Osteogenesis imperfecta is a hereditary disease characterized by bone fragility due to a defect in type I collagen synthesis. The diagnosis is typically suspected based on suggestive ultrasound findings and confirmed ...Osteogenesis imperfecta is a hereditary disease characterized by bone fragility due to a defect in type I collagen synthesis. The diagnosis is typically suspected based on suggestive ultrasound findings and confirmed through genetic studies. We present a case of osteogenesis imperfecta suspected during obstetrical ultrasound at 19 weeks’ gestation, which was later confirmed radiographically through computed tomography. Due to the severity of the condition, therapeutic termination of pregnancy was indicated.展开更多
Osteogenesis imperfecta(OI)is a genetically heterogeneous monogenic disease characterized by decreased bone mass,bone fragility,and recurrent fractures.The phenotypic spectrum varies considerably ranging from prenatal...Osteogenesis imperfecta(OI)is a genetically heterogeneous monogenic disease characterized by decreased bone mass,bone fragility,and recurrent fractures.The phenotypic spectrum varies considerably ranging from prenatal fractures with lethal outcomes to mild forms with few fractures and normal stature.The basic mechanism is a collagen-related defect,not only in synthesis but also in folding,processing,bone mineralization,or osteoblast function.In recent years,great progress has been made in identifying new genes and molecular mechanisms underlying OI.In this context,the classification of OI has been revised several times and different types are used.The Sillence classification,based on clinical and radiological characteristics,is currently used as a grading of clinical severity.Based on the metabolic pathway,the functional classification allows identifying regulatory elements and targeting specific therapeutic approaches.Genetic classification has the advantage of identifying the inheritance pattern,an essential element for genetic counseling and prophylaxis.Although genotype-phenotype correlations may sometimes be challenging,genetic diagnosis allows a personalized management strategy,accurate family planning,and pregnancy management decisions including options for mode of delivery,or early antenatal OI treatment.Future research on molecular pathways and pathogenic variants involved could lead to the development of genotype-based therapeutic approaches.This narrative review summarizes our current understanding of genes,molecular mechanisms involved in OI,classifications,and their utility in prophylaxis.展开更多
Being such a rare condition in paediatrics, osteogenesis imperfecta (OI) is not a diagnosis which is made often. It is however, a diagnosis necessitating early diagnosis and timeous and effective management to improve...Being such a rare condition in paediatrics, osteogenesis imperfecta (OI) is not a diagnosis which is made often. It is however, a diagnosis necessitating early diagnosis and timeous and effective management to improve morbidity and increase the quality of life for our patients. We report two cases of osteogenesis imperfecta in this case report to highlight the different phenotypic presentations. Both of these patients are unique in their presentations and each case highlights the importance of a high clinical index of suspicion by the practitioner in making the diagnosis of osteogenesis imperfecta. The first case is a patient who was diagnosed with osteogenesis imperfecta on day one of life. She had disproportionate short stature, blue sclera, a small chest and bowing of her lower limbs with swellings and tenderness over both of her femurs. A babygram radiograph revealed multiple fractures, with the presence of callus formation at some fracture sites suggesting intrauterine fractures. The second case is a patient who had normal anthropometry and was well at birth. She was subsequently diagnosed at two weeks of age when she presented to the Chris Hani Baragwanath Academic Hospital with an E. coli meningitis and she was suspected to have a right clavicular fracture and possibly rib fractures as she had pain on palpation over these areas. She was noted to have no blue sclera. Subsequent X-rays confirmed a right clavicular fracture as well as left and right rib fractures at different stages of healing. A lateral skull radiograph revealed Wormian bones. With no available genetic testing in South Africa, both diagnoses were made clinically. Both of our patients were started on zoledronic acid at three months of age and were followed up by the Metabolic Unit at the Chis Hani Baragwanath Academic Hospital. This case report of two patients highlights the characteristics important in diagnosing and treating this uncommon condition with varying phenotypical presentations, thus ensuring that the diagnosis is not missed or misdiagnosed: one disorder, two different faces.展开更多
Osteogenesis imperfecta(OI) is a rare inherited connective tissue disorder caused by mutation of collagen which results in a wide spectrum of clinical manifestations including long bone fragility fractures and deformi...Osteogenesis imperfecta(OI) is a rare inherited connective tissue disorder caused by mutation of collagen which results in a wide spectrum of clinical manifestations including long bone fragility fractures and deformities. While the treatment for these fractures was recommended as using intramedullary fixation for minimizing stress concentration, the selection of the best implant in the adolescent OI patients for the surgical reconstruction of femur was still problematic, due to anatomy distortion and implant availability. We are reporting the surgical modification by using a humeral nail for femoral fixation in three adolescent OI patients with favorable outcomes.展开更多
Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications...Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.展开更多
The allogenic bone marrow derived mesenchymal stem cells transplantation was given to the newborn girl diagnosed with osteogenesis imperfecta type III, with multiple bone fractures, extreme shortness and limbs deformi...The allogenic bone marrow derived mesenchymal stem cells transplantation was given to the newborn girl diagnosed with osteogenesis imperfecta type III, with multiple bone fractures, extreme shortness and limbs deformities. The treatment was performed at the age of 4 and 6 weeks. The clinical diagnosis was supported by biochemical analysis of collagen type I recovered from culture medium of cultivated patient’s skin fibroblast, which revealed its triple helix instability at temperature about 2?C lower than normal. Sequencing of both genes encoding procollagen type I revealed heterozygous substitution G23569Ain COL1A2 gene causing change of glycine at position 517 to aspartate. The donor of mesenchymal stem cells was the girl’s father. She received two intravenous infusions of suspended cultured mesenchymal cells in 16 days apart without any side effects. An analysis of procollagen type I secreted to the culture medium by bone marrow-derived mesenchymal stem cells obtained from the patient, 3 months following transplantation revealed its normal triple helix stability. During the subsequent two years of follow up two new bone fractures were noted. Currently a two-year-old girl’s presents extreme growth and weight deficiency. The motoric development is also retarded, but the patient constantly improves and makes progresses.展开更多
The use of near-infrared spectroscopy (NIRS) as a means of assessing regional oxygen supply is a method that has gained recent support and interest. Given the potential of NIRS, this technology was utilized in an infa...The use of near-infrared spectroscopy (NIRS) as a means of assessing regional oxygen supply is a method that has gained recent support and interest. Given the potential of NIRS, this technology was utilized in an infant patient with a case of severe osteogenesis imperfecta that precluded conventional blood pressure monitoring. Using NIRS as a monitor and titrating the anesthetic accordingly produced a good outcome, with no post-operative evidence of detrimental intra-operative hypotension or ischemia.展开更多
Osteogenesis imperfecta (OI) belongs to a group of congenital osteoporosis which hallmark feature is “affecting skeleton, increasing bone fragility that fracture easily and decreasing bone density due to quantitative...Osteogenesis imperfecta (OI) belongs to a group of congenital osteoporosis which hallmark feature is “affecting skeleton, increasing bone fragility that fracture easily and decreasing bone density due to quantitative and/or qualita-tive abnormalities”. We report a female sibling’s involvement in 3 cases with probable recessive inheritance pattern. Only female aged between 5 and 13 years were affected with skeletal lesions in the lower limbs. The boy of this family had no skeletal or extra-skeletal lesions. Their parents had no affection and no bond of consanguinity. The observed malformations can be classified as type V or VI according to Sillence’s clinical classification. Lack of genetic test in our context has limited accuracy of the diagnosis as new data evoke a genetic classification into 12 types that leading an effective therapeutic management.展开更多
Osteogenesis Imperfecta is a rare genetic disorder of connective tissue that is caused by an error in collagen formation. The disease is characterized by abnormal bone fragility, osteopenia, blue discoloration of the ...Osteogenesis Imperfecta is a rare genetic disorder of connective tissue that is caused by an error in collagen formation. The disease is characterized by abnormal bone fragility, osteopenia, blue discoloration of the sclerae and hearing loss. Chronic non-suppurative otitis media is frequent in Osteogenesis Imperfecta patients and usually attributed to Eustachian tube dysfunction due to cranial molding and deformities. In some cases of severe Osteogenesis Imperfecta, the fragile bone of the petrous carotid canal can be broken down by the pulsations of the carotid artery, this may result in prolapse of the carotid artery into the protympanum with resultant Eustachian tube obstruction and tympanic membrane retraction with adhesion to prolapsed carotid artery, a condition called myringocarotidopexy.展开更多
