Biallelic FKBP10 variants cause autosomal recessive osteogenesis imperfecta(OI) type XI (OI-XI) and Bruck syndrome type 1 (BS-1), both characterized by bone fragility. However, BS-1 is additionally marked by joint contractures, leading to diagnostic overlap with OI-XI. To present two FKBP10-related cases illustrating the phenotypic continuum and diagnostic challenges between BS-1 and OI-XI. Case 1, a 3.5-month-old male, had multiple fractures, progressive joint contractures, and scoliosis. Genetic testing revealed a novel homozygous FKBP10 variant, c.603T>A (p.Tyr201Ter), confirming BS-1. Case 2, a 13-day-old male, presented with recurrent fractures but no contractures or pterygium. A pathogenic homozygous FKBP10 variant, c.890_897dupTGATGGAC (p.Gly300Ter), confirmed OI-XI. Despite bisphosphonate therapy, the BS-1 case continued to experience fractures, whereas the OI-XI patient remained fracture-free with improved bone mineral density. These cases demonstrate that FKBP10-related disorders represent a phenotypic continuum rather than distinct entities. Long-term follow-up is crucial, as BS-1 features such as contractures and scoliosis may become more evident or progressive over time. Recognition of evolving phenotypes is essential for accurate diagnosis and management.

Lysyl hydroxylase 2 (LH2), encoded by the procollagen lysine 2-oxoglutarate 5-dioxygenase 2 (Plod2) gene, catalyzes the hydroxylation of lysine residues in the fibrillar collagen telopeptides. This post-translational modification is essential for forming the stable hydroxylysine-aldehyde derived collagen cross-links that play a critical role in collagen stability, mechanical strength, and bone formation. Defective LH2 activities have been implicated in bone disorders including Bruck syndrome, however, effective agents that control LH2 activity have not been developed until now. In this study, using in silico docking simulations, we identified a small molecule (KS122-0485428) that specifically binds LH2, and assessed the effects of this compound on collagen cross-linking, cell proliferation, and mineralization using the murine osteoblastic cell line MC3T3-E1. While KS122-0485428 did not affect cell proliferation and LH2 expression, it significantly accelerated mineralization. The hydroxylysine-aldehyde derived collagen cross-links were also significantly increased at the expense of the lysine-aldehyde derived cross-link. These results demonstrate that KS122-0485428 enhances LH2 activity leading to accelerated mineralization. Thus, this novel LH2 activator has the potential as a therapeutic agent for bone repair and regeneration.

Osteogenesis imperfecta (OI) type XI or Bruck syndrome is an extremely rare genetic disorder characterized by congenital joint contractures and bone fragility. OI presents unique and considerable challenges in the perioperative and anesthetic management of affected patients. A 29-year-old primigravida with OI type XI (100 cm, 26 kg) and severe kyphoscoliosis underwent urgent Caesarean delivery at 32 weeks under general anesthesia (sevoflurane/nitrous oxide). A female infant (1470 g) required resuscitation. Postoperative recovery was uneventful. The rarity of this syndrome, along with the physiological changes associated with pregnancy, creates an unprecedented clinical scenario that demands a thorough and cautious approach to patient care. Osteogenesis imperfecta (OI) type XI necessitates careful anesthetic management in pregnancy. This case highlights the anesthetic management challenges and the use of a multidisciplinary approach to enhance clinical understanding and improve patient outcomes.

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis and is known to be associated with mutations in the FKBP10 (FKBP prolyl isomerase 10) and PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2) genes. These genes encode endoplasmic reticulum proteins that play an important role in the biosynthesis of type I collagen, which in turn affects the structure and strength of connective tissues and bones in the body. Mutations are associated with disturbances in both the primary collagen chain and its post-translational formation, but the mechanism by which mutations lead to Bruck syndrome phenotypes has not been determined, not only because of the small number of patients who come to the attention of researchers but also because of the lack of disease models. In our work, we investigated the cellular effects of two forms of the wild-type PLOD2 gene, as well as the PLOD2 gene with homozygous mutation c.1885A>G (p.Thr629Ala). The synthesized genetic constructs were transfected into HEK293 cell line and human skin fibroblasts (DF2 line). The localization of PLOD2 protein in cells and the effects caused by the expression of different isoforms-long, short, and long with mutation-were analyzed. In addition, the results of the transcriptome analysis of a patient with Bruck syndrome, in whom this mutation was detected, are presented.