Generation of skin-derived iPSCs from an Osteogenesis imperfecta patient carrying WNT1c.677C>T mutation / 中华医学遗传学杂志

OBJECTIVE@#To obtain skin-derived induced pluripotent stem cells (iPSCs) from an Osteogenesis imperfecta (OI) patient carrying WNT1c.677C>T mutation in order to provide a new cell model for investigating the underlying molecular mechanism and stem cell therapy for OI.@*METHODS@#The pathogenic variant of the patient was identified by Sanger sequencing. With informed consent from the patient, skin tissue was biopsied, and primary skin fibroblasts were cultured. Skin fibroblasts were induced into iPSCs using Sendai virus-mediated non-genomic integration reprogramming method. The iPSC cell lines were characterized for pluripotency, differentiation capacity, and karyotyping assay.@*RESULTS@#The patient was found to carry homozygous missense c.677C>T (p.Ser226Leu) mutation of the WNT1 gene. The established iPSC lines possessed self-renewal and capacity for in vitro differentiation. It also has a diploid karyotype (46,XX).@*CONCLUSION@#A patient-specific WNT1 gene mutation (WNT1c.677C>T) iPSC line was established, which can provide a cell model for the study of OI caused by the mutation.

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.

Analysis of COL1A1 and COL1A2 gene variants in two fetuses with osteogenesis imperfecta / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of two fetuses with an osteogenesis imperfecta (OI) phenotype.@*METHODS@#Two fetuses diagnosed at the Affiliated Hospital of Weifang Medical College respectively on June 11, 2021 and October 16, 2021 were selected as the study subjects. Clinical data of the fetuses were collected. Amniotic fluid samples of the fetuses and peripheral blood samples of their pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing (WES) and Sanger sequencing were carried out to identify the candidate variants. Minigene splicing reporter analysis was used to validate the variant which may affect the pre-mRNA splicing.@*RESULTS@#For fetus 1, ultrasonography at 17+6 weeks of gestation had revealed shortening of bilateral humerus and femurs by more than two weeks, in addition with multiple fractures and angular deformities of long bones. WES revealed that fetus 1 had harbored a heterozygous c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in exon 49 of the COL1A1 gene (NM_000088.4). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting) for disrupting the downstream open reading frame resulting in premature translational termination, being de novo in origin, and lacking records in the population and disease databases.For fetus 2, ultrasonography at 23 weeks of gestation also revealed shortening of bilateral humerus and femurs by one and four weeks, respectively, in addition with bending of bilateral femurs, tibias and fibulas. Fetus 2 had harbored a heterozygous c.1557+3A>G variant in intron 26 of the COL1A2 gene (NM_000089.4). Minigene experiment showed that it has induced skipping of exon 26 from the COL1A2 mRNA transcript, resulting in an in-frame deletion (c.1504_1557del) of the COL1A2 mRNA transcript. The variant was inherited from its father and had been previously reported in a family with OI type 4. It was therefore classified as a pathogenic variant (PS3+PM1+PM2_Supporting+PP3+PP5).@*CONCLUSION@#The c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in the COL1A1 gene and c.1557+3A>G variant in the COL1A2 gene probably underlay the disease in the two fetuses. Above findings not only have enriched the mutational spectrum of OI, but also shed light on the correlation between its genotype and phenotype and provided a basis for genetic counseling and prenatal diagnosis for the affected pedigrees.

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

Analysis of LRP5 gene variants in a Chinese pedigree affected with Osteoporosis-pseudoglioma syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree with two individuals suffering from congenital blindness.@*METHODS@#Clinical data and peripheral blood samples of the pedigree were collected. Whole exome sequencing was carried out. Suspected variants were verified by Sanger sequencing. Pathogenicity of candidate variants was validated through searching of PubMed and related databases, and analyzed with bioinformatics software.@*RESULTS@#Both patients had congenital blindness and a history of multiple fractures. Other features have included microphthalmia and cornea opacity. One patient had normal intelligence, whilst the other had a language deficit. Both patients were found to harbor compound heterozygous variants of the LRP5 gene, namely c.1007_1015delGTAAGGCAG (p.C336X), c.4400G>A (p.R1467Q) and c.4600C>T (p.R1534X). The first one was derived from their mother, whilst the latter two were derived from their father. None of the three variants was detected in their elder sister.@*CONCLUSION@#The compound heterozygous variants of c.1007_1015delGTAAGGCAG (p.C336X) and c.4600C>T (p.R1534X) of the LRP5 gene probably underlay the pathogenesis of the Osteoporosis-pseudoglioma syndrome in this pedigree. The clinical significance of the c.4400G>A (p.R1467Q) variant has remained uncertain. Above finding has enriched the mutational spectrum of Osteoporosis-pseudoglioma syndrome.

