Treacher Collins syndrome (TCS) is a genetic defect characterized by congenital craniofacial abnormalities. The condition is also known as mandibulofacial dysostosis, since the cheek and jaw bones are primarily affected. Major characteristics of the condition are downward slanting eyes, small lower jaw and chin, notched lower eyelids (coloboma), and malformed or missing ears. Some patients may also present with a cleft palate, receding chin, scalp hair extending onto cheeks, breathing problems, including sleep apnea, and/or eating difficulties. Malformations in the outer and middle ear may lead to hearing difficulties. However, not all affected patients suffer in the same way. The severity of the disease presentation varies greatly, with some patients showing the entire range of disease features, and some others hardly showing any symptoms at all. One in every 50,000 children is estimated to be born with this genetic defect. Diagnosis is principally based on the clinical features. Differential diagnoses to be considered include Goldenhar syndrome, Nager syndrome, Miller syndrome, Pierre Robin Sequence, and Nonsyndromic Mandibular Hypoplasia.
Mutations in the TCOF1 gene are responsible for TCS. This gene codes for a protein called treacle, which is expected to play an important role in the embryonal development of facial bones. Mutations in the TOCF1 gene result in defective or lowered levels of treacle, which causes the facial bone cells to undergo apoptosis. About 90-95% of patients with TCS, in whom the TCOF1 gene has been studied, have shown mutations in the coding and flanking intronic regions of the gene. TCS, although transmitted in an autosomal recessive manner, shows variable penetrance and marked variability in expressivity, sometimes, even within the same family.