Cleidocranial dysplasia (CCD) and the Rubinstein–Taybi syndrome (RTS) are two rare congenital syndromes that have many clinical signs in common. We present an 18‐year‐old‐patient with untypical CCD expression who was misdiagnosed with RTS at the age of 2 years. An extensive craniofacial examination was carried out with respect to morphological and dental aspects. The molecular‐genetic analysis of two underlying genes (CBFA1 and CBP) for CCD and RTS was performed using SSCP, direct sequencing and FISH.

While the clinical examination showed uncharacteristic CCD symptoms with some findings common for RTS, the molecular‐genetic analysis revealed a missense mutation in the CBFA1 gene, which is considered to be the etiological factor for CCD. Our findings with this patient presented clear evidence for the wide morphologic variety that can be related to a certain gene such as CBFA1. The diagnosis of rare diseases is currently based on the clinical phenomenology of small groups or single cases. The use of molecular‐genetic biology extends the horizon of diagnostic and scientific possibilities. In this patient, it allowed us to compare the clinically diagnosis to molecular‐genetic data. We conclude that molecular‐genetic analysis may be a helpful tool in the differential diagnosis of many congenital diseases such as CCD and RTS.