Long-Term Follow-Up Outcomes of 19 Patients with Osteogenesis Imperfecta Type XI and Bruck Syndrome Type I Caused by FKBP10 Variants.

Osteogenesis imperfecta type XI (OI-XI) and Bruck syndrome type I (BS1) are two rare disorders caused by biallelic variants in the FKBP10, characterized by early-onset bone fractures and progressive skeletal deformities. The patients with OI-XI, also co-segregated with autosomal-recessive epidermolysis bullosa simplex caused by KRT14 variant, have been reported. In this study, the follow-up clinical features of the patients with OI-XI and BS1 phenotypes due to biallelic FKBP10 variants are compared. The aim of this study is to investigate the follow-up findings of OI-XI and BS1 phenotypes in patients with the FKBP10 variants. A total of 19 children, ten males and nine females, from 16 unrelated families were included in the study. FKBP10 variants were investigated by next-generation sequencing (NGS) based panel gene test or Sanger sequencing. Seventeen patients were followed between 1.5 and 16.8 years, and the last follow-up age was between 2 and 24.6 years (median 10.7 years). They received intravenous bisphosphonate infusions once every 3 months in follow-up period. We identified four different biallelic FKBP10 variants, two of which are novel (c.890_897dup TGATGGAC, p.Gly300Ter and c.1256 + 1G > A) in 16 families. Five of these patients also had findings of epidermolysis bullosa simplex, and the same biallelic c.612T > A (p.Tyr204Ter) variant in KRT14, as well as FKBP10, were identified. Twelve patients were diagnosed with OI-XI; whereas, seven were diagnosed with BS1. The BS1 phenotype was late-onset and the annual fracture number was lower. After bisphosphonate treatment, bone mineral densitometry Z score at L1-L4 increased (p = 0.005) and the number of annual fractures decreased (p = 0.036) in patients with OI-XI. However, no significant effect of bisphosphonate treatment was found on these values in BS1 patients. Despite the treatment, the rate of scoliosis and long bone deformity had increased in both groups at the last examination; and, only two patients could take a few steps with the aid of a walker, while others were not ambulatory, and they used wheelchairs for mobility. We identified two novel variants in FKBP10. Families originating from the same geographic region and having the same variant suggest founder effects. Although the number of fractures decreased with bisphosphonate treatment, none of our patients were able to walk during the follow-up. This study is valuable in terms of showing the follow-up findings of patients with FKBP10 variants for the first time.

Should early weightbearing be allowed after intramedullary fixation of trochanteric femur fractures? A finite element study.

BACKGROUND: This study aims to investigate the effects of early weightbearing after intramedullary fixation of trochanteric fractures. METHODS: Femurs with different types of trochanteric fractures were modeled according to AO/OTA classification. Fractures were ideally reduced with one mm gap between fragments and fixed with intramedullary nails. Forces were applied simulating single- (Body weight: 60 kg, joint reaction force: 1999.2 N, abductor muscle force:1558.8 N) and double-leg standing positions (Joint reaction force: 196 N). In another model, a 500 Nm rotational force was applied as a simulation of a fall. RESULTS: A higher level of stress was determined at the calcar femorale, the fracture site, the holes for the lag screws, and the hole for the proximal locking screw on the nail, the threadless parts of the lag screws, and the mid-portion of the nail. During the single-leg stance, up to 3 mm displacement was observed with the reverse oblique type of fractures. In the simulation of the fall, 1.5 mm displacement occurred at the fracture site. No displacement was measured at stabile and type 31A2 fracture models. In addition, higher levels of stress were measured at the body of the nail (up to 133 MPa), proximal screws (up to 133 MPa) and at the bone distal to the nail (up to 84.3 MPa), but all values were under the limit of the yield stress of the bone and the titanium. CONCLUSION: Full weightbearing after intramedullary fixation of trochanteric femur fractures may be allowed except in obese patients and patients with 31A3 type fractures according to the AO/OTA classification. The use of support is recommended in order to prevent complications. Implant removal can be discussed with patients after fracture union in order to prevent possible periprosthetic fractures.

Management of persistent coccydynia with transrectal manipulation: results of a combined procedure.

