Treacher Collins syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of facial development which affects approximately 1 in 50 000 live births (1). More than 60% of cases do not appear to have a previous family history and are thought to arise as the result of a de novo mutation (2). On the basis that the tissues affected in TCS develop from the first and second branchial arches, which are populated extensively by cranial neural crest cells (3), several hypotheses were proposed to explain the cellular basis of this disorder. These theories included abnormal neural crest cell migration (4), improper cellular differentiation during development (5) or an abnormality of the extracellular matrix (6). The use of genetic, physical and transcript mapping techniques resulted in the identification of the gene mutated in TCS, designated TCOF1, which was found to encode a low complexity, serine/alanine-rich, nucleolar phosphoprotein that was named Treacle (7). More recently, the integration of molecular biology, cell biology, mouse genetics and experimental embryology has provided novel insights into the molecular pathogenesis of TCS.