223 results on '"Dobbs MB"'
Search Results
2. Polygenic threshold model with sex dimorphism in adolescent idiopathic scoliosis: the Carter effect.
- Author
-
Kruse LM, Buchan JG, Gurnett CA, Dobbs MB, Kruse, Lisa M, Buchan, Jillian G, Gurnett, Christina A, and Dobbs, Matthew B
- Abstract
Background: Adolescent idiopathic scoliosis occurs between two and ten times more frequently in females than in males. The exact cause of this sex discrepancy is unknown, but it may represent a difference in susceptibility to the deformity. If this difference is attributable to genetic factors, then males with adolescent idiopathic scoliosis would need to inherit a greater number of susceptibility genes compared with females to develop the deformity. Males would also be more likely to transmit the disease to their children and to have siblings with adolescent idiopathic scoliosis. Such a phenomenon is known as the Carter effect, and the presence of such an effect would support a multifactorial threshold model of inheritance.Methods: One hundred and forty multiplex families in which more than one individual was affected with adolescent idiopathic scoliosis were studied. These families contained 1616 individuals, including 474 individuals with adolescent idiopathic scoliosis and 1142 unaffected relatives. The rates of transmission from the 122 affected mothers and from the twenty-eight affected fathers were calculated, and the prevalence among siblings was determined in the nuclear families of affected individuals.Results: The prevalence of adolescent idiopathic scoliosis in these multiplex families was lowest in sons of affected mothers (36%, thirty-eight of 105) and highest in daughters of affected fathers (85%, twenty-two of twenty-six). Affected fathers transmitted adolescent idiopathic scoliosis to 80% (thirty-seven) of forty-six children, whereas affected mothers transmitted it to 56% (133) of 239 children (p < 0.001). Siblings of affected males also had a significantly higher prevalence of adolescent idiopathic scoliosis (55%, sixty-one of 110) compared with siblings of affected females (45%, 206 of 462) (p = 0.04).Conclusions: This study demonstrates the presence of the Carter effect in adolescent idiopathic scoliosis. This pattern can be explained by polygenic inheritance of adolescent idiopathic scoliosis, with a greater genetic load required for males to be affected. [ABSTRACT FROM AUTHOR]- Published
- 2012
3. Symptomatic bunionette deformity in adolescents: surgical treatment with metatarsal sliding osteotomy.
- Author
-
Masquijo JJ, Willis BR, Kontio K, and Dobbs MB
- Published
- 2010
- Full Text
- View/download PDF
4. Validity and reliability of intraoperative monitoring in pediatric spinal deformity surgery: a 23-year experience of 3436 surgical cases.
- Author
-
Thuet ED, Winscher JC, Padberg AM, Bridwell KH, Lenke LG, Dobbs MB, Schootman M, and Luhmann SJ
- Published
- 2010
- Full Text
- View/download PDF
5. Evaluation of GPR50, hMel-1B, and ROR-alpha melatonin-related receptors and the etiology of adolescent idiopathic scoliosis.
- Author
-
Shyy W, Wang K, Gurnett CA, Dobbs MB, Miller NH, Wise C, Sheffield VC, Morcuende JA, Shyy, William, Wang, Kai, Gurnett, Christina A, Dobbs, Matthew B, Miller, Nancy H, Wise, Carol, Sheffield, Val C, and Morcuende, Jose A
- Published
- 2010
- Full Text
- View/download PDF
6. A minimally invasive treatment protocol for the congenital dislocation of the knee.
- Author
-
Shah NR, Limpaphayom N, and Dobbs MB
- Published
- 2009
- Full Text
- View/download PDF
7. Complications after pinning of supracondylar distal humerus fractures.
- Author
-
Bashyal RK, Chu JY, Schoenecker PL, Dobbs MB, Luhmann SJ, and Gordon JE
- Published
- 2009
- Full Text
- View/download PDF
8. Urgent reduction, fixation, and arthrotomy for unstable slipped capital femoral epiphysis.
- Author
-
Chen RC, Schoenecker PL, Dobbs MB, Luhmann SJ, Szymanski DA, Gordon JE, Chen, Ryan C, Schoenecker, Perry L, Dobbs, Matthew B, Luhmann, Scott J, Szymanski, Deborah A, and Gordon, J Eric
- Published
- 2009
- Full Text
- View/download PDF
9. Antegrade intramedullary nailing of pediatric femoral fractures using an interlocking pediatric femoral nail and a lateral trochanteric entry point.
- Author
-
Keeler KA, Dart B, Luhmann SJ, Schoenecker PL, Ortman MR, Dobbs MB, Gordon JE, Keeler, Kathryn A, Dart, Bradley, Luhmann, Scott J, Schoenecker, Perry L, Ortman, Madeleine R, Dobbs, Matthew B, and Gordon, J Eric
- Published
- 2009
- Full Text
- View/download PDF
10. Skeletal muscle contractile gene (TNNT3, MYH3, TPM2) mutations not found in vertical talus or clubfoot.
- Author
-
Gurnett CA, Alaee F, Desruisseau D, Boehm S, Dobbs MB, Gurnett, Christina A, Alaee, Farhang, Desruisseau, David, Boehm, Stephanie, and Dobbs, Matthew B
- Abstract
Unlabelled: Arthrogryposis presents with lower limb contractures that resemble clubfoot and/or vertical talus. Recently, mutations in skeletal muscle contractile genes MYH3 (myosin heavy chain 3), TNNT3 (troponin T3), and TPM2 (tropomyosin 2) were identified in patients with distal arthrogryposis DA2A (Freeman-Sheldon syndrome) or DA2B (Sheldon-Hall syndrome). We asked whether the contractile genes responsible for distal arthrogryposis are also responsible for cases of familial clubfoot or vertical talus. We determined the frequency of MYH3, TNNT3, and TPM2 mutations in patients with idiopathic clubfoot, vertical talus, and distal arthrogryposis type 1 (DA1). We resequenced the coding exons of the MYH3, TNNT3, and TPM2 genes in 31 patients (five with familial vertical talus, 20 with familial clubfoot, and six with DA1). Variants were evaluated for segregation with disease in additional family members, and the frequency of identified variants was determined in a control population. In one individual with DA1, we identified a de novo TNNT3 mutation (R63H) previously identified in an individual with DA2B. No other causative mutations were identified, though we found several previously undescribed single-nucleotide polymorphisms of unknown importance. Although mutations in MYH3, TNNT3, and TPM2 are frequently associated with distal arthrogryposis syndromes, they were not present in patients with familial vertical talus or clubfoot. The TNNT3 R63H recurrent mutation identified in two unrelated individuals may be associated with either DA1 or DA2B.Level Of Evidence: Level II, prospective study. See the Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
11. Interobserver and intraobserver reliability in the evaluation of mechanical axis deviation.
- Author
-
Gordon JE, Chen RC, Dobbs MB, Luhmann SJ, Rich MM, Schoenecker PL, Gordon, J Eric, Chen, Ryan C, Dobbs, Matthew B, Luhmann, Scott J, Rich, Margaret M, and Schoenecker, Perry L
- Published
- 2009
- Full Text
- View/download PDF
12. Case report: Congenital knee dislocation in a patient with larsen syndrome and a novel filamin B mutation.
- Author
-
Dobbs MB, Boehm S, Grange DK, Gurnett CA, Dobbs, Matthew B, Boehm, Stephanie, Grange, Dorothy K, and Gurnett, Christina A
- Abstract
We treated a patient with multiple congenital joint dislocations and facial dysmorphisms consistent with Larsen syndrome. Sequencing of the FLNB gene resulted in identification of a novel, de novo 508G>C point mutation resulting in substitution of proline for a highly conserved alanine (A170P). This mutation has not been described previously but is likely causative because this alanine is highly conserved and is located in the calponin homology domain where other mutations have been described. We also report the successful use of a minimally invasive technique in achieving initial correction of bilateral congenital knee dislocations in this patient. The technique consists of serial manipulations and castings followed by an open quadriceps tenotomy. Longer followup is needed to ensure maintenance of correction and to avoid the need for more extensive surgery, which has been the traditional treatment for congenital knee dislocation associated with Larsen syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
