A case report of multicentric carpotarsal osteolysis syndrome: Depiction of a debilitating disease course.

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by progressive osteolysis involving the carpal and tarsal bones, and often associated with nephropathy. It is caused by heterozygous mutation in the MAF bZIP transcription factor B (MAFB) gene. Heterogeneous clinical manifestation and wide spectrum of disease severity have been observed in patients with MCTO. Here, we report a case of a male patient who presented with kidney failure in childhood with progressive disabling skeletal deformity. He was diagnosed with MCTO at 31-years-old, where a de novo pathogenic heterozygous variant in NM_005461.5:c.212C>A: p.(Pro71His) of the MAFB gene was identified. While there has been little data on the long-term prognosis and life expectancy of this disease, this case report sheds light on the debilitating disease course with multiple significant morbidities of a patient with MCTO throughout his lifetime of 33 years.

Clinical Effects of Tibial Posterior Tendon Reconstruction in the Treatment of Young Athletes With Accessory Navicular Bone Syndrome.

OBJECTIVE: To compare the effects of anchor reconstruction of posterior tibial tendon with the traditional Kidner's procedure for accessory navicular bone syndrome. METHODS: A retrospective analysis was conducted on 40 young athletes diagnosed with accessory navicular bone syndrome who were admitted to our hospital from 2018 to 2021. Among them, 20 patients underwent the modified Kidner procedure for the anchor reconstruction of the posterior tibial tendon (Experimental group), while the remaining 20 patients were treated with the traditional Kidner's procedure (Control group). Regular follow-ups were conducted to evaluate the degree of relief of foot symptoms and functional recovery. RESULTS: All patients were followed up for 12 to 24 months (mean duration: 18.6±3.7) after the operation. At the last follow-up, significant differences were observed in the function and symptom relief of the affected foot compared to the preoperative state. The experimental group had a mean operation time of 52.10 ± 3.41 minutes, significantly shorter than the control group's 61.25 ± 2.75 minutes. The mean time to return to normal activity was 12.65 ± 1.23 weeks for the experimental group, compared to 15.25 ± 1.16 weeks for the control group. CONCLUSION: The modified Kidner procedure demonstrates a higher patient satisfaction rate compared to the traditional Kidner procedure. This is attributed to its shorter duration, reduced trauma, and quicker recovery of normal activity.

Hazard of Failed Nonoperative Management for Symptomatic Accessory Navicular in Children and Adolescents: A Population-Based Case-Cohort Study.

BACKGROUND: The accessory navicular (AN) is an idiopathic condition of the foot present in 4% to 21% of the population. Most ANs remain asymptomatic, but children and adolescents who develop symptoms can have remarkably reduced quality of life. Although many respond to conservative measures, surgery is occasionally needed. Our purpose was to determine factors associated with the failure of nonoperative management. METHODS: This single-institution retrospective case-cohort study included patients up to age 19 years presenting between 2000 and 2021 with symptomatic AN and treated with standard-of-care. All 298 surgical cases, indicating failed nonoperative treatment, were included. For the subcohort, 299 patients were randomly sampled from all eligible patients, regardless of treatment. Baseline characteristics were summarized for the surgical cases and subcohort. Proportional hazards assumptions were checked and stratification implemented when necessary. Marginal structural proportional hazard modeling was used to estimate hazard ratios with 95% confidence intervals via inverse probability and LinYing weighting methods. RESULTS: The 298 surgical cases failed nonoperative management at a median of 5.2 months (IQR, 2.0-11.6 mo). In the subcohort, 86 failures of nonoperative management and 213 nonfailures constituted a 28.8% surgery rate. In both cohorts, nearly all patients played sports. Univariate proportional hazard modeling found older age ( P =0.02) and activity limitation ( P <0.001) at presentation, female sex ( P =0.002), higher BMI ( P =0.01), AN on the right ( P <0.001), and bone marrow edema of the AN ( P <0.001) and navicular body ( P <0.001) on MRI were associated with increased hazard of nonoperative failure. Nearly all of the surgical cohort reported improvement in pain (278/296, 94%) and returned to their primary sport (236/253, 93%) after surgery. Most also experienced full resolution of symptoms (187/281, 67%). CONCLUSIONS: Symptomatic AN predominantly affects female athletes, leading to surgery in 28.8% of our subcohort. Conservative treatment may be less successful-and therefore surgery could be more strongly considered-in older age, activity limitation at presentation, female sex, higher BMI, right-sided AN, and bone marrow edema on MRI. Surgery is effective for symptomatic and functional improvement. LEVEL OF EVIDENCE: Case-cohort-Level III.

