Display options
Cite
Specchio N, Di Micco V, Trivisano M, et al. The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy. Epilepsia. 2021;63(1):6-21doi: 10.1111/epi.17115.
Specchio, N., Di Micco, V., Trivisano, M., Ferretti, A., & Curatolo, P. (2022). The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy. Epilepsia, 63(1), 6-21. https://doi.org/10.1111/epi.17115
Specchio, Nicola, et al. "The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy." Epilepsia vol. 63,1 (2022): 6-21. doi: https://doi.org/10.1111/epi.17115
Specchio N, Di Micco V, Trivisano M, Ferretti A, Curatolo P. The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy. Epilepsia. 2022 Jan;63(1):6-21. doi: 10.1111/epi.17115. Epub 2021 Nov 06. PMID: 34741464.
Copy Download .nbib Format: NLM
Share it on

Epilepsia. 2022 Jan;63(1):6-21. doi: 10.1111/epi.17115. Epub 2021 Nov 06.

The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy.

Epilepsia

Nicola Specchio, Valentina Di Micco, Marina Trivisano, Alessandro Ferretti, Paolo Curatolo

Affiliations

  1. Rare and Complex Epilepsy Unit, Division of Neurology, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy.
  2. Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, Rome, Italy.

PMID: 34741464 DOI: 10.1111/epi.17115

Abstract

Autism spectrum disorder (ASD) is frequently associated with infants with epileptic encephalopathy, and early interventions targeting social and cognitive deficits can have positive effects on developmental outcome. However, early diagnosis of ASD among infants with epilepsy is complicated by variability in clinical phenotypes. Commonality in both biological and molecular mechanisms have been suggested between ASD and epilepsy, such as occurs with tuberous sclerosis complex. This review summarizes the current understanding of causal mechanisms between epilepsy and ASD, with a particularly genetic focus. Hypothetical explanations to support the conjugation of the two conditions include abnormalities in synaptic growth, imbalance in neuronal excitation/inhibition, and abnormal synaptic plasticity. Investigation of the probable genetic basis has implemented many genes, although the main risk supports existing hypotheses in that these cluster to abnormalities in ion channels, synaptic function and structure, and transcription regulators, with the mammalian target of rapamycin (mTOR) pathway and "mTORpathies" having been a notable research focus. Experimental models not only have a crucial role in determining gene functions but are also useful instruments for tracing disease trajectory. Precision medicine from gene therapy remains a theoretical possibility, but more contemporary developments continue in molecular tests to aid earlier diagnoses and better therapeutic targeting.

© 2021 International League Against Epilepsy.

Keywords: autistic spectrum disorders; developmental and epileptic encephalopathy; genes; precision medicine; tuberous sclerosis

