RARE DISEASE
Isolated pseudoarthrosis of the limbs
Isolated pseudoarthrosis of the limbs
Isolated pseudoarthrosis of the limbs
Synonyms: Congenital pseudoarthrosis of the limbs, Isolated congenital pseudarthrosis of the limbs
Synonyms: Congenital pseudoarthrosis of the limbs, Isolated congenital pseudarthrosis of the limbs
Synonyms: Congenital pseudoarthrosis of the limbs, Isolated congenital pseudarthrosis of the limbs
Drug discovery
2
drugs
With orphan designations
Overview
Isolated pseudoarthrosis of the limbs is a rare genetic disorder characterized by non-union or delayed union of long bones, resulting in progressive limb deformities, instability, and functional impairment. It typically manifests with anterolateral bowing, limb shortening, and pathological fractures, often associated with neurofibromatosis type 1 (NF1) or osteofibrous dysplasia. Diagnosis involves clinical evaluation, imaging, and histopathological confirmation of fibromatosis-like tissue proliferation [1][14].
Therapies
Surgical: Excision of pseudarthrosis tissue, bone grafting, intramedullary fixation, and Ilizarov distraction osteogenesis to manage defects [3][7][19]
Adjunctive: Use of rhBMP-2 to enhance bone healing and vascularized fibular grafts for complex cases [7][15]
Prophylactic: Bracing or osteotomy to prevent progressive deformity in pre-fracture cases [7][10]
Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare genetic diseases
Research Papers
115 drug discovery papers about Isolated pseudoarthrosis of the limbs, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
115 drug discovery papers about Isolated pseudoarthrosis of the limbs, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2025-12-15 | Vascularized Radial Periosteal Pedicled Flap for Recalcitrant Ulnar Nonunion in Children: Anatomical Study and Case Report.
Pediatric cases of bone nonunion are rare and often a result of complex local vascular limitations. The periosteum plays a key role in bone healing through its regenerative properties. Vascularized periosteal grafts have previously been effective in treating complex cases. This study explores the vascular anatomy of the radial periosteum supplied by the anterior interosseous vessels and introduces the vascularized radial periosteal graft (VRPG), successfully implemented in a case of ulnar nonunion. Cadaveric studies of ten upper limbs were conducted under ×2.5 loupe magnification following injection of colored natural latex through the brachial artery. Anterior interosseous vessels (AIOV) branches supplying the radial shaft periosteum were studied with regards to AIOV length, number of periosteal branches, and their respective distances from the distal radioulnar joint (DRUJ). As part of our case report, two pediatric cases of complex ulnar shaft nonunion underwent treatment with a VRPG: one a 15-year-old with a multioperated ulnar nonunion and the other a 5-year-old with congenital pseudoarthrosis. The mean AIOV length was 15.9 cm (range 14.2-17.8). They were found to have an average of 9.6 (range 8-13) periosteal branches with a mean distance to the DRUJ of 16 mm (range 11-23 mm) from the most distal branch and 111 mm (98-136) from the most proximal periosteal branch. Case report follow-up of both cases showed a very early initially ossified prominent callus and early bone union and callus remodeling with excellent function. The AIOV reliably supplies the radial periosteal shaft, allowing for successful harvest of a pedicled periosteal flap. This flap has proven effective in treating 2 cases of pediatric ulnar nonunion and warrants further evaluation and consideration in similar cases in the future.
2025-03-09 | Mother to Child Non-Vascularized Fibula Transfer in Congenital Pseudoarthrosis of Tibia
Introduction: Congenital pseudoarthrosis tibia (CPT) is a relatively rare disease, characterized by anterolateral bowing of the tibia, non-union, and limb length discrepancy. Various surgical treatments have been described in literature for its management with differing favorable outcomes. Case Report: In this report, we present a case of 3-year-old child with CPT of Crawford type IV, with associated fibular dysplasia. Maternal fibula was harvested and used as a bone graft and was stabilized by intra-medullary fixation. Complete union was achieved at 1 year after the primary surgery. No re-fractures were seen in a follow-up period of 2 years. Conclusion: Using maternal fibula as an alternative to use as a bone graft in the management of congenital pseudoarthrosis tibia may prove beneficial. Moreover, it is cheaper and readily available and needs less surgical expertise when compared to its alternatives such as use of bone morphogenetic protein 7, allogenic cadaveric grafting, or use of vascularized fibular graft. Keywords: Allograft, mother’s fibula, fixation, congenital pseudoarthrosis tibia.
