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Introduction: Treacher Collins syndrome is a rare congenital disease characterized by the multiple craniofacial malformations. Although the deformities affecting patients with Treacher Collins syndrome have been well characterized, the effects of these malformations to clinical severity of the syndrome are not well understood., Objective: To determine the association of specific Treacher Collins mandibular malformations with clinical severity., Design: A retrospective radiographic observational study ., Setting: Study conducted at a single institution, a quaternary craniofacial care center., Patients: 54 patients with Treacher Collins syndrome., Interventions: Computed tomography (CT), clinical photographs and medical history were included in this analysis. Mandibles were isolated from CT data and reconstructed in three dimensions using Mimics software. Cephalometric measurements were performed on CT data. Clinical severity was determined by Teber and Vincent scores. Association of craniofacial dysmorphology to clinical severity was determined by Spearman rank coefficient., Main Outcome Measures: The main results obtained were the measurements of the mandibles and the quantification of the malformations of the evaluated patients., Results: Among the most frequent findings in the sample are hypoplasia of the zygomatic complex, descending palpebral cleft and mandibular hypoplasia. Patients with a lower ramus/corpus ratio had a higher (more severe) Teber and Vincent classification., Conclusion: Patients with the most compromised mandible are also the patients with the highest number of malformations, thus, the most severe patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Here we trained an automatic phenotype assessment tool to recognize syndromic ears in two syndromes in fetuses-=CHARGE and Mandibulo-Facial Dysostosis Guion Almeida type (MFDGA)-versus controls., Method: We trained an automatic model on all profile pictures of children diagnosed with genetically confirmed MFDGA and CHARGE syndromes, and a cohort of control patients, collected from 1981 to 2023 in Necker Hospital (Paris) with a visible external ear. The model consisted in extracting landmarks from photographs of external ears, in applying geometric morphometry methods, and in a classification step using machine learning. The approach was then tested on photographs of two groups of fetuses: controls and fetuses with CHARGE and MFDGA syndromes., Results: The training set contained a total of 1489 ear photographs from 526 children. The validation set contained a total of 51 ear photographs from 51 fetuses. The overall accuracy was 72.6% (58.3%-84.1%, p < 0.001), and 76.4%, 74.9%, and 86.2% respectively for CHARGE, control and MFDGA fetuses. The area under the curves were 86.8%, 87.5%, and 90.3% respectively for CHARGE, controls, and MFDGA fetuses., Conclusion: We report the first automatic fetal ear phenotyping model, with satisfactory classification performances. Further validations are required before using this approach as a diagnostic tool., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

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., (© 2023 International Federation of Gynecology and Obstetrics.)

Objective: To study prenatal diagnosis of congenital Treacher Collins syndrome, an etiology of craniofacial abnormalities., Case Report: We present a case of fetal craniofacial abnormalities identified by antepartum sonography screening in the third trimester (28 weeks); features of micrognathia, hypoplastic zygomatic arches and bilateral low-set microtia were detected. Due to the unknown severity of the craniofacial abnormalities and poor prognosis, the parents decided to terminate the fetus after through counselling. A normal female karyotype was detected. The parents consented to chromosome microarray analysis (CMA), which identified a de novo mutation of the TCS1 gene locus on chromosome 5., Conclusion: Molecular CMA is an effective tool for prenatal diagnosis of congenital craniofacial abnormalities associated with Treacher Collins syndrome., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2022. Published by Elsevier B.V.)

Background: Mandibulofacial dysostosis with microcephaly (MFDM) is a rare multiple malformation syndrome characterized by malar and mandibular hypoplasia and congenital- or postnatal-onset microcephaly induced by haploinsufficiency of (elongation factor Tu GTP-binding domain-containing 2) EFTUD2., Methods: We report the case of a 16-month-old boy with MFDM symptoms, including malar and mandibular hypoplasia, microcephaly, micrognathia, midline cleft palate, microtia, auditory canal atresia, severe sensorineural hearing loss, and developmental delay. Whole-exome sequencing (WES) analysis of the patient's family was performed to identify the genetic etiology responsible for this phenotype., Results: We identified a novel de novo missense mutation (c.671G>T, p.Gly224Val) in the EFTUD2. According to the American College of Medical Genetics and Genomics (ACMG) 2015 guidelines, the c.671G>T mutation was classified as likely pathogenic (PS2, PM1, PM2, and PP3). Based on our findings, prenatal diagnosis was performed on the second baby of the proband's parents to exclude the mutation and it was confirmed that the baby did not have the MFDM phenotype after 14 months of follow-up. Furthermore, the zebrafish model confirmed that the EFTUD2 c.671G>T mutation caused a loss of gene function in EFTUD2, and the pathogenicity of the EFTUD2 c.671G>T mutation was classified as pathogenic (PS2, PS3, PM1, and PM2)., Conclusion: Our results indicate that WES is a useful tool for identifying potentially pathogenic mutations, particularly in rare disorders, and is advantageous for genetic counseling and subsequent prenatal diagnosis. Moreover, the importance of functional assays cannot be underestimated, which could further confirm the pathogenicity of the genetic variants., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Otodental syndrome and Treacher Collins syndrome are rare diseases that have similar clinical features, which can complicate the diagnostic process. These syndromes cause skeletal and dental abnormalities, the differential diagnosis can be based on clinical signs but only the genetic analysis can confirm it. The aim of this case report is to describe and compare clinical signs of these syndromes., Case Report: A 7-year-old patient came to our department: he presented abnormal tooth shapes and sizes, delayed teeth replacement and micrognathia. After extra- and intra-oral examination and radiographic exams, a clinical diagnosis of otodental syndrome was made, and a genetic testing was requested to confirm the diagnosis., Conclusion: Dental management of patients with otodental syndrome is challenging due to agenesis, teeth malformation, lack of space for permanent dentition. Proper treatment decision is crucial to obtain the best result for the patient.

