Métodos de avaliação cognitiva de pacientes com Síndrome de Apert e de Crouzon / Cognitive assessment methods of patients with Apert and Crouzon syndrome

A Craniossinostose Coronal bilateral implica em diminuição do Perímetro Craniano (PC) no eixo ântero-posterior (Braquicefalia) e frequentemente se associa ao aumento do eixo céfalo-caudal (vertical-altura) do crânio (Turricefalia), sendo um dos achados mais comuns nas Síndromes de Crouzon e Apert. Objetivo: Identificar, analisar e sintetizar os métodos de avaliação cognitiva apropriados para o acompanhamento da evolução de pacientes com cranioestenoses sindrômicas, em particular as síndromes de Apert e de Crouzon. Método: Trata-se de uma revisão de escopo. Para a formulação da pergunta norteadora da pesquisa e da estratégia de busca, foi utilizada a estratégia Population [((Apert OR Crouzon) AND (Disease OR Syndrom*))], Concept [((cognit* OR neurobehavioral OR neurocognit* OR neuropsyc*) AND (evaluation OR evaluations OR assessment OR "test" OR tests OR status OR development OR disorder OR disorders OR impairment OR impairments OR impaired OR function OR functions))] e Context (em qualquer contexto). Foram inclusos os artigos escritos em inglês, português e espanhol em qualquer período. A busca foi realizada nas bases de dados: Embase, Scopus, PubMed/MEDLINE e rede BVS Salud. Resultados:Inúmeros testes de avaliação cognitiva validados internacionalmente foram aplicados aos pacientes com Apert e Crouzon, mas não se observou uma padronização (protocolo) seguida pelas várias unidades de assistência. Dos 75 tipos de Testes Cognitivos aplicados houve o predomínio da Escala de Inteligência de Wechsler (e seus subtestes), 50%. Na população avaliada predominou duas faixas etárias: escolares e adolescentes. As crianças com Apert e Crouzon obtiveram escores piores nos transtornos de socialização, atenção e internalização quando comparadas com o grupo normativo, sendo os piores resultados encontrados em Apert. Fatores que interferem no desenvolvimento neuropsicomotor: pressão intracraniana, malformações encefálicas, genética, idade na correção cirúrgica (postergação da primeira cirurgia após um ano de idade associou-se a um quociente de inteligência mais baixo), institucionalização, ambiente familiar, escolaridade dos cuidadores e nível socioeconômico. Considerações finais: os resultados obtidos contribuíram para maior conhecimento do perfil cognitivo dos pacientes com estas síndromes. Somente conhecendo as habilidades e dificuldades neuropsicomotoras, cognitivas e psicossociais dos pacientes com Apert e Crouzon é que as equipes de saúde, da escola e de cuidadores poderão entender melhor a capacidade perceptiva destes no processo de aprendizado e estarão mais aptas em atender as necessidades especiais destes pacientes e poderão ofertar os estímulos mais adequados no momento mais oportuno (AU).

