دورية أكاديمية
Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures.
| العنوان: | Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. |
|---|---|
| المؤلفون: | Tang S; Evelina London Children's Hospital, London, UK.; Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK., Addis L; Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.; Eli Lilly and Company, Erl Wood, Surrey, UK., Smith A; Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK., Topp SD; Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK., Pendziwiat M; Clinic for Neuropediatrics, Schleswig-Holstein University Clinics, Kiel, Germany., Mei D; Meyer Children's Hospital, University of Florence, Florence, Italy., Parker A; Addenbrooke's Hospital, Cambridge, UK., Agrawal S; Birmingham Children's Hospital National Health Service Foundation Trust, Birmingham, UK., Hughes E; Evelina London Children's Hospital, London, UK.; King's College Hospital, London, UK., Lascelles K; Evelina London Children's Hospital, London, UK., Williams RE; Evelina London Children's Hospital, London, UK., Fallon P; St George's National Health Service Health Care Trust, London, UK., Robinson R; Great Ormond Street Hospital for Children National Health Service Trust, London, UK., Cross HJ; Great Ormond Street Hospital for Children National Health Service Trust, London, UK.; Clinical Neurosciences, UCL - Institute of Child Health, London, UK., Hedderly T; Evelina London Children's Hospital, London, UK., Eltze C; Great Ormond Street Hospital for Children National Health Service Trust, London, UK., Kerr T; St George's National Health Service Health Care Trust, London, UK., Desurkar A; Sheffield Children's National Health Service Foundation Trust, Sheffield, UK., Hussain N; University Hospital of Leicester National Health Service Trust, Leicester, UK., Kinali M; Chelsea and Westminster Hospital National Health Service Foundation Trust, London, UK., Bagnasco I; Child Neurology and Psychiatry Unit, Martini Hospital, Turin, Italy., Vassallo G; Manchester Children's Hospital, Manchester, UK., Whitehouse W; University of Nottingham, Nottingham, UK., Goyal S; Evelina London Children's Hospital, London, UK.; King's College Hospital, London, UK., Absoud M; Evelina London Children's Hospital, London, UK., Møller RS; Danish Epilepsy Center, Dianalund, Denmark., Helbig I; Clinic for Neuropediatrics, Schleswig-Holstein University Clinics, Kiel, Germany.; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; Epilepsy NeuroGenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania., Weber YG; Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tübingen, Germany.; Department of Neurosurgery, University of Tübingen, Tübingen, Germany., Marini C; Meyer Children's Hospital, University of Florence, Florence, Italy., Guerrini R; Meyer Children's Hospital, University of Florence, Florence, Italy., Simpson MA; Division of Genetics and Molecular Medicine, King's College London, London, UK., Pal DK; Evelina London Children's Hospital, London, UK.; Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.; King's College Hospital, London, UK.; Medical Research Council Centre for Neurodevelopmental Disorders, King's College London, London, UK. |
| مؤلفون مشاركون: | EuroEPINOMICS-RES Consortium |
| المصدر: | Epilepsia [Epilepsia] 2020 May; Vol. 61 (5), pp. 995-1007. Date of Electronic Publication: 2020 May 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Science Country of Publication: United States NLM ID: 2983306R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-1167 (Electronic) Linking ISSN: 00139580 NLM ISO Abbreviation: Epilepsia Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Malden, MA : Blackwell Science Original Publication: Copenhagen : Munskgaard |
| مواضيع طبية MeSH: | Epilepsies, Myoclonic/*pathology , Epilepsy, Generalized/*pathology , Seizures/*pathology, Age of Onset ; Attention Deficit Disorder with Hyperactivity/complications ; Attention Deficit Disorder with Hyperactivity/genetics ; Attention Deficit Disorder with Hyperactivity/pathology ; Autism Spectrum Disorder/complications ; Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/pathology ; Child ; Child, Preschool ; Electroencephalography ; Epilepsies, Myoclonic/complications ; Epilepsies, Myoclonic/genetics ; Epilepsy, Generalized/complications ; Epilepsy, Generalized/genetics ; Female ; Humans ; Infant ; Intellectual Disability/complications ; Intellectual Disability/genetics ; Intellectual Disability/pathology ; Male ; Neuroimaging ; Phenotype ; Seizures/genetics ; Exome Sequencing |
