{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:51:44Z","timestamp":1790805104217,"version":"4.1.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870373"],"award-info":[{"award-number":["81870373"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81500449"],"award-info":[{"award-number":["81500449"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["16ZR1428700"],"award-info":[{"award-number":["16ZR1428700"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Hospital Development Center New Frontier Technology Joint Research Project","award":["SHDC12017115"],"award-info":[{"award-number":["SHDC12017115"]}]},{"name":"Shanghai Municipal Commission of Health and Family Planning Key Project","award":["2017ZZ02019"],"award-info":[{"award-number":["2017ZZ02019"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth disorder with variable clinical features and cancer predisposition. In this study, we aim to characterize the clinical features and molecular defects of BWS patients in China.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty-one patients with clinical suspicion of BWS were retrospectively recruited to the study from Shanghai Children\u2019s Hospital between January 2014 and December 2017. Clinical data, including demographics, clinical features, and molecular testing results were extracted and systematically analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-one patients with a BWS score\u2009\u2265\u20094 (6, IQR 4, 7) were clinically diagnosed with BWS, and 10 children with a BWS score\u2009\u2265\u20092 and\u2009&lt;\u20094 (2, IQR 2, 3) were clinically suspected BWS patients. The most common cardinal feature of clinically diagnosed patients was macroglossia (71.4%) followed by lateralized overgrowth (33.3%) and exomphalos (14.3%), and the major suggestive features were umbilical hernia and\/or diastasis recti (65.0%) and ear creases or pits (61.9%). Among 10 clinically suspected BWS patients, macroglossia and lateralized overgrowth were observed in 3 (30%) and 2 (20%) patients, and umbilical hernia and\/or diastasis recti occurred in 7 (70.0%) patients. Seven (33.3%) clinically diagnosed patients and 3 (30%) suspected patients were identified with loss of methylation at KCNQ1OT1:TSS differentially methylated region (DMR; IC2 LOM), 5 (23.8%) clinically diagnosed BWS patients were identified with gain of methylation at H19\/IGF2:IG-DMR (IC1 GOM), and 1 (4.8%) clinically diagnosed BWS patients was identified with paternal uniparental isodisomy 11 (pUPD11). The phenotype-genotype correlation analysis showed no significant difference among patients with IC2 LOM, IC1 GOM, and pUPD11.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The current study presents the first cohort study of BWS patients in mainland China. The clinical and molecular features of the patients are similar to those of other reported BWS patients in the Chinese population.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13052-020-0819-3","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T19:03:17Z","timestamp":1588186997000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical and molecular features of children with Beckwith-Wiedemann syndrome in China: a single-center retrospective cohort study"],"prefix":"10.1186","volume":"46","author":[{"given":"Ruixue","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9390-8864","authenticated-orcid":false,"given":"Yizhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"issue":"4","key":"819_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/nrendo.2017.166","volume":"14","author":"F Brioude","year":"2018","unstructured":"Brioude F, Kalish JM, Mussa A, et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14(4):229\u201349.","journal-title":"Nat Rev Endocrinol"},{"key":"819_CR2","volume-title":"Annual Meeting of Western Society of Pediatric Research. Los Angeles, California","author":"JB Beckwith","year":"1963","unstructured":"Beckwith JB. Extreme cytomegaly of the adrenal fetal cortex, omphalocele, hyperplasia of kidneys and pancreas, and Leydig-cell hyperplasia: another syndrome? In: Annual Meeting of Western Society of Pediatric Research. Los Angeles, California; 1963."},{"key":"819_CR3","first-page":"223","volume":"13","author":"HR Wiedemann","year":"1964","unstructured":"Wiedemann HR. Familial malformation complex with umbilical hernia and Macroglossia--a \"new syndrome\"? J Genet Hum. 1964;13:223\u201332.","journal-title":"J Genet Hum"},{"issue":"10","key":"819_CR4","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1002\/ajmg.a.36080","volume":"161A","author":"A Mussa","year":"2013","unstructured":"Mussa A, Russo S, De Crescenzo A, et al. Prevalence of Beckwith-Wiedemann syndrome in north west of Italy. Am J Med Genet A. 2013;161A(10):2481\u20136.","journal-title":"Am J Med Genet A"},{"issue":"1","key":"819_CR5","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/ejhg.2009.106","volume":"18","author":"R Weksberg","year":"2010","unstructured":"Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2010;18(1):8\u201314.","journal-title":"Eur J Hum Genet"},{"issue":"3","key":"819_CR6","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/ajmg.c.30267","volume":"154C","author":"S Choufani","year":"2010","unstructured":"Choufani S, Shuman C, Weksberg R. Beckwith-Wiedemann syndrome. Am J Med Genet C Semin Med Genet. 2010;154C(3):343\u201354.","journal-title":"Am J Med Genet C Semin Med Genet"},{"issue":"2","key":"819_CR7","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/ajmg.c.31363","volume":"163C","author":"S Choufani","year":"2013","unstructured":"Choufani S, Shuman C, Weksberg R. Molecular findings in Beckwith-Wiedemann syndrome. Am J Med Genet C Semin Med Genet. 