Neural Crest.

This chapter discusses the role of cardiac neural crest cells in the formation of the septum that divides the cardiac arterial pole into separate systemic and pulmonary arteries. Further, cardiac neural crest cells directly support the normal development and patterning of derivatives of the caudal pharyngeal arches, including the great arteries, thymus, thyroid, and parathyroids. Recently, cardiac neural crest cells have also been shown to indirectly influence the development of the secondary heart field, another derivative of the caudal pharynx, by modulating signaling in the pharynx. The contribution and function of the cardiac neural crest cells has been learned in avian models; most of the genes associated with cardiac neural crest function have been identified using mouse models. Together these studies show that the neural crest cells may not only critical for normal cardiovascular development but also may be involved secondarily because they represent a major component in the complex tissue interactions in the caudal pharynx and outflow tract. Cardiac neural crest cells span from the caudal pharynx into the outflow tract, and therefore may be susceptible to any perturbation in or by other cells in these regions. Thus, understanding congenital cardiac outflow malformations in human sequences of malformations resulting from genetic and/or environmental insults necessarily requires better understanding the role of cardiac neural crest cells in cardiac development.

Possible germline mosaicism in a pedigree with Treacher Collins syndrome: A case report and brief review.

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.

The application of three-dimensional printing in the management of a difficult airway due to Treacher Collins syndrome.

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.

Pediatric Temporomandibular Joint Pathology.

Pediatric temporomandibular joint (TMJ) disorders represent a broad range of congenital and acquired diagnoses. Dentofacial deformities, including facial asymmetry, retrognathism, and malocclusion, commonly develop. Compared with adult TMJ conditions, pain and articular disc pathology are less common. Accurate diagnosis is paramount in planning and prognostication. Several specific considerations apply in preparation for skeletal correction, including timing in relation to disease progression and growth trajectory, expectation for postcorrection stability, reconstructive technique as it applies to expected durability and need for future revision, management of occlusion, and need for ancillary procedures to optimize correction. This article reviews common conditions and treatment considerations.

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.

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. CONCLUSION: 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.

A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome.

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.

Systematic Review of Current Audiological Treatment Options for Patients with Treacher Collins Syndrome (TCS) and Surgical and Audiological Experiences of an Otorhinolaryngologist with TCS.

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.

A relevância da odontologia na Síndrome Treacher Collins: relato de caso / The relevance of dentistry in Treacher Collins Syndrome: case report

Treacher Collins também chamada de disostose mandibulofacial, é uma alteração genética dominante rara caracterizada pela má-formação dos ossos e tecidos da face. É uma síndrome crânio-facial que apresenta alterações bilaterais e simétricas de estruturas originadas do primeiro e segundo arcos branquiais. A maioria dos casos possui transmissão autossômica dominante e expressividade variável. O objetivo do presente estudo é realizar um relato de caso sobre o impacto do tratamento odontológico na qualidade de vida do paciente portador de Treacher Collins. Paciente, 39 anos, sexo feminino compareceu a uma clínica odontológica em Belo Horizonte, com a queixa principal de falhas dentárias e sensibilidade. Durante a anamnese a paciente relatou ter a STC, durante o exame clínico extraoral verificou a presença de hipoplasia malar e mandibular, malformação dos pavilhões auriculares com perda auditiva, obliquidade e coloboma palpebral inferior. Ao exame intraoral observou ser classe II de Angle, ausência dos dentes 11, 12, 13, 21 e 22 e extrusão do dente 41 e recessão gengival e periodontite estágio I grau A. Após exames de periodontograma e complementares foi realizado uma raspagem nas áreas com profundidade de sondagem maior que 3mm, frenectomia labial inferior, aplicação de laser para sensibilidade, enxerto gengival e colocação de prótese parcial removível. A paciente ao final do tratamento relatou ter se sentido realizada e contente com a sua conclusão, ela foi encaminhada ao Sistema único de Saúde para realizar as cirurgias para corrigir as alterações crânio-faciais. O tratamento odontológico deve ser adaptado a cada indivíduo de acordo com sua necessidade, tendo uma abordagem multidisciplinar, possibilitando uma melhora na qualidade de vida e estética do paciente(AU)