Male elite soccer players have a higher incidence of accessory ossicles in the foot and ankle.

PURPOSE: Accessory ossicles are caused by the failure of the fusion of secondary ossification centres and are more likely to occur due to heavy loading during the growth period or improper treatment after injury. This study aimed to investigate the incidence of foot and ankle accessory ossicles in male professional soccer players. METHODS: This study included male professional soccer players who underwent medical checkups at our hospital between 2017 and 2023 as the soccer group. Medical checkups included radiographs of bilateral anteroposterior and oblique foot, as well as bilateral anteroposterior and lateral ankle. Male patients age-matched with the soccer group who visited our hospital undergoing anteroposterior and oblique foot or anteroposterior and lateral ankle radiography were included in the control group. The incidence of accessory ossicles was investigated and compared between the soccer and control groups. RESULTS: In this study, 276 ankles and 276 feet, as well as 121 ankles and 79 feet, were included in the soccer and control groups, respectively. The incidence of accessory ossicles in the soccer and control groups was as follows: accessory navicular 35.9%, 24% (P = .049), os peroneum 8.0%, 2.5% (P = .09); os supranaviculare 7.6%, 1.3% (P = .039); os infranaviculare 1.4%, 1.3% (P = .090); os calcaneus secundarius 4.3%, 0% (P = .059); os vesalianum 0%, 0%; os subfiblare 12.7%, 2.5% (P < .001); os subtibiale 18.1%, 2.5% (P = .001); and os trigonum 89%, 24% (P < .001). CONCLUSIONS: Male professional soccer players had a higher incidence of accessory navicular, os supranaviculare, os subfiblare, os subtibiale, and os trigonum.

The prevalence and anatomy of accessory navicular bone: a meta-analysis.

PURPOSE: There have been over 40 descriptions of the common developmental variants of the accessory ossicles of the feet. Although predominantly asymptomatic, they sometimes may be linked to painful conditions. One of the most common accessory ossicles in the foot is the accessory navicular bone (AN), located on the medial side of the foot. Our research provides a first meta-analysis on this topic that establishes its frequency by contrasting 39 studies from across the globe. METHODS: Up to February 2024, PubMed and Embase databases were thoroughly searched for research on the AN. Eligible data regarding AN prevalence was extracted. This study strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 39 studies, 11,015 patients, and 36,837 feet were analyzed in our study. The pooled prevalence estimate (PPE) of AN was found to be 17.5% (95%CI: 11.5-25.7) and 12.6% (95%CI: 10.1-15.5) in patients and feet analyses, respectively. Accessory navicular occurred bilaterally in 50.0% of patients, with similar distribution in gender-based groups (21.1% of males and 22.0% of females were confirmed with AN). Accessory navicular was most prevalent in the East Asian population (38.4%) and least prevalent in North Americans (8.0%). No significant differences in AN prevalence were found when comparing different imaging modalities (X-ray and cadaver dissection). CONCLUSION: Accessory navicular is a common finding in imaging studies. Its prevalence depends on the population covered by the study but is not affected by the patient's gender or the imaging modality utilized for AN assessment.

A novel variant in the ROR2 gene underlying brachydactyly type B: a case report.

BACKGROUND: Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type B1 (BDB1) and brachydactyly type B2 (BDB2). BDB1 is the most severe form of brachydactyly and is caused by truncating variants in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene. CASE PRESENTATION: Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein. CONCLUSION: The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.

