{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:38:17Z","timestamp":1790285897209,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>To determine the frequency of isolated blepharophimosis\u2010ptosis\u2010epicanthus inversus syndrome (BPES) versus systemic genetic disorders in patients presenting with blepharophimosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective clinical records review. The records of all patients with blepharophimosis seen in the Division of Ophthalmology at the Children's Hospital of Philadelphia during a 12\u2010year\u2010period (2009\u20102020) were reviewed for medical history, clinical examination findings and results of genetic analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 135 patients identified with blepharophimosis included 72 females (53%) and 63 males (47%) whose mean\u2009\u00b1\u2009standard deviation age at first visit was 3.5\u2009\u00b1\u20096.4\u2009years (range 0\u201039.8\u2009years). Sixty\u2010seven of the patients (50%) had undergone genetic testing for <jats:italic>FOXL2<\/jats:italic> gene mutation. Fifty\u2010four (81%) harboured <jats:italic>FOXL2<\/jats:italic> gene mutations and 13 (19%) did not. Altogether, 126 patients (93%) had a final diagnosis of isolated BPES. The remaining nine (7%) had syndromic diagnoses (\u201cblepharophimosis\u2010plus\u201d), including Dubowitz syndrome (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), Ohdo syndrome (<jats:italic>n<\/jats:italic>\u00a0=\u00a01), 22q11.2 duplication (<jats:italic>n<\/jats:italic>\u00a0=\u00a01) and 3q22 deletion (<jats:italic>n<\/jats:italic>\u00a0=\u00a02). Three patients with multiple congenital anomalies remain undiagnosed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Blepharophimosis is an eyelid feature occurring most commonly in isolation due to <jats:italic>FOXL2<\/jats:italic> gene mutation, but can also be a harbinger of multisystem disease not exclusive to isolated BPES, as observed in 7% of cases in this series. The ophthalmologist is often the first to recognise these unique features, and must consider and rule out non\u2010BPES syndromes before establishing a diagnosed classic BPES. A comprehensive genetic evaluation is, therefore, indicated in all cases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.13933","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T04:35:49Z","timestamp":1619066149000},"page":"448-453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["\u201cBlepharophimosis\u2010plus\u201d syndromes: Frequency of systemic genetic disorders that also include blepharophimosis"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0910-3829","authenticated-orcid":false,"given":"Daphna","family":"Landau Prat","sequence":"first","affiliation":[{"name":"Division of Ophthalmology, Oculoplastic and Orbital Surgery Service, The Children's Hospital of Philadelphia and The Edwin and Fannie Gray Hall, Center for Human Appearance, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Goldschleger Eye Institute Sheba Medical Center  Tel Hashomer Israel"},{"name":"Sackler School of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Oculoplastic and Orbital Surgery Service, The Children's Hospital of Philadelphia and The Edwin and Fannie Gray Hall, Center for Human Appearance, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna","family":"Strong","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Katowitz","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Oculoplastic and Orbital Surgery Service, The Children's Hospital of Philadelphia and The Edwin and Fannie Gray Hall, Center for Human Appearance, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Katowitz","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Oculoplastic and Orbital Surgery Service, The Children's Hospital of Philadelphia and The Edwin and Fannie Gray Hall, Center for Human Appearance, Perelman School of Medicine The University of Pennsylvania  Philadelphia Pennsylvania 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