Introduction: Treacher Collins syndrome (TCS) and nonsyndromic Pierre Robin sequence (PRS) share mandibular deficiency as a similar clinical finding. This study aimed to compare the mandibular size and morphology of subjects with TCS and PRS., Methods: Group TCS was composed of 17 subjects (7 male, 10 female) with a mean age of 11.5 years (standard deviation, 4.4) from a single center. Group PRS was composed of 17 subjects paired by age and sex with group TCS. Preorthodontic cone-beam computed tomography examinations of all patients were evaluated using Mimics Innovation Suite 17.0 (Materialise, Leuven, Belgium). Nine 3-dimensional measurements were performed in segmented 3D images of the mandible. Intragroup comparisons were performed using paired t tests. Intergroup comparisons were performed using analysis of variance and Tukey tests. The significance level considered was 5%., Results: TCS showed a significant dimensional difference between less and more affected sides for ramus, condyles, and mandibular body. The mandibular dimensions in PRS were more symmetrical. Group TCS presented a smaller mandibular effective length and mandibular body length compared with PRS. The condyle width and height and the ramus width were also decreased in TCS. The gonial angle was greater in TCS compared with the PRS group., Conclusions: Young subjects with TCS presented a smaller, more vertical, and more asymmetrical mandible compared with nonsyndromic PRS., (Copyright © 2021. Published by Elsevier Inc.)

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., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abstract: This study evaluated age-associated morphology changes in the cranial base, facial development, and upper airway of patients with Treacher Collins syndrome (TCS). A total of 33 preoperative computed tomographic images (TCS, n = 14; control, n = 19) were included in the study and divided into three age-related subgroups (2-6 years, 7-18 years, and older than 18 years). Linear, angular cephalometric measurements and upper airway volumes were collected. All measurements were analyzed using ProPlan CMF software (version 3.0; Materialize, Leuven, Belgium). The association between aging and upper airway morphology was analyzed. Compared to control subjects, TCS patients had a smaller cranial base, maxilla, and nose; they also had reduced upper airway volume compared to control subjects. The observed differences were most significant in patients between the ages of 7 and 18 years. This study used computed tomography-based three-dimensional analyses to provide a detailed description of age-related changes that occur in craniofacial measurements and upper airway volumes in children, adolescents, and young adult patients with TCS in China. These data can be used to evaluate individual patients with TCS and to select treatment to improve the growth of the craniofacial region., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Facial dysostoses are clinically and genetically heterogeneous conditions characterized by congenital craniofacial anomalies which result from abnormal development of the first two pharyngeal arches and their derivatives during embryogenesis. Mandibulofacial dysostosis Guion-Almeida type (MFDGA) is a rare and relatively new syndrome described in the literature, first identified by Guion-Almeida et al. in 2000 and 2006. Another 108 cases have been documented after that. Prenatal diagnosis of this syndrome has not been described yet. Here we present the prenatal ultrasound findings in a case where MFDGA was confirmed after delivery. We suggest that MFDGA should be included in the prenatal differential diagnosis of syndromes with micrognathia and craniofacial anomalies., (©2021 JOURNAL of MEDICINE and LIFE.)

Treacher collins syndrome (TCS) or Franceschetti syndrome is an autosomal dominant inherited disorder with variable expressivity. It affects mainly craniofacial structure that derives from 1st and 2nd branchial arches approximately between the 20th day and 12th week of intrauterine life. This syndrome has different clinical types. Most common features are antimongoloid slanting of the palpebral fissures, hypoplasia of zygoma, maxilla & mandible with various eye and ear abnormalities. Here we present a case of an 11 days old female neonate, who was ill looking, dyspnoeic having significant facial profile, multiple congenital anomalies and dolicocephaly; admitted in the department of Neonatology, Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh on 7th August 2020. After taking all the diagnostic assistance of the multidisciplinary approach mainly on the basis of clinical features and radiology we diagnosed the case as TCS. We managed the patient by maintaining temperature, giving nutritional support and injectable antibiotic, took consultation from Otolaryngology department then we discharged the baby with proper counseling, advised regarding further follow up and to consult with paediatric surgeon and cardiologist.

Objective: To three-dimensionally calculate the craniofacial parameters of midface of patients with Treacher Collins syndrome (TCS) in China, in order to understand the changes in the spatial position relationship between the various anatomical structures of the midface., Methods: CT imaging data of TCS patients and age- and gender-matched normal populations between January 2013 and July 2020 was retrospectively analyzed. A total of 33 cases met the selection criteria for inclusion in the study, including 14 cases in the TCS group and 19 cases in the control group. ProPlan CMF 3.0 software was used to perform three-dimensional digital reconstruction of the craniofacial bone, measure the anatomical parameters of the midface, and analyze its morphological structure; at the same time perform three-dimensional digital reconstruction of the upper airway for morphological analysis (measure upper airway volume)., Results: CT images analysis revealed that all 14 patients with TCS presented the typical features with downward slanting of the palpebral fissures and different degrees of zygomatico-orbital complex dysplasia. Cephalometric and morphological analysis of the midface revealed that, multiple transverse diameters of the midface of TCS patients were significantly decreased when compared with the control group ( P <0.05), such as the width of the maxillary base, the length of the maxillary complex, and some distances related to the nasal morphology; but the distance between bilateral orbitales increased in TCS group ( P <0.05). Several anteroposterior distances in TCS group were decreased significantly when compared to control group and the distance between the skull base point and the posterior nasal spine was the most shortened ( P <0.05). But there was no significant difference of the distance between nasion and anterior nasal spine, which represented anterior midface height, between groups ( P >0.05). The skull base angle and SNB angle (the angle between the sella point-nose root point-inferior alveolar seat point) of the TCS group both decreased when compared with the control group ( P <0.05), but there was no significant difference in SNA angle (the angle between the sella point-nose root point-upper alveolar seat point) between the two groups ( P >0.05). The total volume of the upper airway was (24 621.07±8 476.63) mm 3 in the TCS group, which was significantly lower than that of the control group [(32 864.21±13 148.74) mm 3 ] ( t =2.185, P =0.037)., Conclusion: The transverse distances, anteroposterior distances, and multiple craniofacial angles measurement of TCS patients were significantly decreased when compared to the control group, presented with different degrees of zygomatico-orbital complex dysplasia, nasal and maxillary dysplasia, but there was no obvious restriction in face height development. Reduced internal diameters of the upper airway maybe responsible for the decreased upper airway volume of patients with TCS.

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.

