Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder, typically inherited as an autosomal dominant condition. Here, we report on a family in which germline mosaicism for TCS was likely present. The proband was diagnosed with TCS based on the typical clinical features and a pathogenic variant TCOF1 (c.4369_4373delAAGAA, p.K1457Efs*12). The mutation was not detected in his parents\' peripheral blood DNA samples, suggesting a de novo mutation had occurred in the proband. However, a year later, the proband\'s mother became pregnant, and the amniotic fluid puncture revealed that the fetus carried the same mutation as the proband. Prenatal ultrasound also indicated a maxillofacial dysplasia with unilateral microtia. The mother then disclosed a previous birth history in which a baby had died of respiratory distress shortly after birth, displaying a TCS-like phenotype. Around the same time, the proband\'s father was diagnosed with mild bilateral conductive hearing loss. Based on array data, we concluded that the father may have had germline mosaicism for TCOF1 mutation. Our findings highlight the importance of considering germline mosaicism in sporadic de novo TCOF1 mutations when providing genetic consulting, and prenatal diagnosis is important when the proband\'s parents become pregnant again.

Treacher Collins syndrome (TCS) is a rare congenital craniofacial condition that affects approximately one out of fifty thousand births. Different ratios of TCS patients have conductive hearing loss: 88%1 vs. 91.4-100.00%2. For this reason, it was examined which hearing solutions can be used with this condition and how effective they are. A systematic literature review was conducted, which showed that the bone-anchored hearing aid (BAHA, OSIA), the bone conduction implant (Bonebridge) or the active implant of the middle ear (Soundbridge) are reliable methods for the treatment of conductive hearing loss in TCS patients. After the implantation of all available hearing solutions, improved hearing and speech comprehension were observed. Additionally, a statement regarding the treatment of TCS and a personalized point of view of a clinical expert with TCS were provided. However, due to the small amount of data, no general recommendations can be given for the treatment of hearing loss in TCS patients; therefore, it is advised to collect more data on hearing solutions for TCS patients in future research.

Treacher Collins syndrome (TCS) should be suspected if the triad of micrognathia, glossoptosis, and posterior cleft palate, and deformed external ears are observed during prenatal ultrasonography, excepting Pierre Robin sequence. Visualization of the fetal zygomatic bone and down-slanting palpebral fissures are conducive to differentiation. Molecular genetics testing can establish a definite diagnosis. A 28-year-old pregnant Chinese woman was referred for systematic ultrasound examination at 24 weeks. Two-dimensional and three-dimensional ultrasound showed polyhydramnios, micrognathia, absence of nasal bone, microtia, secondary cleft palate, mandibular hypoplasia, glossoptosis, and normal limbs and vertebrae. Pierre Robin sequence was misdiagnosed with the triad of micrognathia, glossoptosis, and posterior cleft palate. Final diagnosis of TCS was confirmed by whole-exome sequencing. Visualization of the fetal zygomatic bone and down-slanting palpebral fissures can facilitate a differential diagnosis between Pierre Robin sequence and TCS, with the triad of micrognathia, glossoptosis, and posterior cleft palate.

Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between phenotypic variability and their relative variants are very limited. This systematic review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype-phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified. While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5-bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies.

OBJECTIVE: Treacher Collins syndrome (TCS) is a severe congenital mandibulofacial dysostosis that occurs one in every 50,000 births. The main clinical treatment of this rare disorder is reconstruction surgery. However, the high invasion, low security and long period of surgical intervention make it essential to explore prevention methods to decrease morbidity. The authors\' aim is to summarize the prevention methods based on known mechanisms of TCS.
METHODS: A systematic review was conducted through an electronic search of PubMed, EMBASE and Web of Science databases through November 2019 using the following items: \'Treacher Collins syndrome OR TCS OR Franceschetti-Zwahlein-Klein syndrome OR Berry syndrome\', \'gene therapy OR prevention\'. Four causative gene names were also used. Articles which published in English language and explored the prevention methods for TCS were included and data concerning animal model, intervention, phenotype, conclusion were gathered.
RESULTS: Sixty-five studies were reviewed in total, and seven articles were included in this systematic review. Four articles used prevention methods related to the inhibition of p53, and three related to preclusion of oxidative stress-induced DNA damage.
CONCLUSIONS: This article provides a comprehensive review of the prevention methods for craniofacial abnormalities characteristic of TCS based on known pathogenesis in the current literatures. The craniofacial phenotype could be rescued through several treatment methods experimentally such as p53 inhibition and antioxidant administration.

