{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T13:05:39Z","timestamp":1793711139102,"version":"4.6.1"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471430"],"award-info":[{"award-number":["82471430"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To characterize the clinical, electrophysiological, and genetic spectrum of pediatric CMS and evaluate genotype\u2010informed outcomes using an integrated phenotype\u2013electrophysiology\u2013genomics approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively reviewed 36 pediatric CMS patients evaluated at a single center between 2015 and 2025. Clinical features, RNS, targeted NGS\/WES variants, ventilator use, treatments, ACMG\/AMP classifications, and MG\u2010ADL outcomes were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 36 patients, 28 (77.8%) developed symptoms in the neonatal period or infancy. Biallelic variants involved 17 CMS genes; postsynaptic CMS was most common (55.6%, 20\/36).\n                      <jats:italic>COLQ<\/jats:italic>\n                      and\n                      <jats:italic>CHRNE<\/jats:italic>\n                      were the most frequent genes (13.9%, 5\/36 each), followed by\n                      <jats:italic>CHAT<\/jats:italic>\n                      (11.1%, 4\/36). VUS were detected in 19 patients (52.8%, 19\/36), including 8 with biallelic VUS supported by phenotype, neuromuscular transmission findings, treatment response, and follow\u2010up. RNS showed a \u2265\u200910% decrement in 16\/21 tested patients (76.2%).\n                      <jats:italic>CHAT<\/jats:italic>\n                      \u2010CMS was associated with higher ventilator use (3\/4 vs. 6\/32;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.041) and early mortality (3\/4 vs. 1\/32;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Median MG\u2010ADL improved from 5 to 3 after genotype\u2010informed therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Pediatric CMS shows marked genetic heterogeneity and frequent VUS\u2010related uncertainty. Integrating phenotype, electrophysiology, and genomics supports diagnosis and mechanism\u2010guided therapy.\n                      <jats:italic>CHAT<\/jats:italic>\n                      \u2010CMS is high risk for early respiratory failure and mortality.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71123","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:21:41Z","timestamp":1788600101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pragmatic Phenotype\u2013Electrophysiology\u2013Genomics Integration in Pediatric Congenital Myasthenic Syndromes: Insights From 36 Patients in a Single\u2010Center Study in China"],"prefix":"10.1002","volume":"32","author":[{"given":"Liya","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Neurology Beijing Children's Hospital, Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4302-3371","authenticated-orcid":false,"given":"Kaiyue","family":"Ma","sequence":"additional","affiliation":[{"name":"Bio\u2010X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education, International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory of Embryo Original Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaona","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurology Beijing Children's Hospital, Capital Medical University, National Center for Children's Health  Beijing 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