{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:46:04Z","timestamp":1760060764891,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background and Clinical Significance: Binder syndrome or maxillonasal dysplasia is a rare developmental disorder affecting the anterior maxilla and nasal complex, characterized by midfacial hypoplasia, a flattened nasal bridge, and increased nasofrontal angle. Case Presentation: We present a case series of seven fetuses diagnosed with Binder phenotype through targeted ultrasound examination at our prenatal diagnosis center during the SARS-CoV-2 pandemic, between September 2021 and July 2023, including the first case described in the literature before 14 weeks. The median gestational age at diagnosis was 21 weeks. Ultrasound features included flattened fetal facial profile, increased nasofrontal angle (&gt;143\u00b0), verticalized nasal bones and widened maxillary alveolar arch. Five cases presented as isolated anomalies, while two showed associated findings including growth restriction and polyhydramnios. Invasive prenatal diagnosis was offered in all cases, with three patients consenting to amniocentesis, all revealing normal karyotype and chromosomal microarray. Pregnancy outcomes varied: three patients opted for termination of pregnancy, one case resulted in intrauterine fetal demise, one delivered prematurely with confirmed postnatal phenotype, and two continued pregnancy with normal delivery. Conclusions: This relatively high case frequency within a short timeframe suggests that Binder syndrome, while rare, may not be as uncommon as previously reported. Accurate ultrasound diagnosis combined with comprehensive genetic counseling enables appropriate pregnancy management and optimal perinatal outcomes.<\/jats:p>","DOI":"10.3390\/reports8030188","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T11:18:16Z","timestamp":1758539896000},"page":"188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal Ultrasound Diagnosis of Binder Phenotype: Case Series of Seven Patients and Literature Review"],"prefix":"10.3390","volume":"8","author":[{"given":"Silvia","family":"Andrietti","sequence":"first","affiliation":[{"name":"Prenatal Diagnosis and Perinatal Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5994-4485","authenticated-orcid":false,"given":"Alessia","family":"Maccarrone","sequence":"additional","affiliation":[{"name":"Department of Neurology, Rehabilitation, Ophtalmology, Genetics, Maternal and Infant Health (DiNOGMI), 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4269-4269","authenticated-orcid":false,"given":"Giuseppe","family":"Gullo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Billone","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4631-1061","authenticated-orcid":false,"given":"Lina","family":"De Paola","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Gaggero","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis and Perinatal Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diliana","family":"Beleva","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis and Perinatal Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Calcagno","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis and Perinatal Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierangela","family":"De Biasio","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis and Perinatal Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1097\/SCS.0b013e3181ef2b71","article-title":"Binder Phenotype: Associated Findings and Etiologic Mechanisms","volume":"21","author":"Wenzel","year":"2010","journal-title":"J. Craniofac Surg."},{"key":"ref_2","first-page":"160","article-title":"Prenatal Diagnosis of Binder Phenotype, Naso-Maxillar Hypoplasia","volume":"66","author":"Pop","year":"2020","journal-title":"Acta Marisiensis\u2014Ser. Medica"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Beighton, P., and Beighton, G. (1997). The Person Behind the Syndrome, Springer.","DOI":"10.1007\/978-1-4471-0925-9"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1136\/jmg.27.6.384","article-title":"Maxillonasal Dysplasia (Binder\u2019s Syndrome)","volume":"27","author":"Quarrell","year":"1990","journal-title":"J. