{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T22:08:10Z","timestamp":1785708490969,"version":"3.56.0"},"reference-count":17,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dept. of Medical and Surgical Sciences of the University of Foggia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Loeys\u2013Dietz syndrome (LDS) is a rare autosomal-dominant disorder of the connective tissue with some typical vascular findings, skeletal manifestations, craniofacial features, and cutaneous findings with a wide phenotypic spectrum. Six different genes are involved in LDS and the diagnosis is based on the identification of a heterozygous pathogenic variant in TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, or SMAD2 in children with suggestive findings. These genes distinguish LDS into six classes (LDS1\u2013LDS6, respectively). Delay in diagnosis of Loeys\u2013Dietz syndrome may be associated with an adverse prognosis due to a very high augmented risk of early complications such as aortic or vascular rupture. The present report describes a case of an early diagnosis of LDS in a neonate with cleft soft palate and aortic root dilatation.<\/jats:p>","DOI":"10.3390\/children9091290","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T21:22:56Z","timestamp":1661721776000},"page":"1290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cleft Palate and Aortic Dilatation as Clues for Loeys\u2013Dietz Syndrome"],"prefix":"10.3390","volume":"9","author":[{"given":"Pierluigi","family":"Zaza","sequence":"first","affiliation":[{"name":"Ospedali Riuniti Foggia Italy-U.O.C. Neonatologia e Terapia Intensiva Neonatale, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9789-7878","authenticated-orcid":false,"given":"Flavia","family":"Indrio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science Pediatric Section, University of Foggia, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Fracchiolla","sequence":"additional","affiliation":[{"name":"Ospedali Riuniti Foggia Italy-U.O.C. Neonatologia e Terapia Intensiva Neonatale, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Ospedali Riuniti Foggia Italy-U.O.C. Neonatologia e Terapia Intensiva Neonatale, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Meliota","sequence":"additional","affiliation":[{"name":"Ospedale Giovanni XXIII U.O. Cardiologia Pediatrica, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Salatto","sequence":"additional","affiliation":[{"name":"DAI Materno-Infantile, Azienda Ospedaliera-Universitaria Federico II di Napoli, 80100 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4475-5280","authenticated-orcid":false,"given":"Antonio","family":"Bonacaro","sequence":"additional","affiliation":[{"name":"School of Health and Sports Sciences, University of Suffolk, Ipswich IP4 1QJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Maffei","sequence":"additional","affiliation":[{"name":"Ospedali Riuniti Foggia Italy-U.O.C. Neonatologia e Terapia Intensiva Neonatale, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-94-007-7893-1_7","article-title":"Loeys-Dietz Syndrome","volume":"Volume 802","author":"Halper","year":"2014","journal-title":"Progress in Heritable Soft Connective Tissue Diseases"},{"key":"ref_2","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Mirzaa, G.M., and Amemiya, A. (2008). Loeys-Dietz Syndrome. GeneReviews\u00ae, University of Washington."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Camerota, L., Ritelli, M., Wischmeijer, A., Majore, S., Cinquina, V., Fortugno, P., Monetta, R., Gigante, L., Marfan Syndrome Study Group Tor Vergata University Hospital, and Sangiuolo, F.C. (2019). Genotypic Categorization of Loeys-Dietz Syndrome Based on 24 Novel Families and Literature Data. Genes, 10.","DOI":"10.3390\/genes10100764"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/ng.744","article-title":"Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis","volume":"43","author":"Oldenburg","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1056\/NEJMoa055695","article-title":"Aneurysm syndromes caused by mutations in the TGF-beta receptor","volume":"355","author":"Loeys","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/ng.2348","article-title":"TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome","volume":"44","author":"Boileau","year":"2012","journal-title":"Nat. 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Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1199","DOI":"10.1542\/peds.2006-2886","article-title":"Importance of the Clinical Recognition of Loeys-Dietz Syndrome in the Neonatal Period","volume":"119","author":"Yetman","year":"2007","journal-title":"Pediatrics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/ajmg.a.33263","article-title":"Progressive aortic root and pulmonary artery aneurysms in a neonate with Loeys-Dietz syndrome type 1B","volume":"152A","author":"Muramatsu","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/gim.2014.11","article-title":"Loeys-Dietz syndrome: A primer for diagnosis and management","volume":"16","author":"MacCarrick","year":"2014","journal-title":"Genet. 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