13. Early results of a new method of treatment for idiopathic congenital vertical talus. Surgical technique.
- Author
-
Dobbs MB, Purcell DB, Nunley R, Morcuende JA, Dobbs, Matthew B, Purcell, Derek B, Nunley, Ryan, and Morcuende, Jose A
- Abstract
Background: The treatment of idiopathic congenital vertical talus has traditionally consisted of manipulation and application of casts followed by extensive soft-tissue releases. However, this treatment is often followed by severe stiffness of the foot and other complications. The purpose of this study was to evaluate a new method of manipulation and cast immobilization, based on principles used by Ponseti for the treatment of clubfoot deformity, followed by pinning of the talonavicular joint and percutaneous tenotomy of the Achilles tendon in patients with idiopathic congenital vertical talus.Methods: The cases of eleven consecutive patients who had a total of nineteen feet with an idiopathic congenital vertical talus deformity were retrospectively reviewed at a minimum of two years following treatment with serial manipulations and casts followed by limited surgery consisting of percutaneous Achilles tenotomy (all nineteen feet), fractional lengthening of the anterior tibial tendon (two) or the peroneal brevis tendon (one), and percutaneous pin fixation of the talonavicular joint (twelve). The principles of manipulation and application of the plaster casts were similar to those used by Ponseti to correct a clubfoot deformity, but the forces were applied in the opposite direction. Patients were evaluated clinically and radiographically at the time of presentation, immediately postoperatively, and at the time of the latest follow-up. Radiographic measurements obtained at these times were compared. In addition, the radiographic data at the final evaluation were compared with normal values for an individual of the same age as the patient.Results: Initial correction was obtained both clinically and radiographically in all nineteen feet. A mean of five casts was required for correction. No patient underwent extensive surgical releases. At the final evaluation, the mean ankle dorsiflexion was 25 degrees and the mean plantar flexion was 33 degrees . Dorsal subluxation of the navicular recurred in three patients, none of whom had had pin fixation of the talonavicular joint. At the time of the latest follow-up, there was a significant improvement (p < 0.0001) in all of the measured radiographic parameters compared with the pretreatment values, and all of the measured angles were within normal values for the patient's age.Conclusions: Serial manipulation and cast immobilization followed by talonavicular pin fixation and percutaneous tenotomy of the Achilles tendon provides excellent results, in terms of the clinical appearance of the foot, foot function, and deformity correction as measured radiographically at a minimum two years, in patients with idiopathic congenital vertical talus. [ABSTRACT FROM AUTHOR]- Published
- 2007
14. Management of juvenile idiopathic scoliosis.
- Author
-
Lenke LG, Dobbs MB, Lenke, Lawrence G, and Dobbs, Matthew B
- Published
- 2007
15. Anterior/posterior spinal instrumentation versus posterior instrumentation alone for the treatment of adolescent idiopathic scoliotic curves more than 90 degrees.
- Author
-
Dobbs MB, Lenke LG, Kim YJ, Luhmann SJ, Bridwell KH, Dobbs, Matthew B, Lenke, Lawrence G, Kim, Yongjung J, Luhmann, Scott J, and Bridwell, Keith H
- Abstract
Study Design: A retrospective review of patients with adolescent idiopathic scoliosis (AIS), with curves more than 90 degrees treated with either a combined anterior/posterior spinal fusion or a posterior spinal fusion alone.Objectives: To assess the results of spinal fusion for AIS curves >90 degrees and determine whether the use of a posterior-only approach with an all-pedicle screw construct can decrease the need for anterior release surgery.Summary Of Background Data: Treatment of AIS curves >90 degrees often consists of anterior release and posterior fusion to improve coronal correction and fusion rate. However, the use of pedicle screws has allowed improved coronal curve correction rates even in large curves, which may decrease the need for anterior release surgery.Methods: A total of 54 consecutive patients with AIS with curves >90 degrees who underwent a spinal fusion procedure at 1 institution between 1987 and 2001, with either a combined anterior/posterior spinal fusion (hooks and screws) or a posterior spinal fusion alone with an all-pedicle screw construct, were included for analysis. All patients had a minimum 2-year follow-up (mean 6.0; range 2.0-14.5), and were analyzed radiographically as well as with pulmonary function tests. Statistical analyses were performed between groups using the Wilcoxon-Mann-Whitney tests.Results: There were 20 patients treated with an anterior/posterior spinal fusion and 34 with a posterior spinal fusion alone. There were no statistically significant differences between the groups for gender, age, number of levels fused, preoperative coronal/sagittal Cobb measurements, coronal curve flexibility, or amount of postoperative coronal Cobb correction. There was less of a negative effect on pulmonary function in the group treated with posterior spinal fusion versus the group treated with a combined anterior/posterior spinal fusion (P < 0.005). There were no complications/reoperations in either group.Conclusion: In this patient population with often restrictive preoperative pulmonary function, a posterior-only approach with the use of an all-pedicle screw construct has the advantage of providing the same correction as an anterior/posterior spinal fusion, without the need for entering the thorax and more negatively impacting pulmonary function. [ABSTRACT FROM AUTHOR]- Published
- 2006
- Full Text
- View/download PDF
16. Early results of a new method of treatment for idiopathic congenital vertical talus.
- Author
-
Dobbs MB, Purcell DB, Nunley R, Morcuende JA, Dobbs, Matthew B, Purcell, Derek B, Nunley, Ryan, and Morcuende, Jose A
- Abstract
Background: The treatment of idiopathic congenital vertical talus has traditionally consisted of manipulation and application of casts followed by extensive soft-tissue releases. However, this treatment is often followed by severe stiffness of the foot and other complications. The purpose of this study was to evaluate a new method of manipulation and cast immobilization, based on principles used by Ponseti for the treatment of clubfoot deformity, followed by pinning of the talonavicular joint and percutaneous tenotomy of the Achilles tendon in patients with idiopathic congenital vertical talus.Methods: The cases of eleven consecutive patients who had a total of nineteen feet with an idiopathic congenital vertical talus deformity were retrospectively reviewed at a minimum of two years following treatment with serial manipulations and casts followed by limited surgery consisting of percutaneous Achilles tenotomy (all nineteen feet), fractional lengthening of the anterior tibial tendon (two) or the peroneal brevis tendon (one), and percutaneous pin fixation of the talonavicular joint (twelve). The principles of manipulation and application of the plaster casts were similar to those used by Ponseti to correct a clubfoot deformity, but the forces were applied in the opposite direction. Patients were evaluated clinically and radiographically at the time of presentation, immediately postoperatively, and at the time of the latest follow-up. Radiographic measurements obtained at these times were compared. In addition, the radiographic data at the final evaluation were compared with normal values for an individual of the same age as the patient.Results: Initial correction was obtained both clinically and radiographically in all nineteen feet. A mean of five casts was required for correction. No patient underwent extensive surgical releases. At the final evaluation, the mean ankle dorsiflexion was 25 degrees and the mean plantar flexion was 33 degrees . Dorsal subluxation of the navicular recurred in three patients, none of whom had had pin fixation of the talonavicular joint. At the time of the latest follow-up, there was a significant improvement (p < 0.0001) in all of the measured radiographic parameters compared with the pretreatment values, and all of the measured angles were within normal values for the patient's age.Conclusions: Serial manipulation and cast immobilization followed by talonavicular pin fixation and percutaneous tenotomy of the Achilles tendon provides excellent results, in terms of the clinical appearance of the foot, foot function, and deformity correction as measured radiographically at a minimum two years, in patients with idiopathic congenital vertical talus. [ABSTRACT FROM AUTHOR]- Published
