{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:55:17Z","timestamp":1773028517350,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004229","name":"Fondazione Pierfranco e Luisa Mariani","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004229","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>SMC1A<\/jats:italic> epilepsy syndrome or developmental and epileptic encephalopathy\u201085 with or without midline brain defects (DEE85, OMIM #301044) is an X\u2010linked neurologic disorder associated with mutations of the <jats:italic>SMC1A<\/jats:italic> gene, which is also responsible for about 5% of patients affected by Cornelia de Lange syndrome spectrum (CdLS). Only described in female patients, <jats:italic>SMC1A<\/jats:italic> epilepsy syndrome is characterized by the onset of severe refractory epileptic seizures in the first year of life, global developmental delay, a variable degree of intellectual disability, and dysmorphic facial features not typical of CdLS. This was a descriptive observational study for the largest international cohort with this specific disorder. The main goal of this study was to improve the knowledge of the natural history of this phenotype with particular attention to the psychomotor development and the epilepsy data. The analyzed cohort shows normal prenatal growth with the subsequent development of postnatal microcephaly. The incidence of neonatal problems (seizures and respiratory compromise) is considerable (51.4%). There is a significant prevalence of central nervous system (20%) and cardiovascular malformations (20%). Motor skills are generally delayed. The presence of drug\u2010resistant epilepsy is confirmed; the therapeutic role of a ketogenic diet is still uncertain. The significant regression of previously acquired skills following the onset of seizures has been observed. Facial dysmorphisms are variable and no patient shows a classic CdLS phenotype. To sum up, <jats:italic>SMC1A<\/jats:italic> variants caused drug\u2010resistant epilepsy in these patients, more than two\u2010thirds of whom were shown to progress to developmental and epileptic encephalopathy. The <jats:italic>SMC1A<\/jats:italic> gene variants are all different from each other (apart from a couple of monozygotic twins), demonstrating the absence of a mutational hotspot in the <jats:italic>SMC1A<\/jats:italic> gene. Owing to the absence of phenotypic specificity, whole\u2010exome sequencing is currently the diagnostic gold standard.<\/jats:p>","DOI":"10.1002\/ajmg.a.63577","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T12:26:19Z","timestamp":1709209579000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>SMC1A<\/i> epilepsy syndrome: clinical data from a large international cohort"],"prefix":"10.1002","volume":"194","author":[{"given":"Elisabetta","family":"Gibellato","sequence":"first","affiliation":[{"name":"Pediatric Department, \u201cMariani\u201d Center for Fragile Child, ASST Lariana Sant'Anna Hospital  Como Italy"},{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6548-4128","authenticated-orcid":false,"given":"Paola","family":"Cianci","sequence":"additional","affiliation":[{"name":"Pediatric Department, \u201cMariani\u201d Center for Fragile Child, ASST Lariana Sant'Anna Hospital  Como Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Mariani","sequence":"additional","affiliation":[{"name":"Pediatric Department, \u201cMariani\u201d Center for Fragile Child, ASST Lariana Sant'Anna Hospital  Como Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Parma","sequence":"additional","affiliation":[{"name":"Pediatric Department, \u201cMariani\u201d Center for Fragile Child, ASST Lariana Sant'Anna Hospital  Como Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Huisman","sequence":"additional","affiliation":[{"name":"Pediatric Department, Academic Medical Center University of Amsterdam  Amsterdam Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"\u015amigiel","sequence":"additional","affiliation":[{"name":"Pediatric Department, Endocrinology, Diabetology and Metabolic Diseases Wroclaw Medical University  Wroclaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Marie","family":"Bisgaard","sequence":"additional","affiliation":[{"name":"Pediatric Department and Adolescent Medicine Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2246-9515","authenticated-orcid":false,"given":"Valentina","family":"Massa","sequence":"additional","affiliation":[{"name":"Department of Health Sciences University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-7935","authenticated-orcid":false,"given":"Cristina","family":"Gervasini","sequence":"additional","affiliation":[{"name":"Department of Health Sciences University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-825X","authenticated-orcid":false,"given":"Alex","family":"Moretti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca  Monza Italy"},{"name":"Pediatrics, Fondazione IRCCS San Gerardo dei Tintori  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Cattoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca  Monza Italy"},{"name":"Pediatrics, Fondazione IRCCS San Gerardo dei Tintori  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca  Monza Italy"},{"name":"Pediatrics, Fondazione IRCCS San Gerardo dei Tintori  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6187-3727","authenticated-orcid":false,"given":"Angelo","family":"Selicorni","sequence":"additional","affiliation":[{"name":"Pediatric Department, \u201cMariani\u201d Center for Fragile Child, ASST Lariana Sant'Anna Hospital  Como Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738221081244"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14040852"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41439-019-0053-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.09.007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e3283645439"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38279"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12729"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0031-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz210"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(91)90143-3"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37364"},{"key":"e_1_2_10_13_1","volume-title":"Nelson essentials of pediatrics","author":"Marcdante K. J.","year":"2019"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1779"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/aian.AIAN_518_19"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2019.06.001"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.2.257"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13669"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38030"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0085-6"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T15:28:50Z","timestamp":1717774130000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,29]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/ajmg.a.63577"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63577","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,29]]},"assertion":[{"value":"2023-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63577"}}