Objectives: First arch syndromes are congenital defects caused by failure of neural crest cells to migrate into the first branchial arch. First arch syndrome is classified into 2 main clinical manifestations: Treacher Collins syndrome, characterized by bilateral underdevelopment of the zygomatic bones; and Pierre Robin sequence. The aim of this study was to describe the feasibility of visualization of the fetal zygomatic bone and assess its application in cases referred for features suggestive of first arch syndrome., Methods: A prospective cohort study was conducted. The feasibility of visualization of the zygomatic bone was performed in 50 sequential fetuses with a normal anatomic scan between 12 and 24 weeks' gestation using 3-dimensional sonography. Following this, cases referred for targeted scans for suspected first branchial arch syndrome were assessed for the presence or absence of the zygomatic bones., Results: Visualization of the fetal zygomatic bone was feasible in all low-risk cases. Cases referred for targeted scans included 11 isolated cases of micrognathia or retrognathia, 3 cases of microtia, and 3 cases of auricular or facial vestiges. Within this group, the zygomatic bones were visualized in all but 2 cases. No associated extrafacial malformations were detected; therefore, this phenotype was consistent with Treacher Collins syndrome., Conclusions: Prenatal imaging of the zygomatic bones offers a clinically based sonographic approach to cases referred for features suggestive of first arch syndrome and enables differentiation between the 2 main clinical manifestations: Treacher Collins syndrome and Pierre Robin sequence., (© 2020 by the American Institute of Ultrasound in Medicine.)

Background: Treacher Collins syndrome (TCS) is the most common mandibulofacial dysostosis with an autosomal dominant or rarely recessive manner of inheritance. It is still challenging to make a definite diagnosis for affected fetuses with TCS only depending on the ultrasound screening. Genetic tests can contribute to the accurate diagnosis for those prenatal cases., Methods: Targeted exome sequencing was performed in a fetus of a Chinese family, who presenting an abnormal facial appearance by prenatal 2D and 3D ultrasound screening, including micrognathia, nasal bridge pit, and abnormal auricle. The result was validated with multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR (qPCR)., Results: A novel 2-6 exons deletion of TCOF1 gene was identified and confirmed by the MLPA and qPCR in the fetus, which was inherited from the affected father with similar facial anomalies., Conclusion: The heterozygous deletion of 2-6 exons in TCOF1 results in the TCS of this Chinese family. Our findings not only enlarge the spectrum of mutations in TCOF1 gene, but also highlight the values of combination of ultrasound and genetics tests in diagnosis of craniofacial malformation-related diseases during perinatal period., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The neural crest is an important transient structure that develops during embryogenesis in vertebrates. Neural crest cells are multipotent progenitor cells that migrate and develop into a diverse range of cells and tissues throughout the body. Although neural crest cells originate from the ectoderm, they can differentiate into mesodermal-type or endodermal-type cells and tissues. Some of these tissues include the peripheral, autonomic, and enteric nervous systems; chromaffin cells of the adrenal medulla; smooth muscles of the intracranial blood vessels; melanocytes of the skin; cartilage and bones of the face; and parafollicular cells of the thyroid gland. Neurocristopathies are a group of diseases caused by the abnormal generation, migration, or differentiation of neural crest cells. They often involve multiple organ systems in a single person, are often familial, and can be associated with the development of neoplasms. As understanding of the neural crest has advanced, many seemingly disparate diseases, such Treacher Collins syndrome, 22q11.2 deletion syndrome, Hirschsprung disease, neuroblastoma, neurocutaneous melanocytosis, and neurofibromatosis, have come to be recognized as neurocristopathies. Neurocristopathies can be divided into three main categories: dysgenetic malformations, neoplasms, and combined dysgenetic and neoplastic syndromes. In this article, neural crest development, as well as several associated dysgenetic, neoplastic, and combined neurocristopathies, are reviewed. Neurocristopathies often have clinical manifestations in multiple organ systems, and radiologists are positioned to have significant roles in the initial diagnosis of these disorders, evaluation of subclinical associated lesions, creation of treatment plans, and patient follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare condition that causes abnormalities of the head and face. Other major extracranial malformations may also be found. The authors present a case of an MFDM in a 35 weeks newborn with antenatal growth restriction. The patient required resuscitation at birth and was diagnosed with oesophageal atresia with tracheoesophageal fistula at day 1. At physical examination he presented multiple congenital malformations including prominent forehead, plagiocephaly, low-set ears, malformed auricles, hypertelorism, downward-slanting eyes, micrognathia, everted lower lip, short neck, wide-spaced nipples and inguinal hernia. Imaging investigation showed dysplasia of the inner ear with agenesis of the vestibular-cochlear nerves and global cerebral atrophy. Analysis of the EFTUD2 gene revealed that the patient was a heterozygous carrier of a pathogenic mutation (c.831&#95;832del[p.Lys277Asnsf*7]), which has not been previously described. This case illustrates the challenges faced in diagnosing and treating MFDM patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We present a case with prenatal diagnosis of Treacher-Collins syndrome in which micrognathia and other facial and ear abnormalities were described using a three- and four-dimensional (3D/4D) ultrasonography in utero., Case Report: A 39-year-old Japanese pregnant woman was referred because of polyhydramnios at 29 weeks' gestation. Conventional ultrasonography showed a hypoplastic mandible on the sagittal section of fetal head. Continuous observation using a 3D ultrasonography additionally demonstrated bilateral downslanting palpebral fissures with symmetry and macrostomia as well as micrognathia. Both ears were microtia and no polydactyly or missing fingers were found., Conclusion: The advantage of the rendering mode of 3D images covering entire face including ears and limbs was enhanced by a continuous observation, so called 4D ultrasonography, under a condition of polyhydramnios, providing visual diagnosis in utero., (Copyright © 2019. Published by Elsevier B.V.)

Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly., Competing Interests: No potential conflict of interest relevant to this article was reported.