- 2006
17. Long-term follow-up of patients with clubfeet treated with extensive soft-tissue release.
- Author
-
Dobbs MB, Nunley R, Schoenecker PL, Dobbs, Matthew B, Nunley, Ryan, and Schoenecker, Perry L
- Abstract
Background: Although long-term follow-up studies have shown favorable results, in terms of foot function, after treatment of idiopathic clubfoot with serial manipulations and casts, we know of no long-term follow-up studies of patients in whom clubfoot was treated with an extensive surgical soft-tissue release.Methods: Forty-five patients (seventy-three feet) in whom idiopathic clubfoot was treated with either a posterior release and plantar fasciotomy (eight patients) or an extensive combined posterior, medial, and lateral release (thirty-seven patients) were followed for a mean of thirty years. Patients were evaluated with detailed examination of the lower extremities, a radiographic evaluation that included grading of osteoarthritis, and three independent quality-of-life questionnaires, including the Short Form-36 Medical Outcomes Study.Results: At the time of follow-up, the majority of patients in both treatment groups had significant limitation of foot function, which was consistent across the three independent quality-of-life questionnaires. No significant difference between groups was noted with regard to the results of the quality-of-life measures, the range of motion of the ankle or the position of the heel, or the radiographic findings. Six patients who had been treated with only one surgical procedure had better ranges of motion of the ankle and subtalar joints (p < 0.004) than those who had had multiple surgical procedures.Conclusions: Many patients with clubfoot treated with an extensive soft-tissue release have poor long-term foot function. We found a correlation between the extent of the soft-tissue release and the degree of functional impairment. Repeated soft-tissue releases can result in a stiff, painful, and arthritic foot and significantly impaired quality of life. [ABSTRACT FROM AUTHOR]- Published
- 2006
18. Femoral deformity in tibia vara.
- Author
-
Gordon JE, King DJ, Luhmann SJ, Dobbs MB, Schoenecker PL, Gordon, J Eric, King, David J, Luhmann, Scott J, Dobbs, Matthew B, and Schoenecker, Perry L
- Abstract
Background: Previous studies have suggested that compensatory valgus deformity of the femur is common in patients with tibia vara, or Blount disease. The availability and routine use of standing long-cassette radiographs of the lower extremities to assess angular deformities has allowed quantitative evaluation of this hypothesis.Methods: The cases of all patients with tibia vara, two years of age or older, seen at our institution prior to treatment, over a thirteen-year period, were reviewed. Seventy-three patients with a total of 109 involved lower limbs were identified and were classified as having either infantile tibia vara (thirty-seven patients with fifty-six involved limbs) or late-onset tibia vara (thirty-six patients with fifty-three involved limbs). Standardized standing radiographs of the lower extremity were examined to assess the deformity at the distal part of the femur and the proximal part of the tibia by measuring the lateral distal femoral angle and the medial proximal tibial angle.Results: The distal part of the femur in the children with infantile tibia vara either was normal or had mild varus deformity, with a mean lateral distal femoral angle of 97 degrees (range, 82 degrees to 129 degrees). The mean medial proximal tibial angle in these children was 72 degrees (range, 32 degrees to 84 degrees). Older children with infantile tibia vara were noted to have little distal femoral deformity, with no more than 4 degrees of valgus compared with either normal values or the contralateral, normal limb. Children with late-onset tibia vara had a mean lateral distal femoral angle of 93 degrees (range, 82 degrees to 110 degrees) and a mean medial proximal tibial angle of 73 degrees (range, 52 degrees to 84 degrees). On the average, the varus deformity of the distal part of the femur constituted 30% (6 degrees of 20 degrees) of the genu varum deformity in these patients.Conclusions: Patients with infantile tibia vara most commonly had normal alignment of the distal parts of the femora; substantial valgus deformity was not observed. Distal femoral varus constituted a substantial portion of the genu varum in children with late-onset disease. When correction of late-onset tibia vara is planned, the surgeon should be aware of the possibility that distal femoral varus is a substantial component of the deformity. [ABSTRACT FROM AUTHOR]- Published
- 2006
19. Use of an intramedullary rod for the treatment of congenital pseudarthrosis of the tibia. Surgical technique.
- Author
-
Dobbs MB, Rich MM, Gordon JE, Szymanski DA, Schoenecker PL, Dobbs, Matthew B, Rich, Margaret M, Gordon, J Eric, Szymanski, Deborah A, and Schoenecker, Perry L
- Abstract
Background: The treatment of congenital pseudarthrosis of the tibia remains difficult and controversial. The purpose of this study was to evaluate the long-term results of a technique consisting of excision of the pseudarthrosis, autologous bone-grafting, and insertion of a Williams intramedullary rod into the tibia.Methods: Twenty-one consecutive patients with congenital pseudarthrosis of the tibia were managed with this technique between 1978 and 1999, and the results were retrospectively reviewed. The mean age of the patients at the time of the latest follow-up was 17.2 years (range, seven to twenty-five years), and the mean duration of postoperative follow-up was 14.2 years (range, three to twenty years).Results: Initial consolidation occurred in eighteen of the twenty-one patients. Refracture occurred in twelve patients; five fractures healed with closed treatment, five healed after an additional surgical procedure, and two ultimately required amputation. Ten patients had an ankle valgus deformity after tibial union. Eleven patients had a residual limb-length discrepancy of >2 cm; six required a contralateral distal femoral and/or proximal tibial epiphyseodesis, two had a tibial lengthening, and one used a shoe-lift. Five patients had an amputation: two, because of a recalcitrant fracture; two, because of a limb-length discrepancy (6 and 9 cm); and one, because of a chronic lower-extremity deformity.Conclusions: This technique produced a satisfactory long-term functional outcome in sixteen of twenty-one patients and should be considered for the management of congenital pseudarthrosis of the tibia. [ABSTRACT FROM AUTHOR]- Published
- 2005
20. Can we predict the ultimate lumbar curve in adolescent idiopathic scoliosis patients undergoing a selective fusion with undercorrection of the thoracic curve?
- Author
-
Dobbs MB, Lenke LG, Walton T, Peelle M, Rocca GD, Steger-May K, Bridwell KH, Dobbs, Matthew B, Lenke, Lawrence G, Walton, Tim, Peelle, Michael, Della Rocca, Greg, Steger-May, Karen, and Bridwell, Keith H
- Abstract
Study Design: Retrospective review of anterior and posterior fusions for treatment of adolescent idiopathic thoracic scoliosis.Objectives: To delineate the best factors determining final lumbar curve magnitude in patients with adolescent idiopathic scoliosis undergoing a selective thoracic anterior or posterior spinal fusion at or proximal to the first lumbar vertebra.Summary Of Background Data: Although spontaneous lumbar curve correction occurs consistently following a selective thoracic anterior or posterior spinal fusion, the degree of correction is somewhat unpredictable.Methods: One hundred consecutive patients with major thoracic-compensatory lumbar adolescent idiopathic scoliosis treated by a single surgeon with either selective posterior spinal fusion (n = 44) or anterior spinal fusion (n = 56) of the main thoracic region with an unfused lumbar spine with a lumbar B modifier (lumbar apex touching the center sacral vertical line) or lumbar C modifier (lumbar apex completely lateral to the center sacral vertical line) were retrospectively reviewed.Results: Those patients who maintained excellent postoperative coronal balance, with spontaneous lumbar curve correction, had their thoracic Cobb corrected intraoperatively to a measurement very close to but not more than that of the preoperative thoracic push-prone Cobb. Stepwise multiple linear regression analysis was used to develop a formula to help predict lumbar response in those patients undergoing selective thoracic fusion. This is represented in the following formula: Final lumbar Cobb = 14.4 + 3.06 (lumbar modifier; 0 = B, 1 = C) + 0.30 (preoperative standing lumbar Cobb) - 0.18 (preoperative supine lower Cobb) + 0.81(preoperative push/prone lumbar Cobb) - 0.15(preoperative standing thoracic Cobb) - 0.16(% thoracic Cobb change from preoperative to immediate postoperative). Final model R2 = 0.72.Conclusions: Of the preoperative measurements examined, the preoperative push-prone is the best preoperative flexibility radiograph to predict the final lumbar curve measurement and, along with other factors, can be used to formulate a model that will help the treating surgeon more confidently predict the final lumbar curve response in patients undergoing a selective thoracic fusion. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