Treacher Collins syndrome is a rare dominant genetic disorder characterized by malformation of the bones and tissues of the face. It is a craniofacial syndrome that presents bilateral and symmetrical alterations of structures originating from the first and second branchial arches. The aim of the present study is to perform a case report on the impact of dental treatment on the quality of life of a patient with CTS. Patient, 39 years old, female, attended a dental clinic in Belo Horizonte, with the main complaint of dental flaws and sensitivity. During the anamnesis the patient reported having CTS, during the extraoral clinical examination she verified the presence of malar and mandibular hypoplasia, malformation of the pinnae with hearing loss, obliquity and lower eyelid coloboma. Intraoral examination revealed Angle class II, missing teeth 11, 12, 13, 21 and 22, extrusion of tooth 41, gingival recession and stage I periodontitis grade A. After periodontogram and complementary exams it was performed a scaling in areas with a probing depth greater than 3mm, lower lip frenectomy, laser application for sensitivity, gingival graft and placement of partial removable prosthesis. The patient at the end of treatment reported feeling fulfilled and happy with its completion, she was referred to the Unique Health System to undergo surgery to correct the craniofacial changes. The current treatment aims at functional and aesthetic correction and the need for psychosocial support, having the joint participation of a multidisciplinary team to achieve this goal(AU)

Measurement of the normal mandible in neonates in east China.

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

[TCOF1 Gene variation in Treacher Collins syndrome and evaluation of speech rehabilitation after bone bridge surgery].

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.

Prenatal diagnosis of Treacher Collins syndrome: A case report and literature review.

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.

Bonebridge Implantation in Treacher-Collins Syndrome With Conductive Hearing Loss-Case Report.

The Bonebridge (BB) was the first active transcutaneous implantation system for bone conduction. The main indications are conductive or mixed hearing loss and single-sided deafness. Treacher-Collins syndrome (TCS) is a rare genetic disease that affects craniofacial development. The disorder results in deformations of facial structure including ear malformations, especially microtia and ear canal atresia. These patients suffer from conductive hearing loss. CT scans often show unfavorable temporal bone anatomy making placement of an implant difficult. For implantable hearing rehabilitation, patients may decide for conduction implants, such as a BAHA, a Ponto, a Vibrant Soundbridge, or a Bonebridge. In this case report, we present 2 patients with TCS implanted with the Bonebridge system, their audiological results, and quality of life.

Full Mouth Dental Restoration on a Treacher-Collins Patient Without Intubation.

Patients with Treacher Collins syndrome have a known difficult airway particularly if intubation is required. In most institutions that perform full mouth dental restoration (FMDR) procedures the patient is nasally intubated to protect the airway from debris and irrigation fluid. For patients with Treacher Collins syndrome the actual intubation and securing the airway can be more difficult and traumatic than the actual dental restoration itself. However, there is an airway technique using nasopharyngeal airways combined with a dental technique called "dry prepping" that can provide those patients a safe way of receiving an FMDR without intubation. A recent case report of a 29-month-old child with Treacher Collins syndrome received an FMDR without intubation.

An automatic facial landmarking for children with rare diseases.

Two to three thousand syndromes modify facial features: their screening requires the eye of an expert in dysmorphology. A widely used tool in shape characterization is geometric morphometrics based on landmarks, which are precise and reproducible anatomical points. Landmark positioning is user dependent and time consuming. Many automatic landmarking tools are currently available but do not work for children, because they have mainly been trained using photographic databases of healthy adults. Here, we developed a method for building an automatic landmarking pipeline for frontal and lateral facial photographs as well as photographs of external ears. We evaluated the algorithm on patients diagnosed with Treacher Collins (TC) syndrome as it is the most frequent mandibulofacial dysostosis in humans and is clinically recognizable although highly variable in severity. We extracted photographs from the photographic database of the maxillofacial surgery and plastic surgery department of Hôpital Necker-Enfants Malades in Paris, France with the diagnosis of TC syndrome. The control group was built from children admitted for craniofacial trauma or skin lesions. After testing two methods of object detection by bounding boxes, a Haar Cascade-based tool and a Faster Region-based Convolutional Neural Network (Faster R-CNN)-based tool, we evaluated three different automatic annotation algorithms: the patch-based active appearance model (AAM), the holistic AAM, and the constrained local model (CLM). The final error corresponding to the distance between the points placed by automatic annotation and those placed by manual annotation was reported. We included, respectively, 1664, 2044, and 1375 manually annotated frontal, profile, and ear photographs. Object recognition was optimized with the Faster R-CNN-based detector. The best annotation model was the patch-based AAM (p < 0.001 for frontal faces, p = 0.082 for profile faces and p < 0.001 for ears). This automatic annotation model resulted in the same classification performance as manually annotated data. Pretraining on public photographs did not improve the performance of the model. We defined a pipeline to create automatic annotation models adapted to faces with congenital anomalies, an essential prerequisite for research in dysmorphology.

RNA Polymerases I and III in development and disease.

