The First Patient with Tibial Hemimelia-Polysyndactyly-Triphalangeal Thumb Syndrome Caused by De Novo c.423+4916 T>C ZRS Variant: A Case Report.

Genetic variants in the zone of polarizing activity regulatory sequence (ZRS) that induce ectopic expression of the SHH gene have been associated with different ZRS-related phenotypes. We report the first patient with a de novo variant, c.423+4916 T>C, in ZRS (previously classified as a variant of uncertain significance) that causes tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome (THPTTS). A two-month-old male patient presented with bilateral preaxial polydactyly, triphalangeal thumb, and tibial agenesis and was heterozygous for the variant c.423+4916T>C (neither of his parents was a carrier). The findings obtained from the family study were sufficient to reclassify the variant from "uncertain significance" to "likely pathogenic" according to three criteria from the American College of Medical Genetics and Genomics guidelines, as follows: (1) absence of gnomAD, (2) confirmation of paternity and maternity, and (3) strong phenotype-genotype association. In ZRS-associated syndromes, a wide clinical spectrum has been observed, ranging from polydactyly to THPTTS; our patient has the most severe and rare phenotype. We did not perform functional assays. However, the c.423+4916T>C variant is flanked by three variants, which have been proven not only to cause the phenotype but also to increase the expression of SHH. Through all this data gathering, we consider the c.423+4916T>C variant to be causative of THPTTS.

The transcription of the main gene associated with Treacher-Collins syndrome (TCOF1) is regulated by G-quadruplexes and cellular nucleic acid binding protein (CNBP).

Treacle ribosome biogenesis factor 1 (TCOF1) is responsible for about 80% of mandibular dysostosis (MD) cases. We have formerly identified a correlation between TCOF1 and CNBP (CCHC-type zinc finger nucleic acid binding protein) expression in human mesenchymal cells. Given the established role of CNBP in gene regulation during rostral development, we explored the potential for CNBP to modulate TCOF1 transcription. Computational analysis for CNBP binding sites (CNBP-BSs) in the TCOF1 promoter revealed several putative binding sites, two of which (Hs791 and Hs2160) overlap with putative G-quadruplex (G4) sequences (PQSs). We validated the folding of these PQSs measuring circular dichroism and fluorescence of appropriate synthetic oligonucleotides. In vitro studies confirmed binding of purified CNBP to the target PQSs (both folded as G4 and unfolded) with Kd values in the nM range. ChIP assays conducted in HeLa cells chromatin detected the CNBP binding to TCOF1 promoter. Transient transfections of HEK293 cells revealed that Hs2160 cloned upstream SV40 promoter increased transcription of downstream firefly luciferase reporter gene. We also detected a CNBP-BS and PQS (Dr2393) in the zebrafish TCOF1 orthologue promoter (nolc1). Disrupting this G4 in zebrafish embryos by microinjecting DNA antisense oligonucleotides complementary to Dr2393 reduced the transcription of nolc1 and recapitulated the craniofacial anomalies characteristic of Treacher Collins Syndrome. Both cnbp overexpression and Morpholino-mediated knockdown in zebrafish induced nolc1 transcription. These results suggest that CNBP modulates the transcriptional expression of TCOF1 through a mechanism involving G-quadruplex folding/unfolding, and that this regulation is active in vertebrates as distantly related as bony fish and humans. These findings may have implications for understanding and treating MD.

Severity of Mandibular Dysmorphology in Treacher Collins Syndrome for Stratification of Perioperative Airway Risk.

