{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:54:22Z","timestamp":1793382862805,"version":"4.5.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    The\n                    <jats:italic>MYBPC1<\/jats:italic>\n                    gene, mapping to chromosome 12q23.2, encodes the slow myosin binding protein-C (sMyBP-C), a sarcomeric accessory protein, expressed mainly in slow skeletal muscle fibers, that aids in the regulation of actomyosin cross-bridges and provides thick filament stability. Biallelic molecular defects in\n                    <jats:italic>MYBPC1<\/jats:italic>\n                    are associated with a lethal congenital form of myopathy (Lethal congenital contracture syndrome 4); meanwhile, heterozygous damaging variants lead to a form of distal arthrogryposis (distal arthrogryposis type 1B) and an early\u2010onset congenital myopathy with tremor (congenital myopathy-16, CMYO16). To date, only 20 cases have been documented, all presenting a mild axial\u2013proximal myopathy consistently coupled with a distinctive tremor phenotype. We report the case of a young Italian woman presenting with mild axial and proximal weakness, associated with a high-frequency postural tremor affecting the limbs and tongue, with apparent exacerbation of symptoms after hormonal stimulation. Laboratory tests showed normal creatine kinase levels. Electromyography revealed diffuse mild myopathic changes. Muscle MRI was substantially normal. Polygraphic tremor analysis confirmed the presence of a postural tremor at a frequency of 10\u201311\u00a0Hz. Muscle biopsy showed selective type 1 fiber hypotrophy. Clinical exome sequencing revealed the heterozygous c.788T&amp;gt;G p.(Leu263Arg) variant in exon 11 in the\n                    <jats:italic>MYBPC1<\/jats:italic>\n                    gene. This variant has been previously reported in multiple independent subjects displaying skeletal muscle weakness and myogenic tremor. Our case helps further define the phenotypic spectrum of this disorder, providing additional clinical and pathologically relevant insides, including the possible influence of hormonal stimulation and a detailed characterization of muscle biopsy findings. Knowledge of this myopathic phenotype may allow identification of individuals with\n                    <jats:italic>MYBPC1<\/jats:italic>\n                    variants without arthrogryposis.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2026.1809063","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:10:18Z","timestamp":1778710218000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["MYBPC1-associated congenital myopathy with tremor: further delineation of the clinical and pathological phenotype in the first Italian case"],"prefix":"10.3389","volume":"17","author":[{"given":"Daniele","family":"Velardo","sequence":"first","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, 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Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Napoli","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Zanotti","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Ripolone","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele Giovanni","family":"Croce","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioural Sciences, University of Pavia","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioural Sciences, University of Pavia","place":["Pavia, Italy"]},{"name":"Translational Neurophysiology Research Unit, IRCCS Mondino Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Tumminello","sequence":"additional","affiliation":[{"name":"Department of Cardio-Thoracic-Vascular Diseases, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Unit of Neurosurgery, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico of Milan","place":["Milan, Italy"]},{"name":"Department of Medical-Surgical Physiopathology and Transplantation, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo Pietro","family":"Comi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan","place":["Milan, Italy"]},{"name":"Neurology Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Corti","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]},{"name":"Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Ravaglia","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, IRCCS Mondino Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan","place":["Milan, Italy"]},{"name":"Neurology Unit, IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"652065","DOI":"10.1155\/2010\/652065","article-title":"Myosin binding protein-C slow: an intricate subfamily of proteins","volume":"2010","author":"Ackermann","year":"2010","journal-title":"J. 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