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It is characterized by rippling wave\u2010like muscle contractions induced by mechanical stretch or voluntary contraction followed by sudden stretch, painful muscle stiffness, percussion\u2010induced rapid muscle contraction (PIRC), and percussion\u2010induced muscle mounding (PIMM). RMD can be hereditary (hRMD) or immune\u2010mediated (iRMD). hRMD is caused by pathogenic variants in caveolin\u20103 (<jats:italic>CAV3<\/jats:italic>) or caveolae\u2010associated protein 1\/ polymerase I and transcript release factor (<jats:italic>CAVIN1\/PTRF<\/jats:italic>). <jats:italic>CAV3<\/jats:italic> pathogenic variants are autosomal dominant or less frequently recessive while <jats:italic>CAVIN1\/PTRF<\/jats:italic> pathogenic variants are autosomal recessive. <jats:italic>CAV3<\/jats:italic>\u2010RMD manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic creatine kinase elevation to severe muscle weakness. Overlapping phenotypes are common. Muscle caveolin\u20103 immunoreactivity is often absent or diffusely reduced in <jats:italic>CAV3<\/jats:italic>\u2010RMD. <jats:italic>CAVIN1\/PTRF<\/jats:italic>\u2010RMD is characterized by congenital generalized lipodystrophy (CGL, type 4) and often accompanied by several extra\u2010skeletal muscle manifestations. Muscle cavin\u20101\/PTRF immunoreactivity is absent or reduced while caveolin\u20103 immunoreactivity is reduced, often in a patchy way, in <jats:italic>CAVIN1\/PTRF<\/jats:italic>\u2010RMD. iRMD is often accompanied by other autoimmune disorders, including myasthenia gravis. Anti\u2010cavin\u20104 antibodies are the serological marker while the mosaic expression of caveolin\u20103 and cavin\u20104 is the pathological feature of iRMD. Most patients with iRMD respond to immunotherapy. Rippling, PIRC, and PIMM are usually electrically silent. Different pathogenic mechanisms have been postulated to explain the disease mechanisms. In this article, we review the spectrum of hRMD and iRMD, including clinical phenotypes, electrophysiological characteristics, myopathological findings, and pathogenesis.<\/jats:p>","DOI":"10.1002\/mus.28270","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T05:10:02Z","timestamp":1728277802000},"page":"9-21","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The spectrum of rippling muscle disease"],"prefix":"10.1002","volume":"71","author":[{"given":"Hebatallah R.","family":"Rashed","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-9007","authenticated-orcid":false,"given":"Margherita","family":"Milone","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.57.3.344"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1989.00520400065020"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20307"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2009.01.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4598(200103)24:3<340::AID-MUS1003>3.0.CO;2-X"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10156"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21589"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000116809"},{"issue":"10","key":"e_1_2_9_10_1","first-page":"1915","article-title":"Phenotypic variability in rippling muscle disease. 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