A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

Complicaciones relacionadas al manejo anestésico de pacientes pediátricos con osteogénesis imperfecta sometidos a procedimientos ortopédicos / Complications related to the anesthetic management of pediatric patients with osteogenesis imperfecta undergoing orthopedic procedures

Resumen: Introducción: la osteogénesis imperfecta es un trastorno sistémico del tejido conectivo, se caracteriza por una densidad ósea menor y variabilidad de la fragilidad ósea. Material y métodos: se realizó un estudio retrospectivo, observacional, descriptivo de casos consecutivos, cuyo objetivo principal fue determinar las complicaciones relacionadas al procedimiento anestésico en pacientes pediátricos con diagnóstico de osteogénesis imperfecta sometidos a procedimientos ortopédicos en el Hospital Infantil de México «Federico Gómez¼ mediante la revisión de expedientes clínicos. Se incluyeron pacientes con diagnóstico de osteogénesis imperfecta, menores de 18 años, sometidos a cirugía ortopédica electiva. Se utilizaron medidas de tendencia central y dispersión así como pruebas de hipótesis diversas. Resultados: se incluyeron 86 registros anestésicos. La mayoría del tipo III de osteogénesis imperfecta. La anestesia general balanceada fue la técnica más frecuente con intubación orotraqueal. De las complicaciones reportadas hubo intubación difícil en dos casos (2.3%). En seis casos (6.9%) se consideró ventilación difícil. Otra de las complicaciones reportadas fue el sangrado, encontrando un sangrado mayor al previsto en 33 casos (38.4%). Conclusiones: la anestesia requerida en los pacientes con osteogénesis imperfecta se llevó a cabo con un mínimo de complicaciones.

Abstract: Introduction: osteogenesis imperfecta is a systemic disorder of connective tissue, characterized by decreased bone density and variability of bone fragility. Material and methods: a retrospective, observational, descriptive study of consecutive cases was carried out, whose main objective was to determine the complications related to the anesthetic procedure in pediatric patients with a diagnosis of osteogenesis imperfecta undergoing orthopedic procedures at the «Federico Gómez¼ Children's Hospital of Mexico, through the review of clinical records. Patients diagnosed with osteogenesis imperfecta, under 18 years of age, undergoing elective orthopedic surgery, were included. Measures of central tendency and dispersion were used, as well as tests of various hypotheses. Results: 86 anesthetic records were included. Most of the type III of osteogenesis imperfecta. Balanced general anesthesia was the most frequent technique with orotracheal intubation. Of the reported complications, difficult intubation was found in two cases (2.3%). In six cases (6.9%) ventilation was considered difficult. Another of the complications reported was bleeding, finding bleeding greater than expected in 33 cases (38.4%). Conclusions: the anesthesia required in patients with osteogenesis imperfecta was carried out with a minimum of complications.

An Exploratory Study to Assess the Knowledge & Attitude of Parents Regarding Play Needs of Children (under 5 years of age) in Selected Hospital of Durg (C.G.)

Background-The human life has a distinct sphere– the world of play makes childhood more meaningful, happy & motivate the child to learn, develop & mature. Parents, teachers, nurses, psychologists are becoming increasingly aware of the importance of play and its influence upon bringing of children. The study was designed to assess the knowledge and attitude of parents regarding play needs of children. Materials & Methods- 100 couples were selected using purposive sampling technique. A structured questionnaire was prepared for assessing the knowledge & attitude of parents regarding play needs of children (under 5 years of age). Results- 20% of them had moderately adequate knowledge whereas 22% had moderately adequate attitude with. Knowledge & attitude of parents correlated. There is no significant association between socio demographic variables and knowledge except gender, religion, and mass media exposure, type of family, and monthly income and number of children as demographic variables. There is no significant association between socio demographic variables and attitude except gender, religion, qualification, type of family, and number of children as demographic variables. Conclusion-This study was conducted in Govt. Hospital of Durg (Chattisgarh) with the parents having children under 5 years of age. The findings of the study recommended the further interventional approaches regarding play needs of children. Parents need to be educated about meaning and importance of play for child. It creates awareness play know, attitudes, play needs, under five.

Use of the SARC-F Score as an Aid in Fragility Fractures Prevention / O uso do escore SARC-F como auxiliar na prevenção de fraturas por fragilidade

Abstract Objective The present study aimed to relate the strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) score with the presence or absence of fragility fracture in the population over 60 years of age. Methods The risk of sarcopenia was determined through the application of the SARC-F questionnaire, and the patients were divided into 2 groups, according to the occurrence or not of fragility fracture (n = 100). Results Thirty-two cases of distal radius fractures and eighteen cases of proximal femur fractures were identified. A higher score on the SARC-F is determinant between having or not a fragility fracture, estimating that for each point in the score there is a 70% increase in the chance of a patient having a fracture, regardless of age, gender, and body mass index (BMI). Conclusion There was a direct correlation between a higher score on the SARC-F and an increase in the chance of fragility fracture.

Resumo Objetivo O presente estudo teve como objetivo relacionar o escore strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) com a presença ou não de fratura por fragilidade na população acima de 60 anos. Métodos O risco de sarcopenia foi determinado por meio da aplicação do questionário SARC-F, sendo os pacientes divididos em 2 grupos, de acordo com a ocorrência ou não de fratura por fragilidade (n = 100). Resultados Foram levantados 32 casos de fratura de rádio distal e 18 casos de fratura de fêmur proximal. Uma maior pontuação no SARC-F determina bem entre ter ou não ter fratura por fragilidade, estimando que a cada ponto a mais no escore há um acréscimo de 70% na chance de o paciente ter fratura, independentemente da idade, sexo e índice de massa corporal (IMC). Conclusão Houve correlação direta entre uma maior pontuação no SARC-F e aumento na chance de fratura por fragilidade.

