{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:51:57Z","timestamp":1791820317236,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T00:00:00Z","timestamp":1560902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Childhood\u2010onset dystonia is often genetically determined. Recently, <jats:italic>KMT2B<\/jats:italic> variants have been recognized as an important cause of childhood\u2010onset dystonia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To define the frequency of <jats:italic>KMT2B<\/jats:italic> mutations in a cohort of dystonic patients aged &lt;18 years at onset, the associated clinical and radiological phenotype, and the natural history of disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing or customized gene panels were used to screen a cohort of 65 patients who had previously tested negative for all other known dystonia\u2010associated genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 14 patients (21.5%) carrying <jats:italic>KMT2B<\/jats:italic> variants, of which 1 was classified as a variant of unknown significance. We also identified 2 additional patients carrying pathogenic mutations in <jats:italic>GNAO1<\/jats:italic> and <jats:italic>ATM<\/jats:italic>. Overall, we established a definitive genetic diagnosis in 23% of cases. We observed a spectrum of clinical manifestations in <jats:italic>KMT2B<\/jats:italic> variant carriers, ranging from generalized dystonia to short stature or intellectual disability alone, even within the same family. In 78.5% of cases, dystonia involved the lower limbs at onset, with later caudocranial generalization. Eight patients underwent pallidal DBS with a median decrease of Burke\u2010Fahn\u2010Marsden Dystonia Rating Scale\u2010Motor score of 38.5% in the long term. We also report on 4 asymptomatic carriers, suggesting that some <jats:italic>KMT2B<\/jats:italic> mutations may be associated with incomplete disease penetrance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>\n<jats:italic>KMT2B<\/jats:italic> mutations are frequent in childhood\u2010onset dystonia and cause a complex neurodevelopmental syndrome, often featuring growth retardation and intellectual disability as additional phenotypic features. A dramatic and long\u2010lasting response to DBS is characteristic of DYT\u2010<jats:italic>KMT2B<\/jats:italic> dystonia. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.27771","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T16:11:02Z","timestamp":1560960662000},"page":"1516-1527","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Frequency and phenotypic spectrum of <i>KMT2B<\/i> dystonia in childhood: A single\u2010center cohort study"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-5477","authenticated-orcid":false,"given":"Miryam","family":"Carecchio","sequence":"first","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"},{"name":"Molecular Neurogenetics Unit Fondazione IRCCS Istituto Neurologico 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