Bilateral Coronal Craniosynostosis implies a decrease in the Cranial Perimeter (CP) in the anteroposterior axis (Brachycephaly) and is frequently associated with an increase in the cephalocaudal (vertical height) axis of the skull (Turrycephaly); being one of the most common findings in Crouzon and Apert Syndromes (Syndromic Craniosynostosis). In this Scope Review study, among the Syndromic Craniosynostosis, Apert and Crouzon Syndromes will be of special interest. Objective: This study aimed to identify, analyze, and synthesize the appropriate cognitive assessment methods for monitoring the evolution of patients with syndromic craniosynostosis, in particular Apert's and Crouzon's syndromes. Method: This is a scope review. In order to formulate the research guiding question and the searching strategy, the Population [((Apert OR Crouzon) AND (Disease OR Syndrom*))], Concept [((cognit* OR neurobehavioral OR neurocognit* OR neuropsyc*) AND (evaluation OR evaluations OR assessment OR "test" OR tests OR status OR development OR disorder OR disorders OR impairment OR impairments OR impaired OR function OR functions))] and Context (in any context) strategy was used. The articles written in English, Portuguese, and Spanish in any period were included. The search was performed in the following databases: Embase, Scopus, National Library of Medicine (PubMed/MEDLINE), and in the BVS Salud network (PAHO, WHO, BIREME, LILACS). Results: many internationally validated cognitive assessment tests were applied to patients with Apert and Crouzon, but no standardization (protocol) was followed. Of the 75 types of Cognitive Tests applied, the Wechsler Intelligence Scale predominated, 50%. In the evaluated population, two age groups predominated: school children and adolescents. Children with Apert and Crouzon had worse scores on disorders of socialization, attention, and internalization when compared to the normative group, with the worst results found in Apert. Factors that interfere with cognitive development: intracranial pressure, brain malformations, genetics, age at surgical correction, institutionalization, family environment, caregiver education, and socioeconomic status. Conclusion: the results contributed to a better understanding of the cognitive profile of patients with these syndromes and only by knowing about the neuropsychomotor, cognitive, and psychosocial skills and difficulties of these patients with Apert and Crouzon that health, school, and caregiver teams will be able to understand the perceptive capacity in the learning process of these patients deeply and will be able to offer the most appropriate stimuli at the most opportune time. Keywords: Apert, Crouzon, Neuropsyc, Tests, Development (AU).

A case of Crouzon syndrome with plagiocephaly and scaphocephaly / 中华整形外科杂志

In October 2017, a female patient, 3 years and 5 months of age, with Crouzon syndrome, associated with multiple craniosynostoses was admitted to Plastic Surgery Hospital. Combined intracranial and extracranial approaches of fronto-orbital advancement and cranial suture release were performed to treat plagiocephaly and scaphocephaly. The patient′s families were investigated. Corresponding mutations were detected by DNA sequencing. Therapeutic effect was satisfactory. The mutation was inherited for 5 generations. Genomic sequencing results showed that the exons of fibroblast growth factor receptor 2 gene in the child was mutated, which excessively activated downstream signals and caused craniosynostosis.

Proteomic analysis of serum exosomes derived from Crouzon syndrome patients carrying a mutant FGFR2C342Y / 中华整形外科杂志

Objective@#Reveal the global expression profile of serum exosomal proteins of Crouzon syndrome patients.@*Methods@#We isolated microvesicles from serum of Crouzon children with a C342Y mutation in FGFR2 by ultracentrifugation, which were further characterized by electron microscopy and immunoblotting. The protein profiling in normal subjects and Crouzon patients was systematically compared by iTRAQ proteomic analysis.@*Results@#The result demonstrated that microvesicles were between 30—100 nm in diameter, round shape with cup-like concavity and expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1. We identified a total number of 62 proteins, among which 22 proteins overlap with ExoCarta database and were different between the Crouzon patient and the normal subject. The Ingenuity Pathway Analysis showed that the functions of these proteins are mostly involved in Developmental Disorder, Hereditary Disorder, Skeletal and Muscular Disorders, which are all related to the clinical manifestations of Crouzon syndrome. In addition, the proteins were focused on the network of "Organismal Injury and Abnormalities, Hematological System Development and Function, Cell-To-Cell Signaling and Interaction" . The central protein FN1 was presented as the key protein in the network.@*Conclusions@#Our data demonstrated that serum exosomes harbor informative proteins and FN1 was selected as a potential candidate for its role in promoting osteoblast adhesion, proliferation and mineralization.

