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22.02.2024 | Original Article

Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort

verfasst von: Ayberk Türkyılmaz, Safiye Güneş Sağer, Emine Tekin, Kerem Teralı, Hanife Düzkalır, Metin Eser, Yasemin Akın

Erschienen in: Neurogenetics | Ausgabe 2/2024

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Abstract

The terms developmental epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) designate a spectrum of conditions that are typified by different combinations of motor, cognitive, language, and behavioral regression linked to robust spike-and-wave activity during sleep. In this study, we aimed at describing the clinical and molecular findings in “(developmental) epileptic encephalopathy with spike-and-wave activation in sleep” (D)EE-SWAS) patients as well as at contributing to the genetic etiologic spectrum of (D)EE-SWAS. Single nucleotide polymorphism (SNP) array and whole-exome sequencing (WES) techniques were used to determine the underlying genetic etiologies. Of the 24 patients included in the study, 8 (33%) were female and 16 (67%) were male. The median age at onset of the first seizure was 4 years and the median age at diagnosis of (D)EE-SWAS was 5 years. Of the 24 cases included in the study, 13 were compatible with the clinical diagnosis of DEE-SWAS and 11 were compatible with the clinical diagnosis of EE-SWAS. Abnormal perinatal history was present in four cases (17%), and two cases (8%) had a family history of epilepsy. Approximately two-thirds (63%) of all patients had abnormalities detected on brain computerized tomography/magnetic resonance (CT/MR) imaging. After SNP array and WES analysis, the genetic etiology was revealed in 7 out of 24 (29%) cases. Three of the variants detected were novel (SLC12A5, DLG4, SLC9A6). This study revealed for the first time that Smith-Magenis syndrome, SCN8A-related DEE type 13 and SLC12A5 gene variation are involved in the genetic etiology of (D)EE-SWAS. (D)EE-SWAS is a genetically diverse disorder with underlying copy number variations and single-gene abnormalities. In the current investigation, rare novel variations in genes known to be related to (D)EE-SWAS and not previously reported genes to be related to (D)EE-SWAS were discovered, adding to the molecular genetic spectrum. Molecular etiology enables the patient and family to receive thorough and accurate genetic counseling as well as a personalized medicine approach.

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Rubboli G, Gardella E, Cantalupo G, Alberto Tassinari C (2023) Encephalopathy related to status epilepticus during slow sleep (ESES). Pathophysiological insights and nosological considerations. Epilepsy Behav 140:109105. https://doi.org/10.1016/j.yebeh.2023.109105CrossRefPubMed

Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P et al (2022) International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia 63:1398–1442. https://doi.org/10.1111/epi.17241CrossRefPubMed

Fernández IS, Chapman KE, Peters JM, Kothare SV, Nordli DR Jr, Jensen FE et al (2013) The tower of Babel: survey on concepts and terminology in electrical status epilepticus in sleep and continuous spikes and waves during sleep in North America. Epilepsia 54:741–750. https://doi.org/10.1111/epi.12039CrossRefPubMed

Loddenkemper T, Fernández IS, Peters JM (2011) Continuous spike and waves during sleep and electrical status epilepticus in sleep. J Clin Neurophysiol 28:154–164. https://doi.org/10.1097/WNP.0b013e31821213ebCrossRefPubMed

Tassinari CA, Rubboli G, Volpi L, Meletti S, d’Orsi G, Franca M et al (2000) Encephalopathy with electrical status epilepticus during slow sleep or ESES syndrome including the acquired aphasia. Clin Neurophysiol 111(Suppl 2):S94–S102. https://doi.org/10.1016/s1388-2457(00)00408-9CrossRefPubMed

Arican P, Gencpinar P, OlgacDundar N, Tekgul H (2021) Electrical Status Epilepticus During Slow-wave Sleep (ESES): Current Perspectives. J Pediatr Neurosci 16:91–96. https://doi.org/10.4103/jpn.JPN_137_20CrossRefPubMedPubMedCentral

