Osteogenesis imperfecta (OI) is a hereditary bone disorder caused by defects of type I collagen. Although up to 90% of patients harbor pathogenic variants in the COL1A1/2 gene, which codes for collagen α1/2 chains, the spectrum of OI genotypes may differ between populations, and there is academic controversy around OI genotype-phenotype correlations. In the current study, 94 Ukrainian OI families were interviewed. Clinical and genealogical information was collected from patients in spoken form, and their phenotypes were described. To identify the spectrum of collagen I pathogenic variants, COL1A1/2 mutational analysis with Sanger sequencing was performed on the youngest affected individual of every family. Of the 143 patients investigated, 67 (46.85%) had type I OI, 24 (16.78%) had type III, 49 (34.27%) had type IV, and III (2.10%) had type V. The mean number of fractures suffered per patient per year was 1.32 ± 2.88 (type I 0.50 ± 0.43; type III 3.51 ± 6.18; type IV 1.44 ± 1.77; and type 5 0.77 ± 0.23). 87.23% of patients had skeletal deformations of different severity. Blue sclera, dentinogenesis imperfecta, and hearing loss were present in 87%, 55%, and 22% of patients, respectively. COL1A1/2 pathogenic variants were harbored by 60 patients (63.83%). 27 pathogenic variants are described herein for the first time. The majority of the pathogenic variants were located in the COL1A1 gene (76.19%). Half (49.21%) of the pathogenic variants were represented by structural variants. OI phenotype severity was highly correlated with type of collagen I defect. The current article presents an analysis of the clinical manifestations and COL1A1/2 mutational spectrum of 94 Ukrainian OI families with 27 novel COL1A1/2 pathogenic variants. It is hoped that this data and its analysis will contribute toward the increased understanding of the phenotype development and genetics of the disorder.

Background Osteogenesis imperfecta (OI) is a rare genetic bone fragility disorder. In the current study, differences between the genotypes and phenotypes of de novo and inherited collagen‐related OI were investigated. Methods A comparative analysis was performed of the genotypes and phenotypes of 146 unrelated inherited and de novo collagen I OI cases from Estonia, Ukraine, and Vietnam. Mutational analysis of the subjects and all available parents were performed with Sanger sequencing. Results Results showed that 56.16% of the OI cases were caused by de novo pathogenic variants. The proportion of OI types OI1, OI4, and OI3 among subjects with inherited OI was 45.31%, 46.88%, and 7.81%, respectively. Among subjects with de novo OI, the proportions of OI types (OI1, OI4, and OI3) were almost equal. Both inherited and de novo OI pathogenic variants occurred more often in the COL1A1 gene than in the COL1A2 . The majority of de novo cases were missense pathogenic variants, whereas inherited OI was mostly caused by loss of function pathogenic variants. Conclusion In summary, there were significant differences between the phenotypes and genotypes of subjects with de novo and inherited OI. These findings may promote the further understanding of OI etiology, and assist with diagnostics procedures, as well as with family planning.

Background Osteogenesis imperfecta (OI) covers a spectrum of bone fragility disorders. OI is classified into five types; however, the genetic causes of OI might hide in pathogenic variants of 20 different genes. Often clinical OI types mimic each other. This sometimes makes it impossible to identify the OI type clinically, which can be a risk for patients. Up to 90% of OI types I–IV are caused by pathogenic variants in the COL1A1/2 genes. OI type V is caused by the c.-14C > T pathogenic variant in the 5′UTR of the IFITM5 gene and is characterized by hyperplastic callus formation and the ossification of interosseous membranes. Results In the current study, we performed IFITM5 5′UTR region mutational analysis using Sanger sequencing on 90 patients who were negative for COL1A1 / 2 pathogenic variants. We also investigated the phenotypes of five patients with genetically confirmed OI type V. The proportion of OI type V patients in our cohort of all OI patients was 1.48%. In one family, there was a history of OI in at least three generations. Phenotype severity differed from mild to extremely severe among patients, but all patients harbored the same typical pathogenic variant. One patient had no visible symptoms of OI type V and was suspected to have had OI type IV previously. We also identified a case of extremely severe hyperplastic callus in a 15-year-old male, who has hearing loss and brittleness of teeth. Conclusions OI type V is underlined with some unique clinical features; however, not all patients develop them. The phenotype spectrum might be even broader than previously suspected, including typical OI features: teeth brittleness, bluish sclera, hearing loss, long bones deformities, and joint laxity. We suggest that all patients negative for COL1A1 / 2 pathogenic variants be tested for the presence of an IFITM5 pathogenic variant, even if they are not expressing typical OI type V symptoms. Further studies on the pathological nature and hyperplastic callus formation mechanisms of OI type V are necessary.