OBJECTIVE: We compared the results of manual therapy combined with steroid injection with single steroid injection in the treatment of persistent coccydynia. PATIENTS AND METHODS: Combined therapy was performed in 21 patients (Group 1) and steroid injection in 23 patients (Group 2). We compared two groups and investigated the combined therapy group in details. Patients were classified according to the underlying cause, BMI, anatomic type of coccyx and duration of symptoms (< 6 or ≥ 6 months). RESULTS: Mean age was 30.5 years at the time of procedures. Mean followup time was 27.8 months. VAS scores were decreased in both groups but combined therapy group had much more better results. Complete pain relief was achieved in 61.9% of patients in Group 1 whereas it was only 17.4% in Group 2. In 23.8% of Group 1, the VAS score was significantly decreased but the feeling of uncomfortability persisted. This was 73.9% in Group 2. We had no relapse in Group 1 but in Group 2 the relapse rate was 56.5%. Underlying cause, body mass index, anatomic type of coccyx and duration of symptoms had no effect on results. CONCLUSION: Manual therapy combined with steroid injection would be an alternative method in case of persistent coccydynia. It is a safe and easy option before surgical treatment.

Risk Factors of Refracture and Morbidity During Removal of Titanium Pediatric Proximal Femoral Locking Plates in Children With Cerebral Palsy.

BACKGROUND: Pediatric proximal femoral locking plates (PFLPs) are widely used when performing proximal femoral osteotomy in children with cerebral palsy (CP). The purpose of this study is to report the difficulties and risk factors of titanium PFLPs removal in CP. METHODS: PFLP removal was performed in 58 hips of 33 patients (17 males, 16 females). The mean age at the time of surgery (plate removal) was 10.9 (range, 5.7 to 19.2) years. The patients were divided into 2 groups as group 1 and 2, if any difficulty was observed during surgery or not. RESULTS: Difficulty was not detected in 42 (72.4%) hips (group 1). Difficulties were encountered in 16 (27.6%) hips (group 2). A total of 364 screws were used (259 in group 1, 105 in group 2). The mean plate screw density ratios were 0.88 in group 1 and 0.94 in group 2. The difference between group 1 and 2 was statistically significant. The mean duration between the insertion and removal of the PFLP was 14.9 months (11.9 mo in group 1, 22.7 mo in group 2). The difference between group 1 and 2 was statistically significant. The screw heads were cut and the shafts were left in the bone in 4 hips (4 screws); 3 of these 4 screws were calcar screws. Therefore, calcar screw application can be accepted as a handicap for screw removal. CONCLUSIONS: As a conclusion, this study suggested that difficulty in titanium PFLP removal in CP is common and PFLP removal is not a harmless procedure. A longer time from internal fixation to removal, increased plate screw density ratio, and calcar screw application are risk factors for difficulties in titanium PFLP removal in CP. LEVEL OF EVIDENCE: Level III.

Reconstruction of neglected achilles tendon ruptures with gastrocnemius flaps: excellent results in long-term follow-up.

OBJECTIVE: Repair of the neglected achilles tendon ruptures can be challenging due to retraction of tendon stumps. Different repair and augmentation techniques were described. This study aims to investigate long-term results of neglected achilles tendon rupture repair with gastrocnemius flaps. PATIENTS AND METHODS: Between 1995 and 2005, 21 neglected achilles tendon rupture reconstructions were performed with using gastrocnemius fascial flaps. Mean age was 32.1 years. Mean period between rupture and operation was 8.4 weeks. Ankle range of motion, calf circumference, heel raise test, Visual Analog Scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) hindfoot and Foot and Ankle Disability Index (FADI) scores were checked. RESULTS: The average gap length was 6.4 cm. Mean follow-up was 145.3 months. Median dorsiflexion/plantar flexion values for operated and uneffected sides were 18°/30° and 19°/30°, respectively. The mean values for AOFAS and FADI scores were 98.5 points and 98.9 %, respectively. VAS score was 0 point for all patients. With the numbers available, no significant difference could be detected in terms of ankle range of motion, calf circumference measures and dynamometric analysis. Mean time for return to daily activities was 11.1 (8-16) weeks after surgery. Prerupture activity level was achieved 14.1 months postoperatively. All patients were able to perform heel raise test. CONCLUSION: Repair of neglected achilles tendon ruptures with gastrocnemius flaps has satisfactory long-term results.