Functional status of individuals with osteogenesis imperfecta: data from a reference center

Abstract Objective: To evaluate the functional status of individuals with Osteogenesis Imperfecta (OI) followed up at a reference center in the state of Bahia. Materials and methods: This is an observational, cross-sectional, descriptive study, which evaluated individuals with OI, based on a non-probabilistic sampling. To assess motor function, the Motor Function Measure (MFM) score was used, in addition to the measurement of muscle strength using the Medical Research Council (MRC) score. Functional performance was measured using the Pediatric Assessment of Disability Inventory, Computerized Adaptive Testing (PEDI-CAT). Results: Thirty-one individuals aged between two and 18 years old were evaluated. The overall score of MFM was 74.2%, and the lowest score was found in participants with type III OI (56.3%). The median of the MRC index was 80. The mobility domain was the most affected in the PEDI-CATevaluation, with a mean T score of 23.9, (14.2 in type III OI). Conclusions: Among the evaluated individuals, functional alterations were identified, reduced global gross motor functionality and muscle strength, impacting the mobility domain, with the most relevant findings in individuals with type III OI.

Cirugía en coxa vara por osteogénesis imperfecta. Reporte de dos casos / Coxa vara surgery for osteogenesis imperfecta. A report of two cases

Introducción. La coxa vara es una disminución del ángulo cervicodiafisiario (<110°) y se puede presentar hasta en el 10% de los pacientes con osteogénesis imperfecta (OI), siendo más frecuente en el tipo III. Sus manifestaciones clínicas son alteración en la marcha, acortamiento de la pierna, genu valgo y dolor.Presentación de los casos. Varones de 13 años y 8 años con OI tipo III, signo positivo de Trendelenburg, movilidad articular adecuada y antecedentes de fracturas recurrentes y cirugías previas por deformidades en los que se realizó cirugía para la corrección de coxa vara. Se realizó una evaluación radiográfica y una funcional (escala de Harris) a los 6 y 68 meses de la cirugía, respectivamente.En el caso 1 se logró una corrección de 46° en el ángulo cervicodiafisiario (ángulo inicial: 84°; ángulo final: 130°) y el puntaje en la escala de Harris fue de 70 puntos. En el caso 2, se logró una corrección de 50° (82° vs. 132°), con un puntaje en la escala de Harris de 68 puntos. Conclusiones. la técnica de corrección mediante osteotomía subtrocantérica y la utilización de clavo endomedular y agujas de Kirschner es una opción efectiva para el tratamiento de coxa vara en pacientes con osteogénesis imperfecta

Introduction. Coxa vara is a deformity characterized by a decrease in the neck-shaft angle (<110°) that can occur in up to 10% of patients with osteogenesis imperfecta (OI), being more frequent in type III OI. Its clinical manifestations are gait disturbance, leg shortening, genu valgum, and pain.Case presentation. Male patients aged 13 and 8 years presenting with type III OI, positive Trende-lenburg sign, adequate joint mobility, and a history of recurrent fractures and previous surgeries for deformities, including surgery for coxa vara correction. Radiographic and functional evaluation (Harris scale) were performed 6 and 68 months after surgery, respectively.In the first case, a correction of 46° was obtained (initial angle: 84°; final angle: 130°), as well as a Harris score was 70. In the second case, a correction of 50° (82° vs. 132°) was achieved, with a Harris score of 68 points. Conclusions. Subtrochanteric osteotomy and intramedullary K-wire nailing are effective options for the treatment of coxa vara in patients with osteogenesis imperfecta

Osteogénesis imperfecta tipo III con presentación inusual / An unusual presentation of osteogenesis imperfecta type III

Introducción: la osteogénesis imperfecta (OI) es el trastorno óseo hereditario más común con incidencia mundial de 1 en 10.000 a 25.000 nacimientos, causado por mutaciones de los genes que codifican las cadenas del colágeno tipo I. La mayoría presenta patrón de herencia autosómico dominante. Las manifestaciones clínicas varían de asintomáticos con mayor predisposición a fracturas, talla normal y sin incidencia en la expectativa de vida, hasta alta letalidad perinatal con deformidades esqueléticas severas, incapacidad motora y talla muy baja. Objetivos: reportar un paciente con presentación inusual de OI tipo III con fracturas in útero para contribuir en la orientación diagnóstica. Caso clínico: recién nacido con sospecha in útero de OI tipo II, nació a término vía cesárea, Ballard de 37 semanas y bajo peso con fracturas múltiples y defectos de osificación (braquicefalia). A los 4 meses con sobrevida mayor a la esperada, presentaba escleróticas grisáceas, braquicefalia, fontanelas amplias, fragilidad ósea generalizada y deformidades angulares en extremidades; confirmándose la OI tipo III mediante secuenciación exómica. Conclusiones: el diagnóstico de la OI se basa en la clínica y las características típicas. La supervivencia, los hallazgos radiográficos y el resultado de los estudios genéticos moleculares permiten la adecuada clasificación.

