| #248390 | ||||||||||||
| TREACHER COLLINS SYNDROME 3; TCS3 | ||||||||||||
| Alternative titles; symbols | ||||||||||||
| MANDIBULOFACIAL DYSOSTOSIS, TREACHER COLLINS TYPE, AUTOSOMAL RECESSIVE | ||||||||||||
| Phenotype Gene Relationships | ||||||||||||
| ||||||||||||
| Phenotypic Series | ||||||||||||
| Clinical Synopsis | ||||||||||||
| TEXT | ||||||||||||
| A number sign (#) is used with this entry because Treacher Collins syndrome-3 is caused by compound heterozygous mutation in the POLR1C gene (610060) on chromosome 6. | ||||||||||||
| Description | ||||||||||||
| Treacher Collins syndrome is a disorder of craniofacial development characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss (Dauwerse et al., 2011). For additional phenotypic information and a discussion of genetic heterogeneity of Treacher Collins syndrome, see TCS1 (154500). | ||||||||||||
| Clinical Features | ||||||||||||
| In 2 sisters in an inbred Hutterite kindred, Lowry et al. (1985) described mandibulofacial dysostosis and raised the question of an autosomal recessive form of Treacher Collins syndrome. The palpebral fissures were downward slanting, the outer third of the lower lids showed coloboma, and malar hypoplasia and abnormal pinnae were present. The parents had no signs of mandibulofacial dysostosis. The father and relatives in 3 generations had an apparently isolated dental anomaly characterized by small, widely spaced primary teeth and complete lack of secondary dentition. This appeared to be an independent, autosomal dominant trait. Lowry et al. (1985) found 9 other descriptions of possible autosomal recessive mandibulofacial dysostosis. Some other mechanism such as gonadal mosaicism is possible in this and other reported cases. Richieri-Costa et al. (1993) and Splendore et al. (2000) also reported affected sibs who were born to normal parents. The possibility of either nonpenetrance or germline mosaicism in one of the parents could not be discarded. | ||||||||||||
| Inheritance | ||||||||||||
| Treacher Collins syndrome-3 is an autosomal recessive disorder (Dauwerse et al., 2011). | ||||||||||||
| Molecular Genetics | ||||||||||||
| Dauwerse et al. (2011) analyzed the POLR1C gene in 252 individuals with Treacher Collins syndrome and identified 3 patients, including 1 from a family previously studied by Splendore et al. (2000), with compound heterozygous mutations (610060.0001-610060.0005, respectively). | ||||||||||||
| REFERENCES | ||||||||||||
| ||||||||||||
| ||||||||||||