- View/download PDF
21. Genetics of clubfoot.
- Author
-
Dobbs MB, Gurnett CA, Dobbs, Matthew B, and Gurnett, Christina A
- Published
- 2012
- Full Text
- View/download PDF
22. CORR Insights™: Can a triple pelvic osteotomy for adult symptomatic hip dysplasia provide relief of symptoms for 25 years?
- Author
-
Dobbs MB and Dobbs, Matthew B
- Abstract
This CORR Insights™ is a commentary on the article ''Can a Triple Pelvic Osteotomy for Adult Symptomatic Hip Dysplasia Provide Relief of Symptoms for 25 Years?" By van Stralen and colleagues available at DOI 10.1007/s11999-012-2701-0 . [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
23. Long-term follow-up of patients with clubfeet treated with extensive soft-tissue release.
- Author
-
Goyal R, Gujral S, Paton RW, Dobbs MB, Nunley R, Schoenecker PL, Goyal, Ravi, Gujral, Subjeet, and Paton, Robin W
- Published
- 2006
24. Immobilization After Pinning of Supracondylar Distal Humerus Fractures in Children: Use of the A-frame Cast.
- Author
-
McKeon KE, O'Donnell JC, Bashyal R, Hou CC, Luhmann SJ, Dobbs MB, and Gordon JE
- Published
- 2012
- Full Text
- View/download PDF
25. Isolated navicular-medial cuneiform tarsal coalition revisited: a case report.
- Author
-
Ross JR, Dobbs MB, Ross, James R, and Dobbs, Matthew B
- Published
- 2011
- Full Text
- View/download PDF
26. Letter to the editor.
- Author
-
Dobbs MB and Gurnett CA
- Published
- 2011
- Full Text
- View/download PDF
27. The life and legacy of Ignacio Ponseti.
- Author
-
Dobbs MB and Khan SA
- Published
- 2010
- Full Text
- View/download PDF
28. Genetic linkage localizes an adolescent idiopathic scoliosis and pectus excavatum gene to chromosome 18 q.
- Author
-
Gurnett CA, Alaee F, Bowcock A, Kruse L, Lenke LG, Bridwell KH, Kuklo T, Luhmann SJ, Dobbs MB, Gurnett, Christina A, Alaee, Farhang, Bowcock, Anne, Kruse, Lisa, Lenke, Lawrence G, Bridwell, Keith H, Kuklo, Timothy, Luhmann, Scott J, and Dobbs, Matthew B
- Published
- 2009
- Full Text
- View/download PDF
29. Genetics in orthopaedics: editorial comment.
- Author
-
Dobbs MB
- Published
- 2007
- Full Text
- View/download PDF
30. Exome sequencing of 1190 non-syndromic clubfoot cases reveals HOXD12 as a novel disease gene.
- Author
-
Charng WL, Nikolov M, Shrestha I, Seeley MA, Josyula NS, Justice AE, Dobbs MB, and Gurnett CA
- Subjects
- Female, Humans, Male, Exome genetics, Genetic Predisposition to Disease, Pedigree, Transcription Factors genetics, Clubfoot genetics, Clubfoot pathology, Exome Sequencing, Homeodomain Proteins genetics
- Abstract
Background: Clubfoot, presenting as a rigid inward and downward turning of the foot, is one of the most common congenital musculoskeletal anomalies. The aetiology of clubfoot is poorly understood and variants in known clubfoot disease genes account for only a small portion of the heritability., Methods: Exome sequence data were generated from 1190 non-syndromic clubfoot cases and their family members from multiple ethnicities. Ultra-rare variant burden analysis was performed comparing 857 unrelated clubfoot cases with European ancestry with two independent ethnicity-matched control groups (1043 in-house and 56 885 gnomAD controls). Additional variants in prioritised genes were identified in a larger cohort, including probands with non-European ancestry. Segregation analysis was performed in multiplex families when available., Results: Rare variants in 29 genes were enriched in clubfoot cases, including PITX1 (a known clubfoot disease gene), HOXD12 , COL12A1 , COL9A3 and LMX1B . In addition, rare variants in posterior HOX genes ( HOX9-13 ) were enriched overall in clubfoot cases. In total, variants in these genes were present in 8.4% (100/1190) of clubfoot cases with both European and non-European ancestry. Among these, 3 are de novo and 22 show variable penetrance, including 4 HOXD12 variants that segregate with clubfoot., Conclusion: We report HOXD12 as a novel clubfoot disease gene and demonstrate a phenotypic expansion of known disease genes (myopathy gene COL12A1 , Ehlers-Danlos syndrome gene COL9A3 and nail-patella syndrome gene LMX1B ) to include isolated clubfoot., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
31. BrAIST-Calc: Prediction of Individualized Benefit From Bracing for Adolescent Idiopathic Scoliosis.
- Author
-
Dolan LA, Weinstein SL, Dobbs MB, Flynn JMJ, Green DW, Halsey MF, Hresko MT, Krengel WF 3rd, Mehlman CT, Milbrandt TA, Newton PO, Price N, Sanders JO, Schmitz ML, Schwend RM, Shah SA, Song K, and Talwalkar V
- Subjects
- Humans, Adolescent, Retrospective Studies, Prospective Studies, Prognosis, Braces, Treatment Outcome, Disease Progression, Scoliosis therapy
- Abstract
Study Design: Prospective multicenter study data were used for model derivation and externally validated using retrospective cohort data., Objective: Derive and validate a prognostic model of benefit from bracing for adolescent idiopathic scoliosis (AIS)., Summary of Background Data: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) demonstrated the superiority of bracing over observation to prevent curve progression to the surgical threshold; 42% of untreated subjects had a good outcome, and 28% progressed to the surgical threshold despite bracing, likely due to poor adherence. To avoid over-treatment and to promote patient goal setting and adherence, bracing decisions (who and how much) should be based on physician and patient discussions informed by individual-level data from high-quality predictive models., Materials and Methods: Logistic regression was used to predict curve progression to <45° at skeletal maturity (good prognosis) in 269 BrAIST subjects who were observed or braced. Predictors included age, sex, body mass index, Risser stage, Cobb angle, curve pattern, and treatment characteristics (hours of brace wear and in-brace correction). Internal and external validity were evaluated using jackknifed samples of the BrAIST data set and an independent cohort (n=299) through estimates of discrimination and calibration., Results: The final model included age, sex, body mass index, Risser stage, Cobb angle, and hours of brace wear per day. The model demonstrated strong discrimination ( c -statistics 0.83-0.87) and calibration in all data sets. Classifying patients as low risk (high probability of a good prognosis) at the probability cut point of 70% resulted in a specificity of 92% and a positive predictive value of 89%., Conclusion: This externally validated model can be used by clinicians and families to make informed, individualized decisions about when and how much to brace to avoid progression to surgery. If widely adopted, this model could decrease overbracing of AIS, improve adherence, and, most importantly, decrease the likelihood of spinal fusion in this population., Competing Interests: M.L.S.: consultant to Stryker, Orthofix, and OrthoPediatrics. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
32. Clubfoot: Emphasis on the Complex and Atypical Subsets.
- Author
-
Williams ML and Dobbs MB
- Subjects
- Humans, Child, Infant, Treatment Outcome, Casts, Surgical, Foot surgery, Clubfoot diagnosis, Clubfoot therapy, Orthopedic Procedures methods
- Abstract
The Ponseti method has proven to be successful in the treatment of both isolated and non-isolated clubfoot. The method should be executed prior to any pediatric invasive procedures and likewise should be attempted with any pediatric recurrence. A thorough neurologic examination and attention to clinical signs will help distinguish the atypical clubfoot. Despite this approach some children do require return to serial casting, physical therapy, and or surgery to achieve a plantigrade functional foot. Bracing strategies at a time of growth remain key., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
33. Effect of Length Stability on Complications in the Treatment of Preadolescent Diaphyseal Femur Fractures Treated With Elastic Stable Intramedullary Nailing.
