Cornelia de Lange Syndrome: A Variable Disorder of Cohesin Pathology

Abstract

Cornelia de Lange syndrome (CdLS) is a rare multiple malformation syndrome including small stature, distinctive craniofacial features, limb anomalies, neurodevelopmental and behavioral abnormalities, and other organ system pathology. Recent literature has demonstrated that typical CdLS and related overlapping disorders display a broad range of severity and pleiotropy, suggesting that considering these diagnoses as a spectrum may be more appropriate. A molecular basis has been identified in many individuals, with mutations in five genes primarily responsible. These genes encode structural or regulatory proteins of the cohesin protein complex, important in chromatid division, cell cycle function, DNA repair, and epigenetic control. This review summarizes clinical findings, current management recommendations, and recent advances in understanding the underlying biologic mechanisms of these overlapping disorders of cohesin pathology.