{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T13:22:36Z","timestamp":1771507356808,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"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":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Now in its 7th edition, <jats:italic>Smith's Recognizable Patterns of Human Malformation<\/jats:italic> was first published in 1970. This 1st edition comprised 135 \u201cdysmorphic syndromes of multiple primary defects\u201d and 12 \u201csingle syndromic malformations resulting in secondary defects.\u201d Of the former, other than a few chromosomal and environmental disorders, most were heritable conditions of then unknown etiology. In 2021, the majority of these conditions are now \u201csolved,\u201d a notable exception is Hallermann\u2010Streiff syndrome. The \u201csolved\u201d conditions were typically clinically delineated decades prior to understanding the underlying etiology, which rarely required recent technologies such as exome sequencing (ES) to elucidate. The 7th edition includes nearly 300 syndromes, sequences, and associations. An increasing number of conditions first appearing in the latest editions are sporadic, with many solved using either array CGH or ES. We have reviewed all syndromes that have appeared in \u201c<jats:italic>Smith's<\/jats:italic>\u201d with a focus on inheritance, heterogeneity, and year and method of etiologic discovery. Several themes emerge. Genetic heterogeneity and pleiotropy of genes are frequent. Several of the currently \u201cunresolved\u201d syndromes are clinically diverse such as Dubowitz syndrome. Multiple recurrent constellations of embryonic malformations, with VACTERL association as a paradigm, are increasingly likely to have a shared pathogenesis requiring further study.<\/jats:p>","DOI":"10.1002\/ajmg.a.62240","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T10:04:02Z","timestamp":1620295442000},"page":"2653-2669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Fifty years of recognizable patterns of human malformation: Insights and opportunities"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-5467","authenticated-orcid":false,"given":"A. Micheil","family":"Innes","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Alberta Children's Hospital Research Institute  Calgary Alberta Canada"},{"name":"Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle C.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61847"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1834"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31666"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31660"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37684"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22837"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.07.011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.04.004"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.11.013"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5058"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31665"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.02.040"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38493"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61926"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcd.0000220603.09661.7e"},{"key":"e_1_2_9_18_1","first-page":"1","article-title":"The mystery of monozygotic twinning I: What can amyoplasia tell us about monozygotic twinning and the possible role of twin\u2010twin transfusion?","author":"Hall J. 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