Ciliopathic micrognathia is caused by aberrant skeletal differentiation and remodeling.

Ciliopathies represent a growing class of diseases caused by defects in microtubule-based organelles called primary cilia. Approximately 30% of ciliopathies are characterized by craniofacial phenotypes such as craniosynostosis, cleft lip/palate and micrognathia. Patients with ciliopathic micrognathia experience a particular set of difficulties, including impaired feeding and breathing, and have extremely limited treatment options. To understand the cellular and molecular basis for ciliopathic micrognathia, we used the talpid2 (ta2 ), a bona fide avian model for the human ciliopathy oral-facial-digital syndrome subtype 14. Histological analyses revealed that the onset of ciliopathic micrognathia in ta2 embryos occurred at the earliest stages of mandibular development. Neural crest-derived skeletal progenitor cells were particularly sensitive to a ciliopathic insult, undergoing unchecked passage through the cell cycle and subsequent increased proliferation. Furthermore, whereas neural crest-derived skeletal differentiation was initiated, osteoblast maturation failed to progress to completion. Additional molecular analyses revealed that an imbalance in the ratio of bone deposition and resorption also contributed to ciliopathic micrognathia in ta2 embryos. Thus, our results suggest that ciliopathic micrognathia is a consequence of multiple aberrant cellular processes necessary for skeletal development, and provide potential avenues for future therapeutic treatments.

Association between ARID2 and RAS-MAPK pathway in intellectual disability and short stature.

BACKGROUND: ARID2 belongs to the Switch/sucrose non-fermenting complex, in which the genetic defects have been found in patients with dysmorphism, short stature and intellectual disability (ID). As the phenotypes of patients with ARID2 mutations partially overlap with those of RASopathy, this study evaluated the biochemical association between ARID2 and RAS-MAPK pathway. METHODS: The phenotypes of 22 patients with either an ARID2 heterozygous mutation or haploinsufficiency were reviewed. Comprehensive molecular analyses were performed using somatic and induced pluripotent stem cells (iPSCs) of a patient with ARID2 haploinsufficiency as well as using the mouse model of Arid2 haploinsufficiency by CRISPR/Cas9 gene editing. RESULTS: The phenotypic characteristics of ARID2 deficiency include RASopathy, Coffin-Lowy syndrome or Coffin-Siris syndrome or undefined syndromic ID. Transient ARID2 knockout HeLa cells using an shRNA increased ERK1 and ERK2 phosphorylation. Impaired neuronal differentiation with enhanced RAS-MAPK activity was observed in patient-iPSCs. In addition, Arid2 haploinsufficient mice exhibited reduced body size and learning/memory deficit. ARID2 haploinsufficiency was associated with reduced IFITM1 expression, which interacts with caveolin-1 (CAV-1) and inhibits ERK activation. DISCUSSION: ARID2 haploinsufficiency is associated with enhanced RAS-MAPK activity, leading to reduced IFITM1 and CAV-1 expression, thereby increasing ERK activity. This altered interaction might lead to abnormal neuronal development and a short stature.

SMARCE1-related Coffin-Siris Syndrome: Case report and otolaryngologic manifestations of the syndrome.

Coffin-Siris Syndrome (CSS) is a genetic syndrome associated with multiple congenital anomalies due to mutations in the BAF-complex or SOX gene. Although well characterized overall, the subunits of the BAF-complex or SOX gene affected demonstrate phenotypic differences which are continuing to be defined. Among the variants is the SMARCE1 mutation, the least common identified genotype. This case report presents a pediatric patient with SMARCE1-related CSS, the seventh case reported in the literature. The congenital anomalies are discussed and compared to the reported cases of SMARCE1-related CSS and CSS overall with an emphasis on otolaryngologic manifestations.

Virtual Surgical Planning Assisted Management for Cleft-Related Maxillary Hypoplasia.

