{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:19:30Z","timestamp":1787998770060,"version":"build-2784847793"},"reference-count":36,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["SNF Grants 310030_138288 and 31003A_173183"],"award-info":[{"award-number":["SNF Grants 310030_138288 and 31003A_173183"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by generalized joint laxity, severe congenital hypotonia, progressive kyphoscoliosis, hyperextensible and easily bruised skin, ocular abnormalities, and significant vascular complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We report on nine patients from seven families, eight of them carrying the common homozygous duplication of exons 10-16 in\n                      <jats:italic toggle=\"yes\">PLOD1<\/jats:italic>\n                      . Longitudinal clinical assessments included muscle ultrasound (n=6) and vascular ultrasound (n=4). Genetic diagnostics varied, with most patients ultimately undergoing trio exome or genome sequencing. Urine pyridinoline analysis was performed in seven of nine patients. A literature review and age-stratified recalculation of vascular incidence, including our cohort, were conducted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Diagnosis was challenging in five families, as the exon 10\u201316 duplication often escaped detection due to its high allele frequency. Seven patients were initially diagnosed with congenital myopathy. Muscle ultrasound revealed abnormalities in five of six sonographically examined cases. Severe vascular events included neonatal intracranial hemorrhage, fatal aortic aneurysm rupture at the age of 13 years, multiple aneurysms\/dissections (ages 14\u201319 years), and mesenteric dissection at the age of 10 years. Four younger patients (aged 3\u20139 years have had no vascular complications to date. Urine pyridinoline analysis was abnormal in all tested cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">PLOD1<\/jats:italic>\n                      -related kEDS often presents with a phenotype of congenital myopathy, complicating genetic diagnosis and potentially leading to underdiagnosis - especially in cases where the common\n                      <jats:italic toggle=\"yes\">PLOD1<\/jats:italic>\n                      duplication may be missed by strict frequency filters in exome or genome sequencing data. Literature and our data indicate a vascular event incidence from childhood age of \u223c25%.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/22143602261457531","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:53:23Z","timestamp":1787997203000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Between myopathy and mortality: Challenges in the diagnosis of\n                    <i>PLOD1<\/i>\n                    -related kyphoscoliotic Ehlers-Danlos syndrome"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1925-7538","authenticated-orcid":false,"given":"Katharina","family":"Vill","sequence":"first","affiliation":[{"name":"LMU University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Brunet","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technical University of Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Brugger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technical University of Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matias","family":"Wagner","sequence":"additional","affiliation":[{"name":"LMU University Hospital"},{"name":"Institute of Human Genetics, Technical University of Munich"},{"name":"Institute of Neurogenomics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Baumann","sequence":"additional","affiliation":[{"name":"Medical University of Innsbruck"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Schatz","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technical University of Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Pechmann","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Hannibal","sequence":"additional","affiliation":[{"name":"LMU University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Tacke","sequence":"additional","affiliation":[{"name":"LMU University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Giunta","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital Zurich and University of Zurich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Wohlgemuth","sequence":"additional","affiliation":[{"name":"Martin-Luther University Halle-Wittenberg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Wildgruber","sequence":"additional","affiliation":[{"name":"LMU University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"M\u00fcller-Felber","sequence":"additional","affiliation":[{"name":"LMU University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Blaschek","sequence":"additional","affiliation":[{"name":"LMU University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Rohrbach","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital Zurich and University of Zurich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Huf","sequence":"additional","affiliation":[{"name":"Catholic Children\u2019s Hospital Hamburg Wilhelmstift"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197205112861901"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2018-224423"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-46"},{"key":"e_1_3_4_6_2","volume-title":"GeneReviews(R)","author":"Rohrbach M","year":"1993","unstructured":"Rohrbach M, Giunta C. 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