{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:41:29Z","timestamp":1790707289791,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005235","name":"Institute for Advanced Study","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005235","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005713","name":"Technical University of Munich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Federal Ministry of Education and Research","award":["01GM2302"],"award-info":[{"award-number":["01GM2302"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    Myoclonus-dystonia syndrome (MDS) is a clinically and genetically heterogeneous movement disorder characterized by myoclonus and dystonia as its core features. While mutations in the\n                    <jats:italic>epsilon-<\/jats:italic>\n                    sarcoglycan gene (SGCE) account for most familial cases, heterozygous pathogenic variants in\n                    <jats:italic>KCTD17<\/jats:italic>\n                    and\n                    <jats:italic>KCNN2<\/jats:italic>\n                    have recently been described as novel genetic causes of MDS.\n                    <jats:italic>W<\/jats:italic>\n                    e describe three patients from two Polish families presenting with progressive movement disorder combined with other features. Exome sequencing (ES) identified a novel heterozygous\n                    <jats:italic>KCTD17<\/jats:italic>\n                    variant c.461\u202fT\u202f&amp;gt;\u202fA, p.(Met154Lys) in a five-year-old girl with abnormal gait, postural instability, myoclonus, and tongue dyskinesia. In a 38-year-old woman and her 17-year-old daughter, both showing tremor, myoclonus, dystonia, and psychiatric symptoms, ES detected a heterozygous canonical splice-site c.1780-2A\u202f&amp;gt;\u202fG variant in\n                    <jats:italic>KCNN2<\/jats:italic>\n                    . Neuropsychological evaluation suggested a gene-specific effect of\n                    <jats:italic>KCNN2<\/jats:italic>\n                    on psychiatric and cognitive functioning, including significant episodic memory impairment. This study broadens the clinical and molecular spectrum of\n                    <jats:italic>KCTD17<\/jats:italic>\n                    - and\n                    <jats:italic>KCNN2<\/jats:italic>\n                    -related MDS and highlights distinctive features compared with\n                    <jats:italic>SGCE<\/jats:italic>\n                    -MDS, focusing on disease progression, treatment response, and neuropsychiatric involvement. Recognition of these patterns may guide molecular diagnosis and the management of specific MDS types.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2026.1728361","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:12:26Z","timestamp":1774843946000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Beyond SGCE: expanding the clinical and molecular spectrum of KCTD17- and KCNN2-related myoclonus-dystonia"],"prefix":"10.3389","volume":"17","author":[{"given":"Magdalena","family":"Krygier","sequence":"first","affiliation":[{"name":"Department of Developmental Neurology, Medical University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia J.","family":"Sitek","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Neuropsychology, Neurolinguistics and Neuropsychotherapy, Division of Neurological and Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]},{"name":"Department of Neurology, St. Adalbert Hospital, Copernicus PL Ltd.","place":["Gdansk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Chyli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Adult Neurology, Medical University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon","family":"Zi\u0119tkiewicz","sequence":"additional","affiliation":[{"name":"Intercollegiate Faculty of Biotechnology, University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zawadzka","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology, Medical University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Dulski","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Adalbert Hospital, Copernicus PL Ltd.","place":["Gdansk, Poland"]},{"name":"Department of Neurology, Neurodegenerative Diseases and Neuroimmunology, Faculty of Health Sciences, Medical University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Schinwelski","sequence":"additional","affiliation":[{"name":"Division of Neurological and Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]},{"name":"Neurocentrum-Miwomed, Neurological Clinic","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Kostrzewa","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Wierzba","sequence":"additional","affiliation":[{"name":"Department of Internal and Pediatric Nursing, Institute of Nursing and Midwifery, Medical University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142","family":"P\u0142oski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zech","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health, Technical University of Munich","place":["Munich, Germany"]},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen","place":["Munich, Germany"]},{"name":"Institute for Advanced Study, Technical University of Munich","place":["Garching, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mazurkiewicz-Be\u0142dzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology, Medical