- Author
-
Nixon DC, Mardam-Bey S, Miller ML, Dobbs MB, Schoenecker PL, Luhmann SJ, and Gordon JE
- Subjects
- Humans, Child, Child, Preschool, Adolescent, Retrospective Studies, Diaphyses surgery, Femur surgery, Leg Length Inequality etiology, Fracture Fixation, Intramedullary adverse effects, Femoral Fractures diagnostic imaging, Femoral Fractures surgery
- Abstract
Objectives: To examine the effectiveness and complication rates in age- and size-appropriate patients with either stable or unstable fracture patterns treated with elastic stable intramedullary nailing (ESIN)., Design: Retrospective case series., Setting: Academic tertiary care children's hospital., Patients/participants: This was a consecutive series of 106 preadolescent children with femoral shaft fractures. The mean age of the patients was 8.0 years (range, 4.0-16.0 years)., Intervention: All children were treated by retrograde ESIN., Main Outcome Measures: Fractures were categorized as either length stable or unstable. Length stability and complications were assessed. A subset of patients with final full-length, standing x-rays was also evaluated., Results: We analyzed 63 stable and 43 length unstable fractures. The mean age and weight of the patients with stable and unstable fractures were similar. There was no difference in complication rates between groups (χ2(1) = 0.00, P = 0.99). There was no difference (t(96.93) = 0.53, P = 0.59) in femoral shaft length change. Leg length discrepancies as assessed by full-length standing radiographs at follow-up were similar (χ2(2) = 1.52, P = 0.47)., Conclusions: Preadolescent children younger than 10 years do not experience increased complications after ESIN of length unstable femur fractures [odds ratio (OR) = 1.68 (0.18-16.87), P = 0.65]. Length unstable femur fractures are not at increased risk of more complications [OR = 0.90 (0.26-2.92), P = 0.87], early femoral shortening [OR = (0.42-2.02), P = 0.85], or leg length discrepancy [OR = (0.13-1.56), P = 0.21] when treated with ESIN., Level of Evidence: Prognostic Level III. See Instructions for Authors for complete description of levels of evidence., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
34. Editorial: What CORR® Seeks From Papers About New Implants and Techniques.
- Author
-
Leopold SS, Dobbs MB, Gebhardt MC, Gioe TJ, Manner PA, Porcher R, Rimnac CM, and Wongworawat MD
- Subjects
- Humans, Prostheses and Implants, Surveys and Questionnaires, Biomedical Research, Orthopedics
- Abstract
Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.
- Published
- 2022
- Full Text
- View/download PDF
35. A pathogenic mechanism associated with myopathies and structural birth defects involves TPM2-directed myogenesis.
- Author
-
McAdow J, Yang S, Ou T, Huang G, Dobbs MB, Gurnett CA, Greenberg MJ, and Johnson AN
- Subjects
- Animals, Humans, Mice, Muscle Development genetics, Tropomyosin genetics, Zebrafish, Myopathies, Nemaline metabolism, Myopathies, Structural, Congenital metabolism
- Abstract
Nemaline myopathy (NM) is the most common congenital myopathy, characterized by extreme weakness of the respiratory, limb, and facial muscles. Pathogenic variants in Tropomyosin 2 (TPM2), which encodes a skeletal muscle-specific actin binding protein essential for sarcomere function, cause a spectrum of musculoskeletal disorders that include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA). The in vivo pathomechanisms underlying TPM2-related disorders are unknown, so we expressed a series of dominant, pathogenic TPM2 variants in Drosophila embryos and found 4 variants significantly affected muscle development and muscle function. Transient overexpression of the 4 variants also disrupted the morphogenesis of mouse myotubes in vitro and negatively affected zebrafish muscle development in vivo. We used transient overexpression assays in zebrafish to characterize 2 potentially novel TPM2 variants and 1 recurring variant that we identified in patients with DA (V129A, E139K, A155T, respectively) and found these variants caused musculoskeletal defects similar to those of known pathogenic variants. The consistency of musculoskeletal phenotypes in our assays correlated with the severity of clinical phenotypes observed in our patients with DA, suggesting disrupted myogenesis is a potentially novel pathomechanism of TPM2 disorders and that our myogenic assays can predict the clinical severity of TPM2 variants.
- Published
- 2022
- Full Text
- View/download PDF
36. Diagnostic yield of exome sequencing in congenital vertical talus.
- Author
-
Tayebi N, Charng WL, Dickson PI, Dobbs MB, and Gurnett CA
- Subjects
- Chromosome Deletion, DNA Copy Number Variations, Exome genetics, Humans, Pedigree, Exome Sequencing, Flatfoot
- Abstract
Background: Congenital vertical talus (CVT), also known as "rocker-bottom foot", is a rare foot deformity associated with a dislocation of the talonavicular joint. Although genetic causes of CVT have been described in single isolated and syndromic families, whole-exome sequencing (WES) of large cohorts have not yet been reported., Methods: In this study, 62 probands with CVT were evaluated for likely causative single nucleotide variants (SNVs) and copy number variants (CNVs) using WES. Segregation of variants within families was determined by Sanger sequencing., Results: In this cohort, CVT occurred as an isolated anomaly in 75.8% (47/62) and was familial in 19.3% (12/62) of cases. Analysis of WES data led to the identification of likely causative variants in known disease genes in 30.6% (19/62) of all CVT probands. More than one proband had likely causative SNVs in TSHZ1, GDF5, and LMX1B. Only two probands had likely causative CNVs: a chromosome 12q13.13 deletion of the 5' HOXC gene cluster, and a chromosome 18q22.3q23 deletion involving TSHZ1. Familial CVT was strongly predictive of identifying a molecular diagnosis [75% (9/12) of familial cases compared to 20% (10/50) of non-familial cases (Chi-square test, P-value = 0.0002)]. There was no difference in the solved rate based on isolated or syndromic presentation, unilateral or bilateral affectation, or sex., Conclusions: CVT is genetically heterogeneous and more often caused by SNVs than CNVs. There is a high yield of WES in familial CVT cases (∼75%). Additional research is needed to identify the causes of sporadic CVT, which had much lower solved rates., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
