Musculoskeletal phenotypes in 3q29 deletion syndrome.

3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000-197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry of 206 individuals (3q29deletion.org) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 min or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome.

Musculoskeletal phenotypes in 3q29 deletion syndrome.

3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000â€"197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry ( 3q29deletion.org ) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 minutes or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population, suggesting 3q29del impacts bone strength. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome.

Primary Aneurysmal Bone Cyst of the Spine in Children: Updated Outcomes of a Modern Surgical Technique.

OBJECTIVE: Aneurysmal bone cysts (ABC) are benign but locally aggressive lesions. Treating children with spinal ABC poses risks due to the proximity of the lesion to the spinal cord and the need to preserve spinal stability after surgery. This study reports the updated outcomes of a uniform aggressive initial surgical technique for the treatment of spinal ABC in children. METHODS: Twenty-nine cases of spinal ABC were collected from a tertiary pediatric tumor center over a 24-year period (January 1990-September 2014). The study patients were divided into 2 groups based on the performed procedure: a traditional approach consisting of curettage and bone grafting (group 1) and a 4-step approach consisting of intralesional curettage, high-speed bur, electrocautery, and bone grafting (group 2). RESULTS: The study population was composed of 12 males and 17 females with a mean age of 12.2 years at the time of diagnosis and a mean postoperative follow-up of 4.03 years. Twenty-one patients underwent the 4-step approach, while 8 patients were treated with the traditional technique. The recurrence rate was 50% (4/8 patients) with the traditional technique (group 1) and 19% (4/21) in the 4-step technique (group 2) (P = .164). Regardless of the technique used, the presence of sensory symptoms at the time of presentation was a statistically significant factor for recurrence (P = .016). CONCLUSIONS: We suggest that addressing spinal ABC in pediatric patients with a 4-step approach is a safe technique that may decrease long-term recurrence and reoperation rates compared to the traditional technique of intralesional curettage and bone grafting. LEVEL OF EVIDENCE: 4.

Cost Analysis of Magnet-driven Growing Rods for Early-onset Scoliosis at 5 Years.

STUDY DESIGN: Prospective case series of nine children with early-onset scoliosis (EOS) treated by a single surgeon with a novel implant, the magnet-driven growing rod (MdGR) in a publicly funded health care service accounting for "payer costs" (PC) incurred. OBJECTIVE: The aim of this study was to compare the cost-effectiveness of MdGR versus conventional growing rods (CGRs) with respect to the PC incurred for treating EOS at 5 years. SUMMARY OF BACKGROUND DATA: Cost estimate and mathematical modeling study projections of MdGR have shown despite high insertional costs, it breaks even with CGR by 3 to 4 years. However, no clinical study to date exists either supporting or refuting this hypothesis. METHODS: Nine patients with EOS secondary to idiopathic (two), congenital (one), syndromic (three), and neuromuscular (three) etiologies treated by submuscular insertion of MdGR against stringent inclusion criteria formed the study cohort. We collected costs incurred with all aspects of care over the lifetime of device (or at least 5 years) from payers' perspective to compute and report average PC incurred per patient. We performed this cost analysis by comparing the MdGR PC against literature reported PC for CGR at 5 years. RESULTS: There were five single rod (SR) and two dual rod (DR) de novo MdGR insertions, while two patients had conversion of CGR to MdGR. MdGR alone accounted for at least 50% of overall budget. The MdGR was at least 40% more cost-effective in comparison to the CGR (£34,741 vs. £52,293) and there were seven MdGR graduates. CONCLUSION: The first study reporting direct PC incurred in EOS treated by MdGR that is devoid of any mathematical modeling and deterministic sensitivity analysis is presented. The true societal/human cost savings taking into consideration indirect costs are likely to be significantly higher. MdGR is a promising novel implant that may eventually become the "standard of care" for certain EOS etiologies. LEVEL OF EVIDENCE: 4.

Clinical and radiographic presentation of pelvic sarcoma in children.