Procedural outcomes of double vs. single fluoroscopy for fixing intertrochanteric femur fractures.

OBJECTIVE: This study compares reducing radiation and operation time between single and double C-arm fluoroscopy in the treatment of intertrochanteric femur fractures with intramedullary nails. PATIENTS AND METHODS: Forty four patients participated in the study. Patients were divided into two groups as single (23 patients) and double fluoroscope (21 patients). The time of preparation, the duration of the surgery, the total amount of blood loss, and the total duration of radiation exposure were compared, retrospectively. The collo-diaphyseal angle was compared with that of the contralateral hip on postoperative radiographs. Furthermore, the tip-apex distance and the position of the screws in the femoral head were recorded. RESULTS: The mean preparation periods, collo-diaphyseal angles and blood loss did not differ between groups. In the double-fluoroscopy group, the duration of surgery was 15.9 min shorter (p < 0.001), and the radiation time was 25.7 s shorter (p < 0.001). CONCLUSION: The double fluoroscopy technique can significantly reduce surgical and radiation exposure times during surgery.

Graft position in arthroscopic anterior cruciate ligament reconstruction: anteromedial versus transtibial technique.

INTRODUCTION: When treating anterior cruciate ligament (ACL) injuries, the position of the ACL graft plays a key role in regaining postoperative knee function and physiologic kinematics. In this study, we aimed to compare graft angle, graft position in tibial tunnel, and tibial and femoral tunnel positions in patients operated with anteromedial (AM) and transtibial (TT) methods to those of contralateral healthy knees. MATERIALS AND METHODS: Forty-eight patients who underwent arthroscopic ACL reconstruction with ipsilateral hamstring tendon autograft were included. Of these, 23 and 25 were treated by AM and TT techniques, respectively. MRI was performed at 18.4 and 19.7 months postoperatively in AM and TT groups. Graft angles, graft positions in the tibial tunnel and alignment of tibial and femoral tunnels were noted and compared in these two groups. The sagittal graft insertion tibia midpoint distance (SGON) has been used for evaluation of graft position in tunnel. RESULTS: Sagittal ACL graft angles in operated and healthy knees of AM patients were 57.78° and 46.80° (p < 0.01). With respect to TT patients, ACL graft angle was 58.87° and 70.04° on sagittal and frontal planes in operated knees versus 47.38° and 61.82° in healthy knees (p < 0.001). ACL graft angle was significantly different between the groups on both sagittal and frontal planes (p < 0.001). Sagittal graft insertion tibia midpoint distance ratio was 0.51 and 0.48 % in the operated and healthy knees of AM group (p < 0.001) and 0.51 and 0.48 % in TT group (p < 0.001). Sagittal tibial tunnel midpoint distance ratio did not differ from sagittal graft insertion tibia midpoint distance of healthy knees in either group. Femoral tunnel clock position was better in AM [right knee 10:19 o'clock-face position (310° ± 4°); left knee 1:40 (50° ± 3°)] compared with TT group [right knee 10:48 (324° ± 5°); left knee 1:04 (32° ± 4°)]. With respect to the sagittal plane, the anterior-posterior position of femoral tunnel was better in AM patients. Lysholm scores and range of motion of operated knees in the AM and TT groups showed no significant difference (p > 0.05). CONCLUSIONS: Precise reconstruction on sagittal plane cannot be obtained with either AM or TT technique. However, AM technique is superior to TT technique in terms of anatomical graft positioning. Posterior-placed grafts in tibial tunnel prevent ACL reconstruction, although tibial tunnel is drilled on sagittal plane.

Reconstruction of Traumatic Composite Tissue Defect of Medial Longitudinal Arch With Free Osteocutaneous Fibular Graft.

A 34-year-old male sustained a crush injury resulting in bone and soft tissue loss along the medial longitudinal arch of his left foot. Specifically, the injury resulted in loss of first metatarsal without injury to the medial cuneiform or proximal phalanx, fracture of the third metatarsal, and a 5-cm × 9-cm soft tissue defect overlying the dorsomedial aspect of the right foot. After debridement and daily wound care, the defect was subsequently reconstructed using a free osteocutaneous fibular graft. Approximately 6 months after reconstructive surgery, the patient returned to his job without pain, and his pedogram showed almost equal weightbearing distribution on both feet.

