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).

Síndrome de Apert: alternativas de tratamiento ortodóntico - quirúrgico y tiempos de ejecución. Una revisión de la literatura / Apert Syndrome: Orthodontic - Surgical treatment alternatives and execution times. A review of the literature

Objetivo: realizar una revisión de la literatura acerca de los tratamientos ortodónticos y quirúrgicos del síndrome de Apert durante las diferentes etapas de crecimiento y desarrollo. Métodos: se llevó a cabo una búsqueda en las bases de datos MedLine (PubMed), Science Direct, Scopus y Wiley Online Library con la combinación de los siguientes términos: Syndromic craniosynostosis, Dental treatment, orthodontic treatment, Apert Syndrome, surgical treatment, dental care. Se incluyeron revisiones sistemáticas y de literatura, estudios retrospectivos, longitudinales y de cohorte, series y revisiones de caso publicados entre 1990 y 2020 en español o inglés; se excluyeron artículos relacionados con otros síndromes, así como estudios en animales. Los artículos fueron seleccionados según su pertinencia y disponibilidad de texto completo; hallazgos repetidos fueron eliminados; adicionalmente, se utilizó el sistema bola de nieve en los artículos seleccionados; la calidad de la evidencia fue evaluada mediante el sistema GRADE. Resultados: 34 artículos fueron incluidos (calidad alta: 2, moderada: 1, baja: 19 y muy baja: 12). Entre estos, se identificaron discusiones relacionadas con la etapa de crecimiento a la que se recomienda realizar los procedimientos quirúrgicos requeridos para minimizar sus impactos negativos. La mayoría de los artículos apoyan el manejo terapéutico ejecutado por equipos multidisciplinarios. Conclusiones: un plan de tratamiento combinado de ortodoncia y cirugía ortognática se presentó como la mejor opción para obtener los mejores resultados funcionales y estéticos para la población en cuestión. El momento adecuado durante el crecimiento y desarrollo de los individuos para implementar cada fase de tratamiento fue decidido por cada equipo multidisciplinario.

Objective: Carry out a literature review about the orthodontic and surgical treatments of Apert Syndrome, during the different stages of growth and development. Methods: A search was made in the MedLine (PubMed), Science Direct, Scopus, and Wiley Online Library databases with the combination of the following terms: Syndromic craniosynostosis; Dental treatment; orthodontic treatment; Apert Syndrome; surgical treatment; dental care. Types of the study included: Systematic and literature reviews, retrospective, longitudinal, and cohort studies, series, and case reviews that were published between 1990-2020 in Spanish or English; articles related to other syndromes and animal, or laboratory studies were excluded. The articles were selected according to relevance and availability of full text; repeated findings were eliminated; additionally, the snowball system was used in the selected articles; the quality of the evidence was evaluated using the GRADE system. Results: 34 articles were included (High Quality: 2; Moderate: 1; Low: 19; Very Low: 12). Controversies were found related to the stage of growth to which it is recommended to perform the required surgical procedures to minimize the negative impacts. Most of the articles support therapeutic management by multidisciplinary teams. Conclusions: A combined orthodontic and orthognathic surgery treatment plan was presented as the indicated option to obtain the best possible functional and aesthetic results for the population in question. The appropriate time during the growth and development of individuals to implement each treatment phase was decided by each multidisciplinary team.

Síndrome de Apert: Acrocefalosindactilia, Caso Clínico / Apert Syndrome: Acrocephalosyndactyly, Clinical Case

