Intervención fisioterapéutica en una niña con síndrome de Pfeiffer. Reporte de caso / Physiotherapeutic intervention in a girl with Pfeiffer syndrome. Case Report

Introducción: El síndrome de Pfeiffer es un trastorno congénito autosómico dominante que afecta a 1 entre 100.000 nacidos vivos. El objetivo de este reporte de caso es describir la intervención fisioterapéutica en una niña con síndrome de Pfeiffer tipo 2, la cual se basó en el concepto del entrenamiento centrado en tareas específicas, el análisis de cambios en el control postural y la educación y empoderamiento a los padres. Presentación del caso: Niña que inició tratamiento de fisioterapia con una frecuencia de dos sesiones semanales, desde los 6 meses hasta los dos años, cuando logró deambular por ocho pasos consecutivos de manera independiente. A los 12 meses logró la sedestación independiente, a los 18 meses la niña se ubicó en el percentil 50 según la escala Alberta y a los 24 meses pudo dar ocho pasos seguidos sin asistencia y realizar alcances y manipulación bimanual con objetos modificados. Conclusión: El entrenamiento basado en tareas y el enfoque centrado en el paciente y su familia permitieron que una niña con síndrome de Pfeiffer tipo 2, con deficiencias en las funciones y estructuras corporales musculoesqueléticas y relacionadas con el movimiento, lograra deambular por ocho pasos de manera independiente a los dos años y se interesara por manipular y explorar su entorno inmediato. La intervención en fisioterapia puede beneficiar a los niños con síndrome de Pfeiffer o síndromes similares, que evolucionan con deficiencias en su neurodesarrollo, mejorando su calidad de vida.

Introduction: Pfeiffer syndrome is an autosomal dominant congenital disorder that affects 1 in 100,000 live births. Variable malformations, developmental delay, and neurological complications occur. The objective of this case report is to describe the physical therapy intervention on a girl with type 2 Pfeiffer syndrome, which was based on the concept of training focused on specific tasks, the analysis of changes in postural control, and education and empowerment to parents. Case presentation: A girl who began physiotherapy treatment with a frequency of two weekly sessions, from 6 months to two years, when she managed to walk independently for eight consecutive steps. At 12 months, she achieved independent sitting, at 18 months the girl was in the 50th percentile according to the Alberta scale, and at 24 months she was able to take eight continuous steps without assistance and perform bimanual reaching and manipulation with modified objects. Conclusion: Task-based training and a patient and family-centered approach allowed a girl with type 2 Pfeiffer syndrome, with deficiencies in musculoskeletal and movement-related bodily functions and structures, to ambulate independently for eight steps at two years and to be interested in manipulating and exploring her immediate environment. Physiotherapy intervention can benefit children with Pfeiffer syndrome or similar syndromes, who evolve with deficiencies in their development, improving their quality of life.

Síndrome de Saethre-Chotzen: a propósito de un caso / Saethre-Chotzen syndrome: a case report

El síndrome de Saethre-Chotzen es un síndrome malformativo craneofacial caracterizado por una sinostosis de las suturas coronales y alteraciones de extremidades. Tiene una prevalencia de 1 de cada 25 000-50 000 recién nacidos vivos. Se presenta el caso de un neonato sin antecedentes de interés con alteraciones craneofaciales al nacer. Ante los rasgos fenotípicos del paciente, se realizó una tomografía axial computada craneal, que mostró la fusión parcial de la sutura coronal y evidenció la presencia de huesos wormianos en localización metópica y lambdoidea derecha. Con la sospecha clínica de síndrome malformativo craneofacial, se solicitó análisis del exoma dirigido, que confirmó que el paciente era portador heterocigoto de la variante patogénica c.415C>A, que inducía un cambio de prolina a treonina en la posición 139 del gen TWIST1, responsable del síndrome. La presencia de huesos wormianos, hallazgo no descrito hasta ahora en la literatura, amplía la variabilidad fenotípica conocida de este síndrome.

