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The majority of thoracic dystrophies are due to biallelic alterations in genes needed for normal ciliary function. However, despite the identification of over 20 genes as causal for the thoracic dystrophy phenotype, around 20% of patients remain without a molecular diagnosis. We present two unrelated families with a clinical diagnosis of thoracic dystrophy with associated respiratory insufficiency without a molecular diagnosis on previous genetic testing. Both harbor rare biallelic and predicted deleterious missense substitutions in <jats:italic>FGF4<\/jats:italic>, a gene known to be essential for formation of the thoracic skeleton in mice. We demonstrate that the phenotype is restricted to short ribs, abnormally narrow chest, and respiratory insufficiency, without other diagnostic clinical or radiological signs. We suggest that biallelic alterations in <jats:italic>FGF4<\/jats:italic> are a newly identified disease association of thoracic dystrophy.<\/jats:p>","DOI":"10.1111\/cge.14758","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T03:49:03Z","timestamp":1745293743000},"page":"479-485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic <scp><i>FGF4<\/i><\/scp> Variants Linked to Thoracic Dystrophy and Respiratory Insufficiency"],"prefix":"10.1111","volume":"108","author":[{"given":"Laura M.","family":"Watts","sequence":"first","affiliation":[{"name":"Oxford NIHR Biomedical Research Centre, Centre for Human Genetics University of Oxford  Oxford UK"},{"name":"Oxford Centre for Genomic Medicine Nuffield Orthopaedic Centre  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Kinning","sequence":"additional","affiliation":[{"name":"West Midlands Regional Genetics Service Birmingham Women's Hospital  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0324-6916","authenticated-orcid":false,"given":"Donald R.","family":"Latner","sequence":"additional","affiliation":[{"name":"HudsonAlpha Institute for Biotechnology  Huntsville Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marla","family":"Johnston","sequence":"additional","affiliation":[{"name":"Children's Hospital New Orleans  New Orleans Louisiana USA"},{"name":"Department of Pediatrics Louisiana State University Health Sciences Center  New Orleans Louisiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Patrick\u2010Esteve","sequence":"additional","affiliation":[{"name":"Children's Hospital New Orleans  New Orleans Louisiana USA"},{"name":"Department of Pediatrics Louisiana State University Health Sciences Center  New Orleans Louisiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5509-9923","authenticated-orcid":false,"given":"Gregory M.","family":"Cooper","sequence":"additional","affiliation":[{"name":"HudsonAlpha Institute for Biotechnology  Huntsville Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen R. 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