Identification of pathogenic variant and preimplantation genetic testing for a Chinese family affected with osteogenesis imperfecta / 中华医学遗传学杂志

OBJECTIVE@#To identify the pathogenic variant for a husband with osteogenesis imperfecta and provide preimplantation genetic testing (PGT) for the couple.@*METHODS@#High-throughput sequencing and Sanger sequencing were carried out to identify the pathologic variant in the husband patients. PGT of embryos was performed through direct detection of the mutation site. Meanwhile, chromosome aneuploidy of the blastocysts was screened. Following transplantation, cytogenetic and genetic testing of fetal amniotic fluid sample was carried out during mid-pregnancy. Chromosome copy number variant (CNV) was detected at multiple sites of the placenta after delivery.@*RESULTS@#The husband was found to harbor heterozygous c.544-2A>G variant of the COL1A1 gene. The same variant was not detected in either of his parents. PGT revealed that out of three embryos of the couple, one was wild-type for the c.544-2A site but mosaicism for duplication of 16p13.3.11.2. The other two embryos were both heterozygous for the c.544-2A>G variant. Following adequate genetic counseling, the wild-type embryo was transplanted. Amniotic fluid testing confirmed that the fetus had normal chromosomes and did not carry the c.544-2A>G variant. The copy number of chromosomes at different parts of placenta was normal after birth.@*CONCLUSION@#For couples affected with monogenic disorders, e.g., osteogenesis imperfecta, direct detection of the mutation site may be used for PGT after identifying the pathogenic variant. After adequate genetic counseling, prenatal diagnosis must be carried out to ensure the result.

Repetitive stress fracture: a warning sign of genetic susceptibility to fracture? A case report of a heterozygous variant in SERPINF1

SUMMARY The occurrence of fractures in young individuals is frequently overlooked by physicians, especially when associated with exercise or trauma. Nevertheless, multiple fractures should always be investigated since underlying conditions can predispose to such events. We describe here the case of a young, healthy woman who sustained multiple fractures in the lower limbs, which were initially considered to be "stress fractures". Further investigation, including a panel of genes associated with osteogenesis imperfecta, revealed that the patient is a heterozygous carrier of a SERPINF1 variant. According to criteria recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, this variant is classified as likely benign (PM2, PP3, PP4, BP1, and BP4). The patient's mother and brother were also asymptomatic carriers of the variant and had sustained previous minor fractures. The patient had normal biochemical profile and bone density. This condition has been rarely described and is not associated with low bone mineral density or altered bone turnover markers. This case highlights the importance of investigating multiple fractures in young patients who are otherwise healthy since these may be a warning sign of rare genetic conditions associated with fragility fractures.

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.

Preimplantation genetic testing for a couple where the husband is affected by osteogenesis imperfecta combined with balanced translocation using karyomapping technique / 中华医学遗传学杂志

OBJECTIVE@#To carry out preimplantation genetic testing (PGT) for a couple where the husband was affected by osteogenesis imperfecta combined with balanced translocation using the karyomapping technique.@*METHODS@#Blastocysts were detected using karyomapping, the carrier status of COL1A1 c.760G>A (p.Gly254Arg) variant and the carrier status of the translocated chromosome were analyzed simultaneously.@*RESULTS@#For a total of 10 blastocysts, two euploid blastocysts were found to not carry the COL1A1 c.760G>A (p.Gly254Arg) variant but a balanced translocation. After transplanting one of the blastocysts, clinical pregnancy was achieved. Amniocentesis at 18th gestational week and prenatal genetic testing was in keeping with the result of PGT.A healthy female was born at 40+4 weeks gestation.@*CONCLUSION@#For patients simultaneously carrying genetic variant and balanced chromosomal translocation, PGT can be performed with efficiency by the use of karyomapping method.