Rotational malalignment after closed intramedullary nailing of femoral shaft fractures and its influence on daily life.

BACKGROUND: Any intraoperative rotational malalignment during intramedullary nailing (IMN) of femoral shaft fractures will become permanent. We hypothesized that rotational malalignment of the femur and its compensatory biomechanics may induce problems in the hip, knee, patellofemoral and ankle joints. We purposed to clarify the influence of a femoral rotational malalignment of ≥10° on daily activities. METHODS: Twenty-four femoral shaft fracture patients treated with closed antegrade IMN were included. At last follow-up, to reveal any rotational malalignment, computerized tomography (CT) scans of both femurs (injured and uninjured sides) were examined. The patient groups with or without CT-detected true rotational malalignment ≥10° were compared with respect to the activity scores. RESULTS: Ten of the 24 patients (41.7%) had a CT-detected true rotational malalignment of ≥10° compared with the unaffected side. The AOFAS scores were 100.00 for all of the patients. LKS, WOMAC knee, and WOMAC hip scores were significantly decreased in the patients with rotational malalignment compared to those without. Patients without rotational malalignment tolerated climbing stairs significantly better than those with rotational malalignment. Patients who could not tolerate climbing stairs were consistently complaining of anterior knee pain. CONCLUSIONS: A femoral rotational malalignment of ≥10° is symptomatic for the patients, and the hip, knee, and patellofemoral joints were affected. Because of the possibly altered joint loadings and biomechanics, these could render patients prone to degenerative joint disease. In addition, due to the high rates of rotational malalignment after femoral shaft fracture and consequent malpractice claims, it is important for surgeons to be more aware of rotational alignment during surgery.

Midterm treatment results of congenital dislocation of the knee in 14 knees of nine cases.

Patients with congenital dislocation of the knee (CDK) should be promptly treated surgically if conservative measures fail. This study aimed to achieve a better understanding of the diagnosis and management of CDK through sharing our experience and contributing to the existing literature. Nine patients with a total of 14 knees were included in the study. All patients except one were initially treated with gentle manipulation and serial casting. Surgery was performed on patients in whom sufficient joint mobility could not be achieved. Active and passive range of motion of the knees and functional outcome were measured. Of the 14 knees, five were classified as first grade, four as second grade and five as third grade. The mean age of the patients was 4.09 months and the follow-up period was 70 months. The initial mean flexion angle (MFA) was 18.2° (0-90) and the mean extension angle (MEA) was 8.2° (0-15). At the final follow-up, the mean MFA was 109.2° (80-140) and MEA was -2.85° (0 to -10). No patient had instability by the final follow-up. The results were classified as excellent (5 knees), good (5 knees) and moderate (4 knees) according to outcome assessment criteria. The functional outcomes were classified as excellent (7 knees), good (3 knees) and fair (4 knees) according to the functional outcome scoring. Treatment of CDK should be started in the first days of life, and if the desired functional outcome cannot be achieved through conservative treatment, surgical treatment should be planned without delay.

Match the Metatarsal Heads: A Case of All-Metatarsal Fractures After a Motorcycle Accident.

Metatarsal bone fractures are one of the most frequent foot injuries, especially after motor vehicle accidents in children. This case report briefly demonstrated a rare instance of pediatric all-metatarsal fractures of the left foot in an adolescent patient with polytrauma after a motorcycle accident. This case report illustrated the surgical procedure's potential for healing pediatric foot fractures in teenage patients after polytrauma. In the examination of a 16-year-old male patient brought to the emergency department after a motorcycle accident, we detected a right foot third finger proximal phalanx open fracture, right foot fourth finger proximal phalanx fracture, left foot first metatarsal proximal fracture, left foot second, third, fourth, and fifth metatarsal distal fractures, left foot cuboid, and navicular bone fractures. The patient's left foot's metatarsals were all fractured. The posterolateral wall fracture of the patient's right maxilla was also detected. All metatarsals were displaced, the second metatarsal paired with the third, etc., and because of this displacement, the closed reduction was impossible, and even the open reduction was challenging to reach the correct pairs. We performed closed reduction and fixation with Kirschner wire for the left foot's first metatarsal fracture and open reduction and fixation with Kirschner wire for the left foot's second, third, and fourth metatarsal distal fractures. We also performed closed reduction and fixation with Kirschner wire for the right foot third and fourth proximal phalanx fractures. We observed callus formation in the sixth week and removed the patient's K-wires. At eight weeks, the X-ray demonstrated the correct alignment of all metatarsals. The proper alignment of all metatarsals and the full range of motion of all foot and ankle joints were achieved with early surgical intervention, open reduction, and timely rehabilitation. This case also emphasizes the importance of open reduction in such irreducible and heavily displaced cases of multiple fractures as all-metatarsal fractures and contributes to the literature with a specific treatment modality in the case of all-metatarsal fractures lacking in the literature.

