Treacher Collins综合征的致病基因和临床治疗策略

Treacher Collins综合征是以常染色体显性遗传为主要遗传方式的先天颅面畸形。由于神经嵴细胞和神经上皮细胞核糖体的生物合成受阻,神经嵴细胞迁移到颅面部的数量减少,引起第一、二鳃弓发育不全,导致疾病发生。目前明确的致病基因包括细胞质核糖体生物发生因子1（tcof1）、聚合酶Ⅰ亚基c（polr1c）和聚合酶Ⅰ亚基d（polr1d）。本文就目前针对该综合征的3个主要致病基因的遗传学研究和发病机制探索,以及该综合征的临床表现、预防及临床治疗策略作一综述。     

Treacher Collins综合征1例

Treacher Collins综合征患者临床上较为少见。我科2004年8月收治了一例Treacher Collins综合征患者,现报告如下。     

综合征与非综合征型腭裂患者颅颌面结构特征的对比研究

目的比较和认识综合征型与非综合征型腭裂患者颅颌面结构的差异和特点,揭示综合征型腭裂患者上下颌骨生长发育的规律以及腭裂与颌面部其他畸形之间的关系。方法采集符合特定条件的混合牙列期男性腭裂患者57例,其中Treacher Collins综合征8例,Pierre Robin综合征9例、非综合征型腭裂患者40例。所有患者行侧位头影测量检查,对侧位片进行定点分析并且选择18项指标进行测量,使用SPSS 12.0软件对其结果进行统计学分析。结果与非综合征型腭裂患者相比,综合征型腭裂患者下颌骨生长发育的差异主要表现为SNB的减小和ANB的增大（P<0.05）,提示综合征型腭裂患者下颌骨在前后方向上的发育较非综合征型腭裂患者相对不足;而两组患者的上颌骨前后向发育无统计学差异（P>0.05）,颅底的生长发育亦无统计学差异（P>0.05）。结论综合征型腭裂患者的上颌骨形态结构以及生长发育与非综合征型腭裂患者基本类似,两者之间存在着相似的生长发育潜力;腭裂患者颅颌面诸骨的生长发育既相互影响又相对独立。     

小鼠颅神经嵴细胞的培养和特征

目的：在体外原代培养Balb/c小鼠胚胎的颅神经嵴细胞。为颅面部各种组织细胞的发育研究提供细胞来源。方法：采用胰酶消化法分离小鼠胚胎第8.5天的颅神经管，从小鼠颅神经管中游离出来的细胞即为颅神经嵴细胞，用免疫组织化学方法鉴定细胞的来源，并测定细胞的生长曲线。结果：成功地培养出小鼠的颅神经嵴细胞，其形态类似成纤维样细胞，免疫组化检测结果表明，神经特异性烯醇化酶（NSE）抗体染色结果阳性。细胞的群体倍增时间为43.65h。结论：原代培养的小鼠颅神经嵴细胞生长稳定，来源明确，是颅面部各种细胞的发育和分化研究中一种有用的工具。     

牙齿发育异常及颅面异常综合征致病基因研究的新进展

基因突变是导致牙颌面畸形的重要原因。目前我国牙颌面畸形的发病率高达67．87％，其中遗传性畸形占有较高的比例。随着人类基因组计划的完成和功能基因组计划的实施以及生命科学领域前沿技术向口腔医学的广泛渗透，一系列牙颌面畸形相关基因及其突变正在被逐步阐明。以下拟从先天性牙齿缺失、多生牙、牙本质发育不全、颌骨及软组织异常、非综合征性唇腭裂畸形五个方面概述相关基因及其突变的最新进展。     

颅神经嵴细胞的迁移及特性

颅神经嵴细胞(CNCC)是动物胚胎发育过程中出现的一个暂时性、可迁移、多潜能细胞群,它对颅颌面发育具有十分重要的意义.起源于背侧神经管的CNCC,在多种因素的调控下,于胚胎内经过长距离的、精确的迁移.最终到达其目标区域,并进一步衍生为骨、软骨、神经、结缔组织等多种组织,构成了颅颌面大部分重要的软硬组织结构.因此,CNC...     

颅神经嵴细胞迁移的调控

<正>颅神经嵴细胞(cranial neural crest cells,CNCC)起源于背侧神经管,是一个对颅颌面部各种软硬组织的衍生都具有十分重要作用的细胞群。其产生后便向腹侧迁移,并向多种方向进行分化,如骨细胞、神经元细胞、神经胶质细胞、色素细胞、肌细胞等等[1],而这些细胞则进一步组织构建成颅颌面大部分的软硬结缔组织,因此,颅神经嵴细胞对于颅颌面发育具有十分重要的意义。颅神经嵴细胞迁移的启动、迁移     