Analysis of COL1A1 gene variation and clinical prevention and treatment in patients with Van der Hoeve syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinical phenotype, treatment and prevention of Van der Hoeve syndrome, and analyze the variation characteristics of its related gene COL1A1. Methods: Hearing and sequencing data of syndromic deafness patients who had undergone genetic testing for deafness at the Chinese People's Liberation Army General Hospital since January 2008 to October 2020 were retrospectively reviewed. The variation of the COL1A1 gene and return visits to traceable patients and families were summarized, the disease progress and clinical treatment effects were analyzed, and the prevention strategies were discussed. Results: A total of 7 patients with COL1A1 gene mutation underwent clinical intervention. The mutation sites were c.1342A>T (p.Lys448*), c.124C>T (p.Gln42*), c.249insG(p.Ala84*), c.668insC(p.Gly224*), c.2829+1G>C, c.1081C>T (p.Arg361*), c.1792C>T (p.Arg598*), of which c.1081C>T and c.1792C>T had been previously reported, and the remaining 5 were novo mutations that have not been reported. All the 7 probands underwent stapes implantation and received genetic counseling and prevention guidance. Conclusions: Van der Hoeve syndrome belongs to osteogenesis imperfecta type Ⅰ. The disease has high penetrance. Timely surgical intervention for hearing loss can improve the life quality in patients. Accurate genetic counseling and preimplantation genetic diagnosis can achieve the primary prevention for the disease.

Qualidade de vida dos cuidadores de crianças/adolescentes vinculados ao Centro de Referência em Osteogênese Imperfeita do Rio de Janeiro no ano COVID-19 / Quality of life of caregivers of children/adolescents linked to the Reference Center for Osteogenesis Imperfecta in Rio de Janeiro in the year COVID-19

Introdução: A Osteogênese Imperfeita é uma doença crônica, caraterizada pela fragilidade óssea e fraturas recorrentes, que evoluem em deformidades ósseas e limitações funcionais. Devido a isto, as crianças e adolescentes com a doença, precisam de um cuidador que os auxilie em suas atividades básicas da vida diária. Embora toda a família seja afetada pela situação, é o integrante que assume o rol de cuidador quem sofre maior impacto na sua vida, pois ele abnega de outras atividades e projetos pessoais para dedicar se ao cuidado da criança. Além disto, geralmente ele está envolvido em outras tarefas; este acúmulo de tarefas contribui para a sobrecarga do cuidador, afetando diretamente a sua vida pessoal, social e familiar, e consequentemente influenciando de forma direta a sua qualidade de vida. Objetivo: Avaliar a qualidade de vida e sobrecarga de cuidadores de crianças e adolescentes com osteogênese imperfeita durante a pandemia de COVID 19.Metodologia: Trata-se de uma pesquisa analítica de abordagem quantitativa do tipo transversal, que foi realizada no Centro de Referência em Osteogênese Imperfeita do Instituto Nacional Fernandes Figueira. Participaram deste estudo 64 cuidadores cadastrados, que responderam via telefônica, o questionário socioeconômico e demográfico, o WHOQOL-bref e o Zarit Burden Interview. Os dados foram analisados pelos testes não paramétricos: exato de Fischer, Mann-Whitney, Kruskal-Wallis; e, regressão linear múltipla, via software SPSS, versão 21.0. Resultados: A sobrecarga foi associada a classe social e rotina de sobrecarga modificada na pandemia. Houve correlação inversa entre sobrecarga e todos os domínio de qualidade de vida. No modelo final da regressão linear múltipla, o domínio Físico foi associado a frequência religiosa, quantidade de dependentes, presença de cuidador secundário, regime terapêutico e sobrecarga; o domínio Psicológico à classe social, rotina de sobrecarga modificada na pandemia e o fator de sobrecarga impacto na prestação de cuidados; o domínio Relações Sociais a grau de instrução, trabalho remunerado, classe social, frequência religiosa, faixa etária da criança e sobrecarga; o domínio Meio Ambiente à faixa etária do cuidador, grau de instrução, presença de cuidador secundário, rotina de sobrecarga modificada na pandemia, regime terapêutico, nível de dependência da criança e o fator de sobrecarga percepção de auto eficácia. Considerações Finais: A incorporação do cuidador no plano de cuidados é um grande desafio para o sistema de saúde brasileiro, para isto as equipes de saúde devem criar estratégias que considerem o cuidador como um receptor dos cuidados, minimizando os impactos negativos do cuidar.