Galanopoulou AS, Bojko A, Lado F, Moshé SL (2000) The spectrum of neuropsychiatric abnormalities associated with electrical status epilepticus in sleep. Brain Dev 22:279–295. https://doi.org/10.1016/s0387-7604(00)00127-3CrossRefPubMed

Eriksson MH, Baldeweg T, Pressler R, Boyd SG, Huber R, Cross JH et al (2023) Sleep homeostasis, seizures, and cognition in children with focal epilepsy. Dev Med Child Neurol 65:701–711. https://doi.org/10.1111/dmcn.15403CrossRefPubMed

Monteiro JP, Roulet-Perez E, Davidoff V, Deonna T (2021) Primary neonatal thalamic haemorrhage and epilepsy with continuous spike-wave during sleep: a longitudinal follow-up of a possible significant relation. Eur J Paediatr Neurol 5:41–47. https://doi.org/10.1053/ejpn.2001.0403CrossRef

10.

Rubboli G, Huber R, Tononi G, Tassinari CA (2019) Encephalopathy related to Status Epilepticus during slow Sleep: a link with sleep homeostasis? Epileptic Disord 21:62–70. https://doi.org/10.1684/epd.2019.1059CrossRefPubMed

11.

Sánchez Fernández I, Takeoka M, Tas E, Peters JM, Prabhu SP, Stannard KM et al (2012) Early thalamic lesions in patients with sleep-potentiated epileptiform activity. Neurology 78:1721–1727. https://doi.org/10.1212/WNL.0b013e3182582ff8CrossRefPubMedPubMedCentral

12.

Sánchez Fernández I, Loddenkemper T, Peters JM, Kothare SV (2012) Electrical status epilepticus in sleep: clinical presentation and pathophysiology. Pediatr Neurol 47:390–410. https://doi.org/10.1016/j.pediatrneurol.2012.06.016CrossRefPubMed

13.

van den Munckhof B, de Vries EE, Braun KP, Boss HM, Willemsen MA et al (2016) Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome. Epilepsia 57:e45-50. https://doi.org/10.1111/epi.13274CrossRefPubMed

14.

Caraballo RH, Veggiotti P, Kaltenmeier MC, Piazza E, Gamboni B, Lopez Avaria MF et al (2013) Encephalopathy with status epilepticus during sleep or continuous spikes and waves during slow sleep syndrome: a multicenter, long-term follow-up study of 117 patients. Epilepsy Res 105:164–173. https://doi.org/10.1016/j.eplepsyres.2013.02.010CrossRefPubMed

15.

Gong P, Xue J, Jiao X, Zhang Y, Yang Z (2021) Genetic Etiologies in Developmental and/or Epileptic Encephalopathy With Electrical Status Epilepticus During Sleep: Cohort Study. Front Genet 12:607965. https://doi.org/10.3389/fgene.2021.607965CrossRefPubMedPubMedCentral

16.

Kessi M, Peng J, Yang L, Xiong J, Duan H, Pang N et al (2018) Genetic etiologies of the electrical status epilepticus during slow wave sleep: systematic review. BMC Genet 19:40. https://doi.org/10.1186/s12863-018-0628-5CrossRefPubMedPubMedCentral

17.

Alsini H, Alghamdi A, Alshafi S, Hundallah K, Almehmadi S, Alsowat D et al (2023) Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep in Saudi Arabia: Electroclinical, etiologic, genetic, and outcome multicenter study. Seizure 107:146–154. https://doi.org/10.1016/j.seizure.2023.04.013CrossRefPubMed

18.

Sonnek B, Döring JH, Mütze U, Schubert-Bast S, Bast T, Balke D et al (2021) Clinical spectrum and treatment outcome of 95 children with continuous spikes and waves during sleep (CSWS). Eur J Paediatr Neurol 30:121–127. https://doi.org/10.1016/j.ejpn.2020.10.010CrossRefPubMed

19.