The Saethre-Chotzen syndrome is a craniofacial malformation syndrome characterized by synostosis of coronal sutures and limb anomalies. The estimated prevalence of this syndrome is 1 in 25 000-50 000 live births. We present a case report of a neonate, without relevant family history, who presented craniofacial alterations at birth. Given the phenotypic features, a cranial computed tomography scan was performed, showing partial fusion of the coronal suture, evidencing the presence of wormian bones in the metopic and right lambdoid location. With the clinical suspicion of craniofacial malformation syndrome, an analysis of the directed exome was requested confirming that the patient is a heterozygous carrier of the pathogenic variant c.415C>A, which induces a change of proline to threonine at position 139 of the TWIST1 gene, responsible for Saethre-Chotzen syndrome.The presence of wormian bones, a finding not described so far in the literature, extends the well-known phenotypic variability of this syndrome.

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.

Syndromic craniosynostosis: neuropsycholinguistic abilities and imaging analysis of the central nervous system / Craniossinostoses sindrômicas: habilidades neuropsicolinguísticas e análise por imagem do sistema nervoso central

ABSTRACT Objective: To characterize patients with syndromic craniosynostosis with respect to their neuropsycholinguistic abilities and to present these findings together with the brain abnormalities. Methods: Eighteen patients with a diagnosis of syndromic craniosynostosis were studied. Eight patients had Apert syndrome and 10 had Crouzon syndrome. They were submitted to phonological evaluation, neuropsychological evaluation and magnetic resonance imaging of the brain. The phonological evaluation was done by behavioral observation of the language, the Peabody test, Token test and a school achievement test. The neuropsychological evaluation included the WISC III and WAIS tests. Results: Abnormalities in language abilities were observed and the school achievement test showed abnormalities in 66.67% of the patients. A normal intelligence quotient was observed in 39.3% of the patients, and congenital abnormalities of the central nervous system were observed in 46.4% of the patients. Conclusion: Abnormalities of language abilities were observed in the majority of patients with syndromic craniosynostosis, and low cognitive performance was also observed.

RESUMO Objetivo: Caracterizar as habilidades neuropsicolinguísticas de indivíduos com craniossinostoses sindrômicas e apresentar esses achados com as anomalias do sistema nervoso central. Métodos: Participaram do estudo 18 sujeitos com diagnóstico clínico de craniossinostose sindrômica, 44,4% com a síndrome de Apert e 55,6% síndrome de Crouzon. Todos os sujeitos foram submetidos a avaliação fonoaudiológica, psicológica e exames de ressonância magnética do encéfalo. A avaliação fonoaudiológica foi contemplada pela Observação Comportamental da Linguagem, Teste Peabody (TVIP), Teste Token e Teste de Desempenho Escolar (TDE); enquanto a psicológica utilizou a WISC-III e a WAIS. Resultados: Observou-se alteração nas habilidades de linguagem em todos os protocolos utilizados, sendo o TDE o que apresentou maior porcentagem de alteração (66,67%).A avaliação cognitiva evidenciou quociente de inteligência dentro da média em 39,3% dos sujeitos, enquanto que 46,4% apresentaram malformações congênitas do sistema nervoso central. Conclusão: Constatou-se alterações nas habilidades de linguagem na maioria dos sujeitos com craniossinostoses sindrômicas, bem como o baixo desempenho cognitivo.

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.