Diagnosis and Treatment Planning of Developmental Hip Dysplasia: Evaluation of Care Practices of the Members of the Turkish Pediatric Orthopedics Association.

OBJECTIVE: Developmental dysplasia of the hip is one of the most important causes of childhood disabilities. Although there are accepted treatment algorithms for developmental dysplasia of the hip, diagnosis and treatment approaches can show variations in the management among physicians. This study aimed to develop a diagnosis and treatment algorithm for developmental dysplasia of the hip according to the preferences of members of the Turkish Pediatric Orthopedics Association. MATERIALS AND METHODS: An interview by telephone call was made with 76 orthopedists (group 1: more experienced 39 physicians, group 2: less experienced 37 physicians) who are members of the Turkish Pediatric Orthopedics Association. Participants were q uesti onnai red ab out their demographic information, experiences, diagnostic criteria that they use for developmental dysplasia of the hip, and treatment approaches to patient scenarios of different ages. RESULTS: Most of the participants recommended universal screening at the age of 4 weeks. It was observed that the most significant physical examination finding was limited hip abduction, and the most frequently used radiographic evaluation on x-ray was acetabular index measurement. The most frequently used description for dysplasia was found as acetabular index >30°. CONCLUSIONS: Although there are some differences among orthopedists in the diagnosis, treatment, and follow-up approach of developmental dysplasia of the hip, there was no significant difference according to the experience-based grouping. The treatment algorithm, which was created with the most frequently given answers, was designed, which we think may be beneficial for pediatricians and orthopedists.

The molecular spectrum of Turkish osteopetrosis and related osteoclast disorders with natural history, including a candidate gene, CCDC120.

BACKGROUND: Osteopetrosis and related osteoclastic disorders are a heterogeneous group of inherited diseases characterized by increased bone density. The aim of this study is to investigate the molecular spectrum and natural history of the clinical and radiological features of these disorders. METHODS: 28 patients from 20 families were enrolled in the study; 20 of them were followed for a period of 1-16 years. Targeted gene analysis and whole-exome sequencing (WES) were performed. RESULTS: Biallelic mutations in CLCN7 and TCIRG1 were detected in three families each, in TNFRSF11A and CA2 in two families each, and in SNX10 in one family in the osteopetrosis group. A heterozygous variant in CLCN7 was also found in one family. In the osteopetrosis and related osteoclast disorders group, three different variants in CTSK were detected in five families with pycnodysostosis and a SLC29A3 variant causing dysosteosclerosis was detected in one family. In autosomal recessive osteopetrosis (ARO), a malignant infantile form, four patients died during follow-up, two of whom had undergone hematopoietic stem cell transplantation. Interestingly, all patients had osteopetrorickets of the long bone metaphyses in infancy, typical skeletal features such as Erlenmeyer flask deformity and bone-in-bone appearance that developed toward the end of early childhood. Two siblings with a biallelic missense mutation in CLCN7 and one patient with the compound heterozygous novel splicing variants in intron 15 and 17 in TCIRG1 corresponded to the intermediate form of ARO (IARO); there was intrafamilial clinical heterogeneity in the family with the CLCN7 variant. One of two patients with IARO and distal tubular acidosis was found to have a large deletion in CA2. In one family, two siblings with a heterozygous mutation in CLCN7 were affected, whereas the father with the same mutation was asymptomatic. In WES analysis of three brothers from a family without mutations in osteopetrosis genes, a hemizygous missense variant in CCDC120, a novel gene, was found to be associated with high bone mass. CONCLUSION: This study extended the natural history of the different types of osteopetrosis and also introduced a candidate gene, CCDC120, potentially causing osteopetrosis.

