Ki-Sun Sung

Mutations in DDX58, which Encodes RIG-I, Cause Atypical Singleton-Merten Syndrome

Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

Short-term Results of Total Ankle Arthroplasty for End-stage Ankle Arthritis With Severe Varus Deformity

Background: Many authors have reported that an ankle varus deformity more than 10 to 15 degrees may be the cause of failures in total ankle arthroplasty. Our study aim was to analyze short-term outcomes of total ankle arthroplasty with additional procedures accompanied by more than 20 degrees of varus deformity. Methods: Among the patients who received total ankle arthroplasty for end-stage osteoarthritis between June 2006 and May 2012, 103 cases that were followed for more than 6 months were reviewed. Depending on the degree of varus deformity, 24 cases with more than 20 degrees of coronal deformity were allocated into group A, and 79 cases with less than 20 degrees were allocated into group B. Soft tissue balancing, bony realignment osteotomy, and subtalar arthrodesis were also performed intraoperatively. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, visual analogue scale (VAS) for pain, and ankle range of motion (ROM) were analyzed preoperatively and postoperatively. Subjective satisfaction of the patients (excellent, good, fair, or poor) and complications (major or minor) were identified. Results: The average AOFAS and VAS scores significantly improved in both groups (P < .001), but there was no significant difference between the groups. Patients’ subjective satisfaction levels also improved in both groups. Conclusion: Short-term follow-up of total ankle arthroplasty, according to the degree of varus deformity, revealed clinically satisfactory progress in both groups without significant differences. There were no significant differences between the 2 groups in postoperative complications and early implant failures. Level of Evidence: Level III, comparative series.

Short-Term Operative Outcome of Tarsal Tunnel Syndrome Due to Benign Space-Occupying Lesions

Background: It has been reported that the operative outcome of tarsal tunnel syndrome caused by space-occupying lesions is more favorable than those caused by other reasons. The purpose of this clinical study was to report our clinical results after surgical treatment for tarsal tunnel syndrome caused by benign space-occupying lesions. Materials and Methods: From July 2004 to February 2007, 20 patients underwent surgical decompression for tarsal tunnel syndrome in our institution. Out of them, 13 cases were due to space-occupying lesions around the tarsal tunnel. The average age was 51.3 and the mean symptom duration was 16.5 months. The operation included complete release of the tarsal tunnel and removal of the space-occupying lesion. The clinical outcomes measured were a pain visual analogue scale (VAS), AOFAS score and the degree of subjective satisfaction. Results: Ganglion was the most frequent cause (10 cases). Other pathologies included synovial chondromatosis, a Schwannoma and a talocalcaneal coalition. There was a significant improvement after surgery in term of VAS (6.4/2.2) and AOFAS score (77.8/92.7). Seven of 13 were satisfied with the results, three felt they had a fair result, and three were dissatisfied. Conclusion: Though significant improvement was found in the average VAS and AOFAS score, subjective satisfaction was less favorable (54%) than expected. We believe surgeons should be more cautious concerning outcomes when expectations of surgery are discussed with patients. Level of Evidence: IV, Retrospective Case Study

The Effect of Ossicle Resection in the Lateral Ligament Repair for Treatment of Chronic Lateral Ankle Instability

Background: The management of an ossicle or avulsion fragment of the fibular tip in chronic lateral ankle instability is an open question. Some authors maintain the necessity of osteosynthesis for reconstruction of the lateral ligamentous structure if the fragment is large. We hypothesized that the modified Broström procedure with resection of the ossicle would result in good outcomes compared to that of the same procedure for chronic lateral instability patients without ossicle. Methods: Between December 2004 and December 2010, 102 patients underwent the modified Broström procedure for chronic lateral instability. Of these, 82 patients (86 ankles) were available for this study. Forty ankles had ossicles at the fibular tip (group O), 46 had no ossicle (group N). The average follow-up period was 33 months in group O and 37 months in group N. Irrespective of size, if there were ossicles we resected all fragments and performed the modified Broström procedure. To analyze the surgical outcome, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot pain and function scales and Karlsson scores were compared between the 2 groups preoperatively and postoperatively. Results: Preoperative scores in the 2 groups showed no significant difference, except for AOFAS pain score. There was no significant difference in postoperative AOFAS pain and function score between the groups. Postoperative Karlsson score was significantly higher in group O than in group N (P = .001). Group O was divided into 2 subgroups by the largest diameter of the ossicle (< 10 mm and ≥ 10 mm); there was no significant difference in surgical outcomes. Conclusions: In the treatment of chronic lateral instability of ankle, if there are ossicles on the fibular tip, osteosynthesis of the ossicles may not be necessary, even if the size is considerable. Modified Broström procedure after resection of the ossicle was successful. Level of Evidence: Level III, retrospective case series.

