Rubinstein-Taybi syndrome (RSTS; Online Mendelian Inheritance in Man 180849, http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim) is a rare genetic multisystem disorder characterized by mental retardation, broad and often angulated thumbs and halluces, and distinctive facial features. 1 Congenital heart abnormalities, including a patent ductus arteriosus, septal defects, and aortic coarctation, have been reported in up to 33% of affected patients. 2 In a minority of cases, other systemic anomalies involving the skin, eye, ear, central nervous system, urinary tract, and musculoskeletal system, as well as an increased risk of developing tumors, have also been described. 3 The reported incidence of this condition ranges from 1 per 100,000 to 1 per 125,000 live births. 3 Although RSTS is categorized as an autosomal dominant disorder, most reported cases are sporadic, deriving from de novo mutations at a locus on band 16p13.3, which encompasses the gene for the transcription cofactor cyclic adenosine monophosphate response element-binding protein-binding protein. 4 This protein is ubiquitously expressed as a coactivator in cyclic adenosine monophosphate-regulated gene expression, which explains the multisystem problems described in affected individuals. The psychosocial prognosis of the syndrome is quite poor because of mental retardation, varying from a moderate to severe degree, and the considerable morbidity due to associated congenital abnormalities. The diagnosis of RSTS is usually made at birth or during infancy and is still essentially clinical. In fact, even with modern molecular genetic testing, a cytogenetic or molecular abnormality can be found in about 55% of affected individuals, thus leaving the diagnosis to rest on clinical features only in most cases. 4 Despite the fact that the acral abnormalities featured in these individuals might be detectable on sonography, as well as the abnormal profile due to the beaked nose, no prenatal description of RSTS has been reported in literature to the best of our knowledge. We report a case in which the diagnosis of RSTS was hypothesized prenatally after sonographic detection of highly suspicious findings in a family without any previous known risk for this condition.