Ilhan A. Bayhan

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.

P 152 – Gender differences in three dimensional gait analysis data from pediatric athletes

Gender can affect the skeletal and muscle morphology. Also, the walking patterns between male and female individuals can be different. Aim of this study was to compare the three dimensional gait analysis vairables between male and female pediatric athletes.

Comparative Results of External Fixation, Plating, or Nonoperative Management for Diaphyseal Clavicle Fractures

Objective: The aim of this study was to compare the treatment outcomes of mid-diaphyseal clavicular fractures between an external fixator and more widely selected treatment options such as plate osteosynthesis or conservative methods. Materials and Methods: The medical records of 64 patients who were treated for mid-diaphyseal clavicular fracture in our clinic from 2009 to 2013 were reviewed. The inclusion criterion was mid-diaphyseal closed clavicular fractures with shortening of more than 2 cm. The Constant and DASH (disabilities of the arm, shoulder, and hand) scores at the final follow-up, initial displacement, nonunion, and complication rates were compared. Statistical differences between groups were assessed with the Kruskal-Wallis test, and pairwise comparison analysis was used to evaluate the differences within the groups. Results: Of the 64 patients, 24 (37.5%) were treated with plate osteosynthesis (group 1), 11 (17.2%) with an external fixator (group 2), and 29 (45.3%) conservatively with a figure-of-eight bandage (group 3). The mean follow-up periods were as follows: group 1: 37 ± 10.4 months, group 2: 33 ± 7 months, and group 3: 35 ± 9.4 months. The initial amount of displacement and DASH score were: group 1: 89.1 ± 7.8, group 2: 89.1 ± 7.8, and group 3: 6.1 ± 6.6) (p = 0.079). The Constant score of group 2 (93 ± 6.1) was significantly higher than that of group 3 (85 ± 8.4) (p = 0.013). No statistical difference was found in the distribution of nonunions (p = 0.387). However, in group 3, the number of malunions (11/29, 37.9%) was significantly higher compared to the other 2 groups (group 1: 1/24, 4.2%; group 2: 2/11, 18.2%) (p = 0.006). Conclusions: This study revealed that the treatment of acute clavicular fractures with an external fixator was a good alternative to plate osteosynthesis or conservative treatment.

Comparison of Salter osteotomy and Tonnis lateral acetabuloplasty with simultaneous open reduction for the treatment of developmental dysplasia of the hip: midterm results.

The aim of this study was to compare the midterm clinical and radiological outcomes of the Salter osteotomy (SO) and Tonnis lateral acetabuloplasty (TLA) with concomitant open reduction for the treatment of developmental dysplasia of the hip. Twenty-five hips of 20 patients who underwent SO with open reduction and 26 hips of 23 patients who underwent TLA with open reduction were evaluated retrospectively. The average age of the patients at the time of the operation was 35.6 months in the SO and 36.6 months in the TLA group, without a statistically significant difference (P=0.836). The average follow-up times in the SO and TLA groups were 59.9 and 54.8 months, respectively (P=0.397). Preoperative (40.6° in the SO vs. 42.2° in the TLA, P=0.451) and last follow-up acetabular index (12° in the SO vs. 14° in the TLA, P=0.227) and center-edge angle measurements (30° in the SO vs. 26° in the TLA, P=0.069) did not show a statistically significant difference between the SO and TLA groups; however, early postoperative acetabular index improvement was better in the TLA group than in the SO group (21.2° in the SO vs. 17.2° in the TLA, P=0.014). According to the Severin grading system, both groups showed a similar number of good outcomes without a statistically significant difference (P=0.936). Clinical assessment on the basis of McKay’s criteria showed similar good and excellent outcomes (P=0.936). Both osteotomy techniques showed similar satisfactory outcomes for the treatment of DDH in patients older than 18 months of age.