Maxillary hypoplasia is a common developmental deformity affecting patients with cleft lip and palate. Various surgical techniques including conventional orthognathic surgery, total maxillary distraction osteogenesis, and anterior maxillary segmental distraction have been applied to address the deformity. With the evolution of 3D computed tomography imaging, the visualization of skeletal complexities in different perspectives is greatly enhanced and comprehensive surgical planning is achieved. Intraoperative efficiency is also improved with the fabrication of 3D-printed templates. The study aims to present different surgical techniques with virtual surgical planning (VSP) and 3D-printed surgical templates and the solution of representative cases. From January 2014 to January 2019, VSP was transferred to actual surgery or distraction precisely in 80 adult patients with cleft-related maxillary hypoplasia. The accuracy was analyzed and the relapse was also estimated and observed in 18 patients after 1-year follow-up. Based on our experience, VSP provides a more reliable and effective option to conventional model surgery. It facilitates the preoperative planning and accurately transfers the virtual plan to correct the cleft-related maxillary hypoplasia.

Intubação de via aérea difícil em paciente com síndrome de Treacher Collins / Difficult airway intubation in a patient with Treacher Collins syndrome - case report

A síndrome de Treacher Collins é uma patologia rara, com gene causador mapeado no braço longo do cromossomo cinco (5q31. 3-q33.3). Conhecida como disostose craniofacial, apresenta-se com hipoplasia malar, hipoplasia mandibular e malformações do pavilhão auricular. Tal condição representa previsão de dificuldade para o ato anestésico de intubação, necessitando de avaliação pré-operatória minuciosa e cuidado intensivo no perioperatório. A anestesia geral costuma ser realizada por indução de anestésicos inalatórios, uma vez que crianças submetidas a procedimentos cirúrgicos são não cooperativas, além de haver dificuldade de se obter acesso venoso. Assim, objetiva-se relatar caso de via aérea de intubação difícil em paciente com síndrome de Treacher Collins, correlacionando às manifestações clínicas, ao diagnóstico e ao tratamento cirúrgico, e revisando a literatura sobre o tema. Relatamos um caso cuja singularidade reside no manejo anestésico diferente dos executados em outros centros médicos, ao abordar pacientes com previsão de via aérea difícil. Ao invés de se utilizar máscara laríngea ou intubação com laringoscópio óptico, procedeu-se a: indução inalatória, sedação sem abolir respiração espontânea, visualização das estruturas para introdução do tubo endotraqueal (Cormack 3), acesso venoso, intubação orotraqueal e, posteriormente, indução anestésica e bloqueio neuromuscular. Julgamos importante divulgar tal relato para expor alternativas na indisponibilidade de certos dispositivos, como o fibroscópio. A técnica de intubação sem máscara laríngea ou fibroscópio em pacientes com síndrome craniofacial pode ocorrer sem intercorrências com a estratégia de não abolir a respiração do paciente, porém com leve sedação, devido à não cooperação e à dificuldade de se obter acesso venoso em crianças. (AU)

Treacher Collins syndrome is a rare disease with the culprit gene mapped on the distal long arm of chromosome five (5q31. 3-q33.3). It is known as craniofacial dysostosis, and presents with malar hypoplasia, mandibular hypoplasia, and pinnae malformations. Such condition represents expected difficult airway intubation during anesthesia, requiring detailed preoperative evaluation, and intensive perioperative care. General anesthesia is usually performed through inhaling anesthetics because children undergoing surgical procedures are not cooperative, and their venous access is difficult. Thus, the aim of the study is to report a case of difficult airway intubation in a patient diagnosed with Treacher Collins syndrome, correlating clinical manifestations, diagnosis e surgical treatment, and reviewing the literature on the subject. We report a case that is unique because the anesthetic management is different from what has been done in other medical centers, since it manages patients with expected difficult airway. Instead of using a laryngeal mask airway (LMA) device or a flexible optical intubation (FOI), an inhaling induction was performed, with preserved spontaneous breathing sedation, and visualization of the structures to receive the endotracheal tube (Cormarck 3), venous access, orotracheal intubation and then, anesthetic induction and neuromuscular block. We consider it important to share this report to give alternatives when some devices, such as the fiberscope, are not available. The intubation technique without laryngeal mask airway device or fiberscope in patients with craniofacial syndrome may take place with no complications, when the patient's spontaneous breathing is not aborted, but with light sedation, because of children's noncooperation, and difficulty venous access. (AU)

Versatility of uniplanar prearthoplastic distraction osteogenesis in the correction of post-ankylosis facial deformities-a report of five different cases.