Introduction: osteogenesis imperfecta (OI) is the most common hereditary bone disorder with a global incidence of 1 in 10,000 to 25,000 births. OI is caused by mutations in the genes encoding the chains of collagen type I and is mostly inherited in an autosomal dominant manner. Clinical manifestations vary from asymptomatic with increased propensity to fractures, normal stature and no impact on life expectancy, to high perinatal lethality, severe skeletal deformities, motor disability and very short stature. Objectives: to report a case of an unusual presentation of OI type III in an infant who had in utero fractures, as a diagnostic resource. Case: a full-term infant born via cesarean section, with suspected in utero OI type II, Ballard score: 37 weeks, low weight and multiple fractures and ossification defects (brachycephaly). At 4 months, a higher survival than the expected, he presented greyish sclerae, brachycephaly, large fontanels, generalized bone fragility and bowing of extremities; OI type III was confirmed by exome sequencing. Conclusions: OI diagnosis is based on the clinical and typical features of the disorder. Survival, radiographic findings and molecular genetic testing allow an adequate classification.

Respiratory function of children and adolescents with osteogenesis imperfecta: respiratory muscle strength, forced vital capacity, and peak expiratory flow / Função respiratória de crianças e adolescentes com osteogênese imperfeita: força muscular respiratória, capacidade vital forçada e pico de fluxo expiratório

Abstract Objective: This study aims to evaluate the respiratory function of children and adolescents with osteogenesis imperfecta (OI) followed up at a referral center. Methods: A cross-sectional study was conducted with a non-probabilistic sample. Manovacuometry was performed with the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), and in addition, peak expiratory flow (PEF) and ventilometry were performed to measure forced vital capacity (FVC). Results: In total, 23 individuals were evaluated, with a mean age of 11.6±3.4 years, 56.5% of whom were females. Regarding the classification of OI, 56.5% of the sample belonged to type IV, 30.5% to type III, and 13% to type I. The mean MIP was 64.4% of the predicted, and the mean MEP was 56.2% of the predicted. Overall, the mean PEF was 213.9 L/min, but only 140.6 L/min in the OI type III group. Median FVC was 1.9 L, corresponding to 110% of the predicted. Conclusions: Respiratory function of the study subjects was altered, with respiratory muscle strength values lower than expected in the whole sample, and peak expiratory flow was significantly reduced in the OI type III group.

RESUMO Objetivo: Avaliar a função respiratória de crianças e adolescentes com osteogênese imperfeita (OI) acompanhados em um centro de referência. Métodos: Realizou-se um estudo de corte transversal, com amostragem não probabilística. Foi realizada manovacuometria com mensuração da pressão inspiratória máxima (PIM) e pressão expiratória máxima (PEM), além do pico de fluxo expiratório (PFE) e da ventilometria para a medida da capacidade vital forçada (CVF). Resultados: Foram avaliados 23 indivíduos, com média de idade de 11,6±3,4 anos, sendo 56,5% do sexo feminino. Com relação à classificação da OI, 56,5% da amostra pertencia ao tipo IV, 30,5% ao tipo III e 13% ao tipo I. A média de PIM foi de 64,4% do previsto, e a PEM foi de 56,2% do previsto. A média de PFE foi de 213,9 L/min, sendo 140,6 L/min no grupo de OI tipo III. A mediana da CVF foi de 1,9 L, correspondendo a 110% do previsto. Conclusões: A função respiratória dos indivíduos estudados encontrava-se alterada, com valores abaixo do esperado em toda a amostra para força muscular respiratória, além do PFE reduzido no grupo OI tipo III.

Treatment of osteogenesis imperfecta using the fassier-duval telescopic rod / Tratamento da osteogênese imperfeita com a haste telescópica fassier-duval

ABSTRACT Objectives: This study aimed to assess the treatment of patients with Osteogenesis Imperfecta (OI) operated on with a telescopic Fassier-Duval (FD) rod in a querterenario hospital from 2010 to 2020. Methods: We analyzed indication for surgical treatment, causes of reoperation, complications and the effectiveness of telescoping rod. Results: The results were compared with the literature and with the same parameters from a previous study which a different telescopic rod developed by the same authors. This was a retrospective study based on the analysis of digital and radiographic clinical records. Fifteen patients with 21 FD rods were evaluated, most were used on the femur (18 rods or 85.7%), eight patients were female (53.3%), with a mean age of 10.47 (3.92 to 16.44) years, most of whom had type III Sillence (46.7%), with a mean follow-up of 5.22 (1.43 to 7.02) years. Seven rods (33.3%) had complications. The main indication was for fracture (57.1%). Regarding the ability to telescope, we observed that 15 rods (71.4%) followed the child's growth. Conclusion: We had good results using FD rods, similar to the data found in the literature and the data obtained with our rod. Level of Evidence III,Retrospective comparative study .

RESUMO Objetivos: O objetivo deste estudo foi avaliar o tratamento de pacientes com Osteogênese Imperfeita (OI) operados com a haste telescopada de Fassier-Duval (FD) num hospital quaternário no período de 2010 a 2020. Métodos: Analisamos a indicação cirúrgica do tratamento, as causas de revisão, suas complicações e a eficácia na telescopagem da haste. Resultados: Os resultados foram comparados com a literatura e com os mesmos parâmetros de um artigo anterior no qual foi utilizada uma haste telescopada desenvolvida pelo nosso grupo. O estudo foi retrospectivo baseado na análise dos prontuários clínicos digitais e radiográficos dos pacientes. Quinze pacientes com 21 hastes de FD foram avaliados, sendo a maioria no fêmur (85,7%), oito pacientes eram do sexo feminino (53,3%), com média de 10,47 (3,92 a 16,44) anos, a maioria do tipo III de Sillence (46,7%), com tempo de seguimento médio de 5,22 (1,43 a 7,02) anos. Deste total, sete hastes (33,3%) apresentaram complicações. A principal indicação cirúrgica foram fraturas (57,1%). Em relação à telescopagem, observamos que 15 hastes (71,4%) acompanharam o crescimento da criança. Conclusão: No presente estudo verificamos bons resultados com as hastes de FD, à semelhança dos dados encontrados na literatura e dos dados encontrados com a haste do nosso serviço. Nível de Evidência III; Estudo retrospectivo comparativo .

