Timur Yildirim

Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin

BACKGROUND Arthrogryposis, defined as congenital joint contractures in 2 or more body areas, is a clinical sign rather than a specific disease diagnosis. To date, more than 400 different disorders have been described that present with arthrogryposis, and variants of more than 220 genes have been associated with these disorders; however, the underlying molecular etiology remains unknown in the considerable majority of these cases. METHODS We performed whole exome sequencing (WES) of 52 patients with clinical presentation of arthrogryposis from 48 different families. RESULTS Affected individuals from 17 families (35.4%) had variants in known arthrogryposis-associated genes, including homozygous variants of cholinergic γ nicotinic receptor (CHRNG, 6 subjects) and endothelin converting enzyme-like 1 (ECEL1, 4 subjects). Deleterious variants in candidate arthrogryposis-causing genes (fibrillin 3 [FBN3], myosin IXA [MYO9A], and pleckstrin and Sec7 domain containing 3 [PSD3]) were identified in 3 families (6.2%). Moreover, in 8 families with a homozygous mutation in an arthrogryposis-associated gene, we identified a second locus with either a homozygous or compound heterozygous variant in a candidate gene (myosin binding protein C, fast type [MYBPC2] and vacuolar protein sorting 8 [VPS8], 2 families, 4.2%) or in another disease-associated genes (6 families, 12.5%), indicating a potential mutational burden contributing to disease expression. CONCLUSION In 58.3% of families, the arthrogryposis manifestation could be explained by a molecular diagnosis; however, the molecular etiology in subjects from 20 families remained unsolved by WES. Only 5 of these 20 unrelated subjects had a clinical presentation consistent with amyoplasia; a phenotype not thought to be of genetic origin. Our results indicate that increased use of genome-wide technologies will provide opportunities to better understand genetic models for diseases and molecular mechanisms of genetically heterogeneous disorders, such as arthrogryposis. FUNDING This work was supported in part by US National Human Genome Research Institute (NHGRI)/National Heart, Lung, and Blood Institute (NHLBI) grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, and US National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS058529 to J.R. Lupski.

Cementless total hip arthroplasty in patients with Crowe type-4 developmental dysplasia

Background Developmental dysplasia of the hip is one of the most common causes of secondary osteoarthritis. The purpose of our study was to review clinical and radiological outcomes of reconstruction surgery using cementless total hip arthroplasty in patients with Crowe type-IV dysplastic hips. Methods This study included eighty-seven primary total hip arthroplasties performed between January 2005 and January 2010 at our clinic in 74 patients who had Crowe type-IV developmental dysplasia of the hip. Cementless total hip arthroplasty was applied in all hips. At the clinical status analysis, any limping, the Harris hip score, surgical approach, the use of bone grafts, the presence of femoral osteotomy, any component migration, union status of the osteotomy site (if present), and any osteolysis or heterotopic ossification were noted. Mean follow-up time was 4.8 years. Results Mean Harris hip score was improved from 41.8 points preoperatively to 86.2 points postoperatively (p<0.001). At the final clinical examination, none of the patients had severe limping. Restoration of the anatomical hip centre was achieved in all hips. Pseudoarthrosis of the femoral osteotomy site was seen in two hips (3.6%). Twelve hips (13.8%) underwent revision surgery. Neurological complications were seen in two hips (2.3%). Heterotopic ossification was detected in one hip. conclusion Cementless total hip arthroplasty with restoration of the anatomic hip centre resulted in satisfactory clinical outcomes in patients with secondary coxarthrosis due to Crowe type IV developmental dysplasia of the hip joint.

The prevalence of femoroacetabular impingement as an aetiologic factor for end-stage degenerative osteoarthritis of the hip joint: analysis of 1,000 cases

Objective The main purpose of the present study was to determine the prevalence of FAI among patients who underwent total hip arthroplasty (THA) with the diagnosis of end-stage osteoarthritis (OA) of the hip joint in a tertiary referral centre. Design A retrospective search of the institutional archive database for patients who had undergone THA between the years 2005 and 2010 was conducted with the analysis of the recorded radiographic images. A total of 1,004 patients including 690 (68.7%) females and 314 (31.3%) males were identified. All radiographs were reviewed by 3 of the authors. Intra- and interobserver consistencies were calculated. The prevalence of femeroacetabular impingement (FAI) as a predisposing diagnosis resulting in end-stage degenerative joint disease treated with THA was determined. Results The most common diagnosis was developmental dysplasia of the hip (DDH). The predisposing aetiologic factor leading to end-stage degenerative hip disease treated with THA was undetermined for 26 patients (2.6%). The number of patients who were diagnosed as cam-type FAI by all of the observers was 83, whereas it was 16 for pincer-type FAI. Interobserver agreement was very high in the evaluation of the stated ethiologies of hip osteoarthritis. The contingency coefficient for the diagnosis of FAI was 0.71 between observers. Conclusions Our study may be a reference for further investigations to develop a better understanding of the underlying pathological factors in patients undergoing THA due to end-stage OA of the hip joint.

