{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:29:21Z","timestamp":1779236961462,"version":"3.51.4"},"reference-count":75,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T00:00:00Z","timestamp":1545264000000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Cenani\u2013Lenz (C\u2013L) syndrome is characterized by oligosyndactyly, metacarpal synostosis, phalangeal disorganization, and other variable facial and systemic features. Most cases are caused by homozygous and compound heterozygous missense and splice mutations of the <jats:italic>LRP4<\/jats:italic> gene. Currently, the syndrome carries one OMIM number (212780). However, C\u2013L syndrome\u2010like phenotypes as well as other syndactyly disorders with or without metacarpal synostosis\/phalangeal disorganization are also known to be associated with specific <jats:italic>LRP4<\/jats:italic> mutations, adenomatous polyposis coli (<jats:italic>APC<\/jats:italic>) truncating mutations, genomic rearrangements of the <jats:italic>GREM1\u2010FMN1<\/jats:italic> locus, as well as <jats:italic>FMN1<\/jats:italic> mutations. Surprisingly, patients with C\u2013L syndrome\u2010like phenotype caused by <jats:italic>APC<\/jats:italic> truncating mutations have no polyposis despite the increased levels of \u03b2 catenin. The LRP4 and APC proteins act on the WNT (wingless\u2010type integration site family) canonical pathway, whereas the GREM\u20101 and FMN1 proteins act on the bone morphogenetic protein (BMP) pathway. In this review, we discuss the different mutations associated with C\u2013L syndrome, classify its clinical features, review familial adenomatous polyposis caused by truncating <jats:italic>APC<\/jats:italic> mutations and compare these mutations to the splicing <jats:italic>APC<\/jats:italic> mutation associated with syndactyly, and finally, explore the pathophysiology through a review of the cross talks between the WNT canonical and the BMP antagonistic pathways.<\/jats:p>","DOI":"10.1002\/ajmg.a.60694","type":"journal-article","created":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T09:26:16Z","timestamp":1545297976000},"page":"266-279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Cenani\u2013Lenz syndrome and other related syndactyly disorders due to variants in <i>LRP4<\/i>, <i>GREM1<\/i>\/<i>FMN1<\/i>, and <i>APC<\/i>: Insight into the pathogenesis and the relationship to polyposis through the WNT and BMP antagonistic pathways"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2936-7044","authenticated-orcid":false,"given":"Mohammad M.","family":"Al\u2010Qattan","sequence":"first","affiliation":[{"name":"Division of Plastic Surgery King Saud University  Riyadh Saudi Arabia"},{"name":"Division of Plastic Surgery King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"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":[[2018,12,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.05.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209439"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753193413491931"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2001.590312.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.2.91"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1044903"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12130"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5368.1455"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/318811"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.12.020"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.02.010"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.034827"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80393-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.2929"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201592757"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.073833"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970627)70:4<341::AID-AJMG1>3.0.CO;2-W"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.580"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-6-71"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120425"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33206"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.02.017"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208303"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0752"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.08.022"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-017-9725-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2263"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e328306a6ed"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121312110"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35920"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010418"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2013.04.007"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1178"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9207"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035826"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209508"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301716200"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23913"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181724"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2004.10.008"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.03.004"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36647"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513812200"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02172"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.18.3961"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.23.5515"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-9-26"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.153"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2011.03.007"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1113"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.4103\/1477-3163.78111"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504612200"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210054"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt578"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102850"},{"key":"e_1_2_9_57_1","first-page":"313","article-title":"Two unusual types of syndactyly in the same family: Cenani\u2013Lenz type and new type versus severe type I syndactyly?","volume":"14","author":"Percin E. F.","year":"2003","journal-title":"Genetic Counseling"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg105"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.093310"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504308200"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11282"},{"key":"e_1_2_9_62_1","first-page":"41","article-title":"A variant of Cenani\u2013Lenz type syndactyly","volume":"11","author":"Seven M.","year":"2000","journal-title":"Genetic Counseling"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199909)180:3<314::AID-JCP2>3.0.CO;2-Y"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12124"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23417"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0118-y"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-200304000-00001"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1086\/368277"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.12.109"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604934103"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400521200"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm267"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2016.09.004"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-014-2010-x"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.299904"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/44157"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.60694","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.60694","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.60694","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.60694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T06:00:46Z","timestamp":1694325646000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.60694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,20]]},"references-count":75,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1002\/ajmg.a.60694"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.60694","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,20]]},"assertion":[{"value":"2018-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}