{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T03:52:28Z","timestamp":1783050748165,"version":"3.54.6"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771409"],"award-info":[{"award-number":["81771409"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore the etiology of infantile spasms (IS) in a large Chinese cohort based on the United States National Infantile Spasms Consortium (NISC) classification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, we recruited IS patients diagnosed at a single center (Xiangya Hospital, Central South University) between Jan 2010 and Aug 2019. Thereafter, we collected their clinical and genetic information retrospectively. Their underlying etiologies were classified according to the NISC classification and then compared in different scenarios to understand their distribution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 541 patients with IS from 18 provinces were included in this study. The underlying etiology was identified in 53.2% of the cases: structural-acquired, 25.3%; genetic, 12.9%; genetic-structural, 7.2%; structural-congenital, 5.0%; metabolic, 2.4%; infections, 0.4% and immune, 0%. Whole-exome sequencing (WES) provided the highest diagnostic yield (26.9%). In structural-acquired IS, the proportion of hypoglycemic brain injuries was significant, second only to hypoxic-ischemic encephalopathy. There was no patient discovered to have Down syndrome. <jats:italic>STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL<\/jats:italic>, and <jats:italic>TSC1<\/jats:italic> were the most frequently implicated genes. Genetic causes were found to be the most common cause of IS in the early onset group, while structural-acquired etiologies were common in males and preterm babies. Patients with pre-spasm seizures were associated with a higher proportion of identified causes than those without. Non-acquired structural etiologies were more common in patients without hypsarrhythmia than in those with hypsarrhythmia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The most prevalent cause of IS was structural acquired followed by genetic causes. When brain MRI fails to detect the etiology, we propose WES as the next step. Structural-acquired IS and cases with genetic disorders are characteristic of the Chinese cohort, however, the etiology differs with the patient's age of onset, gestation age at birth, sex, and the presence\/absence of both pre-spasm seizures, and hypsarrhythmia.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.774828","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T09:30:07Z","timestamp":1646645407000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":35,"title":["Etiologic Classification of 541 Infantile Spasms Cases: A Cohort Study"],"prefix":"10.3389","volume":"10","author":[{"given":"Pan","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Kessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciliu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zou","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.braindev.2013.10.008","article-title":"Infantile spasms syndrome, West syndrome and related phenotypes: what we know in 2013","volume":"36","author":"Pavone","year":"2014","journal-title":"Brain Dev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/S0387-7604(01)00263-7","article-title":"Epidemiological data of West syndrome in Finland","volume":"23","author":"Riikonen","year":"2001","journal-title":"Brain Dev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s40272-017-0225-5","article-title":"Effectiveness and safety of different once-daily doses of adrenocorticotropic hormone for infantile spasms","volume":"19","author":"Yin","year":"2017","journal-title":"Paediatr Drugs."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1111\/j.1528-1167.2010.02695.x","article-title":"The underlying etiology of infantile spasms (West syndrome): information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification","volume":"51","author":"Osborne","year":"2010","journal-title":"Epilepsia."},{"key":"B5","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.seizure.2008.09.006","article-title":"Retrospective study on aetiology based outcome of infantile spasms","volume":"18","author":"Karvelas","year":"2009","journal-title":"Seizure."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1111\/epi.16305","article-title":"The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS)","volume":"60","author":"Osborne","year":"2019","journal-title":"Epilepsia."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1111\/epi.13937","article-title":"The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium","volume":"58","author":"Demarest","year":"2017","journal-title":"Epilepsia."},{"key":"B8","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1111\/epi.12951","article-title":"How should children with West syndrome be efficiently and accurately investigated? 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