INTRODUCTION: Pelvic sarcomas may present with vague symptoms. The aim of this study was to examine the characteristics and clinical presentations of different types of pelvic sarcoma in children. METHODS: This is a retrospective cohort study of patients up to 21 years of age with the diagnosis of pelvic sarcoma between January 2000 and June 2013. Data on demographics, tumor type and location, and clinical presentation were collected from the medical records. RESULTS: A total of 59 patients [37 males (62.7%) and 22 females (37.3%)] were examined in this study. Mean age at presentation was 11.3 ± 5 years (range 0.8-21 years). Thirty-six patients had Ewing sarcoma (61%), 9 osteosarcoma (6.8%), 4 undifferentiated sarcoma (6.8%), 2 (3.4%) rhabdomyosarcoma, 2 synovial cell sarcoma, and one (1.7%) of each fibrosarcoma, dermatofibrosarcoma, fibromyxoid sarcoma, chondrosarcoma, chordoma, and epithelioid sarcoma. Pain at presentation was reported in 41 patients, 13 mass, 8 limping, and 5 neurologic symptoms. Most of the bony tumors were painful (77%), while most of the soft tissue tumors were painless (70%). Nine patients presented with constitutional symptoms. Most patients presented within 4-12 months from symptoms beginning. Twenty-one patients (35.6%) presented with metastases (14 Ewing sarcoma, 6 osteosarcoma, and 1 synovial cell sarcoma). Pelvic radiographs showed lytic lesion in 11 patients, 4 sclerotic lesions, 6 mixed lesion, 6 had only soft tissue mass, 1 radiograph showed osteopenia, and 2 radiographs were reported normal. CONCLUSION: Ewing sarcoma was the most common pelvic sarcoma tumor in children. In most cases, pelvic sarcoma in children presented with pain mimicking other benign conditions. Some patients presented with metastatic disease with no prognostic clinical or radiographical signs or symptoms. Pelvic sarcoma should be considered a differential diagnosis as part of children work up.

Single stage en bloc resection of a recurrent metastatic osteosarcoma of the pediatric lumbar spine through multiple exposures - a novel approach.

To obtain a wide resection and safe margins in recurrent spine osteosarcoma, the surgical approach can include - posterior only, combined posterior and anterior, and combined posterior and anterior with a return to posterior in multiple stages. In our case, we used a novel approach of multiple extensile exposures circumferentially in a single stage with a single surgical prep. We present the case of a 9-year-old female with a history of metastatic osteosarcoma, who previously underwent an attempted en bloc resection with an L3 corpectomy and left below knee amputation. At 1 year follow-up, she developed a recurrent solitary spine lesion at the previous surgical resection site. An additional attempt at complete surgical resection was performed with a complex en bloc L2, L3, L4 corpectomy with removal of deep spinal implants and anterior and posterior spinal fusion with instrumentation and revision decompressive laminectomy. The patient had a good functional outcome without neurological deficits, except those resulting from resection of involved lumbar nerve roots. At last follow-up of 5 months, there was no local recurrence or distant metastasis. This approach for revision resection of recurrent spinal osteosarcoma can be performed successfully with clean margins in a safe manner.

Surgical treatment of pelvic sarcoma in children: outcomes for twenty six patients.

PURPOSE: Pelvic sarcoma is uncommon in children and challenging to treat. This study examined different surgical approaches to treat pelvic sarcoma with the aim of assessing the oncologic, and functional outcomes. METHODS: We retrospectively examined the medical records of patients younger than 21 years of age who underwent surgery for pelvic sarcoma at our institution from 1992 to 2010. The functional status of the patients was examined after a minimum follow-up of two years. RESULTS: Twenty-six patients were included in the analysis. Nineteen (73%) patients were male and seven (27%) were female. Mean age at presentation was 12.0 ± 3.9 years. Nineteen patients had Ewing sarcoma (73%), five had osteosarcoma (19%), one had chondrosarcoma (4%) and one had rhabdomyosarcoma (4%). Iliac wing resection with no reconstruction was done in three patients. Reconstruction with free fibular graft A-frame was performed in four patients, saddle endoproshtesis in five patients, iliac autoclave in one patient, and internal hemipelvectomy in nine patients. Hindquarter amputation was performed in five patients. Median follow-up was 4.6 years (range, 2.6-16 years). Nineteen patients were alive (73%); of those, 13 were known to be without disease, three were with disease and three did not have known tumor status. Six patients were reported deceased, three had osteosarcoma and three had Ewing sarcoma. Function was assessed in 17 patients; 64% were asymptomatic and ambulatory and 36% were symptomatic and ambulatory. CONCLUSIONS: Salvage reconstruction for pelvic sarcoma can be performed through various procedures on the extent of necessary bony resection. Survival rate and functional outcomes were promising in the performed study.

