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Psychiatric symptomatology, namely, alcohol dependence and phobic and obsessive\u2010compulsive disorder, is also part of the clinical picture. Zonisamide has demonstrated effectiveness at reducing both myoclonus and dystonia, and deep brain stimulation seems to be an effective and long\u2010lasting therapeutic option for medication\u2010refractory cases. In a subset of patients, myoclonus\u2010dystonia is associated with pathogenic variants in the epsilon\u2010sarcoglycan gene, located on chromosome 7q21, and up to now, more than 100 different pathogenic variants of the epsilon\u2010sarcoglycan gene have been described. In a few families with a clinical phenotype resembling myoclonus\u2010dystonia associated with distinct clinical features, variants have been identified in genes involved in novel pathways such as calcium channel regulation and neurodevelopment. Because of phenotypic similarities with epsilon\u2010sarcoglycan gene\u2013related myoclonus\u2010dystonia, these conditions can be collectively classified as \u201cmyoclonus\u2010dystonia syndromes.\u201d In the present article, we present myoclonus\u2010dystonia caused by epsilon\u2010sarcoglycan gene mutations, with a focus on genetics and underlying disease mechanisms. Second, we review those conditions falling within the spectrum of myoclonus\u2010dystonia syndromes, highlighting their genetic background and involved pathways. Finally, we critically discuss the normal and pathological function of the epsilon\u2010sarcoglycan gene and its product, suggesting a role in the stabilization of the dopaminergic membrane via regulation of calcium homeostasis and in the neurodevelopmental process involving the cerebello\u2010thalamo\u2010pallido\u2010cortical network. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.27822","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T12:15:32Z","timestamp":1566821732000},"page":"1588-1601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Twenty years on: Myoclonus\u2010dystonia and \u03b5\u2010sarcoglycan \u2014 neurodevelopment, channel, and signaling dysfunction"],"prefix":"10.1002","volume":"34","author":[{"given":"Elisa","family":"Menozzi","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University\u2010Hospital of Modena and Reggio Emilia  Modena Italy"},{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Balint","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Department of Neurology University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-5209","authenticated-orcid":false,"given":"Anna","family":"Latorre","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Department of Human Neurosciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enza Maria","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Neurogenetics Unit IRCCS Santa Lucia Foundation  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1367-6467","authenticated-orcid":false,"given":"John C.","family":"Rothwell","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-286X","authenticated-orcid":false,"given":"Kailash P.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London 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