{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:55Z","timestamp":1791936055471,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"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":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several recurrent malformation associations affecting the development of the embryo have been described in which a genetic etiology has not been found, including LBWC, MURCS, OAVS, OEIS, POC, VACTERL, referred to here as \u201crecurrent constellations of embryonic malformations\u201d (RCEM). All are characterized by an excess of reported monozygotic discordant twins and lack of familial recurrence. We performed a comprehensive review of published twin data across all six phenotypes to allow a more robust assessment of the association with twinning and potential embryologic timing of a disruptive event. We recorded the type of twinning, any overlapping features of another RCEM, maternal characteristics, and the use of ART. Statistically significant associations included an excess of monozygotic twins and 80% discordance rate for the phenotype across all twins. There was an 18.5% rate of ART and no consistently reported maternal adverse events during pregnancy. We found 24 instances of co\u2010occurrence of two RCEM, suggesting a shared pathogenesis across all RCEM phenotypes. We hypothesize the following timing for RCEM phenotypes from the earliest perturbation in development to the latest: LBWC, POC, OEIS, VACTERL, OAVS, then MURCS. The RCEM group of conditions should be considered a spectrum that could be studied as a group.<\/jats:p>","DOI":"10.1002\/ajmg.a.61847","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T16:00:51Z","timestamp":1600963251000},"page":"2646-2661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Recurrent constellations of embryonic malformations re\u2010conceptualized as an overlapping group of disorders with shared pathogenesis"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3437-1507","authenticated-orcid":false,"given":"Aaron P.","family":"Adam","sequence":"first","affiliation":[{"name":"Center for Integrative Brain Research Seattle Children's Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia J.","family":"Curry","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Department of Pediatrics University of California San Francisco  Fresno California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith G.","family":"Hall","sequence":"additional","affiliation":[{"name":"Pediatrics and Medical Genetics, Children's and Women's Health Center of BC, UBC  Vancouver British Columbia Canada"},{"name":"Department of Medical Genetics BC Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim M.","family":"Keppler\u2010Noreuil","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism Rare Disease Institute, Children's National  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret P.","family":"Adam","sequence":"additional","affiliation":[{"name":"Divison of Genetic Medicine, Department of Pediatrics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7681-2844","authenticated-orcid":false,"given":"William B.","family":"Dobyns","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20503"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1512"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000494896"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/01443610903191293"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e328358243c"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320280115"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31665"},{"key":"e_1_2_8_9_1","first-page":"602","article-title":"A syndrome of congenital defects involving the abdominal wall, sternum, diaphragm, pericardium, and heart","volume":"107","author":"Cantrell J. R.","year":"1958","journal-title":"Surgery, Gynecology, & Obstetrics"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1159\/000345205","article-title":"Diabetic embryopathy: A developmental perspective from fertilization to adulthood","volume":"4","author":"Castori M.","year":"2013","journal-title":"Molecular Syndromology"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2013.04.029"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcms.2018.02.005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2015-206302"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(79)80514-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1982.tb09501.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1353\/hub.2006.0044"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701313"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.5114\/pjp.2019.84460"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14237-7"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-6343.2007.00391.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-018-1896-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/03014468000004321"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.24.10.616"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20643"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31897"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/15513815.2017.1332122"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21505"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38016"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103774"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37239"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37985"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.4103\/0971-6866.142906"},{"key":"e_1_2_8_33_1","first-page":"1","article-title":"Trend analysis of the sex ratio at birth in the United States","volume":"53","author":"Mathews T. J.","year":"2005","journal-title":"National Vital Statistics Report"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e32825ea677"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.114880"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.172957"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(73)80024-1"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/ocr.12259"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320260215"},{"key":"e_1_2_8_40_1","volume-title":"Langman's Medical Embryology","author":"Sadler T. W.","year":"2015"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37461"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.2890060313"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31664"},{"key":"e_1_2_8_44_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000345406","article-title":"Exome sequencing and high\u2010density microarray testing in monozygotic twin pairs discordant for features of VACTERL association","volume":"4","author":"Solomon B. D.","year":"2013","journal-title":"Molecular Syndromology"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.054"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38523"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-7-287"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0756.2007.00572.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35561"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320280302"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.11.1317"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1597\/03-110.1"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-007-0336-0"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61847","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.61847","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61847","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T05:55:55Z","timestamp":1693720555000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,14]]},"references-count":52,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/ajmg.a.61847"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61847","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,14]]},"assertion":[{"value":"2020-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}