References

  1. Baxter AJ, Brugha TS, Erskine HE, Scheurer RW, Vos T, Scott JG. The epidemiology and global burden of autism spectrum disorders. Psychol Med. 2015;45(3):601-13. - PubMed
  2. Centers for Disease Control and Prevention. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2014. In: Morbidity and Mortality Weekly Report Surveillance Summaries [Internet]. 2018. - PubMed
  3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Publishing; 2015. - PubMed
  4. Tuchman R. Autism and cognition within epilepsy: social matters. Epilepsy Curr. 2015;15(4):202-5. - PubMed
  5. Berg AT, Plioplys S, Tuchman R. Risk and correlates of autism spectrum disorder in children with epilepsy: a community-based study. J Child Neurol. 2011;26(5):540-7. - PubMed
  6. Saemundsen E, Ludvigsson P, Rafnsson V. Autism spectrum disorders in children with a history of infantile spasms: a population-based study. J Child Neurol. 2007;22(9):1102-7. - PubMed
  7. Tuchman R. What is the relationship between autism spectrum disorders and epilepsy? Semin Pediatr Neurol. 2017;24(4):292-300. - PubMed
  8. Holmes H, Sawer F, Clark M. Autism spectrum disorders and epilepsy in children: a commentary on the occurrence of autism in epilepsy; how it can present differently and the challenges associated with diagnosis. Epilepsy Behav. 2021;117:107813. - PubMed
  9. Richard AE, Scheffer IE, Wilson SJ. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. Neurosci Biobehav Rev. 2017;75:203-33. - PubMed
  10. Hunt A, Dennis J. Psychiatric disorder among children with tuberous sclerosis. Dev Med Child Neurol. 1987;29(2):190-8. - PubMed
  11. Curatolo P, Cusmai R. Autism and infantile spasms in children with tuberous sclerosis. Dev Med Child Neurol. 1987;29(4):551. - PubMed
  12. Specchio N, Pietrafusa N, Trivisano M, Moavero R, De Palma L, Ferretti A, et al. Autism and epilepsy in patients with tuberous sclerosis complex. Front Neurol. 2020;11:639. - PubMed
  13. Mitchell RA, Barton SM, Harvey AS, Ure AM, Williams K. Factors associated with autism spectrum disorder in children with tuberous sclerosis complex: a systematic review and meta-analysis. Dev Med Child Neurol. 2021;63(7):791-801. - PubMed
  14. McDonald NM, Varcin KJ, Bhatt R, Wu JY, Sahin M, Nelson CA, et al. Early autism symptoms in infants with tuberous sclerosis complex. Autism Res. 2017;10(12):1981-90. - PubMed
  15. Moavero R, Kotulska K, Lagae L, Benvenuto A, Emberti Gialloreti L, Weschke B, et al. Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex? Ann Clin Transl Neurol. 2020;7(8):1371-81. - PubMed
  16. Srivastava S, Sahin M. Autism spectrum disorder and epileptic encephalopathy: common causes, many questions. J Neurodev Disord. 2017;9(1):23. - PubMed
  17. Raga S, Specchio N, Rheims S, Wilmshurst JM. Developmental and epileptic encephalopathies: recognition and approaches to care. Epileptic Disord. 2021;23(1):40-52. - PubMed
  18. Scheffer IE, Liao J. Deciphering the concepts behind “Epileptic encephalopathy” and “Developmental and epileptic encephalopathy”. Eur J Paediatr Neurol. 2020;24:11-4. - PubMed
  19. Specchio N, Curatolo P. Developmental and epileptic encephalopathies: what we do and do not know. Brain. 2021;144(1):32-43. - PubMed
  20. Karunakaran S, Menon RN, Nair SS, Santhakumar S, Nair M, Sundaram S. Clinical and genetic profile of Autism Spectrum Disorder-Epilepsy (ASD-E) phenotype: two sides of the same coin! Clin EEG Neurosci. 2020;51(6):390-8. - PubMed
  21. Sierra-Arregui T, Llorente J, Giménez Minguez P, Tønnesen J, Peñagarikano O. Neurobiological mechanisms of autism spectrum disorder and epilepsy, insights from animal models. Neuroscience. 2020;445:69-82. - PubMed
  22. Santini E, Klann E. Reciprocal signaling between translational control pathways and synaptic proteins in autism spectrum disorders. Sci Signal. 2014;7(349):re10. - PubMed
