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We review the type and frequency of the clinical features in 36 reported individuals with features of VDEGS, 15 (42%) of whom had known pathogenic variants in\n                    <jats:italic>SCARF2<\/jats:italic>\n                    , 6 (16%) with negative\n                    <jats:italic>SCARF2<\/jats:italic>\n                    testing, and 15 (42%) not tested. We also report three new individuals with pathogenic variants in\n                    <jats:italic>SCARF2<\/jats:italic>\n                    and clinical features of VDEGS. Of the six persons without known pathogenic variants in\n                    <jats:italic>SCARF2<\/jats:italic>\n                    , three remain unsolved despite extensive genetic testing. Three were found to have pathogenic\n                    <jats:italic>ABL1<\/jats:italic>\n                    variants using whole exome sequencing (WES) or whole genome sequencing (WGS). Their phenotype was consistent with the congenital heart disease and skeletal malformations syndrome (CHDSKM), which has been associated with\n                    <jats:italic>ABL1<\/jats:italic>\n                    variants. Of the three unsolved cases, two were brothers who underwent WGS and targeted long\u2010range sequencing of both\n                    <jats:italic>SCARF2<\/jats:italic>\n                    and\n                    <jats:italic>ABL1<\/jats:italic>\n                    , and the third person who underwent WES and RNA sequencing for\n                    <jats:italic>SCARF2<\/jats:italic>\n                    . Because these affected individuals with classical features of VDEGS lacked a detectable pathogenic\n                    <jats:italic>SCARF2<\/jats:italic>\n                    variant, genetic heterogeneity is likely. Our study shows the importance of performing genetic testing on individuals with the VDEGS \u201cphenotype,\u201d either as a targeted gene analysis (\n                    <jats:italic>SCARF2<\/jats:italic>\n                    ,\n                    <jats:italic>ABL1<\/jats:italic>\n                    ) or WES\/WGS. Additionally, individuals with the combination of arachnodactyly and blepharophimosis should undergo echocardiography while awaiting results of molecular testing due to the overlapping physical features of VDEGS and CHDSKM.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62194","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T11:18:17Z","timestamp":1617103097000},"page":"2136-2149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Further delineation of van den\n                    <scp>Ende\u2010Gupta<\/scp>\n                    syndrome: Genetic heterogeneity and overlap with congenital heart defects and skeletal malformations syndrome"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6254-5925","authenticated-orcid":false,"given":"Clara C.","family":"Hildebrandt","sequence":"first","affiliation":[{"name":"Genetics Unit MassGeneral Hospital for Children  Massachusetts USA"},{"name":"Boston Children's Hospital Medical Biochemical Fellowship  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-1078","authenticated-orcid":false,"suffix":"Jr.","given":"John M.","family":"Graham","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Pediatrics Cedars\u2010Sinai Medical Center  Los Angeles California USA"},{"name":"Department of Pediatrics David Geffen School of Medicine at University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9647-0861","authenticated-orcid":false,"given":"Michael","family":"Bamshad","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington School of Medicine  Seattle Washington USA"},{"name":"Department of Genome Sciences University of Washington  Seattle Washington USA"},{"name":"Brotman Baty Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9954-4897","authenticated-orcid":false,"given":"Deborah A.","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences University of Washington  Seattle Washington USA"},{"name":"Brotman Baty Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janson J.","family":"White","sequence":"additional","affiliation":[{"name":"Brotman Baty Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colby T.","family":"Marvin","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6096-8601","authenticated-orcid":false,"given":"Danny E.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington School of Medicine  Seattle Washington USA"},{"name":"Department of Genome Sciences University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"University of Washington Center for Mendelian Genomics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katheryn L.","family":"Grand","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Pediatrics Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1181-7828","authenticated-orcid":false,"given":"Pedro A.","family":"Sanchez\u2010Lara","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Pediatrics Cedars\u2010Sinai Medical Center  Los Angeles California USA"},{"name":"Department of Pediatrics David Geffen School of Medicine at University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Schweitzer","sequence":"additional","affiliation":[{"name":"Division of Pediatric Genetics, Department of Pediatrics University of California Los 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