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
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
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
Background:There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease(ADPKD)and connective tissue disorders.A simultaneous occurrence of osteogenesis imperfecta(OI)type ...Background:There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease(ADPKD)and connective tissue disorders.A simultaneous occurrence of osteogenesis imperfecta(OI)type I and ADPKD has not been observed so far.Methods:This report presents the first patient with OI type I and ADPKD.Results:Mutational analysis of PKD1 and COL1A1 in the index patient revealed a heterozygous mutation in each of the two genes.Mutational analysis of the parents indicated the mother as a carrier of the PKD1 mutation and the father as a carrier of the COL1A1 mutation.The simultaneous occurrence of both disorders has an estimated frequency of 3.5:100000000.Conclusion:In singular cases,ADPKD can occur in combination with other rare disorders,e.g.connective tissue disorders.展开更多
Background:To present a female child patient with osteogenesis imperfecta who had bilateral papilledema.Case presentation:A twelve-year-old girl with osteogenesis imperfecta was referred to our clinic.Bilateral best c...Background:To present a female child patient with osteogenesis imperfecta who had bilateral papilledema.Case presentation:A twelve-year-old girl with osteogenesis imperfecta was referred to our clinic.Bilateral best corrected visual acuity of the patient was 5/10(corrected with+3.50 for right eye,+5.00 for left eye)with a standard Snellen scale at a distance of a 6 m.Anterior chamber,iris and lens examination of both of her eyes were unremarkable.In her fundus examination,bilateral stage 2 papilledema and the wrinkles in papillomacular area were noticed.Optical coherence tomography images revealed the macular pucker and thickening in the retinal nerve fibre layers of both eyes.Computed tomography images revealed that there were ossifications in the optic chiasma and occlusion in all periorbital sinus areas.Conclusion:Osteogenesis imperfecta is a rare,autosomal dominant connective tissue disorder characterised by bone fractures,deafness and blue sclera.We would like to draw attention to the clinical course of our patient with computed tomography,optical coherence tomography and visual field findings.展开更多
Congenital osteogenesis imperfecta is a rare autosomal dominant genetic disease.Pregnant women with the disease pose a treatment challenge to doctors who cannot predict the pregnancy outcome and recommend an appropria...Congenital osteogenesis imperfecta is a rare autosomal dominant genetic disease.Pregnant women with the disease pose a treatment challenge to doctors who cannot predict the pregnancy outcome and recommend an appropriate abortive approach.We present the case report of a 26-year-old female who showed typical symptom of congenital osteogenesis imperfecta.Considering the heredity of the disease,the patient and her family decided to prematurely terminate the gestation.The patient presented with a treatment dilemma was difficult to identify a route of uterine entry because it was impossible to prop the patient in a lithotomy position.After consulting with the patient,the pregnancy was terminated by cesarean delivery.The surgery was successful;in our opinion,however,the cesarean delivery was not the best abortive approach to use in this case because of the severity of the procedure and the complications that could have arisen from it.Further studies are needed to identify a better abortive approach for similar cases.展开更多
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.
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.
文摘Background:There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease(ADPKD)and connective tissue disorders.A simultaneous occurrence of osteogenesis imperfecta(OI)type I and ADPKD has not been observed so far.Methods:This report presents the first patient with OI type I and ADPKD.Results:Mutational analysis of PKD1 and COL1A1 in the index patient revealed a heterozygous mutation in each of the two genes.Mutational analysis of the parents indicated the mother as a carrier of the PKD1 mutation and the father as a carrier of the COL1A1 mutation.The simultaneous occurrence of both disorders has an estimated frequency of 3.5:100000000.Conclusion:In singular cases,ADPKD can occur in combination with other rare disorders,e.g.connective tissue disorders.
文摘Background:To present a female child patient with osteogenesis imperfecta who had bilateral papilledema.Case presentation:A twelve-year-old girl with osteogenesis imperfecta was referred to our clinic.Bilateral best corrected visual acuity of the patient was 5/10(corrected with+3.50 for right eye,+5.00 for left eye)with a standard Snellen scale at a distance of a 6 m.Anterior chamber,iris and lens examination of both of her eyes were unremarkable.In her fundus examination,bilateral stage 2 papilledema and the wrinkles in papillomacular area were noticed.Optical coherence tomography images revealed the macular pucker and thickening in the retinal nerve fibre layers of both eyes.Computed tomography images revealed that there were ossifications in the optic chiasma and occlusion in all periorbital sinus areas.Conclusion:Osteogenesis imperfecta is a rare,autosomal dominant connective tissue disorder characterised by bone fractures,deafness and blue sclera.We would like to draw attention to the clinical course of our patient with computed tomography,optical coherence tomography and visual field findings.
文摘Congenital osteogenesis imperfecta is a rare autosomal dominant genetic disease.Pregnant women with the disease pose a treatment challenge to doctors who cannot predict the pregnancy outcome and recommend an appropriate abortive approach.We present the case report of a 26-year-old female who showed typical symptom of congenital osteogenesis imperfecta.Considering the heredity of the disease,the patient and her family decided to prematurely terminate the gestation.The patient presented with a treatment dilemma was difficult to identify a route of uterine entry because it was impossible to prop the patient in a lithotomy position.After consulting with the patient,the pregnancy was terminated by cesarean delivery.The surgery was successful;in our opinion,however,the cesarean delivery was not the best abortive approach to use in this case because of the severity of the procedure and the complications that could have arisen from it.Further studies are needed to identify a better abortive approach for similar cases.
