Non-Classic Cornelia de Lange Syndrome Due to BRD4 Gene Alterations: A Literature Review

Cornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterised by distinctive facial features, growth retardation, limb abnormalities and developmental delays. It is characterised by genetic heterogeneity and also presents a broad clinical variability, with a spectrum of manifestations ranging from mild to severe, with milder phenotypes that can be difficult to ascertain based on physical characteristics. Pathogenic variations in the NIPBL gene account for the majority of cases, but variations in several other genes, including BRD4, have been identified as causative factors for non-classic or milder forms of the syndrome. This review aims to analyse the roles that BRD4 plays in the various pathways in which it is involved and to summarise current knowledge on atypical CdLS associated with BRD4 gene alterations, highlighting clinical features, molecular mechanisms, and implications for diagnostic assessment and patient care.