  23. Guang S, Pang N, Deng X, Yang L, He F, Wu L, et al. Synaptopathology involved in autism spectrum disorder. Front Cell Neurosci. 2018;12. - PubMed
  24. Bourgeron T. A synaptic trek to autism. Curr Opin Neurobiol. 2009;19(2):231-4. - PubMed
  25. Nelson SB, Valakh V. Excitatory/inhibitory balance and circuit homeostasis in autism spectrum disorders. Neuron. 2015;87(4):684-98. - PubMed
  26. Shao L-R, Habela CW, Stafstrom CE. Pediatric epilepsy mechanisms: expanding the paradigm of excitation/inhibition imbalance. Children. 2019;6(2):23. - PubMed
  27. Kang J-Q, Barnes G. A common susceptibility factor of both autism and epilepsy: functional deficiency of GABAA receptors. J Autism Dev Disord. 2013;43(1):68-79. - PubMed
  28. Stafstrom CE, Benke TA. Autism and epilepsy: exploring the relationship using experimental models. Epilepsy Curr. 2015;15(4):206-10. - PubMed
  29. Buckley AW, Holmes GL. Epilepsy and autism. Cold Spring Harb Perspect Med. 2016;6(4):a022749. - PubMed
  30. Keller R, Basta R, Salerno L, Elia M. Autism, epilepsy, and synaptopathies: a not rare association. Neurol Sci. 2017;38(8):1353-61. - PubMed
  31. Rosenberg EC, Lippman-Bell JJ, Handy M, Soldan SS, Rakhade S, Hilario-Gomez C, et al. Regulation of seizure-induced MeCP2 Ser421 phosphorylation in the developing brain. Neurobiol Dis. 2018;116:120-30. - PubMed
  32. Brooks-Kayal A. Molecular mechanisms of cognitive and behavioral comorbidities of epilepsy in children. Epilepsia. 2011;52:13-20. - PubMed
  33. Stefanski A, Calle-López Y, Leu C, Pérez-Palma E, Pestana-Knight E, Lal D. Clinical sequencing yield in epilepsy, autism spectrum disorder, and intellectual disability: a systematic review and meta-analysis. Epilepsia. 2021;62(1):143-51. - PubMed
  34. Ontario Health (Quality). Genome-wide sequencing for unexplained developmental disabilities or multiple congenital anomalies: a health technology assessment. Ont Health Technol Assess Ser. 2020;20(11):1-178. - PubMed
  35. Reilly J, Gallagher L, Leader G, Shen S. Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation. PLoS One. 2020;15(12):e0242773. - PubMed
  36. Pineda E, Shin D, You SJ, Auvin S, Sankar R, Mazarati A. Maternal immune activation promotes hippocampal kindling epileptogenesis in mice. Ann Neurol. 2013;74(1):11-9. - PubMed
  37. Oyrer J, Maljevic S, Scheffer IE, Berkovic SF, Petrou S, Reid CA. Ion Channels in genetic epilepsy: from genes and mechanisms to disease-targeted therapies. Pharmacol Rev. 2018;70(1):142-73. - PubMed
  38. Turner TJ, Zourray C, Schorge S, Lignani G. Recent advances in gene therapy for neurodevelopmental disorders with epilepsy. J Neurochem. 2021;157(2):229-62. - PubMed
  39. Daghsni M, Rima M, Fajloun Z, Ronjat M, Brusés JL, M'rad R, et al. Autism throughout genetics: perusal of the implication of ion channels. Brain Behav. 2018;8(8):e00978. - PubMed
  40. Scheffer IE, Nabbout R. SCN1A-related phenotypes: epilepsy and beyond. Epilepsia. 2019;60(S3):S17-S24. - PubMed
  41. Reynolds C, King MD, Gorman KM. The phenotypic spectrum of SCN2A-related epilepsy. Eur J Paediatr Neurol. 2020;24:117-22. - PubMed
  42. Gardella E, Møller RS. Phenotypic and genetic spectrum of SCN 8A -related disorders, treatment options, and outcomes. Epilepsia. 2019;60(S3):S77-S85. - PubMed
  43. Bar C, Barcia G, Jennesson M, Le Guyader G, Schneider A, Mignot C, et al. Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature. Hum Mutat. 2020;41(1):69-80. - PubMed
  44. Marini C, Porro A, Rastetter A, Dalle C, Rivolta I, Bauer D, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141(11):3160-78. - PubMed
  45. Camp CR, Yuan H. GRIN2D/GluN2D NMDA receptor: unique features and its contribution to pediatric developmental and epileptic encephalopathy. Eur J Paediatr Neurol. 2020;24:89-99. - PubMed
