{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:50:29Z","timestamp":1787503829113,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002721","name":"Charcot-Marie-Tooth Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>In 2019, we conducted a cross\u2010sectional study, collecting information on 50 patients with CMT4B, an ultrarare CMT subtype, to better define the clinical phenotype. We now aimed at investigating disease progression in 26 patients with CMT4B1\/CMT4B2, recruited from the previous study and among the Inherited Neuropathy Consortium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We retrospectively analysed disease progression in patients with CMT4B1\/CMT4B2, collecting MRC scores from nine muscle pairs, Charcot\u2010Marie\u2010Tooth Examination Score (CMTES), and a minimal dataset of clinical information (walking difficulties, aids dependency, upper limb impairment, cranial nerves involvement) at baseline and follow\u2010up visits. Thirteen centres from four continents were involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirteen CMT4B1 and 13 CMT4B2 patients were followed up for 7.1\u2009\u00b1\u20094.9 and 7.9\u2009\u00b1\u20094.5\u2009years, respectively. During follow\u2010up, walking aid dependency increased: two CMT4B1 patients adopted AFOs (overall 11\/12 at follow\u2010up), and one started using wheelchair (6\/12 at follow\u2010up) at the age of 19; among CMT4B2 patients, two more required unilateral support in walking (4\/11 at follow\u2010up) by the age of 33 and 49\u2009years, respectively. We found that disease progression, as measured by CMTES, was faster in CMT4B1 as compared to CMT4B2 patients (\u0394CMTES\/year 0.7 vs. 0.3,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037) but tended to slow down over time as burden of disease increased. At the end of follow\u2010up, CMT4B1 was associated to higher disability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This international collective effort enabled collection of relevant data for characterizing natural history and estimating disease progression of CMT4B1\/CMT4B2 ultrarare diseases, aiming at improving their management and paving the way for designing future clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70084","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T04:09:32Z","timestamp":1739419772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Disease Progression in Charcot\u2010Marie\u2010Tooth Disease Type\n                    <scp>4B<\/scp>\n                    (\n                    <scp>CMT4B<\/scp>\n                    ) Associated With Mutations in Myotubularin\u2010Related Proteins 2 and 13"],"prefix":"10.1111","volume":"32","author":[{"given":"Alessandro","family":"Bertini","sequence":"first","affiliation":[{"name":"Unit of Rare Neurological Diseases, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3850-076X","authenticated-orcid":false,"given":"Chiara","family":"Pisciotta","sequence":"additional","affiliation":[{"name":"Unit of Rare Neurological Diseases, Department of Clinical Neurosciences Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2546-4357","authenticated-orcid":false,"given":"Stefano C.","family":"Previtali","sequence":"additional","affiliation":[{"name":"Institute of Experimental Neurology (InSpe), Division of Neuroscience IRCCS Ospedale San Raffaele  Milan Italy"},{"name":"Neurology Unit IRCCS Ospedale San Raffaele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesim","family":"Parman","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit Istanbul University, Istanbul Faculty of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Battaloglu","sequence":"additional","affiliation":[{"name":"Bogazici University Department of Molecular Biology and Genetics  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Laur\u00e0","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Blake","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London England"},{"name":"Department of Clinical Neurophysiology Norfolk and Norwich University Hospital  Norfolk UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Sacconi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur Service Syst\u00e8me Nerveux P\u00e9riph\u00e9rique, Muscle et SLA, Centre Hospitalier Universitaire de Nice  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Attarian","sequence":"additional","affiliation":[{"name":"Reference Center for Neuromuscular Disorders and ALS, CHU la Timone Aix\u2010Marseille University  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"APHP, Sorbonne Universit\u00e9 H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, Centre de r\u00e9f\u00e9rence Des Maladies Neuromusculaires Nord\/Est\/Ile de France  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounia","family":"Bellatache","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Research Laboratory Benyoucef Benkheda University  Algiers Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Nouioua","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Research Laboratory Benyoucef Benkheda University  Algiers Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Tazir","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Research Laboratory Benyoucef Benkheda University  Algiers Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arman","family":"Cakar","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit Istanbul University, Istanbul Faculty of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7384-3074","authenticated-orcid":false,"given":"Antonio","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Department of Neurology Universit\u00e0 Magna Graecia di Catanzaro  Catanzaro 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