Introducción:El síndrome de Apert tiene una incidencia variable. Se ha estimado una prevalencia de 1:160milnacimientos. Es de herencia autosómica dominante y se han encontrado algunos factores relacionados, como edad paterna avanzada. Caso:Niña, recién nacida a término, con dificultad respiratoria, hipotonía, sindactiliay retardo del neurodesarrollo. Con Tomografía de Senos paranasales se reportó una malformación del canal semicircular lateral y del vestíbulo bilateral, se confirmó la presencia de una estenosis nasal derecha con desviación septal hacia la derecha y la presencia de estenosis bilateral de coanas. Con una TAC de cráneo se reportó Plagiocefalia unilateral izquierdaylapresencia de craneosinostosis. Evolución: En hospitalización se logró el retiro del oxígeno suplementario, recibió terapia miofuncional con lo que toleró adecuadamente la alimentación oral y se programó la corrección de estenosis de coanas en forma ambulatoria la cual se realizó a los 14 meses. A los18 meses se realizó la cirugía de corrección de craneosinostosis con un avance fronto-orbitario, durante el período post-operatorio la paciente desarrolló una neumonía que fue tratada con antibióticos. Al resolverse el cuadro, fue dada de alta. Conclusión:el Síndrome de Apert, un desorden congénito caracterizado por craneosinostosis coronal, sindactilia simétrica en las cuatro extremidades y malformaciones craneofaciales. El diagnóstico es clínico.El tratamiento es sintomático, relacionado con las diferentes malformaciones asociadas y se debe realizar un manejo interdisciplinario

Introduction: Apert syndrome has a variable incidence. A prevalence of 1: 160 thousand births has been estimated. It is autosomal dominant and some related factors have been found, such as advanced paternal age. Case: Girl, newborn at term, with respiratory distress, hypotonia, syndactyly and neurodevelopmental delay. With Paranasal Sinus Tomography, a malformation of the lateral semicircular canal and the bilateral vestibule was reported, the presence of a right nasal stenosis with septal deviation to the right and the presence of bilateral choanal stenosis was confirmed. With a CT of the skull, left unilateral plagiocephaly and the presence of craniosynostosis were reported. Evolution: In hospitalization, the withdrawal of supplemental oxygen was achieved, he received myofunctional therapy with which he tolerated oral feeding adequately and the correction of choanal stenosis was scheduled on an outpatient basis, which was performed at 14 months. At 18 months, craniosynostosis correction surgery was performed with a fronto-orbital advance, during the postoperative period the patient developed pneumonia that was treated with antibiotics. When the picture was resolved, she was discharged. Conclusion: Apert Syndrome, a congenital disorder characterized by coronal craniosynostosis, symmetric syndactyly in all four limbs, and craniofacial malformations. The diagnosis is clinical. Treatment is symptomatic, related to the different associated malformations and interdisciplinary management must be carried out

Síndrome de Apert. Reporte de caso / Apert syndrome. Case report

RESUMEN Fundamento: El síndrome de Apert consiste en una enfermedad genética con anomalía craneofacial denominada acrocefalosindactilia; produce malformaciones en el cráneo como craneosinostosis, además de alteraciones en cara, manos y pies, puede ser hereditaria, secundaria a mutaciones esporádicas del gen FGFR2 y otros genes. Debido a los programas de pesquisaje genético el diagnóstico prenatal de este síndrome posibilita el asesoramiento genético y la asistencia médica multidisciplinaria. Objetivo: Ilustrar la importancia del diagnóstico prenatal del síndrome de Apert como elemento esencial para la atención multidisciplinaria posnatal del futuro niño. Reporte de caso: Se presenta un neonato de sexo masculino, nacido a las 39 semanas de gestación por parto eutócico, con signos de craneosinostosis y sindactilia en las manos y los pies por lo que se le realizó el diagnóstico posnatal de síndrome de Apert. Conclusiones: Los pacientes con el síndrome de Apert deben ser diagnosticados oportunamente durante la pesquisa prenatal, considerando el conjunto de sus signos y alteraciones y no como anomalías aisladas, como puede ocurrir de realizarse el diagnóstico en el período posnatal. De efectuarse el diagnóstico prenatal se lograría el tratamiento de forma multidisciplinaria y se podría garantizar al paciente una calidad de vida superior.

