{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T09:29:02Z","timestamp":1792834142270,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths. Workup revealed the absence of the corpus callosum and the presence of a brain midline lipoma, wide sutures, and a Chiari I malformation with cerebellar herniation. We conducted a systematic review of the literature and compared all the cases described as diprosopus. In 96% of these, the central nervous system is affected, with anencephaly being the most commonly associated abnormality. Other associated anomalies include cardiac malformations (86%), cleft palate (63%), diaphragmatic hernia (13%), and disorder of sex development (DSD) (13%). Although the facial features are those that first strike the eye, the almost obligate presence of cerebral malformations suggests a disruptive event in the cephalic pole of the forming embryo. No major monogenic contribution has been recognized today for this type of malformation.<\/jats:p>","DOI":"10.3390\/genes14091745","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T09:42:53Z","timestamp":1693474973000},"page":"1745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Diprosopus: A Rare Case of Craniofacial Duplication and a Systematic Review of the Literature"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5224-8073","authenticated-orcid":false,"given":"Viola","family":"Trevisani","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, Department of Mother and Child, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Post-Graduate School of Pediatrics, Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Balestri","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Mother and Child, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Napoli","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-7854","authenticated-orcid":false,"given":"Stefano Giuseppe","family":"Caraffi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Mother and Child, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6184-6582","authenticated-orcid":false,"given":"Maria Chiara","family":"Baroni","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Mother and Child, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"},{"name":"Department of Medical and Surgical Science, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Peluso","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Mother and Child, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5869-2068","authenticated-orcid":false,"given":"Anna","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Biomedical Technologies, School of Dentistry, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-7872","authenticated-orcid":false,"given":"Lorenzo","family":"Iughetti","sequence":"additional","affiliation":[{"name":"Post-Graduate School of Pediatrics, Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Gargano","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Mother and Child, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3543-7531","authenticated-orcid":false,"given":"Andrea","family":"Superti-Furga","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Lausanne University Hospital (CHUV), University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Garavelli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Mother and Child, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/tera.1420250205","article-title":"Facial duplication: Case, review, and embryogenesis","volume":"25","author":"Barr","year":"1982","journal-title":"Teratology"},{"key":"ref_2","unstructured":"Gorlin, R.J., Cohen, M.M.J., and Levin, L.S. (1990). Syndrome of the Head and Neck, Oxford University Press. [3rd ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ajmg.a.30694","article-title":"Craniofacial defects of blastogenesis: Duplication of pituitary with cleft palate and orophgaryngeal tumors","volume":"135","author":"Slavotinek","year":"2005","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1097\/SCS.0b013e3182953b1f","article-title":"Clinical presentation of epignathus teratoma with cleft palate; and duplication of cranial base, tongue, mandible, and pituitary gland","volume":"24","author":"Maeda","year":"2013","journal-title":"J. Craniofac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1399-0004.1983.tb00079.x","article-title":"Aberrant twinning (diprosopus) associated with anencephaly","volume":"24","author":"Moerman","year":"1983","journal-title":"Clin. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"687","DOI":"10.3109\/00016348509158218","article-title":"Prenatal diagnosis of conjoined twins (diprosopus) with myelomeningocele","volume":"64","author":"Rydnert","year":"1985","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/ajmg.1320280112","article-title":"Diprosopus with associated malformations: Report of two cases","volume":"28","author":"Pavone","year":"1987","journal-title":"Am. J. Med. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0028-2243(94)01937-3","article-title":"Craniofacial duplication (diprosopus): Report of a case with a review of the literature","volume":"58","author":"Amr","year":"1995","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1002\/ajmg.a.10195","article-title":"Conjoined twins: Morphogenesis of the heart and a review","volume":"120A","author":"Opitz","year":"2003","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3109\/15513815.2010.505628","article-title":"Diprosopus conjoined twins: Radiologic, autoptic, and histologic study of a case","volume":"29","author":"Falleti","year":"2010","journal-title":"Fetal Pediatr. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1017\/thg.2014.20","article-title":"Siamese twins with craniofacial duplication and bilateral cleft lip\/palate in a ceramic representation of the Chim\u00fa culture (Peru): A comparative analysis with a current case","volume":"17","author":"Pachajoa","year":"2014","journal-title":"Twin Res. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/bdra.23549","article-title":"Diprosopus: Systematic review and report of two cases","volume":"106","author":"Bidondo","year":"2016","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e192","DOI":"10.1097\/IOP.0000000000001238","article-title":"A Case of Diprosopus Tetraophthalmos: Ocular Findings and Surgical Treatment of Exposure Keratopathy","volume":"34","author":"Yazici","year":"2018","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13023-023-02617-5","article-title":"Brain malformations in diprosopia observed in clinical cases, museum specimens and artistic representations","volume":"18","author":"Rehder","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/bdra.23327","article-title":"Oropharyngeal teratoma, oral duplication, cervical diplomyelia and anencephaly in a 22-week fetus: A review of the craniofacial teratoma syndrome","volume":"103","author":"Morlino","year":"2015","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.7453\/gahmj.2013.008","article-title":"The CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development","volume":"2","author":"Gagnier","year":"2013","journal-title":"Glob. Adv. Health Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ydbio.2016.02.009","article-title":"Hedgehog receptor function during craniofacial development","volume":"415","author":"Xavier","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0028-2243(80)90083-0","article-title":"Etiological aspects of double monsters","volume":"10","author":"Jaschevatzky","year":"1980","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"374","DOI":"10.2350\/08-11-0555.1","article-title":"Janiceps conjoined twins with extreme asymmetry: Case report with complete autopsy and histopathologic findings","volume":"12","author":"Kastenbaum","year":"2009","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/(SICI)1097-0223(199806)18:6<618::AID-PD304>3.0.CO;2-A","article-title":"Antenatal diagnosis of complete facial duplication--a case report of a rare craniofacial defect","volume":"18","author":"Rai","year":"1998","journal-title":"Prenat. Diagn."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1148\/radiol.2261011754","article-title":"Craniofacial duplication (diprosopus): CT, MR imaging, and MR angiography findings case report","volume":"226","author":"Schramm","year":"2003","journal-title":"Radiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1159\/000076706","article-title":"Diprosopus associated with neural tube defect and facial cleft in the first trimester","volume":"19","author":"Bulbul","year":"2004","journal-title":"Fetal Diagn. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1097\/01.prs.0000252247.55433.43","article-title":"Operative correction and follow-up of craniofacial duplication","volume":"119","author":"Kotrikova","year":"2007","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1159\/000109232","article-title":"Prenatal diagnosis of monocephalic bifacial tetraophthalmic diprosopus (conjoined twin)","volume":"23","author":"Dhaifalah","year":"2008","journal-title":"Fetal Diagn. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1259\/bjr\/79093458","article-title":"Diprosopus tetraophthalmus: CT as a complement to autopsy","volume":"85","author":"Laor","year":"2012","journal-title":"Br. J. Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1447-0756.2011.01708.x","article-title":"First trimester diagnosis of parapagus diprosopus dibrachius dipus twins with cranirachischisis totalis by three-dimensional ultrasound","volume":"38","author":"Akyer","year":"2012","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10943-013-9737-7","article-title":"Ischiopagus and diprosopus in India: Two pairs of conjoined twins perceived as incarnations of Hindu deities","volume":"54","author":"Tubbs","year":"2015","journal-title":"J. Relig. Health"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.tjog.2015.10.010","article-title":"Prenatal diagnosis of parapagus diprosopus dibrachius dipus twins with spina bifida in the first trimester using two- and THREE-dimensional ultrasound","volume":"54","author":"Yang","year":"2015","journal-title":"Taiwan J. Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.4103\/ajns.AJNS_202_17","article-title":"Diprosopus a Rare Craniofacial Malformation","volume":"13","author":"Bhuyan","year":"2018","journal-title":"Asian J. Neurosurg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0165-5876(98)00044-5","article-title":"Supernumerary nostril: A rare congenital deformity","volume":"44","author":"Williams","year":"1998","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1597\/06-115.1","article-title":"Supernumerary nostril with complete unilateral cleft lip: A case report and review","volume":"44","author":"Powar","year":"2007","journal-title":"Cleft Palate Craniofac. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000209400","article-title":"Supernumerary nostril. A rare congenital nasal deformity: Case report and literature review","volume":"42","author":"Sun","year":"2009","journal-title":"Eur. Surg. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1097\/SCS.0b013e3181d879d8","article-title":"The supernumerary nostril","volume":"21","author":"Matsumura","year":"2010","journal-title":"J. Craniofac. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0901-5027(05)80565-X","article-title":"Syndromology: An updated conceptual overview. VIII. Deformations and disruptions","volume":"19","author":"Cohen","year":"1990","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1597\/09-033","article-title":"Facial clefts and associated limb anomalies: Description of three cases and a review of the literature","volume":"47","author":"Obdeijn","year":"2010","journal-title":"Cleft Palate Craniofac. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S1010-5182(05)80106-4","article-title":"Bilateral transverse facial clefts and accessory maxillae--variant or separate entity?","volume":"21","author":"Cheung","year":"1993","journal-title":"J. Craniomaxillofac. Surg."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/9\/1745\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:43:41Z","timestamp":1760129021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/9\/1745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,31]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["genes14091745"],"URL":"https:\/\/doi.org\/10.3390\/genes14091745","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,31]]}}}