Apresentação clínica de osteogênese XV em um menino brasileiro de 4 anos / Clinical presentation of osteogenesis imperfecta XV in a four-year-old brazilian boy

Introdução: Osteogênese Imperfeita (OI) é uma doença genética rara com fragilidade óssea. A classificação inclui muitos tipos. Além do risco de recorrência, o manejo pode variar com o tipo de OI. Relato do caso: Apresentamos um paciente do sexo masculino nascido com 39 semanas, de pais não consanguíneos e saudáveis. A hidrocefalia foi diagnosticada no pré-natal. Com 50 dias de vida, detectamos muitas fraturas e calos ósseos. O teste molecular identificou uma deleção em homozigose do éxon 4 do gene WNT1. Considerações finais: Concluímos que o caso apresentado tinha características clínicas de OI XV, e o teste molecular foi fundamental para o diagnóstico preciso e aconselhamento genético.

Introduction: Osteogenesis Imperfecta (OI) is a rare genetic disease with bone fragility. The classification includes many types. In addition, the risk of a recurrence, the management can vary with the kind of OI. Case report: We report a male patient born at 39 weeks from non-consanguineous healthy parents. The patient was diagnosed with Hydrocephalus at prenatal. At 50 days of life, we detected many fractures and bone calluses. The molecular test identified a homozygous deletion of exon 4 of the WNT1 gene. Final considerations: We conclude this case had clinical features of OI XV, and the molecular test was fundamental for the precise diagnosis and the genetic counseling.

Osteogénesis Imperfecta / Osteogenesis Imperfecta

La osteogenesis imperfecta (OI) es un grupo de trastornos del tejido conectivo que genera anomalías esqueléticas caracterizadas por fragilidad y deformidades óseas. Las características genéticas son variables y se han descrito nuevos subgrupos los últimos años agregando información a las clasificaciones tradicionales. Su incidencia es de 1/10.000 a 20.000 RN vivos. Existe un amplio espectro de manifestaciones clínicas, que van desde una leve fragilidad ósea, en niños asintomáticos, hasta versiones que son letales al momento de nacer. El diagnóstico es principalmente clínico y debe diferenciarse de otras anomalías del esqueleto que producen fragilidad y de lesiones por maltrato infantil. El tratamiento es multidisciplinario y está orientado a mejorar la calidad de vida de los pacientes. Para lo que se debe mejorar la densidad ósea, a través de medicamentos, buena musculatura y cargas fisiológicas. Las fracturas se tratan con períodos cortos de inmovilización y carga precoz, o con cirugías que limiten el tiempo de inmovilización. Por otro lado, las deformidades esqueléticas deben tratarse en forma quirúrgica utilizando osteosíntesis que sean extensibles y mantengan la corrección a medida que el niño crece. El manejo coordinado de los distintos profesionales involucrados es de gran importancia para lograr los mejores resultados en esta enfermedad crónica que involucra al niño y todo su entorno

Osteogenesis Imperfecta (OI) is a group of connective tissue disorders involved in skeletal abnormalities characterized by bone fragility and deformities. Genetic abnormalities are variable and new subgroups have been described recently, adding information to traditional classifications. There is a wide spectrum of clinical manifestations, ranging from mild bone fragility, in otherwise asymptomatic children, to versions that are lethal at birth. Its incidence is 1/10.000-20.000 newborns. The diagnosis is mainly clinical and must be distinguished from other skeletal abnormalities and child abuse. The treatment is multidisciplinary, and it is aimed to improve the quality of life of patients. For which the bone density must be improved, through medications, strong musculature, and physiological loads. Fractures are treated by immobilizing for short periods, trying to load at soon as possible, or by surgeries that limit immobilization time. On the other hand, skeletal deformities should be treated surgically using dynamic rods that are extensible and maintain correction as the child grows. The coordinated management of the different professionals involved is of the utmost importance to achieve the best results in this chronic disease that involves the child and his entire environment

Bladder and bowel symptoms experienced by children with osteogenesis imperfecta / Sintomas urinários e intestinais apresentados por crianças com osteogênese imperfeita

Abstract Objective: To estimate the prevalence and presentation of bladder, bowel, and combined bladder and bowel symptoms experienced by children with osteogenesis imperfecta and to describe the socio-demographic and clinical profile of these children. Method: A descriptive study was conducted with a convenience sample of parent-child pairs of toilet-trained children aged from 3 to 18 years. Pairs were interviewed using three tools: (1) Socio-Demographic and Clinical Questionnaire; (2) Dysfunctional Voiding Scoring System; (3) Rome III Criteria along with the Bristol Stool Scale. Data were stratified by socio-demographic and clinical variables and analyzed using descriptive statistics. Results: Thirty-one parent-child pairs participated in the study; 38.7% (n = 12) children reported bowel symptoms, 19.4% (n = 6) reported a combination of bladder issues (such as holding maneuvers and urgency) and bowel symptoms (such as hard or painful bowel movements and large diameter stools). There were no reports of isolated bladder issues. Among the child participants, 16 (51.7%) identified as female and 20 (64.5%) were 5-14 years old. The most prevalent type of osteogenesis imperfecta was type III (n = 12; 38.7%) and eight (25.8%) children reported using a wheelchair. Conclusion: This is the first study to examine the prevalence and presentation of bladder, bowel, and combined bladder and bowel symptoms in children with osteogenesis imperfecta, offering a preliminary socio-demographic and clinical profile of these children. This research is an important step toward effective screening, detection, and access to care and treatment, especially for clinicians working with this group of very fragile patients.

