Rubinstein-Taybi syndrome: clinical and molecular cytogenetic studies

The Rubinstein-Taybi syndrome (RTS) is a rare but well-defined condition characterized by growth and mental retardation, broad thumb-hallux, and distinctive facial features. Ten unrelated Taiwanese children (6 boys and 4 girls) with clinical features suggestive of RTS were evaluated. The associated anomalies included cryptochidism (6/6 males), microcephaly (9/10), congenital heart diseases (8/10), pectus excavatum (5/10), low IGF-I level (4/10), strabismus/nystagmus (4/10), epilepsy (3/10), glaucoma (2/10), cleft palate (2/10), web neck (2/10), limb hypoplasia (2/10), sleep apnea (1/10), and vesico-ureteral reflux (1/10). All of them had normal thyroid function. High-resolution chromosome studies by both G- and R-banding were applied to detect any microscopic chromosomal deletion, particularly over the 16p13 region (responsible for RTS locus). A panel of five cosmids spanning the human cyclic AMP-responsive element binding (CREB) binding protein (CREBBP or CBP) gene in terms of RT100, RT102, RT191, RT203 and RT166 (Leiden, the Netherlands) were used for fluorescence in situ hybridization on the metaphases of those patients. Three cases showed whole or partial deletion of one copy of the CBP gene. Thus, the rate for detecting interstitial submicroscopic deletion of this region by FISH was about 30% in these RTS patients. The disease severity seemed to be correlated with size of the deletion.