Genetic Syndromes Associated with Craniosynostosis

Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various complications including neurologic, ophthalmic and respiratory dysfunction. Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. Both environmental factors and genetic factors are associated with development of craniosynostosis. Nonsyndromic craniosynostosis accounts for more than 70% of all cases. Syndromic craniosynostosis with a certain genetic cause is more likely to involve multiple sutures or bilateral coronal sutures. FGFR2, FGFR3, FGFR1, TWIST1 and EFNB1 genes are major causative genes of genetic syndromes associated with craniosynostosis. Although most of syndromic craniosynostosis show autosomal dominant inheritance, approximately half of patients are de novo cases. Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, and Antley-Bixler syndrome are related to mutations in FGFR family (especially in FGFR2), and mutations in FGFRs can be overlapped between different syndromes. Saethre-Chotzen syndrome, Muenke syndrome, and craniofrontonasal syndrome are representative disorders showing isolated coronal suture involvement. Compared to the other types of craniosynostosis, single gene mutations can be more frequently detected, in one-third of coronal synostosis patients. Molecular diagnosis can be helpful to provide adequate genetic counseling and guidance for patients with syndromic craniosynostosis.

Effects of Different Doses of Sufentanil Citrate on Analgesic Effects of Crouzon Syndrome Children with Cra-niofacial Reconstruction / 中国药房

OBJECTIVE:To investigate the effects of different doses of sufentanil citrate on hemodynamic indexes and stress response indexes of Crouzon syndrome children with craniofacial reconstruction. METHODS:60 cases of Crouzon syndrome under-going craniofacial reconstruction were selected from our hospital during Jan. 2010-Jan. 2016,and then randomly divided into group A,group B and group C,with 20 cases in each group. 3 groups were given pump injection of Propofol injection 4-8 mg/(kg·h)for anesthesia induction+Sufentanil citrate injection [group A 0.3 μg/(kg·h),pump injection;group B 0.6 μg/(kg·h),pump injection;group C 1.0 μg/kg,iv,0.5 h/time] for anesthesia maintenance, Cisatracurium besilate for injection 0.1 mg/kg,iv,every 40 min, drug withdrawal 5 min before the end of surgery. The hemodynamic indexes(MAP,HR)and stress response indexes(ACTH,cor-tisol)were observed in 3 groups at different time points as well as the occurrence of ADR. RESULTS:MAP levels of group C at 5 min after skin incision,1 h after operation and immediately at the end of surgery were significantly higher than before anesthesia, while those of group B were significantly higher than group C at same time points. HR of group A at 1 h after surgery and that of group B at 5 min after skin incision and 1 h after surgery were significantly higher than before anesthesias;HR of group B at 1 h after surgery was significantly lower than that of group A,and its HR at 5 min after skin incision and 1 h after surgery were signifi-cantly lower than those of group C. ACTH levels of 3 groups at 5 min after skin incision,1 h after surgery and immediately after the end of surgery were significantly higher than before anesthesia. ACTH levels of group B at 5 min after skin incision,1 h after surgery and immediately after the end of surgery were significantly lower than those of group A and C,and the group A was signifi-cantly lower than the group C at same time points. Cortisol levels of group A at 1 h after surgery,and those of group C at 5 min af-ter skin incision,1 h after surgery and immediately after the end of surgery were significantly higher than before anesthesia. Corti-sol levels of group B at 1 h after surgery were significantly lower than those of group A;cortisol levels of group A at 5 min after skin incision and immediately after the end of surgery and those of group B at 5 min after skin incision,1 h after surgery and imme-diately after the end of surgery were all significantly lower than those of group C. There were statistical significance all above(P<0.05). No obvious ADR was found in 3 groups. CONCLU-SIONS:Pump injection of sufentanil citrate 0.6 μg/(kg·h) can maintain analgesic effect of Crouzon syndrome children with craniofacial reconstruction,can keep hemodynamics sta-ble and effectively inhibit stress response during surgery with good safety.

Arteriovenous Malformation in Crouzon Syndrome: A Case Report.

Crouzon syndrome, a hereditary syndrome of craniofacial dysostosis, is a triad of skull deformities, facial anomalies and exophthalmos . It accounts for approximately 4.8% of all cases of craniosynostosis with the prevalence of approximately 1 per 25,000 live births worldwide. This is a case of Crouzon syndrome with arteriovenous malformation over vertex which has not been reported so for in the literature.