2024-11-21 | Persistent Congenital Tibial Pseudoarthrosis until Adulthood Treated with Vascularised Fibular Graft: A 17-year Follow-up
A 39-year-old woman diagnosed with persistent congenital tibial pseudoarthrosis until adulthood presented with a right leg angular deformity, associated pain, and significant limb length discrepancy. Over a 17-year period, the case was closely monitored and treated through excision of the pseudarthrosis, vascularised fibular graft with bone marrow-derived and cultured mesenchymal cells, combined with highly purified β-tricalcium phosphates, internal fixation, and the application of a ring Ilizarov fixator. The successful union of bones and correction of deformities was achieved through consideration of both mechanical and biological aspects.
2024-08-01 | Free fibula flap to achieve bone union after congenital pseudoarthrosis of the forearm in neurofibromatosis: Technical report based on 3 cases, and literature review.
Congenital pseudarthrosis of the forearm bones (CPFBs) is rare, with only 106 reported cases, and is frequently associated with neurofibromatosis (NF). Approximately 5% of patients with NF develop pseudarthrosis, and 50% of patients with pseudarthrosis have NF. Achieving bone union is difficult in congenital pseudarthrosis. Many methods have been attempted, including casting, internal fixation with or without grafting, and electrical stimulation, but failure is frequent. Free vascularized fibular flaps (FVFs) have been used to bridge long bone defects since 1975 and in tibial pseudarthrosis since 1979. In CPFB, FVF is more successful than other methods in achieving union and is the current treatment of choice. Here, we presented three cases of forearm pseudarthrosis treated with FVF, reviewed the literature on CPFB, and discussed some technical aspects of FVF treatment. Three cases of congenital pseudoarthrosis were treated with free fibula flaps, diagnosed at ages of 7 years (ulna), 15 months (radius), and 9 years (radius and ulna). Two flaps were stabilized with intramedullary wires and latterly, one with compression plates. One persistent nonunion received revision nonvascularized bone grafting and plating. All patients achieved union by 11 months after index surgery. Reconstruction with vascularized fibula is the treatment of choice because it offers the highest published union rates and good functional results. Complete resection of the affected bone and stable fixation, latterly with compression plates are critical to success. Surgery is technically demanding, and complications are common. Secondary surgery may be required, but outcomes are favorable. LEVEL OF EVIDENCE: IV.
2024-07-28 | Congenital pseudoarthrosis of the tibia in children. The role of microsurgery in limb reconstruction
The analysis of domestic and foreign literature sources on сongenital pseudoarthrosis of the tibia in children. First part of the article describes about etiology and pathogenesis, methods and timing of conservative and surgical treatment, complications in the treatment of сongenital pseudoarthrosis of the tibia in children. Special attention is paid to cases of сongenital pseudoarthrosis of the tibia in combination with neurofibromatosis type 1. Indications and possible complications of the microsurgical stage – replacement of an extensive tibial defect with a free bloodsupplied fibular bone flap. The section description of the clinical case presents the result of treatment of a pediatric patient with сongenital pseudoarthrosis of the tibia against the background of neurofibromatosis type 1, complicated by an extensive defect of the tibia.
2025-12-15 | Vascularized Radial Periosteal Pedicled Flap for Recalcitrant Ulnar Nonunion in Children: Anatomical Study and Case Report.
Pediatric cases of bone nonunion are rare and often a result of complex local vascular limitations. The periosteum plays a key role in bone healing through its regenerative properties. Vascularized periosteal grafts have previously been effective in treating complex cases. This study explores the vascular anatomy of the radial periosteum supplied by the anterior interosseous vessels and introduces the vascularized radial periosteal graft (VRPG), successfully implemented in a case of ulnar nonunion. Cadaveric studies of ten upper limbs were conducted under ×2.5 loupe magnification following injection of colored natural latex through the brachial artery. Anterior interosseous vessels (AIOV) branches supplying the radial shaft periosteum were studied with regards to AIOV length, number of periosteal branches, and their respective distances from the distal radioulnar joint (DRUJ). As part of our case report, two pediatric cases of complex ulnar shaft nonunion underwent treatment with a VRPG: one a 15-year-old with a multioperated ulnar nonunion and the other a 5-year-old with congenital pseudoarthrosis. The mean AIOV length was 15.9 cm (range 14.2-17.8). They were found to have an average of 9.6 (range 8-13) periosteal branches with a mean distance to the DRUJ of 16 mm (range 11-23 mm) from the most distal branch and 111 mm (98-136) from the most proximal periosteal branch. Case report follow-up of both cases showed a very early initially ossified prominent callus and early bone union and callus remodeling with excellent function. The AIOV reliably supplies the radial periosteal shaft, allowing for successful harvest of a pedicled periosteal flap. This flap has proven effective in treating 2 cases of pediatric ulnar nonunion and warrants further evaluation and consideration in similar cases in the future.