Hematogenous Osteomyelitis in Infants and Children: Imaging of a Changing Disease.

In children, hematogenous osteomyelitis is an infection that primarily affects the most vascularized regions of the growing skeleton. The disease has increased in frequency, virulence, and degree of soft-tissue involvement. The change in clinical manifestations and management over the past 2 decades should be reflected in the current imaging approach to the disease. Imaging of infection must depict the location of a single focus or of multiple foci of involvement and the presence of drainable collections. This review provides an overview of the imaging implications directed by the changing epidemiology, the newer insights of anatomy and pathophysiology, the imaging characteristics with emphasis on specific locations and disease complications, and the differential diagnosis considerations. In addition, basic imaging guidelines for appropriate extent of area to image based on patient age are provided. © RSNA, 2017.

Rod fracture and lengthening intervals in traditional growing rods: is there a relationship?

PURPOSE: Is there any relationship between lengthening intervals and rod fracture in traditional growing rod (TGR) surgery? METHODS: A multicenter EOS database was queried for patients who had: (1) dual growing rods for EOS; (2) minimum 2-year follow-up; (3) a minimum of 2 lengthenings; and (4) revision surgery due to rod fracture. Of 138 patients who met the criteria: 56 patients experienced at least one-rod fracture (RF group) and 82 patients had no rod fractures (NRF group). In addition to each patient's lengthening intervals, demographics, construct details, and radiographic parameters were compared. RESULTS: RF and NRF patients had a mean pre-op age of 5.7 years (range 1.3-10.7) and 7.3 years (range 1.6-12.8), respectively (p < 0.001). There was no significant association between etiologies and rod fracture or between BMI and rod fracture (p = 0.979). There was no significant difference between lengthening intervals between the RF and NRF groups (p > 0.05). RF and NRF patients had statistically similar mean pre-op major curve size and max kyphosis (p = 0.279; p = 0.619, respectively). Stainless steel rods fractured more frequently compared with Titanium rods (SS 49.2 % vs. Ti 38 %; p = 0.004). Rod fracture occurred more in rods smaller than 4 mm (p = 0.011). CONCLUSIONS: Lengthening intervals were not statistically different in RF and NRF groups and there was no association between lengthening interval and rod fracture in TGR cases. It was shown that patients who had rod fracture were younger and were more likely to have SS rods with smaller than 4 mm diameter.

Surgical resection of osteoid osteoma and osteoblastoma of the spine.

Intraoperative radiographic guidance has traditionally been utilized in orthopedic surgery through 2-D navigation with the C-arm and recently with 3-D navigation with the O-arm. The aim of this study was to describe the outcome of surgical treatment of spinal osteoblastoma and osteoid osteoma with the utilization of the O-arm and conventional C-arm guidance. This is a retrospective cohort study of patients with spinal osteoid osteoma and or osteoblastoma who were treated at our institution between 2002 and 2011. Seventeen patients were examined in this study including seven with spinal osteoblastoma and 10 with spinal osteoid osteoma. The mean age of the patients at surgery was 11.5±3.9 years. The O-arm was used in seven patients and the C-arm in 10 patients. The C-arm failed to identify the tumor in one case and needed transport to perform a computed tomographic-scan. The length of surgery was shorter when the O-arm was used, especially in the osteoblastoma group. Thirteen patients were pain free at the last follow-up visit and two patients developed recurrence. Radiographs at the last follow-up did not show signs of vertebral instability following tumor resection. Safe and effective localization of spine tumors and confirmation of tumor removal during surgery was achieved by intraoperative radiographic guidance specifically with the O-arm 3-D navigation system. LEVEL OF EVIDENCE: III.

