Rubinstein-Taybi syndrome is characterized by congenital anomalies (microcephaly, specific facial characteristics, broad thumbs and halluces and postnatal growth retardation), intellectual deficit and behavioural characteristics. Birth prevalence is 1 in 100,000 to 125,000. Facial features, which become more prominent with age, include highly arched eyebrows, long eyelashes, downslanting palpebral fissures, beaked nose, 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, and refractive errors), a variety of congenital heart defects, joint hypermobility, and skin anomalies (in particular keloid formation). 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 behaviour become gradually more frequent. An increased risk of tumours (mainly leukaemia in childhood and meningeoma in adulthood) has been observed. The syndrome is almost always sporadic. Causes include: microdeletion of chromosome 16p13.3, CREB-binding protein mutations (CBP, 16p13.3) and E1A-binding protein mutations (EP300, 22q13). CBP and EP300 show a very high degree of homology and both play important roles as global transcriptional coactivators. The exact pathogenesis of the syndrome remains uncertain. The diagnosis is in essence based on clinical examination. A cytogenetic or molecular abnormality can be detected in about 55% of patients. The syndrome can sometimes be difficult to differentiate from Saethre-Chotzen syndrome and Cornelia de Lange syndrome (see these terms). The recurrence risk for parents of an index case is low (0.1%). There are no reports of affected children of siblings of an index case. The chance of patients having an affected child may be as high as 50%. If a cytogenetic or molecular abnormality was found in the affected child, reliable prenatal diagnosis is possible during future pregnancies through chorionic villus biopsy. Prenatal ultrasound only rarely allows a reliable diagnosis. Patient management is mainly symptomatic. Specialised educational programs are required, with early emphasis on psychomotor development and speech therapy. Life expectancy does not seem to be altered, except in children with complex cardiac defects. Malignancies and respiratory infections are the most common causes of death.
Last update: July 2007