Abstract

Rubinstein-Taybi syndrome is characterised by mental retardation, growth retardation and a particular dysmorphology. The syndrome is rare, with a frequency of approximately one affected individual in 100,000 newborns. Mutations in two genes - CREBBP and EP300 - have been identified to cause the syndrome. These two genes show strong homology and encode histone acetyltransferases (HATs), which are transcriptional co-activators involved in many signalling pathways. Loss of HAT activity is sufficient to account for the phenomena seen in Rubinstein-Taybi patients. Although some mutations found in CREBBP are translocations, inversions and large deletions, most are point mutations or small deletions and insertions. Mutations in EP300 are comparatively rare. Extensive screening of patients has revealed mutations in CREBBP and EP300 in around 50% of cases. The cause of the syndrome in the remaining patients remains to be identified, but other genes could also be involved. Here, we describe the clinical presentation of Rubinstein-Taybi syndrome, review the mutation spectrum and discuss the current understanding of causative molecular mechanisms.