Observational Analysis of Changing Trends in Level of Evidence of Scoliosis Research Society Annual Meeting Podium Presentations in the New Millennium (2001-2013).

STUDY DESIGN: Observational quantitative evaluation of all Scoliosis Research Society annual meeting (SRS-AM) podium presentations over a 6-year period in the new millennium for changing trends in Level of Evidence (LoE). OBJECTIVES: To report the LoE of SRS-AM podium presentations over a 13-year period in the new millennium and to compare the trends in LoE over a 3-year period between the two decades, that is, 2001-2003 versus 2011-2013. SUMMARY OF BACKGROUND DATA: LoE is a rating system introduced by the American Academy of Orthopaedic Surgeons (AAOS) in 2003 to reflect the quality of clinical studies. No study has looked into any of AAOS-affiliated spinal specialist societies' LoE, hence this study. METHODS: The SRS-AM proceedings books from two 3-year periods, 2001-2003 and 2011-2013, were retrieved. Two orthopedic surgeons independently graded each abstract on two occasions, 1 month apart, assigning them LoE from I to V, in accordance with the stringent guidelines published by AAOS. They also categorized all studies into types (ie, therapeutic, prognostic, diagnostic, economic or decision-modeling analysis, or LoE not applicable). Any disagreement between the two assessors over the LoE or the nature of study was discussed, and agreed upon by consensus. Thus, analyzed abstracts of the two groups were subsequently compared and subjected to statistical tests to determine significance. RESULTS: 637 free-papers from six annual meeting proceedings (264 in Group I and 373 in Group II) were analyzed in total. LoE I and II studies have more than doubled (p<.0001), and LoE IV studies have fallen by half in 2011-2013 as compared to 2001-2003. CONCLUSION: The SRS-AM podium presentation has shown an increase in LoE I and II studies in the new millennium. SRS is the first AAOS-affiliated subspecialty society to have undertaken an in-depth analysis of its AM podium presentations, setting a standard for other societies to emulate. LEVEL OF EVIDENCE: Not applicable.

Outcomes of Spinal Fusion for Cervical Kyphosis in Children with Neurofibromatosis.

BACKGROUND: Cervical kyphosis may occur with neurofibromatosis type I (NF1) and is often associated with vertebral dysplasia. Outcomes of cervical spinal fusion in patients with NF1 are not well described because of the rarity of the condition. We aimed to (1) characterize the clinical presentation of cervical kyphosis and (2) report the outcomes of posterior and anteroposterior cervical fusion for the condition in these children. METHODS: The medical records and imaging studies of 22 children with NF1 who had undergone spinal fusion for cervical kyphosis (mean, 67°) at a mean age of 11 years and who had been followed for a minimum of 2 years were reviewed. RESULTS: Thirteen children presented with neck pain; 10, with head tilt; 9, with a previous cervical laminectomy or fusion; and 5, with a neurologic deficit. Two patients had spontaneous dislocation of the mid-cervical spine without a neurologic deficit. Eleven had scoliosis, with the major curve measuring a mean of 61°. Nine patients underwent posterior and 13 underwent anteroposterior surgery. Twenty-one received spinal instrumentation, and 1 was not treated with instrumentation. Preoperative halo traction was used for 9 patients, and it reduced the mean preoperative kyphosis by 34% (p = 0.0059). At the time of final follow-up, all spinal fusion sites had healed and the cervical kyphosis averaged 21° (mean correction, 69%; p < 0.001). The cervical kyphosis correction was significantly better after the anteroposterior procedures (83%) than after the posterior-only procedures (58%) (p = 0.031). Vertebral dysplasia and erosion continued in all 17 patients who had presented with dysplasia preoperatively. Thirteen patients had complications, including 5 new neurologic deficits and 8 cases of junctional kyphosis. Nine patients required revision surgery. Junctional kyphosis was more common in children in whom ≤5 levels had been fused (p = 0.054). CONCLUSIONS: Anteroposterior surgery provided better correction of cervical kyphosis than posterior spinal fusion in children with NF1. Erosion of vertebral bodies continued during the postoperative follow-up period in all patients who had presented with dysplastic changes preoperatively. The cervical spine should be screened in all children with NF1. Fusion should include at least 6 levels to prevent junctional kyphosis. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Bi-planar spinal stereoradiography of adolescent idiopathic scoliosis: considerations in 3D alignment and functional balance.

