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These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith\u2013Lemli\u2013Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders.\u00a0Here we present the first in\u2010depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state\u2010of\u2010the\u2010art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31.\u00a0Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (<jats:styled-content style=\"fixed-case\">CNVII<\/jats:styled-content>) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as <jats:styled-content style=\"fixed-case\">TGIF<\/jats:styled-content>, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures. Our study of a T18 specimen emphasizes the intricate interplay between bone and brain development in midline craniofacial abnormalities in general.<\/jats:p>","DOI":"10.1111\/joa.12326","type":"journal-article","created":{"date-parts":[[2015,5,28]],"date-time":"2015-05-28T14:42:46Z","timestamp":1432824166000},"page":"21-33","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic\u2013neural development"],"prefix":"10.1111","volume":"227","author":[{"given":"Shaina N.","family":"Reid","sequence":"first","affiliation":[{"name":"Laboratory for Neurodevelopment Department of Anatomy Howard University College of Medicine Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine 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