Acrofrontofacionasal Dysostosis type 1 (AFFND1) is an extremely rare, autosomal recessive syndrome, comprising facial and skeletal abnormalities, short stature and intellectual disability. We analyzed an Indian family with two affected siblings by exome sequencing and identified a novel homozygous truncating mutation in the Neuroblastoma-Amplified Sequence (NBAS) gene in the patients' genome. Mutations in the NBAS gene have recently been associated with different phenotypes mainly involving skeletal formation, liver and cognitive development. The NBAS protein has been implicated in two key cellular processes, namely the non-sense mediated decay and the Golgi-to-Endoplasmic Reticulum retrograde traffic. Both functions were impaired in HEK293T cells overexpressing the truncated NBAS protein, as assessed by Real-Time PCR, Western blot analysis, co-immunoprecipitation, and immunofluorescence analysis. We examined the expression of NBAS protein in mouse embryos at various developmental stages by immunohistochemistry, and detected expression in developing chondrogenic and osteogenic structures of the skeleton as well as in the cortex, hippocampus and cerebellum, which is compatible with a role in bone and brain development. Functional genetics in the zebrafish model showed that depletion of endogenous z-nbas in fish embryos results in defective morphogenesis of chondrogenic cranial skeletal elements. Overall, our data point to a conserved function of NBAS in skeletal morphogenesis during development, support the hypothesis of a causative role of the mutated NBAS gene in the pathogenesis of AFFND1 and extend the spectrum of phenotypes associated with defects in this gene., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The surgical management of midface hypoplasia in the setting of Nager syndrome remains a significant challenge for craniofacial surgeons. This study describes a novel technique using distraction osteogenesis and modified osteotomies for the treatment of midface bony defects in an 11-year-old child with Nager syndrome.Presurgical 3-dimensional planning was performed to design the osteotomies and placement of distractors. The surgical approach required upper buccal sulcus and extended transconjunctival incisions only. Osteotomies were performed from the pyriform aperture through the orbit to include the lateral orbital wall, with bilateral osteotomy of the zygomas through the anterior arch via the transconjunctival incision. Distraction of the en bloc midface segment was successfully performed using external distractors. Bone grafting was not required. There were no complications.External distraction was well tolerated and there were no intraoperative or postoperative complications. The distractors were removed uneventfully after consolidation. The midface was successfully advanced without the need for bone grafting or bicoronal incision. The occlusal plane was leveled and the aesthetic appearance of the child was improved.Symmetrical midface hypoplasia in the context of Nager syndrome can be successfully corrected with en bloc distraction osteogenesis of the maxilla and bilateral zygomas through modified osteotomies that exclude the upper nasal pyramid. The approach is simplified and the need for bicoronal incision and bone grafting is mitigated in this technique, which the authors have named Lefort 2.5.

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., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: This clinical report is the first literature report exploring the issues of an absent epiglottis in children diagnosed with Nager syndrome. Absent epiglottis has previously been described in children with Pierre Robin sequence and other syndromes., Conclusion: The function of the epiglottis and its contribution to swallowing has always been debated. In this article and from our literature review, we felt that absent epiglottis possibly contributed to the aspiration risk and may partly explain the long-term feeding issues in these children despite corrective surgeries.

We report a case of mandibulofacial dysostosis with microcephaly presenting with seizures. The proband, a 6-year-old Korean boy, had microcephaly, malar and mandibular hypoplasia, and deafness. He showed developmental delay and had suffered recurrent seizures beginning at 21months of age. Electroencephalography revealed occasional spike discharges from the right frontal area. Head magnetic resonance imaging revealed dilatation of the lateral ventricles and a small frontal lobe volume. Whole exome sequencing revealed a de novo frame shift mutation, c.2698&#95;2701 del, of EFTUD2. The epileptic focus was consistent with the reduced frontal lobe volume on head magnetic resonance imaging. Seizures are thus a main feature of mandibulofacial dysostosis with microcephaly, which results from an embryonic development defect due to the EFTUD2 mutation., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Midface hypoplasia as exemplified by Treacher Collins Syndrome (TCS) can impair appearance and function. Reconstruction involves multiple invasive surgeries with variable long-term outcomes. This study aims to describe normal and dysmorphic midface postnatal development through combined modelling of skeletal and soft tissues and to develop a surgical evaluation tool., Materials and Methods: Midface skeletal and soft tissue surfaces were extracted from computed tomography scans of 52 control and 14 TCS children, then analysed using dense surface modelling. The model was used to describe midface growth, morphology, and asymmetry, then evaluate postoperative outcomes., Results: Parameters responsible for the greatest variation in midface size and shape showed differences between TCS and controls with close alignment between skeletal and soft tissue models. TCS children exhibited midface dysmorphology and hypoplasia when compared with controls. Asymmetry was also significantly higher in TCS midfaces. Combined modelling was used to evaluate the impact of surgery in one TCS individual who showed normalisation immediately after surgery but reversion towards TCS dysmorphology after 1 year., Conclusion: This is the first quantitative analysis of postnatal midface development using combined modelling of skeletal and soft tissues. We also provide an approach for evaluation of surgical outcomes, laying the foundations for future development of a preoperative planning tool., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The acrofacial dysostoses (AFD) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities. Rodriguez syndrome is a severe, usually perinatal lethal AFD, characterized by severe retrognathia, oligodactyly and lower limb abnormalities. Rodriguez syndrome has been proposed to be a severe form of Nager syndrome, a non-lethal AFD that results from mutations in SF3B4, a component of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Furthermore, a case with a phenotype intermediate between Rodriguez and Nager syndromes has been shown to have an SF3B4 mutation. We identified heterozygosity for SF3B4 mutations in Rodriguez syndrome, confirming that the phenotype is a dominant disorder that is allelic with Nager syndrome. The mutations led to reduced SF3B4 synthesis and defects in mRNA splicing, primarily exon skipping. The mutations also led to reduced expression in growth plate chondrocytes of target genes, including the DLX5, DLX6, SOX9, and SOX6 transcription factor genes, which are known to be important for skeletal development. These data provide mechanistic insight toward understanding how SF3B4 mutations lead to the skeletal abnormalities observed in the acrofacial dysostoses., Competing Interests: The authors have declared that no competing interests exist.