PURPOSE: A prospective, cross-sectional study to determine the impact of arm position on the 3D spine and pelvic parameters and postural balance in adolescent idiopathic scoliosis. METHODS: A total number of 37 adolescent idiopathic scoliosis patients were enrolled prospectively. Three arm positions, (1) 45° shoulder flexion with knuckles on clavicles, (2) 90° shoulder and elbow flexion with forearms and palms on the front wall, and (3) arms hanging on either side, were instructed to the cohort. Bi-planar low dose X-ray images of the spine and pelvis were registered in a stereoradiography system in the first and second arm positions. A pressure mat recorded the position of the center of pressure in each arm position. Spinal and pelvic parameters were measured for the cohort. Statistical analysis was performed to determine the agreement between the spinal and pelvic parameters and standing balance in different arm positions. RESULTS: Thoracic kyphosis, sacral slope, sagittal vertical axis, T1 tilt, and spinal height were significantly different between the knuckles on clavicle and forearms on the wall positions p < 0.05. Significant differences were observed in the pressure distribution under the feet between the wall and freestanding positions. Bland-Altman plots determined disagreements between the first and second arm positions in clinical measurements and postural assessment of adolescent idiopathic scoliosis. CONCLUSION: The knuckles on clavicles position replicates the functional standing balance in AIS. Significant differences between the spinal and pelvic parameters suggest that the wall and clavicle arm positions should not be used interchangeably in AIS postural assessment. LEVEL OF EVIDENCE: Diagnostic level II.

Characterizing the differences between the 2D and 3D measurements of spine in adolescent idiopathic scoliosis.

PURPOSE: Although adolescent idiopathic scoliosis (AIS) is known to impact the 3D orientation of the spine and pelvis, the impact of the vertebral position relative to the X-ray scanner on the agreement between 2D and 3D measurements of a curve has not been evaluated. The purpose of this study was to investigate the agreement between 2D and 3D measurements of the scoliotic curve as a function of the 3D spinal parameters in AIS. METHODS: Three independent observers measured the thoracic and lumbar Cobb angles, Kyphosis, and lordosis on the posterior-anterior and lateral X-rays of AIS patients. The 3D reconstructions were created from bi-planar X-rays and the 3D spinal parameters were calculated in both radio and patient planes using SterEOS software. The degree of agreement between the 2D and 3D measurements was tested and its relationship with the curve axial rotation was determined. RESULTS: 2D and 3D measurements of the sagittal plane spinal parameters were significantly different (p < 0.05). The differences between the 2D and 3D measurements were related to the apical vertebrae rotation, the orientation of the plane of maximum curvature, pelvic axial rotation, and the curve magnitude. Differences between the radio plane and patient plane measurements were related to the pelvic axial rotation, Cobb angles, and apical vertebrae rotation, p < 0.05. CONCLUSION: Clinically and statistically significant differences were observed between the 2D and 3D measurements of the scoliotic spine. The differences between the 2D and 3D techniques were significant in sagittal plane and were related to the spinal curve and pelvic rotation in transverse plane.

Delayed Postoperative Neurologic Deficits in Spinal Deformity Surgery.