ABSTRACT Background: Apert syndrome consists of a genetic disease with craniofacial anomaly called acrocephalosyndactyly; it produces malformations in the skull such as craniosynostoses, in addition to alterations in the face, hands and feet, it can be inherited, secondary to sporadic mutations of the FGFR2 gene and some other genes. Due to genetic screening programs, the prenatal diagnosis of this syndrome enables genetic counseling and multidisciplinary medical assistance. Objective: To illustrate the importance of prenatal diagnosis of Apert syndrome as an essential element for the postnatal multidisciplinary care of the future child. Case report: A male neonate, born at 39 weeks of gestation by eutocic delivery, with signs of craniosynostoses and syndactyly on the hands and feet, so he was made the postnatal diagnosis of Apert syndrome. Conclusions: Patients with Apert syndrome should be diagnosed appropriately in time during prenatal screening, considering all their signs and alterations and not as isolated abnormalities, as may occur if the diagnosis is made in the postnatal period. If the prenatal diagnosis was made, the treatment would be achieved in a multidisciplinary way and a better quality of life could be guaranteed to the patient.

Clinical and genetic findings of two cases with Apert syndrome / Hallazgos clínicos y genéticos de dos casos con síndrome de Apert

Abstract Background: Craniosynostosis is described as the premature fusion of cranial sutures that belongs to a group of alterations which produce an abnormal phenotype. Case report: Two unrelated female patients with clinical findings of Apert syndrome-characterized by acrocephaly, prominent frontal region, flat occiput, ocular proptosis, hypertelorism, down-slanted palpebral fissures, midfacial hypoplasia, high-arched or cleft palate, short neck, cardiac anomalies and symmetrical syndactyly of the hands and feet-are present. In both patients, a heterozygous missense mutation (c.755C>G, p.Ser252Trp) in the FGFR2 gene was identified. Conclusions: Two cases of Apert syndrome are described. It is important to recognize this uncommon entity through clinical findings, highlight interdisciplinary medical evaluation, and provide timely genetic counseling for the family.

Resumen Introducción: Las craneosinostosis se describen como la fusión prematura de las suturas craneales y resultan un grupo de alteraciones que producen un fenotipo anormal. Caso clínico: En este informe de casos se presentan dos pacientes de sexo femenino no emparentadas con hallazgos clínicos del síndrome de Apert, caracterizado por acrocefalia, región frontal prominente, occipucio plano, proptosis ocular, hipertelorismo, fisuras palpebrales hacia abajo, hipoplasia mediofacial, paladar alto o hendido, cuello corto, cardiopatía congénita y sindactilia simétrica en manos y pies. En ambas pacientes se identificó una mutación cambio de sentido en heterocigosis (c.755C>G, p.Ser252Trp) en el gen FGFR2. Conclusiones: Se presentan dos casos de síndrome de Apert. Es importante reconocer a través de los hallazgos clínicos esta entidad infrecuente, resaltar la evaluación médica interdisciplinaria y proporcionar un oportuno asesoramiento genético a la familia.

Apert Syndrome Presenting with Omphalocele

Apert syndrome is a congenital acrocephalosyndactylysyndrome. It is mainly presented by craniosynostosis,syndactyly of the hands and feet and dysmorphic facialfeatures. The condition has an autosomal dominantinheritance assigned to mutations in the FibroblastGrowth Factor Receptors (FGFR-2) gene. The reportedcase is a 9 months old boy with clinical suspicion ofApert syndrome as he had turricephaly, stubby handswith short fingers, omphalocele measuring 10 × 10 cm,bilateral undescended testes, Congenital TalipesEquinovarus (CTEV) and polydactyl and syndactyl ofgreat and second toes. He was developmentallynormal. The omphalocele was surgically repaired.Early diagnosis and intervention helps rehabilitation ofpatients with Apert syndrome and help them to lead abetter life.

Severe Hyperhidrosis in Apert Syndrome: A Case Report / 대한피부과학회지

Apert syndrome is a rare genetic disorder characterized by malformations of the skull, face, hands, and feet. We report a case of severe hyperhidrosis in a 13-month-old female infant with Apert syndrome who was born with craniosynostosis, midface hypoplasia, and syndactyly of both hands. She had a history of excessive sweating since birth and this was confirmed using the iodine-starch test. Hyperhidrosis was first reported as a key cutaneous manifestation of Apert syndrome in 1993. However, the main focus in the field of dermatology is on antibiotic-refractory acne, which serves as another cutaneous hallmark of the disease. This is the first report in the Korean literature that describes hyperhidrosis in Apert syndrome. We highlight the presentation of hyperhidrosis as a key cutaneous manifestation in Apert syndrome.