PURPOSE: Unilateral or bilateral ankylosis can lead to severe micrognathia and facial deformity that requires multiple, often, staged surgical corrections. To date, there is no ideal treatment modality that satisfactorily corrects the complex anatomy, restores the ramal height, and corrects the micrognathia and microgenia. Distraction osteogenesis has been acclaimed as a successful modality for the treatment of such deformities. It is a cost-effective approach with low morbidity and less relapse thus providing better functional and esthetic outcomes. It allows the surgeon to correct the deformity in various planes by using various devices by changing osteotomy designs and vectors, with simultaneous hard tissue and soft tissue reconstruction. PATIENTS AND METHODS: Here, we present a series of five cases where different types of distraction osteogenesis were combined with various other procedures to correct post-ankylotic facial asymmetry. In one case, simultaneous maxillo-mandibular distraction [Molina's technique] was used. RESULTS: All patients showed significant improvement in function and esthetics. Outcome assessment was made using clinical photographs and radiographs. CONCLUSION: Pre-arthroplastic distraction osteogenesis is a versatile cost effective approach that can be customized for every patient based on their needs.

The Pierre Robin Mandible is Hypoplastic and Morphologically Abnormal.

BACKGROUND: For Pierre Robin sequence (PRS) patients, there is incomplete characterization of 3D differences and effects of mandibular distraction osteogenesis (MDO) on the mandible compared to normal controls. METHODS: PRS infants who underwent MDO at 2 craniofacial referral centerals with pre- and postoperative computed tomography (CT) scans were identified. A group of age-matched control patients with CTs were identified in the PACS database. Demographic and perioperative data were recorded. Mandibular lengths, angles, and volumes were measured. Morphologic and outcomes data were analyzed in a case-control comparison. RESULTS: Sixty-three CT scans were analyzed. Fifteen pre-op PRS patient and 15 control CTs were well matched in terms of age and sex. Mandibular volume (78%), ramus length (87%), and body length (95%) were all decreased in the PRS patients. Anterior symphyseal angle (84%) was significantly reduced in PRS patients while mandibular angle (102%) was maintained. Eighteen post-op PRS patient and 15 control CTs were well matched in terms of age and gender. Mandibular volumes (106%) were normalized following distraction with shorter mandibular rami (88%) and longer mandibular bodies (109%). Postoperatively, mandibular angle (100%) and anterior symphyseal angle (99%) were ultimately indistinguishable from controls. CONCLUSIONS: The mandible in PRS is dysmorphic compared to age-matched controls. Overall, they have a smaller volume, shorter ramus, and an obtuse symphyseal angle. MDO improves mandibular volume and normalizes the symphyseal angle, but results in a longer mandibular body and shorter mandibular ramus.

A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature.

BACKGROUND: Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11A2 procollagen genes cause Stickler syndrome. Marshall syndrome, caused by a COL11A1 mutation, has clinical overlap with Stickler syndrome. CASE PRESENTATION: A 2-year-old Japanese boy was presented to our hospital with short stature (79.1 cm, -2.52 standard deviation). His past medical history was significant for soft cleft palate and bilateral cataracts. He had a flat midface, micrognathia, and limitations in bilateral elbow flexion. Radiographs showed mild spondyloepiphyseal dysplasia. Initially, we suspected Marshall syndrome, but no mutation was identified in COL11A1. At 8 years old, his height was 116.2 cm (-1.89 standard deviation), and his orofacial characteristics appeared unremarkable. We analyzed the COL2A1 gene and found a novel heterozygous mutation (c.1142 G > A, p.Gly381Asp). CONCLUSIONS: In this case report, we identify a novel missense mutation in the COL2A1 gene in a patient with Stickler syndrome type 1, and we describe age-related changes in the clinical phenotype with regard to orofacial characteristics and height. Genetic analysis is helpful for the diagnosis of this clinically variable and genetically heterogeneous disorder.

Application of Bidirectional Distraction Osteogenesis for the Treatment of Mandibular Micriognathia Caused by Temporomandibular Joint Ankylosis.

BACKGROUND: Temporomandibular joint (TMJ) ankylosis is a joint disorder that refers to bone or fibrous adhesion of the anatomic joint components and the ensuing loss of function. When it happens on children, it is always accompanied by dentofacial deformities. The objective of this study was to describe the authors' experience of bidirectional distraction osteogenesis for the treatment of mandibular deformities caused by TMJ ankylosis. METHODS: Sixteen patients with TMJ ankylosis and severe secondary mandibular deformities were treated with bidirectional distraction osteogenesis and release of joint from January 2013 to December 2015. Clinical outcomes were assessed based on the oral function, radiography, and medical photography. RESULTS: No reankylosis was found during the follow-up period. Sufficient volume and density new bone had been formed after the consolidation period. All patients have maintained stable improvement in oral function during the follow-up period. Most of the patients achieved satisfactory outcomes. CONCLUSIONS: Bidirectional transport distraction osteogenesis technique is a good and effective therapeutic option in treatment of bilateral or unilateral TMJ ankylosis patients associated with mandibular micrognathia.