2013;163C(2):131\u201340.","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"819_CR8","doi-asserted-by":"crossref","unstructured":"Eggermann T, Algar E, Lapunzina P, et al. Clinical utility gene card for: Beckwith-Wiedemann Syndrome. Eur J Hum Genet. 2014;22(3):435.","DOI":"10.1038\/ejhg.2013.132"},{"issue":"4","key":"819_CR9","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1002\/ajmg.a.61109","volume":"179","author":"KA Duffy","year":"2019","unstructured":"Duffy KA, Sajorda BJ, Yu AC, et al. Beckwith-Wiedemann syndrome in diverse populations. Am J Med Genet A. 2019;179(4):525\u201333.","journal-title":"Am J Med Genet A"},{"issue":"5","key":"819_CR10","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/sj.ejhg.5202001","volume":"16","author":"M Priolo","year":"2008","unstructured":"Priolo M, Sparago A, Mammi C, et al. MS-MLPA is a specific and sensitive technique for detecting all chromosome 11p15.5 imprinting defects of BWS and SRS in a single-tube experiment. Eur J Hum Genet. 2008;16(5):565\u201371.","journal-title":"Eur J Hum Genet"},{"issue":"9","key":"819_CR11","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/jhg.2013.67","volume":"58","author":"BH Lee","year":"2013","unstructured":"Lee BH, Kim GH, Oh TJ, et al. Quantitative analysis of methylation status at 11p15 and 7q21 for the genetic diagnosis of Beckwith-Wiedemann syndrome and silver-Russell syndrome. J Hum Genet. 2013;58(9):604\u201310.","journal-title":"J Hum Genet"},{"issue":"6","key":"819_CR12","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/sj.ejhg.5200649","volume":"9","author":"V Gaston","year":"2001","unstructured":"Gaston V, Le Bouc Y, Soupre V, et al. Analysis of the methylation status of the KCNQ1OT and H19 genes in leukocyte DNA for the diagnosis and prognosis of Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2001;9(6):409\u201318.","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"819_CR13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1868-7083-6-11","volume":"6","author":"A Ibrahim","year":"2014","unstructured":"Ibrahim A, Kirby G, Hardy C, et al. Methylation analysis and diagnostics of Beckwith-Wiedemann syndrome in 1,000 subjects. Clin Epigenetics. 2014;6(1):11.","journal-title":"Clin Epigenetics"},{"issue":"1\u20132","key":"819_CR14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ymgme.2016.07.003","volume":"119","author":"HY Lin","year":"2016","unstructured":"Lin HY, Chuang CK, Tu RY, et al. Epigenotype, genotype, and phenotype analysis of patients in Taiwan with Beckwith-Wiedemann syndrome. Mol Genet Metab. 2016;119(1\u20132):8\u201313.","journal-title":"Mol Genet Metab"},{"issue":"1","key":"819_CR15","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1515\/jpem-2016-0094","volume":"30","author":"HM Luk","year":"2017","unstructured":"Luk HM. Clinical and molecular characterization of Beckwith-Wiedemann syndrome in a Chinese population. J Pediatr Endocrinol Metab. 2017;30(1):89\u201395.","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"1","key":"819_CR16","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1136\/jmg.40.1.62","volume":"40","author":"ER Maher","year":"2003","unstructured":"Maher ER, Brueton LA, Bowdin SC, et al. Beckwith-Wiedemann syndrome and assisted reproduction technology (ART). J Med Genet. 2003;40(1):62\u20134.","journal-title":"J Med Genet"},{"issue":"6","key":"819_CR17","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1111\/cge.12096","volume":"84","author":"T Zhang","year":"2013","unstructured":"Zhang T, Xie X, Xu D, et al. Beckwith-Wiedemann syndrome: first epigenetic confirmed case report in China. Clin Genet. 2013;84(6):603\u20134.","journal-title":"Clin Genet"},{"key":"819_CR18","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13039-017-0347-z","volume":"10","author":"Q Wang","year":"2017","unstructured":"Wang Q, Geng Q, Zhou Q, et al. De novo paternal origin duplication of chromosome 11p15.5: report of two Chinese cases with Beckwith-Wiedemann syndrome. Mol Cytogenet. 2017;10:46.","journal-title":"Mol Cytogenet"},{"issue":"5","key":"819_CR19","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1086\/374824","volume":"72","author":"C Gicquel","year":"2003","unstructured":"Gicquel C, Gaston V, Mandelbaum J, et al. In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. Am J Hum Genet. 2003;72(5):1338\u201341.","journal-title":"Am J Hum Genet"}],"container-title":["Italian Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-020-0819-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13052-020-0819-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-020-0819-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T23:10:44Z","timestamp":1722813044000},"score":1,"resource":{"primary":{"URL":"https:\/\/ijponline.biomedcentral.com\/articles\/10.1186\/s13052-020-0819-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,29]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["819"],"URL":"https:\/\/doi.org\/10.1186\/s13052-020-0819-3","relation":{},"ISSN":["1824-7288"],"issn-type":[{"value":"1824-7288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,29]]},"assertion":[{"value":"11 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Written informed consent was obtained from the parents of the patients for the genetic study and publication of this study. The study was approved by the Regional Ethical Review Board in Shanghai Children\u2019s Hospital.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have read and approved the content, and they agree to submit it for consideration for publication in the journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"55"}}