Dental anomalies in individuals with osteogenesis imperfecta: a systematic review and meta-analysis of prevalence and comparative studies

Abstract Background Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as brittle bone disease. Objective This study aims to describe the prevalence of dental anomalies (except dentinogenesis imperfecta) in individuals with OI, and compare the prevalence of dental anomalies between individuals with and without OI and between individuals with different types of OI. Search methods Searches in PubMed, Web of Science, Scopus, Ovid, and gray literature were performed in October 2022. Selection criteria Observational studies (with or without a comparison group) that evaluated the prevalence of dental anomalies in individuals with OI. Data collection and analysis: Data items were extracted by two authors. Quality assessment employing the Joanna Briggs Institute checklists and meta-analyses was conducted. Results were provided in prevalence values and odds ratio (OR) / 95% confidence interval (CI). Strength of evidence was determined. Results Eighteen studies were included. Most prevalent dental anomalies in individuals with OI included pulp obliteration (46.4%), dental impaction (33.5%), dental impaction of second molars (27%), and tooth agenesis (23.9%). Individuals with OI type III/IV had 20.16-fold greater chance of exhibiting tooth discoloration in comparison with individuals with OI type I (CI: 1.10-370.98). In comparison with the group without OI, the individuals with OI had 6.90-fold greater chance of exhibiting dental impaction (CI: 1.54-31.00). High methodological quality was found in 47% of the studies. Strength of evidence was low or very low. Conclusions Pulp obliteration, dental impaction, and tooth agenesis were the most prevalent dental anomalies in the OI group. Individuals with OI were more likely to have dental impaction than individuals without OI. Individuals with OI type III/IV (severe-moderate) are more likely to have tooth discoloration than individuals with OI type I (mild).

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.

Uso de protocolos de examen radiográfico para la evaluación diagnóstica de la osteogénesis imperfecta / Use of radiographic examination protocols for diagnostic evaluation of osteogenesis imperfecta

RESUMEN La osteogénesis imperfecta (OI), también conocida como enfermedad de los huesos de cristal, es una enfermedad rara, causada principalmente por mutaciones en los genes COL1A1 y COL1A2. Aunque el 85-90% de los eventos son causados por mutaciones en el propio colágeno, las formas recesivas pueden ser el resultado de otros defectos. Dado que pueden ocurrir hallazgos similares entre la OI y otras enfermedades, es necesario un diagnóstico diferencial para una adopción más rápida de los tratamientos apropiados. Debido a la necesidad constante de exámenes, estos pacientes tienen más probabilidades de tener complicaciones por la radiación ionizante, por lo que es muy importante cumplir estrictamente con todos los requisitos de protección radiológica. OBJETIVO Verificar la existencia de protocolos de imagen utilizados en el diagnóstico de la OI y describir las técnicas radiográficas involucradas en el proceso. METODOLOGIA Se trata de un estudio cualitativo en el que se utilizaron las revistas PubMed, BIREME, CAPES y ScienceDirect, con el objetivo de verificar la presencia de investigaciones dirigidas a la creación de protocolos de imagen para auxiliar el diagnóstico de la OI. CONSIDERACIONES FINALES: Si bien ha demostrado ser de gran utilidad, debido a los riesgos a los que están expuestos los pacientes con OI, el uso de herramientas que liberan radiaciones ionizantes debe ser monitoreado constantemente. Por lo tanto, los protocolos deben revisarse para que, incluso con una reducción de la dosis, no se pierda la resolución y el detalle de la imagen.

ABSTRACT: The osteogenesis imperfecta (OI), also known as brittle bone disease, is a rare disease, mainly caused by mutations in genes COL1A1 and COL1A2. Although 85-90% of events are caused by mutations in collagen itself, the recessive forms may be the result of other defects. Since similar findings may occur between OI and other diseases, a differential diagnosis is required for faster adoption of appropriate treatments. Due to the constant need for tests, these patients are more likely to have complications due to ionizing radiation, so it is very important to strictly comply with all radiological protection requirements. OBJETIVO To verify the existence of imaging protocols used in the diagnosis of OI and to describe the radiographic techniques involved in the process. METHODOLOGY This is a qualitative study in which PubMed, BIREME, CAPES y ScienceDirect databases were used, with the objective of verifying the presence of research aimed at the creation of imaging protocols to assist in the diagnosis of OI. FINAL CONSIDERATIONS Although it has proved very useful, because of the risks to which patients with OI are exposed, the use of tools that release ionizing radiation should be monitored constantly. With this, the protocols should be reviewed so that even with a dose reduction, the resolution and detail of the image are not lost

Treatment of Malrotation and Limb Length Discrepancy in Osteogenesis Imperfecta Patients: Report of Two Cases

@#Malunion of recurrent fractures in Osteogenesis Imperfecta (OI) patients causes limb length discrepancy and malrotation. These cause added difficulty for OI patients to ambulate. Lengthening with distraction osteogenesis using an external fixator in OI patients is challenging. Acute lengthening with autologous bone graft is a known method in a normal bone but not a known procedure in OI patients. We present two clinic cases of adolescent OI patients with limb length discrepancy and externally rotated lower limb that underwent acute lengthening and rotational correction using a locked intramedullary nail and ipsilateral autologous iliac bone graft. Both patients obtained union and improvement of ambulatory capability without recurrence of fracture within five years of follow-up. Acute lengthening by 2cm and rotational correction with intramedullary nail improved the gait efficiency in the OI patients. Harvesting large amounts of the tricortical iliac bone graft, followed by controlled weight-bearing is a safe procedure.

