NEW TRENDS IN TREACHER COLLINS SYNDROME: BONY RECONSTRUCTION AND REGENERATIVE THERAPY


New Trends In Treacher Collins Syndrome: Bony Reconstruction And Regenerative Therapy


Luigi Clauser1, Chiara Gardin2, Letizia Ferroni2, Antonio Lucchi1, Carolina Sannino1, Maria Elena de Notariis1 and Barbara Zavan2 

1Unit of Maxillo-Facial Surgery, Istituto Stomatologico Italiano, Via Pace, 21, 20122 Milano, Italy;
2 Department of Biomedical Sciences, University of Padova, 35100 Padova, Italy


Aim:Treacher Collins syndrome is a rare congenital disorder of craniofacial development with a  highly variable pheonotype. This syndrome occurs with an incidence of 1:50,000, and more than 60% of  the cases have no previous family history and arise as the result of de novo mutations. The disorder displays an intricate underlying dysmorphology. Affected patients may suffer life-threatening airway complications and functional difficulties involving sight, hearing, speech, and feeding. Deformation of facial structures produces a characteristic appearance that includes malar-zygomatic  hypoplasia, periorbital soft tissue anomalies, maxillomandibular hypoplasia, and ear anomalies. Management requires a specialized craniofacial team, as comprehensive care starts at birth and may require life-long follow-up. Standard craniofacial procedures for bony and soft tissue reconstruction are used. This article outlines current treatment strategies and future concepts for surgical and regenerative management.

Methods:The new field of regenerative medicine and therapy  offers the promise to improve some of these treatments. In particular, Structural Fat Grafting (lipostructure) seems to be a good strategy to restore the normal volume and contour of the face, and to provide a source of adipose-derived stem cells (ADSCs) with a multilineage differentiation potential. In this work, we present the case of a young girl with Treacher Collins Syndrome who underwent serial sessions of fat grafting in addition to other surgical bony reconstructive techniques. ADSCs have been isolated from the patient’s lipoaspirate, and compared for their stemness properties with those of a healthy subject.

Conclusion:Screening of the genome of the Treacher Collins patient using array-Comparative Genomic Hybridization (array-CGH) allowed us to identify some chromosomal imbalances that are probably associated with the syndrome.Correction of these imbalances and asymmetries by modulating ADSCs could be an innovative approach to improve and stabilize  the results of the surgical treatment of Treacher Collin Syndrome.


Keywords: Craniofacial surgery,Treacher Collins syndrome, regenerative medicine, structural fat grafting, adipose-derived stem cells, gene expression; array-CGH,tissue engineering

Free Full-text PDF


How to cite this article:

Luigi Clauser, Chiara Gardin, Letizia Ferroni, Antonio Lucchi, Carolina Sannino, Maria Elena de Notariis and Barbara Zavan. New Trends In Treacher Collins Syndrome: Bony Reconstruction And Regenerative Therapy. .American Journal of Surgical Research and Reviews, 2021, 4:22. DOI:10.28933/ajsrr-2021-05-3106


