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The recent literature has demonstrated that the phenotypic variability of HPE ranges from aprosencephaly\u2013atelencephaly, at the most severe end, to milder forms such as the \u201cmiddle interhemispheric variant\u201d of HPE at the less severe end of the spectrum. Between them, different intermediate forms demonstrate a continuum in a wide phenotypic spectrum rather than well\u2010defined categories. Although the term \u201cHPE\u201d suggests a disorder affecting only the prosencephalon, other brain structures are involved, underlining the complexity of the malformation. Because of close spatiotemporal interactions and common signaling pathways contributing to the development of both brain and face, concomitant facial and ocular anomalies are associated with brain malformation. In this review, the characteristic neuropathological features of the various forms of HPE are described as well as their associated brain, face, and ocular malformations, to delineate the different phenotypes.<\/jats:p>","DOI":"10.1002\/ajmg.c.31623","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T04:59:05Z","timestamp":1532494745000},"page":"214-228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Neuropathology of holoprosencephaly"],"prefix":"10.1002","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8213-8748","authenticated-orcid":false,"given":"Catherine","family":"Fallet\u2010Bianco","sequence":"first","affiliation":[{"name":"Department of Pathology, CHU Sainte\u2010Justine\u2010Chemin de la C\u00f4te Sainte\u2010Catherine Universit\u00e9 de Montreal, Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-199804000-00013"},{"issue":"1","key":"e_1_2_8_3_1","first-page":"43","article-title":"22.5 MB deletion of 13q31.1\u2010q34 associated with HPE, DWM and HSCR: A case report and redefining the smallest deleted regions","volume":"27","author":"Alp M. 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