Cornelia de Lange Syndrome: insights into neural development from clinical studies and animal models

Abstract Cornelia de Lange syndrome (CdLS) is a multisystem birth defect disorder characterized by growth retardation, craniofacial dysmorphia and other structural abnormalities, deficits in cognition and communication, and behavioral changes. In this chapter, we discuss discovery of haploinsufficiency for the NIPBL gene as the cause of most cases of CdLS and genetic heterogeneity of the syndrome. We summarize what is known concerning structural and functional changes in the nervous system and discuss cognitive and behavioral features, with particular emphasis on the prevalence of autistic behaviors in CdLS. Animal model systems of CdLS are described, with emphasis on discoveries from models of Nipbl deficiency. Neurodevelopmental and behavioral changes observed in model systems are discussed in the context of global changes in gene expression that are a major consequence of Nipbl deficiency and a causative factor in CdLS phenotypes. We place CdLS in the context of other transcriptomopathies and discuss approaches to therapeutics.