BACKGROUND: Patients with Treacher Collins syndrome (TCS) and attendant airway dysmorphology may be predisposed to airway complications in the perioperative period. However, limited data correlates severity of mandibular hypoplasia and airway status. This study aims to improve risk stratification for perioperative airway insufficiency in TCS by using a previously proposed mandibular severity index. METHODS: Patient demographics, perioperative airway status, difficulty of intubation, and Cormack Lehane grade were collected and compared using a TCS mandibular hypoplasia severity grading scale in patients with TCS treated between 2000 and 2022. RESULTS: Twenty-six patients underwent 222 procedures with institutional mandibular severity gradings as follows: 23% Grade I, 31% Grade II, 39% Grade III, 8% Grade IV. Our severity index was associated with intubation difficulty ( P <0.001) and difficult airway status ( P <0.001), with 72% of difficult airways found in grade III and grade IV patients. Mandibular retrusion and ramal hypoplasia subscores were positively correlated with measures of airway severity ( P <0.001), whereas the gonial angle was negatively correlated ( P <0.001). Age was negatively correlated with difficult visualization for endotracheal intubation ( P =0.02) but had no association with difficult airway status ( P =0.2). CONCLUSIONS: This study found a positive correlation between severity of maxillomandibular dysmorphology and perioperative airway difficulty in TCS patients. Our findings suggest that severely affected patients require heightened vigilance throughout life, as difficult airways may not completely resolve with aging. Given the risk of morbidity and mortality associated with airway complications, proper identification and preparation for challenging airways is critical for TCS patients.

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)

Dental and health aspects in the co-occurrence of Treacher Collins and Down syndromes: Case report.

The goal of this case report is to identify the dental care of a patient who has co-occurrence of Treacher Collins and Down syndromes. It is the third case reported in the literature and the first relating dental treatment under general anesthesia and multidisciplinary importance. It was necessary the child's nutritional assessment in this case. This case highlights the importance of individualizing therapeutic protocols, due to the behavioral aspects of patients with special needs, optimizing treatment results in a single session under general anesthesia. Oral health is closely related to overall health, and it is important for awareness that the whole influences the success of medical treatment.

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)

Descripción clínica y hallazgos polisomnográficos en tres pacientes con Síndrome de Treacher Collins / Clinical description and polysomnographic findings in three patients with Treacher Collins

El Síndrome de Treacher Collins (STC) es una enfermedad congénita del desarrollo craneofacial, siendo una complicación frecuente la obstrucción de la vía aérea. Objetivo: Describir clínicamente tres casos de STC y sus hallazgos polisomnográficos. Diseño: Estudio observacional, descriptivo y retrospectivo. Revisión de fichas clínicas y polisomnografías (PSG). Resultados: Se incluyeron tres pacientes con STC, de 1, 17 y 20 años, dos hombres. Todos presentaron malformaciones faciales compatibles con el STC. El paciente menor tuvo apneas desde el nacimiento. En las PSG, todos presentaron eficiencia del sueño disminuida e índice de microdespertares aumentado. Solo un paciente tuvo diagnóstico de Síndrome de Apnea/Hipoapnea Obstructiva del Sueño (SAHOS) severo. Conclusiones: Aún cuando las anomalías craneofaciales no difirieron entre los pacientes, hubo sólo un caso de SAHOS severo. Las otras alteraciones descritas en la PSG afectan la calidad de vida, siendo relevante la búsqueda activa de trastornos respiratorios del sueño en estos pacientes.

Treacher Collins Syndrome (STC) is a congenital craniofacial disorder, being the airway obstruction a frequent complication. Objective: To describe clinical and polysomnographic findings of three cases with STC. Methods: An observational, descriptive and retrospective study. Review of clinical records and nocturnal polysomnography was carried out. Results: Three patients with STC were included of 1, 17 and 20 years old, two were males. All of them with facial malformations compatible with STC. Only the youngest presented apneas since birth. All patients had decreased sleep efficiency and increased arousal index. Only one patient presented with severe Obstructive Sleep Apnea Syndrome (OSAS). Conclusions: Despite the fact that all the patients had similar craniofacial anomalies, only one presented with severe OSAS. The other abnormalities described in the polysomnography affect the quality of life, being relevant performing an active screening of breathing-related sleep disorders in these patients.

