{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:10:23Z","timestamp":1772169023353,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.3-33.v1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T00:00:00Z","timestamp":1432684800000}}],"reference-count":21,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T00:00:00Z","timestamp":1432684800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Cornelia de Lange Syndrome (CdLS) (also called Bushy Syndrome or Amsterdam dwarfism), is a genetic disorder that can lead to several alterations. This disease affects both physical and neuropsychiatric development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation.<\/ns4:p>\n                  <ns4:p>We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy.<\/ns4:p>","DOI":"10.12688\/f1000research.3-33.v2","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T07:06:26Z","timestamp":1432710386000},"page":"33","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Atypical Cornelia de Lange Syndrome"],"prefix":"10.12688","volume":"3","author":[{"given":"Vito","family":"Leanza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Rubbino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Leanza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2015,5,27]]},"reference":[{"key":"ref-1","first-page":"412-3","article-title":"Cornelia de Lange syndrome.","volume":"22","author":"N Noor","year":"2012","journal-title":"J Coll Physicians Surg Pak."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"22-3","DOI":"10.1097\/MCD.0b013e32834c4afc","article-title":"An atypical facial appearance and growth pattern in a child with Cornelia de Lange Syndrome: an intragenic deletion predicting loss of the N-terminal region of NIPBL.","volume":"21","author":"J Murray","year":"2012","journal-title":"Clin Dysmorphol."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"507-15","DOI":"10.1016\/j.gyobfe.2007.03.012","article-title":"Increased nuchal translucency with normal karyotype.","volume":"35","author":"M Senat","year":"2007","journal-title":"Gynecol Obstet Fertil."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"34-41","DOI":"10.1002\/uog.10059","article-title":"Increased nuchal translucency and normal karyotype: perinatal and pediatric outcomes at 2 years of age.","volume":"39","author":"R Mula","year":"2012","journal-title":"Ultrasound Obstet Gynecol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"567-569","DOI":"10.1002\/(SICI)1097-0223(199906)19:6<567::AID-PD581>3.0.CO;2-P","article-title":"The prenatal diagnosis of Pierre-Robin sequence.","volume":"19","author":"Y Hsieh","year":"1999","journal-title":"Prenat Diagn."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"333-336","DOI":"10.1136\/adc.81.4.333","article-title":"Behavioural phenotype of Cornelia de Lange syndrome.","volume":"81","author":"T Berney","year":"1999","journal-title":"Arch Dis Child."},{"key":"ref-7","first-page":"713-719","article-title":"Sur un type nouveau d degenerescence (typus Amestelodamensis)","volume":"36","author":"C de Lange","year":"1933"},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"568-575","DOI":"10.1136\/jmg.2005.038240","article-title":"Genotype-phenotype correlations of 39 patients with Cornelia de Lange syndrome: the Dutch experience.","volume":"43","author":"Z  Bhuiyan","year":"2006","journal-title":"J Med Genet."},{"key":"ref-9","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/568351","article-title":"Three-dimensional ultrasound findings in cornelia de lange syndrome: a case report.","volume":"2012","author":"Y Akahori","year":"2012","journal-title":"Obstet Gynecol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"341-2","DOI":"10.1002\/uog.12285","article-title":"Ultrasound Detection of Eyelashes: A Clue for Prenatal Diagnosis of Cornelia de Lange Syndrome.","volume":"41","author":"E Spaggiari","year":"2013","journal-title":"Ultrasound Obstet Gynecol."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3389\/fgene.2012.00171","article-title":"Diverse developmental disorders from the one ring: distinct molecular pathways underlie the cohesinopathies.","volume":"3","author":"J Horsfield","year":"2012","journal-title":"Front Genet."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"313-7","DOI":"10.1038\/nature11316","article-title":"HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.","volume":"489","author":"M Deardorff","year":"2012","journal-title":"Nature."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"1848-56","DOI":"10.1002\/ajmg.a.35410","article-title":"Identification of a prenatal profile of Cornelia de Lange syndrome (CdLS): a review of 53 CdLS pregnancies.","volume":"158A","author":"D Clark","year":"2012","journal-title":"Am J Med Genet A."},{"key":"ref-14","article-title":"Cornelia de Lange Syndrome","author":"M Deardorff","year":"2011"},{"key":"ref-15","article-title":"Fundamental obstetric and gynecologic elements.","author":"V Leanza","year":"2011"},{"key":"ref-16","article-title":"OBSTETRICS","author":"V Leanza","year":"2009"},{"key":"ref-17","first-page":"218-20","article-title":"Incisional hernia in Day Surgery: our personal experience.","volume":"33","author":"G Zangh\u00ec","year":"2012","journal-title":"G Chir."},{"key":"ref-18","first-page":"41-48","article-title":"A specific application of two psychological measures on female urinary incontinence: perceived negative affective self-efficacy scale and stress psychological measure.","volume":"25","author":"V Leanza","year":"2011","journal-title":"Urogynaecologia International Journal."},{"key":"ref-19","first-page":"262-264","article-title":"Double atresic uterus associated with agenesis of cervix and third upper of vagina.","volume":"35","author":"G Leanza","year":"2013","journal-title":"Giornale Italiano di Ostetricia e Ginecologia."},{"key":"ref-20","first-page":"259-263","article-title":"Epidemiological study on toxoplasmosis in pregnancy: Effectiveness of the screening.","volume":"33","author":"F Genovese","year":"2011","journal-title":"Giornale Italiano di Ostetricia e Ginecologia."