbey; 2002: 33-44.
17. Cohen R, Basel-Vanagaite L, Goldberg-Stern H, et al. Two siblings with early infantile myoclonic encephalopathy due to mutation in the gene encoding mitochondrial glutamate/H+ symporter SLC25A22. Eur J Paediatr Neurol. 2014; 18: 801-805.
18. Molinari F, Raas-Rothschild A, Rio M, et al. Impaired mitochondrial glutamate transport in autosomal recessive neonatal myoclonic epilepsy. Am J Hum Genet. 2005; 76: 334-339.
19. Aicardi J, ed. Disease of Nervous System in Childhood. Infantile Spasms. 3rd ed. New York: MacKeith press; 2009; 593-597.
20. Trevathan E, Murphy CC, Yeargin-Allsopp M,. The descriptive epidemiology of infantile spasms among Atlanta children. Epilepsia. 1999; 40: 748-751.
21. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989; 30: 389-399.
22. Pavone P, Striano P, Falsaperla R, Pavone L, Ruggieri M,. Infantile spasms syndrome, West syndrome and related phenotypes: what we know in 2013. Brain Dev. 2014; 36: 739-751.
23. Widjaja E, Go C, McCoy B, Snead OC,. Neurodevelopmental outcome of infantile spasms: a systematic review and meta-analysis. Epilepsy Res. 2015; 109: 155-162.
24. Nash K, Sullivan J,. Myoclonic seizures and infantile spasms. In: Swaiman KF, Ferriero DM, Schor NF, eds. Swaiman's Pediatric Neurology: Principles and Practice. 5th ed. Edinburgh: Elsevier Saunders; 2012: 774-789.
25. Riikonen R,. Long-term outcome of patients with West syndrome. Brain Dev. 2001; 23: 683-687.
26. Kato M, Das S, Petras K, et al. Polyalanine expansion of ARX associated with cryptogenic West syndrome. Neurology. 2003; 61: 267-276.
27. Nemos C, Lambert L, Giuliano F, et al. Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature. Clin Genet. 2009; 76: 357-371.
28. Allen AS, Berkovic SF, Cossette P, et al. Epi4 K Consortium; Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature. 2013; 501: 217-221.
29. Marshall CR, Young EJ, Pani AM, et al. Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.11. Am J Hum Genet. 2008; 83: 106-111.
30. Otsuka M, Oguni H, Liang JS, et al. STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome: result of Japanese cohort study. Epilepsia. 2010; 51: 2449-2452.
31. Wallace RH, Hodgson BL, Grinton BE, et al. Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms. Neurology. 2003; 61: 765-769.
32. 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: 1046-1053.
33. EuroEPINOMICS-RES Consortium; Epilepsy Phenome/Genome Project; Epi4 K Consortium. De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. Am J Hum Genet. 2014; 95: 360-370.
34. Dravet C,. The core Dravet syndrome phenotype. Epilepsia. 2011; 52: 3-9.
35. Wolff M, Casse-Perrot C, Dravet C,. Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuropsychological findings. Epilepsia. 2006; 47: 45-48.
36. Korff C, Laux L, Kelley K, et al. Dravet syndrome (severe myoclonic epilepsy in infancy): a retrospective study of 16 patients. J Child Neurol. 2007; 22: 185-194.
37. Bureau M, Dalla Bernardina B,. Electroencephalographic characteristics of Dravet syndrome. Epilepsia. 2011; 52: 13-23.
38. Dravet C, Bureau M, Oguni H, et al. Severe myoclonic epilepsy in infancy: Dravet syndrome. In: Roger J, Bureau M, Dravet C, et al, eds. Epileptic Syndromes in Infancy, Childhood and Adolescence. Montrouge, France: John Libbey Eurotext Ltd.; 2005: 89-113.
39. Catarino CB, Liu JY, Liagkouras I, et al. Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology. Brain. 2011; 134: 2982-3010.
40. Genton P, Velizarova R, Dravet C,. Dravet syndrome: the long-term outcome. Epilepsia. 2011; 52: 44-49.
41. Johnson JN, Hofman N, Haglund CM, Cascino GD, Wilde AA, Ackerman MJ,. Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy. Neurology. 2009; 72: 224-231.
42. Nashef L, Hindocha N, Makoff A,. Risk factors in sudden death in epilepsy (SUDEP): the quest for mechanisms. Epilepsia. 2007; 48: 859-871.
43. Depienne C, Trouillard O, Gourfinkel-An I, et al. Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome. J Med Genet. 2010; 47: 404-410.
