{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:51:50Z","timestamp":1782755510306,"version":"3.54.5"},"reference-count":81,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Otofaciocervical syndrome (OTFCS) is a rare disorder characterized by facial, auditory, and shoulder girdle anomalies. Its significant phenotypic overlap with branchiootorenal spectrum disorders (BORSD)\u2014both linked to EYA1 (EYA transcriptional coactivator and phosphatase 1) gene defects\u2014has raised questions about whether they are distinct entities or part of a single clinical spectrum. We report a novel OTFCS patient with a de novo microdeletion spanning EYA1 and review all published cases of EYA1-related disorders. Our analysis reveals that all EYA1 variant types (truncating, missense, CNV, etc.) can cause BORSD, OTFCS, or hybrid phenotypes, firmly supporting their status as allelic disorders. Crucially, all reported OTFCS patients with EYA1 variants had renal anomalies, a feature previously considered a hallmark of BORSD. We conclude that BORSD and OTFCS constitute a single EYA1-related diagnostic continuum. This reclassification mandates the development of follow-up protocols that integrate renal, otologic, and skeletal surveillance in EYA1-related disorders, including OTFCS, and refines prognostic and genetic counseling.<\/jats:p>","DOI":"10.3390\/genes16111267","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T09:16:07Z","timestamp":1761642967000},"page":"1267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Otofaciocervical Syndrome and Its Overlap with Branchiootorenal Spectrum: An Integrated Literature Analysis of EYA1-Related Disorders, Including a Novel Case with an 8q13.2q13.3 Deletion"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-7388","authenticated-orcid":false,"given":"Ludovico","family":"Graziani","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Genetics and Developmental Biology Unit, Azienda Ospedaliera Universitaria Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Lucia","family":"Carriero","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Melchionda","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7475-6976","authenticated-orcid":false,"given":"Bartolomeo","family":"Augello","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-3482","authenticated-orcid":false,"given":"Orazio","family":"Palumbo","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Bengala","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Medical Genetics Unit, \u201cTor Vergata\u201d University Hospital, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-602X","authenticated-orcid":false,"given":"Giuseppe","family":"Novelli","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Medical Genetics Unit, \u201cTor Vergata\u201d University Hospital, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3174\/ajnr.A2072","article-title":"Syndromes of the First and Second Branchial Arches, Part 1: Embryology and Characteristic Defects","volume":"32","author":"Johnson","year":"2011","journal-title":"Am. 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