Ankylosis of temporomandibular joints after mandibular distraction osteogenesis in patients with Nager syndrome: Report of two cases and literature review.

Nager syndrome, also known as Nager acrofacial dysostosis, was first described by Nager and de Reynier in 1948. The patients commonly present with micrognathia, and a preventive tracheostomy is necessary when there are symptoms of upper airway obstruction. Mandibular distraction osteogenesis is considered as an effective procedure, which not only improves micrognathia but also minimizes the chances of tracheostomy. However, mandibular distraction osteogenesis has some complications such as relapse, teeth injury, infection, and injury of the temporomandibular joints (TMJs). In this study, the author reported two patients with Nager syndrome who suffered from ankylosis of TMJs after mandibular distraction osteogenesis. In addition, a comprehensive literature review of post-distraction ankylosis of TMJs in patients with Nager syndrome was performed. Few studies demonstrated the condition of TMJs after mandibular distraction osteogenesis, and three studies were identified from the review. One study reported ankylosis of bilateral coronoid processes, in which coronoidectomies were necessary. Another study reported the use of prostheses to replace the ankylosed joints in a patient who had undergone many surgeries of the joints, such as gap arthroplasties, reconstructions with costochondral grafts, etc. One other study raised the concept of unloading the condyles during the mandibular distraction to prevent subsequent ankylosis. It seems that multiple factors are related to the ankylosis of TMJs after mandibular distraction osteogenesis in patients with Nager syndrome. Prevention of post-distraction ankylosis of the joints is important because the treatment is difficult and not always effective. We should conduct more studies about protection of the joints during mandibular distraction in the future.

Secuencia malformativa de Pierre Robin: informe de un caso y revisión de la literatura / Pierre Robin sequence: case report and literature review

Durante la infancia es muy frecuente encontrar alteraciones del desarrollo,las cuales derivan de una defi ciente formación de las estructurasanatómicas durante la embriogénesis. Puede encontrarse un sinnúmerode alteraciones del desarrollo que afectan la región bucal y maxilofacial.La gran mayoría de estas alteraciones han sido catalogadas como síndromes de orden genético; sin embargo, no todas pueden describirse como tales, pues existen anomalías del desarrollo que aparecen como consecuencia de una deficiente embriogénesis de la región facial, provocando alteraciones anatómicas y funcionales, pero que se apartan de componentes genéticos y cromosómicos específi cos. La secuencia malformativa de Pierre Robin es una de ellas, ya que esta condición es producida por una afección inicial, de la cual derivarán otras afeccionesadicionales a nivel del paladar y de la mandíbula que ocasionarán en elpaciente dificultad para la alimentación y respiración. Debido a que las alteraciones de esta condición afectan directamente la cavidad bucal,es crucial que el odontólogo se encuentre familiarizado con esta anomalía. El objetivo del presente artículo es describir las característicasque configuran esta entidad nosológica mediante la exposición de un caso clínico y revisión de la literatura.

During childhood, it is frequent to find development disorders whichare linked to the weak formation of anatomic structures duringembryogenesis. It is possible to find a plethora of developmentdisorders that aff ect the oral and maxillofacial region. The majorityof these disorders has been classifi ed as genetic malformations butnot all can be described as such. That is because some developmentdisorders appear as a result of a defi cient embryogenesis of the face,producing thus anatomic and functional malformations but that standapart from genetic and chromosomic specifi c components. The Pierre Robin sequence is one of them, given that this condition is producedby an initial disorder, followed by other disorders in the palate andjaw; provoking alimentary and breathing disabilities in the patient.Due to these disorders and their impact on the mouth, it is crucial thatdentists be familiarized with such anomalies. The aim of this article isto describe the key characteristics that defi ne this disease through thepresentation of a clinical case and a literature review.

Etiology and pathogenesis of robin sequence in a large Dutch cohort.

