{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:44:59Z","timestamp":1785167099476,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Literature on the genotypic spectrum of Infantile Epileptic Spasms Syndrome (IESS) in children is scarce in developing countries. This multicentre collaboration evaluated the genotypic and phenotypic landscape of genetic IESS in Indian children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between January 2021 and June 2022, this cross\u2010sectional study was conducted at six centers in India. Children with genetically confirmed IESS, without definite structural\u2010genetic and structural\u2010metabolic etiology, were recruited and underwent detailed in\u2010person assessment for phenotypic characterization. The multicentric data on the genotypic and phenotypic characteristics of genetic IESS were collated and analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 124 probands (60% boys, history of consanguinity in 15%) with genetic IESS, 105 had single gene disorders (104 nuclear and one mitochondrial), including one with concurrent triple repeat disorder (fragile X syndrome), and 19 had chromosomal disorders. Of 105 single gene disorders, 51 individual genes (92 variants including 25 novel) were identified. Nearly 85% of children with monogenic nuclear disorders had autosomal inheritance (dominant\u201055.2%, recessive\u201014.2%), while the rest had X\u2010linked inheritance. Underlying chromosomal disorders included trisomy 21 (n\u2009=\u200914), Xq28 duplication (n\u2009=\u20092), and others (n\u2009=\u20093). Trisomy 21 (n\u2009=\u200914), <jats:italic>ALDH7A1<\/jats:italic> (n\u2009=\u200910), <jats:italic>SCN2A<\/jats:italic> (n\u2009=\u20097), <jats:italic>CDKL5<\/jats:italic> (n\u2009=\u20096), <jats:italic>ALG13<\/jats:italic> (n\u2009=\u20095), <jats:italic>KCNQ2<\/jats:italic> (n\u2009=\u20094), <jats:italic>STXBP1<\/jats:italic> (n\u2009=\u20094), <jats:italic>SCN1A<\/jats:italic> (n\u2009=\u20094), <jats:italic>NTRK2<\/jats:italic> (n\u2009=\u20094), and <jats:italic>WWOX<\/jats:italic> (n\u2009=\u20094) were the dominant single gene causes of genetic IESS. The median age at the onset of epileptic spasms (ES) and establishment of genetic diagnosis was 5 and 12\u2009months, respectively. Pre\u2010existing developmental delay (94.3%), early age at onset of ES (&lt;6\u2009months; 86.2%), central hypotonia (81.4%), facial dysmorphism (70.1%), microcephaly (77.4%), movement disorders (45.9%) and autistic features (42.7%) were remarkable clinical findings. Seizures other than epileptic spasms were observed in 83 children (66.9%). Pre\u2010existing epilepsy syndrome was identified in 21 (16.9%). Nearly 60% had an initial response to hormonal therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our study highlights a heterogenous genetic landscape and phenotypic pleiotropy in children with genetic IESS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12811","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T05:10:46Z","timestamp":1692421846000},"page":"1383-1404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Landscape of genetic infantile epileptic spasms syndrome\u2014A multicenter cohort of 124 children from India"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4315-9882","authenticated-orcid":false,"given":"Balamurugan","family":"Nagarajan","sequence":"first","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vykuntaraju K.","family":"Gowda","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Indira Gandhi Institute of Child Health  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeetha","family":"Yoganathan","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Neurological Sciences Christian Medical College  Vellore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-7218","authenticated-orcid":false,"given":"Indar Kumar","family":"Sharawat","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Division, Department of Pediatrics All India Institute of Medical Sciences  Rishikesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Bharati Vidyapeeth Deemed University Medical College  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitish","family":"Vora","sequence":"additional","affiliation":[{"name":"Royal Institute of Child Neurosciences  Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Badheka","sequence":"additional","affiliation":[{"name":"Royal Institute of Child Neurosciences  Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Danda","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Christian Medical College  Vellore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Kalane","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Division, Department of Pediatrics All India Institute of Medical Sciences  Rishikesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupriya","family":"Kaur","sequence":"additional","affiliation":[{"name":"Genetics and Metabolic Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Madaan","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"},{"name":"Department of Pediatric Neurology Amrita Institute of Medical Sciences  Faridabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv","family":"Mehta","sequence":"additional","affiliation":[{"name":"Royal Institute of Child Neurosciences  Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Negi","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7831-9271","authenticated-orcid":false,"given":"Prateek Kumar","family":"Panda","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Division, Department of Pediatrics All India Institute of Medical Sciences  Rishikesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-7440","authenticated-orcid":false,"given":"Surekha","family":"Rajadhyaksha","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Bharati Vidyapeeth Deemed University Medical College  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arushi Gahlot","family":"Saini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-0736","authenticated-orcid":false,"given":"Lokesh","family":"Saini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"},{"name":"Department of Pediatrics All India Institute of Medical Sciences  Jodhpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Shah","sequence":"additional","affiliation":[{"name":"Royal Institute of Child Neurosciences  Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varunvenkat M.","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Indira Gandhi Institute of Child Health  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Suthar","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Thomas","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Neurological Sciences Christian Medical College  Vellore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Vyas","sequence":"additional","affiliation":[{"name":"Division of Neuroimaging and Interventional Neuroradiology, Department of Radiodiagnosis and Imaging Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen","family":"Sankhyan","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5194-9951","authenticated-orcid":false,"given":"Jitendra Kumar","family":"Sahu","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17239"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.02404.x"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13670"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2019.12.020"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12951"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02695.x"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12439"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03516.x"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(15)00250\u20101"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098\u2010019\u201003059\u20103"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu199"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2019.11.010"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2018.04.012"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2020.106398"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2020.100397"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0143-7"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12548"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12419"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2021.08.008"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/jpn.JPN_99_20"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2022.06.001"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000613"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.4103\/jpn.JPN_101_21"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/neurolint13040055"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098\u2010021\u201003918\u2010y"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2022.5648"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.02.022"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2014.11.012"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2020.01.015"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16468"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12008"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2021.106629"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2019.12.008"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12811","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T10:38:57Z","timestamp":1702723137000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,25]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/epi4.12811"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12811","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,25]]},"assertion":[{"value":"2023-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}