{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T04:16:13Z","timestamp":1746591373865,"version":"3.40.5"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100019579","name":"singhealth","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019579","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100022247","name":"precise","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022247","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>The Kleefstra syndrome spectrum (KSS) is a group of neurodevelopmental disorders characterized by intellectual disability, behavioral disorders, growth and neurodevelopmental delay, facial dysmorphism and neurological deficits. Kleefstra syndrome 2 (KLEFS2) is a part of KSS and is due to heterozygous loss-of-function variants in the <jats:italic>KMT2 C<\/jats:italic> gene. We report the long-term clinical course and multi-organ manifestations of a patient with KLEFS2 caused by a novel heterozygous pathogenic variant in <jats:italic>KMT2 C<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A patient with KSS phenotype developed proteinuria with progressive kidney dysfunction secondary to focal segmental glomerular sclerosis. She subsequently developed recurrent episodes that mimicked mitochondrial stroke-like episodes. The phenotype included encephalopathy, stroke-like episodes with focal status epilepticus with impaired consciousness associated with cortical and subcortical T2\/FLAIR signal hyperintensities that partially responded to intravenous arginine infusions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Exome sequencing revealed a heterozygous pathogenic nonsense variant in <jats:italic>KMT2 C<\/jats:italic> (NM_170606.3) c.3940C\u2009&gt;\u2009T (p.Gln1314Ter). Nuclear and mitochondrial DNA variants associated with mitochondrial disorders have been excluded.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Discussion<\/jats:title>\n            <jats:p>This is a case of KLEFS2 with longitudinal 10\u00a0year follow up and its previously unreported multi-organ clinical manifestations including stroke-like episodes and nephrotic disease. Our report further expands the phenotypic spectrum of KLEFS2. Further reports of patients with KLEFS2 with multi-organ involvement should be sought to confirm our findings.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12883-025-04210-8","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T11:22:19Z","timestamp":1746530539000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long term follow-up of multiorgan disease in Kleefstra syndrome 2 in an adult \u2013 case report"],"prefix":"10.1186","volume":"25","author":[{"given":"Zhiyong","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia Liang","family":"Kwek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru Sin","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan Rong","family":"Yong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alwin Hwai Liang","family":"Loh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weng Khong","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing Xian","family":"Teo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karine Su Shan","family":"Tay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng Soon","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"4210_CR1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ajhg.2012.05.003","volume":"91","author":"T Kleefstra","year":"2012","unstructured":"Kleefstra T, Kramer JM, Neveling K, Willemsen MH, Koemans TS, Vissers LELM, et al. 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