The work aimed to evaluate the effectiveness of the developed distraction system based on the rod external monolateral fixation mechanisms by comparing it with the classical technique of long tubular bones distraction based on the circular multi-axial system. The study included patients with a genetically confirmed diagnosis of achondroplasia. The experimental group consisted of 14 patients who underwent surgical limb lengthening by the rod monolateral external fixator with a distraction system developed by the authors. The lengthening was performed on 28 segments of tubular bones. The majority of the experimental group patients achieved the lengthening value close to the planned one and the deformation correction. The fixation period was averagely 83.8 ± 3.7 days, the regenerate length was 8.5 ± 0.6 cm, and the mechanical strength of the distraction regenerate was 10.3° ± 2.18°. The rod external fixator with a control distraction system developed by the authors has small dimensions and low weight of the external supporting elements of high durability. It is reported to provide a good psychological tolerance of the treatment process and significantly outperforms the circular multi-axis system. Considering the aforementioned, the proposed apparatus can grant good orthopedic care to patients with achondroplasia.

Background. Congenital pseudarthrosis of the lower leg bones belongs to the group of orphan diseases and manifests itself in non-union (pseudarthrosis) of the lower leg bones, which leads to the formation of deformity and shortening of the limb, and, as a result, is accompanied by a persistent violation of the limb’s supportability. To date, the question of choosing a surgical technique and optimal fixation in the surgical treatment of congenital pseudarthrosis of the lower leg bones remains unresolved. The purpose was to investigate the stress-strain state of the shin model with pseudarthrosis of its bones in the lower third during their osteosynthesis using a titanium mesh. Materials and methods. Osteosynthesis was simulated with an intramedullary nail, wires, and a block of bone grafts on both shin bones with the imposition of a titanium mesh over the grafts under the influence of two types of compression and torsion loads. Results. Studies have shown that additional fixation of the bone graft block with a titanium mesh allows reducing the stress level at almost all control points of the model of osteosynthesis of the lower leg bones in their congenital pseudarthrosis, both under compression and torsion. As the most positive changes, we can note a decrease in the stress values on the tibia around the nonunion line. This can be explained by the fact that the bone graft block reinforced with a titanium mesh takes on a great load. The same fact contributes to the increase in the level of stress at the lower border of the graft block and tibia. The negative factors include an increase in the level of stress along the line of non-union of the fibula. This is also explained by an increase in the modulus of elasticity of the bone graft block, which further loads the fibula. Conclusions. The use of a titanium mesh for additional fixation of the shin bones in the treatment of their congenital pseudarthrosis has a positive effect on the stress-strain state of the model, which is confirmed by a decrease in the stress level at almost all control points of the model, both under compression and torsion loads. The most positive changes are observed along the line of non-union of the tibia.

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Різниця довжини нижніх кінцівок (РДНК) є досить поширеною патологією в дітей та дорослих, вона має поліетіологічний характер. За даними різних авторів, РДНК зустрічається в 40–70 % населення в популяції. Клінічне значення РДНК у дітей визначається комплексними біомеханічними та анатомо-фізіологічними порушеннями опорно-рухового апарату. Етіологічний чинник та ступінь вираженості РДНК (незначний, помірний, значний) визначає тактику подальшого лікування. Для лікування РДНК у дітей запропоновано багато різноманітних хірургічних методів. Корекція РДНК проводиться шляхом вкорочення більш довгої кінцівки або подовження сегментів вкороченої кінцівки. Методи корекції РДНК, механізм дії яких базується на керуванні функцією наросткової зони (НЗ) довгих кісток, є перспективними, упродовж останніх 80 років вони були об’єктом пильних досліджень та експериментальних пошуків. Сучасна тенденція лікування ортопедичної патології в дітей орієнтована на використання малоінвазивних методик хірургічного лікування, саме тому концепція керованого росту, що передбачає використання різних методів впливу на функцію НЗ (епіфізеодез, степлювання, PETS-техніка, тимчасове блокування пластинами), набуває широкої популярності. Саме лікування помірної РДНК (3–6 см) у дітей може ефективно проводитися з використанням методів керованого росту. Використання тимчасового двобічного блокування НЗ пластинами з гвинтами є перспективним напрямком, адже дозволяє проводити оборотне гальмування росту здорової (довшої) кінцівки, чим досягається лікувальний ефект, при цьому значно розширюються показання до використання цього методу. У висновках можна зазначити, що оптимізація та вдосконалення методів лікування РДНК у дітей за рахунок використання малоінвазивних методик, що впливають на функцію НЗ, є актуальною та недостатньо вивченою проблемою, яка потребує подальших досліджень.

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