The role of double-step advancement genioplasty and bilateral coronoidectomy in Nager Syndrome: A case report.

AIM: To report the surgical management of bilateral mandibular coronoid processes hyperplasia and mandibular retrognathism associated with trismus and convex facial profile in an individual diagnosed with Nager syndrome (NS). CASE REPORT: A 21 years old female was referred to the Department of Oral and Maxillofacial Surgery, presenting limited mouth opening and an unpleasant convex facial profile. The tomography exhibited hyperplasia of mandibular coronoid processes with no evidence of intracapsular ankylosis of the temporomandibular joint. The treatment objectives were to increase mouth opening through a bilateral coronoidectomy and gain chin projection using the double-step advancement genioplasty technique. The 9-month postoperative follow-up revealed a 22.22% (6 mm) gain in jaw opening, improved masticatory function, and facial profile. CONCLUSIONS: The NS is a complex craniofacial anomaly due to its clinical heterogeneity. Thus, treatment planning must be done individually, considering the patients' main complaints and respecting the limitations regarding anatomy and availability of proper surgical materials. In the present case, a bilateral coronoidectomy associated with immediate physiotherapy improved the patient's mouth opening, and the double-step genioplasty promoted a much more significant chin advancement than would be obtained with the single-step traditional osteotomy.

Caso clínico: aproximación a la vía aérea difícil en neonatología. Síndrome de Treacher-Collins / Clinical case: approach to the difficult airway in neonatology. Treacher-Collins syndrome

Cuando los recién nacidos presentan obstrucción de la vía aérea, requieren un manejo urgente y experto para evitar la mortalidad y la morbilidad. La definición de vía aérea difícil se relaciona con problemas en la intubación endotraqueal o en la ventilación a presión positiva con bolsa y máscara o reanimador de pieza en T. El manejo debe basarse en la comprensión del mecanismo fisiopatológico responsable de la vía aérea difícil. Las causas en el recién nacido pueden ser congénitas y/o adquiridas.Se presenta el caso de una recién nacida con síndrome de Treacher-Collins tipo 1 [OMIM #154500] con una disostosis mandibulofacial, micrognatia, hipoplasia malar, paladar hendido, sin cardiopatía congénita, asociado con intubación extremadamente difícil

f newborns have an airway obstruction, they require urgent and expert management to avoid mortality and morbidity. The definition of difficult airway includes problems in endotracheal intubation or positive pressure ventilation with bag and mask or T-piece resuscitator. Management should be based on an understanding of the pathophysiological mechanism responsible for difficult airway. The causes of difficult airway in the newborn can be congenital or acquired.We present the case of a newborn with Treacher-Collins syndrome Type 1 [OMIM # 154500] with a mandibulofacial dysostosis, micrognathia, malar hypoplasia, cleft palate, without congenital heart disease, associated with extremely difficult intubation

[Clinical case: approach to the difficult airway in neonatology. Treacher-Collins syndrome]. / Caso clínico: aproximación a la vía aérea difícil en neonatología. Síndrome de Treacher-Collins.

If newborns have an airway obstruction, they require urgent and expert management to avoid mortality and morbidity. The definition of difficult airway includes problems in endotracheal intubation or positive pressure ventilation with bag and mask or T-piece resuscitator. Management should be based on an understanding of the pathophysiological mechanism responsible for difficult airway. The causes of difficult airway in the newborn can be congenital or acquired. We present the case of a newborn with Treacher-Collins syndrome Type 1 [OMIM # 154500] with a mandibulofacial dysostosis, micrognathia, malar hypoplasia, cleft palate, without congenital heart disease, associated with extremely difficult intubation.