Resumo Objetivo: Estimar a prevalência e a apresentação de sintomas urinários, intestinais e urinários e intestinais combinados sofridos por crianças com osteogênese imperfeita e descrever o perfil sociodemográfico e clínico dessas crianças. Método: Foi realizado um estudo descritivo com uma amostra de conveniência de pares de pais-filhos de crianças treinadas para usar o banheiro com idades entre três e 18 anos. Os pares foram entrevistados utilizando três instrumentos: 1) o Questionário Sociodemográfico e Clínico; 2) o questionário Dysfunctional Voiding Scoring System; 3) os Critérios de Roma III juntamente com a Escala de Bristol para Consistência de Fezes. Os dados foram estratificados por variáveis sociodemográficas e clínicas e analisados com estatísticas descritivas. Resultados: Participaram do estudo 31 pares de pais-filhos, 38,7% (n = 12) crianças relataram sintomas intestinais, 19,4% (n = 6) relataram uma combinação de problemas urinários (como segurar e urgência miccional) e sintomas intestinais (como fezes duras ou evacuações dolorosas e fezes de grande dimensão). Não houve relatos de problemas urinários isolados. Entre as crianças, 16 (51,7%) eram meninas e 20 (64,5%) tinham entre 5 e 14 anos. O tipo mais prevalente de osteogênese imperfeita foi o III (n = 12; 38,7%) e 8 (25,8%) crianças relataram usar cadeira de rodas. Conclusão: Este é o primeiro estudo a examinar a prevalência e a apresentação de sintomas urinários, intestinais e urinários e intestinais combinados em crianças com osteogênese imperfeita e que mostra um perfil sociodemográfico e clínico preliminar dessas crianças. Nossa pesquisa é um passo importante com relação ao efetivo rastreamento, detecção e acesso ao cuidado e tratamento, principalmente para os profissionais de saúde que trabalham com esse grupo de pacientes tão frágeis.

¿A qué pregunta responde "el hueso"?: una cuestión de direccionalidad estructural y organización biológica (hueso y huesos, del big-bang a la osteoporosis) / To which question is 'bone' the answer?: a matter of structural directionality and biological organization (bone and bones, from the big bang to osteoporosis)

La "razón de ser" de nuestros huesos y esqueletos constituye un dilema centralizado en los conceptos biológicos de "estructura" y "organización", cuya solución necesitamos comprender para interpretar, diagnosticar, tratar y monitorear correctamente las osteopatías fragilizantes. Últimamente se ha reunido conocimiento suficiente para proponer aproximaciones razonables a ese objetivo. La que exponemos aquí requiere la aplicación de no menos de 6 criterios congruentes: 1) Un criterio cosmológico, que propone un origen común para todas las cosas; 2) Un criterio biológico, que explica el origen común de todos los huesos; 3) Un enfoque epistemológico, que desafía nuestra capacidad de comprensión del concepto concreto de estructura y del concepto abstracto de organización, focalizada en la noción rectora de direccionalidad espacial; 4) Una visión ecológica, que destaca la importancia del entorno mecánico de cada organismo para la adecuación de la calidad mecánica de sus huesos a las "funciones de sostén" que les adjudicamos; 5) Una correlación entre todo ese conocimiento y el necesario para optimizar nuestra aptitud para resolver los problemas clínicos implicados y 6) Una jerarquización del papel celular en el manejo de las interacciones genético-ambientales necesario para asimilar todo el problema a una simple cuestión de organización direccional de la estructura de cada hueso. Solo aplicando estos 6 criterios estaríamos en condiciones de responder a la incógnita planteada por el título. La conclusión de esta interpretación de la conducta y función de los huesos debería afectar el fundamento de la mayoría de las indicaciones farmacológicas destinadas al tratamiento de la fragilidad ósea. (AU)