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"025","DOI":"10.1055\/s-0044-1786170","article-title":"Binder Phenotype\u2014Prenatal Diagnosis, Management, and Postnatal Outcome: Insights from a Case Series and Updated Review of the Literature","volume":"11","author":"Brinda","year":"2024","journal-title":"J. Fetal Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/pd.2167","article-title":"Binder Phenotype: Clinical and Etiological Heterogeneity of the so-Called Binder Maxillonasal Dysplasia in Prenatally Diagnosed Cases, and Review of the Literature","volume":"29","author":"Levaillant","year":"2009","journal-title":"Prenat. Diagn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1046\/j.1469-0705.2000.00259.x","article-title":"The Prenatal Diagnosis of Binder Syndrome before 24 Weeks of Gestation: Case Report","volume":"16","author":"Cook","year":"2000","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000085090","article-title":"Maxillo-Nasal Dysplasia (Binder Syndrome): Antenatal Discovery and Implications","volume":"20","author":"Cuillier","year":"2005","journal-title":"Fetal Diagn. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s00247-018-4098-8","article-title":"Severe Nasomaxillary Hypoplasia (Binder Phenotype) on Prenatal US\/MRI: An Important Marker for the Prenatal Diagnosis of Chondrodysplasia Punctata","volume":"48","author":"Blask","year":"2018","journal-title":"Pediatr. Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s40556-020-00283-2","article-title":"Prenatal Binder Phenotype: Physician\u2019s Dilemma-A Case Report","volume":"8","author":"Gupta","year":"2021","journal-title":"J. Fetal Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"279","DOI":"10.12891\/ceog2089.2016","article-title":"Prenatal Diagnosis of Binder\u2019s Syndrome: Report of Two Cases","volume":"43","author":"Cantarell","year":"2016","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1002\/uog.24888","article-title":"ISUOG Practice Guidelines (Updated): Performance of the Routine Mid-Trimester Fetal Ultrasound Scan","volume":"59","author":"Salomon","year":"2022","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/uog.984","article-title":"Two- and Three-Dimensional Sonographic Assessment of the Fetal Face. 1. A Systematic Analysis of the Normal Face","volume":"23","author":"Rotten","year":"2004","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/jcu.20735","article-title":"Evaluation of Fetal Nasofrontal Angle in the Second Trimester in Normal Pregnancies","volume":"39","author":"Ipek","year":"2011","journal-title":"J. Clin. Ultrasound"},{"key":"ref_15","first-page":"42","article-title":"Enhancing Patient Safety and Delineating Professional Liability in Radiological Procedures Involving Contrast Medium Administration","volume":"176","author":"Martines","year":"2025","journal-title":"Clin. Ter."},{"key":"ref_16","first-page":"64","article-title":"Assessment of the Informed Consent Related to Healthcare Decisions for Medically Fragile Child in Italy: A Pilot Study","volume":"175","author":"Bruno","year":"2024","journal-title":"Clin. Ter."},{"key":"ref_17","first-page":"5290","article-title":"Ethical and Medico-Legal Remarks on Uterus Transplantation: May It Solve Uterine Factor Infertility?","volume":"21","author":"Zaami","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20251144","DOI":"10.1515\/med-2025-1144","article-title":"The Era of Increasing Cancer Survivorship: Trends in Fertility Preservation, Medico-Legal Implications, and Ethical Challenges","volume":"20","author":"Napoletano","year":"2025","journal-title":"Open Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1007\/s00404-024-07722-9","article-title":"Obstetric Violence: If You Can Recognize It, You Can Prevent It","volume":"310","author":"Napoletano","year":"2024","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_20","first-page":"240","article-title":"Binders Syndrome: A Review","volume":"4","author":"Subhada","year":"2019","journal-title":"Saudi J. Oral. Dent. Res."},{"key":"ref_21","unstructured":"Zuckerkandl, E. (1892). Normale und Pathologische Anatomie der Nasenh\u00f6hle und Ihrer Pneumatischen Anh\u00e4nge, Wilhelm Braum\u00fcller."