37. Whole Exome Sequencing in Individuals with Idiopathic Clubfoot Reveals a Recurrent Filamin B (FLNB) Deletion.
- Author
-
Quiggle A, Charng WL, Antunes L, Nikolov M, Bledsoe X, Hecht JT, Dobbs MB, and Gurnett CA
- Subjects
- Adolescent, Adult, Aged, Child, Female, Genotype, Humans, Male, Middle Aged, Mutation, Phenotype, Young Adult, Clubfoot genetics, Filamins genetics, Exome Sequencing
- Abstract
Background: Clubfoot, a congenital deformity that presents as a rigid, inward turning of the foot, affects approximately 1 in 1000 infants and occurs as an isolated birth defect in 80% of patients. Despite its high level of heritability, few causative genes have been identified, and mutations in known genes are only responsible for a small portion of clubfoot heritability., Questions/purposes: (1) Are any rare gene variants enriched (that is, shared) in unrelated patients with isolated clubfoot? (2) Are there other rare variants in the identified gene (Filamin B) in these patients with clubfoot?, Methods: Whole-exome sequence data were generated from a discovery cohort of 183 unrelated probands with clubfoot and 2492 controls. Variants were filtered with minor allele frequency < 0.02 to identify rare variants as well as small insertions and deletions (indels) resulting in missense variants, nonsense or premature truncation, or in-frame deletions. A candidate deletion was then genotyped in another cohort of 974 unrelated patients with clubfoot (a replication cohort). Other rare variants in the candidate gene were also investigated. A segregation analysis was performed in multigenerational families of individuals with clubfoot to see if the genotypes segregate with phenotypes. Single-variant association analysis was performed using the Fisher two-tailed exact test (exact p values are presented to give an indication of the magnitude of the association)., Results: There were no recurrent variants in the known genes causing clubfoot in this study. A three-base pair in-frame codon deletion of Filamin B (FLNB) (p.E1792del, rs1470699812) was identified in 1.6% (3 of 183) of probands with clubfoot in the discovery cohort compared with 0% of controls (0 of 2492) (odds ratio infinity (inf) [95% CI 5.64 to inf]; p = 3.18 x 10-5) and 0.0016% of gnomAD controls (2 of 125,709) (OR 1.01 x 103 [95% CI 117.42 to 1.64 x 104]; p = 3.13 x 10-8). By screening a replication cohort (n = 974 patients), we found two probands with the identical FLNB deletion. In total, the deletion was identified in 0.43% (5 of 1157) of probands with clubfoot compared with 0% of controls and 0.0016% of gnomAD controls (OR 268.5 [95% CI 43.68 to 2.88 x 103]; p = 1.43 x 10-9). The recurrent FLNB p.E1792del variant segregated with clubfoot, with incomplete penetrance in two families. Affected individuals were more likely to be male and have bilateral clubfoot. Although most patients had isolated clubfoot, features consistent with Larsen syndrome, including upper extremity abnormalities such as elbow and thumb hypermobility and wide, flat thumbs, were noted in affected members of one family. We identified 19 additional rare FLNB missense variants located throughout the gene in patients with clubfoot. One of these missense variants, FLNB p.G2397D, exhibited incomplete penetrance in one family., Conclusion: A recurrent FLNB E1792 deletion was identified in 0.43% of 1157 isolated patients with clubfoot. Given the absence of any recurrent variants in our discovery phase (n = 183) for any of the known genes causing clubfoot, our findings support that novel and rare missense variants in FLNB in patients with clubfoot, although rare, may be among the most commonly known genetic causes of clubfoot. Patients with FLNB variants often have isolated clubfoot, but they and their family members may be at an increased risk of having additional clinical features consistent with Larsen syndrome., Clinical Relevance: Identification of FLNB variants may be useful for determining clubfoot recurrence risk and comorbidities., Competing Interests: Each author certifies that there are no commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of Bone and Joint Surgeons.)
- Published
- 2022
- Full Text
- View/download PDF
38. Clubfoot.
- Author
-
Rieger MA and Dobbs MB
- Subjects
- Casts, Surgical, Foot, Humans, Infant, Recurrence, Treatment Outcome, Clubfoot therapy
- Abstract
Clubfoot or talipes equinovarus deformity is one of the most common anomalies affecting the lower extremities. This review provides an update on the outcomes of various treatment options used to correct clubfoot. The ultimate goal in the treatment of clubfoot is to obtain a fully functional and pain-free foot and maintain a long-term correction. The Ponseti method is now considered the gold standard of treatment for primary clubfoot. Relapse is common after primary treatment with the Ponseti method, and other interventions are discussed that are used to provide for long-term successful outcomes., Competing Interests: Disclosure M.A. Rieger and M.B. Dobbs: No disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
39. A Decade in Review after Idiopathic Scoliosis Was First Called a Complex Trait-A Tribute to the Late Dr. Yves Cotrel for His Support in Studies of Etiology of Scoliosis.
- Author
-
Tang NLS, Dobbs MB, Gurnett CA, Qiu Y, Lam TP, Cheng JCY, and Hadley-Miller N
- Subjects
- Animals, Child, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeodomain Proteins genetics, Humans, Phenotype, Scoliosis diagnostic imaging, Spine diagnostic imaging, Transcription Factors genetics, Multifactorial Inheritance, Scoliosis etiology, Scoliosis genetics
- Abstract
Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development.
- Published
- 2021
- Full Text
- View/download PDF
40. Models of Distal Arthrogryposis and Lethal Congenital Contracture Syndrome.
- Author
-
Whittle J, Johnson A, Dobbs MB, and Gurnett CA
- Subjects
- Animals, Arthrogryposis pathology, Drosophila melanogaster, Genetic Loci, Mice, Mutation, Zebrafish, Arthrogryposis genetics, Disease Models, Animal
- Abstract
Distal arthrogryposis and lethal congenital contracture syndromes describe a broad group of disorders that share congenital limb contractures in common. While skeletal muscle sarcomeric genes comprise many of the first genes identified for Distal Arthrogyposis, other mechanisms of disease have been demonstrated, including key effects on peripheral nerve function. While Distal Arthrogryposis and Lethal Congenital Contracture Syndromes display superficial similarities in phenotype, the underlying mechanisms for these conditions are diverse but overlapping. In this review, we discuss the important insights gained into these human genetic diseases resulting from in vitro molecular studies and in vivo models in fruit fly, zebrafish, and mice.
- Published
- 2021
- Full Text
- View/download PDF
41. Rare and de novo coding variants in chromodomain genes in Chiari I malformation.
- Author
-
Sadler B, Wilborn J, Antunes L, Kuensting T, Hale AT, Gannon SR, McCall K, Cruchaga C, Harms M, Voisin N, Reymond A, Cappuccio G, Brunetti-Pierri N, Tartaglia M, Niceta M, Leoni C, Zampino G, Ashley-Koch A, Urbizu A, Garrett ME, Soldano K, Macaya A, Conrad D, Strahle J, Dobbs MB, Turner TN, Shannon CN, Brockmeyer D, Limbrick DD, Gurnett CA, and Haller G
