Fetal malformations of cortical development: review and clinical guidance

Abstract

Malformations of cortical development (MCDs) are a heterogeneous family of congenital brain malformations that originate from disturbed development of the cerebral cortex. MCDs can arise from primary genetic disorders that lead to dysfunction of the molecular processes controlling neuronal proliferation, neuronal migration, cortical folding or cortical organization. MCDs can also result from secondary, disruptive causes, such as congenital infection or other in utero brain injuries. Sequelae of MCDs can include epilepsy, intellectual disability and cerebral palsy, among other symptoms, with a high burden of paediatric morbidity. Advances in antenatal genetic testing and imaging have improved the ability to diagnose MCDs, yet limited literature exists to aid clinicians in prognostication of outcomes and perinatal management. These clinical realities can make it challenging for clinicians caring for fetal neurological conditions to counsel families and make recommendations for interdisciplinary care. We aim to review the literature on fetal MCDs and present practice guidelines for clinicians regarding the pre- and postnatal management of MCDs.

Keywords: fetal neurology; heterotopia; lissencephaly; polymicrogyria; prenatal diagnosis; schizencephaly.

Figure 1

Timeline of typical corticogenesis or malformations of cortical development. Timeline of events in typical corticogenesis (top) or MCD onset (bottom). GW = gestational weeks; MCDs = malformations of cortical development.

Figure 2

Fetal MRI examples of malformations of cortical development. Hemimegalencephaly: axial (A) and coronal (E) T2-single shot fast spin echo (SSFSE) images from fetal MRI of a 24-week gestational age fetus with right hemimegalencephaly, demonstrating asymmetric enlargement of the right cerebral hemisphere with decreased cerebral mantle lamination, consistent abnormality of neuronal migration. There is asymmetric enlargement of the right ganglionic eminence (black arrow), consistent with abnormality of neuronal proliferation, and mild irregularity of the right cerebral cortex (white arrows), consistent with co-existing polymicrogyria. Schizencephaly: axial (B) and coronal (F) T2-SSFSE images of a 23-week gestational age fetus show a large left open-lipped schizencephalic cleft (black arrows) with a thin-walled associated ventricular diverticulum. Note the cleft is lined by dysplastic grey matter. Periventricular grey matter heterotopia: axial (C) and coronal (G) T2-SSFSE images of a 28-week gestational age fetus with severe ventriculomegaly secondary to aqueductal stenosis and nodularity of the ependymal margins (black arrows) consistent with extensive grey matter heterotopia. Polymicrogyria: axial (D) and coronal (H) T2-SSFSE images from a 27-week gestational age fetus with abnormal sulcation and diffuse irregularity of the right cerebral cortex (black arrows) consistent with polymicrogyria.

Figure 3

Pre- and postnatal imaging from a patient with subcortical band heterotopia. Coronal T2-weighted (A) fetal MRI at 22 gestational weeks, showing agenesis of the corpus callosum and shallow Sylvian fissures with absence of the expected multi-layered pattern. Axial T1-weighted (B) postnatal MRI showing subcortical band heterotopia and lissencephaly-pachygyria due to pathogenic DCX variant.