Ribosomes are macromolecular machines that are globally required for the translation of all proteins in all cells. Ribosome biogenesis, which is essential for cell growth, proliferation and survival, commences with transcription of a variety of RNAs by RNA Polymerases I and III. RNA Polymerase I (Pol I) transcribes ribosomal RNA (rRNA), while RNA Polymerase III (Pol III) transcribes 5S ribosomal RNA and transfer RNAs (tRNA) in addition to a wide variety of small non-coding RNAs. Interestingly, despite their global importance, disruptions in Pol I and Pol III function result in tissue-specific developmental disorders, with craniofacial anomalies and leukodystrophy/neurodegenerative disease being among the most prevalent. Furthermore, pathogenic variants in genes encoding subunits shared between Pol I and Pol III give rise to distinct syndromes depending on whether Pol I or Pol III function is disrupted. In this review, we discuss the global roles of Pol I and III transcription, the consequences of disruptions in Pol I and III transcription, disorders arising from pathogenic variants in Pol I and Pol III subunits, and mechanisms underpinning their tissue-specific phenotypes.

Combination CPAP and bilateral hypoglossal nerve stimulation for obstructive sleep apnea in Treacher Collins syndrome: first case report.

We report the first case of bilateral hypoglossal nerve stimulator implantation in a patient with Treacher Collins syndrome and very severe obstructive sleep apnea, who was initially intolerant of continuous positive airway pressure (CPAP) treatment. Novel bilateral hypoglossal nerve stimulation in combination with CPAP allowed near obliteration of snoring, improved sleep quality, and ability to maintain the CPAP mask in position in the setting of craniofacial changes associated with this condition. CITATION: Wong ACL, Jones A, Stone A, MacKay SG. Combination CPAP and bilateral hypoglossal nerve stimulation for obstructive sleep apnea in Treacher Collins syndrome: first case report. J Clin Sleep Med. 2023;19(1):197-199.

A systematic review on Treacher Collins syndrome: Correlation between molecular genetic findings and clinical severity.

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.

Misdiagnosis of Tracher-Collins Syndrome Initially Attributed to Drug Teratogenicity: A Moroccan Case Report.

Background: 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. Case presentation: 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. Conclusions: 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.

Tratamento ortodôntico de paciente portador de síndrome de Treacher Collins ­ relato de caso / Orthodontic treatment of a patient with Treacher Collins syndrome ­ case report

Resumo Este trabalho é uma descrição de um caso clínico de paciente portador de Síndrome de Treacher Collins (STC). O paciente em questão é menor de idade e foi submetido a tratamento ortodôntico interceptivo de má oclusão de classe II, característica da síndrome devido à retrognatia, no Centro de Atenção e Pesquisa em Anomalia Craniofacial (CEAPAC), Cascavel ­ PR. As disostoses faciais são um conjunto de anomalias raras do esqueleto craniofacial, a mais comumente descrita é a STC, que é uma doença rara, sem predisposição por sexo ou raça. Os sintomas e a severidade desta síndrome diferem de indivíduo para indivíduo, mesmo entre membros da mesma família. Suas características comuns são as anormalidades dos pavilhões auriculares, hipoplasia dos ossos da face, obliquidade antimongolóide das fendas palpebrais com coloboma palpebral inferior e fissura palatina e o principal problema anatômico é a hipoplasia do terço médio da face e o hipodesenvolvimento da mandíbula e mento, o que leva o paciente portador desta síndrome apresentar por suas características faciais uma má oclusão de classe II muitas vezes associadas à mordida aberta, além de outros problemas orais como, por exemplo, as patologia das glândulas salivares, respiração bucal e apinhamento dentário. O tratamento ortodôntico intercepetivo do menor, embora após terminado tenha permanecido com má oclusão de classe II, obteve mudanças em parâmetros cefalométricos e faciais do paciente.(AU)

Abstract This work is a description of a clinical case of a patient with Treacher Collins Syndrome (CTS). The patient in question is younger and underwent interceptive orthodontic treatment of class II malocclusion, characteristic of the syndrome due to retrognathia, at the Center for Attention and Research in Craniofacial Anomaly (CEAPAC), Cascavel ­ PR. Facial dysostosis is a set of rare anomalies of the craniofacial skeleton, the most commonly described being CTS, it is a rare disease, without predisposition by sex or race. The symptoms and severity of this syndrome differ from individual to individual, even among members of the same family. Its common features are auricular pavilion abnormalities, facial bone hypoplasia, antimongoloid obliquity of the palpebral fissures with lower palpebral coloboma and cleft palate, and the main anatomical problem is hypoplasia of the middle third of the face and hypodevelopment of the mandible and chin, which Due to their facial characteristics, patients with this syndrome have a Class II malocclusion, often associated with an open bite, in addition to other oral problems such as salivary gland pathology, mouth breathing and dental crowding. The minor's interceptive orthodontic treatment, although after it ended, he remained with class II malocclusion, resulted in changes in the patient's cephalometric and facial parameters.(AU)

TCOF1 Gene variation in Treacher Collins syndrome and evaluation of speech rehabilitation after bone bridge surgery / 临床耳鼻咽喉头颈外科杂志

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.