Risk Factors for Persistent Pain Requiring Surgical Treatment in Adult Symptomatic Accessory Navicular.

OBJECTIVE: Identifying the risk factors for persistent pain despite proper conservative treatment in adult symptomatic accessory navicular may reduce the need for surgical treatment. The aim of this study was to identify any such risk factors. DESIGN: Cohort study. SETTING: University hospital foot and ankle clinic. PATIENTS: A retrospective review of 313 patients who presented with adult symptomatic accessory navicular was performed. ASSESSMENT OF RISK FACTORS: Potential risk factors were identified via medical records and foot radiographs. The possible risk factors included age, gender, body mass index, smoking status, occurrence/cause of symptoms, occupation, type of accessory navicular, and radiographic foot parameters. MAIN OUTCOME MEASURES: Predictors that relate to persistent pain requiring surgical treatment in adult accessory navicular were analyzed using logistic regression analysis. RESULTS: Of the 313 patients included, 30 (9.6%) underwent surgical treatment due to failure of conservative treatment. The odds of needing surgical treatment decreased by 0.96 per year of age at symptom onset (P = 0.030), but those odds were 8.52 times higher in patients who had a type IIB accessory navicular (P = 0.001). Other variables did not reach statistical significance. CONCLUSIONS: Younger age at symptom onset and type IIB were the risk factors for persistent pain requiring surgical treatment in adult symptomatic accessory navicular.

What is New in Pediatric Orthopaedic Foot and Ankle.

BACKGROUND: This paper aims to report on the last 5 years of relevant research on pediatric foot and ankle pathology with specific focus on clubfoot, congenital vertical talus, toe walking, tarsal coalitions, pes planovalgus with or without accessory navicular, foot and ankle trauma, and talar dome osteochondritis dessicans. METHODS: The Browzine platform was used to review the table of contents for all papers published in the following target journals related to the treatment of pediatric foot and ankle conditions. Search results were further refined to include clinical trials and randomized controlled trials published from March 1, 2015 to November 15, 2021. RESULTS: A total of 73 papers were selected for review based on new findings and significant contributions in treatment of clubfoot, congenital vertical talus, toe walking, tarsal coalitions, pes planovalgus with or without accessory navicular, foot and ankle trauma, and talar dome osteochondritis dessicans. Also included were several papers that did not fit into any of these categories but provided new insight into specific foot and ankle pathologies. CONCLUSIONS: Treatment strategies for children with foot and ankle pathology are continually evolving. We review many of the most recent publications with the goal of improving understanding of these pathologies and highlighting current best practices. LEVEL OF EVIDENCE: Level III.

Talocalcaneal Tarsal Coalition Size: Evaluation and Reproducibility of MRI Measurements.

BACKGROUND: The size of talocalcaneal tarsal coalitions (TCCs) is one of the main factors that is thought to influence patient outcomes after resection. Magnetic resonance imaging (MRI) is increasingly being used to diagnose and characterize TCCs. However, there is no reproducible MRI-based measurement of TCC size reported in the literature. The purpose of this study was to create a method to reproducibly measure TCC size using MRI. METHODS: Twenty-seven patients with TCCs diagnosed by a hindfoot coronal proton density (PD) MRI between 2017 and 2020 were included. Five independent raters measured coalition width, healthy posterior facet width, and healthy middle facet width on individual slices of coronal PD hindfoot MRIs using discrete MRI measurement guidelines. Individual slice measurements were summed to determine total size of the coalition and the remaining healthy cartilage of the posterior and middle facets. Inter-rater reliability of MRI measurements between the 5 independent examiners was evaluated using intraclass correlation coefficient (ICC). ICC was calculated for total coalition width, total healthy posterior facet width, total coalition width/total healthy posterior facet width, total coalition width/total healthy middle facet width, total coalition width/total healthy subtalar facet width (posterior facet+middle facet), and total coalition width/total subtalar facet width (coalition+posterior facet+middle facet). RESULTS: The ICC scores for all but one of the MRI measurements indicated good to excellent inter-rater reliability among the 5 examiners. The ICC was 0.932 (95% confidence interval: 0.881-0.966) for measurement of total coalition width/total healthy posterior facet width and 0.948 (95% confidence interval: 0.908-0.973) for measurement of total coalition width/total subtalar facet width (middle+posterior+coalition). CONCLUSIONS: Measurements of coalition size using novel MRI guidelines were reproducible with good to excellent inter-rater reliability. These guidelines allow for determination of TCC size using coronal PD MRI. LEVEL OF EVIDENCE: Level II-diagnostic reproducibility study.