| مستخلص: | Objective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE). Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies. Results: We analyzed 101 patients with MAE (70% male). The median age of seizure onset was 34 months (range = 6-72 months). The main seizure types were myoclonic atonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absence in 60%, and tonic seizures in 19% of patients. We observed intellectual disability in 62% of patients, with extremely low adaptive behavioral scores in 69%. In addition, 24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivity symptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, including five previously published patients. These were pathogenic genetic variants in SYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2, SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three new candidate genes, ASH1L, CHD4, and SMARCA2 in one patient each. Significance: MAE is associated with significant neurodevelopmental impairment. MAE is genetically heterogeneous, and we identified a pathogenic genetic etiology in 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestation of several etiologies rather than a discrete syndromic entity. (© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.) |
| التعليقات: | Comment in: Epilepsy Curr. 2020 Aug 27;20(6):351-352. (PMID: 34025252) |
| References: | 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;51:676-85. Doose H, Gerken H, Leonhardt R, Völzke E, Völz C. Centrencephalic myoclonic-astatic petit mal. Clinical and genetic investigation. Neuropadiatrie. 1970;2:59-78. Kaminska A, Ickowicz A, Plouin P, et al. Delineation of cryptogenic Lennox-Gastaut syndrome and myoclonic astatic epilepsy using multiple correspondence analysis. Epilepsy Res. 1999;36:15-29. Oguni H, Tanaka T, Hayashi K, et al. Treatment and long-term prognosis of myoclonic-astatic epilepsy of early childhood. Neuropediatrics. 2002;33:122-32. Kilaru S, Bergqvist AG. Current treatment of myoclonic astatic epilepsy: clinical experience at the Children's Hospital of Philadelphia. Epilepsia. 2007;48:1703-7. Trivisano M, Specchio N, Cappelletti S, et al. Myoclonic astatic epilepsy: an age-dependent epileptic syndrome with favorable seizure outcome but variable cognitive evolution. Epilepsy Res. 2011;97:133-41. Nolte R, Wolff M. Behavioural and developmental aspects of primary generalized myoclonic-astatic epilepsy. Epilepsy Res Suppl. 1992;6:175-83. Nabbout R. Absence of mutations in major GEFS+ genes in myoclonic astatic epilepsy. Epilepsy Res. 2003;56:127-33. Wallace RH, Wang DW, Singh R, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998;19:366-70. Escayg A, Heils A, MacDonald BT, et al. A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus-and prevalence of variants in patients with epilepsy. Am J Hum Genet. 2001;68:866-73. Mullen SA. Glucose transporter 1 deficiency as a treatable cause of myoclonic astatic epilepsy. Ann Neurol. 2011;68:1152-5. Carvill GL, Heavin SB, Yendle SC, et al. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genet. 2013;45:825-30. Mignot C, von Stulpnagel C, Nava C, et al. Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy. J Med Genet. 2016;53:511-22. Syrbe S, Hedrich UBS, Riesch E, et al. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy. Nat Genet. 2015;47:393-9. Schubert J, Siekierska A, Langlois M, et al. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes. Nat Genet. 2014;46:1327-32. Carvill G, McMahon J, Schneider A, et al. Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures. Am J Hum Genet. 2015;96:808-15. Balestrini S, Milh M, Castiglioni C, et al. TBC1D24 genotype-phenotype correlation: epilepsies and other neurologic features. Neurology. 2016;87:77-85. de Lange IM, Helbig KL, Weckhuysen S, et al. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy. J Med Genet. 2016;53:850-8. Wolff M, Johannesen KM, Hedrich UBS, et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain. 2017;140:1316-36. Moller RS, Wuttke TV, Helbig I, et al. Mutations in GABRB3: from febrile seizures to epileptic encephalopathies. Neurology. 2017;88:483-92. Routier L, Verny F, Barcia G, et al. Exome sequencing findings in 27 patients with myoclonic-atonic epilepsy: is there a major genetic factor? Clin Genet. 2019;96:254-60. Helbig I, Lopez-Hernandez T, Shor O, et al. A recurrent missense variant in AP2M1 impairs clathrin-mediated endocytosis and causes developmental and epileptic encephalopathy. Am J Hum Genet. 