{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:28:30Z","timestamp":1740144510199,"version":"3.37.3"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,10]],"date-time":"2024-03-10T00:00:00Z","timestamp":1710028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,10]],"date-time":"2024-03-10T00:00:00Z","timestamp":1710028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Cornelia de Lange (CdLS) is a rare genetic disorder that affects most body systems. Variants in multiple genes including <jats:italic>NIPBL<\/jats:italic> and <jats:italic>SMC1A,<\/jats:italic> can cause the syndrome. To date, literature on genotype\u2013phenotype associations in individuals with CdLS is extremely limited, although studies suggest some differences in clinical phenotype severity across variants. This study aimed to examine and compare neurobehavioral differences and developmental variability across CdLS genes, specifically <jats:italic>NIPBL<\/jats:italic> and <jats:italic>SMC1A,<\/jats:italic> and identify genotype\u2013phenotype correlations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Participants and methods<\/jats:title>\n                <jats:p>This patient-reported outcomes study included accessing data from the Coordination of Rare Diseases registry at Sanford. Parents of a total of 26 children\/adults with CdLS and a known variant in <jats:italic>NIPBL<\/jats:italic> (Mean age\u2009=\u200920.46\u00a0years, SD\u2009=\u200911.21) and 12 with a known variant in <jats:italic>SMC1A<\/jats:italic> (Mean age\u2009=\u200911.08\u00a0years, SD\u2009=\u20099.04) completed a series of questionnaires regarding their child\u2019s developmental history. This included attainment of common language and motor milestones, intervention history, and behavior functioning. Developmental history and reported behavior regulation difficulties were compared across variant groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Overall, individuals with a pathogenic variant in <jats:italic>NIPBL<\/jats:italic> or <jats:italic>SMC1A<\/jats:italic> were similarly delayed across motor and language milestones with about 70% not using phrase speech and 30\u201350% not walking by 5\u00a0years of age. However, those with <jats:italic>NIPBL<\/jats:italic> variants showed more severity in behavioral phenotype, namely with more repetitive behaviors, tantrums, and withdrawn behaviors. In addition, these individuals were more likely than those with <jats:italic>SMC1A<\/jats:italic> variants to demonstrate self-injurious behaviors, and anxiety. Both groups yielded a similar proportion of participants who participated in speech and occupational therapy, however those with <jats:italic>SMC1A<\/jats:italic> variants were more likely to engage in physical therapy. Both clinical groups report low rate of communicative or assistive device use despite a large proportion of participants never mastering single word or sentence use.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Study results are consistent with recent investigations highlighting more severe behavioral phenotype, particularly autistic features, anxiety, and behavior regulation challenges, among those with <jats:italic>NIPBL<\/jats:italic> variants albeit comparable developmental milestones. Both groups endorsed very elevated attention problems. Findings highlight importance of early interventions, including behavioral health services.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03104-1","type":"journal-article","created":{"date-parts":[[2024,3,10]],"date-time":"2024-03-10T23:01:28Z","timestamp":1710111688000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neurobehavioral and developmental profiles: genotype\u2013phenotype correlations in individuals with Cornelia de Lange syndrome"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7193-4300","authenticated-orcid":false,"given":"Rowena","family":"Ng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deirdre","family":"Summa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonie D.","family":"Kline","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,10]]},"reference":[{"key":"3104_CR1","doi-asserted-by":"publisher","first-page":"4763","DOI":"10.1007\/s10803-021-05343-8","volume":"52","author":"PF Ajmone","year":"2022","unstructured":"Ajmone PF, Allegri B, Cereda A, Michelini G, Dall\u2019Ara F, Mariani M, Rigamonti C, Selicorni A, Vizziello P, Costantino MAJ. 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