The nature of the general behavior of our bones as weight-bearing structures is a matter of two biological concepts, namely, structure and organization, which are relevant to properly interpret, diagnose, treat, and monitor all boneweakening diseases. Different approaches can be proposed to trace the corresponding relationships. The one we present here involves six congruent criteria, namely, 1) a cosmological proposal of a common origin for everything; 2) a biological acknowledgement of a common origin for all bones; 3) the epistemological questioning of our understanding of the concrete concept of structure and the abstract notion of organization, focused on the lead idea of directionality; 4) the ecological insight that emphasizes the relevance of the mechanical environment of every organism to the naturally-selected adjustment of the mechanical properties of their mobile bones to act as struts or levers; 5) The clinical aspects of all the alluded associations; 6) The central role of bone cells to control the genetics/ environment interactions of any individual as needed to optimize the directionality of the structure of each of his/her bones to keep their mechanical ability within physiological limits. From our point of view, we could only solve the riddle posed by the title by addressing all of these six criteria. The striking conclusion of our analysis suggests that the structure (not the mass) of every bone would be controlled not only to take care of its mechanical ability, but also to cope with other properties which show a higher priority concerning natural selection. The matter would be that this interpretation of bone behavior and 'function' should affect the rationales for most pharmacological indications currently made to take care of bone fragility. (AU)

Osteogénesis imperfecta de tipo III en niño ecuatoriano / Osteogenesis imperfecta type III in an Ecuadorian child

Introducción: la osteogénesis imperfecta es una rara enfermedad genética hereditaria caracterizada por su heterogeneidad causada por defectos del tejido conectivo con el rasgo de fragilidad ósea determinante de múltiples fracturas, incluso prenatales; deformidades de huesos largos y columna vertebral y otros síntomas extra-esqueléticos, como escleróticas de color azul, dentinogénesis imperfecta, trastorno de audición y afectación cardiovascular. Objetivo: Presentar un paciente con las características clínicas e imagenológicas de osteogénesis imperfecta de tipo III. Presentación del caso: Niño ecuatoriano de 4 años de edad de baja talla con antecedente de fracturas múltiples desde los 8 meses de nacido, con deformidad en columna vertebral demostrada por radiología por cifoescoliosis en forma de "S" y fracturas vertebrales, con deformidad progresiva en huesos largos; ha sufrido 16 fracturas, no deambula, sensorio presente, orientado en tiempo y espacio, desarrollo cognitivo normal para la edad. La fragilidad ósea del niño según el fenotipo clasifica al diagnóstico de tipo III de osteogénesis imperfecta, el cual es progresivo e invalidante por las deformidades óseas y múltiples fracturas demostradas en exámenes imagenológicos, sin modificaciones en el color de escleróticas, de herencia presumiblemente dominante. Conclusiones: La descripción clínica y radiológica de osteogénesis imperfecta, afección poco conocida, correspondiente al fenotipo III de la enfermedad, reportada en niño ecuatoriano de 4 años de edad, con talla baja que no deambula, expresión de la severidad de su afección genética, con severas alteraciones óseas por su fragilidad con fracturas múltiples en huesos largos y vértebras(AU)

Introduction: Osteogenesis imperfecta is a rare hereditary genetic disease characterized by its heterogeneity caused by connective tissue defects with the feature of bone fragility determining multiple fractures, even prenatal ones; also deformities of long bones and spine, and other extra-skeletal symptoms, such as blue sclerotic, dentinogenesis imperfecta, hearing disorder and cardiovascular affectations. Objective: To present a patient with clinical and radiological findings of osteogenesis imperfect type III. Case presentation: Ecuadorean male child of 4 years old, with a short height, history of multiple fractures from 8 months of age, with spinal deformity demonstrated by radiology due to "S" shaped kyphoscoliosis and vertebral fractures, with progressive deformity in long bones. The boy has suffered 16 fractures, he does not wander, and he is sensory present, oriented in time and space, with normal cognitive development for his age. The bone fragility of the child according to the phenotype classifies in the type III diagnosis of osteogenesis imperfecta, which is progressive and invalidating due to bone deformities and multiple fractures evidenced in imaging tests, without changes in the color of sclerotics and of presumably dominant inheritance. Conclusions: The clinical and radiological description of osteogenesis imperfecta, which is little-known pathology, corresponding to type III phenotype is reported in a 4-year-old boy who, due to his involvement, has a short height and does not wander as a consequence of the severity of bone affectations with fractures in long bones and vertebrae, mainly produced by the fragility of the bones due to his genetic disease(AU)

Osteogénesis imperfecta: hallazgos clínicos y epidemiológicos en una serie de pacientes pediátricos / Osteogenesis imperfect: clinical and epidemiological findings in a series of pediatric patients

Resumen Introducción: La osteogénesis imperfecta (OI) es el trastorno óseo hereditario más común, con una incidencia de 1 en 10,000 a 25,000 nacimientos. Este trastorno está causado principalmente por mutaciones de los genes que codifican las cadenas del colágeno tipo I. En la mayoría de los casos, se presenta un patrón de herencia autosómico dominante. La OI se caracteriza principalmente por un aumento en la fragilidad ósea que da lugar a fracturas frecuentes que producen dolor, deformidad y discapacidad asociada con otras alteraciones. El objetivo del estudio fue exponer las características clínicas y epidemiológicas de una serie de pacientes pediátricos con diagnóstico de OI evaluados en la Universidad de Los Andes. Métodos: El presente trabajo consiste en el análisis de una serie de 37 casos pediátricos con diagnóstico de OI, de acuerdo a la clasificación clínica y radiológica de Sillence, evaluados en la consulta de la Unidad de Genética Médica de la Universidad de Los Andes, entre enero de 2006 y diciembre de 2018. Resultados: La OI tipo I fue la de presentación más frecuente, con 31 pacientes (83.78%). El fémur fue el hueso más afectado de manera conjunta. Las escleras azules fueron el hallazgo adicional más frecuente, en 32 pacientes (86.49%). Conclusiones: La OI representa el principal motivo de consulta por alteraciones en el sistema esquelético en la Unidad de Genética Médica de la Universidad de Los Andes. Ante la amplia forma clínica de presentación, la evaluación debe ser individual e interdisciplinaria. A través de un estudio más profundo se podrá brindar el oportuno asesoramiento genético familiar.