Cuando los recién nacidos presentan obstrucción de la vía aérea, requieren un manejo urgente y experto para evitar la mortalidad y la morbilidad. La definición de vía aérea difícil se relaciona con problemas en la intubación endotraqueal o en la ventilación a presión positiva con bolsa y máscara o reanimador de pieza en T. El manejo debe basarse en la comprensión del mecanismo fisiopatológico responsable de la vía aérea difícil. Las causas en el recién nacido pueden ser congénitas y/o adquiridas. Se presenta el caso de una recién nacida con síndrome de Treacher-Collins tipo 1 [OMIM #154500] con una disostosis mandibulofacial, micrognatia, hipoplasia malar, paladar hendido, sin cardiopatía congénita, asociado con intubación extremadamente difícil.

Comparison Between Treacher Collins Syndrome and Pierre Robin Sequence: A Cephalometric Study.

OBJECTIVE: The aim of this study was to compare the dentoskeletal pattern of Treacher Collins syndrome (TCS) and nonsyndromic Pierre Robin sequence (PRS). DESIGN: Retrospective. SETTING: Single center. PATIENTS: Eighteen patients diagnosed with TCS (Group TCS) or PRS (Group PRS) in rehabilitation treatment at a single center. Group TCS was composed of 9 patients (4 male, 5 female) with a mean age of 12.9 years (standard deviation = 4.8). Group PRS was composed of 9 patients paired by age and sex with group TCS. MAIN OUTCOME MEASURE(S): Cone beam computed tomography-derived cephalometric images taken before the orthodontic or the orthodontic-surgical treatment were analyzed using Dolphin Imaging (Dolphin Imaging 11.0 & Management Solutions). Variables evaluating the cranial base, the maxillary and mandibular skeletal components, maxillomandibular relationship, the vertical components and the dentoalveolar region were measured. Intergroup comparisons were performed using t tests. The significance level considered was 5%. RESULTS: Intergroup differences in the mandible size and growth pattern were observed. Group TCS showed a smaller mandibular length (Co-Go, Co-Gn) and a higher palatal plane (SN-Palatal Plane) and mandibular plane angles (SN-Go.Gn) compared to group PRS. No differences between TCS and PRS were observed for the sagittal position of the maxilla, maxillomandibular relationship, and dental components. CONCLUSIONS: Treacher Collins syndrome presented a decreased mandible and a more severe vertical growth pattern compared to PRS.

Assessment of craniofacial and dental characteristics in individuals with treacher collins syndrome. A review.

Treacher Collins Syndrome (TCS) is a genetic disorder with predominantly autosomal dominant inheritance, associated with different mutations in specific genes. This review aimed to evaluate the facial, temporomandibular, zygomatic and bucco-dental phenotype in TCS individuals, and describe surgical and non-surgical solutions for each case in order to improve the quality of life of these individuals. A review of the literature on the craniofacial characteristics of the TCS was carried out, using the PICO strategy, and then a systematic search method was performed in Medline, Scopus, LILACS and SCIELO databases, identifying articles of impact and relevance until 10 June 2020, 240 articles were recovered and only 35 fulfilled the selection criteria. We found the main craniofacial and oral morphological characteristics of these individuals, and the possible functional alterations inducing repercussion in the stomatognathic apparatus. Among other characteristics, the most representative include hypoplasia in the zygomatic and mandibular complex, which can cause difficulty in breathing and feeding. In some cases, cleft palate and malocclusions such as anterior open bite may lead to Angle's Class II malocclusion, sometimes causing problems in the temporomandibular joint. In conclusion, individuals with TCS have specific craniofacial features including maxillary hypoplasia, altered orbital zones, mandibular retrognathia, and temporomandibular disorders. Oral deformities produce to a higher prevalence of caries and calculus formation because of poor hygiene due to the malformations present in these patients.