Osteogenesis imperfecta is a rare hereditary bone disease which is commonly classified into types I-IV,each of varying severity.The clinical symptoms of the disease consist of increased bone brittleness and recurrent ...Osteogenesis imperfecta is a rare hereditary bone disease which is commonly classified into types I-IV,each of varying severity.The clinical symptoms of the disease consist of increased bone brittleness and recurrent fractures coupled with a variety of complications.The disease damages children’s body functions and restricts their daily activities,thus affects their psychological experience of living conditions and reduces their quality of life.The quality of life of children with osteogenesis imperfecta is primarily assessed through a universal scale and so far there is no osteogenesis imperfecta-specific quality of life scale,which is of great value to the assessment of quality of life.Pain symptoms,related complications,and limitations on physical exercise have been shown to be related to the assessment of quality of life and negatively affect the physical and psychological aspects of quality of life in children with osteogenesis imperfecta.This negative effect is found to be more serious in children diagnosed with severe types of osteogenesis imperfecta.Initial research into bisphosphonate therapy as a treatment for osteogenesis imperfecta has shown promising results in providing a better quality of life,but this treatment needs to be further studied and guided by the assessing results of quality of life.In the future,better methods of assessment and improvement of quality of life for children with osteogenesis imperfecta still rely on the efforts of all sectors of society.展开更多
Due to the incurable characteristics of osteogenesis imperfecta,health management plays a crucial role for children in healthy growth,independent life and integrating into society.This paper summarizes three dimension...Due to the incurable characteristics of osteogenesis imperfecta,health management plays a crucial role for children in healthy growth,independent life and integrating into society.This paper summarizes three dimensions of "biology-psychology-society",which summarize the research progress for health management in children with osteogenesis imperfecta.In the dimension of biology,the management on diet and complications about children is relatively definite,but more experiments are still needed in order to find out the appropriate values for the using doses of bisphosphonate and treatment time.Additionally,there is a lack of tools to assess the painful degree in children and sports management methods with different types of children with osteogenesis imperfecta nowadays.In the dimension of psychology,it is found that children with osteogenesis imperfecta,their families and carers are all expected to maintain a good state of mind.In the social dimension,we have known the need of children and their families,but their supporting systems are still expected to be improved through practice.展开更多
Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta, COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21- 22 and COLIA2 at 7q22.1. T...Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta, COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21- 22 and COLIA2 at 7q22.1. The Linkage （ Version 5. 1 ） was used for 2-point analysis. DNA sequencing was used to screen and identify the mutation. Results A linkage to the markers on chromosome 17q21-22 was observed. Se- quence analysis of COLIA1 revealed a splicing mutation （IVSS-2A 〉 G） that converted the 3＇ end of intron 8 from AG to GG. Conclusion This mutation （ IVS 8-2A 〉 G） is novel, and has not yet been registered in the Human Type I and Type Ⅲ Collagen Mutations Database.展开更多
文摘Osteogenesis imperfecta is a hereditary disease characterized by bone fragility due to a defect in type I collagen synthesis. The diagnosis is typically suspected based on suggestive ultrasound findings and confirmed through genetic studies. We present a case of osteogenesis imperfecta suspected during obstetrical ultrasound at 19 weeks’ gestation, which was later confirmed radiographically through computed tomography. Due to the severity of the condition, therapeutic termination of pregnancy was indicated.
文摘Osteogenesis imperfecta(OI)is a genetically heterogeneous monogenic disease characterized by decreased bone mass,bone fragility,and recurrent fractures.The phenotypic spectrum varies considerably ranging from prenatal fractures with lethal outcomes to mild forms with few fractures and normal stature.The basic mechanism is a collagen-related defect,not only in synthesis but also in folding,processing,bone mineralization,or osteoblast function.In recent years,great progress has been made in identifying new genes and molecular mechanisms underlying OI.In this context,the classification of OI has been revised several times and different types are used.The Sillence classification,based on clinical and radiological characteristics,is currently used as a grading of clinical severity.Based on the metabolic pathway,the functional classification allows identifying regulatory elements and targeting specific therapeutic approaches.Genetic classification has the advantage of identifying the inheritance pattern,an essential element for genetic counseling and prophylaxis.Although genotype-phenotype correlations may sometimes be challenging,genetic diagnosis allows a personalized management strategy,accurate family planning,and pregnancy management decisions including options for mode of delivery,or early antenatal OI treatment.Future research on molecular pathways and pathogenic variants involved could lead to the development of genotype-based therapeutic approaches.This narrative review summarizes our current understanding of genes,molecular mechanisms involved in OI,classifications,and their utility in prophylaxis.