Prenatal diagnosis of Apert syndrome by sonography / 中华医学超声杂志（电子版）

Objective To discuss the prenatal ultrasound manifestations of Apert syndrome. Methods The prenatal ultrasound features of 4 fetuses identified as Apert syndrome after detailed antenatal ultrasound examinations between January, 2010 to Februry, 2014 in our hospital were analyzed. The ultrasound images and postnatal outcome or autopsy were compared to analysis the sonographic features of Apert syndrome in prenatal. Results The prenatal ultrasound characteristics and pregnant outcome of the 4 fetuses were showed as followings:(1) Skull deformity:4 fetuses were all appeared as acrocephaly, coronal suture premature close and frontal protrusion, while 3 cases (case 1-3) had“clover leaf skull deformity”features. (2) Midfacial malformation deformity:3 cases (case 1-3) were all with hypertelorism and mid-sagittal facial proifle abnormal and only 1 case (case 2) had nose hypoplasia. (3) Limbs abnormal:4 cases were all appeared as bilateral symmetry syndactyly of hands and 1 case (case 2) was diagnosed as bilateral symmetry syndactyly of feet. (4) Associated abnormality:persistent right umbilical vein in 1 case (case1), thoracic spine stenosis in 1 case (case 2), hyperechogenic renal parenchyma in 1 case (case 3) and left-diaphragmatic hernia in 1 case (case 4). (5) The pregnant outcome:3 cases underwent pregnancy termination and 1 case was labored at term. The 3 cases (case1-3) were diagnosed as bilateral symmetry syndactyly of feet after induced labor. The cleft palate and bilateral symmetry syndactyly of feet were misdiagnosed in the full-time infant (case 3), who was died two days after birth. Conclusions The Apert syndrome is a rare syndrome. It generally has typical characteristic of prenatal ultrasound, such as coronal suture premature close, acrocephaly, mid-sagittal facial profile abnormal and bilateral symmetry syndactyly of hands and feet. Prenatal diagnosis of Apert syndrome can play an important role in genetic counseling and postnatal treatment.

Apert syndrome: clinical and radiographic features and case report / Síndrome de Apert: características clínicas e radiográficas e relato de caso

PURPOSE: Apert syndrome is a rare type I acrocephalosyndactyly syndrome characterized by craniosynostosis, severe syndactyly of the hands and feet, and dysmorphic facial features. Presents autosomal dominant inheritance assigned to mutations in the fibroblast growth factor receptors gene. The oral cavity of Apert patients includes a reduction in the size of the maxilla, tooth crowding, anterior open-bite of the maxilla, impacted teeth, delayed eruption, ectopic eruption, supernumerary teeth, and thick gingiva. The mandible usually is within normal size and shape, and simulates a pseudoprognathism. CASE DESCRIPTION: A female patient, 13 years old, with diagnosis of Apert syndrome, attended a dental radiology clinic. The clinical signs were occular anomalies, dysmorphic facial features, syndactyly and oral features observed clinically and radiographically. The patient was referred to a specialized center of clinical care for patients with special needs. CONCLUSION: Because of the multiple alterations in patients with Apert syndrome, a multidisciplinary approach, including dentists and neurosurgeons, plastic surgeons, ophthalmologists and geneticists, is essential for a successful planning and treatment.

OBJETIVO: A síndrome de Apert é um tipo raro de acrocefalossindactilia do tipo I caracterizada por cranioestenose, sindactilia severa das mãos e dos pés, e características faciais dismórficas. Apresenta herança autossômica dominante atribuída a mutações no gene referente aos receptores do fator de crescimento de fibroblastos. A cavidade oral de pacientes de Apert apresenta uma redução no tamanho da maxila, apinhamento dentário, mordida aberta anterior da mandíbula superior, dentes retidos, erupção atrasada, erupção ectópica, dentes supranumerários, gengival e espessura. A mandíbula é no tamanho e forma normais, e simula um pseudoprognatismo. Um caso de síndrome de Apert é apresentado. DESCRIÇÃO DO CASO: Paciente do sexo feminino, 13 anos de idade, com diagnóstico de síndrome de Apert, foi atendida em um serviço de radiologia odontológica. A paciente apresentava anomalias oculares, características faciais dismórficas e sindactilia, aos exames clínico e radiográfico. A paciente foi encaminhada a um centro especializado para atenção a pessoas com necessidades especiais. CONCLUSÃO: Uma abordagem multidisciplinar, incluindo cirurgiões-dentistas e neurocirurgiões, cirurgiões plásticos, oftalmologistas e geneticistas, é essencial para um planejamento bem sucedido e tratamento de casos de síndrome de Apert devido às múltiplas alterações nesses pacientes.

