{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T17:21:36Z","timestamp":1777742496370,"version":"3.51.4"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T00:00:00Z","timestamp":1607212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002736","name":"Citizens United for Research in Epilepsy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000912","name":"March of Dimes Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chromosome 1q41\u2010q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41\u2010q42 microdeletion, <jats:italic>WDR26<\/jats:italic> and <jats:italic>FBXO28<\/jats:italic>, have been implicated in monogenic disease. Patients with <jats:italic>WDR26<\/jats:italic> encephalopathy overlap clinically with those with 1q41\u2010q42 deletion syndrome, whereas only one patient with <jats:italic>FBXO28<\/jats:italic> encephalopathy has been described. Seizures are a prominent feature of 1q41\u2010q42 deletion syndrome; therefore, we hypothesized that pathogenic <jats:italic>FBXO28<\/jats:italic> variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with <jats:italic>FBXO28<\/jats:italic> pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5\u00a0months (range 8\u00a0months to 5\u00a0years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41\u2010q42 deletion syndrome and <jats:italic>WDR26<\/jats:italic> encephalopathy. We distinguish <jats:italic>FBXO28<\/jats:italic> encephalopathy from both of these disorders with more severe intellectual impairment, drug\u2010resistant epilepsy, and hyperkinetic movement disorders.<\/jats:p>","DOI":"10.1111\/epi.16784","type":"journal-article","created":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T08:21:46Z","timestamp":1607242906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>FBXO28<\/i> causes developmental and epileptic encephalopathy with profound intellectual disability"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5260-7187","authenticated-orcid":false,"given":"Amy L.","family":"Schneider","sequence":"first","affiliation":[{"name":"Epilepsy Research Centre Department of Medicine, Austin Health The University of Melbourne Heidelberg Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candace T.","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Genetic Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9420-085X","authenticated-orcid":false,"given":"Alison M.","family":"Muir","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Genetic Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Calvert","sequence":"additional","affiliation":[{"name":"Department of Neurology Queensland Children\u2019s Hospital South Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Basinger","sequence":"additional","affiliation":[{"name":"Genetics Cook Children's Fort Worth TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-846X","authenticated-orcid":false,"given":"M. Scott","family":"Perry","sequence":"additional","affiliation":[{"name":"Justin Neurosciences Center Cook Children\u2019s Medical Center Fort Worth TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lance","family":"Rodan","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA USA"},{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine L.","family":"Helbig","sequence":"additional","affiliation":[{"name":"Division of Neurology Children\u2019s Hospital of Philadelphia Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chelsea","family":"Chambers","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of Virginia Charlottesville VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen M.","family":"Gorman","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neurophysiology Children\u2019s Health Ireland at Temple Street Dublin Ireland"},{"name":"School of Medicine and Medical Sciences University College Dublin Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary D.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neurophysiology Children\u2019s Health Ireland at Temple Street Dublin Ireland"},{"name":"School of Medicine and Medical Sciences University College Dublin Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Donkervoort","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariane","family":"Soldatos","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nino","family":"Spataro","sequence":"additional","affiliation":[{"name":"Genetics Laboratory UDIAT\u2010Centre Diagnostic Parc Taul\u00ed University Hospital Parc Taul\u00ed I3PT Research and Innovation Institute University of Barcelona Sabadell Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Gabau","sequence":"additional","affiliation":[{"name":"Paediatric Unit Parc Taul\u00ed University Hospital Parc Taul\u00ed I3PT Research and Innovation Institute University of Barcelona Sabadell Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Arellano","sequence":"additional","affiliation":[{"name":"Neuropediatrics Unit Pediatric Service MutuaTerrassa University Hospital Terrassa Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerarda","family":"Cappuccio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Federico II University Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine Pozzuoli, Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Brunetti\u2010Pierri","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Federico II University Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine Pozzuoli, Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9304-9385","authenticated-orcid":false,"given":"Elsa","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte\u2010Justine Research Center Montreal Quebec Canada"},{"name":"Department of Neurosciences and Department of Pediatrics University of Montreal Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadi F.","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte\u2010Justine Research Center Montreal Quebec Canada"},{"name":"Department of Pediatrics University of Montreal Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques L.","family":"Michaud","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte\u2010Justine Research Center Montreal Quebec Canada"},{"name":"Department of Neurosciences and Department of Pediatrics University of Montreal Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Balak","sequence":"additional","affiliation":[{"name":"Neurogenomics Division Centre for Rare Childhood Disorders (C4RCD) Translational Genomics Research Institute Phoenix AZ USA"},{"name":"Department of Cellular and Molecular Medicine School of Medicine University of California San Diego La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather C.","family":"Mefford","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Genetic Medicine University of Washington Seattle WA 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