We describe the use of three-dimensional printing to create precise airway models for a patient with Treacher Collins syndrome who presented for bimaxillary temporomandibular joint prostheses, and for whom airway management was predicted to be difficult. The model was based on pre-operative cone beam computed tomography images and printed in the 3D Lab of Hospital Universitario La Paz. Transparent models allowed clear visualisation for simulation and iterative refinement of airway management techniques and aided in risk assessment and instrument sizing. This case report emphasises the utility of this approach in complex airway scenarios.

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.

BACKGROUND: Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder.
METHODS: To investigate the genetic features of a four-generation Chinese family with TCS, clinical examinations, hearing tests, computed tomography, whole-exome sequencing (WES), Sanger sequencing, reverse transcription (RT)-PCR, and the Minigene assay were performed.
RESULTS: The probands, an 11-year-old male and his cousin exhibited typical clinical manifestations of TCS including conductive hearing loss, downward slanting palpebral fissures, and mandibular hypoplasia. Computed tomography revealed bilateral fusion of the anterior and posterior stapedial crura and malformation of the long crura of the incus. WES of both patients revealed a novel heterozygous intronic variant, i.e., c.4342 + 5_4342 + 8delGTGA (NM_001371623.1) in TCOF1. Minigene expression analysis revealed that the c.4342 + 5_4342 + 8delGTGA variant in TCOF1 caused a partial deletion of exon 24 (c.4115_4342del: p.Gly1373_Arg1448del), which was predicted to yield a truncated protein. The deletion was further confirmed via RT-PCR and sequencing of DNA from proband blood cells. A heterozygous variant in the POLR1C gene (NM_203290; exon6; c.525delG) was found almost co-segregated with the TCOF1 pathogenic variant.
CONCLUSIONS: In conclusion, we identified a heterozygous TCOF1 splicing variant c.4342 + 5_4342 + 8delGTGA (splicing) in a Chinese TSC family with ossicular chain malformations and facial anomalies. Our findings broadened the spectrum of TCS variants and will facilitate diagnostics and prognostic predictions.

UNASSIGNED: Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development characterized by numerous developmental anomalies that are restricted to the head and neck. Most TCS cases are inherited in an autosomal dominant manner. The diagnosis of TCS relies on clinical and radiographic findings. The four genes involved in TCS are TCOF1, POLR1D, POLR1C, and POLR1B.
UNASSIGNED: In this report, we present the case of a 7-year-old Moroccan boy who exhibited distinctive dysmorphic features, including coloboma and zygomatic bone hypoplasia. Upon genetic analysis, a mutation in the TCOF1 gene was identified, conclusively confirming the presence of Treacher Collins Syndrome. It is worthy that the correct etiological diagnosis was significantly delayed due to the initial misperception that the observed malformation syndrome was a result of drug teratogenicity.
UNASSIGNED: This case highlights the importance of seeking pharmacovigilance advice if any adverse event occurs following medication use. Furthermore, requesting a genetic consultation to establish a confirmed etiological diagnosis for any malformation syndrome can significantly reduce the protracted social and psychological suffering that patients and their families may endure.

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology.
METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing.
RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before.
CONCLUSIONS: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

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.

UNASSIGNED: We aimed to measure the related indicators of the neonatal mandible in East China. This provides basic data for the study of the mandible position and morphology of normal newborns and can also provide data support for the diagnosis, evaluation, and treatment of the Pierre Robin sequence.
UNASSIGNED: First, we collected the CT data of normal neonates at the Nanjing Children\'s Hospital Affiliated with Nanjing Medical University between January 2013 and January 2019. The data included the maxilla and mandible, and neonates had no craniomaxillofacial-related malformation. We exported the data in DICOM format. In the second step, we imported the data into MIMICS 21.0 to reconstruct the data into a 3D model, and then we used the model to measure the different measurement items. Specific measurement items were as follows: ① Measurement of the angle α: We imported the CT data of the neonate into the software and reconstructed a 3D model. We observed the 3D model to find the left and right gonions (LGo and RGo) and the Menton (Me) and used the angle measurement tool of the software to appoint Me as the apex, and we connected the points LGo, Me, and RGo as angle α. ② Measurement of the distance between the left and right gonions: The distance measurement tool of the software was used to measure the distance between the bilateral gonions as a. ③ Measurement of the distance from the Me to the line between LGo and RGo: The LGo and RGo were connected as a line on the 3D model, then the distance between Me and the line was measured as b. ④ Measurement of the distance between the upper and lower jaw: The median sagittal view was found and the distance c between the foremost point of the upper jaw and the foremost point of the lower jaw was measured. We imported the measurement results into the SPSS software for statistical analysis.
UNASSIGNED: Specific measurement results: ① Angle α: 86.34 ± 8.58°. ② Distance a: 63.63 ± 6.83 mm. ③ Distance b: 31.99 ± 3.70 mm. ④ Distance c: 2.28 ± 1.04 mm. Among all the above indicators, there was no statistical difference between gender.
UNASSIGNED: In this study, 132 neonates were initially screened, of which 117 met the inclusion criteria and were finally included. There were 69 male and 48 female neonates. The indicators α, a, b, and c showed no statistical differences between male and female neonates; therefore, we combined the results to obtain the normal reference value: angle α: 86.34 ± 8.58°; distance a: 63.63 ± 6.83 mm; distance b: 31.99 ± 3.70 mm; distance c: 2.28 ± 1.04 mm.

Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome（TCS）, the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG（p. A451Gfs*43） and c. 4362_4366del（p. K1457Efs*12）, resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance（CAP） score was 6, and the Speech Intelligibility Rating（SIR） score was 4. Assessment using the Meaningful Auditory Integration Scale（MAIS） showed notable improvement in the patient\'s auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children\'s Benefit Inventory and quality of life assessment revealed significant improvements in the child\'s self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.
目的：对2例Treacher Collins综合征（Treacher Collins syndrome，TCS）患者的临床表型特点及基因序列进行分析，确定其生物学致病原因，并探讨骨桥植入的听力干预疗效。 方法：收集2个家系成员的临床资料，签署知情同意书，抽取先证者及其家系成员的外周血，提取DNA，进行全外显子组测序，并针对变异位点对家系成员进行Sanger测序验证，对患者进行TCOF1基因变异分析，并对家系2先证者在声场下评估并比较裸耳及佩戴骨桥后的听阈及言语识别率。 结果：2个家系中先证者均有耳廓畸形、颧骨和下颌骨发育不全、小下颌、眼裂下斜、内侧睫毛发育不全的表现。家系1先证者合并右侧前鼻孔狭窄、牙齿发育不全等特殊表现，均符合TCS的临床诊断。对2个家系进行基因检测，检测出TCOF1基因有2个杂合突变：c.1350_1351dupGG（p.A451Gfs*43）、c.4362_4366del（p.K1457Efs*12），导致氨基酸发生移码突变。家系1先证者父母TCOF1基因Sanger测序验证未检测到突变，先证者1TCOF1c.1350_1351dupGG杂合变异此前未见报道。家系2先证者术后单音节言语识别率为76%，听觉行为分级（CAP）为6分，言语可懂度分级（SIR）为4分，行有意义听觉整合量表（MAIS）评估，患者对声音的觉察能力、理解能力及助听装置的使用情况均获得明显改善。行格拉斯格儿童收益量表及生活质量测定量表评估，患儿家长认为患儿在生活自理能力、日常生活学习、社会交际及心理健康方面有显著提高。 结论：本研究明确了TCS生物学致病原因，丰富了中国人群TCOF1基因突变谱，骨桥植入可提高TCS患者听力及言语识别率。.

Treacher Collins syndrome (TCS) is a rare genetic disorder that affects craniofacial development due to malformation of the first and second branchial arches. The TCOF1 gene is mainly responsible for this condition. Here, we present a case of a 13-year-old adolescent girl with complaints of maligned teeth with conductive deafness. On clinical examination, she had retrognathia, a broad nose, maligned teeth, a high arch palate, and midfacial hypoplasia. On the basis of the clinical findings, a diagnosis of a mild-variant TCS was made as eyes were not involved and supportive treatment was given to the patient. The symptoms of the disease have a varying range of severity. Early diagnosis and supportive treatments, which include multidisciplinary treatment involving pediatrics, otolaryngologists, audiologists, orthodontists, and psychologists, are very important for the management of such cases.

UNASSIGNED: Treacher Collins syndrome (TCS), also known as mandibulofacial dysostosis, is an inherited craniofacial defect. Here, we report a TCS family in which the members carry the same POLR1D variant but present with phenotypic variability.
UNASSIGNED: A 19-year-old healthy primigravida was revealed by ultrasound at 12 weeks of gestation to have a fetus with micrognathia. Prenatal genetic testing detected a heterozygous single-nucleotide deletion (NM_015972:c.91del, p.Q31Rfs*10) in the POLR1D gene, inherited from the healthy mother. Variants of POLR1D have been reported to be associated with TCS. Family studies found that a paternal healthy cousin of the mother had a similar pregnancy outcome, with a fetus of TCS and the same POLR1D variant.
UNASSIGNED: Our study results pose a great challenge to prenatal diagnosis of TCS. The prenatal diagnosis cannot only rely on genetic testing. Instead, an early detailed sonographic survey will be helpful for the identification of TCS.