8 out of 10 patients do well after surgery for tarsal coalitions: A systematic review on 1284 coalitions.

BACKGROUND: The primary aim was to determine the clinical success rate after treatment for talocalcaneal (TCC) and calcaneonavicular coalitions (CNC). The secondary aim was to evaluate the complication, recurrence and revision rate. METHODS: A search was carried out in MEDLINE, EMBASE and Cochrane Library. Methodological quality was assessed using the Methodological Index for Non-Randomised Studies (MINORS) criteria. The primary outcome was the clinical success rate and was pooled per type of coalition and treatment modality. 95% Confidence Intervals (CI) of the success rates were calculated. Secondary outcomes included complication rates, coalition recurrence rates, revision rates and pain improvement using the Visual Analogue Scale (VAS). A sub-analysis on interposition material was performed. RESULTS: 43 articles comprising of 1284 coalitions were included, with a pooled mean follow-up of 51 months. Methodological quality was fair. The overall pooled success rate for TCCs was 79% (95% CI, 75%-83%). Conservative treatment, open resection and arthroscopic resection of TCCs resulted in success rates of 58% (95% CI, 42%-73%), 80% (95% CI, 76%-84%) and 86% (95% CI, 71%-94%), respectively. CNCs have an overall success rate of 81% (95% CI, 75%-85%), with 100% (95% CI, 34%-100%), 80% (95% CI, 74%-85%) and 100% (95% CI, 65%-100%) for conservative treatment, open resection and arthroscopic resection, respectively. Pooled complication rates of 4% (95% CI, 3%-7%) for TCCs and 6% (95% CI, 4%-11%) for CNCs were found. The success rates of resection with and without interposition material for TCCs were 83% (95% CI, 78%-87%) and 79% (95% CI, 65%-88%), and for CNCs 81% (95% CI, 76%-86%) and 69% (95% CI, 44%-85%), respectively. CONCLUSION: Treatment of tarsal coalitions can be considered good to excellent as well as safe, with an overall clinical success rate of 79% for TCCs and 81% for CNCs. Arthroscopic resection of the coalition appears to be non-inferior to open resection of TCCs and CNCs. LEVEL OF EVIDENCE: Level IV, Systematic Review.

Multiple synostoses syndrome: Clinical report and retrospective analysis.

Multiple synostoses syndrome (SYNS1; OMIM# 186500) is a rare autosomal dominant disorder reported in a few cases worldwide. We report a Chinese pedigree characterized by proximal symphalangism, conductive hearing loss, and distinctive facies. We examined the genetic cause and reviewed the literature to discuss the pathogeny, treatment, and prevention of SYNS1. Audiological, ophthalmological, and radiological examinations were evaluated. Whole-exome sequencing (WES) was performed to identify mutations in the proband and her parents. Sanger sequencing was used to verify the results for the proband, parents, and grandmother. The literature on the genotype-phenotype correlation was reviewed. The patient was diagnosed with multiple synostoses syndrome clinically. WES and bioinformatic analysis revealed a novel missense mutation in the NOG gene, c.554C>G (p.Ser185Cys), cosegregated in this family. The literature review showed that the phenotype varies widely, but the typical facies, conductive hearing loss, and proximal symphalangism occurred frequently. All reported mutations are highly conserved in mammals based on conservation analysis, and there are regional hot spots for these mutations. However, no distinct genotype-phenotype correlations have been identified for mutations in NOG in different races. Regular systematic examinations and hearing aids are beneficial for this syndrome. However, the outcomes of otomicrosurgery are not encouraging owing to the regrowth of bone. This study expanded the mutation spectrum of NOG and is the first report of SYNS1 in a Chinese family. Genetic testing is recommended as part of the diagnosis of syndromic deafness. A clinical genetic evaluation is essential to guide prevention, such as preimplantation genetic diagnosis.

