Purpose or Case Report: To illustrate the developmental, genetic, and imaging spectrum of malformations of cortical development (MCD) from fetal life through adolescence by integrating principles of normal corticogenesis, key genetic pathways, and evolving MRI patterns.
This exhibit emphasizes:
1. Normal neuronal proliferation, migration, and post-migrational organization.
2. Developmental stage–specific MRI features linked to corresponding disruptions in these processes.
3. Major molecular pathways (LIS1/DCX, TUBB2B, MCPH1, CDK6, PIK3, PTEN, HEPACAM, mTOR) associated with characteristic imaging phenotypes.
4. The role of longitudinal imaging in evaluating cortical maturation, prognosis, and presurgical planning.
Methods & Materials: A retrospective review of representative fetal, neonatal, pediatric, and adolescent MCD cases from a tertiary care institution over 20 years was performed. Genetic results were integrated from literature and institutional databases, encompassing monogenic, chromosomal, and mosaic variants. Comparative imaging analyses correlated developmental stage, morphology, and progression patterns.
Results: Characteristic imaging appearances correspond to the timing of developmental arrest: early lesions due to abnormal neurogenesis and proliferation (lissencephaly, primary microcephaly, megalencephaly, focal cortical dysplasia), migrational disturbances (heterotopia, polymicrogyria), and late organizational anomalies (focal cortical dysplasia). Integrating genetic profiles refined etiologic classification, improved prenatal and presurgical counseling, and underscored the continuum of cortical dysgenesis. Cases illustrated include the result of abnormal neurogenesis and proliferation (primary microcephaly and megalencephaly), corticogenesis pathways such as LIS1/DCX-related migration disorders, TUBB2B-related microtubule dysfunction, mTOR-pathway dysregulation, and FLNA & ARFGEF2-associated heterotopias). Serial imaging demonstrates MCD evolution over the child's lifespan, reinforcing the value of longitudinal assessment in clinical decision-making.
Conclusions: Malformations of cortical development reflect the complex interplay between genetic blueprints and developmental breakpoints shaping cortical architecture and their maging appearance over time. Understanding the genetic and imaging trajectories from fetus to adolescence enhances diagnostic accuracy, informs prognosis, and promotes multidisciplinary collaboration in managing these complex disorders.