Anestesia en paciente pediátrico con Síndrome de Treacher Collins / Anesthesia in a pediatric patient withTreacher Collins Syndrome / Anestesia em paciente pediátrico com Síndrome de Treacher Collins

El Síndrome de Treacher Collins (STC) constituye un reto para el anestesiólogo por malformaciones craneofaciales que complican el manejo de su vía aérea e intubación. Presentamos el caso de una paciente (8 años) con diagnóstico de STC que debía someterse a una cirugía de colocación de implante de conducción ósea bajo anestesia general. Presentaba un antecedente de intubación difícil, marcada micrognatia y distancia tiromentoniana de 2 cm. Se planteó un esquema de intubación en dos etapas secuenciales. En la primera etapa se realizó una evaluación de la vía aérea (visualización de la glotis) bajo sedación con dexmedetomidina, remifentanilo y propofol. Al visualizar la glotis se pasó a la segunda etapa para realizar la intubación posterior a la inducción anestésica.El manejo exitoso se fundamentó en una sedación adecuada y la utilización de un videolaringoscopio con pala curva para la evaluación previa de la vía aérea y posterior intubación sin complicaciones

Treacher Collins Syndrome (TCS) constitutes a challenge for the anesthesiologist due to craniofacial malformations that make management of the airway and intubation difficult. We present a case of a patient (8-year-old) diagnosed with TCS who had to undergo surgery for the placement of a bone conduction implant under general anesthesia. She had a history of difficult intubation, marked micrognathia and a thyromental distance of 2 cm. An intubation scheme in two sequential stages was proposed. In the first stage, an evaluation of the airway (visualization of the glottis) was carried out under sedation with dexmedetomidine, remifentanil and propofol. When the glottis was visualized, we proceeded to the second stage to carry out intubation after anesthetic induction.The successful management of this case was based on adequate sedation and the use of a video laryngoscope with a curved blade for prior evaluation of the airway and subsequent intubation without complications

A síndrome de Treacher Collins (STC) constitui um desafio para o anestesiologista devido às malformações craniofaciais que dificultam o manejo da via aérea e a intubação. Apresentamos o caso de uma paciente (8 anos) com diagnóstico de STC que foi submetida a uma cirurgia para colocação de implante de condução óssea sob anestesia geral. Ela tinha história de intubação difícil, micrognatia acentuada e distância tiromentoniana de 2 cm. Foi proposto um esquema de intubação em duas etapas sequenciais. Na primeira etapa, foi realizada avaliação das vias aéreas (visualização da glote) sob sedação com dexmedetomidina, remifentanil e propofol. Quando a glote foi visualizada, a segunda etapa foi realizada para realização da intubação após a indução anestésica. O manejo bem-sucedido baseou-se na sedação adequada e no uso de videolaringoscópio com lâmina curva para avaliação prévia da via aérea e posterior intubação sem complicações

Narrativas sobre a vida e o início do tratamento de uma paciente com Síndrome de Treacher Collins: um estudo de caso / Stories about life and treatment onset of a patient with Treacher Collins syndrome: case study

Síndrome de Treacher Collins (STC) é uma anomalia do desenvolvimento craniofacial rara de manifestação clínica variável. Este estudo teve por objetivo principal analisar a experiência de uma mulher de 26 anos com STC que iniciou a reabilitação na idade adulta, buscando aprofundar possíveis impactos para o seu desenvolvimento. Com aprovação do Comitê de Ética em Pesquisa (CAAE 00981418.3.0000.5441), realizou-se um estudo de caso clínico por meio da análise documental do prontuário multiprofissional e uma entrevista semiestruturada gravada em áudio, transcrita integralmente e analisada qualitativamente pela técnica de Análise de Conteúdo de Bardin. Evidenciaram-se duas categorias temáticas que sinalizam a experiência de vida da participante dividida em dois momentos: (1)"Desenvolvimento até a fase adulta" que abarcou as subcategorias: "O que eu tenho?"; "Relacionamento com a mãe"; "Eu sofri bullying: desafio da escolarização" (2) "Ser alguém com Síndrome de Treacher Collins", e subcategorias: "Existem outros como eu: conhecendo o diagnóstico"; "Início do tratamento: desafios e expectativas"; "A psicologia e a equipe interdisciplinar"; "Mas hoje eu sou feliz: planos para o futuro". STC, sendo uma malformação facial, pode implicar em conviver com o estigma de não apresentar o rosto dentro dos padrões sociais impostos. No caso analisado, apontou-se sofrimento emocional, sendo este intensificado pelo não pedido de ajuda. Por outro lado, o diagnóstico da síndrome possibilitou o processo de identificação com outros sujeitos acometidos, o início da reabilitação e a vivência de impactos positivos em sua qualidade de vida. A psicologia figurou como espaço de escuta e possibilidade de reflexão sobre o processo de reabilitação.