  46. Damaj L, Lupien-Meilleur A, Lortie A, Riou É, Ospina LH, Gagnon L, et al. CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms. Eur J Hum Genet. 2015;23(11):1505-12. - PubMed
  47. Wild B, Nelson SL. STXBP1-related developmental and epileptic encephalopathy. Pediatr Neurol Briefs. 2019;33:6. - PubMed
  48. Al Shehhi M, Forman EB, Fitzgerald JE, McInerney V, Krawczyk J, Shen S, et al. NRXN1 deletion syndrome; phenotypic and penetrance data from 34 families. Eur J Med Genet. 2019;62(3):204-9. - PubMed
  49. Trivisano M, Specchio N. The role of PCDH19 in refractory status epilepticus. Epilepsy Behav. 2019;101:106539. - PubMed
  50. Vlaskamp DRM, Shaw BJ, Burgess R, Mei D, Montomoli M, Xie H, et al. SYNGAP1 encephalopathy. Neurology. 2019;92(2):e96-107. - PubMed
  51. Kanani F, Titheradge H, Cooper N, Elmslie F, Lees MM, Juusola J, et al. Expanding the genotype-phenotype correlation of de novo heterozygous missense variants in YWHAG as a cause of developmental and epileptic encephalopathy. Am J Med Genet Part A. 2020;182(4):713-20. - PubMed
  52. Olson HE, Jean-Marçais N, Yang E, Heron D, Tatton-Brown K, van der Zwaag PA, et al. A recurrent De Novo PACS2 heterozygous missense variant causes neonatal-onset developmental epileptic encephalopathy, facial dysmorphism, and cerebellar dysgenesis. Am J Hum Genet. 2018;102(5):995-1007. - PubMed
  53. Bell S, Rousseau J, Peng H, Aouabed Z, Priam P, Theroux J-F, et al. Mutations in ACTL6B cause neurodevelopmental deficits and epilepsy and lead to loss of dendrites in human neurons. Am J Hum Genet. 2019;104(5):815-34. - PubMed
  54. Baldassari S, Picard F, Verbeek NE, van Kempen M, Brilstra EH, Lesca G, et al. The landscape of epilepsy-related GATOR1 variants. Genet Med. 2019;21(2):398-408. - PubMed
  55. Brunklaus A, Du J, Steckler F, Ghanty II, Johannesen KM, Fenger CD, et al. Biological concepts in human sodium channel epilepsies and their relevance in clinical practice. Epilepsia. 2020;61(3):387-99. - PubMed
  56. Rylaarsdam L, Guemez-Gamboa A. Genetic causes and modifiers of autism spectrum disorder. Front Cell Neurosci. 2019;13. http://doi.org/10.3389/fncel.2019.00385 - PubMed
  57. Lima Caldeira G, Peça J, Carvalho AL. New insights on synaptic dysfunction in neuropsychiatric disorders. Curr Opin Neurobiol. 2019;57:62-70. - PubMed
  58. Emberti Gialloreti L, Enea R, Di Micco V, Di Giovanni D, Curatolo P. Clustering analysis supports the detection of biological processes related to autism spectrum disorder. Genes. 2020;11(12):1476. - PubMed
  59. Bhandari R, Paliwal JK, Kuhad A. Neuropsychopathology of Autism Spectrum Disorder: Complex Interplay of Genetic, Epigenetic, and Environmental Factors. In. 2020. p. 97-141. - PubMed
  60. Hamza M, Halayem S, Mrad R, Bourgou S, Charfi F, Belhadj A. Implication de l’épigénétique dans les troubles du spectre autistique: revue de la littérature. Encephale. 2017;43(4):374-81. - PubMed
  61. Lo-Castro A, Curatolo P. Epilepsy associated with autism and attention deficit hyperactivity disorder: Is there a genetic link? Brain Dev. 2014;36(3):185-93. - PubMed
  62. Nguyen LH, Mahadeo T, Bordey A. mTOR hyperactivity levels influence the severity of epilepsy and associated neuropathology in an experimental model of tuberous sclerosis complex and focal cortical dysplasia. J Neurosci. 2019;39(14):2762-73. - PubMed
  63. Iffland PH, Carson V, Bordey A, Crino PB. GATOR opathies: the role of amino acid regulatory gene mutations in epilepsy and cortical malformations. Epilepsia. 2019;60(11):2163-73. - PubMed
  64. Dobyns WB, Mirzaa GM. Megalencephaly syndromes associated with mutations of core components of the PI3K-AKT-MTOR pathway: PIK3CA, PIK3R2, AKT3, and MTOR. Am J Med Genet C Semin Med Genet. 2019;181(4):582-90. - PubMed