Pavlidis E, Møller RS, Nikanorova M, Kölmel MS, Stendevad P, Beniczky S et al (2019) Idiopathic encephalopathy related to status epilepticus during slow sleep (ESES) as a “pure” model of epileptic encephalopathy. An electroclinical, genetic, and follow-up study. Epilepsy Behav 97:244–252. https://doi.org/10.1016/j.yebeh.2019.05.030CrossRefPubMed

20.

Kalia LV, Kalia SK, Salter MW (2008) NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol 7:742–755. https://doi.org/10.1016/S1474-4422(08)70165-0CrossRefPubMedPubMedCentral

21.

Bonanni P, Negrin S, Volzone A, Zanotta N, Epifanio R, Zucca C et al (2017) Electrical status epilepticus during sleep in Mowat-Wilson syndrome. Brain Dev 39:727–734. https://doi.org/10.1016/j.braindev.2017.04.013CrossRefPubMed

22.

Zanni G, Barresi S, Cohen R, Specchio N, Basel-Vanagaite L, Valente EM et al (2014) A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES). Epilepsy Res 108:811–815. https://doi.org/10.1016/j.eplepsyres.2014.02.009CrossRefPubMed

23.

Ergun-Longmire B, Nguyen MHN, Com G (2022) Electrical status epilepticus during sleep in a child with Prader-Willi syndrome: a case report. AME Case Rep 6:7. https://doi.org/10.21037/acr-21-34CrossRefPubMedPubMedCentral

24.

Öktem F, Gençöz T, Erden G, Sezgin N, Uluç S (2013) Turkish version of Wechsler Intelligence Scale for Children-IV (WISC-IV) application and scoring handbook. Ankara Turkish Psychological Association Publications

25.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424. https://doi.org/10.1038/gim.2015.30CrossRefPubMedPubMedCentral

26.

Fan X, Huang J, Jin X, Yan N (2023) Cryo-EM structure of human voltage-gated sodium channel Nav1.6. Proc Natl Acad Sci U S A 120:e2220578120. https://doi.org/10.1073/pnas.2220578120CrossRefPubMedPubMedCentral

27.

Chi X, Li X, Chen Y, Zhang Y, Su Q, Zhou Q (2021) Cryo-EM structures of the full-length human KCC2 and KCC3 cation-chloride cotransporters. Cell Res 31:482–484. https://doi.org/10.1038/s41422-020-00437-xCrossRefPubMed

28.

Lomize MA, Pogozheva ID, Joo H, Mosberg HI, Lomize AL (2012) OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res 40:D370–D376. https://doi.org/10.1093/nar/gkr703CrossRefPubMed

29.

Floden EW, Tommaso PD, Chatzou M, Magis C, Notredame C, Chang JM (2016) PSI/TM-Coffee: a web server for fast and accurate multiple sequence alignments of regular and transmembrane proteins using homology extension on reduced databases. Nucleic Acids Res 44:W339–W343. https://doi.org/10.1093/nar/gkw300CrossRefPubMedPubMedCentral

30.

Robert X, Gouet P (2014) Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res 42:W320–W324. https://doi.org/10.1093/nar/gku316CrossRefPubMedPubMedCentral

31.

Kulandaisamy A, Zaucha J, Sakthivel R, Frishman D, Michael Gromiha M (2020) Pred-MutHTP: Prediction of disease-causing and neutral mutations in human transmembrane proteins. Hum Mutat 41:581–590. https://doi.org/10.1002/humu.23961CrossRefPubMed

32.

Pires DEV, Rodrigues CHM, Ascher DB (2020) mCSM-membrane: predicting the effects of mutations on transmembrane proteins. Nucleic Acids Res 48(W1):W147–W153. https://doi.org/10.1093/nar/gkaa416CrossRefPubMedPubMedCentral

33.

Ittisoponpisan S, Islam SA, Khanna T, Alhuzimi E, David A, Sternberg MJE (2019) Can Predicted Protein 3D Structures Provide Reliable Insights into whether Missense Variants Are Disease Associated? J Mol Biol 431:2197–2212. https://doi.org/10.1016/j.jmb.2019.04.009CrossRefPubMedPubMedCentral

34.

