Treacher Collins Syndrome: Genetics, Clinical Features and Management.

Bożena Anna Marszałek-Kruk,Piotr Wójcicki,Krzysztof Dowgierd,Robert Śmigiel

doi:10.3390/genes12091392

Abstract

Treacher Collins syndrome (TCS) is associated with abnormal differentiation of the first and second pharyngeal arches, occurring during fetal development. Features of TCS include microtia with conductive hearing loss, slanting palpebral fissures with possibly coloboma of the lateral part of lower eyelids, midface hypoplasia, micrognathia as well as sporadically cleft palate and choanal atresia or stenosis. TCS occurs in the general population at a frequency of 1 in 50,000 live births. Four subtypes of Treacher Collins syndrome exist. TCS can be caused by pathogenic variants in the TCOF1, POLR1D, POLR1C and POLR1B genes. Genetically, the TCOF1 gene contains 27 exons which encodes the Treacle protein. In TCOF1, over 200 pathogenic variants have been identified, of which most are deletions leading to a frame-shift, that result in the formation of a termination codon. In the presented article, we review the genetics and phenotype of TCS as well as the management and surgical procedures utilized for treatment.

Highlights

The incidence is about 1 in 50,000 live births [4] with 40% of cases involving a family history, while the remaining 60% occur as a result of de novo mutations
In the case of Treacher Collins syndrome patients, no correlation is observed between the type of the pathogenic variants and the phenotype
View beforeofmajor treatment, large deformation of the middle face and forming the shape of face, transplant taken from the cranial vault mounted in place of the zygomatic bone; despite late mandible resulting in closure of the upper airway, absence of zygomatic bone, coloboma of the lower notification of the therapy, noticeable improvements in facial features

Summary

Genetics

Treacher Collins syndrome (TCS, OMIM 154500), referred to as Franceschetti syndrome or mandibulofacial dysostosis (MFD1), is a rare developmental disorder. Beygo et al [30] identified a 3.367kb deletion in one patient with a clinical diagnosis of TCS This deletion concerned exon 3 and is the first described single exon deletion within the TCOF1 gene. Liu et al [31] identified a novel 2–6 exon deletion of TCOF1 This was the first report of a fetal for TCS in a Chinese population. Zhang et al [27] identified five novel variants (two nonsense, one missense and one splicing) in TCOF1 in Chinese patients. Dauwerse et al [7] detected pathogenic variants in genes POLR1C and in POLR1D (20 heterozygous variants) in TCS patients, while a report by Sanchez et al [6] identified three novel pathogenic variants in POLR1B. In the case of Treacher Collins syndrome patients, no correlation is observed between the type of the pathogenic variants and the phenotype

Clinical Features–Phenotype

Management and Surgical Treatment

Findings

4.4.Conclusions