Introduction: Osteogenesis Imperfecta is a chronic disease, characterized by bone fragility and recurrent fractures, which evolve into bone deformities and functional limitations. Because of this, children and adolescents with the disease need a caregiver to assist them in their basic activities of daily living. Although the whole family is affected by the situation, it is the member who assumes the role of caregiver who suffers the greatest impact on his/her life, as he/she abandons other activities and personal projects to dedicate himself/herself to the care of the child. In addition, he/she is usually involved in other tasks; this accumulation of tasks contributes to the caregiver's burden, directly affecting his/her personal, social and family life, and consequently directly influencing quality of life. Objective: To evaluate the Quality of Life and burden of caregivers of children/adolescents with Osteogenesis Imperfecta associated with socioeconomic, demographic and clinical characteristics, during the pandemic of COVID-19. Methodology: This is an analytical research with a quantitative approach of the transversal type, which was performed at the Reference Center for Osteogenesis Imperfecta of the Fernandes Figueira National Institute. 64 registered caregivers participated in this study, who answered via telephone, the socioeconomic and demographic questionnaire, the WHOQOL-bref and the Zarit Burden Interview. The data were analyzed by non-parametric tests: Fischer's exact, Mann-Whitney, Kruskal-Wallis; and, multiple linear regression, via SPSS software, version 21.0. Results: Overload was associated with social class and modified overload routine in the pandemic. There was an inverse correlation between overload and all quality of life domains. In the final model of multiple linear regression, the Physical domain was associated with religious frequency, number of dependents, presence of secondary caregiver, therapeutic regime and burden; the psychological domain to the social class, modified overload routine in the pandemic and the overload factor impact on the provision of care; the Social Relations domain in terms of education level, paid work, social class, religious frequency, child's age and overload; the Environment domain to the caregiver's age, education level, presence of secondary caregiver, modified overload routine in the pandemic, therapeutic regime, child's level of dependence and the perceived self-efficacy overload factor. Final Considerations: The incorporation of the caregiver in the care plan is a major challenge for the Brazilian health system, for which the health teams must create strategies that consider the caregiver as a receiver of care, minimizing the negative impacts of care.

Trajetórias afetivo-sexuais de jovens e adultos com osteogênese imperfeita / Affective-sexual trajectories of young people and adults with osteogenesis imperfecta

O presente estudo tem como objetivo geral estudar as trajetórias afetivo-sexuais de jovens e adultos homens e mulheres com osteogênese imperfeita (OI). Considerando que a juventude é uma etapa da vida onde as relações de afetividade e sexualidade passam a ser mais significativas e onde a autonomia desses sujeitos é fundamental nessas relações. Trata-se de uma pesquisa de natureza qualitativa, o campo de pesquisa foi o ambulatório de osteogênese imperfeita do Instituto Estadual de Diabetes e Endocrinologista (IEDE). O método utilizado para a coleta de dados foi o de história de vida de 18 a 49 anos, com posterior análise temática proposta por Bardin. Foram convidados 16 jovens, dos quais quatro se recusaram a participar. Perfazendo um total de 12 entrevistas. Para os resultados emergiram quatro núcleos temáticos : 1) A Construção da masculinidade e da feminilidade no contexto da deficiência; 2) Dependência x independência: a questão da autonomia e suas implicações nas trajetórias afetivo-sexuais; 3) Vida afetiva, sexual e reprodução: entre medos e desejos; 4) O papel da internet e das redes sociais digitais na sexualidade das pessoas com osteogênese imperfeita. As conclusões deste estudo apontam para a necessidade de desconstruções dos padrões normativos impostos ao corpo; a superproteção por parte dos pais repercute negativamente nas relações afetivas e sexuais das pessoas com OI; as pessoas com OI tem dificuldade em conversar sobre sexualidade com os pais e com os profissionais de saúde; a internet acaba por se tornar uma ferramenta bastante utilizada para suprir a necessidade dessas informações; espaços coletivos de discussão com pessoas que enfrentam as mesmas questões são muito importantes; também verificou-se a necessidade de políticas públicas voltada para a sexualidade da pessoa com deficiência.