University of Gda\u0144sk","place":["Gda\u0144sk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.4103\/aomd.aomd_55_21","article-title":"A clinical approach to the patients with combination of dystonia and myoclonus","volume":"5","author":"Chouksey","year":"2022","journal-title":"Ann Mov Disord"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1007\/s12035-016-9712-x","article-title":"Genetic aspects of myoclonus-dystonia syndrome (MDS)","volume":"54","author":"Rachad","year":"2017","journal-title":"Mol Neurobiol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/B978-0-444-52014-2.00041-0","article-title":"Myoclonus-dystonia syndrome","volume":"100","author":"Nardocci","year":"2011","journal-title":"Handb Clin Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1097\/WCO.0000000000000577","article-title":"Myoclonus-dystonia: classification, phenomenology, pathogenesis, and treatment","volume":"31","author":"Roze","year":"2018","journal-title":"Curr Opin Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1111\/dmcn.15298","article-title":"Early recognition of SGCE-myoclonus-dystonia in children","volume":"65","author":"Correa-Vela","year":"2023","journal-title":"Dev Med Child Neurol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.1007\/s00415-014-7488-3","article-title":"SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype","volume":"261","author":"Peall","year":"2014","journal-title":"J Neurol"},{"key":"ref7","first-page":"20301587","volume-title":"GeneReviews\u00ae","author":"Raymond","year":"2003"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1002\/mds.27822","article-title":"Twenty years on: myoclonus-dystonia and \u03b5-sarcoglycan - neurodevelopment, channel, and signaling dysfunction","volume":"34","author":"Menozzi","year":"2019","journal-title":"Mov Disord"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"105929","DOI":"10.1016\/j.parkreldis.2023.105929","article-title":"The expanding genetic landscape of myoclonus-dystonia syndrome: YY1 and ATP1A3 are added to the list","volume":"117","author":"Brooker","year":"2023","journal-title":"Parkinsonism Relat Disord"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1002\/ana.27272","article-title":"The Spectrum of neurologic phenotypes associated with NUS1 pathogenic variants: a comprehensive case series","volume":"98","author":"Brooker","year":"2025","journal-title":"Ann Neurol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.ajhg.2015.04.008","article-title":"A missense mutation in KCTD17 causes autosomal dominant myoclonus-dystonia","volume":"96","author":"Mencacci","year":"2015","journal-title":"Am J Hum Genet"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.parkreldis.2018.12.001","article-title":"A novel KCTD17 mutation is associated with childhood early-onset hyperkinetic movement disorder","volume":"61","author":"Graziola","year":"2019","journal-title":"Parkinsonism Relat Disord"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.parkreldis.2019.01.004","article-title":"Childhood onset progressive myoclonic dystonia due to a de novo KCTD17 splicing mutation","volume":"61","author":"Marc\u00e9-Grau","year":"2019","journal-title":"Parkinsonism Relat Disord"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.parkreldis.2020.07.026","article-title":"KCTD17-related myoclonus-dystonia syndrome: clinical and electrophysiological findings of a patient with atypical late onset","volume":"78","author":"Todisco","year":"2020","journal-title":"Parkinsonism Relat Disord"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"105925","DOI":"10.1016\/j.parkreldis.2023.105925","article-title":"Childhood onset myoclonus-dystonia associated with a novel KCTD17 variant in an Indian patient","volume":"117","author":"Garg","year":"2023","journal-title":"Parkinsonism Relat Disord"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1111\/ene.14228","article-title":"KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia","volume":"27","author":"Balint","year":"2020","journal-title":"Eur J Neurol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.3390\/genes14071380","article-title":"A novel KCNN2 variant in a family with essential tremor plus: clinical characteristics and in silico analysis","volume":"14","author":"d'Apolito","year":"2023","journal-title":"Genes (Basel)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1002\/mdc3.13535","article-title":"Early-onset neurodevelopmental movement disorder secondary to novel mutation in KCNN2","volume":"9","author":"Fearon","year":"2022","journal-title":"Mov Disord Clin Pract"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2","DOI":"10.5334\/tohm.668","article-title":"KCNN2 mutation in pediatric tremor myoclonus dystonia syndrome with electrophysiological evaluation","volume":"12","author":"Lavenstein","year":"2022","journal-title":"Tremor Other Hyperkinet Mov (N Y)"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3564","DOI":"10.1093\/brain\/awaa346","article-title":"Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders","volume":"143","author":"Mochel","year":"2020","journal-title":"Brain"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"107260","DOI":"10.1016\/j.parkreldis.2025.107260","article-title":"Insufficient effect of deep brain stimulation in a patient with KCNN2-associated myoclonus-dystonia","volume":"131","author":"Pauly","year":"2025","journal-title":"Parkinsonism Relat Disord"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"7736","DOI":"10.3390\/ijms26167736","article-title":"Long-Term Efficacy of Bilateral Globus Pallidus Internus Deep Brain Stimulation in Myoclonus-Dystonia Associated with KCNN2 Gene Mutation:","volume":"26","author":"Stodulska","year":"2025","journal-title":"A Case Study. Int J Mol Sci."