Aberrant growth of the anterior cranial base relevant to severe midface hypoplasia of Apert syndrome / 대한악안면성형재건외과학회지

BACKGROUND: A 9-year-old male showed severe defects in midface structures, which resulted in maxillary hypoplasia, ocular hypertelorism, relative mandibular prognathism, and syndactyly. He had been diagnosed as having Apert syndrome and received a surgery of frontal calvaria distraction osteotomy to treat the steep forehead at 6 months old, and a surgery of digital separation to treat severe syndactyly of both hands at 6 years old. Nevertheless, he still showed a turribrachycephalic cranial profile with proptosis, a horizontal groove above supraorbital ridge, and a short nose with bulbous tip. METHODS: Fundamental aberrant growth may be associated with the cranial base structure in radiological observation. RESULTS: The Apert syndrome patient had a shorter and thinner nasal septum in panthomogram, PA view, and Waters’ view; shorter zygomatico-maxillary width (83.5 mm) in Waters’ view; shorter length between the sella and nasion (63.7 mm) on cephalogram; and bigger zygomatic axis angle of the cranial base (118.2°) in basal cranial view than a normal 9-year-old male (94.8 mm, 72.5 mm, 98.1°, respectively). On the other hand, the Apert syndrome patient showed interdigitating calcification of coronal suture similar to that of a normal 30-year-old male in a skull PA view. CONCLUSION: Taken together, the Apert syndrome patient, 9 years old, showed retarded growth of the anterior cranial base affecting severe midface hypoplasia, which resulted in a hypoplastic nasal septum axis, retruded zygomatic axes, and retarded growth of the maxilla and palate even after frontal calvaria distraction osteotomy 8 years ago. Therefore, it was suggested that the severe midface hypoplasia and dysostotic facial profile of the present Apert syndrome case are closely relevant to the aberrant growth of the anterior cranial base supporting the whole oro-facial and forebrain development.

Manifestações bucais da síndrome de apert: relato de caso clínico / Expressions of oral apert syndrome: clinical case report

A Síndrome de Apert, também chamada de acrocefalossindactilia tipo 1, é caracterizada pelo encerramento prematuro das suturas cranianas (craniossinostose), sindactilia simétrica das mãos e dos pés e anomalias faciais. Outras anormalidades observadas são atraso mental, anquilose articular e anomalias da coluna vertebral. Destacam-se, ainda, a hipoplasia da face média com Classe III, lábios hipotônicos, úvula bífida, erupção ectópica, má oclusão e pseudofenda palatina. A cavidade bucal desses pacientes apresenta normalmente uma redução no tamanho da maxila, em particular na direção anteroposterior. Essa redução pode resultar em apinhamento dentário e uma mordida aberta anterior. A mandíbula está dentro do tamanho e da forma normal, e simula um pseudoprognatismo. Anomalias dentárias, tais como dentes inclusos, erupção retardada, agenesia dentária, hipoplasia do esmalte, dentes ectópicos ou supranumerários são comumente observadas. Diante da necessidade de um tratamento multidisciplinar e da relevância do cirurgião-dentista no acompanhamento desses pacientes, o objetivo deste relato é descrever as manifestações bucais da síndrome, enfatizando as características mais frequentes no período de transição da dentição decídua para a dentição permanente.

Apert syndrome, also called acrocephalosyndactyly type 1, is characterized by the premature closure of the cranial sutures (craniosynostosis), symmetric syndactyly of the hands and feet and facial anomalies of the midline. People with Aper syndrome have craniofacial abnormalities as exophthalmos, ocular hy-pertelorism, broad and short nose with a bulbous tip. The patients have hypoplasia midface with Class III, hypotonic lips, cleft uvula, ectopic eruption, malocclusion and pseudo cleft palate. The oral cavity usually these patients showed a reduction in the size of the jaw, in particular in the rearward direction. This reduc¬tion may result in tooth crowding and in an anterior open bite. The jaw size is within the normal way and simulates a pseudoprognathism. Dental anomalies, such as impacted teeth, delayed eruption, tooth agenesis, enamel hypoplasia, ectopic or supernumerary teeth are commonly observed. Given the need for a multidis¬ciplinary approach and the relevance of the dentist in monitoring these patients, the objective of this report is to describe the oral manifestations of the syndrome emphasizing the most common features in the transition period of the deciduous dentition to the permanent dentition.

