EP098: Exome sequencing of >500 individuals with brain malformation phenotypes reveals marked genetic heterogeneity

Abstract

Brain malformations are developmental brain disorders (DBD) associated with high rates of morbidity and mortality among affected individuals. DBD include brain growth abnormalities such as microcephaly (MIC; small brain size), megalencephaly (MEG; large brain size), malformations of cortical development (MCD; such as lissencephaly, polymicrogyria), and mid-hindbrain malformations (MHM; such as cerebellar malformations). Establishing a precise genetic diagnosis in affected individuals is often challenging due to the complexity of the clinical and neuroimaging features of DBD, the variability in neuroimaging quality, the rarity of individual disorders and clinical findings, as well as the rapidly expanding number of causal genes and variants, attributed in part to the wide use multi-gene panels and exome sequencing (ES) and increasingly genome sequencing.