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.clinph.2019.07.025","article-title":"Standards of instrumentation of EMG","volume":"131","author":"Tankisi","year":"2020","journal-title":"Clin Neurophysiol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1002\/mus.25204","article-title":"Establishing high-quality reference values for nerve conduction studies: a report from the normative data task force of the American association of Neuromuscular & Electrodiagnostic Medicine","volume":"54","author":"Dillingham","year":"2016","journal-title":"Muscle Nerve"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3390\/genes15010125","article-title":"A study of polish family with scoliosis and limb contractures expands the MYH3 disease Spectrum","volume":"15","author":"Frasu\u0144ska","year":"2024","journal-title":"Genes (Basel)"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: the human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/cge.14516","article-title":"Genebe.net: implementation and validation of an automatic ACMG variant pathogenicity criteria assignment","volume":"106","author":"Stawi\u0144ski","year":"2024","journal-title":"Clin Genet"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.jmb.2009.01.030","article-title":"Pentameric assembly of potassium channel tetramerization domain-containing protein 5","volume":"387","author":"Dementieva","year":"2009","journal-title":"J Mol Biol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: a web-based graphical user Interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J Comput Chem"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD - visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J Mol Graph"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"3747","DOI":"10.1042\/BCJ20170527","article-title":"Structural complexity in the KCTD family of Cullin3-dependent E3 ubiquitin ligases","volume":"474","author":"Pinkas","year":"2017","journal-title":"Biochem J"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s12013-009-9062-7","article-title":"Functions and modulation of neuronal SK channels","volume":"55","author":"Faber","year":"2009","journal-title":"Cell Biochem Biophys"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"5081","DOI":"10.1038\/ncomms6081","article-title":"Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension","volume":"5","author":"Kasahara","year":"2014","journal-title":"Nat Commun"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.parkreldis.2015.07.003","article-title":"Non-motor symptoms in genetically defined dystonia: homogenous groups require systematic assessment","volume":"21","author":"Peall","year":"2015","journal-title":"Parkinsonism Relat Disord"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/acn3.263","article-title":"Psychiatric disorders, myoclonus dystonia and SGCE: an international study","volume":"3","author":"Peall","year":"2015","journal-title":"Ann Clin Transl Neurol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s11910-022-01233-3","article-title":"Cognitive and neuropsychiatric impairment in dystonia","volume":"22","author":"Bailey","year":"2022","journal-title":"Curr Neurol Neurosci Rep"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1002\/mdc3.70085","article-title":"New progressive generalized dystonia phenotype in a patient with NBEA-related neurodevelopmental disease","volume":"12","author":"Schinwelski","year":"2025","journal-title":"Mov Disord Clin Pract"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1002\/mds.29022","article-title":"Neuropsychological functioning in primary dystonia: updated and expanded multidomain meta-analysis","volume":"37","author":"Aita","year":"2022","journal-title":"Mov Disord"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1007\/s00429-016-1258-1","article-title":"Small-conductance calcium-activated potassium type 2 channels (SK2, KCa2.2) in human brain","volume":"222","author":"Willis","year":"2017","journal-title":"Brain Struct Funct"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s13195-025-01833-4","article-title":"Long-term retrieval performance is associated with CA1 hippocampal volume in older adults and individuals at risk for dementia","volume":"17","author":"Bartels","year":"2025","journal-title":"Alzheimer's Res Ther"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"112040","DOI":"10.1016\/j.pscychresns.2025.112040","article-title":"Hippocampal subfield volumes and memory deficits in schizophrenia","volume":"352","author":"Alkan","year":"2025","journal-title":"Psychiatry Res Neuroimaging"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1728361\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:12:32Z","timestamp":1774843952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1728361\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":43,"alternative-id":["10.3389\/fneur.2026.1728361"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1728361","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]},"article-number":"1728361"}}