Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. WOMEN’S IMAGING 275 Holoprosencephaly: A Survey of the Entity, with Embryology and Fetal Imaging 1 Structural malformations of the brain are an important cause of childhood mortality and morbidity, with the latter having long-term financial and psychosocial implications for the affected child and family. Holoprosencephaly (HPE) is a severe brain malformation characterized by abnormal cleavage of the prosencephalon in the 5th gestational week. Aprosencephaly and atelencephaly occur ear- lier because of failure in the formation of the prosencephalon and telencephalon, respectively. The HPE spectrum classically includes alobar, semilobar, and lobar forms, although there are no clear-cut defining features. The middle interhemispheric variant (MIH), also known as syntelencephaly, is classified as a variant of HPE with midline interhemispheric fusion. Other conditions sometimes included in the spectrum of HPE include septo-optic dysplasia (SOD); “minimal” HPE, which is associated with subtle craniofa- cial malformations and mild developmental delay; and microform HPE, which by definition excludes brain involvement. The focus of this article will be on the spectrum of findings visible in fetal manifestation of the HPE spectrum. Brain embryology; the imag- ing characteristics, epidemiology, and embryology of HPE; and the more common associated anomalies, particularly those of the face (“the face predicts the brain”) are reviewed. Recognition of these anomalies is important for accurate parental counseling, since the prognosis is poor but not invariably lethal; children with the milder forms may live well into their teens with severe developmental de- lays, endocrine dysfunction, and disrupted homeostasis. Available data on outcome in surviving children are summarized. Illustrative fetal ultrasonographic and magnetic resonance images are present- ed with clinical, autopsy, and postnatal imaging correlation. © RSNA, 2015 • radiographics.rsna.org Thomas C. Winter, MD Anne M. Kennedy, MBBCh Paula J. Woodward, MD Abbreviations: HPE = holoprosencephaly, MIH = middle interhemispheric variant of HPE, RARE = rapid acquisition with relaxation en- hancement, SOD = septo-optic dysplasia RadioGraphics 2015; 35:275–290 Published online 10.1148/rg.351140040 Content Codes: 1 From the Abdominal Imaging Section, De- partment of Diagnostic Radiology, University of Utah Medical Center, 30 N 1900 E, Room 1A071, University Hospital, Salt Lake City, UT 84132-2140. Presented as an education exhibit at the 2004 RSNA Annual Meeting. Received February 18, 2014; revision requested May 14 and received May 27; accepted May 30. For this journal-based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant relationships. Address correspondence to T.C.W. (e-mail: thomas.winter@hsc.utah.edu). After completing this journal-based SA-CME activity, participants will be able to: ■ Identify the various forms of brain mal- formation that constitute the spectrum of holoprosencephaly. ■ Discuss the likely prognosis for a fetus with holoprosencephaly. ■ Describe possible causative factors in order to understand recurrence risk in future pregnancies. See www.rsna.org/education/search/RG. SA-CME LEARNING OBJECTIVES Introduction Structural abnormalities of the brain are an important cause of childhood mortality and morbidity, with the latter having long-term financial and psychosocial implications for the affected child and family. Holoprosencephaly (HPE) is often thought of as lethal, but in fact, HPE is a spectrum of malformations with widely variable outcome; in isolation, the milder forms are often associated with