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.

Genotype-phenotype analysis in Apert syndrome / 临床儿科杂志

Objectives To analyze the clinical features and gene types of Apert syndrome (AS). Methods The clinical data of one boy with AS were retrospectively revisited and FGFR 2 of the boy and his father were analyzed with PCR amplification and gene sequencing. The relevant literatures were reviewed. Results The boy was one year and one month old, with brachycephaly, exophthalmos, hypertelorism, low set ears, micrognathia, high-vaulted arch, without cleft palate, and with syndactyly of both ifngersⅠ-Ⅴ and toesⅠ-Ⅴ. A heterozygous mutation (c. 758 C?>?G,p.P 253 R) in exon 7 of FGFR 2 was detected in the boy, supporting the diagnosis of AS. The relevant gene mutation was not detected in his father. Among the 24 cases of AS retrieved from literature, 22 cases were with obvious craniofacial malformations, one with mild craniofacial malformations and one without craniofacial malformations. All cases were with syndactyly of both ifngers and toes. Thirteen cases of FGFR 2 were with S 252 W mutation, 3 cases with P 253 R , 3 cases with Alu insertion, one with 1 . 93-kb deletion, removing exon IIIc and substantial portions of the lfanking introns, one case with a heterozygous 1372 bp deletion between FGFR 2 exons IIIb and IIIc, 2 cases with (c.756_758delGCCinsCTT) in the IgIIe-IgIIIa linker region and one case with sequence variant T78.501A in intron 8. Conclusions Apert syndrome present with craniofacial malformations and syndactyly of hands and feet, S 252 W and P 253 R are main mutations of AS.

Molecular analysis of exons 8, 9 and 10 of the fibroblast growth factor receptor 2 (FGFR2) gene in two families with index cases of Apert Syndrome / Análisis molecular de los exones 8, 9 y 10 del gen del factor de crecimiento de fibroblastos (FGFR2) en dos familias con casos índice de síndrome de Apert

Introduction: Apert syndrome (AS) is a craniosynostosis condition caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2) gene. Clinical features include cutaneous and osseous symmetric syndactily in hands and feet, with variable presentations in bones, brain, skin and other internal organs. Methods: Members of two families with an index case of Apert Syndrome were assessed to describe relevant clinical features and molecular analysis (sequencing and amplification) of exons 8, 9 and 10 of FGFR2 gen. Results: Family 1 consists of the mother, the index case and half -brother who has a cleft lip and palate. In this family we found a single FGFR2 mutation, S252W, in the sequence of exon 8. Although mutations were not found in the study of the patient affected with cleft lip and palate, it is known that these diseases share signaling pathways, allowing suspected alterations in shared genes. In the patient of family 2, we found a sequence variant T78.501A located near the splicing site, which could interfere in this process, and consequently with the protein function.

Introducción: El síndrome Apert (SA) es un síndrome que cursa con craneosinostosis el cual es ocasionado por mutaciones en el gen del Receptor 2 del Factor de Crecimiento de Fibroblastos (FGFR2). Se caracteriza clínicamente por presentar sindactilias cutáneas y óseas en manos y pies de forma simétrica, cursa además con manifestaciones variables esqueléticas, cerebrales, en piel y otros órganos internos. Métodos: Miembros de dos familias con caso índice de Síndrome Apert fueron evaluados con el objetivo de describir las características clínicas relevantes y el análisis molecular (secuenciación y amplificación) de los exones 8, 9 y 10 del gen FGFR2. Resultados: La familia 1 está constituida por la madre, el caso índice y un medio hermano que presenta labio y paladar hendido. En esta familia solo se encontró la mutación S252W en la secuencia del exón 8 del gen FGFR2 del caso índice. A pesar no encontrarse mutaciones dentro del estudio realizado al paciente afectado con labio y paladar hendido, se conoce que estas patologías comparten vías de señalización, lo que permite sospechar alteraciones en genes compartidos. En la familia 2, el resultado molecular del caso índice reportó la variante T78.501A en la secuencia del intrón 8, la cual se sitúa cercana al sitio de splicing, pudiendo alterar este proceso con una consecuente alteración de la función de la proteína.