Abstract Background: Osteogenesis imperfecta (OI) is the most common hereditary bone disorder with an incidence of one in 10,000-25,000 births. It is caused mainly by mutations in the genes that code for Type I collagen chains. In most cases, it shows an autosomal dominant inheritance pattern. OI is characterized by an increase in bone fragility that leads to frequent fractures, which cause pain, deformity and disability associated with other alterations. The objective of this study was to present the clinical and epidemiological characteristics of a series of pediatric patients diagnosed with OI evaluated at the University of Los Andes. Methods: A series of 37 pediatric cases with diagnosis of OI according to the clinical and radiological classification of sillence is analyzed, which were evaluated in the medical genetics unit of the University of Los Andes consultation between January 2006 and December 2018. Results: Type I was the most frequent OI type, with 31 patients (83.78%). Additionally, the femur was the most affected bone. Blue scleras were the most frequent additional finding in 32 patients (86.49%). Conclusions: OI represents the main reason for consultation of alterations in the skeletal system in the medical genetics unit of the University of Los Andes. Given the broad clinical presentation, the evaluation must be individual and interdisciplinary. Further study will provide timely family genetic counseling.

Fetal Skeletal Lethal Dysplasia: Case Report Displasia Esquelética Letal Fetal: Relato de Caso

Abstract The clinical management and decision-making in pregnancies in which there is suspicion of lethal fetal malformations during the prenatal period, such as lethal skeletal dysplasia (SD), demand a multidisciplinary approach coordinated by an experienced physician. Based on the presentation of a case of osteogenesis imperfecta type IIA, we offer and discuss recommendations with the intention of organizing clinical and laboratory investigations aiming toward the clinical management, prognosis, and etiological diagnosis of these malformations, as well as genetic counselling to patients who wish to become pregnant.

Resumo O manejo clínico e a tomada de decisões médicas em gestantes com suspeita de malformação letal em um feto no período pré-natal, tal qual uma displasia esquelética letal, demandam uma abordagem multidisciplinar coordenada por um médico experiente. Baseado na apresentação de um caso de osteogênese imperfeita tipo IIA, recomendações são apresentadas e discutidas com a intenção de organizar as investigações clínicas e laboratoriais visando o manejo clínico, o prognóstico, e o diagnóstico etiológico dessas malformações, e o aconselhamento genético para as pacientes que desejam engravidar.

Características clínicas e padrão de fraturas no momento do diagnóstico de osteogênese imperfeita em crianças / Clinical features and pattern of fractures at the time of diagnosis of osteogenesis imperfecta in children

RESUMO Objetivo: Caracterizar o padrão de fraturas e a história clínica no momento do diagnóstico de osteogênese imperfeita. Métodos: Neste estudo retrospectivo, foram incluídos todos os pacientes com osteogênese imperfeita de ambos os sexos, com idades entre 0 e 18 anos, que realizaram tratamento entre 2002 e 2014. Os prontuários médicos foram revisados para coleta de dados clínicos, incluindo presença de escleras azuladas, dentinogênese imperfeita, história familiar positiva para a doença e locais das fraturas, além de achados radiográficos no momento do diagnóstico. Resultados: Foram incluídos no estudo 76 pacientes (42 do sexo feminino), com idade, no momento do diagnóstico, entre 0 e 114 meses [mediana (p25-p75) de idade de 38 (6-96) meses]. Escleras azuladas estavam presentes em 93,4% dos pacientes, dentinogênese imperfeita foi observada em 27,6% e ossos wormianos em 29,4%. O número de fraturas ao diagnóstico variou entre 0 e 17, com uma mediana de 3 (2-8) fraturas. Em 40 (57%) pacientes, as fraturas eram de membros superiores e inferiores no momento do diagnóstico e, em 9 pacientes também havia fratura vertebral. O diagnóstico foi realizado ao nascimento em 85,7% dos pacientes com o tipo 3 e em 39,3% daqueles com tipo 4/5 da doença. Conclusões: Osteogênese imperfeita é uma doença genética com características clínicas distintas, tais como fragilidade óssea, fraturas recorrentes, escleras azuladas e dentinogênese imperfeita. É importante saber identificar essas características, facilitando o diagnóstico, otimizando o tratamento e diferenciando de outras doenças que também podem causar fraturas.

