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

TL;DR

This paper reviews non-classic Cornelia de Lange Syndrome caused by BRD4 gene mutations, focusing on clinical features and genetic mechanisms.

Contribution

It provides a focused literature review on BRD4-related atypical CdLS, enhancing understanding of its clinical and molecular basis.

Findings

BRD4 gene alterations are linked to non-classic or milder forms of Cornelia de Lange Syndrome.

CdLS shows genetic heterogeneity and variable clinical severity, with BRD4 contributing to atypical presentations.

BRD4 plays roles in multiple pathways, influencing developmental and molecular mechanisms in CdLS.

Abstract

What are the main findings?

Review of the literature on the main clinical manifestations and genetic characteristics of Cornelia de Lange syndrome.

Review of the literature on Cornelia de Lange syndrome caused by pathogenic variations in the BRD4 gene sequence.

What are the implications of the main findings?

Improve paediatricians’ knowledge of the clinical spectrum and molecular basis of this condition.

Provide valuable information for diagnosis.

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.

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