Tarsal coalition.

PURPOSE OF REVIEW: Tarsal coalitions may cause painful pes planovalgus and recurrent sprains, and can lead to arthrosis if improperly managed. In this review, we discuss the current topics related to talocalcaneal and calcaneonavicular coalitions. RECENT FINDINGS: Tarsal coalitions are initially managed with conservative therapy, and when this approach fails, surgery is performed. Treatment of calcaneonavicular coalitions involves resection of the coalition and interposition of the extensor digitorum brevis muscle or fat, and in cases of marked valgus deformity, correction of the deformity. In talocalcaneal coalitions, recommendations include coalition resection for those affecting less than 50% of the area of the posterior facet and with a less than 16° valgus, coalition resection and valgus correction for those affecting less than 50% of the area and valgus greater than 16°, and isolated valgus correction for those affecting more than 50% of the area and with a more than or less than 16° valgus. Arthrodesis is reserved as a salvage procedure. SUMMARY: Talocalcaneal and calcaneonavicular coalitions can cause painful pes planovalgus. Their diagnoses are confirmed by plain radiograph, computed tomography, and, in cases of fibrous or cartilaginous coalitions, MRI. Initial treatment is conservative, and when symptoms persist, resection of the coalition is recommended along with tissue graft interposition with or without associated valgus correction. Arthrodesis is indicated as a salvage procedure whenever treatment fails or with advanced arthrosis.

Do Not Judge an Ossicle by Its Size: Type 1 Ossicles Associated With Posterior Tibial Tendon Dysfunction.

INTRODUCTION: Patients with type II navicular ossicles have traditionally been considered to be symptomatic, whereas patients with type I and III bones are considered asymptomatic without additional relevant imaging findings. The main objective of this study is to investigate the association of type I os naviculare with clinical symptomology and magnetic resonance imaging findings in comparison to types II and III ossicles. METHODS: Three hundred nine subjects with accessory navicular bone types were identified, and their associations with focal navicular pain, pes planus alignment, ossicle or proximal navicular bone marrow edema pattern presence (BMEP), and posterior tibial tendon (PTT) sheath fluid distension were assessed. Fisher's exact test was used for categorical data and unpaired t tests for continuous data. Intraobserver and interobserver agreement was calculated. RESULTS: Overall, 28% (85/309) of type I, 57% (176/309) of type II, and 16% (48/309) of type III accessory bones had focal navicular pain (type I vs type II, P = 0.17; type III vs type II, P = 0.001). Thirty-two percent of type I, 38% type II, and 8% type III accessory bones had pes planus (type I vs II, P = 0.3; type III vs type II, P = 0.001). Nine percent of type I, 48% of type II, and 6% of type III accessory bones had BMEP (type I vs II, P < 0.0001; type III vs type II, P = 0.001). Thirty-three percent of type I, 42% of type II, and 6% of type III accessory bones had PTT intrasheath fluid (type I vs II, P = 0.16; type III vs type II, P = 0.001). CONCLUSIONS: Symptomatic type I navicular ossicle patients demonstrate an increased tendency to present with early findings of PTT dysfunction and morphologic pes planus to a greater degree than previously recognized. LEVEL OF CLINICAL EVIDENCE: 3.

Bipartite medial cuneiform: magnetic resonance imaging findings and prevalence of this rare anatomical variant.