44. Bayat A, Hjalgrim H, Møller RS,. The incidence of SCN1A -related Dravet syndrome in Denmark is 1:22,000: a population-based study from 2004 to 2009. Epilepsia. 2015; 56: e36-e39.
45. Harkin LA, McMahon JM, Iona X, et al. The spectrum of SCN1A -related infantile enceptic encephalopathies. Brain. 2007; 130 (Pt 3): 843-852.
46. Singh R, Andermann E, Whitehouse WP, et al. Severe myoclonic epilepsy of infancy: extended spectrum of GEFS. Epilepsia. 2001; 42: 837-844.
47. Scheffer IE, Zhang YH, Jansen FE, Dibbens L,. Dravet syndrome or genetic (generalized) epilepsy with febrile seizure plus? Brain Dev. 2009; 31: 394-400.
48. Gospe SM Jr,. Neonatal vitamin-responsive epileptic encephalopathies. Chang Gung Med J. 2010; 33: 1-12.
49. Rossi S, Daniele I, Bastrenta P, et al. Early myoclonic encephalopathy and nonketotic hyperglycinemia. Pediatr Neurol. 2009; 41: 371-374.
50. Wheless JW, Gibson PA, Rosbeck KL, et al. Infantile spasms (West syndrome): update and resources for pediatricians and providers to share with parents. BMC Pediatr. 2012; 12: 108-116.
51. Sorge G, Sorge A,. Epilepsy and chromosomal abnormalities. Ital J Pediatr. 2010; 3: 36.
52. Prasad AN, Hoffman GF,. Early onset epilepsy and inherited metabolic disorder: diagnosis and management. Can J Neurol Sci. 2010; 37: 350-358.
53. Deprez L, Weckhuysen S, Holmgren P, et al. Clinical spectrum of early onset epileptic encephalopathies associated with STXBP1 mutations. Neurology. 2010; 75: 1159-1164.
54. Thomas B, Al Dossary N, Widjaja E,. MRI of childhood epilepsy due to inborn errors of metabolism. AJR Am J Roentgenol. 2010; 194: 367-374.
55. Guerrini R, Striano P, Catarino C, Sisodiya S,. Neuroimaging and neuropathology of Dravet syndrome. Epilepsia. 2011; 52 (suppl 2): 30-34.
56. Vata M, Tennison MB, Aylsworth AS, et al. A novel STXBP1 mutation causes focal seizures with neonatal onset. J Child Neurol. 2012; 27: 811-814.
57. Rickman C, Medine CN, Bergmann A, Duncan RR,. Functionally and spatially distinct modes of MUNC18-syntaxin 1 interaction. J Biol Chem. 2007; 282: 12097-12103.
58. Milh M, Villeneuve N, Chouchane M, et al. Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations. Epilepsia. 2011; 52: 1828-1834.
59. Saitsu H, Kato M, Okada I, et al. STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia. 2010; 51: 2397-2405.
60. Shoubridge C, Fullston T, Gecz J,. ARX spectrum disorders: making inroads into the molecular pathology. Hum Mutat. 2010; 31: 889-900.
61. Archer HL, Evans J, Edwards S, et al. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet. 2006; 43: 729-734.
62. Chaste P, Nygren G, Anckarsäter H, et al. Mutation screening of the ARX gene in patients with autism. Am J Med Genet B Neuropsychiatr Genet. 2007; 144B: 228-230.
63. Kato M, Koyama N, Ohta M, et al. Frameshift mutations of the ARX gene in familial Ohtahara syndrome. Epilepsia. 2010; 51: 1679-1684.
64. Fiermonte G, Palmieri L, Todisco S, et al. Identification of mitochondrial glutamate transporter. J Biol Chem. 2002; 277: 19289-19294.
65. Berkich DA, Ola MS, Cole J, et al. Mitochondrial transport proteins of the brain. J Neurosci Res. 2007; 85: 3367-3377.
66. Kato M, Yamagata T, Kubota M, et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia. 2013; 54: 1282-1287.
67. Singh NA, Westenskow P, Charlier C, et al. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain. 2003; 126: 2726-2737.
68. Steinlein OK, Conrad C, Weidner B,. Benign familial neonatal convulsions: always benign? Epilepsy Res. 2007; 73: 245-249.
69. Montini E, Andolfi G, Caruso A, et al. Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region. Genomics. 1998; 51: 427-433.
70. Kilstrup-Nielsen C, Rusconi L, La Montanara P, et al. What we know and would like to know about CDKL5 and its involvement in epileptic encephalopathy. Neural Plast. 2012; 15: 728267.
