» What causes Cornelia de Lange Syndrome


Changes to the gene HDAC8 were first reported in individuals with classic and non-classic CdLS (18). HDAC8 is also on the X chromosome but it can be inactivated. It is important to note that changes on HDAC8 may also result in characteristics that do not resemble CdLS (39). Currently, variants in HDAC8 have been found in about 5% of individuals with CdLS (24,38-42).

There is a wide variation in the phenotype shown by individuals with a mutation in HDAC8. Typically, individuals with a mutation in HDAC8 have a non-classic CdLS phenotype, but some individuals do fulfil the criteria for classic CdLS. In addition to the features of CdLS, individuals with a change in HDAC8 may show some other distinctive features.

These include: A large anterior fontanel (the soft spot on an infant’s head before the skull bones meet at approximately 2 years of age), widely spaced eyes or a happy personality.

Because HDAC8 is randomly inactivated when there is more than one X chromosome (41), both males and females can be affected when there is a mutation in this gene. Some of these females can be completely healthy, and in those cases, most have non-random inactivation of the HDAC8 with the mutation (41,42).

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