Scalpel Cautery Adenotonsillectomy Done in a Case of Crouzon’s Syndrome.

Background/Objectives: Crouzon syndrome is characterized by premature closure of the cranial sutures, midface hypoplasia, orbital deformities and other associated abnormalities. Children with Crouzon syndrome frequently have obstructive sleep apnea due to the underdevelopment of the midface. Setting: Dept. of ENT, Head and Neck Surgery and Anesthesia, KVG Medical College, Sullia. Case report: A 12-year-old boy of Crouzon syndrome with chronic adenotonsillitis was managed by adenotonsillectomy under general anesthesia by scalpel cautery method. The boy responded well to surgery and the mild sleep disorder disappeared within a week uneventfully. Conclusion: Sleep disorders in this condition can be treated by improving the airway by selective procedures like midface advancement, mandibular expansion, adenotonsillectomy, uvulopalatopharyngoplasty, anterior tongue reduction and endoscopic tracheal granuloma excision.

Craneoestenosis. II. Análisis de las craneoestenosis sindromáticas y diferentes tipos de tratamiento / Craneosynostosis. II. Analysis of syndromatic craniosynostosis and different types of treatment

En esta segunda parte del trabajo de revisión de las craneoestenosis se analizan los diferentes tipos de craneoestenosis sindromáticas, sus características clínicas, imagenológicas y, en los casos que se conocen, las alteraciones genéticas. También se describen los diferentes tipos de tratamientos para las craneoestenosis, tanto sindromáticas como no sindrómaticas, desde los tratamientos quirúrgicos clásicos para lograr la descompresión cerebral, la restauración de la anatomía y proporcionar el mayor grado de estética al menor. Por último, se incluye información acerca de los tratamientos de vanguardia como son las técnicas en ingeniería de tejidos, la utilización de sistemas bioabsorbibles, de sistemas de distracción ósea e, incluso, la cirugía endoscópica. Se espera que pronto exista un mayor número de publicaciones que reporten el éxito de estas nuevas técnicas.

In this second part of the Review Article on craniosynostosis, different types of syndromatic craniosynostosis are analyzed along with clinical and imaging aspects and, in known cases, embryogenetic alterations. Different types of treatments are also described for both syndromic and nonsyndromic craniosynostosis. These range from the classic surgical treatments for achieving brain decompression, restoring the anatomy and providing the highest degree of aesthetics for the child. Last, but not least, information on cutting-edge treatments such as techniques in tissue engineering, use of bioabsorbable bone distractors and even endoscopic surgical systems are included. It is expected that in the near future there should be a greater number of publications that report the success of these new techniques.

Sindrome de Crouzon: diagnóstico radiográfico y tratamiento ortognático de un caso clínico / Crouzon´s syndrome: radiographic diagnosis and orthognathic treatment of a clinical case

El síndrome de Crouzon es un defecto de origen congénito que se caracteriza por malformaciones en el desarrollo, ligado al cierre prematuro de las suturas craneales que producen severos cambios en la conformación de la cara y cráneo. El objetivo de este trabajo es presentar un caso clínico de un paciente con síndrome de Crouzon de 17 años de edad, sexo femenino. Se analizan los diagnósticos clínico, radiográfico y elt ratamiento ortodóntico-quirúrgico.