Exploration of Flexible Pes Planus as a Potential Risk Factor for Cardiac Pathologies in Pediatric Cases.

OBJECTIVE: The aim of this study is to investigate the relationship between flexible pes planus (FPP) and cardiac pathologies in pediatric patients, with a particular emphasis on hypermobility status. METHODS: Between January and June 2022, a retrospective screening was conducted on a total of 68 patients aged between 6 and 18 years who had been diagnosed with FPP. Eight patients were excluded from the study due to suspicion of connective tissue or neuromuscular diseases following systemic examinations conducted by a pediatric specialist. The included 60 patients underwent comprehensive cardiac examinations conducted by pediatric cardiology specialists and were evaluated through echocardiography (ECHO) as part of the study. Simultaneously, a control group of healthy individuals aged 6 to 18, without a diagnosis of pes planus (PP), was selected from those who applied for health reports for the purpose of obtaining sports licenses. Patients diagnosed with FPP were compared to a control group in terms of the presence of cardiac pathology. Furthermore, the Beighton Hypermobility Scores (BHSs) of patients diagnosed with FPP were compared based on the presence of cardiac pathology. RESULTS: A total of 60 patients (40 males, 20 females) diagnosed with FPP were included in the study, and a control group consisting of 453 healthy individuals (287 males, 166 females) was selected. The incidence of cardiac pathology in patients diagnosed with FPP (23.3%) was found to be significantly higher compared to the control group (7%) (p <0.01). The risk of cardiac pathology in patients diagnosed with FPP was determined to be four times higher compared to the control group (Odds ratio: 4 (1.993-8.046), p<0.01). Among patients with FPP, individuals who were found to have cardiac pathology had statistically significantly higher average BHSs compared to those without cardiac pathology (p: 0.043). CONCLUSIONS: Our study suggested that there may be a significant relationship between FPP and high cardiac pathology risk in pediatric patients. We observed a significant increase in the incidence of cardiac pathologies among patients diagnosed with FPP. Additionally, the presence of higher hypermobility scores among patients diagnosed with FPP suggests a potential connection between the two. In the evaluation of FPP in the pediatric population, it should be considered as a potential risk factor for cardiac pathologies and its potential association with hypermobility.

Evaluation of patients' post-operative results operated for hip fracture with computerized dynamic posturography: Proximal femoral nailing versus hip arthroplasty.

BACKGROUND: Proximal femoral nailing (PFN) and hip arthroplasty (HA) are the two most often utilized surgical procedures for treating hip fractures in older patients. The post-operative postural balance and functional outcomes of patients may be significantly influenced by the technical distinctions between PFN and HA. This will influence the surgeon's preferred course of therapy. To examine the functional outcomes of patients treated with PFN and HA following a hip fracture, this study used computerized dynamic posturography (CDP). The aim of that study was to evaluate how the two treatment modalities affected patients' post-operative balance, postural stability, and functional rehabilitation. METHODS: A total of 26 patients who underwent proximal femoral surgery (15 patients PFN [58%] and 11 patients HA [42%]) due to hip fractures were evaluated at least 12 months postoperatively. They were tested by direct radiographs, hip joint examinations, Harris hip score (HHS), and CDP. RESULTS: Twelve (46%) of 26 patients were male and 14 (54%) were female. The mean age of the participants in the study was 67.9±14.2 years. The mean follow-up period was 24 (12-44) months. The average Harris score of PFN group was 79.3 (46.8-100) points and HA group was 83.7 (61.9-99.9) points. There was no significant difference between the groups in terms of Harris Score (P=0.54). The average of the mixed value of the balance results obtained with CDP (the Composite score) for PFN group was 70.5 (56-79) points, and for HA group was 71.9 (56-83) points. There was no significant difference between the groups in terms of the Composite Score (P=0.47). Accordingly, 12 (80%) of the patients who underwent PFN had good results and 3 (20%) of them had bad results. Eight (72.7%) of those who underwent HA had good results and 3 (27.3%) had bad results. There was no statistically significant difference (P=0.66). CONCLUSION: Comparing the composite score for balance results and HHS results for rehabilitation with the data of the patients who underwent PFN and HA, there was no statistically significant difference between these two techniques in terms of postural stabil-ity and balance as a result of CDP examination.

