{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:41:28Z","timestamp":1792586488119,"version":"4.5.0"},"reference-count":92,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Holoprosencephaly (HPE) is the most common malformation of the prosencephalon in humans. It is characterized by a continuum of structural brain anomalies resulting from the failure of midline cleavage of the prosencephalon. The three classic subtypes of HPE are alobar, semilobar and lobar, although a few additional categories have been added to this original classification. The severity of the clinical phenotype is broad and usually mirrors the radiologic and associated facial features. The etiology of HPE includes both environmental and genetic factors. Disruption of sonic hedgehog (SHH) signaling is the main pathophysiologic mechanism underlying HPE. Aneuploidies, chromosomal copy number variants and monogenic disorders are identified in a large proportion of HPE patients. Despite the high postnatal mortality and the invariable presence of developmental delay, recent advances in diagnostic methods and improvements in patient management over the years have helped to increase survival rates. In this review, we provide an overview of the current knowledge related to HPE, and discuss the classification, clinical features, genetic and environmental etiologies and management.<\/jats:p>","DOI":"10.3390\/children10040647","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T02:23:46Z","timestamp":1680143026000},"page":"647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management"],"prefix":"10.3390","volume":"10","author":[{"given":"Ma\u00edsa","family":"Malta","sequence":"first","affiliation":[{"name":"Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada"},{"name":"Division of Child Neurology, Department of Neurology and Neurosurgery, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04024-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowim","family":"AlMutiri","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"National Neuroscience Institute, King Fahad Medical City, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Saint","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Radiology, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Srour","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada"},{"name":"Division of Pediatric Neurology, Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1097\/nen.0b013e3180986e1b","article-title":"The Morphogen Signaling Network in Forebrain Development and Holoprosencephaly","volume":"66","author":"Monuki","year":"2007","journal-title":"J. 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