文摘Being such a rare condition in paediatrics, osteogenesis imperfecta (OI) is not a diagnosis which is made often. It is however, a diagnosis necessitating early diagnosis and timeous and effective management to improve morbidity and increase the quality of life for our patients. We report two cases of osteogenesis imperfecta in this case report to highlight the different phenotypic presentations. Both of these patients are unique in their presentations and each case highlights the importance of a high clinical index of suspicion by the practitioner in making the diagnosis of osteogenesis imperfecta. The first case is a patient who was diagnosed with osteogenesis imperfecta on day one of life. She had disproportionate short stature, blue sclera, a small chest and bowing of her lower limbs with swellings and tenderness over both of her femurs. A babygram radiograph revealed multiple fractures, with the presence of callus formation at some fracture sites suggesting intrauterine fractures. The second case is a patient who had normal anthropometry and was well at birth. She was subsequently diagnosed at two weeks of age when she presented to the Chris Hani Baragwanath Academic Hospital with an E. coli meningitis and she was suspected to have a right clavicular fracture and possibly rib fractures as she had pain on palpation over these areas. She was noted to have no blue sclera. Subsequent X-rays confirmed a right clavicular fracture as well as left and right rib fractures at different stages of healing. A lateral skull radiograph revealed Wormian bones. With no available genetic testing in South Africa, both diagnoses were made clinically. Both of our patients were started on zoledronic acid at three months of age and were followed up by the Metabolic Unit at the Chis Hani Baragwanath Academic Hospital. This case report of two patients highlights the characteristics important in diagnosing and treating this uncommon condition with varying phenotypical presentations, thus ensuring that the diagnosis is not missed or misdiagnosed: one disorder, two different faces.
文摘Osteogenesis imperfecta(OI) is a rare inherited connective tissue disorder caused by mutation of collagen which results in a wide spectrum of clinical manifestations including long bone fragility fractures and deformities. While the treatment for these fractures was recommended as using intramedullary fixation for minimizing stress concentration, the selection of the best implant in the adolescent OI patients for the surgical reconstruction of femur was still problematic, due to anatomy distortion and implant availability. We are reporting the surgical modification by using a humeral nail for femoral fixation in three adolescent OI patients with favorable outcomes.
基金supported by NIAMS,of the National Institutes of Health,under award numbers R01AR062074 (to DJD) and R01AR060636 (to S-JL)the Harry Headley Charitable and Research Foundation,Punta Gorda,FL(to ELG-L)
文摘Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.
基金part financed from Institutional grant KNW-1-010/P/1/0 and KNW-1-007/P/2/0 awarded to ALSco-financed by the EU funds(European Re-gional Development Fund)within the Sectoral Operational Program“Increase of Economic Competitiveness”No.WKP1/1.4/3/2/2005/103/223/565/2007/USilesian Bio-Farma Center for Biotechnology,Bioengineering and Bioinformatics,Project no POIG.02.01.00-00-166/08,THE OPERATIONAL PROGRAMME INNOVATIVE ECONOMY FOR 2007-2013,Priority Axis 2.R&D Infrastructure.
文摘The allogenic bone marrow derived mesenchymal stem cells transplantation was given to the newborn girl diagnosed with osteogenesis imperfecta type III, with multiple bone fractures, extreme shortness and limbs deformities. The treatment was performed at the age of 4 and 6 weeks. The clinical diagnosis was supported by biochemical analysis of collagen type I recovered from culture medium of cultivated patient’s skin fibroblast, which revealed its triple helix instability at temperature about 2?C lower than normal. Sequencing of both genes encoding procollagen type I revealed heterozygous substitution G23569Ain COL1A2 gene causing change of glycine at position 517 to aspartate. The donor of mesenchymal stem cells was the girl’s father. She received two intravenous infusions of suspended cultured mesenchymal cells in 16 days apart without any side effects. An analysis of procollagen type I secreted to the culture medium by bone marrow-derived mesenchymal stem cells obtained from the patient, 3 months following transplantation revealed its normal triple helix stability. During the subsequent two years of follow up two new bone fractures were noted. Currently a two-year-old girl’s presents extreme growth and weight deficiency. The motoric development is also retarded, but the patient constantly improves and makes progresses.
文摘The use of near-infrared spectroscopy (NIRS) as a means of assessing regional oxygen supply is a method that has gained recent support and interest. Given the potential of NIRS, this technology was utilized in an infant patient with a case of severe osteogenesis imperfecta that precluded conventional blood pressure monitoring. Using NIRS as a monitor and titrating the anesthetic accordingly produced a good outcome, with no post-operative evidence of detrimental intra-operative hypotension or ischemia.