OBJECTIVE: To describe the imaging features of bipartite medial cuneiform and to determine the prevalence of this rare anatomical variant in a large group of patients that were evaluated by magnetic resonance imaging (MRI) of the foot. MATERIALS AND METHOD: Seven hundred and fifty-one patients that underwent MRI of the foot from May 2016 to December 2018 were included in the study (mean age 49 years; 540 females; 211 males). All MRIs were retrospectively analyzed to identify bipartite medial cuneiform. For patients with bipartite medial cuneiform, we analyzed partial and complete bipartition, the type of articulation (synchondrosis, syndesmosis, or a combination of these two), and stress changes related to abnormal motion (i.e., subchondral cysts and sclerosis). Bone marrow edema-like signal, diastasis in the cleavage plane, concomitant fractures, and the presence of the E-sign were also evaluated. RESULTS: Nine feet from six patients presented bipartite medial cuneiform on the MRI. Six and three feet exhibited complete and partial bipartition. All patients were referred for MRI because of midfoot pain, of which two had history of trauma prior to imaging. Stress changes related to abnormal motion were observed in three feet (34%), all with complete bipartition. Bone marrow edema-like signal was recorded in five feet (55%) and diastasis in one foot (11%). No fractures were present in the bipartite medial cuneiform. All patients had E-signs. CONCLUSION: Bipartite medial cuneiform is a rare anatomical variant occurring in 0.79% of patients who underwent foot MRI in this study. It is important to be aware of this variant as it is a cause of midfoot pain. Being familiar with the E-sign helps identify and differentiate it from a fracture.

One-Bone Tarsus: A Case Report.

Tarsal coalition is a condition characterized by abnormal connections between ≥2 tarsi. Although tarsal coalition is not rare, tarsal coalitions involving >2 tarsi are very unusual. In this report, we describe a case of multiple tarsal coalitions in a 24-year-old male who experienced progressively worsening pain for 3 to 4 months before presenting for care. This case was unique in that all the tarsal and tarsometatarsal bones in the foot were fused and formed 1 integrated tarsal. All of the metatarsals were fused as well, and the patient had no joints or ranges of motion in the hindfoot or midfoot. The patient's pain was responsive to anti-inflammatory medications, and no surgical intervention was necessary. To the best of our knowledge, this is the most extensive case of multiple tarsal coalitions described in the literature to date.

Cryopreserved Amniotic Membrane and Autogenous Adipose Tissue as an Interpositional Spacer After Resection of a Cubonavicular Coalition: A Case Report and Review of the Literature.

Coalitions of the hindfoot are a relatively rare but challenging condition encountered by foot and ankle surgeons. Those that manifest between the cuboid and navicular (cubonavicular coalitions) are seen even more infrequently and are estimated to comprise ∼1% of all tarsal coalitions. Treatment for cubonavicular coalitions parallels protocols for more common hindfoot coalitions. Typically, resection versus hindfoot arthrodesis procedures are used. The present study describes the case of a 34-year-old male with a painful cubonavicular coalition and early secondary signs of arthrosis. Despite the recommended guidelines of hindfoot arthrodesis, he elected for surgical resection. Autogenous adipose tissue and cryopreserved amniotic membrane were used for interposition at the resection site. This case demonstrates that surgical resection with interpositional grafting can be successful even in advanced disease states.

Comparison of outcomes of arthrodesis and reconstruction (advancement), posterior tibial tendon with excision of accessory tarsal navicular bone (Kidner procedure) in type 2 accessory navicula.

BACKGROUND: The therapeutic outcome of the local arthrodesis surgery for type 2 accessory navicula (AN) is rarely reported. This study aimed to compare the clinical outcomes between Kidner and arthrodesis procedures for type 2 AN. METHODS: Sixteen patients (20 feet) with symptomatic type 2 AN receiving surgical treatment in our hospital between November 2013 and December 2015 were retrospectively included. Ten patients (13 feet) underwent the Kidner surgery (Kidner group) and 6 patients received local arthrodesis procedure (arthrodesis group). Radiographic indices before/after surgery were compared between the two groups. Patient's satisfaction with surgery outcome was evaluated by patient self-assessment questionnaire. RESULTS: The calcaneal pitch angle was significantly increased after surgery in both groups (bothp<0.01), while the talocalcaneal coverage angle and lateral talo-first metatarsal angle were not significantly changed after surgery. There was no significant difference regarding the postoperative changes in the three radiographic indices between the two groups. In the arthrodesis group, 3 patients (4 feet) had an excellent outcome, 2 patients (2 feet) a good outcome, and 1 patient (1 foot) had a fair outcome. In the Kidner group, 6 patients (8 feet), 2 patients (3 feet), 1 patient (1 foot) and 1 patient (1 foot) had excellent, good, fair, and poor treatment outcomes, respectively. The rate of good-to-excellent outcomes was comparable between the arthrodesis group and Kidner group (83% vs. 80%, p=0.696). CONCLUSION: Our results suggested that both the Kidner surgery and arthrodesis surgery were an effective treatment for symptomatic type 2 AN.