2025-03-09 | Mother to Child Non-Vascularized Fibula Transfer in Congenital Pseudoarthrosis of Tibia
Introduction: Congenital pseudoarthrosis tibia (CPT) is a relatively rare disease, characterized by anterolateral bowing of the tibia, non-union, and limb length discrepancy. Various surgical treatments have been described in literature for its management with differing favorable outcomes. Case Report: In this report, we present a case of 3-year-old child with CPT of Crawford type IV, with associated fibular dysplasia. Maternal fibula was harvested and used as a bone graft and was stabilized by intra-medullary fixation. Complete union was achieved at 1 year after the primary surgery. No re-fractures were seen in a follow-up period of 2 years. Conclusion: Using maternal fibula as an alternative to use as a bone graft in the management of congenital pseudoarthrosis tibia may prove beneficial. Moreover, it is cheaper and readily available and needs less surgical expertise when compared to its alternatives such as use of bone morphogenetic protein 7, allogenic cadaveric grafting, or use of vascularized fibular graft. Keywords: Allograft, mother’s fibula, fixation, congenital pseudoarthrosis tibia.
2024-11-21 | Persistent Congenital Tibial Pseudoarthrosis until Adulthood Treated with Vascularised Fibular Graft: A 17-year Follow-up
A 39-year-old woman diagnosed with persistent congenital tibial pseudoarthrosis until adulthood presented with a right leg angular deformity, associated pain, and significant limb length discrepancy. Over a 17-year period, the case was closely monitored and treated through excision of the pseudarthrosis, vascularised fibular graft with bone marrow-derived and cultured mesenchymal cells, combined with highly purified β-tricalcium phosphates, internal fixation, and the application of a ring Ilizarov fixator. The successful union of bones and correction of deformities was achieved through consideration of both mechanical and biological aspects.
2024-08-01 | Free fibula flap to achieve bone union after congenital pseudoarthrosis of the forearm in neurofibromatosis: Technical report based on 3 cases, and literature review.
Congenital pseudarthrosis of the forearm bones (CPFBs) is rare, with only 106 reported cases, and is frequently associated with neurofibromatosis (NF). Approximately 5% of patients with NF develop pseudarthrosis, and 50% of patients with pseudarthrosis have NF. Achieving bone union is difficult in congenital pseudarthrosis. Many methods have been attempted, including casting, internal fixation with or without grafting, and electrical stimulation, but failure is frequent. Free vascularized fibular flaps (FVFs) have been used to bridge long bone defects since 1975 and in tibial pseudarthrosis since 1979. In CPFB, FVF is more successful than other methods in achieving union and is the current treatment of choice. Here, we presented three cases of forearm pseudarthrosis treated with FVF, reviewed the literature on CPFB, and discussed some technical aspects of FVF treatment. Three cases of congenital pseudoarthrosis were treated with free fibula flaps, diagnosed at ages of 7 years (ulna), 15 months (radius), and 9 years (radius and ulna). Two flaps were stabilized with intramedullary wires and latterly, one with compression plates. One persistent nonunion received revision nonvascularized bone grafting and plating. All patients achieved union by 11 months after index surgery. Reconstruction with vascularized fibula is the treatment of choice because it offers the highest published union rates and good functional results. Complete resection of the affected bone and stable fixation, latterly with compression plates are critical to success. Surgery is technically demanding, and complications are common. Secondary surgery may be required, but outcomes are favorable. LEVEL OF EVIDENCE: IV.
2024-07-28 | Congenital pseudoarthrosis of the tibia in children. The role of microsurgery in limb reconstruction
The analysis of domestic and foreign literature sources on сongenital pseudoarthrosis of the tibia in children. First part of the article describes about etiology and pathogenesis, methods and timing of conservative and surgical treatment, complications in the treatment of сongenital pseudoarthrosis of the tibia in children. Special attention is paid to cases of сongenital pseudoarthrosis of the tibia in combination with neurofibromatosis type 1. Indications and possible complications of the microsurgical stage – replacement of an extensive tibial defect with a free bloodsupplied fibular bone flap. The section description of the clinical case presents the result of treatment of a pediatric patient with сongenital pseudoarthrosis of the tibia against the background of neurofibromatosis type 1, complicated by an extensive defect of the tibia.
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Drug Discovery Landscape
2 orphan drug designations for Isolated pseudoarthrosis of the limbs.
2 orphan drug designations for Isolated pseudoarthrosis of the limbs.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Autologous adipose-derived mesenchymal stem cells embedded in an extracellular matrix with hydroxyapatite/beta-tricalcium phosphate particles | cell therapies | EMA | 2024-04-16 | — | Novadip Biosciences |
Autologous Osteogenic Stem Cells | cell therapies | FDA | 2020-09-09 | — | Novadip Biosciences |
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