ABSTRACT Objective: To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. Methods: In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. Results: Seventy-six patients (42 females) were included in the study. Individuals' age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. Conclusions: Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures.

Phase angle and World Health Organization criteria for the assessment of nutritional status in children with osteogenesis imperfecta / Ângulo de fase e critérios da Organização Mundial de Saúde na avaliação do estado nutricional em crianças com osteogênese imperfeita

Abstract Objective: To compare the phase angle of patients with osteogenesis imperfecta treated at a tertiary university hospital with patients in a control group of healthy children, and to assess the nutritional status of these patients through the body mass index proposed by the World Health Organization. Methods: Cross-sectional study carried out in a university hospital that included seven patients with osteogenesis imperfecta and a control group of 17 healthy children of the same gender and age. Weight and height were measured and bioelectrical impedance was performed. Subsequently, the phase angle was calculated based on resistance and reactance values. Results: The phase angle of the group of children with osteogenesis imperfecta was significantly lower than that of the control group (p<0.05). The body mass index criterion for age of the World Health Organization showed no difference between groups. Conclusions: Children with osteogenesis imperfecta have a nutritional risk detected by the phase angle, which is a useful tool for nutritional screening. The calculation result could help in the diet therapy of patients with osteogenesis imperfecta.

Resumo Objetivo: Comparar o ângulo de fase de pacientes com osteogênese imperfeita atendidos em um hospital universitário terciário com pacientes de um grupo controle de crianças saudáveis, bem como avaliar o estado nutricional desses pacientes pelo índice de massa corporal proposto pela Organização Mundial de Saúde. Métodos: Estudo transversal feito em hospital universitário que incluiu sete pacientes com osteogênese imperfeita e um grupo controle composto por 17 crianças saudáveis de mesmo sexo e idade. Foram aferidos peso e estatura e foi feito o exame de impedância bioelétrica. Posteriormente, o ângulo de fase foi calculado a partir dos valores de resistência e reactância. Resultados: O ângulo de fase do grupo de crianças com osteogênese imperfeita foi significativamente menor do que o do grupo controle (p<0,05). O critério de índice de massa corporal por idade da Organização Mundial de Saúde não mostrou diferença entre os grupos. Conclusões: Crianças com osteogênese imperfeita têm um risco nutricional detectado pelo ângulo de fase, é uma ferramenta útil para triagem nutricional. O resultado do cálculo poderia auxiliar a dietoterapia de pacientes com osteogênese imperfeita.

Occipito-thoracic Fusion in Incidental Dystropic Os Odontoideum in a patient suspected with Osteogenesis Imperfecta: A Case Report.

Introduction: Os odontoideum is a rare lesion of the axis. Described as an ossicle, consisting of smooth and separate caudal portions of the odontoid process wherein its etiology has remained controversial. Os odontoideum complicating a possible osteogenesis imperfecta has not been reported before in the literature. Methods: We report the case of a 14-yr male patient presented with progressive weakness of both lower and upper extremities after a head trauma 10 months prior to admission, which presented as transient quadreparesis. Results: Magnetic resonance imaging of cervical spine showing cervicomedullary junction compression. Patient underwent surgical intervention and 3 months post operation, patient was reported to have steady gait and muscle grading of 5/5 on all extremities. Conclusion: Surgical fi xation and fusion in patients with instability may prevent catastrophic neurologic insult after minor trauma in the future.

Osteogénesis imperfecta: estudio de la calidad de vida en los niños / Osteogenesis imperfecta: quality of life in children

La calidad de vida relacionada con la salud (CVRS) en los niños con osteogénesis imperfecta (OI) ha sido poco comunicada. Se la evaluó con el cuestionario Peds QL versión 4.0, en 65 familias y 42 niños, con una media de edad de 7,76 años (35 con OI de tipo I y 30 con OI de tipo III-IV). Hubo diferencias signifcativas en el dominio físico según los niños y los padres, entre los niños con OI de tipo I y aquellos con OI de tipo III-IV. En el dominio social solo los padres consideraron menor CVRS en las formas III-IV. En el análisis multivariado de las formas graves, para los padres la mejor CVRS se asoció con menor défcit de estatura (coef. β = 3,8; p= 0,039), menor número de fracturas (coef. β= 0,69; p= 0,003) y mayor dosis de pamidronato (coef. β= 1,44; p= 0,037). Para los niños, la CVRS fue mejor cuando hubo adherencia al tratamiento (coef. β= 19,41; p= 0,03).

The impact produced by osteogenesis imperfecta in childrens' quality of life almost has not been reported; 65 children, 38 males, were evaluated according to the questionnaire PedsQL 4.0 Argentinean Spanish version. Median age was 7.76 years; 35 children with OI type I were compared with 30 type III-IV (according to Sillence Classifcation) fnding signifcant difference in the physical domain in both visions, children and parents, and only in parents' vision in the social area. Multivariate analysis showed an association between better PedQL scores and treatment compliance (coef. β= 19.41 p= 0.03) in children's vision. In parental report on the other hand, the association was found with greater pamidronate doses (coef. β 1.44 p=0.037), lower height compromise (coef. β= 3.8; p= 0.039) and less number of fractures (coef. β= 0.69; p= 0.003).

