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Treacher Collins syndrome (TCS) (MIM 154500) is a disorder of craniofacial development that is inherited in an autosomal dominant fashion and occurs with an incidence of approximately 1 in 50,000 live births. Forty percent of patients have a previous family history, whereas in 60 percent of patients the syndrome is thought to arise as a result of a de novo mutation.
TCS is characterized by abnormalities of the external ears, conductive hearing loss, lateral downward sloping of the palpebral fissures, cleft palate, and hypoplasia of the mandible and zygomatic complex. These features often are bilaterally symmetrical in nature. A marked variation in phenotype is observed both within and between families.
In the absence of a candidate gene or appropriate mouse model for the disorder, the mutated gene causing TCS (TCOF1) was isolated by positional cloning strategies. So far, approximately 70, mainly family-specific, mutations have been identified within the gene, which maps to chromosome 5q32-q33.1. The majority of these mutations introduce a premature termination codon.
Since database sequence comparisons failed to reveal any strong homology, little was known about the precise function of the protein, treacle, encoded by TCOF1. Recent work on the expression of treacle suggests that it is a member of a family of nucleolar phosphoproteins and, as such, may be involved in shuttling proteins between the nucleus and the cytoplasm.
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Treacher Collins syndrome (TCS) (MIM 154500) is named after the ophthalmologist E. Treacher Collins, who first described the essential components of the syndrome in 1900.1 The first extensive description of the condition was produced by Franceschetti and Klein, who used the term mandibulofacial dysostosis to describe the facial appearance.2 TCS is the most common mandibulofacial dysostosis disorder, affecting approximately 1 in 50,000 live births, and is inherited in an autosomal dominant manner. Although the disease is thought to be highly penetrant, there is marked variation in phenotype, ranging from perinatal death due to a compromised airway to features that are so mild that it is difficult to make an unequivocal diagnosis on clinical grounds alone. The main criteria used in the diagnosis of TCS include bilaterally symmetrical midface hypoplasia (89 percent), downward slanting of the palpebral fissures (89 percent), colobomas (notching) of the lower eyelids with sparse eyelashes (69 percent), cleft palate (28 percent), micrognathia (underdevelopment of the lower jaw, 78 percent), microtia (underdevelopment or absence of pinna, 77 percent), and other deformities of the external ears, which often lead to conductive hearing loss (50 percent).3 The typical facial appearance is depicted in Fig. 296-1.
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