Phenotypic Spectrum and Chromosomal Discordance in Alobar Holoprosencephaly: A Comparative Case Series from a...

Holoprosencephaly (HPE) is a rare congenital malformation of the forebrain caused by incomplete midline cleavage, often accompanied by craniofacial abnormalities. The condition arises from multifactorial etiologies, including genetic, environmental, and maternal factors. Early prenatal diagnosis is essential for parental counseling, management decisions, and detection of associated anomalies.

We report two cases of alobar HPE diagnosed in the third trimester by ultrasonography. The first case involved a 41-year-old primigravida at 32 weeks of gestation, with ultrasound findings of fused thalami, single ventricle, microcephaly, and hypotelorism. The fetus was delivered with severe midline craniofacial abnormalities and a normal female karyotype (46,XX). The second case involved a 41-year-old multiparous woman at 32 weeks of gestation. Ultrasound revealed fused thalami, absent falx cerebri and corpus callosum, and a proboscis. The infant presented with synophthalmia and proboscis, and karyotyping confirmed trisomy 13. Both pregnancies were terminated after counseling, and postnatal findings confirmed the prenatal diagnosis.

This case series demonstrates the phenotypic and chromosomal variability within alobar HPE and underscores the diagnostic value of detailed ultrasonography combined with genetic analysis. Late detection in the third trimester limited reproductive options and highlights the importance of improved anomaly screening pathways. Early diagnosis remains crucial for comprehensive parental counselling and perinatal planning.