RESUMEN

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

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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

Asunto(s)

Humanos , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/etiología , Osteogénesis Imperfecta/terapia , Osteogénesis Imperfecta/clasificación , Diagnóstico Diferencial

RESUMEN

OBJECTIVES: To verify radiomorphometric indices and fractal dimension (FD) in dental panoramic radiographs (DPRs) of children with different types of osteogenesis imperfecta (OI) and also to verify the effect of pamidronate (PAM) treatment in such panoramic analyses. METHODS: In this retrospective study, 197 DPRs of 62 children with OI Types I, III and IV who were in treatment with a comparable dosage of intravenous PAM were selected. The mandibular cortical width (MCW), mandibular cortical index, visual estimation of the cortical width and FD of three standardized trabecular and cortical mandibular regions of interest were obtained from the radiographs. Factorial analysis of variance and Fisher test were used to compare FD and MCW measurements in children with different types of OI for different PAM cycles. RESULTS: Children with all types of OI have thinner and more porous mandibular cortices at the beginning of treatment. There were significant differences between MCW and FD of the cortical bone, regarding different types of OI and number of PAM cycles (p = 0.037 and p = 0.044, respectively). FD measurements of the trabecular bone were not statistically different among OI types nor were PAM cycles (p > 0.05). CONCLUSIONS: Children with OI presented cortical bone alterations after PAM treatment. Both MCW and the FD of the cortical bone were higher in children with OI after PAM treatment. It is argued that cortical bone should be considered for analyzing patients with OI, as well as to monitor the progress of PAM treatment.

Asunto(s)

Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Fractales , Osteogénesis Imperfecta/tratamiento farmacológico , Radiografía Panorámica/métodos , Adolescente , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/tratamiento farmacológico , Niño , Preescolar , Arco Dental/diagnóstico por imagen , Arco Dental/efectos de los fármacos , Difosfonatos/administración & dosificación , Estudios de Seguimiento , Humanos , Inyecciones Intravenosas , Mandíbula/diagnóstico por imagen , Mandíbula/efectos de los fármacos , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/diagnóstico por imagen , Pamidronato , Radiografía Panorámica/estadística & datos numéricos , Estudios Retrospectivos , Adulto Joven

RESUMEN

OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. SOURCES: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. SUMMARY OF THE FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. CONCLUSIONS: Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference. .

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OBJETIVO: Revisão da literatura sobre novos genes relacionados à osteogênese imperfeita (OI) e atualização da sua classificação. FONTE DOS DADOS : Revisão nas bases de dados do PUBMED e OMIM com seleção de referências relevantes. SÍNTESE DOS DADOS: Sillence et al., em 1979, desenvolveram uma classificação dos subtipos de OI baseada em características clínicas e gravidade da doença: OI tipo I, forma leve, comum, com escleras azuladas; OI tipo II, forma perinatal letal; OI tipo III, forma grave e progressivamente deformante com esclera normal; e OI tipo IV, forma de gravidade moderada com esclera normal. Cerca de 90% dos indivíduos com OI são heterozigotos para mutações em COL1A1 e COL1A2, com padrão de herança dominante ou esporádico. A partir de 2006 foram identificadas mutações nos genes CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1 e TMEM38B associadas à OI recessiva e mutação em IFITM5 associada à OI dominante. Mutações em PLS3 foram identificadas recentemente em famílias com osteoporose e fraturas, com padrão de herança ligado ao X. Além da complexidade genética das bases moleculares das OI, extensa variabilidade fenotípica resultante de loci individuais também tem sido documentada. CONCLUSÕES: Face à descoberta de novos genes e à correlação genótipo-fenótipo limitada, o uso de ferramentas de sequenciamento de nova geração torna-se útil no estudo molecular de casos de OI. A recomendação do Grupo de Nosologia da Sociedade Internacional de Displasias Esqueléticas é manter a classificação de Sillence como a forma prototípica e universalmente aceita para classificar o grau de gravidade na OI, e libertá-la de referência ...

Asunto(s)

Humanos , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/genética , Colágeno Tipo I/fisiología , Mutación/genética

RESUMEN

OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. SOURCES: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. SUMMARY OF THE FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. CONCLUSIONS: Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference.

Asunto(s)

Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/genética , Colágeno Tipo I/fisiología , Humanos , Mutación/genética

RESUMEN

The authors present a case of Osteogenesis Imperfecta, emphasizing the clinical and epidemiological characteristics, forms of classification and treatment of the disease. This is an important case not only to the knowledge of pediatricians and orthopedists, but also for other professionals involved with the problem. This article has been jointly described by the Departments of Pediatrics and Neonatology of the Girassol Clinic in Luanda Capital of the Republic of Angola, Africa.