文摘Osteogenesis imperfecta (OI) belongs to a group of congenital osteoporosis which hallmark feature is “affecting skeleton, increasing bone fragility that fracture easily and decreasing bone density due to quantitative and/or qualita-tive abnormalities”. We report a female sibling’s involvement in 3 cases with probable recessive inheritance pattern. Only female aged between 5 and 13 years were affected with skeletal lesions in the lower limbs. The boy of this family had no skeletal or extra-skeletal lesions. Their parents had no affection and no bond of consanguinity. The observed malformations can be classified as type V or VI according to Sillence’s clinical classification. Lack of genetic test in our context has limited accuracy of the diagnosis as new data evoke a genetic classification into 12 types that leading an effective therapeutic management.
文摘Osteogenesis Imperfecta is a rare genetic disorder of connective tissue that is caused by an error in collagen formation. The disease is characterized by abnormal bone fragility, osteopenia, blue discoloration of the sclerae and hearing loss. Chronic non-suppurative otitis media is frequent in Osteogenesis Imperfecta patients and usually attributed to Eustachian tube dysfunction due to cranial molding and deformities. In some cases of severe Osteogenesis Imperfecta, the fragile bone of the petrous carotid canal can be broken down by the pulsations of the carotid artery, this may result in prolapse of the carotid artery into the protympanum with resultant Eustachian tube obstruction and tympanic membrane retraction with adhesion to prolapsed carotid artery, a condition called myringocarotidopexy.
文摘Osteogenesis imperfecta is a rare hereditary bone disease which is commonly classified into types I-IV,each of varying severity.The clinical symptoms of the disease consist of increased bone brittleness and recurrent fractures coupled with a variety of complications.The disease damages children’s body functions and restricts their daily activities,thus affects their psychological experience of living conditions and reduces their quality of life.The quality of life of children with osteogenesis imperfecta is primarily assessed through a universal scale and so far there is no osteogenesis imperfecta-specific quality of life scale,which is of great value to the assessment of quality of life.Pain symptoms,related complications,and limitations on physical exercise have been shown to be related to the assessment of quality of life and negatively affect the physical and psychological aspects of quality of life in children with osteogenesis imperfecta.This negative effect is found to be more serious in children diagnosed with severe types of osteogenesis imperfecta.Initial research into bisphosphonate therapy as a treatment for osteogenesis imperfecta has shown promising results in providing a better quality of life,but this treatment needs to be further studied and guided by the assessing results of quality of life.In the future,better methods of assessment and improvement of quality of life for children with osteogenesis imperfecta still rely on the efforts of all sectors of society.
基金supported by China Association for Science and Technology Graduate Science Communication Ability Promotion Project(Grant kxyjskpxm2019024 and kxyjskpxm2019055)Key Research Base of Philosophy and Social Sciences in Shaanxi Province,Shaanxi Health Culture Research Center Projects(Grand JKWH2019-Q19).
文摘Due to the incurable characteristics of osteogenesis imperfecta,health management plays a crucial role for children in healthy growth,independent life and integrating into society.This paper summarizes three dimensions of "biology-psychology-society",which summarize the research progress for health management in children with osteogenesis imperfecta.In the dimension of biology,the management on diet and complications about children is relatively definite,but more experiments are still needed in order to find out the appropriate values for the using doses of bisphosphonate and treatment time.Additionally,there is a lack of tools to assess the painful degree in children and sports management methods with different types of children with osteogenesis imperfecta nowadays.In the dimension of psychology,it is found that children with osteogenesis imperfecta,their families and carers are all expected to maintain a good state of mind.In the social dimension,we have known the need of children and their families,but their supporting systems are still expected to be improved through practice.
基金Supported by grants from National Nature Science Foundation of China (30470951) and National Science Foundation for Distinguished YoungScholars of China (39925023).
文摘Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta, COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21- 22 and COLIA2 at 7q22.1. The Linkage （ Version 5. 1 ） was used for 2-point analysis. DNA sequencing was used to screen and identify the mutation. Results A linkage to the markers on chromosome 17q21-22 was observed. Se- quence analysis of COLIA1 revealed a splicing mutation （IVSS-2A 〉 G） that converted the 3＇ end of intron 8 from AG to GG. Conclusion This mutation （ IVS 8-2A 〉 G） is novel, and has not yet been registered in the Human Type I and Type Ⅲ Collagen Mutations Database.
