Fetal magnetic resonance imaging features of syndromic megalencephaly: a systematic review of imaging-genotype associations.

Syndromic megalencephaly comprises a heterogeneous group of genetic disorders characterized by abnormal brain overgrowth and variable structural brain abnormalities. Prenatal recognition remains challenging because imaging findings overlap with those of isolated macrocephaly, while genotype-phenotype correlations are incompletely understood. This review summarizes the current literature on fetal magnetic resonance imaging (MRI) findings in molecularly confirmed syndromic megalencephaly and discusses their relationship with the underlying genetic pathways. The available evidence indicates that ventriculomegaly, malformations of cortical development, asymmetric lateral ventricles, hemimegalencephaly, and enlarged extra-axial spaces represent the most frequently reported prenatal MRI abnormalities, although their prevalence varies among genetic subgroups. Emerging imaging patterns suggest pathway-specific associations, particularly between the PIK3CA-AKT-mTOR pathway and hemimegalencephaly, and between RASopathies and enlarged extra-axial spaces. Current evidence is derived predominantly from case reports and small case series, underscoring the rarity of these disorders and the limited availability of systematic prenatal imaging data. Integrating fetal MRI findings with molecular diagnosis may improve prenatal diagnosis, facilitate targeted genetic testing, enhance prenatal counseling, and provide a foundation for future imaging-based diagnostic frameworks in syndromic megalencephaly.