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Os autores apresentam um caso clínico de Osteogenesis Imperfecta, dando ênfase às características clínicas, epidemiológicas, formas de classificação e tratamento da doença. Trata-se de um caso clínico importante para o conhecimento não só de pediatras e ortopedistas, mas também de outros profissionais envolvidos com o problema. O artigo foi descrito juntamente dos Serviços de Pediatria e de Neonatologia da Clínica Girassol, em Luanda, Capital da República de Angola, África.

Asunto(s)

Humanos , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/epidemiología , Osteogénesis Imperfecta/terapia

RESUMEN

OBJETIVO: Fazer uma revisão dos pacientes portadores de Osteogênese Imperfeita avaliando o tratamento cirúrgico das fraturas e deformidades nos membros inferiores para determinar a eficiência da técnica utilizando as hastes fixas (não-extensíveis). CASUÍSTICA E MÉTODO: Foram revisados os prontuários, radiografias pré-operatórias e pós-operatórias de todos os pacientes portadores de Osteogênese Imperfeita que foram tratados no Alfred I duPont Institute (EUA) entre 1965 e 1999. RESULTADOS: Quatorze pacientes (cinco meninos e nove meninas) foram submetidos às hastes fixas nos membros inferiores com um total de 37 procedimentos realizados. CONCLUSÃO: O procedimento de fixação intramedular com hastes não extensíveis mostrou ser um método de baixa morbidade, capaz de manter e até mesmo de melhorar o status de deambulador destes pacientes.

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OBJECTIVE: To provide a review of patients with Osteogenesis Imperfecta by analyzing the deformities, fractures and results of surgical treatment on lower limbs in order to determine the efficiency of the use of non-elongating rods (non extensible). MATERIALS AND METHOD: Medical records, preoperative and postoperative X-ray images of all the patients who had imperfect osteogenesis and treated at the Alfred I duPont Institute (USA) between 1965 and 1999 have been reviewed. RESULTS: Fourteen patients (five boys and nine girls) were submitted to the non-elongating rods on their lower limbs, totaling 37 procedures. CONCLUSION: The procedure of intramedullary fixation with non-elongating rods to treat fractures and deformities on lower limb in Osteogenesis Imperfecta was proven to be a low morbidity method without interfering with the ambulatory status of these patients.

Asunto(s)

Humanos , Masculino , Femenino , Niño , Deformidades Congénitas de las Extremidades Inferiores , Fijación Intramedular de Fracturas/métodos , Enfermedades Genéticas Congénitas , Deformidades Congénitas de las Extremidades Inferiores , Osteogénesis Imperfecta/cirugía , Osteogénesis Imperfecta/clasificación , Brasil , Registros Médicos , Estudios Retrospectivos

Asunto(s)

Masculino , Femenino , Humanos , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/etiología , Osteogénesis Imperfecta/prevención & control

RESUMEN

BACKGROUND: Osteogenesis imperfecta is a genetic disorder characterized by defects in type I collagen. The main symptom is bone fragility and susceptibility to fractures. Other clinical findings are dentinogenesis imperfecta, blue sclera, early deafness and joint laxity. The purpose of this paper is to establish a practical relationship of the clinical differences between the Sillence's groups. METHODS: 22 patients were classified according to Sillence et al criteria and submitted to laboratory tests including blood calcium level and bone densitometry. RESULTS: All clinical and laboratory differences were discussed in the text. CONCLUSIONS: Differences such as results that were found in walking ability, height and bone densitometry were significant and may help to classify patients and to establish prognosis.

Asunto(s)

Osteogénesis Imperfecta/diagnóstico , Absorciometría de Fotón , Adolescente , Adulto , Factores de Edad , Estatura , Calcio/sangre , Niño , Preescolar , Dentinogénesis Imperfecta/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/diagnóstico por imagen , Pronóstico , Esclerótica/anomalías , Factores Sexuales , Estadísticas no Paramétricas

RESUMEN

OBJETIVOS: A osteogênese imperfeita (OI) é uma doenca genética, caracterizando-se por alteracões no colágeno do tipo I, que determinam um espectro amplo de alteracões clínicas, como a dentinogênese imperfeita e escleras azuladas. O objetivo deste estudo é estabelecer uma correlacão prática no diagnóstico diferencial intergrupos dentro da classificacão de Sillence et al. (1979). MÉTODOS: Foram avaliados 22 pacientes mediante critérios clínicos e radiográficos. Após, a subdivisão de acordo com os tipos de Sillence et al. (1979), os pacientes foram também submetidos à avaliacão laboratorial e à densitometria óssea. RESULTADOS: Os dados significantes para diferenciacão entre os tipos da doenca foram a estatura, o número total de fraturas por indivíduo e a densitometria óssea. O cálcio sérico não diferencia os tipos da doenca. CONCLUSÕES: Características como a deambulacão, a estatura e a densitometria óssea podem auxiliar na diferenciacão entre os subtipos dos portadores da doenca, repercutindo diretamente no estabelecimento do seu prognóstico.