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"407-11","DOI":"10.3275\/8658","article-title":"High prevalence of thyroid dysfunction in pregnant women.","volume":"36","author":"M Altomare","year":"2013","journal-title":"J Endocrinol Invest."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/3-33\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/3-33\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/3-33\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T14:48:30Z","timestamp":1543848510000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/3-33\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,27]]},"references-count":21,"URL":"https:\/\/doi.org\/10.12688\/f1000research.3-33.v2","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.4647.r8779","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.4647.r4026","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.4647.r8779","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.4647.r4026","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,27]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/3-33\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.1212.r3450, Jinglan Liu, Department of Pediatrics, Drexel University, Philadelphia, PA, USA, 14 Feb 2014, version 1, 2 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/3-33\/v1#referee-response-3450","order":0,"name":"referee-response-3450","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>vito leanza<\/b>; \n<i>Posted: 01 Sep 2014<\/i>; \n<i>\u201cData from mutational testing on known CdLS genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) would be important for this case. The article published by <\/i>\n<i>Clark et al. (2012)<\/i>\n<i> which was also cited by the authors, recommends molecular analysis of CdLS genes to prenatal diagnosis of CdLS.\u201d<\/i>In our case report, data from mutational testing on known CdLS genes (\n<i>NIPBL, SMC1A, SMC3, RAD21<\/i>, and \n<i>HDAC8<\/i>) are negative , indeed it was called atypical Cornelia de Lange Syndrome (CdLS).Mutations in \n<i>NIPBL<\/i>&nbsp;are not present in all cases and they account for about 60% of CdLS; mutations in \n<i>SMC1A<\/i> and \n<i>SMC3<\/i> account for a small percentage (Deardorff \n<i>et al.<\/i>, 2011).&nbsp;\n<i>\u201cThe authors should compare prenatal findings in the current case with what described in the article by <\/i>\n<i>Clark et al. (2012)<\/i>\n<i>.<\/i>\n<i> Without molecular testing data, I would like to see a table demonstrating the current case presenting prenatal clinical features consistent with what has been documented in the literature by studying a larger cohort of probands.\u201d<\/i>Cornelia de Lange Syndrome (CdLS) is a multisystem developmental disorder characterized by growth retardation, cognitive impairment, external and internal structural malformations, and characteristic facial features. Currently, there are no definitive prenatal screening measures that lead to the diagnosis of CdLS. (Clark \n<i>et al. <\/i>2012).In our case (atypical CdLS) &nbsp;increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation were found.Fewer than 1% of individuals diagnosed with Cornelia de Lange syndrome have an affected parent.Recommendations for the evaluation of parents of a proband with an apparent \n<i>de novo<\/i> mutation include clinical examination for features of CdLS, complete with plotting of growth parameters and molecular genetic testing if the NIPBL mutation has been identified in the proband. In our&nbsp;atypical Cornelia de Lange syndrome molecular tests of parents were negative.&nbsp;&nbsp;\n<i>\u201cIn the discussion, in the beginning of first paragraph, the authors claim that CdLS is diagnosed primarily by morphological characteristic and cited a paper published in 1933. At present, the diagnosis criteria of CdLS cannot be the same as what was 90 years ago, particularly with the identification of specific gene mutations in CdLS probands. Please re-phrase this part, and cite updated references.\u201d<\/i>Diagnosis is based on clinical findings. High-resolution ultrasound examination to follow growth and to evaluate the limbs, heart, diaphragm, palate, and other organs or structures affected in CdLS is fundamental. Reported prenatal ultrasound findings include: increased nuchal translucency in the first trimester [Sekimoto \n<i>et al.<\/i>, 2000; Huang &amp; Porto, 2002]; Growth failure, which typically presents in the second trimester; and the typical \n<i>in utero<\/i> facial profile of a fetus with CdLS consisting of micrognathia, a prominent upper lip, and a depressed nasal bridge with somewhat anteverted nares [Ranzini \n<i>et al<\/i>., 1997; Boog \n<i>et al.,<\/i> 1999; Urban &amp; Hartung, 2001].&nbsp;\n<i>\u201cIn the end of the discussion, what does it mean \u201cgenetic tests are not reliable\u201d? As a matter of fact, molecular testing has become a widely accepted concept and a popular diagnostic approach for individuals with congenital anormalies.\u201d<\/i>Genetic tests are not reliable when negative. On the contrary when positive they are important for syndrome.Indeed, mutations in NIPBL&nbsp; are not present in all cases and they account for about 60% of CdLS; mutations in SMC1A and SMC3 account for a small percentage (Deardorff \n<i>et al.<\/i>, 2011).Minor things:These minor things are easy to correct. I thank the first referee for his clarifications.","URL":"https:\/\/f1000research.com\/articles\/3-33\/v2#referee-comment-957","order":1,"name":"referee-comment-957","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.4647.r8779, Laird Jackson, Department of Obstetrics and Gynecology, Drexel University, Philadelphia, PA, USA, 28 May 2015, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/3-33\/v2#referee-response-8779","order":2,"name":"referee-response-8779","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.4647.r4026, Orkun \u00c7etin, Obstetrics and Gynecology, Istanbul Suleymaniye Birth and Gynecology Training and Research Hospital, Istanbul, Turkey, 10 Dec 2015, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/3-33\/v2#referee-response-4026","order":3,"name":"referee-response-4026","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}