{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T22:47:32Z","timestamp":1754261252311},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>Muenke syndrome is a craniosynostosis syndrome associated with the p.Pro250Arg mutation in FGFR3. An increasing number of individuals with this mutation are reported to not have craniosynostosis. The purpose of this report is to increase awareness of the high phenotypic variability seen in Muenke syndrome. DNA testing for the p.Pro250Arg mutation is routinely performed in Denmark, in children presenting with isolated coronal synostosis. Verified diagnosis entails detailed family history, drawing of family pedigree, DNA testing of the parents, genetic counseling, skull radiographs, clinical photographs, and follow-up. Sixteen individuals from 5 Danish families with Muenke syndrome are presented. Large phenotypic variation was seen both within and across families. The most striking observations were that 6\/16 (38%) cases did not have craniosynostosis and one individual presented with a normal phenotype. In addition, 3 unrelated cases had incomplete cleft palate, submucous cleft palate, and bifid uvula, respectively. There is strong evidence for reduced penetrance of the craniosynostosis trait in Muenke syndrome. We argue that many studies on Muenke syndrome have been influenced by ascertainment bias in regard to craniosynostosis. In addition, it is suggested that oral clefting might be part of the clinical spectrum seen in Muenke syndrome.<\/jats:p>","DOI":"10.1097\/mcd.0000000000000300","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T15:42:56Z","timestamp":1571067776000},"page":"1-9","source":"Crossref","is-referenced-by-count":6,"title":["Phenotypic variability in Muenke syndrome\u2014observations from five Danish families"],"prefix":"10.1097","volume":"29","author":[{"given":"Louise","family":"\u00d6wall","sequence":"first","affiliation":[{"name":"3D Craniofacial Image Research Laboratory (School of Dentistry, University of Copenhagen; Centre of Head and Orthopedics, Copenhagen University Hospital Rigshospitalet; and Department of Applied Mathematics and Computer Science, Technical University of Denmark)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Kreiborg","sequence":"additional","affiliation":[{"name":"3D Craniofacial Image Research Laboratory (School of Dentistry, University of Copenhagen; Centre of Head and Orthopedics, Copenhagen University Hospital Rigshospitalet; and Department of Applied Mathematics and Computer Science, Technical University of Denmark)"},{"name":"Department of Paediatric Dentistry and Clinical Genetics, School of Dentistry, Faculty of Health and Medical Science, University of Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten","family":"Dun\u00f8","sequence":"additional","affiliation":[{"name":"Centre for Rare Diseases, Department of Clinical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuno V.","family":"Hermann","sequence":"additional","affiliation":[{"name":"3D Craniofacial Image Research Laboratory (School of Dentistry, University of Copenhagen; Centre of Head and Orthopedics, Copenhagen University Hospital Rigshospitalet; and Department of Applied Mathematics and Computer Science, Technical University of Denmark)"},{"name":"Department of Paediatric Dentistry and Clinical Genetics, School of Dentistry, Faculty of Health and Medical Science, University of Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tron A.","family":"Darvann","sequence":"additional","affiliation":[{"name":"3D Craniofacial Image Research Laboratory (School of Dentistry, University of Copenhagen; Centre of Head and Orthopedics, Copenhagen University Hospital Rigshospitalet; and Department of Applied Mathematics and Computer Science, Technical University of Denmark)"},{"name":"Department of Oral and Maxillofacial Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanne","family":"Hove","sequence":"additional","affiliation":[{"name":"Centre for Rare Diseases, Department of Paediatrics"},{"name":"The RAREDIS Database, Centre for Rare Diseases, Department of Paediatrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230913","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/ajmg.a.33777","article-title":"Muenke syndrome with pigmentary disorder and probable hemimegalencephaly: an expansion of the phenotype.","volume":"155A","author":"Abdel-Salam","year":"2011","journal-title":"Am J Med Genet A"},{"key":"R2-20230913","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1097\/SCS.0b013e31824db8bb","article-title":"Palatal and oral manifestations of Muenke syndrome (FGFR3-related craniosynostosis).","volume":"23","author":"Agochukwu","year":"2012","journal-title":"J Craniofac Surg"},{"key":"R3-20230913","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1097\/SCS.0b013e31829035c3","article-title":"Muencke syndrome with cleft lip and palate.","volume":"24","author":"Anderson","year":"2013","journal-title":"J Craniofac Surg"},{"key":"R4-20230913","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.3109\/14767058.2013.860520","article-title":"A familial case of muenke syndrome. 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