Cuidados y atención hospitalaria en un niño con osteogénesis imperfecta

RESUMEN Introducción: La osteogénesis imperfecta es un trastorno hereditario del tejido conectivo que condiciona fragilidad ósea y susceptibilidad a fracturas. Es una enfermedad sistémica con posibilidad de afectación esquelética y extraesquelética. Su cuidado es, por tanto, multidisciplinar y el papel de los profesionales de la pediatría es primordial. Objetivo: Aportar información sobre las características y el cuidado de la osteogénesis imperfecta, a través de la descripción de un caso clínico. Pesentación del caso: Niño de 2 años y 3 meses de edad, de origen argelino y de padres consanguíneos. Fue diagnosticado en su país de origen de una forma recesiva de osteogénesis imperfecta en los primeros meses de vida por fracturas a repetición. Conclusiones: La manipulación cuidadosa, el control del dolor y el apoyo emocional, entre otros, son fundamentales. Los profesionales de pediatría, como agentes activos en estos casos, deben conocer las peculiaridades del cuidado de pacientes con osteogénesis imperfecta para evitar y detectar complicaciones asociadas. En las familias el conocimiento conlleva además, una toma de conciencia sanitaria acerca de esta enfermedad.

ABSTRACT Introduction: Osteogenesis imperfecta is an hereditary disorder of the connective tissue that conditions to bone fragility and sensitivity to fractures. It is a systemic disease with a possibility of skeletic and extraskeletic affectations. Therefore, its care is multidisciplinary and the role of Pediatrics professionals is paramount. Objective: Contribute with information on the characteristics and the care of osteogenesis imperfecta through the description of a clinical case. Case presentation: Boy of 2 years and 3 months old, from Algeria and with parents by blood. He was diagnosed in his country with a recesive osteogenesis imperfecta in the first months of life due to repeated fractures. Conclusions: Careful handling, pain control and emotional support, among others, are important. Pediatric professionals as active agents in these cases should know the peculiarities of the care of patients with osteogenesis imperfecta to avoid and detect asssociated complications. In the families, knowledge on this also entails sanitary awareness on the disease.

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

Postural balance, handgrip strength and mobility in Brazilian children and adolescents with osteogenesis imperfecta

Abstract Objective To describe postural balance, handgrip strength and mobility in children and adolescents with different types of osteogenesis imperfecta. Methods Cross-sectional study. Fifty selected subjects diagnosed with types I (n = 11), III (n = 21), and IV (n = 18), followed up at Brazilian reference center for osteogenesis imperfecta in the Midwest region, aged 2-21 years (9.2 ± 5.0), were enrolled in this study. Children and adolescents were evaluated for postural balance in the upright position with eyes-open and eyes-closed conditions, handgrip strength and the mobility domain (Pediatric Dysfunction Assessment Inventory). Data normality and difference between groups was verified. Results Handgrip strength was significantly lower in people with type III of osteogenesis imperfecta when compared to the osteogenesis imperfecta types I and IV, and to the age-specific reference data. Center of pressure length and mean velocity in the condition with eyes closed were worse compared to the open-eyes condition for children and adolescents with type I of osteogenesis imperfecta. There were worse results in the mobility domain for the participants classified with the most severe type of osteogenesis imperfecta. Conclusions It was observed that the severity of the osteogenesis imperfecta disease affected handgrip strength and locomotor function assessed by the mobility domain. Comparing osteogenesis imperfecta types, the higher the severity of osteogenesis imperfecta, the lower the handgrip strength. These results can contribute to new strategies of treatment focused on improving functional capacity and quality of life in people with osteogenesis imperfecta.

Osteogénesis imperfecta: Diagnóstico y manejo de una enfermedad huérfana en un hospital regional peruano. A propósito de un caso

La osteogénesis imperfecta es una enfermedad rara de herencia autosómica dominante en la cual existen anomalías en la síntesis o degradación del colágeno que afecta al tejido conectivo ocasionando múltiples fracturas. Neonato femenino, a término 38 semanas, nacido por cesarea, procedente de Pichari, ingres6 por cuadro de dificultad respiratoria instalada durante atención inmediata. Al examen físico se palpa crepitaciones en articulaciones. La paciente fue diagnosticada de osteogénesis imperfecta en base a los hallazgos clínicos y de imágenes, al carecer de evaluaciones genéticas.

SUMMARY Osteogenesis imperfecta is a rare autosome dominant disease in which there are anomalies in the synthesis of collagen affecting the connective tissue leading to multiple fractures. We present the case of a 38-week newborn from Pichari born of a cesarean section who presented respiratory failure. The patient presented crackles on the joints and was diagnosed on clinical grounds of osteogenesis imperfecta.

