{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T08:26:04Z","timestamp":1786782364762,"version":"build-2736575974"},"reference-count":16,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>DeSanto\u2013Shinawi syndrome (DESSH) is a rare autosomal dominant neurodevelopmental disorder associated with heterozygous pathogenic variants in the WAC gene, most commonly resulting in loss of function. The clinical spectrum of DESSH continues to expand, whereas detailed electroencephalographic descriptions remain limited. We report a 9\u2010year\u2010old male patient presenting with developmental delay, behavioral abnormalities, dysmorphic facial features, epilepsy, and congenital cardiac anomalies. Brain magnetic resonance imaging was normal, while serial electroencephalography demonstrated persistent epileptiform activity involving the bilateral temporo\u2010occipital regions, with left temporo\u2010occipital persistence on follow\u2010up. Whole\u2010exome sequencing identified a novel heterozygous apparently de novo frameshift variant in WAC (NM_016628.5:c.1793delT; p.Met598Serfs*8), which was classified as pathogenic according to ACMG\/AMP criteria. The variant is predicted to result in loss of function, supporting haploinsufficiency as the most plausible disease mechanism. This case expands the mutational and clinical spectrum of DESSH and provides additional electroclinical data on epilepsy associated with WAC\u2010related neurodevelopmental disorder. The coexistence of ventricular septal defect and bicuspid aortic valve further supports the multisystemic nature of the syndrome. Our findings highlight the importance of detailed neurological, electroencephalographic, cardiac, and genetic evaluation in patients with suspected DESSH.<\/jats:p>","DOI":"10.1002\/ajmg.a.70274","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T07:34:06Z","timestamp":1786779246000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel de Novo\n                    <scp>WAC<\/scp>\n                    Frameshift Variant in\n                    <scp>DeSanto\u2013<\/scp>\n                    Shinawi Syndrome With Temporo\u2010Occipital Epileptiform Activity and Congenital Cardiac Anomalies"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2294-2704","authenticated-orcid":false,"given":"Burak","family":"Yavuz","sequence":"first","affiliation":[{"name":"Department of Family Medicine Trakya University Faculty of Medicine  Edirne T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soner","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Trakya University Faculty of Medicine  Edirne T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayhan","family":"K\u00fct\u00fck\u00e7\u00fc","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Trakya University Faculty of Medicine  Edirne T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Karal","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Trakya University Faculty of Medicine  Edirne T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakan","family":"G\u00fcrkan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Trakya University Faculty of Medicine  Edirne T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2020.12.010"},{"key":"e_1_2_8_3_1","article-title":"A Case of DeSanto\u2013Shinawi Syndrome in Bahrain With a Novel Mutation","volume":"2020","author":"Alsahlawi Z.","year":"2020","journal-title":"Case Reports in Genetics"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104534"},{"issue":"11","key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1136\/jmedgenet-2015-103069","article-title":"WAC Loss\u2010Of\u2010Function Mutations Cause a Recognizable Syndrome Characterized by Developmental Delay, Hypotonia and Dysmorphic Features","volume":"52","author":"DeSanto C.","year":"2015","journal-title":"Journal of Medical 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