Prenatal findings and outcomes of the holoprosencephaly spectrum

Abstract

Objective: To estimate ultrasonographic factors associated with genetic abnormalities in holoprosencephaly cases. Methods: This study is a retrospective chart review. Study participants were pregnant women who had an ultrasound scan at our center and diagnosed with fetal holoprosencephaly between 2014 and 2024. We retrieved maternal and fetal features, prenatal ultrasonography characteristics, pregnancy and neonatal outcome data from electronic medical records. Results: Data from 47 cases of holoprosencephaly were analyzed. Genetic results were available in 57.5% (27/47). Of those, 63% (17/27) had a genetic abnormality. There were 11 cases of trisomy 13 (40.7%), 3 cases of trisomy 18 (11.1%), one case of triploidy (3.7%), one case of microarray anomaly and one abnormal exome sequencing result. Lobar (7/47, 14.9%) and semilobar (5/47, 10.6%) variants were less prevalent than alobar holoprosencephaly (35/47, 74.5%). Of 11 trisomy 13 cases, 7 (63.6%) had alobar, 2 (18.2%) semilobar, and 2 (18.2%) lobar type holoprosencephaly. All three trisomy 18 cases had alobar holoprosencephaly. Facial anomalies were the most common group of additional anomalies (31/47, 65.9%), also were associated with genetic abnormalities (75% in those with genetic abnormalities vs. 25%, p=0.03). The majority of cases were terminated (32/47, 68.1%). Only 7 cases were live born, while 5 died postnatally. The 2 children survived both had lobar type holoprosencephaly. Conclusion: Holoprosencephaly is highly associated with aneuploidies, particularly trisomy 13. Thorough investigation for additional anomalies and genetic etiologies is essential for parental counseling, and have an impact on decision of termination.