The palate functions as the roof of the mouth in mammals, separating the oral and nasal cavities. Its complex embryonic development and assembly poses unique susceptibilities to intrinsic and extrinsic disruptions. Such disruptions may cause failure of the developing palatal shelves to fuse along the midline resulting in a cleft. In other cases the palate may fuse at an arch, resulting in a vaulted oral cavity, termed high-arched palate. There are many models available for studying the pathogenesis of cleft palate but a relative paucity for high-arched palate. One condition exhibiting either cleft palate or high-arched palate is Treacher Collins syndrome, a congenital disorder characterized by numerous craniofacial anomalies. We quantitatively analyzed palatal perturbations in the Tcof1(+/-) mouse model of Treacher Collins syndrome, which phenocopies the condition in humans. We discovered that 46% of Tcof1(+/-) mutant embryos and new born pups exhibit either soft clefts or full clefts. In addition, 17% of Tcof1(+/-) mutants were found to exhibit high-arched palate, defined as two sigma above the corresponding wild-type population mean for height and angular based arch measurements. Furthermore, palatal shelf length and shelf width were decreased in all Tcof1(+/-) mutant embryos and pups compared to controls. Interestingly, these phenotypes were subsequently ameliorated through genetic inhibition of p53. The results of our study therefore provide a simple, reproducible and quantitative method for investigating models of high-arched palate., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Genial tubercles (GTs) are bony protuberances on the lingual aspect of the mandible symphysis, where genioglossus and geniohyoid muscles are inserted. In the literature, few papers report their real dimensions. Cleft lip and palate are craniofacial anomalies involving the maxilla, but the anatomical structures of the mandible can be altered when these have associated with the cleft, some syndrome. This study aimed to evaluate the GTs of 30 individuals and to make their measurements in cone beam computed tomography examinations., Methods: A sample of 30 individuals, 19 of them with cleft lip and palate, 6 individuals with Treacher Collins syndrome (TCS), and 5 individuals with Pierre Robin sequence, was used. The GTs were evaluated about the amount and the following measurements were performed: A--distance from the apex of the central incisors to GT, B--mandibular thickness in the region of GT, C-GT height, D-GT width, and E--distance from inferior border of mandible to GT., Results: The individuals presented since the absence of GTs to 3. The TCS group had the highest average of the measurements A, D, and E with statistical difference (P = 0.006) (P = 0.011) and (P = 0.017), respectively. The Pierre Robin sequence group had the highest average measurement of B and C, but there was no statistical difference., Conclusions: The difference in the measurements can be explained perhaps because individuals with TCS have glossoptosis and changes on retrognathic mandible, which would affect the position of the GT.

Introduction: Treacher Collins syndrome is a rare disorder characterized by several orofacial findings including malar deficiency and hypoplastic mandibles. These patients often require a combined orthodontic-orthognathic approach to correct their malocclusion. This is most often characterized by a short posterior vertical height and an anterior open bite. Orthognathic correction often requires Le Fort I and bilateral sagittal split osteotomies. No long-term stability results have been reported after bimaxillary surgery in Treacher Collins patients., Methods: A retrospective review of all Treacher Collins patients evaluated for orthognathic surgery by a single surgeon from 1993 to 2007 was performed. Patients were divided into groups who required surgery and those who did not. Part I analyzed the cephalometric differences between the surgical (S) and nonsurgical (NS) groups. Part II of the study assessed the preorthodontic treatment (T1), preoperative (T2), immediate postoperative (T3), and 1-year postoperative (T4) cephalometric measurement variables to determine the net surgical movement (T3 - T2) and relapse (T4 - T3)., Results: Twenty-two patients met the inclusion criteria, of which 11 had occlusal relationships requiring orthognathic surgery. Nine out of 11 chose to have surgery. At baseline, surgical patients exhibited a statistically significant retruded maxilla as measured by SNA and midface length compared to the NS group. In addition, the S group also had an increased gonial angle. There were significant movements in all maxillary and mandibular measurements. There was a significant relapse in the palatal plane angle when the maxilla was anteriorly impacted, with a 2.8-mm average relapse of the advancement. Relapse of the counterrotation movement of the mandible was identified, but this was not significant. Relapse did not affect the final occlusal result, which may have been compensated with postsurgical orthodontic treatment., Conclusion: Bimaxillary orthognathic surgery in the Treacher Collins patients may be performed safely with long-term dental and skeletal stability., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The Pierre Robin sequence (PRS) and the Treacher Collins syndrome (TCS) are conditions that cause significant abnormalities of jaw. This study was conducted in anticipation of evaluating the morphology of interforaminal region and identify the anatomic variations: anterior loop and mandibular incisive canal, in individuals with PRS and TCS by cone-beam computed tomography and compare them with individuals without craniofacial anomalies. By applying the t-test, the results showed no statistically significant difference, allowing to infer that there are no significant differences in interforaminal mandible morphology between groups and indicated that the prevalence and location of the studied anatomic variations are consistent with those described in literature.

Background: Children with Treacher Collins syndrome frequently present with obstructive sleep apnea and respiratory insufficiency. The purpose of this study was to three-dimensionally calculate upper airway volume in these patients. The authors also assessed the correlation between bony craniofacial morphology and spatial position with airway volume., Methods: Thirty Treacher Collins syndrome patients who have not been operated on were compared with a sample of 35 age- and sex-matched unaffected controls. Upper airway volume was stratified into retropalatal and retroglossal aspects. Three-dimensional craniometric findings were compared between patients and controls. Among Treacher Collins syndrome patients, the authors assessed the relationship of craniofacial morphology and spatial positioning to airway volume. Statistical analyses included independent sample t tests and Pearson correlation coefficient analyses., Results: Decreased total upper airway volume (p = 0.034) was found in the Treacher Collins syndrome group, attributable primarily to a decrease in retroglossal airway volume (p = 0.009). Regarding three-dimensional craniometric variables, maxillary and mandibular length (r = 0.76, p < 0.001; and r = 0.68, p < 0.001), and the anterior and posterior cranial base (r = 0.61, p < 0.001; and r = 0.77, p < 0.001) were positively correlated with airway volume in Treacher Collins syndrome patients. Transverse internal diameters of the upper airway were also positively correlated with airway volume (r = 0.635, p = 0.001; and r = 0.511, p = 0.006); however, no correlation was shown for the anteroposterior airway diameters., Conclusions: Three-dimensional analysis revealed diminished upper airway volume in Treacher Collins syndrome, with the retroglossal region being the most severely constricted. Maxillomandibular dysmorphologies, and their relationship to the cranial base, correlated significantly with airway findings.

