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Five patients presented with a severe congenital phenotype manifesting with profound weakness, significantly delayed or minimal attainment of motor milestones, respiratory insufficiency, and feeding difficulties. Three patients presented with mild\u2010to\u2010moderate muscle weakness and delayed milestones but were able to achieve independent ambulation. Patients were found to have biallelic loss\u2010of\u2010function <jats:italic>COL12A1<\/jats:italic> variants, except for one family (p.I1393Ffs*11\/p.A1110D). Consistent with the variable clinical spectrum, in vitro immunocytochemistry analysis in fibroblasts ranged from complete absence of Collagen XII expression in a patient with severe disease, to a mild reduction in a patient with milder disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Here we characterize the clinical presentation, muscle imaging, and dermal fibroblast immunostaining findings associated with biallelic variants in <jats:italic>COL12A1,<\/jats:italic> further establishing <jats:italic>COL12A1<\/jats:italic> as a recessive myopathic Ehlers\u2013Danlos syndrome (mEDS) gene, and expanding the clinical spectrum to include a milder EDS phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52225","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T07:54:31Z","timestamp":1739260471000},"page":"602-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical characterization of Collagen <scp>XII<\/scp>\u2010related disease caused by biallelic <i>COL12A1<\/i> variants"],"prefix":"10.1002","volume":"12","author":[{"given":"Riley M.","family":"McCarty","sequence":"first","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimah","family":"Saade","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"},{"name":"Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinki","family":"Munot","sequence":"additional","affiliation":[{"name":"The Dubowitz Neuromuscular Centre Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamindra G.","family":"Laverty","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey","family":"Pinz","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Saint Louis University  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqun","family":"Zou","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"McAnally","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pomi","family":"Yun","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuixia","family":"Tian","sequence":"additional","affiliation":[{"name":"Division of Neurology, Cincinnati Children's Hospital Medical Center &amp; Department of Pediatrics University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hu","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Feng","sequence":"additional","affiliation":[{"name":"The Dubowitz Neuromuscular Centre Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Phadke","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, Division of Neuropathology UCL Queen Square Institute of Neurology  Queen Square London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Ceulemans","sequence":"additional","affiliation":[{"name":"Division of Genetics Rady Children's Hospital  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Magoulas","sequence":"additional","affiliation":[{"name":"Department of Genetics Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Skalsky","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rehabilitation Medicine Rady's Children's Hospital  San Diego California USA"},{"name":"Department of Orthopaedic Surgery University of San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California San Diego  San Diego California USA"},{"name":"Rady Children's Institute of Genomic Medicine  San Diego California USA"},{"name":"Department of Pediatrics University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Braddock","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Saint Louis University  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B.","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise M.","family":"Malicki","sequence":"additional","affiliation":[{"name":"Department of Pathology Rady Children's Hospital  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew N.","family":"Bainbridge","sequence":"additional","affiliation":[{"name":"Rady Children's Institute of Genomic Medicine  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shareef","family":"Nahas","sequence":"additional","affiliation":[{"name":"Rady Children's Institute of Genomic Medicine  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Dimmock","sequence":"additional","affiliation":[{"name":"Rady Children's Institute of Genomic Medicine  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Kingsmore","sequence":"additional","affiliation":[{"name":"Rady Children's Institute of Genomic Medicine  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E.","family":"Lotze","sequence":"additional","affiliation":[{"name":"Division of Neurology and Developmental Neuroscience Baylor College of Medicine\/Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-1119","authenticated-orcid":false,"given":"A. 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