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1177\/028418518402500501","article-title":"Maxillo-Nasal Dysplasia (Binder Syndrome) and Associated Malformations of the Cervical Spine","volume":"25","year":"1984","journal-title":"Acta Radiol. Diagn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/uog.19198","article-title":"Binder Syndrome: A Phenotype Rather than a Definitive Diagnosis?","volume":"53","author":"Mazzone","year":"2019","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.anorl.2019.03.002","article-title":"Is Palato-Premaxillary Subduction a Characteristic of Binder\u2019s Syndrome?","volume":"136","author":"Nguyen","year":"2019","journal-title":"Eur. Ann. Otorhinolaryngol. Head. Neck Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.bjorl.2015.08.017","article-title":"Nasal Reconstruction in Binder Syndrome","volume":"83","author":"Arroyo","year":"2017","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102836","DOI":"10.1016\/j.jogoh.2024.102836","article-title":"Obstetrics and Neonatal Outcomes of Binder Phenotype with Antenatal Diagnosis: A Case Report and Literature Review","volume":"53","author":"Bosco","year":"2024","journal-title":"J. Gynecol. Obstet. Human. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.7863\/ultra.15.02050","article-title":"Prenatally Diagnosed Cases of Binder Phenotype Complicated by Respiratory Distress in the Immediate Postnatal Period","volume":"35","author":"Blumenfeld","year":"2016","journal-title":"J. Ultrasound Med."},{"key":"ref_28","first-page":"331","article-title":"Familial Variant of Maxillonasal Dysplasia?","volume":"6","author":"Navon","year":"1986","journal-title":"J. Craniofac Genet. Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1834-7819.1992.tb05901.x","article-title":"Binder\u2019s Syndrome Due to Prenatal Vitamin K Deficiency: A Theory of Pathogenesis","volume":"37","author":"Howe","year":"1992","journal-title":"Aust. Dent. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4081\/aiua.2020.2.121","article-title":"The Impact of Nutrition and Lifestyle on Male Fertility","volume":"92","author":"Benatta","year":"2020","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1834-7819.1994.tb01379.x","article-title":"Vitamin K\u2013Its Essential Role in Craniofacial Development. A Review of the Literature Regarding Vitamin K and Craniofacial Development","volume":"39","author":"Howe","year":"1994","journal-title":"Aust. Dent. J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gullo, G., Scaglione, M., Buzzaccarini, G., Lagan\u00e0, A.S., Basile, G., Chiantera, V., Cucinella, G., and Zaami, S. (2022). Cell-Free Fetal DNA and Non-Invasive Prenatal Diagnosis of Chromosomopathies and Pediatric Monogenic Diseases: A Critical Appraisal and Medicolegal Remarks. J. Pers. Med., 13.","DOI":"10.3390\/jpm13010001"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/nyas.12866","article-title":"Preventing the Transmission of Mitochondrial DNA Disorders Using Prenatal or Preimplantation Genetic Diagnosis","volume":"1350","author":"Smeets","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gullo, G., Scaglione, M., Cucinella, G., Riva, A., Coldebella, D., Cavaliere, A.F., Signore, F., Buzzaccarini, G., Spagnol, G., and Lagan\u00e0, A.S. (2022). Congenital Zika Syndrome: Genetic Avenues for Diagnosis and Therapy, Possible Management and Long-Term Outcomes. J. Clin. Med., 11.","DOI":"10.3390\/jcm11051351"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e079364","DOI":"10.1136\/bmj-2024-079364","article-title":"COVID-19 Infection and Vaccination during First Trimester and Risk of Congenital Anomalies: Nordic Registry Based Study","volume":"386","author":"Magnus","year":"2024","journal-title":"BMJ"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100214","DOI":"10.1016\/j.ajogmf.2020.100214","article-title":"Obstetrics and Gynecology Emergency Services during the Coronavirus Disease 2019 Pandemic","volume":"2","author":"Salsi","year":"2020","journal-title":"Am. J. Obstet. Gynecol. MFM"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s00404-021-06212-6","article-title":"Obstetric A&E Unit Admission and Hospitalization for Obstetrical Management during COVID-19 Pandemic in a Third-Level Hospital of Southern Italy","volume":"305","author":"Carbone","year":"2022","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_38","first-page":"36","article-title":"Hospitalizations for Obstetrical Conditions During and After the COVID-19 Pandemic","volume":"50","author":"Preda","year":"2024","journal-title":"Curr. Health Sci. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1365-3016.2008.00965.x","article-title":"Comparison of Gestational Age at Birth Based on Last Menstrual Period and Ultrasound during the First Trimester","volume":"22","author":"Hoffman","year":"2008","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_40","unstructured":"National Collaborating Centre for Women\u2019s and Children\u2019s Health (UK) (2008). Antenatal Care: Routine Care for the Healthy Pregnant Woman, RCOG Press. National Institute for Health and Clinical Excellence: Guidance."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/j.1471-0528.2010.02592.x","article-title":"First-Trimester Ultrasound Dating of Twin Pregnancy: Are Singleton Charts Reliable?","volume":"117","author":"Dias","year":"2010","journal-title":"BJOG"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/j.1471-0528.2006.00953.x","article-title":"Detection of Malformations in Chromosomally Normal Fetuses by Routine Ultrasound at 12 or 18 Weeks of Gestation-a Randomised Controlled Trial in 39,572 Pregnancies","volume":"113","author":"Saltvedt","year":"2006","journal-title":"BJOG"},{"key":"ref_43","first-page":"400","article-title":"Fetal Nasal Bone Length in Chromosomally Normal and Abnormal Fetuses at 11\u201314 Weeks of Gestation","volume":"11","author":"Cicero","year":"2002","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/uog.176","article-title":"Learning Curve for Sonographic Examination of the Fetal Nasal Bone at 11\u201314 Weeks","volume":"22","author":"Cicero","year":"2003","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000078499","article-title":"Nasal Bone Measurement during the 1st Trimester: Is It Useful?","volume":"58","author":"Kelekci","year":"2004","journal-title":"Gynecol. Obstet. Invest."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/uog.41","article-title":"Nasal Bone Length throughout Gestation: Normal Ranges Based on 3537 Fetal Ultrasound Measurements","volume":"21","author":"Sonek","year":"2003","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1111\/j.1447-0756.2010.01297.x","article-title":"Frontonasal Facial Angle in Chromosomally Normal Fetuses at 11+0 to 13+6 Weeks","volume":"36","author":"Vicario","year":"2010","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhou, X., Ji, C., Sun, L., Yin, L., Deng, X., Pan, Q., Zhang, J., Yang, Z., Zheng, C., and Ling, C. (2022). Clinical Value of Fetal Facial Profile Markers during the First Trimester. BMC Pregnancy Childbirth, 22.","DOI":"10.1186\/s12884-022-05028-9"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/uog.3907","article-title":"Frontomaxillary Facial Angle at 11+0 to 13+6 Weeks\u2019 Gestation-Reproducibility of Measurements","volume":"29","author":"Plasencia","year":"2007","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"International Society of Ultrasound in Obstetrics and Gynecology, Bilardo, C.M., Chaoui, R., Hyett, J.A., Kagan, K.O., Karim, J.N., Papageorghiou, A.T., Poon, L.C., Salomon, L.J., and Syngelaki, A. (2023). ISUOG Practice Guidelines (Updated): Performance of 11\u201314-Week Ultrasound Scan. Ultrasound Obstet. Gynecol., 61, 127\u2013143.","DOI":"10.1002\/uog.26106"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s10462-025-11160-7","article-title":"A Comprehensive Review of Artificial Intelligence\u2014Based Algorithm towards Fetal Facial Anomalies Detection (2013\u20132024)","volume":"58","author":"Sriraam","year":"2025","journal-title":"Artif. Intell. Rev."},{"key":"ref_52","first-page":"77","article-title":"Artificial Intelligence in the Service of Medicine: Current Solutions and Future Perspectives, Opportunities, and Challenges","volume":"176","author":"Marinelli","year":"2025","journal-title":"Clin Ter"}],"container-title":["Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2571-841X\/8\/3\/188\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:59Z","timestamp":1760035619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2571-841X\/8\/3\/188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["reports8030188"],"URL":"https:\/\/doi.org\/10.3390\/reports8030188","relation":{},"ISSN":["2571-841X"],"issn-type":[{"type":"electronic","value":"2571-841X"}],"subject":[],"published":{"date-parts":[[2025,9,22]]}}}