Achados neuropsicolinguísticos na síndrome de Crouzon: relato de caso / Neuropsycholinguistic findings in Crouzon syndrome: case report

O objetivo do trabalho foi relatar um caso clínico sobre a síndrome de Crouzon, englobando as habilidades neuropsicolinguisticas. O estudo foi realizado com uma criança de oito anos e dois meses, do gênero masculino, com diagnóstico clínico da síndrome de Crouzon. Para a caracterização das habilidades foi realizada avaliação interdisciplinar com fonoaudiólogo, psicólogo e neurologista. A avaliação fonoaudiológica incluiu a avaliação das habilidades comunicativas, da linguagem oral, considerando as habilidades fonológicas, sintáticas, semânticas e pragmáticas, e da linguagem escrita. Para a avaliação neuropsicológica utilizou-se a escala Wechsler Scale for Children. A avaliação neurológica foi centrada no exame de ressonância magnética de encéfalo. O paciente também realizou avaliação audiológica, e apresentou perda auditiva condutiva de grau leve. Na avaliação clínica e formal da linguagem oral foi possível observar alterações nos aspectos fonológico e semântico da linguagem. Já com relação à linguagem escrita, observou-se desempenho aquém do esperado para a idade, caracterizado principalmente por alterações na escrita e na aritmética. Os resultados da avaliação neuropsicológica evidenciaram valores de Quociente Intelectual dentro dos padrões da normalidade. O resultado da ressonância magnética do encéfalo demonstrou alteração estrutural do sistema nervoso central. Pode-se concluir que os achados evidenciaram alterações nas habilidades de linguagem oral e escrita, além da presença de alteração estrutural do sistema nervoso central.

The aim of this study was to relate the neuropsycholinguistic abilities of a male child with eigth years and two months, diagnosed with Crouzon syndrome. The characterization of neropsycholinguitic abilities was based on a interdisciplinary evaluation carried out by a speech-language pathologist, a neurologist, and a psychologist. Speech-language evaluation included the assessment of communication skills, oral (phonological, syntactic, semantic and pragmatic abilities) and written language. The neuropsychological assessment used the Wechsler Scale for Children. The neurological evaluation was focused on the results of magnetic resonance imaging. The subject also carried out an audiological evaluation, which showed mild conductive hearing loss. In the oral language assessment, phonological and semantic deficits were observed. Written language performance was also below the expected for the subject's age, characterized mainly by writing and arithmetic deficits. The neuropsychological evaluation showed normal Intellectual Quotient. The results of the magnetic resonance imaging showed structural alterations of the central nervous system. Thus, the findings evidenced oral and written language deficits, and presence of structural alterations of the central nervous system.

Crouzan Syndrome - A Case Report.

Genetic disorders account for a significant amount of morbidity and mortality in children and are of primary interest to the dentist. Crouzan syndrome is one of a rare group of syndromes characterized by craniosynostosis or premature closing of the cranial sutures. The major features are Brachycephaly, ocular proptosis, under developed maxilla, midface hypoplasia, rare cleft lip, palate. Early Craniectomy is often needed to alleviate the raised intracranial pressure. This paper discusses a case report of five year old girl with the features of crouzan syndrome and a multidisciplinary approach to be followed in managing the situation.

Síndrome de Crouzon: revisão de literatura / Crouzon's syndrome: literature review

Introdução: A síndrome de Crouzon ou Disostose crânio-facial tipo I é uma doença rara, que afeta o desenvolvimento do esqueleto crânio-facial. Apesar de ser incomum, possui 50% de risco de transmissão quando um dos pais é portador. Objetivo: Fazer uma revisão da literatura sobre a Síndrome de Crouzon, enfatizando aspectos atuais. Método: Utilizou-se como metodologia consulta as bases de dados on line Cochrane, LILACS, MEDLINE, OMIM e SciELO, aplicando-se à pesquisa o termo Síndrome de Crouzon para artigos publicados até 2007, além da literatura já consagrada em relação ao assunto. Revisão de Literatura: Esta síndrome é caracterizada por anomalias crânios-faciais causadas por perda precoce de flexibilidade do crânio, presentes desde o nascimento e com tendência a agravar-se com o tempo. Os principais sinais clínicos são craniossinostose, hipertelorismo, exoftalmia, estrabismo externo, "nariz de bico de papagaio", lábio superior curto, hipoplasticidade maxilar e relativo prognatismo mandibular, determinando um aspecto de hipoplasia centrofacial. É uma afecção hereditária com transmissão autossômica dominante com 100% de penetrância e larga escala da expressão fenotípica. Considerações Finais: O aconselhamento genético e o estudo individual de cada caso são fundamentais a fim de se promover o avanço no diagnóstico. É necessária uma abordagem precoce multidisciplinar com programa terapêutico específico objetivando a prevenção dos efeitos de um diagnóstico tardio.