In the present article we report a cholesteatoma of the hypotympanum extending to the jugular foramen in a 16-year-old male with Treacher Collins syndrome. Preoperative imaging excluded jugular paraganglioma and set the diagnosis of cholesteatoma. We discuss the operative treatment via a large hypotympanotomy and creation of an open hypotympanic cavity. To the authors' knowledge this is the first description of hypotympanal cholesteatoma with such an extension, being treated through this approach., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Treacher Collins syndrome is the most common mandibulofacial dysostosis of autosomal dominant or, rarely, recessive inheritance. Affected fetuses may be identified by prenatal ultrasound or diagnosed at autopsy in case of perinatal death or pregnancy termination., Methods: We describe the ultrasonographic, autopsy, and molecular findings in a 25-week-gestation affected fetus, and review the clinical, prenatal, and postmortem findings in 15 previously reported fetal and perinatal cases., Results: A nearly complete spectrum of the typical facial characteristics can be present by the early second trimester of gestation, including subtle defects such as lower eyelid colobomas. Mandibular hypoplasia and bilateral auricle defects were constant findings in the affected fetal population. Downslanting palpebral fissures were the second more common feature, followed by midface hypoplasia, polyhydramnios, and ocular defects. Association with Pierre Robin sequence was common (38%) in the reviewed series. Previously unreported pectus carinatum was noted in our case bearing a heterozygous TCOF1 mutation. Other unique reported findings include salivary gland hyperplasia, single umbilical artery, and tracheo-esophageal fistula, all in molecularly unconfirmed cases., Conclusion: Treacher Collins syndrome can be prenatally detected by ultrasound and should be included in the wide range of genetic syndromes that can be diagnosed at perinatal autopsy. Affected fetuses tend to have a more severe phenotype than living patients. The reported association of Treacher Collins syndrome type 1 with pectus carinatum expands the phenotype, provides information on genotype-phenotype correlation, and suggests possible pathogenetic interactions between neural crest cell disorders and the formation of the sternum that merit investigation., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Treacher-Collins syndrome is a rare autosomal dominant condition of varying phenotypic expression. The surgical correction in this syndrome is difficult, and the approach varies between craniofacial departments worldwide. The authors aimed to design standardized tools for planning orbitozygomatic and mandibular reconstruction in Treacher-Collins syndrome using geometric morphometrics., Methods: The Great Ormond Street Hospital database was retrospectively identified for patients with Treacher-Collins syndrome. Thirteen children (aged 2 to 15 years) who had suitable preoperative three-dimensional computed tomographic head scans were included. Six Treacher-Collins syndrome three-dimensional computed tomographic head scans were quantitatively compared using a template of 96 anatomically defined landmarks to 26 age-matched normal dry skulls., Results: Thin-plate spline videos illustrated the characteristic deformities of retromicrognathia and maxillary and orbitozygomatic hypoplasia in the Treacher-Collins syndrome population. Geometric morphometrics was used in the virtual reconstruction of the orbitozygomatic and mandibular region in Treacher-Collins syndrome patients. Intrarater and interrater reliability of the landmarks was acceptable and within a standard deviation of less than 1 mm on 97 percent and 100 percent of 10 repeated scans, respectively., Conclusions: Virtual normalization of the Treacher-Collins syndrome skull effectively describes characteristic skeletal deformities and provides a useful guide to surgical reconstruction. Size-matched stereolithographic templates derived from thin-plate spline warps can provide effective intraoperative templates for zygomatic and mandibular reconstruction in the Treacher-Collins syndrome patient., Clinical Question/level of Evidence: Diagnostic, V.