- Published
- 2021
- Full Text
- View/download PDF
42. Genetic association and characterization of FSTL5 in isolated clubfoot.
- Author
-
Khanshour AM, Kidane YH, Kozlitina J, Cornelia R, Rafipay A, De Mello V, Weston M, Paria N, Khalid A, Hecht JT, Dobbs MB, Richards BS, Vargesson N, Hamra FK, Wilson M, Wise C, Gurnett CA, and Rios JJ
- Subjects
- Animals, Clubfoot pathology, Disease Models, Animal, Extremities pathology, Gene Expression Regulation genetics, Gene Knockout Techniques, Genetic Association Studies, Humans, Mice, Rats, Clubfoot genetics, Follistatin-Related Proteins genetics, Genetic Predisposition to Disease, Homeodomain Proteins genetics
- Abstract
Talipes equinovarus (clubfoot, TEV) is a congenital rotational foot deformity occurring in 1 per 1000 births with increased prevalence in males compared with females. The genetic etiology of isolated clubfoot (iTEV) remains unclear. Using a genome-wide association study, we identified a locus within FSTL5, encoding follistatin-like 5, significantly associated with iTEV. FSTL5 is an uncharacterized gene whose potential role in embryonic and postnatal development was previously unstudied. Utilizing multiple model systems, we found that Fstl5 was expressed during later stages of embryonic hindlimb development, and, in mice, expression was restricted to the condensing cartilage anlage destined to form the limb skeleton. In the postnatal growth plate, Fstl5 was specifically expressed in prehypertrophic chondrocytes. As Fstl5 knockout rats displayed no gross malformations, we engineered a conditional transgenic mouse line (Fstl5LSL) to overexpress Fstl5 in skeletal osteochondroprogenitors. We observed that hindlimbs were slightly shorter and that bone mineral density was reduced in adult male, but not female, Prrx1-cre;Fstl5LSL mice compared with control. No overt clubfoot-like deformity was observed in Prrx1-cre;Fstl5LSL mice, suggesting FSTL5 may function in other cell types to contribute to iTEV pathogenesis. Interrogating published mouse embryonic single-cell expression data showed that Fstl5 was expressed in cell lineage subclusters whose transcriptomes were associated with neural system development. Moreover, our results suggest that lineage-specific expression of the Fstl genes correlates with their divergent roles as modulators of transforming growth factor beta and bone morphogenetic protein signaling. Results from this study associate FSTL5 with iTEV and suggest a potential sexually dimorphic role for Fstl5 in vivo., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
43. Rare and de novo duplications containing SHOX in clubfoot.
- Author
-
Sadler B, Haller G, Antunes L, Nikolov M, Amarillo I, Coe B, Dobbs MB, and Gurnett CA
- Subjects
- Adolescent, Child, Child, Preschool, Chromosome Duplication genetics, Clubfoot pathology, DNA Copy Number Variations genetics, Gene Duplication genetics, Humans, Infant, Microarray Analysis, Middle Aged, Pedigree, Pseudoautosomal Regions genetics, Exome Sequencing, Clubfoot genetics, Genetic Predisposition to Disease, Paired Box Transcription Factors genetics, Short Stature Homeobox Protein genetics, T-Box Domain Proteins genetics
- Abstract
Introduction: Congenital clubfoot is a common birth defect that affects at least 0.1% of all births. Nearly 25% cases are familial and the remaining are sporadic in inheritance. Copy number variants (CNVs) involving transcriptional regulators of limb development, including PITX1 and TBX4 , have previously been shown to cause familial clubfoot, but much of the heritability remains unexplained., Methods: Exome sequence data from 816 unrelated clubfoot cases and 2645 in-house controls were analysed using coverage data to identify rare CNVs. The precise size and location of duplications were then determined using high-density Affymetrix Cytoscan chromosomal microarray (CMA). Segregation in families and de novo status were determined using qantitative PCR., Results: Chromosome Xp22.33 duplications involving SHOX were identified in 1.1% of cases (9/816) compared with 0.07% of in-house controls (2/2645) (p=7.98×10
-5 , OR=14.57) and 0.27% (38/13592) of Atherosclerosis Risk in Communities/the Wellcome Trust Case Control Consortium 2 controls (p=0.001, OR=3.97). CMA validation confirmed an overlapping 180.28 kb duplicated region that included SHOX exons as well as downstream non-coding regions. In four of six sporadic cases where DNA was available for unaffected parents, the duplication was de novo . The probability of four de novo mutations in SHOX by chance in a cohort of 450 sporadic clubfoot cases is 5.4×10-10 ., Conclusions: Microduplications of the pseudoautosomal chromosome Xp22.33 region (PAR1) containing SHOX and downstream enhancer elements occur in ~1% of patients with clubfoot. SHOX and regulatory regions have previously been implicated in skeletal dysplasia as well as idiopathic short stature, but have not yet been reported in clubfoot. SHOX duplications likely contribute to clubfoot pathogenesis by altering early limb development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
- Full Text
- View/download PDF
44. MYH3-associated distal arthrogryposis zebrafish model is normalized with para-aminoblebbistatin.
- Author
-
Whittle J, Antunes L, Harris M, Upshaw Z, Sepich DS, Johnson AN, Mokalled M, Solnica-Krezel L, Dobbs MB, and Gurnett CA
- Subjects
- Animals, Humans, Mutation, Phenotype, Zebrafish, Arthrogryposis genetics, Synostosis
- Abstract
Distal arthrogryposis (DA) is group of syndromes characterized by congenital joint contractures. Treatment development is hindered by the lack of vertebrate models. Here, we describe a zebrafish model in which a common MYH3 missense mutation (R672H) was introduced into the orthologous zebrafish gene smyhc1 (slow myosin heavy chain 1) (R673H). We simultaneously created a smyhc1 null allele (smyhc1
- ), which allowed us to compare the effects of both mutant alleles on muscle and bone development, and model the closely related disorder, spondylocarpotarsal synostosis syndrome. Heterozygous smyhc1R673H/+ embryos developed notochord kinks that progressed to scoliosis with vertebral fusions; motor deficits accompanied the disorganized and shortened slow-twitch skeletal muscle myofibers. Increased dosage of the mutant allele in both homozygous smyhc1R673H/R673H and transheterozygous smyhc1R673H/- embryos exacerbated the notochord and muscle abnormalities, causing early lethality. Treatment of smyhc1R673H/R673H embryos with the myosin ATPase inhibitor, para-aminoblebbistatin, which decreases actin-myosin affinity, normalized the notochord phenotype. Our zebrafish model of MYH3-associated DA2A provides insight into pathogenic mechanisms and suggests a beneficial therapeutic role for myosin inhibitors in treating disabling contractures., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)- Published
- 2020
- Full Text
- View/download PDF
45. Improving musculoskeletal health for children and young people - A 'call to action'.
- Author
-
Foster HE, Scott C, Tiderius CJ, and Dobbs MB
- Subjects
- Adolescent, Child, Humans, Workforce, Musculoskeletal Diseases diagnosis, Musculoskeletal Diseases epidemiology, Musculoskeletal Diseases therapy
- Abstract
This chapter describes the musculoskeletal (MSK) context in children and young people as an important contributor to the global non-communicable disease burden. Through selected MSK conditions, we describe the impact on patients, families and communities and highlight the challenges that need to be addressed. We focus on opportunities for better working together and describe exemplar initiatives to raise awareness, workforce capacity building, models of care and research agendas to have a greater global context., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
46. Selective Dorsal Rhizotomy for the Treatment of Spastic Hemiplegic Cerebral Palsy.
- Author
-
Park TS, Joh S, Walter DM, Meyer NL, and Dobbs MB
- Abstract
Background Selective dorsal rhizotomy (SDR) can remove spasticity in cerebral palsy (CP). Spastic hemiplegia is associated with spasticity in the upper and lower limbs on one side. Only a single report described the outcome of SDR specifically in patients with spastic hemiplegic CP. The effect of SDR on spastic hemiplegia requires further investigation. Objectives To analyze the outcomes of motor functions, the quality of life, and satisfaction of patients who received SDR for the treatment of spastic hemiplegia. Methods A total of 29 children and 1 adult who received SDR were surveyed. The survey questionnaire asked about demographic information, patient's perception of SDR, functional outcomes, SDR surgical outcomes, pain, braces/orthotics, and post-SDR treatment. Results Our study included 30 patients. The age at the time of surgery was 2 to 36 years. The follow-up period ranged from one to six years. Of all parents, 90% of parents reported that SDR benefited their children, and 93% stated that they would recommend the SDR procedure to other families of children with hemiplegic CP. Of all patients, 90% reported improved walking, 63% reported improved sitting, and 87% reported improved balance and posture. In daily life functioning after the SDR, 67% were more independent and confident. Moreover, 33% of patients were pain-free and 43% had reduced pain in their legs and back. In activities of daily living, 93% transferred independently from one position to another. A majority of the patients reported regular strengthening and stretching of the lower limb, and 50% of the patients played sports. A majority (73%) of patients underwent post-SDR orthopedic surgery for heel cord, hamstring, and adductor contractures. Five patients experienced numbness in the small part of the lower limb after SDR. None reported that the numbness affected their daily activities. One child required surgical repair of the cerebrospinal fluid leak. Conclusions In our 29 children and 1 adult with spastic hemiplegia, SDR improved motor function and daily life function. Nearly all parents of children and the one adult felt that SDR was beneficial and that they would recommend surgery to other children with spastic hemiplegia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Park et al.)
