{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T18:27:31Z","timestamp":1777314451679,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We describe the clinical features of nine unrelated individuals with rare de novo missense or in\u2010frame deletions\/duplications within the \u201cHX motif\u201d of exon 7 of\n                    <jats:italic>ATN1<\/jats:italic>\n                    . We previously proposed that individuals with such variants should be considered as being affected by the syndromic condition of congenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA), distinct from dentatorubral\u2010pallidoluysian atrophy (DRPLA) secondary to expansion variants in exon 5 of\n                    <jats:italic>ATN1<\/jats:italic>\n                    . We confirm that the universal phenotypic features of CHEDDA are distinctive facial features and global developmental delay. Infantile hypotonia and minor hand and feet differences are common and can present as arthrogryposis. Common comorbidities include severe feeding difficulties, often requiring gastrostomy support, as well as visual and hearing impairments. Epilepsy and congenital malformations of the brain, heart, and genitourinary systems are frequent but not universal. Our study confirms the clinical entity of CHEDDA secondary to a mutational signature restricted to exon 7 of\n                    <jats:italic>ATN1<\/jats:italic>\n                    . We propose a clinical schedule for assessment upon diagnosis, surveillance, and early intervention including the potential of neuroimaging for prognostication.\n                  <\/jats:p>","DOI":"10.1111\/cge.14022","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T04:49:11Z","timestamp":1625201351000},"page":"468-477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>CHEDDA<\/scp>\n                    syndrome is an underrecognized neurodevelopmental disorder with a highly restricted\n                    <scp>\n                      <i>ATN1<\/i>\n                    <\/scp>\n                    mutation spectrum"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-215X","authenticated-orcid":false,"given":"Elizabeth E.","family":"Palmer","sequence":"first","affiliation":[{"name":"Centre for Clinical Genetics Sydney Children's Hospital  Randwick New South Wales Australia"},{"name":"School of Women's and Children's Health University of New South Wales  Randwick New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-7607","authenticated-orcid":false,"given":"Chloe","family":"Whitton","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of New South Wales  Randwick New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mais O.","family":"Hashem","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics Center for Genomic Medicine, King Faisal Specialist Hospital and Research Centre  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin D.","family":"Clark","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Loma Linda University School of Medicine  Loma Linda CA 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Pediatrics Dayton Children's Hospital  Dayton Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6287-3259","authenticated-orcid":false,"given":"Emily","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Genetics Medical College of Wisconsin with Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2839-9856","authenticated-orcid":false,"given":"Valerie","family":"Cormier\u2010Daire","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, INSERM UMR 1163, H\u00f4pital Necker\u2010Enfants Malades, Institut IMAGINE Universit\u00e9 de Paris  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Chopra","sequence":"additional","affiliation":[{"name":"Rosamund Stone Zander Translational Neuroscience Center Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lance H.","family":"Rodan","sequence":"additional","affiliation":[{"name":"Department of Neurology Division of Genetics and Genomics, Boston Children's Hospital, Boston  Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoffer","family":"Nellaker","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women's and Reproductive Health University of Oxford, Women's Centre, John Radcliffe Hospital  Oxford UK"},{"name":"Institute of Biomedical Engineering, Department of Engineering Science University of Oxford  Oxford UK"},{"name":"Big Data Institute, Li Ka Shing Centre for Health Information and Discovery University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2908-950X","authenticated-orcid":false,"given":"Shenela","family":"Lakhani","sequence":"additional","affiliation":[{"name":"Centre for Neurogenetics, Feil Family Brain and Mind Research Institute Weill Cornell Medicine  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-8807","authenticated-orcid":false,"given":"Eric J.","family":"Mallack","sequence":"additional","affiliation":[{"name":"Centre for Neurogenetics, Feil Family Brain and Mind Research Institute Weill Cornell Medicine  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Panzer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Hospitals and Clinics  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8980-5029","authenticated-orcid":false,"given":"Alpa","family":"Sidhu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Hospitals and Clinics  Iowa City Iowa 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