The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by mental and growth retardation, broad thumbs, broad big toes, and typical face. A locus for a gene involved in the origin of RTS has been determined on chromosome 16 (16p13.3). RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximatively 25% of patients, using fluorescence in situ hybridization with specific probes.