Facial features, which become more prominent with age, include highly arched eyebrows, long eyelashes, downslanting palpebral fissures, convex nasal ridge, low hanging columella, highly arched palate and micrognathia. Talon cusps are very frequent on the permanent incisors. An unusual smile with almost complete closure of the eyes is present in most cases. Other physical findings may include eye anomalies (nasolacrimal duct obstruction, congenital glaucoma, refractive errors), a variety of congenital heart defects (e.g. ventricular and atrial septal defect, patent ductus arteriosus), joint hypermobility, and skin anomalies (in particular keloid formation). Feeding difficulties are frequently observed in the neonatal period, and respiratory infections are very common in infancy and childhood. Constipation is generally a life-long problem, and patients may become overweight during late childhood or early puberty. As children, patients have a marked ability to establish excellent social contacts. In adulthood, sudden mood changes and obsessive-compulsive behavior become gradually more frequent. An increased risk of tumors (mainly leukemia in childhood and meningeoma in adulthood) has been observed.
Causes of Rubinstein-Taybi syndrome include: microdeletion of chromosome 16p13.3, CREB-binding protein mutations (CREBBP, 16p13.3) and E1A-binding protein p300 mutations (EP300, 22q13.2). CREBBP and EP300 show a very high degree of homology and both play important roles as global transcriptional coactivators.
