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Treacher Collins syndrome (TCS)

Treacher Collins syndrome (TCS), also known as mandibulofacial dysostosis and Franceschetti-Zwahlen-Klein syndrome is a rare congenital disorder of craniofacial morphogenesis that arises as the result of mutations in the TCOF1 gene (encodes a nucleolar phosphoprotein, Treacle).

Rare congenital disorder of craniofacial morphogenesis that arises as the result of mutations in the TCOF1 gene (encodes a nucleolar phosphoprotein, Treacle).

  • Also known as mandibulofacial dysostosis and Franceschetti-Zwahlen-Klein syndrome
  • Autosomal dominant inheritance with variable penetrance

History

TCS was first described in 1889 as a congenital neonatal deformity with the colobomata of the lower eyelids by George Andreas Berry. In 1900, an ophthalmologist named Edward Treacher Collins presented two patients with these ocular and periorbital sequelae at a meeting in London and subsequently published one of earliest case reports describing his findings. In the 1940s, Adolphe Franceschetti of Switzerland further characterized the disorder and published extensive reviews with his colleague David Klein. They further characterized the facial features and coined the description, mandibulofacial dysostosis. Today, there are several eponyms for this syndrome as it is known in the United States and United Kingdom as Treacher Collins syndrome, in Europe as Franceschetti-Klein syndrome, and otherwise as mandibulofacial dysostosis.


Etiopathogenesis

TCOF1 mutations:

Neural crest cells are a migratory cell population derived from the neuroepithelium during early embryogenesis that ultimately give rise to the majority of the cartilage, bone, and connective tissue of the head and face. Thus, most craniofacial anomalies, such as those associated with TCS, are thought to arise due to defects in neural crest cell formation, proliferation, migration and/or differentiation. Interestingly, the Tcof1 gene is spatiotemporally expressed in the neuroepithelium and in the neural crest-derived facial mesenchyme during early mouse embryogenesis, implying it plays a role in the development of these tissues.
  • Affects structures of the 1st and 2nd pharyngeal arches
  • Spontaneous mutation (60% cases)
  • Familial/hereditary (40% cases)
Clinical photographs and partial pedigree of a Somalian family wit TCS
Clinical photographs and partial pedigree of a Somalian family wit TCS: 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. | ‘Treacher Collins syndrome’ by Dixon, Trainor and Dixon from ‘In born Errors of Development’ edited by Epstein, Erickson and Wynshaw-Boris (2008). Oxford University Press, 2008.4

Presentation

  • Facial asymmetry
  • Coloboma of lower eyelids
  • External ear defects

Facial bone malformation:

  • Mandibular hypoplasia (78% cases)
    • Mandibular micrognathia and a retro-positioned tongue obstructing the oropharyngeal and hypopharyngeal spaces
  • Zygomatic complex hypoplasia (81% cases)
  • Maxillary hypoplasia (constrict the nasal passages) → Choanal stenosis/atresia
  • Bird-like appearance (prominent nose and midface with a retruded lower third of the face)
    • Due to shortened mandible + normal anterior maxillary height
Characteristic facial findings of Treacher Collins syndrome
Characteristic findings of Treacher Collins syndrome include downward slanting palpebral fissures, lower eyelid colobomas, midface and zygomatic hypoplasia, microtia, and mandibular microretrognathia. Patients can be fitted with a removable bone-assisted hearing aid to help speech and language development prior to definitive implantation after ear reconstruction. | Chang, C. C., & Steinbacher, D. M. (2012). Treacher collins syndrome. Seminars in Plastic Surgery, 26(2), 83–90. https://doi.org/10.1055/s-0032-1320066

Oral/dental abnormalities:

