Novel pathogenic variants in SPARC as cause of osteogenesis imperfecta: Two case reports.

Pathogenic variants in SPARC cause a rare autosomal recessive form of osteogenesis imperfecta (OI), classified as OI type XVII, which was first reported in 2015. Only six patient cases with this specific form of OI have been reported to date. The SPARC protein plays a crucial role in the calcification of collagen in bone, synthesis of the extracellular matrix, and the regulation of cell shape. In this case report, we describe the phenotype of two patients with SPARC-related OI, including a patient with two novel pathogenic variants in the SPARC gene. Targeted Next Generation Sequencing revealed new compound heterozygous variants (c.484G > A p.(Glu162Lys)) and c.496C > T p.(Arg166Cys)) in one patient and a homozygous nonsense pathogenic variant (c.145C > T p.(Gln49*)) in the other. In line with previously reported cases, the two OI patients presented delayed motor development, muscular weakness, scoliosis, and multiple fractures. Interestingly, our study reports for the first time the occurrence of dentinogenesis imperfecta. The study also reports the effectiveness of bisphosphonate treatment for OI type XVII. This article enhances the genetic, clinical, therapeutic, and radiological understanding of SPARC-related OI.

Polyostotic Fibrous Dysplasia Mimicking Bone Involvement in Hodgkin Lymphoma: A Pediatric Case and Literature Review.

Bone involvement in Hodgkin lymphoma (HL) is rare. The differential diagnosis between HL bone localization and other malignant or benign skeletal diseases is challenging. We report the case of a girl affected by classic HL, initially staged IVA because of supradiaphragmatic lymph nodes and skeletal involvement. After 6 ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) cycles, positron emission tomography (PET) showed a complete metabolic response of the nodal localizations and a persistent, high metabolic activity of bone lesions. Salvage treatment followed by autologous stem cell transplant was carried out. After the transplant, the bone lesions maintained a high metabolic activity at PET. A targeted bone biopsy led to the diagnosis of a fibrous dysplasia excluding the presence of HL. To our knowledge, the concomitant presence of HL and fibrous dysplasia has not been previously reported. An in-depth evaluation of disease response to frontline treatment with a biopsy of the PET-hypercaptant bone lesions could have avoided overtreatment in this patient.

Elastic intramedullary nailing of the femur fracture in patients affected by osteogenesis imperfecta type 3: Indications, limits and pitfalls.

INTRODUCTION: Patients with Osteogenesis Imperfecta (OI) Type 3 may exhibit both primitive deformities and secondary fracture malunions on a femoral level. The orthopaedic surgeon's objective is to cure the deformities in order to prevent fractures and to treat the fractures in order to prevent deformities, by using telescopic nails as the gold standard method of fixation. However, the titanium elastic nail (TEN) is indicated as a possible alternative in certain selected cases. MATERIALS AND METHODS: The Centre for Congenital Osteodystrophy of the Sapienza University of Rome follows 485 patients with osteogenesis imperfecta. For the purpose of this study, we selected 36 patients with OI type 3 (15 females and 21 males), aged between 2 and 10 years old, who were surgically treated for femur fractures with Titanium Elastic Nail (TEN) from January 2007 to December 2009. In 12 cases a single TEN was implanted, while 24 of the cases were treated by implanting 2 TENs with the Sliding Nail (SN) technique. A retrospective evaluation was carried out by analysing the data from the medical charts and dossiers related to pain symptoms, knee and hip Range of Motion (ROM), any possible complications that could cause implant revisions (infections, nail slide failure, nail migration, traumatic events following surgery, delayed consolidation, epiphysiodesis). RESULTS: At the 60th post-surgical month, the revision rate was 75%, mostly due to migration, osteolysis, nail slide failure and nail fracture. The Kaplan-Meier's survival curve analysis showed a coefficient of 0.25-60 months (confidence interval -0.31 and 0.81). DISCUSSION: The percentage of complications and the high rate of revisions recorded in our sample confirm that telescopic nail is the gold standard in the treatment of femoral fractures in patients with OI type 3. CONCLUSIONS: In patients under the age of 4, with narrow medullary canals, low life expectancy, few to nil rehabilitative prospectives or severe comorbidities, the use of TEN may be considered as a less invasive approach compared to telescopic nail surgery, however only temporarily, as it will still most probably require a surgical revision a few years down the line.