{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:13:57Z","timestamp":1784110437948,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rubinstein\u2013Taybi syndrome (RSTS) is a rare genetic disorder characterized by distinctive craniofacial, limb, and developmental abnormalities, often identified postnatally. Prenatal diagnosis remains challenging due to a scarcity of ultrasound diagnostic markers and a wide range of phenotypic manifestations. We describe the case of a 28-year-old pregnant patient who presented to our center after fetal abnormalities such as aberrant cranial morphology, a shorter femur, and rocker-bottom feet were detected. A comprehensive ultrasound examination at 26 weeks revealed skeletal and craniofacial characteristics suggestive of RSTS, which prompted genetic counseling and molecular karyotyping. Single-nucleotide polymorphism (SNP) array analysis confirmed a loss on chromosome 16p13.3, including the CREB-binding protein (CREBBP) gene, confirming the suspicion. This case emphasizes the importance of genetic testing and sophisticated prenatal imaging in enabling an early and precise diagnosis of RSTS, offering important information on its prenatal phenotype and supporting family counseling. Extensive research becomes vital in establishing precise ultrasound markers for the early detection of RSTS during pregnancy.<\/jats:p>","DOI":"10.3390\/ijms26115142","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T03:52:08Z","timestamp":1748404328000},"page":"5142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Challenges in Prenatal Ultrasound Diagnosis of Rubinstein\u2013Taybi Syndrome: A Case Report and Comprehensive Literature Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2862-2069","authenticated-orcid":false,"given":"Daniela Roxana","family":"Matasariu","sequence":"first","affiliation":[{"name":"Department of Mother and Child, University of Medicine and Pharmacy \u2018Gr. T. Popa\u2019, 700115 Iasi, Romania"},{"name":"Department of Obstetrics and Gynecology, Cuza Voda Hospital, 700038 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iuliana-Elena","family":"Bujor","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, University of Medicine and Pharmacy \u2018Gr. T. Popa\u2019, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana Maria","family":"Gireada","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, University of Medicine and Pharmacy \u2018Gr. T. Popa\u2019, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza Maria","family":"Guzga","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nativia Clinic, 030167 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florina Mihaela","family":"Nedelea","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, 011171 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Titianu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Cuza Voda Hospital, 700038 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8207-7655","authenticated-orcid":false,"given":"Alexandra","family":"Ursache","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, University of Medicine and Pharmacy \u2018Gr. T. Popa\u2019, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"ref_1","first-page":"1447","article-title":"A clinical characteristics and genetic analysis of a case of Rubinstein-Taybi syndrome with glaucoma","volume":"25","author":"Huang","year":"2021","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_2","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. (2024). Rubinstein-Taybi Syndrome. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/cge.13493","article-title":"Fetal phenotype of Rubinstein-Taybi syndrome caused by CREBBP mutations","volume":"95","author":"Naudion","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s40477-020-00491-6","article-title":"Ultrasound 2-D and 3-D diagnosis of Rubinstein-Taybi syndrome in a 21-week-old fetus","volume":"25","author":"Ronzoni","year":"2022","journal-title":"J. Ultrasound"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/sj.ejhg.5201594","article-title":"Rubinstein-Taybi syndrome","volume":"14","author":"Hennekam","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/00019605-200207000-00017","article-title":"Dandy-Walker malformation in Rubinstein-Taybi syndrome: A rare association","volume":"11","author":"Agarwal","year":"2002","journal-title":"Clin. Dysmorphol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1590\/0004-282X20130207","article-title":"Broad thumbs and broad hallux: The hallmarks for the Rubinstein-Taybi syndrome","volume":"72","author":"Silva","year":"2014","journal-title":"Arq. Neuro-Psiquiatria"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/MCD.0000000000000143","article-title":"Rubinstein-Taybi syndrome type 2: Report of nine new cases that extend the phenotypic and genotypic spectrum","volume":"25","author":"Hamilton","year":"2016","journal-title":"Clin. Dysmorphol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4103\/0971-6866.100751","article-title":"Rubinstein-Taybi syndrome: Clinical profile of 11 patients and review of literature","volume":"18","author":"Kumar","year":"2012","journal-title":"Indian J. Hum. Genet."