Pierre Robin序列征的精准诊断和遗传病因学研究进展

Pierre Robin序列征是一种具有强烈遗传异质性的先天性颅面畸形,主要表现为小下颌、舌后坠和腭裂,致病基因包括SRY-box转录因子9 (SOX9)、内向整流型钾离子通道亚家族J成员2 (KCNJ2)、远端同源异型盒5/6(DLX5/6)、白细胞抗原相关家族受体蛋白酪氨酸磷酸酶（LAR RPTPs）和骨形态发生蛋白2 (BMP2)等;产前影像检查重点围绕小下颌,宫内舌位和形状可帮助判断。本文主要就该序列征的临床表现、遗传病因和诊断作一综述,明确该疾病的病因和发病机制,并指导产前影像检查方法,为该疾病的精准诊断提供支持。     

成纤维细胞生长因子8调控颅面部发育和畸形的研究进展

成纤维细胞生长因子8(fibroblast growth factor 8,FGF8)是一种分泌型多肽,在多种组织器官的发育中扮演着重要角色。研究发现,FGF8可以通过激活丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路调节颅神经嵴细胞的分化,通过调节靶基因的表达影响下颌弓极性的建立以及颅面部的对称性发育。唇腭裂、纤毛病、巨口畸形以及无颌畸形是四种累及颅面部的发育畸形,严重影响患者的生存质量。由基因突变、蛋白构象或表达异常引起的FGF8信号异常与颅面部畸形的发生密切相关,但其中的分子机制和信号通路尚未完全阐明。颅面部发育是由多种信号分子介导的复杂过程,未来需深入探索各种信号分子在颅面部发育和畸形中的作用,为预防和治疗这些颅面部畸形提供新的角度和视野。     

颅面外科三维诊断分析和手术设计系统的建立

目的　探讨正常颅面结构内在美学规律、研究复杂颅面畸形的解剖结构特征及其整复手术设计方法。方法　建立了颅颌面外科三维诊断分析和手术设计计算机系统 (3DCMFCADS) ,并将系统应用于正常颅面分析和颅面畸形整复手术设计。结果　所建系统整机运行稳定 ,测量分析误差微小 ,精密度最大变异系数仅 1.92 % ,手术模拟设计和构建的移植体或植入体三维模型形态逼真、参数准确。所建系统和方法的优特点表现在 :1可同时显示硬、软组织结构并对其进行三维测量分析和手术模拟设计。 2可显示颅面立体结构 ;可定性和定量地诊断分析颅面畸形 ;可进行手术模拟并设计移植或植入修复体三维模型。 3可利用国内较普及的 CT扫描机和微型计算机设备开展工作 ,系统操作方法易于为外科医生掌握使用 ,具有临床实用性。 4定量诊断和手术设计的准确性、精密度高 ,且具有客观性。结论　 3DCMFCAD系统和方法的建立为颅面畸形形成机制研究、诊断分析、手术设计和疗效评价提供了新的科学方法和理论依据。     

Treacher Collins syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development which results from loss-of-function mutations in the gene TCOF1. TCOF1 encodes the nucleolar phosphoprotein, Treacle, which plays a key role in pre-ribosomal processing and ribosomal biogenesis. In mice, haploinsufficiency of Tcof1 results in a depletion of neural crest cell precursors through high levels of cell death in the neuroepithelium, which results in a reduced number of neural crest cells migrating into the developing craniofacial complex. These combined advances have already impacted on clinical practice and provide invaluable resources for the continued dissection of the developmental basis of TCS.     

Marathon of eponyms: 20 Treacher Collins syndrome

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Treacher Collins syndrome.     

The surgical management of Treacher Collins syndrome

Treacher Collins syndrome (TCS), mandibulofacial dysostosis, or Franceschetti–Zwahlen–Klein syndrome, is a rare genetic disorder characterised by dysgenesis of the hard and soft tissues of the first and second branchial arches. Early operations focus on maintaining the airway, protecting the eyes, and supporting auditory neurological development. Later operations include staged reconstruction of the mouth, face, and external ear. Bimaxillary surgery can improve the maxillomandibular facial projection, but correction of malar, orbital rim, and temporal defects may be more difficult. We present a clinical review of the syndrome with a chronological approach to the operations.     

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.     

Extracraniofacial anomalies in Treacher Collins syndrome: A multicentre study of 248 patients

Treacher Collins syndrome (TCS) is a congenital malformation of the craniofacial structures derived from the first and second pharyngeal arches. The craniofacial deformities are well described in the literature. However, little is known about whether there are associated extracraniofacial anomalies. A retrospective study was conducted using data from four craniofacial units. Medical charts were reviewed for the presence and type of extracraniofacial anomalies, as well as age at diagnosis. A possible correlation between the severity of the phenotype and the presence of extracraniofacial anomalies was assessed using the Hayashi classification. A total of 248 patients with TCS were identified; 240 were confirmed to have TCS, of whom 61 (25.4%) were diagnosed with one or more extracraniofacial anomalies. Ninety-five different extracraniofacial anomalies were found; vertebral (n = 32) and cardiac (n = 13) anomalies were most frequently seen, followed by reproductive system (n = 11), central nervous system (n = 7), and limb (n = 7) anomalies. No correlations between tracts were found. Extracraniofacial anomalies were more prevalent in these patients with TCS compared to the general population (25.4% vs 0.001–2%, respectively). Furthermore, a positive trend was seen between the severity of the syndrome and the presence of extracraniofacial anomalies. A full clinical examination should be performed on any new TCS patient to detect any extracraniofacial anomalies on first encounter with the craniofacial team.     