Absceso cerebral por Haemophilus influenzae serotipo e en un paciente pediátrico con Síndrome de Apert / Brain abscess caused by Haemophilus influenzae type e in a pediatric patient suffering from Apert syndrome

Se presenta el caso de un absceso cerebral causado por Haemophilus infl uenzae tipo e, en un paciente de 12 años con síndrome de Apert. El síndrome de Apert se caracteriza por el cierre prematuro de las suturas craneales. En 2010, el paciente presentó traumatismo craneano en región frontal, fractura y fístula de líquido cefalorraquídeo. En febrero de 2013 consultó por fi ebre, vómitos y convulsión tónica clónica generalizada, con deterioro progresivo del sensorio. La tomografía axial computarizada mostró una lesión frontal derecha, edema perilesional, leve dilatación ventricular y pansinusitis. Se diagnosticó absceso cerebral con pioventriculitis y se realizó drenaje. Se obtuvo desarrollo de un cocobacilo gram negativo, que fue identifi cado como H. infl uenzae serotipo e. Se realizó tratamiento empírico con meropenem (120 mg/kg/día) y vancomicina (60 mg/kg/día). Luego del resultado del cultivo, se rotó a ceftriaxona (100 mg/kg/día) y metronidazol (500 mg/8 h). El paciente cumplió 8 semanas de tratamiento y se observó evolución favorable

We report a case of a brain abscess caused by Haemophilus infl uenzae type e in a 12 year-old patient suffering from Apert syndrome. Apert syndrome is characterized by the premature closure of cranial sutures. In 2010 the patient suffered head trauma in the frontal area with cranial fracture and a cerebrospinal fl uid fi stula. In February 2013 he was admitted to hospital with fever, vomiting and generalized tonic-clonic seizure with deteriorating mental status/progressive sensory impairment. The computerized axial tomographic scan showed a right frontal lesion, perilesional edema, mild ventricular dilatation and pansinusitis. A brain abscess was diagnosed and drained. The clinical sample was then cultured. A gram negative coccobacillus was isolated and identifi ed as Haemophilus infl uenzae serotype e. Empirical treatment was started with meropenem (120 mg/kg/day) and vancomycin (60 mg/kg/day), which was later switched to ceftriaxone (100 mg/kg/day) and metronidazole (500 mg/8 h) after culture results arrived. The patient was discharged in good clinical condition

Apert Syndrome with Epibulbar Dermoid Cyst in the Eye - Coincidence or an Additional Clinical Finding: A Case Report.

Craniosynostosis are heterogeneous group of syndromes characterized by premature fusion of suture that may occur alone or together with other anomalies. Apert syndrome, an autosomal dominant disorder, first described by Baumgartner in 1842, accounts for 4.5% of all children with craniosynostosis. We report a case of a 5-year-old female child who presented with complaints of inability to speak, facial dysmorphism and symmetric syndactyly of both hands and feet.

Criança com Síndrome de Apert: diagnóstico clínico-radiográfico, manifestações orofaciais e qualidade de vida / Child with Apert Syndrome: clinical and radiographic diagnosis, orofacial manifestations and quality of life