Osteogénesis imperfecta: caso clínico / Osteogenesis imperfecta: report of a clinical case

Las displasias esqueléticas son un grupo de enfermedades de los huesos, de origen genético, tipo generalizado. Son enfermedades poco frecuentes. Se han descrito aproximadamente 350 tipos de displasias óseas diferentes. Dentro de éstas, se encuentra la osteogénesis imperfecta, en la que hay una alteración del colágeno tipo 1. Este colágeno se encuentra también en la conjuntiva, en los ligamentos y en los dientes; de allí que las manifestaciones pueden observarse también en áreas extraóseas. En el caso clínico, se describe la situación de una paciente pediátrica con diagnóstico de osteogéensis imperfecta tipo 1, la problemática de la enfermedad y las posibilidades de tratamiento odontológico.

Efeito do enxerto ósseo corticoesponjoso na osteogênese em falha cortical ulnar de galinhas domésticas (Gallus domesticus) / Effect of cortico-cancellous bone grafting in osteogenisis of cortical ulnar failure of domestic chickens (Gallus domesticus)

O objetivo do estudo foi avaliar o efeito do enxerto ósseo corticoesponjoso na osteogênese em falha cortical ulnar de galinhas domésticas. Foram utilizadas 18 galinhas, com aproximadamente 70 semanas de idade e peso corpóreo médio de 2,5kg. Criou-se uma falha óssea na porção diafisária média da ulna em ambas as asas, sendo a direita utilizada como grupo-controle (grupo I) e a esquerda como grupo-tratado (grupo II). As aves foram subdivididas aleatoriamente em quatro subgrupos de acordo com o período de observação (14, 35, 60 e 90 dias). No grupo II, dois fragmentos ósseos da carena do esterno foram retirados, seccionados e implantados na falha óssea. Ao término do período de observação de cada subgrupo, as aves foram abatidas com tiopental sódico para realização dos exames histopatológico e radiográfico post-mortem, com classificação dos resultados em escala semiquantitativa (escore). O grupo II demonstrou osteogênese mais evidente aos 35 e 90 dias de pós-cirúrgico (P<0,05). Ao comparar os grupos I e II, sem levar-se em consideração o tempo de observação, foi possível observar que houve diferença estatística significativa (P<0,05). Conclui-se que o enxerto ósseo corticoesponjoso demonstra potencial osteogênico satisfatório na espécie estudada, entretanto retarda o tempo de remodelação óssea quando aplicado sobre falhas estáveis pequenas.

The aim of this survey was to evaluate the effect of cortico-cancellous bone grafting in osteogenesis in cortical ulnar failure in domestic chickens. Eighteen chickens weighing 2.5kg with approximately 70 weeks of age were used. A bone defect in the middle portion of the ulna shaft was created in both wings; the right wing in the control group (Group I) and the left in the treated group (Group II). The birds were randomly divided into four subgroups according to the observation period (14, 35, 60 and 90 days). In group II, two bone fragments of the keel of the sternum were removed, sectioned and implanted in the bone defects. At the end of the observation period for each subgroup, the birds were euthanaized with sodium thiopental to perform the histopathological and radiographic postmortem, with ranking of results in a semi-quantitative scale (score). Group II showed a more evident osteogenisis at 35 and 90 days after surgery (P<0.05). In comparing both groups, without time observation, there was statistical difference (P<0.05). In conclusion, the cortico-cancellous bone graft demonstrated satisfactory osteogenic potential in the specie studied, however, it delays the bone remodeling time when applied in stable small failures.

Fanconi-Bickel syndrome versus osteogenesis imperfeeta: An Iranian case with a novel mutation in glucose transporter 2 gene, and review of literature.

Fanconi-Bickel syndrome is an extremely rare hereditary metabolic disease, characterized by hepatomegaly due to glycogen storage, refractory hypophosphatemic rickets, marked growth retardation and proximal renal tubular acidosis. Recurrent bone fractures are one of the hallmark findings. It is a single gene disorder; the responsible gene belongs to the facilitative glucose transporters 2 (GLUT2) family gene or (SLC2A2) mapped to the q26.1-26.3 locus on chromosome 3, and encodes the GLUT protein 2. This protein is expressed in pancreatic ί-cells, hepatocytes, renal tubules, and intestinal mucosa. Several mutations in the GLUT2 gene have been reported in different ethnicities. Herein we report an Iranian girl with a missed diagnosis of osteogenesis imperfecta. She was referred with the history of frequent fractures, and severe motor delay and was suspected to osteogenesis imperfecta. Following the case we detected refractory rickets instead of OI, sever growth failure, proximal renal tubulopathy and RTA, and enlarged kidneys, progressive hepatomegaly, and GSD on liver biopsy. Glucose and galactose tolerance tests confirmed abnormal carbohydrate metabolism. Molecular analysis on GLUT2 gene revealed a homozygous novel mutation in exon 5; it was 15 nucleotide deletion and 7 nucleotide insertion and caused a frame shift mutation, produced a premature truncated protein (P.A229QFsX19). This mutation has not been reported before in the relevant literature.