The Treacher Collins syndrome (TCS) is a rare anomaly of craniofacial development with variable clinical manifestation. The main goal of this study was to analyze the experience of a 26-year-old woman with TCS who initiated her rehabilitation in adulthood, aiming to deepen the possible impacts on her development. After approval by the Institutional Ethics Review Board (CAAE 00981418.3.0000.5441), the case study was conducted by documental analysis of the multiprofessional patient records and a semi-structured interview recorded in audio, transcribed in full and qualitatively analyzed by the Content Analysis technique of Bardin. Two theme categories were evidenced that indicated the life experience of the participant divided in two periods: (1) "Development up to adulthood", which included the subcategories: "What's wrong with me?"; "Relationship with the mother"; "I suffered bullying: challenge of school education" (2) "Being someone with Treacher Collins syndrome", and subcategories: "There are others like me: knowing the diagnosis"; "Treatment onset: challenges and expectations"; "Psychology and the interdisciplinary team"; "But I am happy today: plans for the future". Since TCS is a facial malformation, it may involve living with the stigma of not presenting a face within the imposed social standards. The present case presented emotional suffering, worsened because she did not ask for help. Conversely, the diagnosis of the syndrome allowed the process of identification with other affected individuals, the onset of rehabilitation and experience of positive impacts on her quality of life. Psychology participated as a space for hearing and possibility of reflecting about the rehabilitation process.

Three-Dimensional Upper Airway Assessment in Treacher Collins Syndrome.

OBJECTIVES: The purpose of this investigation was to assess the pharyngeal dimensions and the craniofacial morphology of individuals with Treacher Collins syndrome (TCS) when compared to vertical skeletal class II individuals. It is our hypothesis that the upper airways of individuals with TCS are reduced in view of the skeletal pattern and the maxillomandibular dysmorphologies. MATERIALS AND METHODS: Cone-beam computed tomography scans of 26 individuals had the pharyngeal volume (V) and minimal cross-sectional area (mCSA) evaluated. Study group (TCS) was formed by 13 scans of patients with TCS (7 males and 6 females; 20.2 ± 4.7 years). Control group (CG) assembled 13 scans of nonaffected individuals with the same type of skeletal pattern (2 males and 11 females; 26.6 ± 5.4 years). Cephalometric data of maxillomandibular position, maxillomandibular dimensions, and growth pattern were assessed. Statistical analysis (P ≤ .05) included Student t test and Pearson correlation coefficient. RESULTS: Although reduced, pharyngeal V and mCSA of TCS were not statistically different from the CG. On both groups, mCSA was mostly at the oropharyngeal level. Individuals with TCS presented retrognathic chin, reduced maxillomandibular dimensions, and increased clockwise rotation of the palatal plane. Maxillary and mandibular lengths were correlated with pharyngeal V and mCSA. CONCLUSIONS: The pharyngeal dimensions of individuals with TCS are impacted by the micrognathia and retrognathia. In association with the skeletal pattern, the reduction of the airways, although not statistically significant, may explain the increased prevalence of airways disorder in this syndrome.

