Congenital pseudarthrosis of the tibia
Congenital pseudarthrosis of the tibia is a rare paediatric disease presenting with a bowing deformity of the tibia at birth or within the first decade of life. It is most commonly associated with Neurofibromatosis type 1. For children with CPT, pathological fracture of the tibia eventually occurs, resulting in persistent nonunion of the fracture site. If left untreated, leg deformities, joint stiffness, leg-length discrepancy and pain will persist. Diagnosis is done clinically and through X-ray imaging, with numerous classifications based on the severity of bowing and presence of fracture or intraosseous lesion.
Pathogenesis of CPT remains unclear. Genetic factors may be related due to its association with NF-1, but does not completely explain the development and location of CPT. It is likely related to the involvement of pathological periosteum in the tibia, resulting in abnormal bone turnover.
Treatment for CPT is through surgical correction, to limit the progression of deformity and to correct shortening of the affected limb. Prognosis of treatment depends on site and type of CPT, and there is a risk of recurrent fracture.
About 1 in 150,000 births present with CPT, but aside from its association with NF-1, not much else is shown from epidemiological studies.
Signs and symptoms
Primary CPT presents at birth or in infants as anterolateral bowing of the tibia. Bowing is observed as shortening of the corresponding leg, and is confirmed with X-ray imaging. It is commonly presented unilaterally, but can be bilateral.Secondary CPT does not present with obvious bowing at birth and may be overlooked, but will eventually progress to pathological fracture as the infant grows. Approximately 50% of fractures occur before the patient is two years of age, when toddlers begin learning to walk.
CPT is characterized by persistent nonunion because of fractures of the tibia and the presence of fibrous tissue between parts of the fractured bone. The persistent nonunion eventually leads to the formation of a false joint, otherwise known as pseudarthrosis. This pseudarthrosis is a non-healing bone lesion, resulting in reduction of mobility and persistent pain in the lower leg.
Associated conditions
CPT is most commonly associated with NF-1, with around 50% of cases of CPT being developed from NF-1. A complete neurological and dermatological examination should be done for a newborn baby with anterolateral bowing of the tibia to screen for NF-1.Diagnosis
Diagnosis is done through clinical examination and confirmed with radiographs of the tibia. Other associated clinical findings for NF-1, such as cafe-au-lait spots, neurofibromas and lisch nodules may also be found. "Early onset" CPT is regarded as fracture occurring <4 years old, while "late onset" CPT is regarded as fracture occurring >4 years old. Numerous other classifications have been proposed for CPT, owing to the heterogeneity of the disease. The Crawford and Boyd classifications are more traditional descriptive classifications emphasizing the presence of sclerosis, cystic and atrophic changes of the tibia. The Paley classification is a more recent classification which also takes into account the fibula for treatment and outcome.Staging
| Type | Findings |
| I | Anterior bowing associated with other congenital malformations |
| II | Anterior bowing with an hourglass appearance to the tibia. A fracture usually occurs before the age of 2. The ends of the bone are thin, rounded and sclerotic with obliteration of the intramedullary canal. This type is more often associated with NF-1 and there is a poor prognosis with frequent recurrence during bone growth |
| III | Pseudarthrosis developing from an intraosseous cyst, usually at the middle and distal third junction. Anterior bowing can precede or follow the development of the fracture. This type has a high rate of union and recurrence is rare |
| IV | Sclerotic bone with no pathological bowing. The medullary canal is partially or completely obliterated. A fatigue fracture may occur and progress to pseudarthrosis. The prognosis is good if treatment begins before the fatigue fracture occurs |
| V | Dysplastic appearance to the fibula. Pseudarthrosis can be located on either of the two bones of the tibial segment. The prognosis is good if the lesion is located only on the fibula, extension to the tibia has a prognosis similar to type II |
| VI | Associated with an intraosseous fibroma or a schwannoma. The prognosis depends on the aggressiveness of the intraosseous lesion |
Pathogenesis
The pathogenesis of CPT remains unclear nowadays. Various theories have been proposed in previous research, including mechanical, vascular, and genetic factors. However, none of these theories provide a comprehensive explanation for the development and location of CPT.Extensive research has highlighted the significant role of fibrous hamartoma and pathological periosteum in the development of CPT. These factors are believed to hinder bone union by interposing mechanically and disrupt normal blood supply to the affected bone. The periosteum, in particular, may create a fibrous band that increases local pressure around the bone, leading to reduced vascularization and bone atrophy. Additionally, thickening of blood vessel walls in the pseudarthrosis area may contribute to the vascularization defect.
The association of NF-1 in a substantial portion of CPT cases suggests a potential genetic disorder. Neurofibromin 1 is a gene that codes for a protein called neurofibromin, which plays a crucial role in regulating the Ras protein—a key player in cell differentiation and proliferation. Neurofibromin normally acts as a tumor suppressor by converting Ras-GTP to an inactive form. However, mutations in the NF1 gene result in the loss of neurofibromin function, leading to sustained activation of Ras. In certain CPT cases associated with NF-1, a double activation of the NF1 gene has been observed in the pseudarthrotic tissue. This genetic abnormality which only presents in some cases, cannot solely explain the pathogenesis of CPT. The loss of neurofibromin function can lead to disturbances in the Ras-MAPK pathway, resulting in impaired osteoblastic differentiation. Additionally, overexpression of the Ras pathway can increase the activity of osteoclasts and their precursors, contributing to bone resorption in CPT and the high incidence of recurrent fractures. In this case, the underlying pathogenic mechanisms of CPT likely involve a combination of signal abnormalities that enhance osteoclast activity, along with disturbances in osteoblastic differentiation, ultimately leading to defective bone remodeling. These processes are further exacerbated by the diminished local vascularization in the affected area.