Sindhu Viswanathan MBChB, Karen L. Oliver PhD, Brigid M. Regan BSc(Hons), Amy L. Schneider MGenCouns, Candace T. Myers PhD, Michele G. Mehaffey MS, Amy J. LaCroix BS, Jayne Antony MD, PhD, Richard Webster MBBS, MSc, Michael Cardamone PhD, MBBS, Gopinath M. Subramanian MBBS, MD, Annie T.G. Chiu MBBS, Eugenia Roza PhD, MD, Raluca I. Teleanu PhD, MD, Stephen Malone MBBS, PhD, Richard J. Leventer MBBS, PhD, Deepak Gill MBBS, Samuel F. Berkovic MD, FRS, Michael S. Hildebrand PhD, Beatrice S. Goad BS, Katherine B. Howell PhD, MBBS (Hon), BMedSc, Joseph D. Symonds PhD, Andreas Brunklaus MD, Lynette G. Sadleir MBChB, MD, Sameer M. Zuberi MBChB, MD, Heather C. Mefford MD, PhD, Ingrid E. Scheffer MBBS, PhD, FRS
{"title":"用睡眠中的尖峰波激活解开发育性和癫痫性脑病的病因（D/EE-SWAS）。","authors":"Sindhu Viswanathan MBChB, Karen L. Oliver PhD, Brigid M. Regan BSc(Hons), Amy L. Schneider MGenCouns, Candace T. Myers PhD, Michele G. Mehaffey MS, Amy J. LaCroix BS, Jayne Antony MD, PhD, Richard Webster MBBS, MSc, Michael Cardamone PhD, MBBS, Gopinath M. Subramanian MBBS, MD, Annie T.G. Chiu MBBS, Eugenia Roza PhD, MD, Raluca I. Teleanu PhD, MD, Stephen Malone MBBS, PhD, Richard J. Leventer MBBS, PhD, Deepak Gill MBBS, Samuel F. Berkovic MD, FRS, Michael S. Hildebrand PhD, Beatrice S. Goad BS, Katherine B. Howell PhD, MBBS (Hon), BMedSc, Joseph D. Symonds PhD, Andreas Brunklaus MD, Lynette G. Sadleir MBChB, MD, Sameer M. Zuberi MBChB, MD, Heather C. Mefford MD, PhD, Ingrid E. Scheffer MBBS, PhD, FRS","doi":"10.1002/ana.27041","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike–wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike–wave activation in sleep (EE-SWAS).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE-SWAS and EE-SWAS. Brain-specific gene co-expression analysis was performed for D/EE-SWAS genes.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE-SWAS and 13/47 (28%) with EE-SWAS. A genetic etiology was identified in 31/91 (34%). D/EE-SWAS genes were highly co-expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE-SWAS genes with a range of functions: <i>ATP1A2</i>, <i>CACNA1A</i>, <i>FOXP1</i>, <i>GRIN1</i>, <i>KCNMA1</i>, <i>KCNQ3</i>, <i>PPFIA3</i>, <i>PUF60</i>, <i>SETD1B, and ZBTB18</i>, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE-SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE-SWAS.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>DEE-SWAS and EE-SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE-SWAS and EE-SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024;96:932–943</p>\n </section>\n </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 5","pages":"932-943"},"PeriodicalIF":8.1000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496008/pdf/","citationCount":"0","resultStr":"{\"title\":\"Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike–Wave Activation in Sleep (D/EE-SWAS)\",\"authors\":\"Sindhu Viswanathan MBChB, Karen L. Oliver PhD, Brigid M. Regan BSc(Hons), Amy L. Schneider MGenCouns, Candace T. Myers PhD, Michele G. Mehaffey MS, Amy J. LaCroix BS, Jayne Antony MD, PhD, Richard Webster MBBS, MSc, Michael Cardamone PhD, MBBS, Gopinath M. Subramanian MBBS, MD, Annie T.G. Chiu MBBS, Eugenia Roza PhD, MD, Raluca I. Teleanu PhD, MD, Stephen Malone MBBS, PhD, Richard J. Leventer MBBS, PhD, Deepak Gill MBBS, Samuel F. Berkovic MD, FRS, Michael S. Hildebrand PhD, Beatrice S. Goad BS, Katherine B. Howell PhD, MBBS (Hon), BMedSc, Joseph D. Symonds PhD, Andreas Brunklaus MD, Lynette G. Sadleir MBChB, MD, Sameer M. Zuberi MBChB, MD, Heather C. Mefford MD, PhD, Ingrid E. Scheffer MBBS, PhD, FRS\",\"doi\":\"10.1002/ana.27041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike–wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike–wave activation in sleep (EE-SWAS).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE-SWAS and EE-SWAS. Brain-specific gene co-expression analysis was performed for D/EE-SWAS genes.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE-SWAS and 13/47 (28%) with EE-SWAS. A genetic etiology was identified in 31/91 (34%). D/EE-SWAS genes were highly co-expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE-SWAS genes with a range of functions: <i>ATP1A2</i>, <i>CACNA1A</i>, <i>FOXP1</i>, <i>GRIN1</i>, <i>KCNMA1</i>, <i>KCNQ3</i>, <i>PPFIA3</i>, <i>PUF60</i>, <i>SETD1B, and ZBTB18</i>, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE-SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE-SWAS.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Interpretation</h3>\\n \\n <p>DEE-SWAS and EE-SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE-SWAS and EE-SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024;96:932–943</p>\\n </section>\\n </div>\",\"PeriodicalId\":127,\"journal\":{\"name\":\"Annals of Neurology\",\"volume\":\"96 5\",\"pages\":\"932-943\"},\"PeriodicalIF\":8.1000,\"publicationDate\":\"2024-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496008/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ana.27041\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ana.27041","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike–Wave Activation in Sleep (D/EE-SWAS)
Objective
To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike–wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike–wave activation in sleep (EE-SWAS).
Methods
All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE-SWAS and EE-SWAS. Brain-specific gene co-expression analysis was performed for D/EE-SWAS genes.
Results
We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE-SWAS and 13/47 (28%) with EE-SWAS. A genetic etiology was identified in 31/91 (34%). D/EE-SWAS genes were highly co-expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE-SWAS genes with a range of functions: ATP1A2, CACNA1A, FOXP1, GRIN1, KCNMA1, KCNQ3, PPFIA3, PUF60, SETD1B, and ZBTB18, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE-SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE-SWAS.
Interpretation
DEE-SWAS and EE-SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE-SWAS and EE-SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024;96:932–943
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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