Orbital volume and shape in Treacher Collins syndrome

Orbito-palpebral reconstruction is a challenge in Treacher Collins syndrome (TCS). This study investigates orbital phenotypes in TCS using cephalometry and orbital shape analysis.Eighteen TCS and 52 control patients were included in this study, using the Dr Warehouse database. Orbital cephalometry was based on 20 landmarks, 10 planes, 16 angles, and 22 distances. Orbits were segmented. Registration-based, age-specific mean models were generated using semi-automatic segmentation, and aligned and compared using color-coded distance maps – mean absolute distance (MAD), Hausdorff distance (HD), and Dice similarity coefficient (DSC). Symmetry was assessed by mirroring and DSC computing.Central orbital depth (COD) and medial orbital depth (MOD) allowed 100% of orbits to be classified. COD and lateral orbital depth (LOD) were different from the controls. Average MAD between TCS and controls was ≤1.5 mm, while for HD it was >1.5 mm, and for DSC <1. TCS orbits were more asymmetrical than controls, and orbital volumes were smaller when age was considered as a confounding factor, and had a trend for normalization with age.This report emphasizes the importance of combining different morphometric approaches in the phenotype characterization of non-trivial structures such as the orbit, and supports composite skeletal and soft-tissue strategies for the management of the peri-orbital region.     

Orofacial functions and oral health associated with Treacher Collins syndrome

Abstract

Objective. The aim of this study was to describe orofacial features and functions and oral health associated with Treacher Collins syndrome (TCS) in relation to the variable phenotypic expression of the condition. Materials and methods. The Nordic Orofacial Test-Screening (NOT-S), MHC Questionnaire, MHC Observation chart and clinical examinations of nasal and pharyngeal conditions and chewing and swallowing function were used to assess 19 individuals aged 5–74 years (median 34 years). TCS severity scores were calculated by a clinical geneticist. Results. Orofacial features characterizing the study group were altered profile, increased mandibular angle, narrow hypopharynx and facial asymmetry. Basic orofacial functions such as breathing, eating, facial expression and speech were affected in all subjects demonstrating orofacial dysfunction in at least two NOT-S domains (median NOT-S total score 4/12, range 2–7). Significant correlation was found between the TCS severity scores reflecting phenotypic expression and the NOT-S total scores reflecting orofacial function. Self-reported experience of dry oral mucosa was common. Overall, dental health was good with few carious lesions diagnosed, but considerable need for orthodontic treatment was documented. Conclusions. Altered orofacial features and functions in TCS are common and often persist into late adolescence and adulthood. The functional level was correlated with the phenotypic variability of the condition. The standard of oral health was satisfactory. The findings indicated that individuals with TCS are likely to require lifelong health services related to their oral condition.     

The etiology,clinical features,and treatment options of hemifacial microsomia

The second most frequent craniomaxillofacial congenital deformity is hemifacial microsomia (HFM). Patients often accompany short mandible, ear dysplasia, facial nerve, and soft tissue dysplasia. The etiology of HFM is not fully understood. To organize the possible up-to-date information on the etiology, craniofacial phenotypes, and therapeutic alternatives in order to fully comprehend the HFM. Reviewing the potential causes, exploring the clinical features of HFM and summarizing the available treatment options. Vascular malformation, Meckel's cartilage abnormalities, and cranial neural crest cells (CNCCs) abnormalities are three potential etiology hypotheses. The commonly used clinical classification for HFM is OMENS, OMENS-plus, and SAT. Other craniofacial anomalies, like dental defects, and zygomatic deformities, are still not precisely documented in the classification. Patients with moderate phenotypes may not need any treatment from infancy through adulthood. However, patients with severe HFM require to undergo multiple surgeries to address facial asymmetries, such as mandibular distraction osteogenesis (MDO), autologous costochondral rib graft (CCG), orthodontic and orthognathic treatment, and facial soft tissue reconstruction. It is anticipated that etiology research will examine the pathogenic mechanism of HFM. A precise treatment for HFM may be possible with thoroughly documented phenotypes and a pathogenic diagnosis.     

Oro-dental and craniofacial anomalies in LEOPARD syndrome

'LEOPARD syndrome' is a syndrome affecting many systems or organs. The main anomalies are summarized in the acronym LEOPARD in which each letter corresponds to the damage of a given organ. In the presented case, there are oro-dental and craniofacial anomalies. The relationship between the LEOPARD syndrome and the given anomalies and the possibilities of the management and the follow-up of the diseased are studied. The clinical case presented is a 4-year-old boy with LEOPARD syndrome showing retardation of dental development, delayed development and possible agenesis of permanent teeth, and craniofacial anomalies (osseous hypodevelopment). The bibliographical study shows that LEOPARD syndrome is due to damage of the neural crest cells. Thus, the dental and craniofacial anomalies arise since neural crest cells participate in the formation of the teeth and some craniofacial bones. Therefore, dental and craniofacial anomalies might be expected in some cases of the disease. The therapeutic management of the lesions, and the follow-up of the patient would be done by a multidisciplinary team.