},{"key":"ref_10","first-page":"136","article-title":"Rubinstein-Taybi syndrom nebo-li syndrom sirok\u00fdch palc\u016f [The Rubinstein-Taybi syndrome or a broad thumb-hallux syndrome]","volume":"147","author":"Hosek","year":"2008","journal-title":"Cas. Lek. Ceskych"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13052-015-0110-1","article-title":"Rubinstein-Taybi syndrome: Clinical features, genetic basis, diagnosis, and management","volume":"41","author":"Milani","year":"2015","journal-title":"Ital. J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/cge.12348","article-title":"Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene","volume":"87","author":"Negri","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1002\/ajmg.a.33598","article-title":"Inheritance and variable expression in Rubinstein-Taybi syndrome","volume":"152A","author":"Bartsch","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"669","DOI":"10.7863\/jum.2009.28.5.669","article-title":"Prenatal sonographic diagnosis of Rubinstein-Taybi syndrome","volume":"28","author":"Greco","year":"2009","journal-title":"J. Ultrasound Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1002\/ajmg.a.36684","article-title":"Unusual prenatal presentation of Rubinstein-Taybi syndrome: A case report","volume":"164A","author":"Bedeschi","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1086\/429130","article-title":"Genetic heterogeneity in Rubinstein-Taybi syndrome: Mutations in both the CBP and EP300 genes cause disease","volume":"76","author":"Roelfsema","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","first-page":"1332","article-title":"A case of Rubinstein-Taybi syndrome and congenital neuroblastoma","volume":"164A","author":"Conneman","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/jum.14342","article-title":"Rubinstein-Taybi Syndrome in a Fetus: Contribution of 2- and 3-Dimensional Ultrasonography","volume":"37","author":"Cardalliac","year":"2017","journal-title":"J. Ultrasound Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13023-020-01378-9","article-title":"Role of the ADCY9 gene in cardiac abnormalities of the Rubinstein-Taybi syndrome","volume":"15","author":"Wu","year":"2020","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1002\/pd.6668","article-title":"Prenatal Sonographic Features of Rubinstein-Taybi Syndrome-A Small Case Series of a Rare Syndrome","volume":"44","author":"Zloto","year":"2024","journal-title":"Prenat. Diagn."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Al-Qattan, M.M., Jarman, A., Rafique, A., Al-Hassnan, Z.N., and Al-Qattan, H.M. (2019). Rubinstein-Taybi syndrome in a Saudi boy with distinct features and variants in both the CREBBP and EP300 genes: A case report. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0747-5"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ismagilova, O.R., Adyan, T.A., Beskorovainaya, T.S., and Polyakov, A.V. (2025). Molecular genetic analysis of Rubinstein-Taybi syndrome in Russian patients. Front. Genet., 16.","DOI":"10.3389\/fgene.2025.1516565"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/ajmg.1320260115","article-title":"Dominant inheritance of a syndrome similar to Rubinstein-Taybi","volume":"26","author":"Cotsirilos","year":"1987","journal-title":"Am. J. Med. Genet."},{"key":"ref_24","first-page":"3388879","article-title":"Rubinstein-Taybi Syndrome in a Filipino Infant with a Novel CREBBP Gene Pathogenic Variant","volume":"2022","author":"Yumul","year":"2022","journal-title":"Case Rep. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ejmhg.2012.03.009","article-title":"Facial dysmorphism, skeletal anomalies, congenital glucoma, dysplastic nails: Mild Rubinstein-Taybi Syndrome","volume":"13","author":"Shawky","year":"2012","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"L\u00f3pez, M., Seidel, V., Santib\u00e1\u00f1ez, P., Cervera-Acedo, C., Castro-de Castro, P., and Dom\u00ednguez-Garrido, E. (2016). First case report of inherited Rubinstein-Taybi syndrome associated with a novel EP300 variant. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0361-8"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/pbc.24765","article-title":"Rubinstein-Taybi syndrome predisposing to non-WNT, non-SHH, group 3 medulloblastoma","volume":"61","author":"Bourdeaut","year":"2014","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, Y.R., Lin, Y.C., Chang, Y.H., Huang, H.Y., Hong, Y.K., Aala, W.F., Tu, W.T., Tsai, M.C., Chou, Y.Y., and Hsu, C.-K. (2022). Genetic Diagnosis of Rubinstein\u2013Taybi Syndrome With Multiplex Ligation-Dependent Probe Amplification (MLPA) and Whole-Exome Sequencing (WES): Case Series with a Novel CREBBP Variant. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.848879"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Azam, H.M.H., R\u00f6\u00dfling, R.I., Geithe, C., Khan, M.M., Dinter, F., Hanack, K., Pr\u00fc\u00df, H., Husse, B., Roggenbuck, D., and Schierack, P. (2024). MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: A comprehensive review. Front. Mol. Neurosci., 17.","DOI":"10.3389\/fnmol.2024.1386735"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1161\/ATVBAHA.112.300141","article-title":"MicroRNAs within the continuum of postgenomics biomarker discovery","volume":"33","author":"Mayr","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1055\/s-0035-1564571","article-title":"Ultra-Rare Syndromes: The Example of Rubinstein-Taybi Syndrome","volume":"4","author":"Spena","year":"2015","journal-title":"J. Pediatr. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.4103\/1119-3077.170820","article-title":"Ethical and legal dilemmas around termination of pregnancy for severe fetal anomalies: A review of two African neonates presenting with ventriculomegaly and holoprosencephaly","volume":"18","author":"Chima","year":"2015","journal-title":"Niger. J. Clin. Pract."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5142\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:41:32Z","timestamp":1760031692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115142"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115142","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,27]]}}}