Use of quadriceps tendon versus hamstring tendon autograft for arthroscopic anterior cruciate ligament reconstruction: a comparative analysis of clinical results.

OBJECTIVES This study aims to evaluate midterm clinical results of the use of two autogenous graft types. PATIENTS AND METHODS Between June 2005 and November 2010, clinical data of 44 patients who were operated were retrospectively analyzed. Quadriceps tendon-patellar bone autograft was used for reconstruction surgery in 23 patients (QT-PB group), while quadrupled hamstring tendon autograft was used in 21 patients (HT group). The Tegners activity scale, Lysholm scoring system, single-leg-hop test and KT-2000 arthrometric measurements were used for data collection. RESULTS The mean length of follow-up was 37.6 months. Although the mean Lysholm score increased in both groups, excellent results in HT group were two-fold higher compared to QT-PB group. The mean laxity for the operated knee joint was 5.65 mm (3.5 to 8.0 mm) in QT-PB group and 3.67 mm (3.0 to 5.5 mm) in HT group. Head-to-head analysis using KT-2000 arthrometer demonstrated that 12 patients (52.1%) in QT-PB group and two patients (9.6%) in HT group had more than 3 mm of anterior laxity difference. CONCLUSION Quadrupled hamstring tendon autograft is superior to central quadriceps tendon-patellar bone in arthroscopic anterior cruciate ligament reconstruction surgery.

Comparison of intramedullary nail and plate fixation in distal tibia diaphyseal fractures close to the mortise

BACKGROUND In this study, we aimed to compare the functional and radiological results of intramedullary nailing and plate fixation techniques in the surgical treatment of distal tibia diaphyseal fractures close to the ankle joint. METHODS Between 2005 and 2011, 55 patients (32 males, 23 females; mean age 42 years; range 15 to 72 years) who were treated with intramedullary nailing (21 patients) or plate fixation (34 patients) due to distal tibia diaphyseal fracture were included in the study. The average follow-up period was 27.6 months (range, 12-82 months). The patients were evaluated with regard to nonunion, malunion, infection, and implant irritation. The AOFAS (American Orthopaedic Foot and Ankle Society) scale was used for the clinical evaluation. RESULTS No statistically significant difference was found between the two surgical methods with respect to unification time, AOFAS score, accompanying fibula fracture, material irritation, and malunion. Nine patients had open fractures, and these patients were treated with plate fixation (p=0.100). Nonunion developed in three patients who were treated with plates. Infection occurred in one patient. Anterior knee pain was significantly higher in patients who were treated with intramedullary nails. There was no malunion in any patient. CONCLUSION As the distal fragment is not long enough, plate fixation technique is usually preferred in the treatment of distal tibia diaphyseal fractures. In this study, we observed that if the surgical guidelines are followed carefully, intramedullary nailing is an appropriate technique in this kind of fracture. The malunion rates are not significantly increased, and it also has the advantages of being a minimally invasive surgery with fewer wound problems.

Long-term follow-up results of foot and ankle tuberculosis in Turkey.

The incidence of tuberculosis has been increasing, especially in the past 2 decades. Skeletal tuberculosis is very rare compared with the frequency of the pulmonary form. In the present study, we have shared our long-term experience with foot and ankle tuberculosis, providing information about the different aspects of the disease. A total of 70 patients with foot and ankle tuberculosis, treated from 1983 to 2005, were evaluated. The mean patient age was 34.4 (range 7 to 85) years at the diagnosis. The mean interval between the first symptoms and the diagnosis was 26.4 months (range 1 month to 15 years). The mean follow-up period was 21.7 (range 8 to 30) years. The infection affected both the joint and the bones in 29 patients, only the joints in 13, only the bones in 22, and the soft tissues alone in the remaining 6 patients. The most common joint location was the tibiotalar joint. The talus was the most commonly infiltrated bone. All patients underwent biopsy, and 28 patients underwent additional surgical procedures. In 18 patients (25.7%), 1 to 4 recurrences developed during the follow-up period. In the last follow-up visits, either severe destruction of the bones or end-stage arthrosis was evident in 39 patients (55.7%), especially in those with osseous tuberculosis. Foot and ankle tuberculosis is very rare. The diagnosis of the disease will often be late owing to the lack of pathognomonic findings. A histopathologic evaluation should not be omitted in cases with suspicion. The incidence of residual deformity or end-stage arthrosis has been high in the long term; however, the patients will usually be without any symptoms.