Desarrollo de un material de fijación ósea inédito (Clavo Gap) para pacientes con talla baja y fragilidad ósea: osteogénesis imperfecta / Development of a bone fixation device (Gap Nail) for patients with short stature and fragile bones: osteogenesis imperfecta

La mayoría de los sistemas de fijación ósea no están diseñados para pacientes de baja estatura con huesos de pequeño diámetro y longitud, como los que se presentan en osteogénesis imperfecta, raquitismo y displasias óseas con afectación de las fisis. En niños con defectos del metabolismo óseo, los clavos telescópicos que se fijan en las fisis, suelen ser los más indicados. El Clavo de Fassier-Duval tiene excelentes reportes, pero no controla la rotación y funciona solo en personas con placas de crecimiento abiertas. Para adultos y adolescentes con huesos pequeños y débiles, no existía un clavo intramedular ajustado a sus tamaños. Esta carencia llevó al autor a involucrarse en el diseño del CLAVO GAP. Tiene diámetros desde 4,8 mm y longitudes hasta 320 mm, canulado, capacidad de bloqueo proximal y distal, se puede utilizar en fémur, tibia y húmero. Es común que estos pacientes presenten debilidad de la cortical lateral del tercio proximal del fémur, por lo que se diseñó para agregarle una fijación al cuello femoral y el trocánter. Presentamos 5 casos realizados por los autores con este sistema de fijación ósea en pacientes con osteogénesis imperfecta. En todos los casos se logró el objetivo de estabilizar los segmentos óseos extremadamente débiles, con diámetros por debajo de los parámetros convencionales, sin requerir uso de férulas post-quirúrgicas(AU)

Most of the systems for bone fixation are not designed for patients of short stature with small bones, like in the patients with osteogénesis imperfecta, rickets and bone dysplasia with affectation of the fisis. In children with defects of the bone metabolism, the nails that telescope and hold in the physes, usually are indicated. Fassier-Duval Nails has excellent reports, but it does not have control of the rotation and it works only in patients with physes open. For adults and adolescents with small and weak bones, did not exist an endomedular nail that fit its sizes. This deficiency was an incentive to the author to become involved in the design of the GAP NAIL. It has diameters from 4.8 mm and lengths to 320 mm. It is canulated. It has capacity of being locked proximal and distally. It can be used in femur, tibia and humerus. It is common that these patients present weakness of the lateral cortex of the proximal third of the femur, reason why was designed to have the possibility to fix the femoral neck and trochanter. We present 5 cases were this system was used in patients with OI. In all the cases the objective was reached, that was to stabilized bones extremely fragile, with diameters below the conventional parameters, without requiring use of braces in the postop(AU)

Osteogenesis Imperfecta Type VI with Severe Bony Deformities Caused by Novel Compound Heterozygous Mutations in SERPINF1

Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

Osteogénesis imperfecta, reporte de un caso / Osteogenesis imperfecta, a case report

INTRODUCCIÓN: La osteogénesis imperfecta (OI) es un trastorno hereditario del tejido conectivo fenotípicamente heterogéneo. Formas leves de OI suelen presentar fragilidad ósea mínima y estatura normal pudiendo manifestarse sólo por osteoporosis precoz o pérdida mineral ósea grave posmenopáusica. El cuadro moderado - severo presenta fracturas múltiples con trauma mínimo (o nulo) y deformidades óseas de grado variable. Forma más severa produce la muerte en el período perinatal. PRESENTACIÓN DEL CASO: Lactante varón 2 años 7 meses, nacido de término por parto normal, pequeño para edad gestacional severo, primogénito de madre adolescente y padre con antecedente OI. Se mantuvo hospitalizado para control de crecimiento ponderal, no encontrándose patología agregada. Tras alta, paciente fue citado a policlínico de genética por antecedente OI, sin asistir. Al año de edad, fue derivado por fractura fémur derecho posterior a trauma aparentemente mínimo, hospitalizándose para manejo con observación de OI y probable violencia intrafamiliar. Primera evaluación genética no impresionó OI, luego endocrinología solicitó estudio bioquímico y radiológico completo ambulatorio. Posteriormente, consultó por fractura fémur izquierdo con fractura tibial derecha previamente no diagnosticada. Tras reevaluación genética, destacaban retraso de talla y múltiples dismorfias corcordantes, diagnosticándose OI leve-moderada por clínica y antecedente familiar. Equipo endocrinología inició tratamiento con bifosfonatos. Evoluciona con fractura codo y nueva fractura fémur derecho tras caída. DISCUSIÓN: La OI es una patología frecuente con manifestaciones heterogéneas con diagnóstico sencillo ante fragilidad ósea, manifestaciones extraesqueléticas e historia familiar positiva. El diagnóstico y tratamiento oportuno permitirían minimizar complicaciones y maximizar capacidad funcional.

