CdLS is a genetically heterogeneous disorder, with only 50–60% of clinically diagnosed probands shown to have mutations in one of the known cohesin-associated genes NIPBL, SMC1A, SMC3, HDAC8 or RAD21. This partial knowledge of the molecular basis of CdLS parallels the wide clinical spectrum, which ranges from extremely mild to severe and includes “borderline” cases, which are often at the interface with other syndromic conditions caused by defects in interconnected cohesion pathways [33]. Here, NIPBL is linked to Cornelia de Lange syndrome.