71. Bahi-Buisson N, Villeneuve N, Caietta E, et al. Recurrent mutations in the CDKL5 gene: genotype-phenotype relationships. Am J Med Genet A. 2012; 15: 1612-1619.
72. Klein KM, Yendle SC, Harvey AS, et al. A distinctive seizure type in patients with CDKL5 mutations: hypermotor-tonic-spasms sequence. Neurology. 2011; 76: 1436-1438.
73. White R, Ho G, Schmidt S, et al. Cyclin-dependent kinase-like 5 (CDKL5) mutation screening in Rett syndrome and related disorders. Twin Res Hum Genet. 2010; 13: 168-178.
74. Mei D, Darra F, Barba C, et al. Optimizing the molecular diagnosis of CDKL5 gene-related epileptic encephalopathy in boys. Epilepsia. 2014; 55: 1748-1753.
75. 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: 427-433.
76. Barcia G, Chemaly N, Gobin S, et al. Early epileptic encephalopathies associated with STXBP1 mutations: could we better delineate the phenotype? Eur J Med Genet. 2014; 57: 15-20.
77. Depienne C, Trouillard O, Saint-Martin C, et al. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet. 2009; 46: 183-191.
78. Mulley JC, Nelson P, Guerrero S, et al. A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic deletions in SCN1A. Neurology. 2006; 67: 1094-1095.
79. Lossin C,. A catalog of SCN1A variants. Brain Dev. 2009; 31: 114-130.
80. Madia F, Striano P, Gennaro E, et al. Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy. Neurology. 2006; 67: 1230-1235.
81. Suls A, Claeys KG, Goossens D, et al. Microdeletions involving the SCN1A gene may be common in SCN1A -mutation-negative SMEI patients. Hum Mutat. 2006; 27: 914-920.
82. Wang JW, Kurahashi H, Ishii A, et al. Microchromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy. Epilepsia. 2008; 49: 1528-1534.
83. Yu MJ, Shi YW, Gao MM, et al. Milder phenotype with SCN1A truncation mutation other than SMEI. Seizure. 2010; 19: 443-445.
84. Kwong AK, Fung CW, Chan SY, Wong VC,. Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome. PLoS One. 2012; 7: e41802.
85. Macdonald RL, Kang JQ,. Molecular pathology of genetic epilepsies associated with GABAA receptor subunit mutations. Epilepsy Curr. 2009; 9: 18-23.
86. Ishii A, Kanaumi T, Sohda M, et al. Association of nonsense mutation in GABRG2 with abnormal trafficking of GABAA receptors in severe epilepsy. Epilepsy Res. 2014; 108: 420-432.
87. Carvill GL, Weckhuysen S, McMahon JM, et al. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology. 2014; 82: 1245-1253.
88. Frank M, Kemler R,. Protocadherins. Curr Opin Cell Biol. 2002; 14: 557-562.
89. Scheffer IE, Turner SJ, Dibbens LM, et al. Epilepsy and mental retardation limited to females: an under-recognized disorder. Brain. 2008; 131: 918-927.
90. Cappelletti S, Specchio N, Moavero R, et al. Cognitive development in females with PCDH19 gene-related epilepsy. Epilepsy Behav. 2015; 42: 36-40.
91. Duszyc K, Terczynska I, Hoffman-Zacharska D,. Epilepsy and mental retardation restricted to females: X-linked epileptic infantile encephalopathy of unusual inheritance. J Appl Genet. 2015; 56: 49-56.
92. Depienne C, Bouteiller D, Keren B, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet. 2009; 5: e1000381.
93. Marini C, Mei D, Parmeggiani L, et al. Protocadherin 19 mutations in girls with infantile-onset epilepsy. Neurology. 2010; 75: 646-653.
94. van Harssel JJ, Weckhuysen S, van Kempen MJ, et al. Clinical and genetic aspects of PCDH19 -related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders. Neurogenetics. 2013; 14: 23-34.
95. Ream MA, Mikati MA,. Clinical utility of genetic testing in pediatric drug-resistant epilepsy: a pilot study. Epilepsy Behav. 2014; 37: 241-248.
96. Mercimek-Mahmutoglu S, Patel J, Cordeiro D, et al. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia. 2015; 56: 707-716.
97. Botstein D, Risch N,. Discovering genotypes underlying human phenotypes: past successes for Mendelian disease, future approaches for complex disease. Nat Genet. 2003; 33: 228-237.
98. Farwell KD, Shahmirzadi L, El-Khechen D, et al. Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genet Med. 2015; 17: 578-586.