  • Facial bone hypoplasia → Dental malocclusion, with anterior open bite
  • Cleft palate (33% cases)
  • Retropositioned tongue
  • Steep occlusal plane
Oral features in a TCS skull
Bifid uvula, crowding of teeth and a high arched palate | Shete, P., Tupkari, J., Benjamin, T., & Singh, A. (2011). Treacher Collins syndrome. Journal of Oral and Maxillofacial Pathology : JOMFP, 15(3), 348–351. https://doi.org/10.4103/0973-029X.86722

Ophthalmic abnormalities:

  • Abnormal palpebral fissures:
    • Downward slanting (89% cases) with notching of the lower eyelids (69% cases)
  • Coloboma of lower eyelid (paucity of lid lashes medial to the defect) (69% cases)

Auricular abnormalities:

  • Bilateral microtia (85% cases): Malformed pinna, low set
  • Conductive hearing loss

Diagnosis

Genetic testing:

  • Direct sequencing of the coding and flanking intronic regions of TCOF1 defects mutations (90-95% cases)

X-ray skull:

Orthopantomograph (OPG):

Orthopantomograph in a TCS skull
Orthopantomograph showing retained deciduous teeth, crowding, periapical lesion | Shetty, S. B., Thomas, A., & Pidamale, R. (2011). Treacher Collins Syndrome: A Case Report and a Brief Review on Diagnostic Aids. International Journal of Clinical Pediatric Dentistry, 4(3), 235–239. https://doi.org/10.5005/jp-journals-10005-1116

3D CT analysis:

3D CT analysis of a TCS skull
The mandible and temporomandibular joint can be severely affected in Treacher Collins syndrome. Condylar malformation can be the most severely affected portion of the mandible and the normal ramus-angle-body relationship can be totally absent. | Chang, C. C., & Steinbacher, D. M. (2012). Treacher collins syndrome. Seminars in Plastic Surgery, 26(2), 83–90. https://doi.org/10.1055/s-0032-1320066

Differential diagnosis:

  • Nager’s acrofacial dysostosis
  • Miller acrofacial dysostosis
  • Oculoauriculovertebral spectrum

Management

The care of individuals affected by TCS requires a multidisciplinary approach and may involve intervention from a number of health-care professionals both pre-and post-operatively

TCS Treatment Algorithm
A treatment timeline is presented for surgical considerations and staging throughout the patient’s childhood. | Chang, C. C., & Steinbacher, D. M. (2012). Treacher collins syndrome. Seminars in Plastic Surgery, 26(2), 83–90. https://doi.org/10.1055/s-0032-1320066

Mandible:

Microretrognathic TCS mandible is a priority for surgical evaluation because it can be markedly hypoplastic and can lead to glossoptosis and upper airway obstruction.
Distraction osteogenesis of the Treacher Collins syndrome mandible
Distraction osteogenesis of the Treacher Collins syndrome mandible usually necessitates two vectors of distraction: Inferior bony length and anterior projection are needed. Newer curvilinear distraction devices aim to correct this multivector deficiency. | Chang, C. C., & Steinbacher, D. M. (2012). Treacher collins syndrome. Seminars in Plastic Surgery, 26(2), 83–90. https://doi.org/10.1055/s-0032-1320066

Oral surgery/dentition:

Post-treatment photograph showing corrected anterior teeth with a removable partial denture
Post-treatment photograph showing corrected anterior teeth with a removable partial denture | Shetty, S. B., Thomas, A., & Pidamale, R. (2011). Treacher Collins Syndrome: A Case Report and a Brief Review on Diagnostic Aids. International Journal of Clinical Pediatric Dentistry, 4(3), 235–239. https://doi.org/10.5005/jp-journals-10005-1116

Ear reconstruction:

Auricular reconstruction in TCS
Auricular reconstruction is performed with autogenous costal cartilage grafts, fabrication of a framework, and staged implant and elevation. | Chang, C. C., & Steinbacher, D. M. (2012). Treacher collins syndrome. Seminars in Plastic Surgery, 26(2), 83–90. https://doi.org/10.1055/s-0032-1320066

Summary

2 replies on “Treacher Collins syndrome (TCS)”

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