Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Mar;17(3):275-83.
doi: 10.1038/ejhg.2008.221. Epub 2008 Dec 24.

Treacher Collins syndrome: etiology, pathogenesis and prevention

Paul A Trainor  1 , Jill Dixon, Michael J Dixon
Affiliations

Treacher Collins syndrome: etiology, pathogenesis and prevention

Paul A Trainor et al. Eur J Hum Genet. 2009 Mar.

Abstract

Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development that arises as the result of mutations in the TCOF1 gene, which encodes a nucleolar phosphoprotein known as Treacle. Individuals diagnosed with TCS frequently undergo multiple reconstructive surgeries, which are rarely fully corrective. Identifying potential avenues for rescue and/or repair of TCS depends on a profound appreciation of the etiology and pathogenesis of the syndrome. Recent research using animal models has not only determined the cellular basis of TCS but also, more importantly, unveiled a successful avenue for therapeutic intervention and prevention of the craniofacial anomalies observed in TCS.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Diagnostic algorithm summarizing the morphological and genetic identification of individuals with Treacher Collins syndrome and their subsequent management. By permission of Oxford University Press, Inc.
Figure 2
Figure 2
Clinical photographs and partial pedigree of a Somalian family. Individual I-2, who has an extensive family history of TCS, exhibits no apparent clinical features of mandibulofacial dysostosis. In contrast, all three children exhibit severe craniofacial anomalies consistent with TCS and furthermore share the same mutation (c.2259delA) as I-2. Adapted from chapter ‘Treacher Collins syndrome' by Dixon, Trainor and Dixon from ‘In born Errors of Development' edited by Epstein, Erickson and Wynshaw-Boris (2008). By permission of Oxford University Press, 2008.
Figure 3
Figure 3
Developmental basis of TCS craniofacial anomalies. Comparative skeletal stains of E18.5 wild-type embryos (a) revealed severe frontonasal hypoplasia in Tcof1+/− littermates (b). Sox10 in situ hybridization of migrating neural crest cells in an E8.5 wild-type embryo (c) uncovered a severe reduction in the neural crest cell population in Tcof1+/− embryos (d). Staining for apoptosis (TUNEL:green) showed low endogenous levels of cell death in E8.5 wild-type embryos (e) and massively elevated levels in Tcof1+/− littermates (f). BrdU incorporation (red) into DAPI-stained nuclei (blue) of E9.0 embryos (g) highlighted a concomitant decrease in cell proliferation in Tcof1+/− embryos (h). Immunostaining for the 28S ribosomal protein (red) in E8.5 embryos (i) uncovered deficient ribosome biogenesis in Tcof1+/− littermates (j). Adapted from Dixon et al (2006).
Figure 4
Figure 4
Prevention of TCS through diminishment of p53 function. Activated capase3 immunostaining revealed low levels of cell death in E9.0 Tcof1+/+ (a) embryos, elevated levels in Tcof1+/− (b) and partially reduced levels in Tcof1+/−; p53+/− (c) littermates. Sox10 in situ hybridization labeled migrating neural crest cells in E9.5 Tcof1+/+ (d) embryos highlighting the reduction in Tcof1+/− (e) and restoration in Tcof1+/−; p53+/− (f) littermates. Bone (red) and cartilage (blue) staining showed normal cranioskeletal patterning in E18.5 Tcof1+/+ (g) embryos, severe frontonasal hypoplasia and dysplasia in Tcof1+/− (h) and complete rescue in Tcof1+/−; p53+/− (f) littermates. Bright field photograph of a 3-month-old Tcof1+/+ mouse (j) and a rescued post-natal viable and fertile Tcof1+/−; p53+/− (k) littermate. Adapted from Jones et al (2008).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Fazen LE, Elmore J, Nadler HL. Mandibulo-facial dysostosis (Treacher-Collins syndrome) Am J Dis Child. 1967;113:405–410. - PubMed
    1. Rovin S, Dachi SF, Borenstein DB, Cotter WB. Mandibulofacial dysostosis, a familial study of five generations. J Pediatr. 1964;65:215–221. - PubMed
    1. Treacher Collins Syndrome Collaborative Group Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. Nat Genet. 1996;12:130–136. - PubMed
    1. Dixon J, Trainor P, Dixon MJ.Treack and Treacher Collins syndromeIn: Epstein, Erickson and Wynshaw-Boris (eds): In born Errors of Development. New York: Oxford University Press, 2008
    1. Jones KL, Smith DW, Harvey MA, Hall BD, Quan L. Older paternal age and fresh gene mutation: data on additional disorders. J Pediatr. 1975;86:84–88. - PubMed

Further Reading

    1. Dixon J, Dixon MJ.TCOF1/Treacle and the Treacher Collins Syndromein Esptein, Erickson and Wynshaw-Boris (eds):Inborn Errors of Development – the Molecular Basis of Clinical Disorders of Morphogenesis New York: Oxford University Press; 2004
    1. Johnston M, Bronsky PT.Craniofacial Embryogenesis – Abnormal developmental mechanismsin: Mooney and Siegel (eds): Understanding Craniofacial Anomalies; Etiopathogenesis of Craniosynostoses and Facial Clefting New York: Wiley-Liss; 2002

Publication types