Características clínicas y radiológicas en individuos con Síndrome Treacher Collins: reporte de casos / Radiologic and clinic characteristics in individuals with Treacher Collins Syndrome: case report

El Síndrome de Treacher Collins es una malformación craneofacial autosómica dominante (STC) que se presenta cuando el gen TCOF1 (5q32-q33.1) sufre una mutación. Su incidencia se estima en 1/50,000 nacidos y presenta manifestaciones en tejidos blandos y duros. Métodos: Seis individuos diagnosticados con STC, remitidos de la Asociación Treacher Collins México AC, para la realización de estudios imagenológicos prequirúrgicos. Objetivo: Describir las características clínicas, radiográficas y morfométricas de individuos con esta condición. Resultados: No existen suficientes estudios en los cuales se determinen patrones específicos en un mismo individuo, e incluso cuando se comparan entre sí, por lo que es necesario establecer protocolos para su manejo. Conclusiones: Las características clínicas del individuo con STC varían de acuerdo con la severidad de expresión genética, las cuales se pueden corroborar con fotografías, imágenes radiográficas y medidas morfométricas que nos orientaran en el manejo y planeación del tratamiento. (AU)

Treacher Collins Syndrome is a craniofacial, autosomal dominant, severe and complex malformation that occurs when the TCOF1 (5q32-q33.1) gene suffers a mutation. Its incidence is estimated at 1/50,000 births and shows manifestations in soft and hard tissues. Methods: Six individuals whit TCS diagnosis refer from Asociacion Treacher Collins México AC to do a pre-surgical imaging studies. Objective: Describe the clinical, radiographic and morphometric characteristics of individuals with this condition. Results: There are not enough studies that may establish specific patterns in the same individual and even when compared to each other, so it is necessary to establish protocols for their management. Conclusions: The clinical characteristics of the individual with TCS vary according to the severity of genetic expression, which can be corroborated with photographs, radiographic images and morphometric measurements that will guide us is the management and planning of treatment. (AU)

Proteasomal inhibition attenuates craniofacial malformations in a zebrafish model of Treacher Collins Syndrome.

Treacher Collins Syndrome (TCS) is a congenital disease characterized by defects in the craniofacial skeleton and absence of mental alterations. Recently we modelled TCS in zebrafish (Danio rerio) embryos through the microinjection of Morpholino® oligonucleotides blocking the translation of the ortholog of the main causative gene (TCOF1). We showed that Cnbp, a key cytoprotective protein involved in normal rostral head development, was detected in lower levels (without changes in its mRNA expression) in TCS-like embryos. As previous reports suggested that Cnbp is degraded through the proteasomal pathway, we tested whether proteasome inhibitors (MG132 and Bortezomib (Velcade®, Millennium laboratories)) were able to ameliorate cranial skeleton malformations in TCS. Here we show that treatment with both proteasome inhibitors produced a robust craniofacial cartilage phenotype recovery. This recovery seems to be consequence of a decreased degradation of Cnbp in TCS-like embryos. Critical TCS manifestations, such as neuroepithelial cell death and cell redox imbalance were attenuated. Thus, proteasome inhibitors may offer an opportunity for TCS molecular and phenotypic manifestation's prevention. Although further development of new safe inhibitors compatible with administration during pregnancy is required, our results encourage this therapeutic approach.

A linguagem na Síndrome de Treacher Collins: uma análise dialógica / Language in Treacher Collins Syndrome: a dialogical analysis