A point mutation in Fgf9 impedes joint interzone formation leading to multiple synostoses syndrome.

Human multiple synostoses syndrome (SYNS) is an autosomal dominant disorder characterized by multiple joint fusions. We previously identified a point mutation (S99N) in FGF9 that causes human SYNS3. However, the physiological function of FGF9 during joint development and comprehensive molecular portraits of SYNS3 remain elusive. Here, we report that mice harboring the S99N mutation in Fgf9 develop the curly tail phenotype and partially or fully fused caudal vertebrae and limb joints, which mimic the major phenotypes of SYNS3 patients. Further study reveals that the S99N mutation in Fgf9 disrupts joint interzone formation by affecting the chondrogenic differentiation of mesenchymal cells at the early stage of joint development. Consistently, the limb bud micromass culture (LBMMC) assay shows that Fgf9 inhibits mesenchymal cell differentiation into chondrocytes by downregulating the expression of Sox6 and Sox9. However, the mutant protein does not exhibit the same inhibitory effect. We also show that Fgf9 is required for normal expression of Gdf5 in the prospective elbow and knee joints through its activation of Gdf5 promoter activity. Signal transduction assays indicate that the S99N mutation diminishes FGF signaling in developmental limb joints. Finally, we demonstrate that the conformational change in FGF9 resulting from the S99N mutation disrupts FGF9/FGFR/heparin interaction, which impedes FGF signaling in developmental joints. Taken together, we conclude that the S99N mutation in Fgf9 causes SYNS3 via the disturbance of joint interzone formation. These results further implicate the crucial role of Fgf9 during embryonic joint development.

Heterozygous Mutations in MAP3K7, Encoding TGF-ß-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome.

Cardiospondylocarpofacial (CSCF) syndrome is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. Whole-exome sequencing identified heterozygous MAP3K7 mutations in six distinct CSCF-affected individuals from four families and ranging in age from 5 to 37 years. MAP3K7 encodes transforming growth factor ß (TGF-ß)-activated kinase 1 (TAK1), which is involved in the mitogen-activated protein kinase (MAPK)-p38 signaling pathway. MAPK-p38 signaling was markedly altered when expression of non-canonical TGF-ß-driven target genes was impaired. These findings support the loss of transcriptional control of the TGF-ß-MAPK-p38 pathway in fibroblasts obtained from affected individuals. Surprisingly, although TAK1 is located at the crossroad of inflammation, immunity, and cancer, this study reports MAP3K7 mutations in a developmental disorder affecting mainly cartilage, bone, and heart.

Accessory navicular syndrome as a cause of foot pain during stroke rehabilitation.

Although usually asymptomatic, an accessory navicular bone can lead to medial foot pain, especially in younger people engaged in high impact sports. In many such cases, the tendon of posterior tibialis (which inverts and plantarflexes the foot) inserts onto the accessory bone resulting in greater strain on the tendon. In the present case, pain due to an accessory navicular bone first developed during stroke rehabilitation in a 69-year-old man. The relative overactivity of posterior tibialis in strokes involving the leg and overuse due to active rehabilitation were likely contributors. An accessory navicular syndrome should be considered as a cause of medial foot pain in patients following a stroke. As in our case, conservative management with rest, ice and elevation is usually successful.