106 Treacher-Collins Syndrome
TCS, Mandibulofacial dysostosis, Franceschetti-Zwahlen-Klein syndrome
Downward slanted palpebral fissures, lower eyelid coloboma, malar hypoplasia, micrognathia, large down-turned mouth, dysplastic ears
Frequency: 1 in 50,000 live births.
Genetics
Autosomal dominant (OMIM 154500), with variable expressivity; high rate of de novo mutations; due to mutation of the TCOF1 gene mapped to 5q32-q33.1.
Clinical Features
Features are bilateral and symmetrical.
• Projection of scalp hair onto lateral cheeks
• Downward slanting palpebral fissures, lower eye- lid coloboma (in outer third), partial absence of lower eyelashes medial to the defect
• Malar hypoplasia, hypoplastic zygomas
• Narrow nares
• Macrostomia, cleft palate
• Mandibular hypoplasia
• Abnormalities of external ears, atresia of external auditory canals, malformations of middle ear ossi- cles, conductive hearing loss, ear tags, fistulas
• Possibility of perinatal death from compromised airway
Differential Diagnosis
• Acrofacial dysostosis, Nager type
• Oculo-auriculo-vertebral spectrum (Goldenhar syndrome)
• Miller syndrome
Radiographic Features Skull
• Hypoplasia/aplasia of the malar bones (80%), zygomatic processes of frontal bones, and ptery- goid plates
• Underdeveloped supraorbital ridges, orbital hy- pertelorism, defective lower margin of the orbit
• Micrognathia (80%), deficient mandibular ramus, severe hypoplasia of condyle and coronoid process, wide mandibular angle, malocclusion
• Underdeveloped paranasal sinuses and mastoids, sclerotic mastoids
• Cleft palate (30%)
• Hypoplasia/absence of external auditory canal and tympanic cavity
• Choanal atresia (not mandatory)
Treacher-Collins Syndrome 912
Fig. 106.1. Patient 1, age 3 months. Note malar and mandibu- lar hypoplasia, downward slanting palpebral fissures, lower eyelid coloboma, narrow nares, macrostomia, and dysplastic ears
Bibliography
Dixon MJ. Treacher Collins syndrome. Hum Mol Genet 1996;
5: 1391–6
Hansen M, Lucarelli MJ, Whiteman DAH, Mulliken JB. Treach- er Collins syndrome: phenotypic variability in a family in- cluding an infant with arrhinia and uveal colobomas. Am J Med Genet 1996; 61: 71–4
Herring SW, Rowlatt UF, Pruzansky S. Anatomical abnormali- ties in mandibulofacial dysostosis. Am J Med Genet 1979; 3:
225–59
Kreiborg S, Dahl E. Cranial base and face in mandibulofacial dysostosis. Am J Med Genet 1993; 47: 753–60
Marsh KL, Dixon J, Dixon MJ. Mutations in the Treacher Collins syndrome gene lead to mislocalization of the nucle- olar protein treacle. Hum Mol Genet 1998; 7: 1795–800
Posnick JC, al-Qattan MM, Moffat SM, Armstrong D. Cranio- orbito-zygomatic measurements from standard CT scans in unoperated Treacher Collins syndrome patients: com- parison with normal controls. Cleft Palate Craniofac J 1995;
32: 20–4
Stovin JJ, Lyon JA, Clemmens RL. Mandibulofacial dysostosis.
Radiology 1960; 74: 225–31
Sulik KK, Johnston MC, Smiley SJ, Speight HS, Jarvis BE.
Mandibulofacial dysostosis (Treacher Collins syndrome): a new proposal for its pathogenesis. Am J Med Genet 1987;
27: 359–72
Treacher Collins Syndrome Collaborative Group: Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. Nat Genet 1996; 12: 130–6
Treacher-Collins Syndrome 913
T
Fig. 106.2 a, b. Patient 2, newborn. Note malar and mandibular hypoplasia, concave horizontal ramus of the mandible and flat mandibular angle, cleft palate, and relative enlargement of the skull, with increased bitemporal diameter
a b
Treacher-Collins Syndrome 914
a
d
c
Fig. 106.3 a–d. Patient 3, young adult. Note a underdeveloped paranasal sinuses, malar and zygomatic hypoplasia, b small mandible, c cleft palate, and d den- tal malocclusion
b
