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FASD <jats:italic>sentinel facial features<\/jats:italic> are unique to the disorder, and microcephaly is common in severe forms of FASD. Retinoic acid deficiency has been shown to cause craniofacial malformations and microcephaly in animal models reminiscent of those caused by prenatal alcohol exposure. Alcohol exposure affects the migration and survival of cranial neural crest cells, which are required for proper frontonasal prominence and pharyngeal arch development. Defects in craniofacial development are further amplified by the many downstream pathways that are transcriptionally controlled retinoic acid target genes, including Shh signaling. Recent evidence shows that alcohol exposure itself is sufficient to induce retinoic acid deficiency in the embryo. These data suggest that retinoic acid deficiency is an important underlying etiology of FASD. In disorders like Vitamin A Deficiency, FASD, DiGeorge (22q11.2 Deletion Syndrome), CHARGE, Smith\u2010Magenis, Matthew\u2010Wood, and Congenital Zika Syndromes, evidence is accumulating to link reduced retinoic acid signaling with developmental defects like craniofacial malformations and microcephaly. Research focus on characterizing the effects of retinoic acid deficiency during early development and on understanding the downstream signaling pathways involved in aberrant head, and craniofacial development will reveal underlying etiologies of these disorders.<\/jats:p>","DOI":"10.1002\/dvg.23278","type":"journal-article","created":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T20:59:13Z","timestamp":1546981153000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder"],"prefix":"10.1002","volume":"57","author":[{"given":"Berardino","family":"Petrelli","sequence":"first","affiliation":[{"name":"Regenerative Medicine Program and the Department of Biochemistry &amp; Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liat","family":"Bendelac","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel\u2010Canada Faculty of Medicine, Hebrew University  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey G.","family":"Hicks","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program and the Department of Biochemistry &amp; Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6368-0416","authenticated-orcid":false,"given":"Abraham","family":"Fainsod","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel\u2010Canada Faculty of Medicine, Hebrew University  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,21]]},"reference":[{"issue":"8","key":"e_1_2_11_2_1","first-page":"1","article-title":"Prenatal ethanol exposure and neocortical development: A transgenerational model of FASD","volume":"28","author":"Abbott C. 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