{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T14:09:47Z","timestamp":1787148587193,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dysmorphology evaluation is important for congenital heart disease (CHD) assessment, but there are no prior investigations quantifying the screening performance compared to standardized genetics evaluations. We investigated this through systematic dysmorphology assessment in CHD patients with standardized genetic testing in primarily pediatric patients with CHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Dysmorphology evaluations preceding genetic testing results allowed us to test for associations between dysmorphic status and genetic diagnoses while adjusting for extracardiac anomalies (ECAs). We use a test\u2010negative case\u2013control design on a pediatric inpatient CHD cohort for our study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 568 patients, nearly 96% of patients completed genetic testing, primarily chromosome microarray (CMA)\u2009\u00b1\u2009exome sequencing\u2010based genetic testing (493\/568, 86.8%). Overall, 115 patients (20.2%) were found to have genetic diagnoses, and dysmorphic patients had doubled risk of genetic diagnoses, after ECA adjustment (OR\u2009=\u20092.10, <jats:italic>p<\/jats:italic>\u2009=\u20090.0030). We found that 7.9% (14\/178) of ECA\u2212\/nondysmorphic patients had genetic diagnoses, which increased to 13.5% (26\/192) in the ECA\u2212\/dysmorphic patients. Nearly 43% of ECA+\/dysmorphic patients had genetic diagnoses (63\/147). The positive predictive value of dysmorphic status was only 26.3%, and the negative predictive value of nondysmorphic status was 88.7%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dysmorphology\u2010based prediction of genetic disorders is limited because of diagnoses found in apparently isolated CHD. Our findings represent one of the only assessments of phenotype\u2010based screening for genetic disorders in CHD and should inform clinical genetics evaluation practices for pediatric CHD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70040","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T06:49:06Z","timestamp":1732603746000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Performance of Dysmorphology\u2010Based Screening for Genetic Disorders in Pediatric Congenital Heart Disease Supports Wider Genetic Testing"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-0202","authenticated-orcid":false,"given":"Benjamin M.","family":"Helm","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Epidemiology Indiana University Richard M. Fairbanks School of Public Health  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey R.","family":"Helvaty","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Conboy","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle C.","family":"Geddes","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-8154","authenticated-orcid":false,"given":"Brett H.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Lah","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-9051","authenticated-orcid":false,"given":"Leah","family":"Wetherill","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Landis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Ware","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Pediatrics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/neo.4\u20104\u2010e99"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37891"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35767"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2022.09.006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.060"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20403"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2015.02.009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061459"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/circgen.123.004104"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gimo.2023.100814"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525\u2010018\u20100049\u20104"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246\u2010017\u20101685\u20107"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61687"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/s104795111600072x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/circgen.122.003791"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2018.00256"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12081244"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd2020076"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/cmt007"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgc4.1498"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001162\u20105"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2015.02.002"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2021.3496"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.122.026369"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2016.00022"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/hcg.0000000000000086"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103476(87)80543\u20107"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742\u20105573\u20103\u201011"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103476(64)80188\u20108"},{"issue":"5","key":"e_1_2_9_31_1","first-page":"477","article-title":"Minor Malformations in the Neonate","volume":"28","author":"M\u00e9hes K.","year":"1973","journal-title":"Helvetica Paediatrica Acta"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2021.04.011"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/circgen.118.002097"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2016.04.008"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100686\u20108"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2331"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2020.07.065"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37820"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.01.002"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61345"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T07:00:07Z","timestamp":1732690807000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/mgg3.70040"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70040","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70040"}}