The present study sought to know the affective-sexual trajectories of young and adult men and women with osteogenesis imperfecta (OI). Considering that youth is a stage of life where the relationships of affection and sexuality become more significant and where the autonomy of these subjects is fundamental in these relationships. It is a qualitative research, the research field was the outpatient osteogenesis imperfect of the State Institute of Diabetes and Endocrinologist (IEDE). The method used for data collection was life history from 18 to 49 years, with subsequent thematic analysis proposed by Bardin. 16 young people were invited, of whom four refused to participate. Making a total of 12 interviews. For the results, four thematic groups emerged: 1) The construction of masculinity and femininity in the context of disability; 2) Dependency x independence: the question of autonomy and its implications for affective-sexual trajectories; 3) Affective, sexual and reproductive life: between fears and desires; 4) The role of the internet and digital social networks in the sexuality of people with imperfect osteogenesis. The conclusions of this study point to the need to deconstruct the normative standards imposed on the body; overprotection on the part of parents has a negative impact on the affective and sexual relationships of people with OI; people with OI find it difficult to talk about sexuality with parents and health professionals; the internet turns out to be a widely used tool to supply the need for this information; collective spaces for discussion with people who face the same issues are very important; there was also a need for public policies aimed at the sexuality of people with disabilitie.

Atividade e participação de crianças e adolescentes com osteogênese imperfeita segundo a Classificação Internacional de Funcionalidade, Incapacidade e Saúde: perfil de incapacidade / Activity and participation of children and adolescents with osteogenesis imperfecta according to the International Classification of Functioning, Disability and Health: disability profile

A osteogênese imperfeita (OI) é um grupo de condições raras que gera repercussões no tecido conjuntivo caracterizada principalmente por fragilidade óssea, afetando o sistema locomotor e levando a disfunções nas estruturas e funções do corpo, consequentemente, interferindo nas suas atividades e participação social. O objetivo deste estudo foi descrever o perfil de funcionalidade pela Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF), sob o enfoque de atividades e participação de crianças e adolescentes com OI. A pesquisa foi do tipo transversal, de caráter observacional e descritivo. Foi realizada uma entrevista estruturada aplicada pelo pesquisador através de questionário baseado em lista reduzida da CIF para a população com OI, com 31 responsáveis/ pacientes apresentando as formas intermediária e grave de OI (48,3% do tipo 3 e 51,6% do tipo IV), com idade mediana de 12 anos (7-22), atendidos no Centro de Referência para tratamento de Osteogênese Imperfeita do Rio de Janeiro, localizado no Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (CROI-IFF). Observamos nesta pesquisa, que, muitos pacientes tiveram limitações em diversas atividades básicas da vida diária, o que ficou ainda mais evidente no capítulo de mobilidade que destacou a dificuldade desses indivíduos em sua locomoção. Mesmo em indivíduos mais velhos houve limitações em atividades como: preparar sua própria refeição e atividades da vida doméstica, o que evidencia a dependência deles em sua vida diária. Foi evidente em muitos indivíduos da amostra a restrição na participação em grande parte das variáveis do capítulo da vida comunitária, social e física. Com a descrição da prevalência de incapacidade relacionada aos domínios de atividade e participação, segundo a CIF, de crianças e adolescentes com os tipos. Com a descrição da prevalência de incapacidade relacionada aos domínios de atividade e participação, segundo a CIF, de crianças e adolescentes com os tipos mais graves de OI, podemos observar que além de apresentarem déficits em funções e estruturas do corpo, muitos também tiveram limitações em atividades e restrições na participação social. Os capítulos que demonstraram maior prevalência de incapacidade foram: "Mobilidade", "autocuidado", "atividades da vida doméstica" e "vida comunitária, social e física". O que ressalta a importância no manejo destes pacientes através do cuidado multiprofissional continuado com abordagem interdisciplinar, podendo refletir em ações de promoção de saúde, prevenção de danos, educação permanente, tratamento e reabilitação.