STUDY DESIGN: A cross-sectional survey of surgeon members of the Scoliosis Research Society (SRS). OBJECTIVE: This study sought to characterize the incidence, clinical presentation, diagnostic workup, treatment, and neurologic prognosis following delayed postoperative neurologic deficit (DPND) in patients undergoing spinal deformity surgery. SUMMARY OF BACKGROUND DATA: DPND is a potentially devastating condition following spinal surgery, characterized by the development of a neurological deficit within hours or days of the surgical procedure. To date, only case reports and small case series have been published on the topic. METHODS: We developed a survey to characterize DPND following spinal deformity surgery. This survey was distributed to surgeon members of the SRS through email and standard mail. The overall response rate was 38% (352/929). RESULTS: Our results suggest an estimated DPND incidence of 1 of 9910 cases (0.01%). Eighty-one surgeons (23%) experienced at least 1 DPND in the past 10 years (92 total cases). Most common diagnoses were scoliosis (69%), kyphosis (23%), and spondylolisthesis (14%); 20% were revision surgeries. The number of hours to deficit onset was as follows: 1 to 12 (36%), 13 to 24 (27%), 25 to 48 (27%), more than 48 (10%). The most commonly cited sources of injury included ischemic injury (38%) and cord compression (15%). Forty-one percent experienced complete neurologic recovery, 26% partial, and 33% no recovery. Twenty-one percent of patients achieved final neurologic status within 1 week, 38% by 1 month, and 73% by 6 months. Patients with compression-related DPND had a significantly greater likelihood of experiencing some neurologic recovery (≥1 ASIA Grade) than ischemia-related DPND (86% versus 51%, P = 0.049). CONCLUSIONS: DPND occurs at an estimated incidence of 0.01%. Sixty-three percent of DPND cases occurred within the first 24 hours and 90% within 48 hours. Complete (41%) or partial (26%) neurologic recovery may be expected, especially in compression-related DPND, emphasizing the need for perioperative vigilance, prompt recognition, and early intervention. LEVEL OF EVIDENCE: 4.

Melorheostosis: segmental osteopoikilosis or a separate entity?

PURPOSE: Melorheostosis is a progressive hyperostotic bone disease that commonly affects the appendicular skeleton. Melorheostosis has a significant degree of overlap with other hyperostosis conditions including osteopoikilosis and likely represent varying degrees of a clinical spectrum. METHODS: This is a report of 2 patients with melorheostosis who presented with different clinical presentations and involvement of different anatomic locations. RESULTS: One of the patients presented with foot size asymmetry along with intermittent foot pain and limping. This patient also had irregular nonblanching yellow plaque-like lesion on the forehead. The second patient presented with abnormal gait but no pain. Radiographs demonstrated endosteal hyperostosis, which were consistent with a mixed picture of melorheostosis and osteopoikilois. Genetic testing of the LEMD3 gene from a blood sample was negative in both cases. CONCLUSIONS: The diagnosis of melorheostosis can be made based on the clinical and radiographic features and can be challenging to differentiate from other hyperostosis conditions. LEVEL OF EVIDENCE: Level V.

Late-onset superior mesenteric artery syndrome four years following scoliosis surgery - a case report.

BACKGROUND: Superior mesenteric artery (SMA) syndrome has been reported as an uncommon condition of external vascular compression of the SMA particularly after rapid weight loss, body casts, or after corrective surgery for spinal deformities, usually within the first few weeks after surgery. METHODS: This is a retrospective report of a case of a non-verbal autistic female patient who started to develop SMA syndrome at the age of 16, 4 years after posterior spinal fusion surgery for scoliosis. She was treated conservatively by increasing oral caloric intake, which resulted in increased body weight and relief of symptoms. RESULTS: Seen at 10 years' follow up, the patient is doing well, and is functional within the limits of her suboptimal cognitive and verbal conditions. She maintains good trunk balance with solid spinal fusion and intact instrumentation at latest follow up. CONCLUSION: Spinal surgeons should maintain a high index of suspicion for diagnosis of SMA syndrome even years after scoliosis surgery, especially for patients with communication problems, like the case we present here. Appropriate conservative measures can succeed in relieving the symptoms, increasing body weight, and preventing complications including the risk of death.