RESUMO A Síndrome de Treacher Collins ou Disostose Mandibulofacial é decorrente de mutações genéticas e caracterizada por malformações craniofaciais. Crianças com essa síndrome podem apresentar dificuldades cognitivas, linguísticas e psicomotoras. São raras as publicações que discorrem sobre a complexidade de seus aspectos terapêuticos, especialmente, voltados à evolução clínica vinculada à linguagem. O presente estudo objetiva analisar o processo terapêutico voltado à oralidade de um menino com essa síndrome, considerando a natureza dialógica da linguagem. Trata-se de um estudo de caso longitudinal e prospectivo, realizado em uma clínica-escola de uma Universidade, situada no sul do Brasil, durante quatro anos, desde 2012 até 2016. Os dados foram coletados a partir de gravações semanais do paciente em interação com os seus terapeutas, sendo, também, considerados os registros arquivados em seu prontuário. Os resultados indicam que a criança apresentou evolução no que se refere à apropriação da linguagem oral. Apesar das dificuldades na produção vocal e na articulação de fonemas, decorrentes de alterações craniofaciais próprias da síndrome em questão, as atividades dialógicas estabelecidas entre o menino, seus terapeutas e sua família, propiciaram mudanças gradativas no seu posicionamento em relação ao outro e à linguagem. Inicialmente, ele fazia uso de gestos, mímicas faciais, apontamentos, os quais eram compreendidos apenas pelas pessoas que faziam parte do seu cotidiano. Atualmente, além dos recursos gestuais, ele passou a usar a oralidade para participar de práticas interativas, indicando mais autonomia para interagir com seus interlocutores.

ABSTRACT The Treacher Collins Syndrome or Mandibulofacial dysostosis is due to genetic mutations and characterized by craniofacial malformations. Children with this syndrome may present cognitive, linguistic and psychomotor difficulties. There are few publications that discuss the complexity of its therapeutic aspects, especially those focused on language clinical evolution. The present study aims to analyze a speech - language clinical work on oral language of a boy who has this syndrome, considering the dialogical nature of language. This is a longitudinal and prospective case study, carried out in a university clinic located in the south of Brazil, during four years, from 2012 to 2016. Data were collected from weekly recordings of the patient interacting with his therapists, and also from his record files. The results indicate that this child presented oral language appropriation evolution. Despite his vocal production and phonemes articulation´s difficulties, due to his craniofacial alterations that characterize this syndrome, the dialogical activities established between the child, his therapists and his family, caused gradual changes in his language use. Initially, he used gestures, facial mimics, pointing, which were understood only by people who were part of his daily life. Nowadays, he still uses gestures, but he also began to use oral language to participate in interactive practices, which indicates his autonomy to interact with other people.

Revisión bibliográfica sobre síndrome de Treacher Collins / Treacher Collins síndrome: A review

INTRODUCTION: Treacher Collins syndrome is a rare disorder of the craniofacial development that constitutes a challenge for anesthesiologists, since it represents a difficult airway in the majority of cases. The main objective of this article is to provide a bibliographic review about how the airway management of patients with Treacher Collins syndrome has been managed. MATERIALS AND METHODS: A literature review was carried out in the following databases: PubMed, EMBASE and ScienceDirect. DISCUSSION: The factors that increase the risk of difficult airway in these patients are presented as well as the strategies to handle it. CONCLUSION: The Treacher Collins syndrome presents a high risk of difficult airway, therefore careful planning of airway management is mandatory and there are different strategies to handle it.

INTRODUCCIÓN: El síndrome de Treacher Collins (STC) es un trastorno inusual del desarrollo craneofacial que constituye un reto para el anestesiólogo, ya que éste condiciona la condición de vía aérea difícil en la mayoría de los casos. El objetivo principal de este artículo es realizar una revisión bibliográfica de cómo se han manejado casos de vía aérea difícil ligados al síndrome de Treacher Collins. MATERIALES Y MÉTODOS: Se realizó una revisión de la literatura disponible en las siguientes bases de datos: PubMed, EMBASE y ScienceDirect. DISCUSIÓN: Se presentan los factores que aumentan el riesgo de vía aérea difícil en estos pacientes, así como las estrategias para manejarla. CONCLUSIÓN: El síndrome de Treacher Collins presenta un alto riesgo de vía aérea difícil, por lo tanto, es obligatoria la planificación cuidadosa de la misma, contando con diferentes estrategias para manejarla.