Asunto(s)

Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Humanos , Masculino , Femenino , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/diagnóstico , Absorciometría de Fotón , Factores de Edad , Estatura , Calcio/sangre , Dentinogénesis Imperfecta/patología , Diagnóstico Diferencial , Osteogénesis Imperfecta , Pronóstico , Esclerótica/anomalías , Factores Sexuales , Estadísticas no Paramétricas

RESUMEN

OBJECTIVE: To evaluate cardiopulmonary function, muscle strength, and cardiopulmonary fitness (VO 2 peak) in patients with osteogenesis imperfecta (OI). STUDY DESIGN: In 17 patients with OI type I (mean age 13.3 +/- 3.9 years) cardiopulmonary function was assessed at rest using spirometry, plethysmography, electrocardiography, and echocardiography. Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Muscle strength in shoulder abductors, hip flexors, ankle dorsal flexor, and grip strength were measured. All results were compared with reference values. RESULTS: Cardiopulmonary function at rest was within normal ranges, but when it was compared with normal height for age and sex, vital capacities were reduced. Mean absolute and relative VO 2 peak were respectively -1.17 (+/- 0.67) and -1.41 (+/- 1.52) standard deviations lower compared with reference values ( P < .01). Muscle strength also was significantly reduced in patients with OI, ranging from -1.24 +/- 1.40 to -2.88 +/- 2.67 standard deviations lower compared with reference values. CONCLUSIONS: In patients with OI type I, no pulmonary or cardiac abnormalities at rest were found. The exercise tolerance and muscle strength were significantly reduced in patients with OI, which might account for their increased levels of fatigue during activities of daily living.

Asunto(s)

Fuerza de la Mano , Pulmón/fisiopatología , Músculos/fisiopatología , Osteogénesis Imperfecta/fisiopatología , Examen Físico , Adolescente , Adulto , Niño , Electrocardiografía , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Osteogénesis Imperfecta/clasificación , Consumo de Oxígeno , Pletismografía Total , Valores de Referencia , Índice de Severidad de la Enfermedad , Espirometría , Capacidad Vital

RESUMEN

Os autores analisam de forma abrangente aspectos da osteogenesis imperfecta, dando ênfase às características clínicas, epidemiol¢gicas, formas de classificação e tratamento da doença. Trata-se de uma atualização com novos conceitos sobre a afecção, tornando-se importante para o conhecimento não s¢ de pediatras e ortopedistas como também de outros profissionais envolvidos com o problema. O artigo foi realizado conjuntamente entre o Departamento de Genética do Shriners Hospital for Children de Montreal e o Grupo de Ortopedia Pediátrica da Santa Casa de Miseric¢rdia de São Paulo, sendo relatadas a experiência clínica do grupo de Montreal e a experiência cir£rgica do Grupo de Ortopedia Pediátrica da Santa Casa de Miseric¢rdia de São Paulo.

Asunto(s)

Humanos , Niño , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/epidemiología , Osteogénesis Imperfecta/terapia

RESUMEN

OBJECTIVES: We studied the predicted value of disease-related characteristics for the ability of children with osteogenesis imperfecta (OI) to walk. STUDY DESIGN: The severity of OI was classified according to Sillence. The parents were asked to report the age at which the child achieved motor milestones, the fracture incidence, and the age and localization of the first surgical intervention. The present main means of mobility was classified according to Bleck. RESULTS: There were 76 replies to the 98 questionnaires, of which 70 were included (type I, 41; type III, 11; type IV, 18). The type of OI was strongly associated with current walking ability, as was the presence of dentinogenesis imperfecta. Patients with type III and IV had a lower chance of ultimately walking compared with those with type I. Children with more than 2 intramedullary rods in the lower extremities had a reduced chance of walking than patients without rods. Rolling over before 8 months, unsupported sitting before 9 months, the ability to get in sitting position without support before 12 months, and the ability to get in a standing position without support before 12 months showed positive odds ratios. In Bleck > or = 4, multivariate analysis revealed that only the presence of rodding (yes/no) in the lower extremities had additional predictive value to the type of OI. The presence of dentinogenesis imperfecta and rodding (yes/no) had additional value in Bleck > or = 5. CONCLUSION: The type of OI is the single most important clinical indicator of the ultimate ability to walk. Information about motor development adds little. The early achievement of motor milestones contributes to the ability of independent walking when the type of OI is uncertain. Intramedullary rodding of the lower extremities is primarily related to the severity of the disease and in this way provides consequences for the ability to walk.