Effect of Lateral Soft Tissue Release on Sesamoid Position in Hallux Valgus Surgery

Background: The effect of lateral soft tissue release (LSTR) regarding the position of the sesamoid is not clear. The purpose of this study was to evaluate the effect of LSTR by comparing the radiologic and clinical outcomes of operative treatment for hallux valgus with or without LSTR. Methods: This study included a consecutive series of chevron osteotomy of 119 feet of 90 patients with symptomatic hallux valgus with incongruent first metatarsophalangeal (MTP) joints. Fifty-one feet underwent an operation with the LSTR procedure (LSTR group), and the remaining 68 feet underwent treatment without LSTR (control non-LSTR group). We evaluated the differences regarding the distance of the fibular sesamoid from the second metatarsal bone between these 2 groups to evaluate the effect of LSTR on sesamoid position. The tibial sesamoid position was also investigated to evaluate the degree of reduction of the metatarsal head to the sesamoids. The hallux valgus angle, intermetatarsal angle, and distal metatarsal articulation angle were analyzed as radiologic outcomes. Additionally, the preoperative and final follow-up American Orthopaedic Foot & Ankle Society hallux MTP-IP scores and complications were evaluated as clinical assessments. The mean follow-up period was 43.3 weeks (range = 12-144). Results: There were no significant differences in the amount and direction of movement of the fibular sesamoid between the LSTR group and non-LSTR group (1.9 mm and 1.6 mm, respectively) (P = .23). The direction was close to the second metatarsal bone in both groups. The complication rate in the LSTR group was 7.8% (n = 4) and 2.9% (n = 2) in the non-LSTR group (P = .40). Conclusions: Although there were significantly improved clinical and radiologic outcomes after surgery, the LSTR procedure did not result in medial shift or reduction of the sesamoid position. Level of Evidence: Level III, retrospective case control study

Atypical Hereditary Sensory and Autonomic Neuropathy Type IV With Neither Mental Retardation Nor Pain Insensitivity

Hereditary sensory and autonomic neuropathy type IV is an autosomal recessive disorder characterized by severe mental retardation and self-mutilation-related complications. Recently, we investigated a 16-year-old Korean boy with normal intelligence. He had preserved pain sensation but was suspected of having hereditary sensory and autonomic neuropathy type IV because of the recurrent bone fractures and painless joint destruction in the absence of any predisposing medical conditions. Genetic analysis of the NTRK1 gene revealed compound heterozygous mutations including c.851-33T>A and c.2303C>T (p.Pro768Leu) in the NTRK1 gene. The p.Pro768Leu mutation has been identified in 2 Japanese patients with a mild phenotype. Therefore, although it is rare, hereditary sensory and autonomic neuropathy type IV should be considered in patients with recurrent bone fractures and painless joint destruction who do not have any predisposing conditions even when they do not have typical clinical features such as mental retardation or pain insensitivity.

Subcutaneous phaeohyphomycosis caused by Exophiala salmonis.

We report a case of subcutaneous infection in a 55-yr-old Korean diabetic patient who presented with a cystic mass of the ankle. Black fungal colonies were observed after culturing on blood and Sabouraud dextrose agar. On microscopic observation, septated ellipsoidal or cylindrical conidia accumulating on an annellide were visualized after staining with lactophenol cotton blue. The organism was identified as Exophiala salmonis by sequencing of the ribosomal DNA internal transcribed spacer region. Phaeohyphomycosis is a heterogeneous group of mycotic infections caused by dematiaceous fungi and is commonly associated with immunocompromised patients. The most common clinical manifestations of subcutaneous lesions are abscesses or cystic masses. To the best of our knowledge, this is the first reported case in Korea of subcutaneous phaeohyphomycosis caused by E. salmonis that was confirmed by molecular analysis and identification of morphological characteristics. This case suggests that E. salmonis infections are no longer restricted to fish.