Introduction: The Crouzon syndrome or craniofacial dysostosis type I is a rare disease that affects the craniofacial skeleton development. Although it is uncommon, it has a transmission risk of 50% when one of the parents is a carrier. Objective: Performing a literature review about the Crouzon Syndrome, with emphasis on the current aspects. Method: As a methodology, a search on databases on-line, such as Cochrane, LILACS, MEDLINE, OMIM and SciELO has been made, by applying for the search the key-word Crouzon's Syndrome for articles published until 2007, in addition to the literature already dedicated to the subject. Literature Review: This syndrome is characterized by craniofacial anomalies caused by the early loss of the cranium flexibility, and present since the birth with tendency to aggravation in time. The main clinic signs are craniosynostosis, hypertelorism, exophthalmia, external strabismus, "parrot-beaked nose", short upper lip, hypoplastic maxilla and a relative mandibular prognathism determining a mid-facial hypoplasia aspect. It is a hereditary affection with an autosomal dominant transmission with 100% of penetrance and large phenotypic scale. Final Considerations: The genetic advising and an individual study of each case are essential to promote the improvement of the diagnosis. An early multidisciplinary approach is necessary, with specific therapeutic program aiming at the prevention of late diagnosis effects.

A Case Report of RED II Distraction Osteogenesis and Early Rigid Fixation by Minimal Invasive Approach Le Fort III Osteotomy in Crouzon's Disease

PURPOSE: Rigid external distraction(RED) is a highly effective technique for correction of maxillary hypoplasia in patients with cleft or syndromic craniosynostosis. Despite many advantages of RED, it also has the problem of relapse as the conventional advancement surgery. Bicoronal approach, that is the common approach to gain access to the craniofacial skeleton, had some morbidity, such as hair loss, sensory loss, wide scar and temporal hollowing. We present our clinical experience of RED distraction with minimal invasive approach and early rigid fixation to overcome these disadvantages. METHODS: A 27-year-old female patient with Crouzon's disease underwent Le Fort III osteotomy and RED device application through the minimal invasive direct skin incisions. After the latent period of 5 days, distraction was undertaken until proper convexity and advancement were obtained. During the rigid retention period, inflammation occurred on the right cheek, and proper conservative managements were done including continuous irrigation. To maintain the stability of distraction, early rigid fixation was undertaken on the osteotomy sites through another skin incisions. Preoperative and postoperative orthodontic treatments were performed. Serial photographs and cephalometric radiographs were obtained preoperatively, after distraction and 6 months after distraction. RESULTS: The cephalometric analysis demonstrated postoperatively significant advancement of the maxilla and improvement of facial convexity. After 6-month follow-up period, the maxilla was stable in the sagittal plane and no relapse was found. Facial scars were not noticeable and other deformity and morbidity did not occur. CONCLUSION: This effective and stable technique will be a good alternative for the patients who need large amount of distraction and for adult patients with severe maxillary hypoplasia or syndromic craniosynostosis.