Here, we report two extraordinarily severe cases of Teacher Collins syndrome. Initially, amniotic bands and plical fold disruption were considered, but downslanting eyes made us consider severe Treacher Collins syndrome. A TCOF1 mutation in exon 24 was identified in Patient 1 (c.4355&#95;4356ins14, resulting in p.1456Thrfs*18). Patient 2, who expired on day 4, is so similar to Patient 1 that severe Treacher Collins syndrome may be inferred in this instance. Neither the TCOF1 mutation nor the well-known variability in the expression in affected families with Treacher Collins syndrome (∼40% of reported cases) can explain the severity of these cases; otherwise, we would be aware of such cases within families from time to time. We are unaware of any recent sporadic cases (∼60% of reported cases) exactly like ours either with a single exception in the case reported by Writzl et al. [2008] with a TCOF1 mutation. The case described by Otto in 1841 is spectacular. We propose several hypotheses to be considered in explaining this developmental amplification, including some promoter effect on the gene, some position effect on the gene, a polymorphism elsewhere in the gene, a point mutation elsewhere in the gene, a polymorphism in another gene, or a point mutation in another gene, such as POLR1C (which maps to 6p21.1) or POLR1D (which maps to13q12.2). We also review the etiology and pathogenesis of Treacher Collins syndrome, and discuss several other severe cases from the past., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: Temporomandibular joint malformation is a complex deformity in Treacher-Collins syndrome (TCS); however, it is not well characterized. This study aimed to better clarify this pathology by volumetrically assessing the mandibular condyle in patients with TCS compared with normal controls and the relative contribution of the condyle to hemimandibular volume., Materials and Methods: A retrospective, cross-sectional analysis of pediatric patients with TCS and unaffected controls was performed. The study sample was comprised of Treacher Collins patients. The predictor variable in this study was disease status (TCS diagnosis vs control), and the outcome variable was condylar volume. Demographic information was collected, and 3-dimensional computed tomographic data were analyzed by computerized segmentation (Materialise). Volumes were obtained for TCS condyles and compared with age-matched controls using the Student t test., Results: Three-dimensional computed tomographic scans were identified in 10 patients with TCS (20 sides) and 14 control subjects (28 sides). The TCS group included 4 female and 6 male patients (age, 0.3 to 213 mo; average age, 66.5 mo). The control cohort included 7 female and 7 male subjects (average age, 68.8 mo). Evaluation of the mandibular condyle showed that patients with TCS had a significantly smaller condylar volume than control patients (TCS, 178.28 ± 182.74 mm(3); control, 863.55 ± 367.20 mm(3); P < .001). Additional intragroup analysis showed no significant differences between the left and right condylar volumes in the TCS group (P = .267). In addition, the condyle for patients with TCS represented a smaller proportion of hemimandibular volume compared with controls (1.37% vs 4.19%, respectively; P < .001)., Conclusions: The results of the this study suggest that condylar volumes are significantly smaller in patients with TCS compared with age-matched controls, and the condyle represents a smaller fraction of the total mandibular volume for patients with TCS than in unaffected children. In addition, there is considerable variability of condylar size in patients with TCS. These facts portend treatment decisions because a functional temporomandibular joint is necessary and may need to be reconstructed as a first stage before effective implementation of distraction procedures., (Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Treacher Collins syndrome (TCS) is a facial dysostosis, the hallmark being bilateral malar hypoplasia. The purpose of this study is to morphologically classify the TCS malar deformity and to volumetrically characterise both the TCS zygoma and masseter muscle, including for left-right symmetry, compared to controls. We hypothesise that the TCS zygoma will be smaller than controls and zygomatic deficiency will portend masseteric hypoplasia., Methods: Demographic and computed tomography (CT) data were recorded. The CT scans were converted into three-dimensional facial renderings, and the zygomatic morphology was grossly evaluated. A classification was reported based on malar structure and presence/absence of normal zygomaticomaxillary complex articulations. The zygoma and masseter muscles were then digitally isolated using 3-D planning software (Materialise, Leuven, Belgium). Volumes and sidedness ratios were calculated and compared using two-sided t-tests., Results: 58 sides were identified (24 TCS: 34 controls), mean age of 60.0 months and normally distributed. The phenotypic dysmorphology was graded as mild, moderate or severe (I, II and III, respectively). TCS malar and masseteric volumes were significantly smaller than controls (p < 0.0001 in both cases). The TCS zygomatic side-side symmetry ratio was 0.66 ± 0.28, compared to 0.97 ± 0.02 for controls (p = 0.002). The TCS masseteric side-side ratio was 0.74 ± 0.20, compared to 0.92 ± 0.09 for controls (p = 0.001)., Conclusions: A range of zygomatic hypoplasia exists in TCS (mild-severe). The decrease in malar volume occurs in concert with masseteric hypoplasia, and the left and right sides are not equally affected., (Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Pierre Robin sequence (PR) and Treacher Collins syndrome (TC) are congenital disorders associated with multiple craniofacial abnormalities. The mandibular malformations linked with these maladies are closely associated with the form and function of the temporalis muscle. Despite these associations, a paucity of research has been directed at quantifying how these malformations affect the tissues of the temporal region. In this paper, we seek to quantify differences in the temporalis muscle and the temporal fat pad using a novel CT-derived analytic program to examine craniofacial morphomic indices within these patient groups in comparison to normal age-matched controls. We posit that the temporalis muscle and temporal fat pad, like other derivatives of the first branchial arch, are hypoplastic in patients with TC and PR compared to age-matched controls., Methods: High-throughput image analysis was used to reconstruct the 3-dimensional (3D) anatomy and quantify morphomic measures of the temporalis muscle and temporal fat pad in children with PR, TC, and age-matched controls. These steps were completed in a semi-automated method using algorithms programmed in MATLAB v13.0. The 3D reconstructions were analyzed in 3 children with PR (6 temporal regions), 3 children with TC (6 temporal regions), and a control group of 19 children (38 temporal regions). We also quantified the same measurements in a localized "core" sample in the area of greatest thickness, providing a more consistent sample of the tissue position. Relationships between the temporal muscle and fat pad values and craniofacial abnormality type were assessed using Wilcoxon nonparametric test using exact distribution, with a P value of less than 0.05 being deemed significant., Results: The mean age of our patients was 6.0 years in PR and 4.5 years in TC cohorts. We were able to establish an automated methodology to quantify the temporalis muscle and temporal fat pad based on CT characteristics. Localized temporalis volume and localized temporalis area were significantly smaller in children with PR than in the control group. Total temporalis fat volume and localized temporalis area were significantly less in children with TC than in the control group. When compared to each other, the PR group had small morphomic values compared to TC group., Conclusions: There are significant morphomic differences in the temporalis muscle and the temporal fat pad in children with either PR or TC when compared to age-matched control group which can be measured from pre-existing CT scans. Specifically, both of these test groups show decreases in the morphomic measures of the temporalis region. The quantification of these changes corroborates and objectifies the clinical findings associated with these congenital deformities while simultaneously allowing for preoperative planning. Furthermore, this finding confirms that the hypoplasia seen in these patient populations is not only hypoplasia of the mandible but also of the surrounding functional matrix, which includes the temporalis muscle and temporal fat pad.

Pierre Robin sequence and Treacher Collins syndrome are both associated with mandibular hypoplasia. It has been hypothesized, however, that the mandible may be differentially affected. The purpose of this study was to therefore compare mandibular morphology in children with Pierre Robin sequence with children with Treacher Collins syndrome using three-dimensional analysis of computed tomographic scans. A retrospective analysis was performed identifying children with Pierre Robin sequence and Treacher Collins syndrome undergoing computed tomography. Three-dimensional reconstruction was performed, and ramus height, mandibular body length, and gonial angle were measured. These were then compared with those in control children with normal mandibles and with the clinical norms corrected for age and sex based on previously published measurements. Mandibular body length was found to be significantly shorter for children with Pierre Robin sequence, whereas ramus height was significantly shorter for children with Treacher Collins syndrome. This resulted in distinctly different ramus height-mandibular body length ratios. In addition, the gonial angle was more obtuse in both the Pierre Robin sequence and Treacher Collins syndrome groups compared with the controls. Three-dimensional mandibular morphometric analysis in patients with Pierre Robin sequence and Treacher Collins syndrome thus revealed distinctly different patterns of mandibular hypoplasia relative to normal controls. These findings underscore distinct considerations that must be made in surgical planning for reconstruction.

In our clinical experience, individuals with Treacher Collins syndrome (TCS) present with more complaints of oral dryness and higher caries activity than seen in the general population. A literature review identified no reports of salivary gland pathology and glandular dysfunction associated with TCS. Twenty-one Norwegian individuals with TCS underwent ultrasound examinations and salivary secretion tests of the submandibular and parotid glands. Intraglandular architecture patterns were analyzed and subsequently classified as either normal, dysplastic, or aplastic. The results were compared with salivary secretion rates and subjective reports of oral dryness. Ultrasound examination revealed pathological appearance of the salivary glands in approximately half (48%) of the individuals, with dysplasia identified in six (29%) participants and aplasia in four (19%). Almost all participants had co-existing low salivary secretion rates. A few individuals had low salivary secretion rates despite normal appearance of the salivary gland tissue on ultrasound examination. Subjective experience of oral dryness did not correlate significantly with low salivary secretion rates. We conclude that mild to severe salivary gland pathology and dysfunction can be associated with TCS. Further investigation is needed to clarify this association., (Copyright © 2012 Wiley Periodicals, Inc.)

