Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS)

被引：4

作者：

Viswanathan, Sindhu ^{[1
,2
]}

Oliver, Karen L. ^{[1
,3
,4
]}

Regan, Brigid M. ^{[1
]}

Schneider, Amy L. ^{[1
]}

Myers, Candace T. ^{[5
]}

Mehaffey, Michele G. ^{[5
,6
]}

LaCroix, Amy J. ^{[6
]}

Antony, Jayne ^{[7
]}

Webster, Richard ^{[7
]}

Cardamone, Michael ^{[8
,9
]}

Subramanian, Gopinath M. ^{[10
]}

Chiu, Annie T. G. ^{[1
]}

Roza, Eugenia ^{[11
,12
]}

Teleanu, Raluca I. ^{[11
,12
]}

Malone, Stephen ^{[13
,14
]}

Leventer, Richard J. ^{[15
,16
]}

Gill, Deepak ^{[7
,17
]}

Berkovic, Samuel F. ^{[1
]}

Hildebrand, Michael S. ^{[1
,16
]}

Goad, Beatrice S. ^{[15
,16
]}

Howell, Katherine B. ^{[15
,16
]}

Symonds, Joseph D. ^{[18
,19
]}

Brunklaus, Andreas ^{[18
,19
]}

Sadleir, Lynette G. ^{[20
]}

Zuberi, Sameer M. ^{[18
,19
]}

Mefford, Heather C. ^{[6
,21
]}

Scheffer, Ingrid E. ^{[1
,15
,16
,22
]}

机构：

[1] Univ Melbourne, Austin Hlth, Epilepsy Res Ctr, Dept Med, Melbourne, Australia

[2] Hosp Pulau Pinang, Dept Paediat, George Town, Malaysia

[3] Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun Div, Parkville, Australia

[4] Univ Melbourne, Dept Med Biol, Melbourne, Australia

[5] Univ Washington, Dept Lab Med & Pathol, Seattle, WA USA

[6] Univ Washington, Dept Pediat, Div Genet Med, Seattle, WA USA

[7] Univ Sydney, Childrens Hosp Westmead, Fac Med & Hlth, TY Nelson Dept Neurol & Neurosurg, Sydney, Australia

[8] Sydney Childrens Hosp, Dept Paediat Neurol, Randwick, Australia

[9] UNSW Sydney, Sch Clin Med, Sydney, Australia

[10] John Hunter Childrens Hosp, Dept Paediat Neurol, New Lambton Hts, Australia

[11] Carol Davila Univ Med & Pharm, Fac Med, Clin Neurosci Dept, Bucharest, Romania

[12] Dr Victor Gomoiu Childrens Hosp, Pediat Neurol Dept, Bucharest, Romania

[13] Univ Queensland, Ctr Adv Imaging, St Lucia, Australia

[14] Queensland Childrens Hosp, Neurosci Dept, South Brisbane, Australia

[15] Univ Melbourne, Royal Childrens Hosp, Dept Neurol, Melbourne, Australia

[16] Murdoch Childrens Res Inst, Neurosci Res Grp, Melbourne, Australia

[17] Kids Neurosci Ctr, Kids Res Inst, Sydney, Australia

[18] Univ Glasgow, Sch Hlth & Wellbeing, Glasgow, Scotland

[19] Royal Hosp Children, Paediat Neurosci Res Grp, Glasgow, Scotland

[20] Univ Otago Wellington, Dept Paediat & Child Hlth, Wellington, New Zealand

[21] St Jude Childrens Res Hosp, Ctr Pediat Neurol Dis Res, Memphis, TN USA

[22] Florey Inst Neurosci & Mental Hlth, Melbourne, Australia

来源：

ANNALS OF NEUROLOGY | 2024年 / 96卷 / 05期

基金：

英国医学研究理事会;

关键词：

GRIN2A MUTATIONS; APHASIA; VARIANTS; SPEECH; PHENOTYPE; FREQUENCY; CHILDREN; GENE;

D O I：

10.1002/ana.27041

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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

引用

页码：932 / 943

页数：12

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