A case of Pfeiffer syndrome with c833_834GC>TG (Cys278Leu) mutation in the FGFR2 gene / 소아과

Pfeiffer syndrome is a rare autosomal dominant disorder characterized by coronal craniosynostosis, brachycephaly, mid-facial hypoplasia, and broad and deviated thumbs and great toes. Pfeiffer syndrome occurs in approximately 1:100,000 live births. Clinical manifestations and molecular genetic testing are important to confirm the diagnosis. Mutations of the fibroblast growth factor receptor 1 (FGFR1) gene or FGFR2 gene can cause Pfeiffer syndrome. Here, we describe a case of Pfeiffer syndrome with a novel c833_834GC>TG mutation (encoding Cys278Leu) in the FGFR2 gene associated with a coccygeal anomaly, which is rare in Pfeiffer syndrome.

Estudo da recidiva após a correção do hiperteleorbitismo / Orbital relapse after hypertelorbitism correction

Introdução: Paul Tessier propôs, na década de 60, a correção das deformidades craniofaciaispor abordagem intracraniana. Objetivo: Os objetivos do presente trabalho foram: 1. Comparara distância interorbital interna (DIO) do período pré e pós-operatório de pacientes submetidosà correção de hiperteleorbitismo; 2. Aferir o índice de recidiva da posição orbital após 6 mesesda cirurgia para a correção do hiperteleorbitismo. Método: Onze pacientes foram submetidosà correção do hiperteleorbitismo. A aferição da DIO foi realizada no período pré-operatório pormeio da telerradiografia cefalométrica de frente. A aferição da DIO pós-operatória foi realizadano intra-operatório com paquímetro e no seguimento pós-operatório por meio da telerradiografiacefalométrica, 6 meses após a correção do hiperteleorbitismo. O teste de Wilcoxon foi utilizadopara a comparação entre DIO pré e pós-operatória. O nível de significância adotado no presenteestudo foi de p<0,05. Resultados: Houve diferença estatisticamente significante entre as DIOpré-operatória (média de 32,14 mm) e pós-operatória (média de 18,73 mm) (p<0,001). O índicede recidiva médio da posição orbital foi de 1,64 mm. Conclusão: A correção do hiperteleorbitismoé uma cirurgia intracraniana que possibilita a mobilização das órbitas medialmente,proporcionando resultados estéticos e funcionais satisfatórios. O índice médio de recidiva daórbita (1,64 mm) representou 12% da extensão da redução óssea média (13,41 mm).

Introduction: When Tessier introduced his concepts of both an intra and extracranial approachto treat severe craniofacial malformations, like hypertelorbitism, the modern field of craniofacialsurgery was ushered in. Objective: The aims of this study were the following: 1. Tocompare preoperative and postoperative interorbital distance in patients with hypertelorbitismwho underwent hyperteleorbitism correction. 2. To evaluate the orbital relapse rate, 6 monthsafter hyperteleorbitism correction. Methods: Eleven patients underwent hypertelorbitismcorrection. The interorbital distance was measured at frontal cephalograms preoperatively, andwith a caliper intraoperatively and at 6 months after surgery using the frontal cephalograms.Orbital relapse was measured by subtracting the follow-up measurement from the intraoperativemeasurement. Wilcoxon test was used to compare preoperative interorbital distance and postoperativeinterorbital distance. A value of p <0.05 was considered to be statistically significant.Results: Statistically significant differences between preoperative interobital distance (31.14mm) and postoperative interorbital distance was shown in this study (18.73 mm) (p < 0.001).The average orbital relapse rate was 1.64 mm. Conclusion: Hypertelorbitism correction allowsthe orbital mobilization trough an intracranial approach, and leads to a satisfactory aestheticand functional outcomes. The average orbital relapse rate was 1.64 mm, corresponding to 12%of bone interorbital reduction.

A Case of Pfeiffer Syndrome

Pfeiffer Syndrome is as rare as Apert syndrome in the Western population. This condition is very rare in the Asian population and has not been previously reported in Korea. The authors report with a review of literature the case of a newborn baby with Pfeiffer syndrome, manifested by bicoronal craniosynostosis, broad thumbs, and big toes. The infant also had bilateral syndactyly of the fingers and toes, mild proptosis, choanal hypoplasia and maxillary hypoplasia.