Robin sequence (RS) can be defined as the combination of micrognathia and upper airway obstruction/glossoptosis causing neonatal respiratory problems, with or without a cleft palate and either isolated or non-isolated. Pathogenesis varies widely. We hypothesize that optimal treatment depends on pathogenesis and therefore patients should be stratified according to diagnosis. Here, we evaluate diagnoses and (presumed) pathogeneses in an RS cohort. Medical records of all RS patients presenting between 1995-2013 in three academic hospitals were evaluated. Four clinical geneticists re-evaluated all information, including initial diagnosis. Diagnoses were either confirmed, considered uncertain, or rejected. If uncertain or rejected, patients were re-evaluated. Subsequent results were re-discussed and a final conclusion was drawn. We included 191 RS patients. After re-evaluation and changing initial diagnoses in 48 of the 191 patients (25.1%), 37.7% of the cohort had isolated RS, 8.9% a chromosome anomaly, 29.3% a Mendelian disorder, and 24.1% no detectable cause. Twenty-two different Mendelian disorders were diagnosed, of which Stickler syndrome was most frequent. Stratification of diagnoses according to (presumed) pathogenic mechanism in 73 non-isolated patients with reliable diagnoses showed 43.9% to have a connective tissue dysplasia, 5.5% a neuromuscular disorder, 47.9% a multisystem disorder, and 2.7% an unknown mechanism. We diagnosed more non-isolated RS patients compared to other studies. Re-evaluation changed initial diagnosis in a quarter of patients. We suggest standardized re-evaluation of all RS patients. Despite the relatively high diagnostic yield pathogenesis could be determined in only 59.7% (71/119), due to limited insight in pathogenesis in diagnosed entities. Further studies into pathogenesis of entities causing RS are indicated.

Visual diagnosis: 8-day-old hypotonic newborn with sparse hair.

A hypotonic newborn or infant with pale skin and sparse, friable, hypopigmented, or depigmented hair should have his copper and ceruloplasmin plasma levels evaluated because this is the usual clinical presentation of Menkes disease. Menkes disease is an X-linked recessive disease caused by a defect in the ATP7A gene, identified in 95% to 98% of the cases. Identifying the mutation confirms the diagnosis and allows for prenatal counseling and diagnosis in a future pregnancy. When administered within the first few months of life, copper histidinate, given subcutaneously in a dose of 50 to 150 mg/kg per day, appears to be effective not only by increasing life expectancy from 3 to 13 years but also by improving neurologic symptoms and neurodevelopmental outcomes in approximately 30% of the patients.

Coffin-Siris syndrome and related disorders involving components of the BAF (mSWI/SNF) complex: historical review and recent advances using next generation sequencing.

This issue of Seminars in Medical Genetics, American Journal of Medical Genetics Part C investigates the human diseases caused by mutations in the BAF complex (also known as the mammalian SWI/SNF complex) genes, particularly focusing on Coffin-Siris syndrome (CSS). CSS is a rare congenital malformation syndrome characterized by developmental delay or intellectual disability (ID), coarse facial appearance, feeding difficulties, frequent infections, and hypoplasia/aplasia of the fifth fingernails and fifth distal phalanges. In 2012, 42 years after the first description of CSS in 1970, five causative genes (SMARCB1, SMARCE1, SMARCA4, ARID1A, ARID1B), all encoding components of the BAF complex, were identified as being responsible for CSS through whole exome sequencing and pathway-based genetic screening. The identification of two additional causative genes (PHF6, SOX11) followed. Mutations in another BAF complex gene (SMARCA2) and (TBC1D24) were found to cause clinically similar conditions with ID, Nicolaides-Baraitser syndrome and DOORS syndrome, respectively. Also, ADNP was found to be mutated in an autism/ID syndrome. Furthermore, there is growing evidences for germline or somatic mutations in the BAF complex genes to be causal for cancer/cancer predisposition syndromes. These discoveries have highlighted the role of the BAF complex in the human development and cancer formation. The biology of BAF is very complicated and much remains unknown. Ongoing research is required to reveal the whole picture of the BAF complex in human development, and will lead to the development of new targeted therapies for related disorders in the future.

Simultaneous costochondral graft and distraction osteogenesis in unilateral TMJ ankylosis associated with mandibular retrognathia and asymmetry.