The type 2 diabetes associated rs7903146 T allele within TCF7L2 is significantly under-represented in Hereditary Multiple Exostoses: insights into pathogenesis.

Hereditary Multiple Exostoses (HME) is an autosomal-dominant disorder characterized by benign cartilage tumors (exostoses) forming near the growth plates, leading to severe health problems. EXT1 and EXT2 are the two genes known to harbor heterozygous loss-of-function mutations that account for the vast majority of the primary genetic component of HME. However, patients present with wide clinical heterogeneity, suggesting that modifier genes play a role in determining severity. Our previous work has pointed to an imbalance of ß-catenin signaling being involved in the pathogenesis of osteochondroma formation. TCF7L2 is one of the key 'gate-keeper' TCF family members for Wnt/ß-catenin signaling pathway, and TCF7L2 and EXT2 are among the earliest associated loci reported in genome wide appraisals of type 2 diabetes (T2D). Thus we investigated if the key T allele of single nucleotide polymorphism (SNP) rs7903146 within the TCF7L2 locus, which is strongly over-represented among T2D cases, was also associated with HME. We leveraged genotype data available from ongoing GWAS efforts from genomics and orthopedic centers in the US, Canada and Italy. Collectively 213 cases and 1890 controls were analyzed and, surprisingly, the T allele was in fact significantly under-represented in the HME patient group [P = 0.009; odds ratio = 0.737 (95% C.I. 0.587-0.926)]; in addition, the direction of effect was consistent within each individual cohort. Immunohistochemical analyses revealed that TCF7L2 is differentially expressed and distributed in normal human growth plate zones, and exhibits substantial variability in human exostoses in terms of staining intensity and distribution. In summary, the data indicate that there is a putative genetic connection between TCF7L2 and EXT in the context of HME. Given this observation, we suggest that these loci could possibly modulate shared pathways, in particular with respect to ß-catenin, and their respective variants interplay to influence HME pathogenesis as well as T2D.

Postural orthostatic tachycardia syndrome (POTS): association with Ehlers-Danlos syndrome and orthopaedic considerations.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is the most common of several types of dysautonomia, characterized by dysfunction of the autonomic nervous system manifesting with symptoms of orthostatic intolerance with or without associated orthostatic hypotension and excessive autonomic excitation. Given the numerous presenting musculoskeletal symptoms of POTS and its known associations with other clinical entities like Ehlers-Danlos syndrome, POTS constitutes an unusual treatment challenge of which the orthopaedic surgeon and other related healthcare providers should be aware. CASE DESCRIPTION: We describe two patients with a diagnosis of POTS and musculoskeletal manifestations. The first is a 13-year-old boy with a concurrent diagnosis of Ehlers-Danlos syndrome and worsening back pain. The patient had resolution of his musculoskeletal symptoms after treatment with a Boston Overlap LSO brace and physical therapy and resolution of his cardiovascular symptoms after pharmacologic treatment. The second patient is a 17-year-old girl with an L1 vertebral hemangioma and pain of sudden onset radiating to her lower extremities. Her symptoms were controlled with therapy and gabapentin. LITERATURE REVIEW: POTS is a poorly understood and controversial clinical entity with lack of awareness and knowledge regarding the syndrome by the majority of medical specialists. Its complex and wide range of clinical presentation has led to being commonly mistaken with malingering, depression and anxiety disorders. Review of the literature did not yield any previous studies addressing POTS and the special considerations for the orthopaedic surgeon caring for these patients; previous studies of large patient series focus on investigating the pathologic substrate of POTS and the efficacy of various treatment modalities on the cardiovascular dysregulation. CLINICAL RELEVANCE: These two cases show that understanding and knowledge of this syndrome and its comorbidities should guide any diagnostic approach or therapeutic intervention by the orthopaedic surgeon caring for patients with this syndrome. It is important that the surgeon is aware of the benefits of detailed patient education and physical conditioning, the increased perioperative complications, and the need for specialized anesthesia.