Fig. 2: The phenotypes classified as Cornelia de Lange syndrome can be defined as a spectrum.

The Cornelia de Lange syndrome (CdLS) spectrum includes individuals with the classic CdLS phenotype in whom a pathogenic variant in a gene involved in cohesin functioning has or has not been identified (if molecular confirmation is absent, the diagnosis can still be determined clinically), as well as individuals with a non-classic CdLS phenotype who harbour a pathogenic variant in a cohesin function-relevant gene. Individuals who carry a presumed pathogenic variant in a cohesin function-relevant gene but exhibit little or no resemblance to the classic CdLS phenotype do not fall within the CdLS spectrum. Please note that mildly affected and severely affected individuals may present both classic and non-classic CdLS. The question mark indicates that there may be genes causing CdLS spectrum that do not have a cohesin function; such genes are unknown at present, but their existence cannot be excluded.