The purpose of this study was to review the long-term effect of simultaneous costochondral graft (CCG) and distraction osteogenesis (DO) in the management of unilateral temporomandibular joint ankylosis associated with severe dentofacial deformities in our clinic. In addition, we sought to analyze the advantages and disadvantages of CCG and DO. Four patients were included in this clinical study during 2005 to 2007. The mean length of ankylosis history was 14.5 years. All patients had significant mandibular retrognathia and asymmetry histories and have been diagnosed with obstructive sleep apnea syndrome by a polysomnogram before surgery. A 1-stage surgery, with gap arthroplasty, CCG, and mandibular DO, was performed. The surgical plan and technique were reviewed. No severe complications were observed after surgery. Distraction was started on day 7 after surgery. The distance of distraction ranged from 20 to 25 mm (mean, 22.5 mm). Mouth opening was increased from 25 to 37 mm (mean, 33.5 mm) during the follow-up period (range of 3.5-5 y). No recurrence of joint ankylosis occurred based on the clinical and radiographic evaluations. All of the patients had significant improvement in obstructive sleep apnea syndrome after surgery. Mandibular asymmetry and retrognathia were well corrected in all of the patietns. In conclusion, a 1-stage surgical treatment with DO and CCG demonstrated its feasibility and effectiveness in management of temporomandibular joint ankylosis combined with severe dentofacial deformity. It is a safe and reliable method of treatment.

A review of the oro-dento-facial characteristics of hereditary sensory and autonomic neuropathy type III (familial dysautonomia).

The oro-dento-facial features and dysfunction of children with hereditary sensory and autonomic neuropathy type III, known as familial dysautonomia or Riley-Day syndrome, was first described in the scientific literature in 1949. They include dental trauma; dental and soft tissue self-mutilation; normal dental age; normal sequence and timing of eruption and exfoliation of teeth; smaller tooth size; different and disproportional tooth components; normal alveolar bone height; small jaws, mild crowding, and malocclusions. These persons have craniofacial morphology that is different from accepted norms but they resemble norms of their ethnic origin. The subjects can have gray, pale, shiny faces with an asymmetric suffering expression; frontal bossing, with eventual hypertelorism and narrow lips; a low-caries rate; drooling, and hypersalivation. They can have changes in salivary composition and content, which influences plaque and calculus and increases the risk of gingival and periodontal diseases. They also have difficulty in controlling oral muscles; a progressive decrease in number of tongue fungiform papillae, accompanied by lack of taste buds; and specific dysgeusia, but a normal sense of smell.

[The treatment of mandibular micrognathia secondary to temporomandibular joint ankylosis with distraction osteogenesis].

OBJECTIVE: To evaluate the clinical effect of distraction osteogenesis for patients with mandibular micrognathia secondary to temporomandibular joint (TMJ) ankylosis. METHODS: 43 patients (aged from 2 to 61 years old) with mandibular micrognathia were treated with mandibular distraction osteogenesis. Two types of mechanical distraction were utilized in this study. Ten patients (age ranged from 2 to 16-years-old, mean age 7.6 years old) with severe micrognathia underwent bilateral mandibular distraction with rigid external distraction (RED) device. Other 33 patients were treated with unilateral(6 cases) or bilateral (27 cases) mandibular distraction using internal distraction device. Distraction was started on the 4th to 8th day after operation and distraction rate was 0.25 mm every time, four times a day. Distractor was removed after 3 to 6 months of consolidation period. RESULTS: Eighty sides of mandible in 43 patients were lengthened. The mean distraction distance was 23.2 mm (ranged from 14 to 35 mm). After distraction, the average posterior airway space (PAS) was enlarged from 4.9 mm to 10.4 mm and average angle of sella-nasion-point B (SNB) was increased from 64.2 degrees to 74.5 degrees. The apnea hypopnea index (AHI) was decrease significantly. The profile was improved and OSA was improved effectively in each patient. No complication occurred during treatment. No persistent numbness of lower lip was observed. All patients were satisfied with the results. After a mean follow-up period of 20.3 months(5 to 103 months) , the result was stable and no obvious relapse of micrognathia was observed. CONCLUSIONS: Distraction osteogenesis is an effective way in correction of mandibular micrognathia secondary to TMJ ankylosis. RED is a new method for treatment of children and adolescence with severe mandibular micrognathia. The procedure is simple and safe with stable result.