Minimally Invasive Fusionless Surgery for Scoliosis in Spinal Muscular Atrophy: Long-term Follow-up Results in a Series of 59 Patients.

BACKGROUND: Treatment of spinal muscular atrophy (SMA) scoliosis has evolved in the last decade, with the emergence of fusionless surgical techniques that allow correction of the deformity before the end of growth spurt. These techniques are expected to delay definitive spine fusion and preserve trunk growth. PURPOSE: The aim was to evaluate long-term clinical, radiologic, and respiratory outcomes of a minimally invasive fusionless surgery (MIFLS) in SMA scoliosis. METHODS: All children affected with SMA scoliosis who underwent MIFLS in our department from 2011 to 2019 were included. The instrumentation consisted in a bilateral sliding rod construct from T1 to the sacrum, anchored proximally by double-hook claws and distally by iliosacral screws. Clinical, genetic, respiratory and radiographic data were retrospectively reviewed. A patient's satisfaction survey was performed. RESULTS: A total of 59 children with genetic confirmation of SMA (9SMA1c, 47SMA2, and 3SMA3) underwent MIFLS at a mean age of 11±1.9 years. All of them were nonwalker at the time of surgery. Twenty-six were treated with intrathecal Nusinersen. Mean follow-up was 5.2 years (2 to 9.6 y). Mean major coronal curve improved from 79±15 to 41±16 degrees and pelvic obliquity decreased from 24±11 to 5.9±4 degrees. Mean space available for lung improved from 77% to 93%. Mechanical or infectious complications occurred in 9 patients, with removal of the implant in 1. 6 children required unplanned surgeries. Postoperative bracing was needed in 13 children. Mean gain weight 3 years after the first surgery was 6 kg. 91.5% of patients had a positive satisfaction of the surgery. There was no significant impact in respiratory function postoperatively. Only 30 children required rod lengthening procedures, with a mean interval between procedures of 1.9 years (0.5 to 3.7 y). No arthrodesis was required at last follow-up in any patient. CONCLUSION: Bipolar MIFLS in SMA preserves spinal and thoracic growth without interference with respiratory function. It provides a significant correction of spinal deformity and pelvic obliquity, having a reduced rate of complications. The correction of spinal deformity was maintained at long term, not requiring definitive fusion at the end of growth. LEVEL OF EVIDENCE: Level IV.

Mutations in the TGFß binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias.

Geleophysic (GD) and acromicric dysplasia (AD) belong to the acromelic dysplasia group and are both characterized by severe short stature, short extremities, and stiff joints. Although AD has an unknown molecular basis, we have previously identified ADAMTSL2 mutations in a subset of GD patients. After exome sequencing in GD and AD cases, we selected fibrillin 1 (FBN1) as a candidate gene, even though mutations in this gene have been described in Marfan syndrome, which is characterized by tall stature and arachnodactyly. We identified 16 heterozygous FBN1 mutations that are all located in exons 41 and 42 and encode TGFß-binding protein-like domain 5 (TB5) of FBN1 in 29 GD and AD cases. Microfibrillar network disorganization and enhanced TGFß signaling were consistent features in GD and AD fibroblasts. Importantly, a direct interaction between ADAMTSL2 and FBN1 was demonstrated, suggesting a disruption of this interaction as the underlying mechanism of GD and AD phenotypes. Although enhanced TGFß signaling caused by FBN1 mutations can trigger either Marfan syndrome or GD and AD, our findings support the fact that TB5 mutations in FBN1 are responsible for short stature phenotypes.

Orthopedics management of acromicric dysplasia: follow up of nine patients.