INTRODUCTION: The osteogenesis imperfecta (OI) is a phenotypically heterogeneous hereditary connective tissue disease. The mild forms of OI tends to show minimum fragility on bones and normal height which could only be manifested as an early osteoporosis or serious postmenopausal bone density loss. The severe clinic picture shows multiple fractures with minimum trauma and bone deformity. The most severe form causes perinatal death. CASE REPORT: A breastfed infant boy of two years and seven months, born by natural birth, very small for gestational age, first born of a teenage mother and a father with OI. He was, first hospitalized for weight and growth control. No pathological findings were recognized. After the discharge, he did not attend to the genetic control. At one year old, he was sent with a right femur fracture after a minimum trauma. He was hospitalized suspecting OI and possible domestic violence. A first genetic evaluation did not match with OI, then endocrinology requested a complete radiological study. The biochemical study was normal. Then, he presented left femur and right tibia fracture. The genetic reevaluation, found multiple dysmorphic characteristic and late size development, which confirmed a mild form of OI. A biphosphonates treatment was initiated. DISCUSSION: The OI is a frequent disease with heterogeneous manifestations. The diagnosis is simple, bases on bone fragility, extra skeletal manifestations and familiar history. An early diagnosis and treatment could minimize complications and maximize mobility and functional capacity.

Dentinogénesis imperfecta tipo I / Dentinogenesis imperfecta, type I

La dentinogénesis imperfecta (DI) es una anomalía dentaria determinada genéticamente y caracterizada clínicamente por una apariencia ámbar opalescente de la dentina. Se presenta la resolución clínica, con seguimiento y control a 3 años, de un paciente con diagnóstico de DI. La identificación temprana de esta entidad y el tratamiento oportuno y multidisciplinario, contribuyen a mejorar el pronóstico de la misma.

Sobrevida de uma haste intramedular extensível (HIMEX) no tratamento de crianças com ostegênese imperfeita / Survival rates of the HIMEX extensible nail in the treatment of children with osteogenesis imperfecta

OBJETIVO: avaliar o desempenho da haste extensível ancorada por ganchos (HIMEX) em deformidades da osteogênese imperfeita (OI). MÉTODOS: Todas as crianças operadas com HIMEX entre 1990 - 2004. Foi comparado o número de fraturas, reaparecimento de deformidades e capacidade de deambulação antes e após a HIMEX; incidência de migração e sobrevida da haste por curvas de sobrevivência. RESULTADOS: 14 pacientes (2 a 18 anos), oito do sexo feminino, incluindo 46 procedimentos, 39 primários e sete re-operações. Idade média na primeira fratura de 148,21 dias e média de 42,6 fraturas/paciente pré colocação da HIMEX. Dos 46 procedimentos, 28 no fêmur e 18 na tíbia. Tempo médio de seguimento de 80,21 ± 36,71 meses. Houve diminuição significativa de fraturas/paciente (0,78) e melhora na deambulação em sete dos 14 pacientes. Porcentagem de re-operação de 18 por cento e migração do implante em 12 por cento (05/39). 80 por cento dos implantes in situ até 108 meses. Implantes na tíbia tiveram sobrevida significativamente menor que os do fêmur. O tipo da OI e a idade na época da cirurgia não influenciaram significativamente a incidência de re-operação. CONCLUSÃO: A HIMEX levou à redução significativa no número de fraturas, incidência menor de migração e sobrevida maior da haste do que a referida na literatura.

OBJECTIVE: To evaluate the performance of an extensible nail with hooks, named HIMEX, in osteogenesis imperfecta (OI) deformities. METHODS: All child patients were operated on with HIMEX from 1990 to 2004. The number of fractures, reappearance of deformities, improvement of motor development before and after the use of HIMEX, and the incidence of the migration and nail survival were compared. RESULTS: Fourteen patients, with ages from 2 to 18 years, including 8 females, underwent 46 procedures, 39 primary and 7 re-operations. The average age at the first fracture was 148.21 days, and there was an average of 42.6 fractures per patient prior to HIMEX placement. Of the forty-six bones affected, 28 were femurs and 18 were tibias. Average follow-up care lasted 80.21±36.71 months. There was a statistically significant decrease (0.78) in the number of fractures per patient and an improvement in walking in seven of the fourteen patients. Revision occurred in 18 percent of patients and migration of the nail occurred in 12 percent (5/39). Eighty percent of the nails remained in situ until 108 months, with femoral procedures lasting significantly longer than tibial procedures. The type of OI and the age at the procedure did not significantly affect the incidence of revision. CONCLUSION: HIMEX significantly reduced the number of fractures, presenting lower incidence of migration and higher survival rates than those described in literature.