Synonyms: also referred to as Treacher Collins–Fransceschetti syndrome and mandibulofacial dysostosis,
consists of hypoplastic zygomatic bones and mandible, ear anomalies, coloboma of the eyelid rather than of the globe, absent lower eyelashes, and displaced hair growth onto cheeks (1). Treacher Collins is an association of Tessier cleft 6-7-8.
Incidence: The incidence of TCS ranges from 1:10,000 to 1:50,000.(2)
Pathogenesis/Etiology: Inheritance of TCS is autosomal dominant with most mutations being de novo.(2) Karyotype would be expected to be normal. There are several genes known to be associated with TCS, including TCOF1, POLR1C, and POLR1D. The TCOF1 gene is the most common and accounts for 71% to 93% of mutations.(3)
Diagnosis: If genetic testing is performed, the TCOF1 gene is typically evaluated first. If no mutation is found, the POLR1D and then the POLR1C genes are evaluated.
Imaging: The reliability of prenatal ultrasound in diagnosing TCS will depend on the severity of the findings. The principal findings in TCS are polyhydramnios, micrognathia, low-set ears, slanting palpebral fissures, and cleft palate .Typical facial features are better illustrated with three dimensional ultrasound than with standard two-dimensional imaging.(4)
Differential Diagnosis: The differential diagnosis may include Goldenhar syndrome, though abnormalities in Goldenhar syndrome are almost always unilateral and involve notching of the upper rather than the lower lid, as well as epibulbar dermoids. Fetuses with Goldenhar may also have vertebral anomalies and cardiac defects. Nager syndrome is also possible, but would have preaxial reduction defects of the upper extremities ranging from hypoplasia to aplasia of the thumb with or without involvement of the radius.
Miller syndrome, also known as postaxial acrofacial dysostosis (POADS), may have similar findings, but is characterized by micrognathia, cleft palate, postaxial reduction defects, and vertebral anomalies.(5)
Pierre-Robin sequence or nonsyndromic mandibular hypoplasia is characterized by early mandibular hypoplasia alone. It should be emphasized that limb anomalies are not a feature of TCS, and if present, Miller and Nager syndromes should be considered.
Prognosis: The prognosis depends on the severity of the phenotype expressed.
Management: Craniofacial abnormalities seen in this syndrome can lead to respiratory distress, requiring special positioning or tracheostomy,(6) and an ex utero intrapartum therapy (EXIT) procedure may be discussed for delivery planning if micrognathia is severe and airway access is questionable. In this instance, the child will remain on placental support until the airway is secured. Management should involve a multidisciplinary craniofacial team. Surgical management is often needed for craniofacial reconstruction and cleft repair.(7) Diagnostic imaging with postnatal CT of the head and face to delineate abnormalities of the zygomatic arch, malar bones, and mandible is often pursued. An ophthalmology examination is important to evaluate for vision loss, amblyopia, refractive errors, and strabismus.(8)
Auricular malformations of ossicles and the tympanic cavity can lead to conductive hearing loss in 40% to 50% of cases.(3). Speech therapy evaluations to assess for swallowing and feeding difficulty may determine the need for gastrostomy tube.(4)
Dental anomalies are present in 60% of TCS cases and can include dental agenesis, enamel abnormalities, and ectopic molars.(10)
Recurrence Risk: The inheritance of TCS is autosomal dominant, and most mutations are de novo.(2)Intrafamilial variability is marked. It is not uncommon for a parent to be mildly affected and undetected, so parental testing should be considered to guide recurrence risk counseling.
References
(1). Dixon MJ. Treacher Collins syndrome. Hum Mol Genet. 1996;5 Spec No:1391–1396.
(2). Trainor PA, Dixon J, Dixon MJ. Treacher Collins syndrome: etiology, pathogenesis and prevention. Eur J Hum Genet. 2009;17:275–283.
(3). Teber OA, Gillessen-Kaesbach G, Fischer S, et al. Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation. Eur J Hum Genet. 2004;12:879–890.
(4). Tanaka Y, Kanenishi K, Tanaka H, et al. Antenatal three-dimensional sonographic features of Treacher Collins syndrome. Ultrasound Obstet Gynecol.2002;19:414–415.
(5). Miller M, Fineman R, Smith DW. Postaxial acrofacial dysostosis syndrome. J Pediatr. 1979;95:970–975.
(6). Moessinger AC. Fetal akinesia deformation sequence: an animal model. Pediatrics. 1983;72:857–863.
(7). Thompson JT, Anderson PJ, David DJ. Treacher Collins syndrome: protocol management from birth to maturity. J Craniofac Surg. 2009;20:2028–2035.
(8). Posnick JC. Treacher Collins syndrome: perspectives in evaluation and treatment. J Oral Maxillofac Surg. 1997;55:1120–1133.
(9). Hayashi T, Sasaki S, Oyama A, et al. New grading system for patients withTreacher Collins syndrome. J Craniofac Surg. 2007;18:113–119.
(10). da Silva Dalben G, Costa B, Gomide MR. Prevalence of dental anomalies, ectopic eruption and associated oral malformations in subjects with Treacher Collins syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
2006;101:588–592.