Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous 
developmental disorder. Clinical features include growth retardation, 
intellectual disability, limb defects, typical facial dysmorphism, and other 
systemic involvement. The increased understanding of the genetic basis of CdLS 
has led to diagnostic improvement and expansion of the phenotype. Mutations in 
five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural 
components of cohesin, have been identified. Approximately 60% of CdLS cases are 
due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and 
one proband was found to carry a mutation in SMC3. To date, 311 CdLS-causing 
mutations are known including missense, nonsense, small deletions and 
insertions, splice site mutations, and genomic rearrangements. Phenotypic 
variability is seen both intra- and intergenically. This article reviews the 
spectrum of CdLS mutations with a particular emphasis on their correlation to 
the clinical phenotype.