Treacher Collins syndrome is a congenital syndrome with characteristic craniofacial malformations, which are well described in the literature. However, the presence of cervical spine dysmorphology in this syndrome has been minimally described. This study reviews cervical spine radiographs of 40 patients with Treacher Collins syndrome. In this sample, 7 of 40 patients displayed cervical spine anomalies, with 3 of these patients displaying multiple cervical spine anomalies. The patterns of spinal anomalies were variable, suggesting that the underlying genetic mutation has variable expressivity in cervical spine development as it does elsewhere in the craniofacial skeleton.

First and second branchial arch syndromes (BAS) manifest as combined tissue deficiencies and hypoplasias of the face, external ear, middle ear and maxillary and mandibular arches. They represent the second most common craniofacial malformation after cleft lip and palate. Extended knowledge of the embryology and anatomy of each branchial arch derivative is mandatory for the diagnosis and grading of different BAS lesions and in the follow-up of postoperative patients. In recent years, many new complex surgical approaches and procedures have been designed by maxillofacial surgeons to treat extensive maxillary, mandibular and external and internal ear deformations. The purpose of this review is to evaluate the role of different imaging modalities (orthopantomogram (OPG), lateral and posteroanterior cephalometric radiographs, CT and MRI) in the diagnosis of a wide spectrum of first and second BAS, including hemifacial microsomia, mandibulofacial dysostosis, branchio-oto-renal syndrome, Pierre Robin sequence and Nager acrofacial dysostosis. Additionally, we aim to emphasize the importance of the systematic use of a multimodality imaging approach to facilitate the precise grading of these syndromes, as well as the preoperative planning of different reconstructive surgical procedures and their follow-up during treatment.

A variety of congenital syndromes affecting the face occur due to defects involving the first and second BAs. Radiographic evaluation of craniofacial deformities is necessary to define aberrant anatomy, plan surgical procedures, and evaluate the effects of craniofacial growth and surgical reconstructions. High-resolution CT has proved vital in determining the nature and extent of these syndromes. The radiologic evaluation of syndromes of the first and second BA should begin first by studying a series of isolated defects (cleft lip with or without CP, micrognathia, and EAC atresia) that compose the major features of these syndromes and allow a more specific diagnosis. After discussion of these defects and the associated embryology, we discuss PRS, HFM, ACS, TCS, Stickler syndrome, and VCFS.

Background: Treacher Collins syndrome is associated with a clockwise mandibular deformity (Plast Reconstr Surg 2008;121:77e-84e). We hypothesize that the Treacher Collins mandible exhibits a more obtuse relation between the body and the ramus compared with unaffected subjects. The purpose of this study was to objectively analyze the body-ramus relation in Treacher Collins compared with control subjects and to investigate the effect of age., Methods: This was a retrospective analysis involving three-dimensional computed tomography (CT) scans. Demographic and CT scan information was obtained for Treacher Collins and control subjects. Measurements were performed on the IDXrad platform. The ramus body angle (RBA) was defined as the intersection of the anterior ramus with the tangent from the alveolar process of the mandible. The mandibular plane angle (MPA) was measured in standard fashion. Left and right hemimandibles were analyzed. Statistical analysis involved the paired t-test (P < 0.005 significance). Subgroups based on age, younger than 3 years and older than 12 years, were then compared, within and between groups., Results: Three-dimensional CT scans were identified in 18 Treacher Collins (36 sides) and 24 control (48 sides) subjects. The MPA was excluded in 6 Treacher Collins and 2 control hemimandibles for absent centric occlusion. The Treacher Collins group consisted of 7 females and 11 males, ranging in age from 0.66 to 204 months (mean, 91.6 months). The control cohort included 13 females and 11 males, aged 0.26 to 204 months (mean, 111.5 months). The mean RBAs for the Treacher Collins and comparison groups were 150.28 and 114.2 degrees (P < 0.0001). The mean MPAs were 38.25 and 31.9 degrees for the Treacher Collins group and control subjects, respectively (P < 0.0001). In children younger than 3 years, the RBAs were 154.40 and 119.36 degrees, and for patients older than 12 years, the RBAs were 148.40 and 111.75 degrees for the Treacher Collins group and control subjects (both P < 0.0001). Comparing Treacher Collins younger than 3 years with those older than 12 years, the mean RBAs were not statistically different at 154.40 and 148.40 degrees (P = 0.1869). Among control subjects younger than 3 years compared with older than 12 years, the RBAs approached significance, but not statistically at 119.36 and 111.75 degrees (P = 0.0122). Notably, among control subjects, the MPA did statistically flatten with increasing age, showing 37.36 and 29.50 degrees (P = 0.0011)., Conclusions: The clockwise relation of the mandibular body relative to the ramus is objectively documented in Treacher Collins subjects. This relation persists despite increasing age, in distinction to control subjects where the mandibular plane flattens in adolescence.

We studied orthognathic correction of dentofacial deformities in patients with craniofacial syndromes (Crouzon, Apert, and Treacher Collins) during a 5-year period. The number of patients treated within this time period was 17 with Crouzon syndrome, 12 with Apert syndrome, and six with Treacher Collins syndrome. Individual follow-up was 2.5 years. Bimaxillary operation, sometimes with genioplasty, has been done after preoperative orthodontic treatment of 1.5-2.5 years. Clinical and radiographic cephalometric evaluations of the orthodontic results were made. The functional and aesthetic results were satisfactory in most patients, although there were large individual variations. The experience of a craniofacial centre such as the one in Gothenburg, Sweden, which has different odontological and medical specialities, is invaluable for an optimal result.

In this paper, we report a boy with remarkable phenotype and noteworthy radiographic abnormalities. He presented with distinctive facies, mesomelic shortening and asymmetry of the extremities, symmetrical ulnar and fibular ray absence in the hands and feet, with unique hypoplastic/dysplastic radiographic abnormalities. His mental development was normal. We believe that he represents a previously unreported form of the postaxial acrofacial dysostosis syndrome.