Este relato de caso mostra o diagnóstico de uma patologia congênita rara: Síndrome de Apert. Paciente do sexo feminino, 12 anos, melanoderma, apresentou aos exames clínico e radiográfico: acrobraquicefalia, sindactilia em mãos e pés, acne facial, nariz disforme, retrusão maxilar, pseudoprognatismo, hipertelorismo, proptose ocular, depressão das fissuras palpebrais laterais, lábios em forma trapezoidal, lábio superior protruso, pseudomacroglossia, mordida aberta anterior, mordida cruzadaposterior, palato em arco bizantino, múltiplas anomalias dentárias de posição (apinhamento dental maxilar e giroversões) e forma (ponte de esmalte pronunciada em incisivos laterais e taurodontismo em segundos molares), e alongamento do processo estilóide bilateral. A qualidade de saúde bucal da paciente era insatisfatória, com excesso de biofilme oral, cárie, doença periodontal e comprometimento endodôntico. O teste AUQEI apontou que a criança possuía baixa a moderada qualidade de vida. Este caso destaca a importância do diagnóstico precoce para intervenções clínico-cirúrgicas mais eficazes e o valor da equipe multidisciplinar no acompanhamento contínuo e na melhora da qualidade de vida de pacientes infantis portadores de anomalias congênitas severas.

This case report shows the diagnosis of a rare congenital pathology: Apert syndrome. A 12-year-old female patient, melanoderm, presented in clinical and radiographic examinations: acrobraquicephalia, syndactilia in hands and feet, facial acne, unshapely nose, maxillary retrusion, pseudoprognatism, hypertelorism, ocular proptosis, depression of the lateral palpebral fissures, trapezoid shaped appearance to the lips, upper lip protrusion, pseudomacroglossia, anterior open bite, posterior crossbite,Byzantine-arch palate, multiple dental anomalies of position (maxillary dental crowding and dental rotation) and shape (pronounced enamel bridge in lateral incisors and taurodontism in second molar teeth) and bilateral elongated styloid process. The quality of oral health was unsatisfactory in the patient, with excessive oral biofilm, carie lesion, periodontal disease and endodontic involvement. The AUQEI test showed that the child had a low to moderate quality of life. This case highlight the importance of an early diagnosis for more effective clinical and surgical interventions and the value of a multidisciplinary team in the continuousmonitoring and improvement of quality of life in pediatric patients with severe congenital abnormalities.

Shape analysis of the sphenoid bone in Apert syndrome using 3D CT scans

Apert syndrome is a rare acrocephalosyndactyly syndrome characterised by craniosynostosis, midface hypoplasia and syndactyly of the hands and feet. The majority of cases arise as the result of one of two mutations of the fibroblast growth factor receptor 2 gene (FGFR2). Due to the involvement of both the cranial and the facial sutures, the keystone of the craniofacial skeleton, the sphenoid bone, is affected by the disease process and as a result is dysmorphic. This may significantly affect craniofacial morphology but it is recognised that there are marked variations in this between different affected individuals. This is a retrospective study examining the morphology of the sphenoid bone using three dimensional reconstructions of computed tomography (CT) scan data. Shape analysis was performed using generalised Procrustes analysis and principal component analysis (GPA/PCA). Comparisons were made between the individuals with Apert syndrome and a group of normal individuals, and between the two genotypic groups. The sphenoid bone in those with Apert syndrome showed marked differences in morphology compared to the normal individuals with a restriction in height and increased angulation of the lesser wings; however, there were no consistent differences between the two genotypic groups. It is possible that fronto-orbital advancement (FOA) surgery indirectly releases the sphenoid bone and allows compensatory growth in this direction.

Análisis genotípico de 11 pacientes colombianos con Síndrome de Apert / Genotypic analysis of 11 Colombian Apert syndrome patients

Antecedentes. El síndrome de Apert (SA) es una de las craneosinostosis sindrómicas más severas que afecta el neuro y viscerocraneo y además presenta alteraciones multisistémicas con repercusiones en aspectos físicos (aspecto general y talla baja), sensoriales (hipoacusia y trastornos visuales), cognoscitivos (retardo mental o trastornos del aprendizaje) y de inclusión laboral (sindactilia severa en manos y pies). Su etiología es la mutación del receptor 2 del factor de crecimiento fibroblástico (FGFR2) y se hereda de forma autosómica dominante. Materiales y métodos. Se analizaron clínica y molecularmente 11 pacientes con sospecha de SA. Se realizó estudio mutacional mediante RFLP para el gen FGFR2. Resultados. Se confirmaron molecularmente los 11 pacientes con SA, cuyas edades oscilaron desde los 0 a 32 años. Todos los pacientes presentaron el fenotipo clásico. Se encontró un 63.6% de pacientes con la mutación S252W y 36.4% con P253R. Discusión. De los pacientes analizados, llamo la atención la presencia de talla baja y RM/RGD en algunos de ellos. Desde el punto de vista genotípico, las frecuencias mutacionales para S252W y P253R no mostraron diferencias con relación a lo reportado mundialmente. Aunque no se disponen de datos de la incidencia de esta patología a nivel local, este estudio podría ser el primer acercamiento para fines epidemiológicos en Colombia.