  65. Kothare SV, Singh K, Chalifoux JR, Staley BA, Weiner HL, Menzer K, et al. Severity of manifestations in tuberous sclerosis complex in relation to genotype. Epilepsia. 2014;55(7):1025-9. - PubMed
  66. Curatolo P, Moavero R, Roberto D, Graziola F. Genotype/phenotype correlations in tuberous sclerosis complex. Semin Pediatr Neurol. 2015;22(4):259-73. - PubMed
  67. Ogórek B, Hamieh L, Hulshof HM, Lasseter K, Klonowska K, Kuijf H, et al. TSC2 pathogenic variants are predictive of severe clinical manifestations in TSC infants: results of the EPISTOP study. Genet Med. 2020;22(9):1489-97. - PubMed
  68. Peron A, Au KS, Northrup H. Genetics, genomics, and genotype-phenotype correlations of TSC: Insights for clinical practice. Am J Med Genet Part C Semin Med Genet. 2018;178(3):281-90. - PubMed
  69. Curatolo P, Moavero R, van Scheppingen J, Aronica E. mTOR dysregulation and tuberous sclerosis-related epilepsy. Expert Rev Neurother. 2018;18(3):185-201. - PubMed
  70. Curatolo P, Bjørnvold M, Dill PE, Ferreira JC, Feucht M, Hertzberg C, et al. The role of mTOR inhibitors in the treatment of patients with tuberous sclerosis complex: evidence-based and expert opinions. Drugs. 2016;76(5):551-65. - PubMed
  71. Llamosas N, Arora V, Vij R, Kilinc M, Bijoch L, Rojas C, et al. SYNGAP1 controls the maturation of dendrites, synaptic function, and network activity in developing human neurons. J Neurosci. 2020;40(41):7980-94. - PubMed
  72. Lignani G, Raimondi A, Ferrea E, Rocchi A, Paonessa F, Cesca F, et al. Epileptogenic Q555X SYN1 mutant triggers imbalances in release dynamics and short-term plasticity. Hum Mol Genet. 2013;22(11):2186-99. - PubMed
  73. Cao F, Liu JJ, Zhou S, Cortez MA, Snead OC, Han J, et al. Neuroligin 2 regulates absence seizures and behavioral arrests through GABAergic transmission within the thalamocortical circuitry. Nat Commun. 2020;11(1):3744. - PubMed
  74. Matsumura K, Seiriki K, Okada S, Nagase M, Ayabe S, Yamada I, et al. Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes. Nat Commun. 2020;11(1):859. - PubMed
  75. Suliman-Lavie R, Title B, Cohen Y, Hamada N, Tal M, Tal N, et al. Pogz deficiency leads to transcription dysregulation and impaired cerebellar activity underlying autism-like behavior in mice. Nat Commun. 2020;11(1):5836. - PubMed
  76. Sahin M, Sur M. Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders. Science. 2015;350(6263):aab3897. - PubMed
  77. Amador A, Bostick CD, Olson H, Peters J, Camp CR, Krizay D, et al. Modelling and treating GRIN2A developmental and epileptic encephalopathy in mice. Brain. 2020;143(7):2039-57. - PubMed
  78. Wong JC, Shapiro L, Thelin JT, Heaton EC, Zaman RU, D'Souza MJ, et al. Nanoparticle encapsulated oxytocin increases resistance to induced seizures and restores social behavior in Scn1a-derived epilepsy. Neurobiol Dis. 2021;147:105147. - PubMed
  79. Vyas Y, Lee K, Jung Y, Montgomery JM. Influence of maternal zinc supplementation on the development of autism-associated behavioural and synaptic deficits in offspring Shank3-knockout mice. Mol Brain. 2020;13(1):110. - PubMed
  80. Ko C, Kim N, Kim E, Song DH, Cheon K-A. The effect of epilepsy on autistic symptom severity assessed by the social responsiveness scale in children with autism spectrum disorder. Behav Brain Funct. 2016;12(1):20. - PubMed
  81. Viscidi EW, Triche EW, Pescosolido MF, McLean RL, Joseph RM, Spence SJ, et al. Clinical characteristics of children with autism spectrum disorder and co-occurring epilepsy. PLoS One. 2013;8(7):e67797. - PubMed
  82. El Achkar CM, Spence SJ. Clinical characteristics of children and young adults with co-occurring autism spectrum disorder and epilepsy. Epilepsy Behav. 2015;47:183-90. - PubMed
  83. Kazdoba TM, Leach PT, Crawley JN. Behavioral phenotypes of genetic mouse models of autism. Genes Brain Behav. 2016;15(1):7-26. - PubMed
