{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T08:42:50Z","timestamp":1783154570469,"version":"3.54.6"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Beckwith\u2013Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the <jats:italic>CDKN1C<\/jats:italic> molecular subtype remains relatively limited. Here, we investigate the role of <jats:italic>CDKN1C<\/jats:italic> in the broader BWSp phenotype. Notably, patients with <jats:italic>CDKN1C<\/jats:italic> variants appear to exhibit a different tumor risk than other BWSp molecular subtypes. We performed a comprehensive literature review using the search term \u201c<jats:italic>CDKN1C<\/jats:italic> Beckwith\u201d to identify 113 cases of patients with molecularly confirmed <jats:italic>CDKN1C\u2010<\/jats:italic>BWSp. We then assessed the genotype and phenotype in a novel cohort of patients with <jats:italic>CDKN1C<\/jats:italic>\u2010BWSp enrolled in the BWS Research Registry. Cardinal and suggestive features were evaluated for all patients reported, and tumor risk was established based on available reports. The most common phenotypes included macroglossia, omphalocele, and ear creases\/pits. Tumor types reported from the literature included neuroblastoma, acute lymphocytic leukemia, superficial spreading melanoma, and intratubular germ cell neoplasia. Overall, this study identifies unique features associated with <jats:italic>CDKN1C<\/jats:italic> variants in BWSp, enabling more accurate clinical management. The absence of Wilms tumor and hepatoblastoma suggests that screening for these tumors may not be necessary, while the neuroblastoma risk warrants appropriate screening recommendations.<\/jats:p>","DOI":"10.1002\/ajmg.a.63777","type":"journal-article","created":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T07:14:21Z","timestamp":1717226061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Expanded phenotype and cancer risk in patients with <scp>Beckwith\u2013Wiedemann<\/scp> spectrum caused by <scp><i>CDKN1C<\/i><\/scp> variants"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-3924","authenticated-orcid":false,"given":"Andrew M.","family":"George","sequence":"first","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania 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