2019;104:1060-72. Tang S, Hughes E, Lascelles K, EuroEPINOMICS RES Myoclonic Astatic Epilepsy Working Group, Simpson MA, Pal DK. New SMARCA2 mutation in a patient with Nicolaides-Baraitser syndrome and myoclonic astatic epilepsy. Am J Med Genet A. 2017;173:195-9. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30:389-99. Oguni H, Fukuyama Y, Tanaka T, et al. Myoclonic-astatic epilepsy of early childhood-clinical and EEG analysis of myoclonic-astatic seizures, and discussions of the nosology of the syndrome. Brain Dev. 2001;23:757-64. Eom S, Fisher B, Dezort C, Berg AT. Routine developmental, autism, behavioral, and psychological screening in epilepsy care settings. Dev Med Child Neurol. 2014;56:1100-5. Meltzer HG, Goodman R, Ford F. Mental health of children and adolescents in Great Britain. London, UK: The Stationery Office, 2000. Suls A, Jaehn J, Kecskés 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. de Ligt J, Willemsen MH, van Bon BWM, et al. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med. 2012;367:1921-9. Hamdan FF, Srour M, Capo-Chichi J-M, et al. De novo mutations in moderate or severe intellectual disability. PLoS Genet. 2014;10:e1004772. Rauch A, Wieczorek D, Graf E, et al. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet. 2012;380:1674-82. Large-scale discovery of novel genetic causes of developmental disorders. Nature. 2015;519:223-8. Allen AS, Berkovic SF, Cossette P, et al. De novo mutations in epileptic encephalopathies. Nature. 2013;501:217-21. O’Roak BJ, Vives L, Girirajan S, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. 2012;485:246-50. Neale BM, Kou Y, Liu LI, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012;485:242-5. Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485:237-41. de Kovel CGF, Syrbe S, Brilstra EH, et al. Neurodevelopmental disorders caused by de novo variants in KCNB1 genotypes and phenotypes. JAMA Neurol. 2017;74:1228-36. Saitsu H, Akita T, Tohyama J, et al. De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing. Sci Rep. 2015;5(1):15199. Zhu T, Liang C, Li D, et al. Histone methyltransferase Ash1L mediates activity-dependent repression of neurexin-1alpha. Sci Rep. 2016;6:26597. Eschbach K, Moss A, Joshi C, et al. Diagnosis switching and outcomes in a cohort of patients with potential epilepsy with myoclonic-atonic seizures. Epilepsy Res. 2018;147:95-101. Caraballo RH, Chamorro N, Darra F, Fortini S, Arroyo H. Epilepsy with myoclonic atonic seizures: an electroclinical study of 69 patients. Pediatr Neurol. 2013;48:355-62. Inoue T, Ihara Y, Tomonoh Y, et al. Early onset and focal spike discharges as indicators of poor prognosis for myoclonic-astatic epilepsy. Brain Dev. 2014;36:613-9. Heyne HO, Singh T, Stamberger H, et al. De novo variants in neurodevelopmental disorders with epilepsy. Nat Genet. 2018;50:1048-53. Parrini E, Marini C, Mei D, et al. Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum Mutat. 2017;38:216-25. De Rubeis S, He X, Goldberg AP, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014;515:209-15. Stessman HAF, Xiong BO, Coe BP, et al. Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017;49:515-26. Weiss K, Terhal PA, Cohen L, et al. De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms. Am J Hum Genet. 2016;99:934-41. Mefford HC, Muhle H, Ostertag P, et al. Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalised and focal epilepsies. PLoS Genet. 2010;6:e1000962. Mefford HC, Yendle SC, Hsu C, et al. Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol. 2011;70:974-85. Møller RS, Liebmann N, Larsen LHG, et al. Parental mosaicism in epilepsies due to alleged de novo variants. Epilepsia. 2019;60:e63-6. |
| معلومات مُعتمدة: | MC_PC_19009 United Kingdom MRC_ Medical Research Council; MR/J011231/1 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Investigator: D Craiu; C Davila; A Obregia; P De Jonghe; AE Lehesjoki; H Muhle; B Neubauer; K Selmer; U Stephani; K Sterbova; P Striano; T Talvik; S von Spiczak; S Weckhuysen; H Caglayan; D Hoffman-Zacharska Keywords: Doose syndrome; epilepsy/seizures; genetics; myoclonic astatic epilepsy |
| تواريخ الأحداث: | Date Created: 20200530 Date Completed: 20201130 Latest Revision: 20240320 |
| رمز التحديث: | 20240320 |
| DOI: | 10.1111/epi.16508 |
| PMID: | 32469098 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1528-1167 |
|---|---|
| DOI: | 10.1111/epi.16508 |