Brain Structural and Dysmaturation Anomalies in First- and Second-Trimester Trisomy 21 Fetuses: Ultrasound, MRI, and Autopsy Findings

Fetuses with trisomy 21 typically exhibit subtle but measurable deviations in early brain growth rather than frequent major malformations. This review synthesizes first-second trimester data from ultrasound, fetal MRI, and autopsy studies to characterize early neurodevelopmental alterations in Down syndrome. Especially, in second trimester, neurosonography reveals mild reductions in head and cerebellar biometry, a characteristic "seagull" cerebral hemisphere configuration, and thinned subplate, while fetal MRI demonstrates global but regionally accentuated brain and cerebellar hypoplasia with relatively preserved gross architecture. Autopsy and microscopic analyses confirm reduced cellularity and delayed lamination in cortex, basal ganglia, and cerebellum, supporting a primary disturbance of neurogenesis rather than migration. Severe structural malformations and obstructive hydrocephalus are rare but documented. Current evidence underscores the prognostic potential-and limitations-of early neuroimaging, highlighting the need for standardized, prospective studies linking prenatal brain metrics with long-term neurodevelopmental outcomes.