  84. Bertelsen N, Landi I, Bethlehem RAI, Seidlitz J, Busuoli EM, Mandelli V, et al. Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry. Commun Biol. 2021;4(1):574. - PubMed
  85. Peng J, Zhou Y, Wang K. Multiplex gene and phenotype network to characterize shared genetic pathways of epilepsy and autism. Sci Rep. 2021;11(1):952. - PubMed
  86. Chow J, Jensen M, Amini H, Hormozdiari F, Penn O, Shifman S, et al. Dissecting the genetic basis of comorbid epilepsy phenotypes in neurodevelopmental disorders. Genome Med. 2019;11(1):65. - PubMed
  87. Rosina E, Battan B, Siracusano M, Di Criscio L, Hollis F, Pacini L, et al. Disruption of mTOR and MAPK pathways correlates with severity in idiopathic autism. Transl Psychiatry. 2019;9(1):50. - PubMed
  88. Mizuguchi M, Ikeda H, Kagitani-Shimono K, Yoshinaga H, Suzuki Y, Aoki M, et al. Everolimus for epilepsy and autism spectrum disorder in tuberous sclerosis complex: EXIST-3 substudy in Japan. Brain Dev. 2019;41(1):1-10. - PubMed
  89. Burger BJ, Rose S, Bennuri SC, Gill PS, Tippett ML, Delhey L, et al. Autistic siblings with novel mutations in two different genes: insight for genetic workups of autistic siblings and connection to mitochondrial dysfunction. Front Pediatr. 2017;5. http://doi.org/10.3389/fped.2017.00219 - PubMed
  90. Chepure A, Somaiya M, Subramanyam A, Kamath R. Epileptic encephalopathy and autism: a complex interplay. J Pediatr Neurosci. 2018;13(2):273. - PubMed
  91. Trivisano M, Specchio N. What are the epileptic encephalopathies? Curr Opin Neurol. 2020;33(2):179-84. - PubMed
  92. Gardella E, Marini C, Trivisano M, Fitzgerald MP, Alber M, Howell KB, et al. The phenotype of SCN8A developmental and epileptic encephalopathy. Neurology. 2018;91(12):e1112-24. - PubMed
  93. Holder JL, Quach MM. The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations. Epilepsia. 2016;57(10):1651-9. - PubMed
  94. Demarest ST, Olson HE, Moss A, Pestana-Knight E, Zhang X, Parikh S, et al. CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development. Epilepsia. 2019;60(8):1733-42. - PubMed
  95. Trivisano M, Pietrafusa N, Terracciano A, Marini C, Mei D, Darra F, et al. Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: a multicenter study. Epilepsia. 2018;59(12):2260-71. - PubMed
  96. Giacomini T, Nuovo S, Zanni G, Mancardi MM, Cusmai R, Pepi C, et al. CASK related disorder: epilepsy and developmental outcome. Eur J Paediatr Neurol. 2021;31:61-9. - PubMed
  97. Raviglione F, Douzgou S, Scala M, Mingarelli A, D'Arrigo S, Freri E, et al. Electroclinical features of MEF2C haploinsufficiency-related epilepsy: a multicenter European study. Seizure. 2021;88:60-72. - PubMed
  98. Frullanti E, Papa FT, Grillo E, Clarke A, Ben-Zeev B, Pineda M, et al. Analysis of the phenotypes in the rett networked database. Int J Genomics. 2019;2019:1-9. - PubMed
  99. Vegas N, Cavallin M, Maillard C, Boddaert N, Toulouse J, Schaefer E, et al. Delineating FOXG1 syndrome. Neurol Genet. 2018;4(6):e281. - PubMed
  100. Alcantara D, Timms AE, Gripp K, Baker L, Park K, Collins S, et al. Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly. Brain. 2017;140(10):2610-22. - PubMed
  101. Wagnon JL. TANGO with SCN1A: can this molecular dance defeat Dravet syndrome? Epilepsy Curr. 2021;21(1):60-1. - PubMed
  102. Li M, Jancovski N, Jafar-Nejad P, Burbano LE, Rollo B, Richards K, et al. Antisense oligonucleotide therapy for SCN2A gain-of-function epilepsy. 2021. - PubMed
  103. Lenk GM, Jafar-Nejad P, Hill SF, Huffman LD, Smolen CE, Wagnon JL, et al. Scn8a antisense oligonucleotide is protective in mouse models of SCN8A encephalopathy and Dravet syndrome. Ann Neurol. 2020;87(3):339-46. - PubMed
  104. Aimiuwu OV, Fowler AM, Sah M, Teoh JJ, Kanber A, Pyne NK, et al. RNAi-based gene therapy rescues developmental and epileptic encephalopathy in a genetic mouse model. Mol Ther. 2020;28(7):1706-16. - PubMed

Publication Types