Sager G, Takis G, Vatansever Pinar Z, Duzkalir H, Turkyilmaz A, Çağ Y et al (2023) Evaluation of long-term neurocognitive functions in patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)/epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS). Neurophysiol Clin 53:102861. https://doi.org/10.1016/j.neucli.2023.102861CrossRefPubMed

35.

Sager SG, Turkyilmaz A, Gunbey HP, Karatoprak EY, Aslan ES, Akın Y (2023) A novel de novo TET3 loss-of-function variant in a Turkish boy presenting with neurodevelopmental delay and electrical status epilepticus during slow-wave sleep. Brain Dev 45:140–145. https://doi.org/10.1016/j.braindev.2022.09.004CrossRefPubMed

36.

Xie Y, Chang S, Zhao C et al (2020) Structures and an activation mechanism of human potassium-chloride cotransporters. Sci Adv 6:eabc5883. https://doi.org/10.1126/sciadv.abc5883CrossRefPubMedPubMedCentral

37.

Stödberg T, McTague A, Ruiz AJ et al (2015) Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures. Nat Commun 6:8038. https://doi.org/10.1038/ncomms9038CrossRefPubMed

38.

Puskarjov M, Seja P, Heron SE, Williams TC, Ahmad F, Iona X et al (2014) A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. EMBO Rep 15:723–729. https://doi.org/10.1002/embr.201438749CrossRefPubMedPubMedCentral

39.

Tang BL (2020) The Expanding Therapeutic Potential of Neuronal KCC2. Cells 9:240. https://doi.org/10.3390/cells9010240CrossRefPubMedPubMedCentral

40.

Moutton S, Bruel AL, Assoum M, Chevarin M, Sarrazin E, Goizet C et al (2018) Truncating variants of the DLG4 gene are responsible for intellectual disability with marfanoid features. Clin Genet 93:1172–1178. https://doi.org/10.1111/cge.13243CrossRefPubMed

41.

Rodríguez-Palmero A, Boerrigter MM, Gómez-Andrés D, Aldinger KA, Marcos-Alcalde Í, Popp B et al (2021) DLG4-related synaptopathy: a new rare brain disorder. Genet Med 23:888–899. https://doi.org/10.1038/s41436-020-01075-9CrossRefPubMed

42.

Kassabian B, Levy AM, Gardella E, Aledo-Serrano A, Ananth AL, Brea-Fernández et al (2023) Developmental epileptic encephalopathy in DLG4-related synaptopathy. Epilepsia https://doi.org/10.1111/epi.17876. Advance online publication. https://doi.org/10.1111/epi.17876

43.

Goldman AM, Potocki L, Walz K, Lynch JK, Glaze DG, Lupski JR et al (2006) Epilepsy and chromosomal rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)]. J Child Neurol 21:93–98. https://doi.org/10.1177/08830738060210021201CrossRefPubMed

44.

Rive Le Gouard N, Jacquinet A, Ruaud L, Deleersnyder H, Ageorges F, Gallard J et al (2021) Smith-Magenis syndrome: Clinical and behavioral characteristics in a large retrospective cohort. Clin Genet 99:519–528. https://doi.org/10.1111/cge.13906CrossRefPubMed

45.

Girirajan S, Vlangos CN, Szomju BB, Edelman E, Trevors CD, Dupuis L et al (2006) Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum. Genet Med 8:417–427. https://doi.org/10.1097/01.gim.0000228215.32110.89CrossRefPubMed

Titel: Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort
verfasst von: Ayberk Türkyılmaz
Safiye Güneş Sağer
Emine Tekin
Kerem Teralı
Hanife Düzkalır
Metin Eser
Yasemin Akın
Publikationsdatum: 22.02.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Neurogenetics / Ausgabe 2/2024
Print ISSN: 1364-6745
Elektronische ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-024-00751-1

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