The Brain-Face Connection in Holoprosencephaly: Case Report and Literature Review

Holoprosencephaly (HPE) is a congenital brain malformation caused by the incomplete division of the forebrain during early embryogenesis. It results in a spectrum of structural abnormalities, ranging from alobar to lobar forms, and milder, more difficult to diagnose variants. Alobar HPE is often associated with midline craniofacial defects due to shared developmental origins. Both malformations are amenable at the first trimester anomaly scan. Case report and systematic review: We present a late diagnosed and complex case, subject of major obstetric complications. The late booking prenatal ultrasound examination revealed alobar HPE associating facial and great vessels anomalies. Subsequently, severe sudden hemorrhage due to central placenta praevia required emergency cesarean section. Neonatal death occurred shortly after birth. We performed a literature review on HPE cases associated with facial defects, aiming to highlight the broad spectrum of cerebral malformations, their associated outcomes, and to analyze maternal and fetal features.

We identified and analyzed 26 studies, including 34 fetuses/neonates. The most severe and common form-the alobar type, was diagnosed prenatally in 22 cases (64.71%). There were 16 reported births and 16 terminations of pregnancy. The neonatal outcome was unfavorable in all alobar HPE cases. In non-alobar forms, neonatal survival beyond several months postpartum was reported in two cases.

HPE is a severe congenital brain malformation, most often lethal. Alobar form can be diagnosed in early pregnancy. Survival beyond the neonatal period is rare and associated with significant neurological impairment.