Aspergillus fumigatus Septic Arthritis of the Wrist: A Report of a Rare Case in an Immunocompromised Patient.

Aspergillus fumigatus is a saprophytic fungus encountered as a pathogen in airborne lung infections. Although it commonly causes pulmonary infectious diseases, when disseminated, it may cause a systemic infection termed invasive aspergillosis, which is associated with high mortality and morbidity. Virtually, all organ systems may be involved. However, the musculoskeletal system is relatively uncommon. Here, we present a case of invasive aspergillosis in an immunocompromised patient involving the wrist joint, an exceedingly rare site. Our treatment choice is serial open debridement, irrigation, and intravenous antibiotics. This case study exemplifies the potential challenges in the identification and treatment of such an uncommon clinical condition. A thorough clinical and microbiological evaluation is essential for accurate diagnosis of fungal septic arthritis of the wrist. Aggressive early surgical treatment combined with appropriate early intravenous antibiotics is crucial for eradicating joint infection.

Phenotypic and Molecular Spectrum of a Turkish Cohort with Hereditary Multiple Osteochondromas.

OBJECTIVE: Hereditary multiple osteochondromas is an autosomal dominant disorder caused by heterozygous pathogenic variants in EXT1 or EXT2. We aimed to evaluate the clinical and molecular findings of a Turkish cohort with hereditary multiple osteochondroma. MATERIALS AND METHODS: Thirty-two patients aged 1.3-49.6 years from 22 families were enrolled. Genetic analyses were made by EXT1 and/or EXT2 sequencing and chromosomal microarray analyses. RESULTS: We found 17 intragenic pathogenic variants in EXT1 (13/17) and EXT2 (4/17), 12 of which are novel. Four probands had EXT1 deletions, including 2 patients with partial EXT1 microdeletions involving exons 2-11 and 5-11, and 2 patients with whole-gene deletions. In 21 variants, the frequency of truncating and missense variants was 76.1% and 23.8%, respectively. Two families had no detectable variants in EXT1 and EXT2. All patients had multiple osteochondromas at the long bones, mainly at the tibia, forearm, femur, and humerus. Bowing deformity of the forearms (9/32) and the lower extremities (2/32), and scoliosis (6/32) were observed. The clinical severity was not different between patients with EXT1 or EXT2 variants. One patient with an EXT2 variant and another with an EXT1 microdeletion had the most severe phenotype with class III disease. Four patients with no EXT1 or EXT2 variants had milder phenotypes. Intrafamilial variability in disease severity was not observed. CONCLUSION: We report a hereditary multiple osteochondroma cohort with clinical and molecular data including 12 novel intragenic variants in EXT1 or EXT2, and 4 microdeletions involving EXT1. Taken together, our data expand the existing knowledge of the phenotype-genotype spectrum in hereditary multiple osteochondroma.

Investigation of 11p15.5 Methylation Defects Associated with Beckwith-Wiedemann Spectrum and Embryonic Tumor Risk in Lateralized Overgrowth Patients.

The Beckwith-Wiedemann spectrum (BWSp) ranges from isolated lateralized overgrowth (ILO) to classic phenotypes. In this broad clinical spectrum, an epigenetic alteration on chromosome 11p15.5 can be detected. The risk for embryonal tumors is high, especially in patients with lateralized overgrowth (LO). The aim of this study is to investigate epigenetic alterations in 11p15.5 and tumor risk in 87 children with LO. The methylation level of 11p15.5 was examined in the blood of all patients and in skin samples or buccal swabs from 40 patients with negative blood tests; 63.2% of patients were compatible with the ILO phenotype, 18.4% were atypical, and 18.4% were classic. The molecular diagnosis rate was 81.2% for the atypical and classic phenotypes, and 10.9% for the ILO phenotype. In patients with epigenetic alterations, LO was statistically significantly more severe than in test negatives. Tumors developed in six (6.9%) of the total 87 patients with LO; four belonged to the atypical or classical phenotype (12.5%) and two to ILO (3.5%). Three of the four patients with atypical/classical phenotypes had pUPD11, one had IC1-GOM alteration, and two ILO patients were negative. We conclude that LO patients should be monitored for tumor risk even if their epigenetic tests are negative.