[A comparison of short-term clinical and radiological results of Tönnis and Steel pelvic osteotomies in patients with acetabular dysplasia].

OBJECTIVES This study aims to compare short-term clinical and radiological results of adult patients with acetabular dysplasia undergoing Tönnis osteotomy or Steel triple pelvic osteotomy. PATIENTS AND METHODS Between March 2003 and January 2010, clinical and radiologic results in 61 patients who were operated due to acetabular dysplasia at Baltalimanı Bone and Joint Diseases Hospital were retrospectively analyzed. The patients were divided into two groups including those undergoing Tönnis osteotomy (Tönnis group) or Steel osteotomy (Steel group). For each patient, anteroposterior and false-profile radiographs of the pelvis were taken and anterior center edge (ACE), lateral center edge (LCE), Sharp angles and acetabular coverage were measured. The relationship between femoral head and acetabulum was assessed. Harris hip score was used for the clinical evaluation. RESULTS According to the evaluation of the clinical and radiological results, postoperative scores were improved significantly in both groups, compared to preoperative scores (p<0.01). No statistically significant difference was found between the groups in terms of improvements in the radiological and clinical scores, except ACE angle (p<0.01). CONCLUSION Our study results suggest that Tönnis and Steel osteotomies offer satisfactory short-term results in the surgical treatment of adult patients with mild to moderate dysplasia.

Art in Science: Orthopaedics Through Philatelic Material

Postage stamps have often been used to educate populations on recent developments, achievements, or figures who made important contributions to humanity [1, 12, 19, 24]. The study of stamps and postal history, called philately, can include different areas of interest, including medical philately [3].

An effective treatment for hip instabilities: pelvic support osteotomy and femoral lengthening

OBJECTIVE In this study, we evaluated the effectiveness of pelvic support osteotomy treatment in hip instabilities due to various etiologies. METHODS We retrospectively evaluated 21 hips of 20 patients that underwent pelvic support osteotomy between 2005 and 2007. Hip instability was caused by a neglected congenital dislocation of the hip in 12 of the patients (13 hips), by septic arthritis in 7 and by an unsuccessful total hip arthroplasty due to infection in the last patient. The mean age of the patients was 22.6 (range: 12 to 34) years. Osteotomy sites were fixed using monolateral external fixators in 11 patients, Ilizarov circular fixators in 8, and locking plates for both hips of the remaining patient. The mean follow-up period was 33.45 (range: 16 to 45) months. RESULTS The mean Harris score increased from 48.3 preoperatively to 80.1 postoperatively. Preoperative mean limb length discrepancy was 53.3 mm and mean proximal migration was 42.9 mm. Residual limb length discrepancy was reduced to 16 mm after an average lengthening of 63.3. The preoperative Trendelenburg gait disappeared completely in 13 of 21 hips and was improved in 8 hips. Sixteen of the 20 patients (17 hips) expressed satisfaction with the operation. CONCLUSION Pelvic support osteotomy is a good treatment option to overcome hip instability as it improves pain and equalizes limb length.

Talectomy and Tibiocalcaneal Arthrodesis With Intramedullary Nail Fixation for Treatment of Equinus Deformity in Adults

Background: Severe equinovarus foot deformity in adults is a challenging problem. Conservative treatment rarely is effective, and operative options are limited. The aim of this study was to evaluate the results of talectomy and tibiocalcaneal arthrodesis with intramedullary nail fixation for the treatment of severe equinovarus deformity in adults. Methods: Twelve patients (average age 39 years, range 15-70 years) with severe equinovarus deformities of the foot were treated with talectomy and tibiocalcaneal arthrodesis with intramedullary nail fixation between March 2010 and February 2013. Average follow-up was 20 months (range 10-37 months). Results: Tibiocalcaneal fusion was achieved in all patients at an average of 12 weeks (range 8-17 weeks). Preoperatively, all patients had severe, irreducible equinovarus deformities; at last follow-up, almost all feet had mild residual deformity, but were plantigrade and did not require a brace or orthosis. The average AOFAS ankle score improved from 41.1 (range 8-66) preoperatively to 78.4 (range 67-86) postoperatively (P = .02). There was a similar improvement in the average VAS score from 6.3 (range 2-10) preoperatively to 0.8 (range 0-4) postoperatively (P = .02). Conclusion: The combination of talectomy and tibiocalcaneal arthrodesis was effective in correcting severe rigid equinovarus deformity in adults. Removal of the talus resulted in laxity of the soft tissues, making correction of the deformity easier. Tibiocalcaneal arthrodesis achieved a stable foot without the problems associated with talectomy alone. Level of Evidence: Level IV, case series.