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).
Also known as mandibulofacial dysostosis and Franceschetti-Zwahlen-Klein syndrome
Autosomal dominant inheritance with variable penetrance
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.
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)
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 complexhypoplasia (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
Facial bone hypoplasia → Dental malocclusion, with anterior open bite
Cleft palate (33% cases)
Steep occlusal plane
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)
Bilateral microtia (85% cases): Malformed pinna, low set
Conductive hearing loss
Direct sequencing of the coding and flanking intronic regions of TCOF1 defects mutations (90-95% cases)
3D CT analysis:
Nager’s acrofacial dysostosis
Miller acrofacial dysostosis
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
Microretrognathic TCS mandible is a priority for surgical evaluation because it can be markedly hypoplastic and can lead to glossoptosis and upper airway obstruction.