UNLABELLED: Acromicric dysplasia (AD) is an autosomal dominant disorder characterized by short stature, short extremities, stiff joint and skeleton features including brachymetacarpia, cone-shaped epiphyses, internal notch of the femoral head, and delayed bone age. Recently, we identified fibrillin 1 (FBN1) as the disease gene of AD. The aim of our study was to further describe the long-term follow up of AD patients with an emphasis on orthopedic management. Nine patients with FBN1 mutations were included in the study ranging in age from 5.5 to 64 years. For all, detailed clinical and radiological data were available. RESULTS: Birth parameters were always normal and patients progressively developed short stature <-3 SD. Carpal tunnel syndrome was observed in four patients. We found discrepancy between the carpal bone age and the radius and ulna epiphysis bone ages, a variable severity of hip dysplasia with acetabular dysplasia, epiphyseal and metaphyseal femoral dysplasia resembling Legg-Perthes-Calvé disease and variable pelvic anteversion and hyperlordosis. Orthopedic surgery was required in two patients for hip dysplasia, in one for limb lengthening and in three for carpal tunnel syndrome. Our observations expand the AD phenotype and emphasize the importance of regular orthopedic survey.

Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations.

The GALNT3 gene encodes GalNAc-T3, which prevents degradation of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Biallelic mutations in either GALNT3 or FGF23 result in hyperphosphatemic familial tumoral calcinosis or its variant, hyperostosis-hyperphosphatemia syndrome. Tumoral calcinosis is characterized by the presence of ectopic calcifications around major joints, whereas hyperostosis-hyperphosphatemia syndrome is characterized by recurrent long bone lesions with hyperostosis. Here we investigated four patients with hyperphosphatemia and clinical manifestations including tumoral calcinosis and/or hyperostosis-hyperphosphatemia syndrome to determine underlying genetic cause and delineate phenotypic heterogeneity of these disorders. Mutational analysis of FGF23 and GALNT3 in these patients revealed novel homozygous mutations in GALNT3. Although the presence of massive calcifications, cortical hyperostosis, or dental anomalies was not shared by all patients, all had persistent hyperphosphatemia. Three of the patients also had inappropriately normal 1,25-dihyroxyvitamin D [1,25(OH)(2)D] and confirmed low circulating intact FGF23 concentrations. The four novel GALNT3 mutations invariably resulted in hyperphosphatemia as a result of low intact FGF23, but other clinical manifestations were variable. Therefore, tumoral calcinosis and hyperostosis-hyperphosphatemia syndrome represent a continuous spectrum of the same disease caused by increased phosphate levels, rather than two distinct disorders.

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive or X-linked inheritance. Up to now, approximately 5% of OI cases remain without mutation demonstrated, supporting the involvement of other genes in the disease spectrum. By whole-exome sequencing, we identified a homozygous variant (c.2T>C) in CCDC134 gene in three patients from two unrelated families with severe bone fragility that did not respond to bisphosphonate treatment, short stature, and gracile long bones with pseudarthroses but no dentinogenesis imperfecta. CCDC134 encodes a secreted protein widely expressed and implicated in the regulation of some mitogen-activated protein kinases (MAPK) signaling pathway. Western blot and immunofluorescence analyses confirmed the absence of CCDC134 protein in patient cells compared with controls. Furthermore, we demonstrated that CCDC134 mutations are associated with increased Erk1/2 phosphorylation, decreased OPN mRNA and COL1A1 expression and reduced mineralization in patient osteoblasts compared with controls. These data support that CCDC134 is a new gene involved in severe progressive deforming recessive osteogenesis imperfecta (type III). © 2020 American Society for Bone and Mineral Research.

Minimally Invasive Surgery for Neuromuscular Scoliosis: Results and Complications in a Series of One Hundred Patients.