Osteogenesis imperfecta (OI) is a group of rare conditions that generate repercussions on the connective tissue, mainly characterized by bone fragility, affecting the locomotors system and leading to dysfunctions in body structures and functions, consequently interfering with their activities and social participation. The aim of this study was to describe the functionality profile according to the International Classification of Functioning, Disability and Health (ICF), under the focus of activities and participation of children and adolescents with OI. The research was cross-sectional, observational and descriptive. A structured interview was conducted by the researcher through a questionnaire based on a short list of the ICF for the population with OI, with 31 guardians/patients presenting the intermediate and severe forms of OI (48.3% of type 3 and 51.6% of the type IV), with a median age of 12 years (7-22), treated at the Centro de Referência para tratamento de Osteogênese Imperfeita do Rio de Janeiro, located in Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (CROI-IFF). We observed in this research that many patients have limitations in basic activities of daily living, which was even more evident in the chapter on mobility, which highlighted the necessary difficulty in their locomotion. Even in older people, there are limitations in activities such as preparing food and household activities, which shows their dependence on their daily life. It was evident in many of the exclusion from the sample the restriction in participation in most of the variables in the chapter on community, social and physical life. Therefore, the prevalence of disability related to the domains of activity and participation, according to the ICF, of children and adolescents with the most severe types of OI emerged from the research. Thus, we can observe that, in addition to presenting deficits in body functions and structures, many also affect activities and restrictions on social participation. The chapters that showed the highest prevalence of disability were "Mobility", "self-care", "household activities" and "community, social and physical life". What emphasizes the importance of managing these patients through continued multidisciplinary care with an interdisciplinary approach, which may reflect on actions of health promotion, damage prevention, continuing education, treatment and rehabilitation.

Avaliação do crescimento de crianças e adolescentes com osteogênese imperfeita em um centro de referência no Rio de Janeiro / Growth assessment of children and adolescents with osteogenesis imperfecta at a reference center in Rio de Janeiro