- Published
- 2020
- Full Text
- View/download PDF
47. Treatment of femoral fractures in children aged two to six.
- Author
-
Gordon JE, Anderson JT, Schoenecker PL, Dobbs MB, Luhmann SJ, and Hoernschemeyer DG
- Subjects
- Age Factors, Child, Child, Preschool, Cohort Studies, Female, Femoral Fractures diagnostic imaging, Follow-Up Studies, Fracture Fixation methods, Hospitals, Pediatric, Humans, Male, Patient Selection, Prospective Studies, Risk Assessment, Time Factors, Casts, Surgical, Femoral Fractures therapy, Fracture Fixation, Intramedullary methods, Fracture Healing physiology, Pain Management methods
- Abstract
Aims: Current American Academy of Orthopaedic Surgeons (AAOS) guidelines for treating femoral fractures in children aged two to six years recommend early spica casting although some individuals have recommended intramedullary stabilization in this age group. The purpose of this study was to compare the treatment and family burden of care of spica casting and flexible intramedullary nailing in this age group., Methods: Patients aged two to six years old with acute, non-pathological femur fractures were prospectively enrolled at one of three tertiary children's hospitals. Either early closed reduction with spica cast application or flexible intramedullary nailing was accomplished under general anaesthesia. The treatment method was selected after discussion of the options by the surgeon with the family. Data were prospectively collected on patient demographics, fracture characteristics, complications, pain medication, and union. The Impact on Family Scale was obtained at the six-week follow-up visit. In all, 75 patients were included in the study: 39 in the spica group and 36 in the nailing group. The mean age of the spica group was 2.71 (2.0 to 6.9) years and the mean age of the nailing group was 3.16 (2.0 to 6.9) years., Results: All fractures healed without evidence of malunion or more than 2.0 cm of shortening. The mean Impact on Family score was 70.2 for the spica group and 63.2 (55 to 99) for the nailing group, a statistically significant difference (p = 0.024) in a univariate analysis suggesting less impairment of the family in the intramedullary nailing group. There was no significant difference between pain medication requirements in the first 24 hours postoperatively. Two patients in the spica group and one patient in the intramedullary nailing group required additional treatment under anaesthesia., Conclusion: Both early spica casting and intramedullary nailing were effective methods for treating femoral fractures in children two to six years of age. Intramedullary stabilization provides an option in this age group that may be advantageous in some social situations that depend on the child's mobility. Fracture treatment should be individualized based on factors that extend beyond anatomical and biological factors. Cite this article: Bone Joint J 2020;102-B(8):1056-1061.
- Published
- 2020
- Full Text
- View/download PDF
48. Selective Dorsal Rhizotomy for the Treatment of Spastic Triplegic Cerebral Palsy.
- Author
-
Park TS, Joh S, Walter DM, and Dobbs MB
- Abstract
Background Spastic triplegia is a recognized subtype of cerebral palsy (CP). In the course of treating spastic triplegic children with selective dorsal rhizotomy (SDR), we found that some children who had "minimal or mild involvement" in the stronger arm improved strikingly after undergoing SDR. Some of them became independent ambulators, which was an outcome that is not usually achieved in spastic quadriplegic children. However, the literature currently contains no data on the natural clinical course and the effects of CP interventions on spastic triplegia. Objectives Our aim was to elucidate the clinical characteristics of spastic triplegia and the effects of SDR on functional outcomes and the quality of life after childhood SDR. Methods The Institutional Review Board of the Washington University School of Medicine approved this quality of life survey (number: 201908177). The subjects of this study were children and adults (ages: 3.9-23.8 years at the time of the survey completion; mean: 12.1 ± 5.1 years) with spastic triplegic CP who had undergone SDR (ages: 2.2-15.9 years; mean: 6.1 ± 3.2 years) between 2003 and 2018 at the St. Louis Children's Hospital. The follow-up period ranged from 1-16 years (mean: 6.0 ± 4.3 years). The study included a 76-patient cohort selected from a total of 253 spastic triplegic CP patients who had undergone SDR. All 253 patients were contacted via email or postal mail soliciting their participation in the study including the survey. The cohort included all patients who responded. The survey included questions on demographic information, quality of life, perceptions of health and the SDR procedure, motor and ambulatory functions, braces and orthotics, pain issues, side effects of SDR, and post-SDR treatment. Results Thirteen patients had presented with scissored gait, and these patients had undergone partial ventral rhizotomy (PVR) of L1-3 ventral roots immediately after the completion of SDR. Of note, 91% of 76 patients reported that SDR improved their quality of life, and 93% would recommend the procedure to other patients. After SDR, 21 more patients were able to run, 14 more played recreational sports, and 18 more could walk without using walking aids. Sixteen fewer patients used a wheelchair for long-distance walking and in crowds; 37 and 32 patients reported an improvement in the more affected arm and hand, respectively. Sixty-eight patients were able to regularly strengthened their muscles at least once a week, and 60 patients regularly stretched their legs. However, 53 patients required assistance with bathing or showering, 50 with getting dressed, and 56 with grooming or hygiene. Forty-eight patients had orthopedic surgery after SDR. Percutaneous hamstring-lengthening was the most common type of orthopedic surgery performed. Three of 13 patients who received PVR and SDR required adductor release. Six patients used medications for spasticity or dystonia. No late side effects of SDR were observed. Conclusions Our report elucidates the clinical features of spastic triplegia before and after SDR. A distinct clinical feature was the wide variation in ambulatory functions, ranging from total independent walking to wheelchair mobility. The vast majority of patients felt that SDR improved their motor functions and quality of life. PVR also resulted in favorable outcomes, with only three of 13 patients requiring additional adductor release surgery. There were no late complications related to SDR surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Park et al.)
- Published
- 2020
- Full Text
- View/download PDF
49. The paediatric global musculoskeletal task force - 'towards better MSK health for all'.
- Author
-
Foster HE, Scott C, Tiderius CJ, and Dobbs MB
- Subjects
- Child, Global Burden of Disease, Health Services Accessibility, Humans, Preventive Health Services, Quality of Health Care, Socioeconomic Factors, Health Promotion methods, Health Promotion organization & administration, Healthcare Disparities organization & administration, International Cooperation, Musculoskeletal Diseases epidemiology, Musculoskeletal Diseases prevention & control, Noncommunicable Diseases epidemiology
- Abstract
There is increasing concern about the emerging global non-communicable diseases (NCDs) burden. The focus has mainly been on NCDs in adults but it is important that MSK morbidity in both children and adults is included in strategic planning. There have been considerable advances in the understanding and treatment options for children and young people (CYP) and clinical outcomes are improving for those who can access such high quality care. However vast inequity exists and there are many CYP who live in areas of the world with high burden of health care challenges, compounded by paucity of specialist care and limited access to treatments. The Paediatric Global Musculoskeletal Task Force aims to raise awareness about unmet needs for CYP with MSK conditions, promotion of MSK health through lifestyle and the avoidance of injury. We aim to leverage change through 'working together better'.
- Published
- 2020
- Full Text
- View/download PDF
50. Editorial: Postcards from War Zones-Personal Experiences During the COVID-19 Pandemic.
- Author
-
Leopold SS and Dobbs MB
- Published
- 2020
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.