So far, most publications agreed that, in roughly 90% of the cases, the pathogenesis of TCS arises from compromised ribosome biogenesis as a direct result of TCOF1 haploinsufficiency.3, 4, 10, 15 However, both the pathogenesis of TCS and the reasons of the high inter- and intra-familial variability in phenotypic severity remain unclear.27, 28, 29. This evidence concerns the gene TCOF1 and Treacher-Collins syndrome.