A Case Report of RED II Distraction Osteogenesis and Early Rigid Fixation by Minimal Invasive Approach Le Fort III Osteotomy in Crouzon's Disease

PURPOSE: Rigid external distraction(RED) is a highly effective technique for correction of maxillary hypoplasia in patients with cleft or syndromic craniosynostosis. Despite many advantages of RED, it also has the problem of relapse as the conventional advancement surgery. Bicoronal approach, that is the common approach to gain access to the craniofacial skeleton, had some morbidity, such as hair loss, sensory loss, wide scar and temporal hollowing. We present our clinical experience of RED distraction with minimal invasive approach and early rigid fixation to overcome these disadvantages. METHODS: A 27-year-old female patient with Crouzon's disease underwent Le Fort III osteotomy and RED device application through the minimal invasive direct skin incisions. After the latent period of 5 days, distraction was undertaken until proper convexity and advancement were obtained. During the rigid retention period, inflammation occurred on the right cheek, and proper conservative managements were done including continuous irrigation. To maintain the stability of distraction, early rigid fixation was undertaken on the osteotomy sites through another skin incisions. Preoperative and postoperative orthodontic treatments were performed. Serial photographs and cephalometric radiographs were obtained preoperatively, after distraction and 6 months after distraction. RESULTS: The cephalometric analysis demonstrated postoperatively significant advancement of the maxilla and improvement of facial convexity. After 6-month follow-up period, the maxilla was stable in the sagittal plane and no relapse was found. Facial scars were not noticeable and other deformity and morbidity did not occur. CONCLUSION: This effective and stable technique will be a good alternative for the patients who need large amount of distraction and for adult patients with severe maxillary hypoplasia or syndromic craniosynostosis.

Craniofacial morphologic alteration induced by bone-targeted mutants of FGFR2 causing Apert and Crouzon syndrome / 대한치과교정학회지

OBJECTIVE: Activating mutations in the fibroblast growth factor receptor-2 (FGFR2) have been shown to cause syndromic craniosynostosis such as Apert and Crouzon syndromes. The purpose of this pilot study was to investigate the resultant phenotypes induced by the two distinctive bone-targeted gene constructs of FGFR2, Pro253Arg and Cys278Phe, corresponding to human Apert and Crouzon syndromes respectively. METHODS: Wild type and a transgenic mouse model with normal FGFR2 were used as controls to examine the validity of the microinjection. Micro-CT and morphometric analysis on the skull revealed the following results. RESULTS: Both Apert and Crouzon mutants of FGFR2 induced fusion of calvarial sutures and anteroposteriorly constricted facial dimension, with anterior crossbite present only in Apert mice. Apert mice differed from Crouzon mice and transgenic mice with normal FGFR2 in the anterior cranial base flexure and calvarial flexure angle which implies a possible difference in the pathogenesis of the two mutations. In contrast, the transgenic mice with normal FGFR2 displayed normal craniofacial phenotype. CONCLUSION: Apert and Crouzon mutations appear to lead to genotype-specific phenotypes, possibly causing the distinctive sites and sequence of synostosis in the calvaria and cranial base. The exact function of the altered FGFR2 at each suture needs further investigation.

Midface Advancement with Rigid External Distraction System in Crouzon's Disease

Distraction osteogenesis has become an alternative technique to treat craniomaxillofacial anomalies. It was initially used to treat mandibular dysplasia and now it is applied to other regions of the craniofacial skeleton. We now present our clinical experience of midface distraction with the use of rigid external distraction for the treatment of an 8-years-old girl with midface hypoplasia in Crouzon's disease, who had undergone fronto-orbital advancement at the age of 6. We performed midface advancement by Le Fort III osteotomy with rigid external distraction system(RED II, KLS Martin, Jacksonville, FL). The active distraction was initiated on the 3rd postoperative day and was continued until the 20th postoperative day for 18 days. The rate of distraction can be adjusted during this time according to clinical judgment and cephalometric assessment. On completion of distraction, the RED II was left in place without activation for 25 days for rigid retention. The RED II was then removed and an orthodontic facemask was applied with elastic traction for 6wks. The total amount of distraction was 18.5mm, 28.5mm, 10.5mm, 14.5mm at right inferior orbital rim, left inferior orbital rim, right intraoral, left intraoral area respectively. The photography, cephalometry, and 3D CT(3 dimensional computed tomography) show that facial convexity was improved. We could correct midface deficiency successfully by LeFort III osteotomy and rigid external distraction.