Asunto(s)

Osteogénesis Imperfecta/fisiopatología , Caminata/fisiología , Adolescente , Adulto , Análisis de Varianza , Niño , Desarrollo Infantil/fisiología , Preescolar , Femenino , Fijación Interna de Fracturas , Fracturas Espontáneas/complicaciones , Fracturas Espontáneas/cirugía , Humanos , Fijadores Internos , Traumatismos de la Pierna/complicaciones , Traumatismos de la Pierna/cirugía , Masculino , Análisis Multivariante , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/complicaciones , Pronóstico , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios

RESUMEN

Apresentam-se dois casos de osteogênese imperfeita (tipo I e tipo III). A investigação foi realizada através de estudos clínicos e radiológicos. Chama-se a atenção para a importância de um cuidadoso diagnóstico, tendo em vista o fato que esta patologia assemelha-se à Síndrome da Criança Espancada

Asunto(s)

Humanos , Femenino , Adolescente , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/diagnóstico , Diagnóstico Diferencial

Asunto(s)

Humanos , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/etiología , Osteogénesis Imperfecta/fisiopatología , Síndrome de Ehlers-Danlos/etiología , Síndrome de Ehlers-Danlos/fisiopatología , Síndrome de Marfan/etiología , Síndrome de Marfan/fisiopatología , Enfermedades Genéticas Congénitas

RESUMEN

Desde su primera descripción en 1751, la osteogénesis imperfecta (OI) es una enfermedad de gran interés para el ortopedista; múltiples han sido los médicos e investigadores que han tratado de explicar la etiología, por lo que se han propuesto varias clasificaciones. De 1979 a 1993, se encontraron 57 expedientes de pacientes con OI en nuestro hospital, de los cuales sólo 39 se incluyeron en este estudio. La edad varió desde recién nacidos hasta 16 años, con un promedio de ocho años. Veinte eran del sexo masculino y 19 del femenino. Usando la clasificación de Seedorf encontramos que nueve pacientes eran del tipo I, 17 al tipo II y 3 del tipo III. La presencia de fracturas fue la manifestación clínica más frecuente, siendo el fémur el hueso predominante, con un promedio de 4.4 fracturas por paciente. Dentro del estudio encontramos que la OI tipo tarda gravis es la más frecuente; las deformidades óseas más frecuentes son en las extremidades inferiores: angulación anterolateral del fémur y tibia en sable. Es ideal la correción temprana de las angulaciones óseas, para permitir la deambulación temprana y mediante la ferulización interna prevenir la presentación de nuevas deformidades

Asunto(s)

Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Adolescente , Osteogénesis Imperfecta/cirugía , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/etiología , Tibia/crecimiento & desarrollo , Tibia/lesiones , Fracturas de la Tibia/cirugía , Fracturas de la Tibia/diagnóstico , Fémur/crecimiento & desarrollo , Fémur/lesiones , Fracturas del Fémur/cirugía , Fracturas del Fémur/diagnóstico

RESUMEN

Se presenta un caso clínico de osteogénesis imperfecta diagnosticado ecográficamente a las 35 semanas de gestación. Los elementos básicos del diagnóstico fueron la deformación y acortamiento del fémur, signos de fracturas costales y menor densidad ósea. Se interrumpe embarazo a las 38 semanas con operación cesárea, corroborándose el diagnóstico prenatal con estudios radiológicos postnatales

Asunto(s)

Humanos , Femenino , Embarazo , Recién Nacido , Adulto , Osteogénesis Imperfecta , Ultrasonografía Prenatal/métodos , Cesárea , Diagnóstico Diferencial , Fémur/anomalías , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/fisiopatología , Tercer Trimestre del Embarazo , Pronóstico

RESUMEN

A propósito de la observación de una forma rara de osteogénesis imperfecta (OI) se recurre a la literatura mundial y se toma la clasificación de Sillence, quien propone la división en 4 grupos de los distintos síndromes descriptos hasta el presente. Se reproducen los consejos de: The OI Society of New South Wales, de OI Foundation Inc. (USA), de The Brittle Bone Society (USA), de The Brittle Bone Society de Inglaterra, Noruega y Sudáfrica. Al final se presenta el caso perteneciente al relator y se lo encuadra siguiendo la clasificación de Sillence

Asunto(s)

Osteogénesis Imperfecta/historia , Osteogénesis Imperfecta/clasificación , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/terapia , Argentina