Tratamiento integral y control a 12 años de paciente con Dentinogénesis Imperfecta tipo I / Manejo clínico e seguimento de 12 anos em paciente com Dentinogênese Imperfeita tipo I / Clinical management and 12 years follow up in a patient with Dentinogenesis Imperfecta type I

La Dentinogénesis Imperfecta 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 12 años de un paciente de 3 años de edad al momento de la consulta, con diagnóstico de Dentinogénesis Imperfecta tipo I asociada a Osteogénesis Imperfecta tipo IB. La identificación temprana de esta entidad y el tratamiento oportuno y multidisciplinario, contribuyen a mejorar el pronóstico de la misma.

Dentinogênese Imperfeita é uma anormalidade dentária geneticamente determinada, caracterizada clinicamente pela aparência opalescente e translúcida da dentina. Manejo clínico e seguimento de 12 anos são relatados, em um paciente de 3 anos com Dentinogênese Imperfeita tipo I associado à Osteogenesis Imperfecta tipo IB. O diagnóstico precoce.

Dentinogenesis Imperfecta is a geneti-cally determinated dental abnormality, characterized clinically by opalescent and translucent appearance of the den-tin. Clinical management and a 12 years follow up are reported, in a 3 years old patient with Dentinogenesis Imperfecta type I associated with Osteogenesis Im-perfecta type IB. The earlier diagnosis and the opportune and multidisciplinary treatment, led to improve the prognosis.

Análise orofacial de indivíduos com Osteogênese Imperfeita: índices radiomorfométricos, dimensão fractal do osso mandibular e má oclusão / Orofacial analysis of individuals with Osteogenesis Imperfecta: radiomorphometric indices, fractal dimension of the mandibular bone and malocclusion

A Osteogênese Imperfeita (OI) é uma doença genética rara, caracterizada por ossos frágeis com fraturas recorrentes. Na maioria dos casos a OI, é causada por mutações nos genes COL1A1 ou COL1A2 os quais codificam o colágeno tipo I. Mutações em novos genes envolvidos na via do metabolismo ósseo têm sido descobertas. A OI está associada a alterações dentárias e craniofaciais, sendo as mais prevalentes a dentinogênese imperfeita e a má oclusão. A literatura tem mostrado que é possível predizer o risco de fratura óssea ao analisarmos índices radiomorfométricos e dimensão fractal (DF) da mandíbula em radiografias panorâmicas. O objetivo desta pesquisa foi verificar se há diferenças no padrão de oclusão, na cortical e no trabeculado ósseo mandibular de indivíduos com OI quando comparados com indivíduos sem OI. Desse modo, a tese conta com a apresentação de dois artigos científicos. O primeiro artigo objetivou analisar dois índices radiomorfométricos, o índice cortical mandibular (ICM) e o índice mentual (IM), e a DF do trabeculado ósseo mandibular de indivíduos com OI e comparar com indivíduos sem OI. Foi realizado um estudo transversal, pareado por idade e sexo, com 20 indivíduos com OI e 40 sem OI. Os dados foram obtidos por meio de radiografias panorâmicas de pacientes com OI e sem OI atendidos na Faculdade de Odontologia da Universidade Federal de Minas Gerais. O estudo foi aprovado pelo Comitê de Ética em Pesquisa da UFMG (protocolo 02470518.3.0000.5149). O teste t pareado (p <0,05) foi usado para comparar os valores de IM e DF. O teste do qui-quadrado (p <0,05) comparou o ICM entre os grupos. A média de idade de ambos os grupos foi 13,10 anos (± 6,57). O valor médio do IM foi de 2.08 (±0.79) no grupo de indivíduos com OI e 2.91 (±0.60) para indivíduos sem OI (p<0,001). O valor médio de DF do grupo OI [0.3248 (±0.7240)] foi inferior ao do grupo sem OI [0.3814 (±0.5587)] no côndilo mandibular (p=0,002). O grau C3 do ICM foi mais frequente entre os indivíduos com OI (p <0,001). Indivíduos com OI apresentaram valores menores nos IM e DF, além de pior morfologia da cortical mandibular. O segundo artigo, uma revisão sistemática e meta-análise (já publicada), objetivou avaliar se indivíduos com OI são mais afetados por má oclusão do que indivíduos normotípicos. Foi realizada uma busca nas principais bases. A avaliação do risco de viés e a análise da força de evidência foram conduzidas. Em comparação com indivíduos sem OI, o grupo com OI teve 19,69 vezes mais chance de apresentar má oclusão de Classe III de Angle (OR = 19,69, IC: 9,00­43,09) e apresentar maior mordida cruzada anterior (MD = 6,08, CI: 2,40­9,77). Indivíduos sem OI tiveram um ângulo ANB (MD= 3,88, IC: 1,15­6,61) e ângulo SNA (MD = 2,11, IC: 0,24­3,98) significativamente maiores em comparação com indivíduos com OI. Nenhuma diferença entre os grupos foi encontrada para SNB (MD = −0,50, IC: −2,21 a 1,21) e mordida aberta (MD = 0,98, IC: −0,29 a 2,25). A maioria dos estudos incluídos teve qualidade metodológica moderada. A força da evidência foi baixa ou muito baixa. A ocorrência de má oclusão Classe III de Angle e mordida cruzada anterior foi maior entre os indivíduos com OI em comparação com aqueles sem OI.