Midfacial distraction osteogenesis of Crouzon syndrome with RED(Rigid External Distraction) system / 대한치과교정학회지

Crouzon syndrome is one of the craniofacial syndromes characterized by craniosynostosis, midfacial hypolpasia and ocular proptosis. Distraction osteogenesis is becoming important technique to treat craniofacial dysplaisa. It has many advantages compared with standard orthognathic surgery. Maxillary distraction osteogenesis after Le Fort III osteotomy with the RED system presents successful maxillary protraction to Crouzon syndrome patient with severe maxillary deficiency. It also allows remarkable improvement of facial esthetics and respiratory functions.

Case Report of Osteomyelitis after Monobloc Advancement for the Treatment of a Crouzon's Syndrome

In 1912, Crouzon described a syndrome compromising the triad of cranial deformity, facial deformity, and exorbitism. Crouzon's syndrome occurs in 1 in 25,000 live births and follows an autosomal dominant mode of transmission. However 30 to 60% of cases are sporadic and represent fresh mutations. The 27-year-old female patient we report here has family history of two cases of Crouzon's syndrome. The patient had mild nasal obstruction and rhinorrhea, which didn't make the surgery absolutely contraindicated. The Monobloc advancement-Le Fort III osteotomy for midfacial advancement and the lamellar split osteotomy of supraobital bandeau for orbitofrontal advancement- were performed. After 8~12 weeks of patient follow up, CSF rhinorrhea was observed and infection was suspected. The primary focus of infection was supposed to be preexisting sinusitis of the patient. The infection didn't spread intracranially, which was contributed by intact inner table of cranium owing to the lamellar split osteotomy. In conclusion, 1) The importance of irradication of preexisting nasal / perinasal infection such as sinusitis cannot be emphasized too much, 2) How to obliterate the dead space between the inner and outer table, and 3) In terms of infection, at least, lamellar split osteotomy can be regarded superior to classical osteotomy, since inner table serves as a barrier of ascending infection.

Modification of Le Fort III Osteotomy and Fronto-orbital Advancement for the Correction of Crouzon's Disease

In 1912, Crouzon reported one of craniofacial dysostosis, which was inherited as an autosomal dominant trait and characterized by craniosynostosis, midface hypoplasia, and exorbitism. In 1950, the first midface advancement was performed by means of a total facial osteotomy by Sir Harold Gillies. In 1967, Tessier accomplished complete craniofacial dysjunction by performing Le Fort III-Tessier I osteotomy on the basis of Le Fort III fracture and laid the foundation for modern craniofacial surgery. Variable combinations of the surgeries and osteotomies are performed considering functional disabilities as well as patient's age, general condition, and aesthetic problems. The nineteen-year-old female patient complained of frog-like face and showed severe exorbitism and midface hypoplasia, while the occlusion, being relatively normal. We applied modified Le Fort III osteotomy and fronto- orbital advancement. Over the follow-up period of six months, her previous normal occlusion was preserved and the exorbitism and midface deformity largely improved aesthetically.

A Case of FGFR2 Exon lllc Mutation in Crouzon Syndrome

Crouzon syndrome, an autosomal dominant disorder, has characteristic features of craniosynostosis, hypertelorism, exophthalmos, maxillary hypoplasia and relative mandibular prognathism. Mutations of fibroblast growth factor receptor 2 (FGFR2) gene are associated with craniosynostotic conditions, such as Crouzon syndrome, Jackson-Weiss syndrome, Pfeiffer syndrome, Apert syndrome and Beare-Stevenson cutis gyrata. We found one child with common morphological features of Crouzon syndrome. Interestingly, she was found to have Cys342Ser mutation in FGFR2 exon lllc which has been previously observed in Jackson-Weiss syndrome. This finding supports the variable expression of FGFR2 in human and allelic heterogeneity in these apparently clinically distinct craniosynostotic conditions.