Treacher Collins syndrome (TCS) is a frequent cause of mandibulofacial dysostosis. To date, TCS-causing mutations in three genes, namely TCOF1, POLR1D, and POLR1C have been identified. TCS is usually inherited in an autosomal dominant manner, with a high clinical variability and no phenotype-genotype correlation. Up-to now, five families have been reported with an autosomal recessive mode of inheritance due to mutations in POLR1D or POLR1C. We report here a new family with two sisters affected by mild TCS carrying compound POLR1C heterozygous mutations, and review the literature on mild forms of TCS, autosomal recessive inheritance in this syndrome and POLR1C mutations.

Treacher Collins syndrome is a congenital disorder with bilaterally symmetric anomalies of the structures developing from the first and second branchial arches. The ocular and orbital features are an obligatory component for the diagnosis. We presented a case of typical, complete syndrome and also reviewed the varied ophthalmological manifestations of the disease in the literature. Antimongoloid slanting of palpebral fissures and lower lid colobomas are constant features of the syndrome. However, varied ocular and lacrimal drainage anomalies are also associated. TCS is a syndrome with multiple ocular and orbital features, a knowledge of which will help in the diagnosis of incomplete forms of the syndrome.

Treacher Collins syndrome (Mandibulofacial dysostosis) is characterized by deafness, hypoplasia of facial bones (mandible, maxilla and cheek bone), antimongoloid slant of palpebral fissures, coloboma of the lower lid and bilateral anomalies of the auricle. Hypoplasia of the facial bones may be the first indicator of the disorder. We present a case report of Treacher Collins syndrome with their extraoral findings, intraoral findings and their treatment plan. We have also included the various etiological factors, clinical diagnostic aids, and multidisciplinary team approach.

Pierre Robin sequence (PRS) is an important craniofacial anomaly that can be seen as an isolated finding or manifestation of multiple syndromes. 22q11.2 deletion and Stickler syndrome are cited as the two most common conditions associated with PRS, but their frequencies are debated. We performed a retrospective study of 66 patients with PRS and reviewed their genetic testing, diagnoses, and clinical findings. The case series is complemented by a comprehensive literature review of the nature and frequency of genetic diagnosis in PRS. In our cohort 65% of patients had associated anomalies; of these, a genetic diagnosis was established in 56%. Stickler syndrome was the most common diagnosis, comprising approximately 11% of all cases, followed by Treacher Collins syndrome (9%). The frequency of 22q11.2 deletion was 1.5%. Chromosome arrays, performed for 72% of idiopathic PRS with associated anomalies, revealed two cases of 18q22→qter deletion, a region not previously reported in association with PRS. A review of the cytogenetic anomalies identified in this population supports an association between the 4q33-qter, 17q24.3, 2q33.1, and 11q23 chromosomal loci and PRS. We found a low frequency of 22q11.2 deletion in PRS, suggesting it is less commonly implicated in this malformation. Our data also indicate a higher frequency of cytogenetic anomalies in PRS patients with associated anomalies, and a potential new link with the 18q22→qter locus. The present findings underscore the utility of chromosomal microarrays in cases of PRS with associated anomalies and suggest that delaying testing for apparently isolated cases should be considered.

Treacher Collins syndrome (TCS) or Franceschetti syndrome is an autosomal dominant disorder of craniofacial development with variable phenotypic expression. It presents with characteristic facial appearance enabling it to be easily recognizable. A case of a 10-year-old girl having TCS is briefly described in this article. A review of the etiology, clinical features, differential diagnosis, and treatment options are also discussed.