Osteogenesis Imperfecta (OI) is a rare genetic disease characterized by fragile bones with recurrent fractures. In most cases, OI is caused by mutations in the COL1A1 or COL1A2 genes which encode type I collagen. Mutations in new genes involved in the bone metabolism pathway have been discovered. OI is associated with dental and craniofacial alterations, the most prevalent being dentinogenesis imperfecta and malocclusion. The literature has shown that it is possible to predict the risk of bone fracture when analyzing radiomorphometric indices and fractal dimension (FD) of the mandible in panoramic radiographs. The objective of this research was to verify if there are differences in the occlusion pattern, in the cortical and in the mandibular bone trabeculate of individuals with OI when compared to individuals without OI. Thus, the thesis has the presentation of two scientific articles. The first article aimed to analyze two radiomorphometric indices, the mandibular cortical index (MCI) and the mentual index (MI), and the FD of the mandibular bone trabeculate of individuals with OI and compare with individuals without OI. A cross-sectional study, matched by age and sex, was carried out with 20 individuals with OI and 40 without OI. Data were obtained through panoramic radiographs of patients with OI and without OI treated at the Faculty of Dentistry of the Federal University of Minas Gerais. The study was approved by the Research Ethics Committee at UFMG (protocol 02470518.3.0000.5149). Paired t-test (p < 0.05) was used to compare MI and DF values. The chi-square test (p < 0.05) compared the ICM between groups. The mean age of both groups was 13.10 years (± 6.57). The mean value of MI was 2.08 (±0.79) in the group of individuals with OI and 2.91 (±0.60) for individuals without OI (p<0.001). The mean FD value of the OI group [0.3248 (±0.7240)] was lower than that of the group without OI [0.3814 (±0.5587)] in the mandibular condyle (p=0.002). ICM grade C3 was more frequent among individuals with OI (p<0.001). Individuals with OI had lower MI and DF values, in addition to worse mandibular cortical morphology. The second article, a systematic review and meta-analysis (already published), aimed to assess whether individuals with OI are more affected by malocclusion than normotypic individuals. A search was carried out in the main bases. Risk of bias assessment and strength of evidence analysis were conducted. Compared with individuals without OI, the group with OI was 19.69 times more likely to have Angle Class III malocclusion (OR = 19.69, CI: 9.00­ 43.09) and to have greater anterior crossbite (MD = 6.08, CI: 2.40­9.77). Subjects without OI had a significantly greater ANB angle (MD= 3.88, CI: 1.15­6.61) and SNA angle (MD= 2.11, CI: 0.24­3.98) compared to subjects with hi. No difference between groups was found for SNB (MD = −0.50, CI: −2.21 to 1.21) and open bite (MD = 0.98, CI: −0.29 to 2.25). Most of the included studies were of moderate methodological quality. The strength of the evidence was low or very low. The occurrence of Angle Class III malocclusion and anterior crossbite was higher among individuals with OI compared to those without OI.

Indivíduos com doenças genéticas raras que afetam o desenvolvimento esquelético: vulnerabilidade aos problemas bucais / Individuals with rare genetic diseases that affect skeletal development: vulnerability to oral problems

Os indivíduos com doenças genéticas raras podem apresentar alterações no sistema nervoso e/ou musculoesquelético, inclusive comprometimento cognitivo, distúrbios neuropsicomotores, más formações craniofaciais e alterações oclusais e dentárias. Posição alterada dos dentes na arcada, alterações na estrutura óssea e na formação dentária, quando associadas a uma dieta cariogênica e a uma escovação deficiente, podem atuar como fatores predisponentes às doenças cárie e gengivite. As Mucopolissacaridoses (MPS) e a Osteogênese Imperfeita (OI) são doenças raras que afetam o desenvolvimento esquelético. Alterações físicas e motoras presentes na maioria dos indivíduos com essas doenças podem aumentar a dificuldade para realização da higiene bucal. Além disso, o desconhecimento de grande parte dos cirurgiões-dentistas em relação às doenças genéticas raras, dificulta muito o acesso dessa parcela da população para atendimento odontológico tanto na rede pública quanto na rede privada. Isso torna esses indivíduos mais vulneráveis aos problemas bucais quando comparados a indivíduos com outras deficiências e à população normotípica. O objetivo da pesquisa foi comparar indivíduos brasileiros com doenças genéticas raras com envolvimento esquelético e indivíduos sem doenças raras em relação à prevalência de problemas bucais. Além disso, objetivou-se sintetizar as modalidades do tratamento ortodôntico e da cirurgia ortognática para correção da má oclusão em indivíduos com OI. Desse modo, a tese conta com a apresentação de dois artigos científicos, sendo um estudo transversal e uma revisão sistemática. O artigo 1 objetivou comparar a prevalência de problemas bucais de indivíduos brasileiros com doenças genéticas raras que afetam o desenvolvimento esquelético e indivíduos sem doenças raras. Foi realizado um estudo transversal, pareado por idade e sexo, com 210 indivíduos [105 com doença genética rara: MPS (n=27) / OI (n=78) e 105 sem doença rara], na faixa etária de dois a 57 anos e os pais/responsáveis. O grupo com doenças raras foi recrutado em ambulatórios médicos de serviços especializados ou de referência em doenças genéticas raras, de cinco estados brasileiros (Ceará, Espírito Santo, Minas Gerais, Rio de Janeiro e São Paulo). Os indivíduos sem doença rara foram recrutados em outros ambulatórios dos mesmos hospitais. Os grupos foram examinados quanto a má oclusão, anomalias dentárias, cárie dentária e gengivite. Os pais/responsáveis responderam um questionário sobre aspectos individuais, sociodemográficos, comportamentais, história médica e odontológica dos indivíduos com doença rara e sem doença rara. O Directed Acyclic Graph (DAG) foi utilizado para identificar possíveis variáveis de confusão. O estudo foi aprovado pelo Comitê de Ética em Pesquisa (CEP) da Universidade Federal de Minas Gerais (CAAE 01480212.4.0000.5149 [MPS] / CAAE 54755516.4.0000.5149 [OI]). Foi realizada a análise descritiva e modelos de regressão logística binária não-ajustados e ajustados (Odds Ratio, método Conditional Backward, IC95%). A média de idade dos indivíduos examinados foi de 14,2 anos (± 12,3). No modelo final permaneceram as variáveis doença genética rara, cor da pele e renda familiar. Apenas a variável doença genética rara foi associada com os problemas bucais. Indivíduos com doença genética rara apresentaram 12,9 vezes mais chance de ter algum problema bucal (IC95% 3,7- 44,7), em comparação com indivíduos sem doença rara. Concluiu-se que indivíduos com doença genética rara apresentaram maior prevalência de problemas bucais quando comparados a indivíduos sem doença rara. O artigo 2 objetivou sintetizar, por meio de uma revisão sistemática, as modalidades de tratamento ortodôntico, cirurgia ortognática e a combinação de ambos os tratamentos, para a correção de má oclusão em indivíduos com OI. A busca em bases de dados identificou 22 artigos, contabilizando 28 casos clínicos. A má oclusão foi considerada grave em 11 casos, com registros de overjet negativo entre 9 e 26 mm. O tratamento ortodôntico foi realizado em quatro casos, a cirurgia ortognática em cinco e o tratamento ortodôntico associado à cirurgia ortognática em 19 casos. Concluiu-se que o tratamento das más oclusões é viável em indivíduos com OI. Quando devidamente indicado, esse tratamento pode proporcionar resultados estéticos e funcionais satisfatórios e com estabilidade adequada.

