Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients
Abstract Background Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. Methods We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients se...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-09-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02906-z |
| _version_ | 1797556545595113472 |
|---|---|
| author | Peikai Chen Yapeng Zhou Zhijia Tan Yunzhi Lin Daniel Li-Liang Lin Jingwei Wu Zeluan Li Hiu Tung Shek Jianbin Wu Yong Hu Feng Zhu Danny Chan Kenneth Man-Chee Cheung Michael Kai-Tsun To |
| author_facet | Peikai Chen Yapeng Zhou Zhijia Tan Yunzhi Lin Daniel Li-Liang Lin Jingwei Wu Zeluan Li Hiu Tung Shek Jianbin Wu Yong Hu Feng Zhu Danny Chan Kenneth Man-Chee Cheung Michael Kai-Tsun To |
| author_sort | Peikai Chen |
| collection | DOAJ |
| description | Abstract Background Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. Methods We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. Results In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9–16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°–25°), 40 (13.8%) moderate (25°–50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07–1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4–3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23–40) postoperatively. Conclusion The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group. |
| first_indexed | 2024-03-10T17:03:26Z |
| format | Article |
| id | doaj.art-efb8c5acdc484a04879c14ec56484031 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-10T17:03:26Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-efb8c5acdc484a04879c14ec564840312023-11-20T10:53:45ZengBMCOrphanet Journal of Rare Diseases1750-11722023-09-0118111310.1186/s13023-023-02906-zScoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patientsPeikai Chen0Yapeng Zhou1Zhijia Tan2Yunzhi Lin3Daniel Li-Liang Lin4Jingwei Wu5Zeluan Li6Hiu Tung Shek7Jianbin Wu8Yong Hu9Feng Zhu10Danny Chan11Kenneth Man-Chee Cheung12Michael Kai-Tsun To13Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Department of Orthopedics and Traumatology, The University of Hong Kong – Shenzhen Hospital (HKU-SZH)Abstract Background Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. Methods We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. Results In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9–16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°–25°), 40 (13.8%) moderate (25°–50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07–1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4–3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23–40) postoperatively. Conclusion The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group.https://doi.org/10.1186/s13023-023-02906-zScoliosisOsteogenesis imperfectaGeneticsProgression rateLogistic regressionMultivariate regression |
| spellingShingle | Peikai Chen Yapeng Zhou Zhijia Tan Yunzhi Lin Daniel Li-Liang Lin Jingwei Wu Zeluan Li Hiu Tung Shek Jianbin Wu Yong Hu Feng Zhu Danny Chan Kenneth Man-Chee Cheung Michael Kai-Tsun To Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients Orphanet Journal of Rare Diseases Scoliosis Osteogenesis imperfecta Genetics Progression rate Logistic regression Multivariate regression |
| title | Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients |
| title_full | Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients |
| title_fullStr | Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients |
| title_full_unstemmed | Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients |
| title_short | Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients |
| title_sort | scoliosis in osteogenesis imperfecta identifying the genetic and non genetic factors affecting severity and progression from longitudinal data of 290 patients |
| topic | Scoliosis Osteogenesis imperfecta Genetics Progression rate Logistic regression Multivariate regression |
| url | https://doi.org/10.1186/s13023-023-02906-z |
| work_keys_str_mv | AT peikaichen scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT yapengzhou scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT zhijiatan scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT yunzhilin scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT daniellilianglin scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT jingweiwu scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT zeluanli scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT hiutungshek scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT jianbinwu scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT yonghu scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT fengzhu scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT dannychan scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT kennethmancheecheung scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients AT michaelkaitsunto scoliosisinosteogenesisimperfectaidentifyingthegeneticandnongeneticfactorsaffectingseverityandprogressionfromlongitudinaldataof290patients |