STUDY DESIGN: A retrospective review. OBJECTIVE: To report the results of an alternative technique using a minimally invasive fusionless surgery. The originality is based on the progressive correction of the deformities with proximal and distal fixation and on the reliability of the pelvic fixation using iliosacral screws on osteoporotic bones. SUMMARY OF BACKGROUND DATA: Spinal deformities are common in neuromuscular diseases. Conventional treatment involves bracing, followed by spinal instrumented fusion. Growing rod techniques are increasingly advocated but have a high rate of complications. METHODS: The technique relies on a bilateral double rod sliding construct anchored proximally by four hooks claws and distally to the pelvis by iliosacral screws through a minimally invasive approach. Hundred patients with neuromuscular scoliosis underwent the same fusionless surgery extended from T1 to the pelvis. The average age at initial surgery was 11 + 6 years. Diagnoses included cerebral palsy (61), spinal muscular atrophy (22), muscular dystrophy (10), and other neurological etiologies (7). Cobb angle and pelvic obliquity were measured before and after initial surgery, and at final follow-up. Complications were reviewed. RESULTS: At latest follow-up 3 + 9 years (range 2 yr-6 + 3 yr), the mean Cobb angle improved from 89° to 35° which corresponds to 61% correction. Mean pelvic obliquity improved from 29° to 5°, which corresponds to 83% correction. Mean T1-S1 length increased from 30.02 to 37.28 cm. Mean preoperative hyper kyphosis was reduced from 68.44° to 33.29°. Complications occurred in 26 patients including mechanical complications (12) and wound infections (16). No arthrodesis was required at last follow-up. CONCLUSION: This original fusionless technique is safe and effective, preserving spinal and thoracic growth. It provides a significant correction of spinal deformities and pelvic obliquity with a reduced complications rate. The strength and stability of this modular construct over time allow the avoidance of final arthrodesis. LEVEL OF EVIDENCE: 4.

Effectiveness of radical resections in malignant dumbbell tumors of the thoracic spine: review of three cases.

We report postoperative evolution and prognosis after radical resection of three dumbbell-shaped neurogenic tumors. It was a malignant schwannoma in all cases. Patients were observed from 8 to 27 months postoperatively. All tumors were completely excised, with histologically controlled extratumoral resection limits. The surgical technique used is the one developed by the authors for extended Pancoast Tobias resections. The patients had been operated on previously with possible local contamination, and the previous surgical wound needed to be excised with the tumor The patients died 8, 12, and 27 months postoperatively. This short series of three malignant dumbbell tumors dramatically shows that prognosis is undoubtedly more related to inadequate previous resection and to the tumor malignancy than to the surgical technique itself. The authors consider that the combined anteroposterior approach is the most efficient technique with minimum complications, even in major multilevel resections. Indications for such extended surgery include the inability to use adjuvant therapy and impending neurologic deficit.

Aneurysmal bone cysts in children: complications of fibrosing agent injection.

PURPOSE: To report complications of direct fibrosing agent injection in the treatment of aneurysmal bone cysts (ABCs) in children. MATERIALS AND METHODS: The authors retrospectively analyzed all cases of ABCs treated with direct fibrosing agent injection (Ethibloc; Ethnor Laboratories, Ethicon, Noderstedt, Germany) at Robert Debré Hospital since 1994. Histologic diagnosis was assigned by means of surgical biopsy findings prior to treatment. Treatment responses were categorized. Injection was administered with general anesthesia, computed tomographic guidance, and use of a 14- to 16-gauge needle. Contrast material was injected to determine presence of intracystic septa and verify absence of venous opacification. Amount of fibrosing agent injected corresponded to amount of contrast material necessary to fully opacify the cyst. Intraosseous needle track was obliterated with histoacryl injection. RESULTS: Fifteen patients were treated. Mean follow-up was 80 months; no patient was lost to follow-up. One patient experienced pulmonary embolus that necessitated a 7-day intensive care unit stay. Four patients experienced early aseptic fistulization after the first injection, which led to surgical débridement and curettage. Five patients had transient inflammatory reaction with mild 38 degrees C fever, which was controlled with analgesic and antiinflammatory drugs. Eleven patients did not require surgery, and results at latest follow-up were considered to indicate complete healing (type 1 results) in nine and incomplete healing (type 2 results) in two. For type 1 results: Six patients received one injection, two received two injections, and one received three injections. For type 2 results: one patient received one injection, and one received three injections. CONCLUSION: A high rate of major local and general complications was encountered with use of direct fibrosing agent injection; the technique has been abandoned for treatment of ABCs.