A osteogênese imperfeita (OI) é uma doença genética rara que afeta a produção de colágeno, uma proteína importante da matriz óssea e do tecido conjuntivo, classificada tradicionalmente em pelo menos quatro tipos. Os indivíduos com OI podem apresentar fraturas recorrentes, escoliose e deformidades ósseas, baixa estatura, além de manifestações extra-esqueléticas. O monitoramento do crescimento infantil é um bom indicador de saúde e alterações desse crescimento podem indicar presença de comorbidades. É comum a ocorrência de déficit de estatura em crianças com OI, porém é necessária referência específica para acompanhar de forma mais sensível alterações de crescimento para este grupo, de modo que, assim como já é feito para outras patologias, seria fundamental a utilização de gráficos de crescimento específicos, para acompanhar o ganho pondero-estatural desses indivíduos e facilitar a detecção de problemas adicionais. O objetivo desse trabalho foi avaliar o estado nutricional antropométrico de crianças e adolescentes com OI de acordo com o subtipo da doença. Trata-se de um estudo descritivo, retrospectivo e longitudinal utilizando dados coletados de prontuários. Os dados foram analisados nos softwares estatísticos STATA® e R, sendo utilizado o pacote estatístico GAMLSS para gerar gráficos de referência de crescimento para peso para-idade, estatura-para-idade e IMC-para-idade, conforme sexo, faixa etária e subtipo de OI, que foram comparados ao padrão da Organização Mundial da Saúde (OMS) para crianças saudáveis. A associação da variação de peso e estatura com outras variáveis de interesse foi avaliada por meio de regressão linear de efeitos mistos. Foram incluídos 237 indivíduos, sendo 134 do tipo I, 41 do tipo III, 57 do tipo IV e 5 do tipo V. No tipo I, observou-se que embora os parâmetros de peso e altura se aproximem do padrão da OMS, ocorre déficit, em ambos os sexos. No tipo III e IV esses parâmetros estão ainda mais comprometidos. O crescimento dos tipos III e IV foi significativamente menor em relação ao tipo I apenas em maiores de 2 anos para o peso e em todas as faixas etárias, para estatura. O sexo masculino apresenta significativamente maior estatura em relação ao feminino; quanto ao peso, embora a curva do sexo masculino seja superior ao feminino, a diferença não foi significativa. Em geral, observa-se maior comprometimento da altura que do peso, de modo que o IMC se mostra mais próximo ao padrão da OMS, às vezes até ultrapassando, em especial nos fenótipos mais graves, como o tipo III. Esse estudo difere-se dos demais por apresentar dados da população brasileira e curvas de crescimento para menores de 2 anos de idade. Entre as limitações, destaca-se o uso de dados retrospectivos e o tamanho reduzido da amostra, especialmente para os tipos III, IV e V. Alguns gráficos para os tipos III e IV não convergiram e para esses subtipos a validação interna não foi tão boa. Deve-se considerar que, dentro do contexto das doenças raras é difícil compilar medidas suficientes capazes de desenvolver gráficos de crescimento com um padrão alto de adequação. Tendo em vista a importância que o acompanhamento do VI crescimento representa clinicamente para a avaliação da saúde das crianças e que comparar o crescimento das crianças com OI à população em geral não representa bem a adequação desse crescimento, se considera esse trabalho um passo importante para facilitar a avaliação clínica desses pacientes com um parâmetro de comparação mais adequado.

Osteogenesis imperfecta (OI) is a rare genetic disease that affects the production of collagen, an important protein in the bone matrix and connective tissue, traditionally classified into at least four types. Individuals with OI can present recurrent fractures, scoliosis and bone deformities, and short stature, in addition to extra-skeletal manifestations. Monitoring child growth is a good indicator of health and changes in growth may indicate the presence of comorbidities. The occurrence of short stature in children with OI is common, but specific references are necessary to monitor growth changes for this group, as is already done for other pathologies. Specific charts to monitor the growth parameters of these individuals would facilitate the detection of additional health problems. The objective of this study was to evaluate the anthropometric nutritional status of children and adolescents with OI according to the subtype of the disease. This is a descriptive, retrospective and longitudinal study using data collected from medical records. Data were analyzed using STATA® and R statistical software, using the GAMLSS statistical package to generate reference growth charts for weight-for-age, height-for-age and BMI-for-age, according to sex, age group and subtype of OI, which were compared to the World Health Organization (WHO) standard for healthy children. The association of weight and height variation with other variables of interest was evaluated using linear mixed effects regression. 237 individuals were included, 134 of type I, 41 of type III, 57 of type IV and 5 of type V. In type I, it was observed that although the parameters of weight and height are close to the WHO standard, there is a deficit, in both sexes. In type III and IV, weight and height are even more compromised. The growth of types III and IV was significantly lower compared to type I only in those older than 2 years for weight and in all age groups, for height. Males are significantly taller than females; as for weight, although the curve for males is higher than for females, the difference was not significant. In general, there is greater impairment of height than weight, so that the BMI is closer to the WHO standard, sometimes even surpassing it, especially in more severe phenotypes, such as type III. This study differs from the others in that it presents data on the Brazilian population and growth charts for children under 2 years of age. Among the limitations, the use of retrospective data and the small sample size stand out, especially for types III, IV and V. Some graphs for types III and IV did not converge and for these subtypes, the internal validation was not so good. It should be considered that, within the context of rare diseases, it is difficult to compile sufficient measures capable of developing growth charts with a high standard of adequacy. Considering the clinical importance of growth monitoring for the assessment of children's health and that comparing the growth of children with OI to the general population does not represent well the adequacy of this growth, this work is considered an important step to facilitate the clinical evaluation of these patients with a more adequate comparison parameter.

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.

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.