HDAC8-deficiency causes an X-linked dominant disorder with a wide range of severity

Boyle et al. recently provided an updated description of the clinical and genetic aspects of Cornelia de Lange syndrome (CdLS) (1). In this review the authors summarise the genotype–phenotype correlations of the five genes associated with CdLS, including the most recently identified HDAC8, encoding the X-linked histone deacetylase 8 enzyme. Boyle et al. describe a spectrum of severity in CdLS, linked to genotype, with mutations in HDAC8 being second in severity only to mutations in NIPBL.