Background. Apert Syndrome (AS) is one of the most severe syndromic craniosynostosis affecting neuro and viscerocranium and presenting with multisystemic anomalies altering physical aspects (general looks and short stature), sensorineural aspects (deafness and visual problems), cognitive development (mental retardation or trouble learning) and work inclusion (severe syndactyly in hands and feet). Its aetiology relies on mutation of the Fibroblast Growth Factor Receptor type 2 (FGFR2) gene, inherited by an autosomal dominant path. Materials and methods. 11 patients with suspicion of AS were clinically evaluated and molecularly tested for mutations in FGFR2 by RFLP. Results. Patients with AS from 0 to 32 years old were analized for mutations in FGFR2 gene. All of them had the classical phenotype of the disease. 63.6% of the patients had the S252W mutation while 36.4% had the P253R mutation. Discussion. Of all patients enrolled in this study it is notwworthy that some of them had short stature, while others had mental retardation or global development delay. Mutational frequencies for S252W and P253R did not show difference according to what has been reported worldwide. Although there is no data about the incidence of this disease locally, this study could be a first approach to its epidemiology in Colombia.

Apert syndrome (Acrocephalosyndactyly): a case report.

Apert syndrome is named for the French physician. Eugene Apert in 1906 described the syndrome acrocephalosyndactylia. It is a rare autosomal dominant disorder characterized by craniosynostosis, craniofacial anomalies, and severe symmetrical syndactyly of the hands and feet (i.e. cutaneous and bony fusion refers to webbing of fingers and toes). Apert syndrome is characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. In addition, a varied number of fingers and toes are fused together (syndactyly). Most cases of Apert syndrome are sporadic, may result from new mutations in the gene. The purpose of this paper is to report a case of Apert syndrome in a female fetus of 30 weeks with asymmetrical skull confirmed by prenatal ultrasonography. Pregnancy was terminated and fetus was submitted for detailed autopsy in anatomy dissection hall. The findings and review of literature were presented in this article.

Apert and Pfeiffer Syndromes: A Report of Two Cases / 대한소아신경학회지

Craniosysostosis syndrome is caused by premature fusion of bones of skull and face during fetal development. It is related to Fibroblast growth factor receptor gene and most common craniosynostosis syndromes are Apert, Pfeiffer and Crouzon. Apert syndrome is one of the severe type of craniosynostosis syndromes which shows mutations in the Fibroblast growth factor receptor 2 (FGFR2) gene. Pfeiffer syndrome is also related with FGFR 1 or 2 gene mutation. We experienced two patients with craniosynostosis syndromes, Apert syndrome and Pfeiffer syndrome. The first baby was a in-born female baby presented with syndactly of the hands and feet and facial dysmorphism including shallow orbit with deep crease above eye brow. Apert syndrome was confirmed by the presence of a mutation in FGFR2. The second patient visited our developmental delay clinic due to developmental delay at seven month old age. He showed facial dysmorphism including cloverleaf-shaped skull, micrognathia, low set ears, low nasal bridge and high-arched palate, but there were no syndactly or limb anomalies. He was suspected of Pfeiffer syndrome, however his FGFR2 gene study was normal. These patients need multidisciplinary team management and regular follow up for visual, auditory, and cognitive development functions Pediatricians have important role on recognizing the patients with facial dysmorphism, planning to evaluate accompanying anomalies and making appropriate decisions about the timing of surgical management to minimize growth and cognitive impairments.

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.