Introduction: Holoprosencephaly (HPE) is a complex cerebral malformation due to an incomplete division of the forebrain, occurring between the 18th and the 28th day of embryonic life and affecting both the brain and the face. There are 3 increasing degrees of severity: the lobar, semi-lobar, and alobar holoprosencephaly. Case Report: We report 4 cases of holoprosencephaly identified following natural childbirth, in 75% of cases in patients of low socioeconomic level, with the first-degree consanguinity in 25% of cases. The pregnancies were not properly monitored, no folic acid supplementation had been provided and, in 25% of cases, consumption of fenugreek was reported. The antenatal diagnosis was performed in 25% of cases with a male predominance, a sex ratio at 2. Discussion: Holoprosencephaly is a complex human brain malformation resulting from incomplete cleavage of the prosencephalon. HPE is usually associated with facial abnormalities, such as cyclopia, proboscis, or cleft lip/palate in severe HPE cases. In our study, the prevalence is assessed at 0.9/10,000 births, l__ampersandsignrsquo;HPE is associated with hexadactyly in 50% of cases and with sexual ambiguity in 25% of cases. Prenatal diagnosis is based on ultrasound and MRI. The aetiology of HPE is multifactorial, and the prognosis depends on the type of HPE and the associated facial anomalies. Conclusion: Holoprosencephaly is a complex brain malformation. For the majority of cases, the prognosis is grim. Indeed, 75% of cases were fetal death in utero (FDIU) and one case died immediate post-partum.