{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:15:51Z","timestamp":1760044551706,"version":"3.37.3"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T00:00:00Z","timestamp":1513900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU 1240\/10\u20101"],"award-info":[{"award-number":["KU 1240\/10\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Elsahy\u2013Waters syndrome (EWS), also known as branchial\u2013skeletal\u2013genital syndrome, is a distinct dysmorphology syndrome characterized by facial asymmetry, broad forehead, marked hypertelorism with proptosis, short and broad nose, midface hypoplasia, intellectual disability, and hypospadias. We have recently published a homozygous potential loss of function variant in <jats:italic>CDH11<\/jats:italic> in a boy with a striking resemblance to EWS. More recently, another homozygous truncating variant in <jats:italic>CDH11<\/jats:italic> was reported in two siblings with suspected EWS. Here, we describe in detail the clinical phenotype of the original <jats:italic>CDH11<\/jats:italic>\u2010related patient with EWS as well as a previously unreported EWS\u2010affected girl who was also found to have a novel homozygous truncating variant in <jats:italic>CDH11<\/jats:italic>, which confirms that EWS is caused by biallelic <jats:italic>CDH11<\/jats:italic> loss of function mutations. Clinical features in the four <jats:italic>CDH11<\/jats:italic> mutation\u2010positive individuals confirm the established core phenotype of EWS. Additionally, we identify upper eyelid coloboma as a new, though infrequent clinical feature. The pathomechanism underlying EWS remains unclear, although the limited phenotypic data on the <jats:italic>Cdh11<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mouse suggest that this is a potentially helpful model to explore the craniofacial and brain development in EWS\u2010affected individuals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38568","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T09:09:22Z","timestamp":1514106562000},"page":"477-482","source":"Crossref","is-referenced-by-count":14,"title":["Elsahy\u2013Waters syndrome is caused by biallelic mutations in <i>CDH11<\/i>"],"prefix":"10.1002","volume":"176","author":[{"given":"Frederike L.","family":"Harms","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheela","family":"Nampoothiri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics Amrita Institute of Medical Sciences &amp; Research Centre Cochin Kerala India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shams","family":"Anazi","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhanya","family":"Yesodharan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics Amrita Institute of Medical Sciences &amp; Research Centre Cochin Kerala India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malik","family":"Alawi","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg\u2010Eppendorf Bioinformatics Core Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-8963","authenticated-orcid":false,"given":"Kerstin","family":"Kutsche","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4158-341X","authenticated-orcid":false,"given":"Fowzan S.","family":"Alkuraya","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia"},{"name":"Department of Anatomy and Cell Biology College of Medicine Alfaisal University Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.015"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.113"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1998.tb03761.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.04.003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.05.023"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33634"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.23729"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-197112000-00004"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds294"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.07.016"},{"issue":"1","key":"e_1_2_6_12_1","first-page":"ALL","article-title":"Gorlin's syndromes of the head and neck fifth edition","volume":"58","author":"Hennekam R. 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