Individuals with rare genetic diseases may present changes in the nervous and/or musculoskeletal system, including cognitive impairment, neuropsychomotor disorders, craniofacial malformations, and occlusal and dental changes. Altered tooth position in the arch, changes in bone structure and tooth formation, when associated with a cariogenic diet and poor brushing, can act as predisposing factors for caries and gingivitis. Mucopolysaccharidoses (MPS) and Osteogenesis Imperfecta (OI) are rare diseases that affect skeletal development. Physical and motor changes present in most individuals with these diseases can increase the difficulty in performing oral hygiene. In addition, the lack of knowledge of most dentists about rare genetic diseases makes it very difficult for this portion of the population to have access to dental care in both the public and private networks. This makes these individuals more vulnerable to oral problems when compared to individuals with other disabilities and the normotypical population. The aim of the study was to compare Brazilian individuals with rare genetic diseases with skeletal involvement and individuals without rare diseases about the prevalence of oral problems. The other aim was to synthesize the modalities of orthodontic treatment and orthognathic surgery to correct malocclusion in individuals with OI. Thus, the thesis has the presentation of two scientific articles, being a cross- sectional study and a systematic review. Article 1 aimed to compare the prevalence of oral problems in Brazilian individuals with rare genetic diseases that affect skeletal development and individuals without rare diseases. A cross-sectional study, paired by age and sex, was carried out with 210 individuals [105 with rare genetic disease: MPS (n=27) / OI (n=78) and 105 without rare disease], aged from two to 57 years and parents/guardians. The group with rare diseases was recruited from medical clinics of specialized or reference services in rare genetic diseases, in five Brazilian states (Ceará, Espírito Santo, Minas Gerais, Rio de Janeiro and São Paulo). Individuals without rare diseases were recruited from other outpatient clinics in the same hospitals. The groups were examined for malocclusion, dental anomalies, tooth decay and gingivitis. Parents/guardians answered a questionnaire on the individual, sociodemographic, behavioral, medical and dental history of individuals with rare diseases and without rare diseases. Directed Acyclic Graph (DAG) was used to identify possible confounding variables. The study was approved by the Research Ethics Committee (CEP) of the Federal University of Minas Gerais (CAAE 01480212.4.0000.5149 [MPS] / CAAE 54755516.4.0000.5149 [OI]). Descriptive analysis and unadjusted and adjusted binary logistic regression models were performed (Odds Ratio, Conditional Backward method, 95%CI). The average age of the individuals examined was 14.2 years (± 12.3). The variables rare genetic disease, skin color and family income remained in the final model. Only the rare genetic disease variable was associated with oral problems. Individuals with a rare genetic disease were 12.9 times more likely to have an oral problem (95%CI 3.7-44.7), compared to individuals without a rare disease. It was concluded that individuals with a rare genetic disease had a higher prevalence of oral problems when compared to individuals without a rare disease. Article 2 aimed to synthesize, through a systematic review, the modalities of orthodontic treatment, orthognathic surgery and the combination of both treatments for the correction of malocclusion in individuals with OI. The search in databases identified 22 articles, accounting for 28 clinical cases. Malocclusion was considered severe in 11 cases, with negative overjet recordings between 9- and 26- mm. Orthodontic treatment was performed in four cases, orthognathic surgery in five, and orthodontic treatment associated with orthognathic surgery in 19 cases. It was concluded that the treatment of malocclusions is feasible in individuals with OI. When properly indicated, this treatment can provide satisfactory aesthetic and functional results and with adequate stability.