Fetal Macrocephaly: Prenatal Findings and Follow-Up in Cases With High Risk for Abnormal Outcome.

OBJECTIVE

Fetal macrocephaly (HC Z-score ≥ +2) is a common reason for referral for neurosonography. While most cases are benign and asymptomatic, syndromic macrocephaly poses a significant risk of abnormal neurodevelopment. This study aimed to describe the sonographic and genetic features of fetuses at the highest risk of syndromic macrocephaly.

METHODS

We retrospectively analyzed 19 fetuses with either HC Z-scores ≥ +2.5 or those with ≥ +2 and associated anomalies, evaluated between January 2015 and October 2024. Assessments included fetal neurosonography, anomaly scans, MRI, and genetic work-up. Outcomes and postnatal/postmortem data were reviewed.

RESULTS

Mean gestational age at the time of diagnosis was 29.6 weeks (range 23-35.4 weeks). Seventeen fetuses (89%) had associated anomalies: large for gestational age (12/19), callosal abnormalities (11/19), malformation of cortical development (13/19), and facial dysmorphism (11/19) were diagnosed. Genetic investigation results (CMA) were available for 17 of the 19 patients. Overall, 14 of the 17 patients had abnormal genetic findings, mostly involving mTOR pathway genes.

CONCLUSION

High Z-scores and additional imaging findings strongly correlate with genetic abnormalities, most often mTOR-related. These results support the integration of exome sequencing into prenatal evaluation of fetal macrocephaly.