Incidence of Peroneal Tendinopathy After Application of a Posterior Antiglide Plate for Repair of Supination External Rotation Lateral Malleolar Fractures

Posterior antiglide plating is widely used to treat lateral malleolar fractures caused by supination-external rotation injuries. Despite its widespread use, this technique can be associated with postoperative peroneal tendinopathy. The purpose of the present observational review was to report the incidence of peroneal tendinopathy after the use of posterior antiglide plating to treat lateral malleolar fractures caused by a supination-external rotation injury. A total of 70 patients were followed up for a minimum of 12 (mean 55, range 12 to 109) months. Bony union was obtained in all cases after a mean of 57 (range 37 to 81) days. The median number of screw holes in the plate was 4.9 (range 4 to 7), and the median number of screws used to fixate the fibula was 6.58 (range 5 to 10). The mean American Orthopaedic Foot and Ankle Society hindfoot-ankle score at the final follow-up examination was 90.8 (range 55 to 100). Clinically, 3 (4.29%) of the 70 patients had lateral or posterolateral ankle pain indicative of peroneal tendinopathy after the index surgery, without any objective evidence. Of the 70 patients, 41 (58.57%) underwent surgical removal of the fibular hardware, 2 (4.87%) because of lateral ankle discomfort. At removal, inspection of the peroneal tendon sheath and/or tendons showed no gross evidence of tendinopathy in any of the patients. We concluded that the incidence of clinically evident peroneal tendon symptoms associated with posterior antiglide plating is low (4.3%), and direct operative inspection revealed no gross evidence of tendinopathy.

Analysis of Prognostic Factors of Pediatric-Type Sarcomas in Adult Patients

Objective: Pediatric-type sarcomas such as Ewing’s sarcoma (EWS)/primitive neuroectodermal tumor family and rhabdomyosarcoma are relatively uncommon in adult patients. Optimal treatment strategies for this population and prognosis in adult patients compared with pediatric patients remain controversial. Methods: We retrospectively reviewed pediatric-type sarcoma patients older than 15 years at a single institution. Results: A total of 84 consecutive patients between 1995 and 2009 were identified at the Samsung Medical Center, Seoul, Korea. Median age was 30 years with a range of 15–74 years. Forty-seven patients (56.0%) were diagnosed with Ewing’s sarcoma/primitive neuroectodermal tumor family, 34 (40.5%) with rhabdomyosarcoma and 3 (3.6%) with desmoplastic round-cell tumor. Median follow-up duration was 5.9 years. Median overall survival for all patients was 33.1 months (95% CI 13.5–52.7) and median event-free survival for all patients was 14.4 months (95% CI 5.9–22.9 months). Multivariate analysis revealed that localized disease was a significant independent prognostic factor for longer overall survival (hazard ratio 0.30, 95% CI 0.14–0.66, p = 0.003), and favorable primary tumor sites were associated with longer event-free survival (hazard ratio 0.33, 95% CI 0.11–0.98, p = 0.045). Conclusion: We identified the prognostic variables which may facilitate risk-adapted therapies for this rare adult sarcoma group, which should be further investigated.

Ankle strength is not strongly associated with postural stability in patients awaiting surgery for chronic lateral ankle instability

Purpose (1) To describe ankle strength and postural stability in patients with chronic lateral ankle instability and (2) to analyse the correlation between deficits in ankle strength and postural stability. Methods Results of preoperative isokinetic and balance tests in 203 patients whose contralateral ankle was normal were retrospectively reviewed. Isokinetic peak torque values of eversion and inversion at 2 angular velocities (30°/s and 120°/s) were measured in the injured and normal ankles. In the balance test, the percent differences of 3 actual scores (overall, anterior–posterior, and medial–lateral) between the injured and normal ankles were calculated. Additional statistical analyses were performed to evaluate weakness of ankle strength, postural stability deficits, and their correlation. Results Significant differences in 4 peak torque values and 4 relative peak torque values (peak torque/body weight) were found between the injured and normal ankles. All 8 values were significantly lower in the injured ankles. Weakness was severe during inversion and at 30°/s. In the balance test, 49 subjects (24.1%) had significant deficits in postural stability and 109 (53.7%) had favourable results. No strong association was found between weakness of ankle strength and deficits in postural stability. Conclusions Strength measurement alone is insufficient to evaluate preoperative functional deficits, and other functional tests are required to measure postural stability. The results of this study provide further evidence for a rehabilitation programme consisting of proprioceptive training as well as strengthening. The proprioceptive training must be an integral part of the rehabilitation programme in addition to strengthening exercise. Level of evidence Case series, Level IV.