{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T06:34:46Z","timestamp":1792305286904,"version":"4.4.0"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/J004189\/1, MRC\/N004566\/1 and MC_PC_17171"],"award-info":[{"award-number":["MR\/J004189\/1, MRC\/N004566\/1 and MC_PC_17171"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["CL-2017-11-003"],"award-info":[{"award-number":["CL-2017-11-003"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002089","name":"Fight for Sight","doi-asserted-by":"publisher","award":["5009\/5010"],"award-info":[{"award-number":["5009\/5010"]}],"id":[{"id":"10.13039\/100002089","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Boston Children\u2019s Hospital Intellectual and Developmental Disabilities Research Center","award":["NICHD 1U54HD090255"],"award-info":[{"award-number":["NICHD 1U54HD090255"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital fibrosis of the extraocular muscles (CFEOM) is a congenital cranial dysinnervation disorder caused by developmental abnormalities affecting cranial nerves\/nuclei innervating the extraocular muscles. Autosomal dominant CFEOM arises from heterozygous missense mutations of KIF21A or TUBB3. Although spatiotemporal expression studies have shown KIF21A and TUBB3 expression in developing retinal ganglion cells, it is unclear whether dysinnervation extends beyond the oculomotor system. We aimed to investigate whether dysinnervation extends to the visual system by performing high-resolution optical coherence tomography (OCT) scans characterizing retinal ganglion cells within the optic nerve head and retina. Sixteen patients with CFEOM were screened for mutations in KIF21A, TUBB3, and TUBB2B. Six patients had apparent optic nerve hypoplasia. OCT showed neuro-retinal rim loss. Disc diameter, rim width, rim area, and peripapillary nerve fiber layer thickness were significantly reduced in CFEOM patients compared to controls (p &lt; 0.005). Situs inversus of retinal vessels was seen in five patients. Our study provides evidence of structural optic nerve and retinal changes in CFEOM. We show for the first time that there are widespread retinal changes beyond the retinal ganglion cells in patients with CFEOM. This study shows that the phenotype in CFEOM extends beyond the motor nerves.<\/jats:p>","DOI":"10.3390\/ijms22052575","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T21:58:07Z","timestamp":1614895087000},"page":"2575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Optic Nerve Head and Retinal Abnormalities Associated with Congenital Fibrosis of the Extraocular Muscles"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-1234","authenticated-orcid":false,"given":"Mervyn G.","family":"Thomas","sequence":"first","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9131-3480","authenticated-orcid":false,"given":"Gail D. E.","family":"Maconachie","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"},{"name":"Division of Ophthalmology &amp; Orthoptics, Health Sciences School, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7681-3062","authenticated-orcid":false,"given":"Helen J.","family":"Kuht","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Man","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland, MD 20815, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viral","family":"Sheth","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hisaund","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"McLean","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Barry","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland, MD 20815, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9526-9058","authenticated-orcid":false,"given":"Bashir","family":"Al-Diri","sequence":"additional","affiliation":[{"name":"Brayford Pool Campus, School of Computer Science, University of Lincoln, Lincoln LN6 7TS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Proudlock","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanhan","family":"Tu","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8194-7738","authenticated-orcid":false,"given":"Elizabeth C.","family":"Engle","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland, MD 20815, USA"},{"name":"Departments of Neurology and Ophthalmology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Departments of Neurology and Ophthalmology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Gottlob","sequence":"additional","affiliation":[{"name":"The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSB, PO Box 65, Leicester LE2 7LX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0960-8966(03)00043-9","article-title":"110th ENMC International Workshop: The congenital cranial dysinnervation disorders (CCDDs). 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