References

1. Treacher Collins E. Case with symmetrical congenital notches in the outer part of each lower lid and defective development of the malar bones. Trans Ophthalmol Soc UK 1900; 20:190-193
2. Sakai D, Trainor PA. Treacher Collins syndrome: unmasking the role of Tcof1/treacle. Int J Biochem Cell Biol 2009;41:1229-1232
3. Poswillo D. The pathogenesis of the Treacher Collins syndrome (mandibulofacial dysostosis). Br J Oral Surg 1975;13:1-26
4. Passos-Bueno M, Ornelas CC, Fanganiello RD. Syndromes of the first and second pharyngeal arches: A review. Am J Med Genet A 2009;149A:1853-1859
5. Dixon J, Jones NC, Sandell LL, et al. Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities. Proc Natl Acad Sci U S A 2006;103:13403-13408
6. Dixon MJ, Marres HA, Edwards SJ, et al. Treacher Collins syndrome: correlation between clinical and genetic linkage studies. Clin Dysmorphol 1994;3:96-103
7. Treacher Collins Syndrome Collaborative Group. Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. Nat Genet 1996;12:130-136
8. Valdez BC, Henning D, So RB, et al. The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor. Proc Natl Acad Sci U S A 2004;101:10709-10714
9. Jones NC, Lynn ML, Gaudenz K, et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 2008;14:125-133
10. Splendore A, Jabs EW, Félix TM, et al. Parental origin of mutations in sporadic cases of Treacher Collins syndrome. Eur J Hum Genet 2003;11:718-722
11. Trainor PA, Dixon J, Dixon MJ. Treacher Collins syndrome: etiology, pathogenesis and prevention. Eur J Hum Genet 2009;17:275-283
12. Arndt EM, Travis F, Lefebvre A, et al. Psychosocial adjustment of 20 patients with Treacher Collins syndrome before and after reconstructive surgery. Br J Plast Surg 1987;40:605-609
13. Clauser L, Tieghi R, Mandrioli S, et al. Facial lipostructure in complex reconstructive surgery. Riv Ital Chir Plast 2005;37:75-79
14. Coleman SR. Structural fat grafting: more than a permanent filler. Plast Reconstr Surg 2006;118:108S-120S
15. Clauser L, Ferroni L, Gardin C, et al. Selective augmentation of stem cell populations in structural fat grafts for maxillofacial surgery. PLoS One 2014;9:e110796
16. Coleman SR. Structural fat grafting. Aesthet Surg J 1998;18:386-388
17. Clauser LC. Optimizing maxillofacial and craniofacial results. In: Coleman SR, Mazzola RF. eds. Fat Injection: From Filling to Regeneration. Thieme Medical, 2009:475-500
18. Herlin C, Doucet JC, Bigorre M, et al. Computer-assisted midface reconstruction in Treacher Collins syndrome part 2: soft tissue reconstruction. J Craniomaxillofac Surg 2013;41:676-680
19. Clauser LC, Tieghi R, Consorti G. Parry-Romberg syndrome: volumetric regeneration by structural fat grafting technique. J Craniomaxillofac Surg 2010;38:605-609
20. Lee K, Kim H, Kim JM, et al. Systemic transplantation of human adipose-derived stem cells stimulates bone repair by promoting osteoblast and osteoclast function. J Cell Mol Med 2011;15:2082-2094
21. Scherberich A, Muller AM, Schafer DJ, et al. Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts. J Cell Physiol 2010;225:348-353
22. Sasaki T, Ito Y, Bringas P Jr, et al. TGFbeta-mediated FGF signaling is crucial for regulating cranial neural crest cell proliferation during frontal bone development. Development 2006;133:371-381
23. Bonilla-Claudio M, Wang J, Bai Y, et al. Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development. Development 2012;139:709-719
24. Xu X, Han J, Ito Y, et al. Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating TGF-beta/BMP signaling during tooth and palate development. Dev Cell 2008;15:322-329
25. Ornitz DM; Itoh N. Fibroblast growth factors. Genome Biol 2001,2:REVIEWS3005
26. Riley BM, Mansilla MA, Ma J, et al. Impaired FGF signaling contributes to cleft lip and palate. Proc Natl Acad Sci U S A 2007;104:4512-4517
27. Komori T, Yagi H, Nomura S, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997;89:755-764
28. Choi KY, Kim HJ, Lee MH, et al. Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development. Dev Dyn 2005;233:115-121
29. Li AW, Murphy PR. Expression of alternatively spliced FGF-2 antisense RNA transcripts in the central nervous system: regulation of FGF-2 mRNA translation. Mol Cell Endocrinol 2000;162:69-78
30. Mead TJ, Yutzey KE. Notch pathway regulation of neural crest cell development in vivo. Dev Dyn 2012;241:376-389
31. Wang YK, Spörle R, Paperna T, et al. Characterization and expression pattern of the frizzled gene Fzd9, the mouse homolog of FZD9 which is deleted in Williams-Beuren syndrome. Genomics 1999;57:235-248
32. Bhandari DR, Seo KW, Roh KH, et al. REX-1 expression and p38 MAPK activation status can determine proliferation/differentiation fates in human mesenchymal stem cells. PLoS One 2010;5:e10493
33. Demais V, Audrain C, Mabilleau G, et al. Diversity of bone matrix adhesion proteins modulates osteoblast attachment and organization of actin cytoskeleton. Morphologie 2014;98:53-64
34. Barnes JW, Tischkau SA, Barnes JA, et al. Requirement of mammalian Timeless for circadian rhythmicity. Science 2003;302:439-442
35. Gotter AL, Manganaro T, Weaver DR, et al. A time-less function for mouse timeless. Nat Neurosci 2000;3:755-756
36. O’Reilly LP, Watkins SC, Smithgall TE. An unexpected role for the clock protein timeless in developmental apoptosis. PLoS One 2011;6:e17157
37. Unsal-Kaçmaz K, Mullen TE, Kaufmann WK, et al. Coupling of human circadian and cell cycles by the timeless protein. Mol Cell Biol 2005;25:3109-3116
38. Fu H, Martin MM, Regairaz M, et al. The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage. Nat Commun 2015;6:6746
39. El Ghamrasni S, Cardoso R, Halaby MJ, et al. Cooperation of Blm and Mus81 in development, fertility, genomic integrity and cancer suppression. Oncogene 2015;34:1780-1789
40. Rezgaoui M, Hermey G, Riedel IB, et al. Identification of SorCS2, a novel member of the VPS10 domain containing receptor family, prominently expressed in the developing mouse brain. Mech Dev 2001;100:335-338


Terms of Use/Privacy Policy/ Disclaimer/ Other Policies:
You agree that by using our site, you have read, understood, and agreed to be bound by all of our terms of use/privacy policy/ disclaimer/ other policies (click here for details).



This work and its PDF file(s) are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.