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CMS has been associated with variants in the <jats:italic>MuSK<\/jats:italic> gene and, to date, 16 patients have been reported. <jats:italic>MuSK\u2010<\/jats:italic>CMS patients present a different phenotypic pattern of limb girdle weakness. Here, we describe four additional patients and discuss the phenotypic and clinical relationship with those previously reported. Two novel damaging missense variants are described: c.1742T\u2009&gt;\u2009A; p.I581N found in homozygosis, and c.1634T\u2009&gt;\u2009C; p.L545P found in compound heterozygosis with p.R166*. The reported patients had predominant limb girdle weakness with symptom onset at 12, 17, 18, and 30 years of age, and the majority exhibited a good clinical response to Salbutamol therapy, but not to esterase inhibitors. Meta\u2010analysis including previously reported variants revealed an increased likelihood of a severe, respiratory phenotype with null alleles. Missense variants exclusively affecting the kinase domain, but not the catalytic site, are associated with late onset. These data refine the phenotype associated with <jats:italic>MuSK<\/jats:italic>\u2010related CMS.<\/jats:p>","DOI":"10.1002\/ajmg.a.38707","type":"journal-article","created":{"date-parts":[[2018,4,28]],"date-time":"2018-04-28T07:35:19Z","timestamp":1524900919000},"page":"1594-1601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Recessive variants of <i>MuSK<\/i> are associated with late onset CMS and predominant limb girdle weakness"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2965-5820","authenticated-orcid":false,"given":"David","family":"Owen","sequence":"first","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"T\u00f6pf","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle 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Neurology National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Cox","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresinha","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dawson","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Thompson","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne United 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