Incidence of ankle sprain and chronic ankle instability is higher in women versus men. One sex-specific factor may be the greater ligamentous laxity in women compared with men, potentially influenced by estrogen and relaxin activity. This study aimed to investigate changes in ankle joint laxity and its association with hormone levels in women with and without recurrent ankle sprains. Eleven female college students with recurrent ankle sprains and seven students with no or a single prior sprain participated. Ankle joint laxity was assessed using an ankle arthrometer with a 125-N load for anterior-posterior displacement and inversion-eversion rotation. Serum estradiol (E2) and relaxin-2 levels were measured. Ankle laxity assessments and blood sampling were performed in the follicular, ovulation, and luteal phases of the participant's individual menstrual cycle. A significant group × phase interaction was found for inversion-eversion ankle joint laxity; however, post hoc analyses adjusted for Bonferroni multiple comparisons were not significant, implying a lack of clinical interest or potential sampling fluctuations. A positive correlation was found between serum relaxin-2 level and anterior-posterior ankle joint laxity during the luteal phase (r = 0.557, p = 0.048). This association should be interpreted as an observational finding that may help generate hypotheses regarding potential hormone-related factors in in ankle sprains in women.

Machine Learning Based Prediction of Tibial Insert Thickness in Total Knee Arthroplasty From Intraoperative Knee Joint Laxity Data.

Ehlers-Danlos syndromes (EDS) are rare heritable connective tissue disorders, most commonly linked to collagen abnormalities. In dogs, reported cases are infrequent and typically involve skin fragility and joint laxity, with limited understanding of underlying genetic causes. This report describes an unusual, aggressive, and fatal case of an Ehlers-Danlos-like syndrome (EDlS) in a Maltese dog, with several uncommon features. Unlike most canine EDS cases, which show collagen defects, this case revealed minimal collagen alterations; instead, elastic fibers were primarily affected. A one-and-a-half-year-old male Maltese dog presented with progressive abdominal masses, skin fragility, joint deformities, and frequent bruising since early life. Clinical examination revealed hyperextensible, fragile skin, hematomas, and contractures of the hind limbs. Imaging confirmed a hernia lacking supportive connective structures. Histopathological analysis showed elastic fiber hypertrophy and fragmentation, with minimal collagen changes. Despite palliative wound management, the patient died within ten days of the initial consultation due to spontaneous evisceration and vascular rupture. The histological features are consistent with a possible Tenascin-X deficiency. Definitive molecular classification was beyond the scope of this case. This report expands the spectrum of EDlS in dogs.

Revealing early subchondral bone structural changes in osteoarthritis progression in a collagenase-induced mouse model using microCT.

PurposeTo compare re-rupture rates and clinical outcomes between bone–patellar tendon–bone (BTB) and hamstring tendon (HT) grafts in anterior cruciate ligament (ACL) reconstruction according to patient risk levels.MethodsThis retrospective cohort study included patients who underwent primary ACL reconstruction at a single institution between 2018 and 2022, with outcomes assessed at a fixed 2-year postoperative follow-up. The primary endpoint was graft re-rupture, defined as a traumatic graft failure confirmed clinically and by magnetic resonance imaging, and the secondary endpoint was the Knee injury and Osteoarthritis Outcome Score (KOOS). High-risk status was defined as the presence of all three risk factors: age ≤ 20 years, posterior tibial slope. (PTS) ≥ 12°, and participation in pivoting sports. For patients with two or fewer risk factors, propensity score matching was performed using age, sex, body weight, generalized joint laxity, knee hyperextension, participation in pivoting sports, and PTS as covariates to compare outcomes between BTB and HT grafts.ResultsIn the high-risk group, the BTB graft showed a significantly lower re-rupture rate compared to the HT graft (12.9% vs. 35.7%, p = 0.03), with no significant difference in KOOS overall score (96.3 ± 3.7 vs. 96.6 ± 6.3, p = 0.85). In the lower-risk group after matching, the BTB graft showed a similar re-rupture rate compared to the HT graft (6.9% vs. 5.2%, p = 0.99), with no significant difference in KOOS overall score (92.6 ± 6.9 vs. 94.8 ± 5.7, p = 0.10).ConclusionBTB grafts reduced re-rupture rates compared to HT grafts in high-risk ACL reconstruction patients, while clinical outcomes were similar. In lower-risk patients, no significant differences were observed between graft types in either re-rupture rates or KOOS overall score.Level of evidenceLevel III.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00402-026-06196-5.

This study aimed (1) to provide a stepwise, reproducible description of a single-bone-tunnel, two-stranded, anchorless ligament-specific ('en Masse') repair for traumatic peripheral TFCC tears, and (2) to evaluate one-year clinical outcomes and exploratory prognostic factors in a retrospective consecutive case series. Forty-eight patients were retrospectively included. Postoperatively, ballottement testing revealed no detectable distal radioulnar joint (DRUJ) laxity (p < 0.001). The mean visual analog scale (VAS) pain score (7.2 to 1.9), grip strength (66.1% to 81.3%), Mayo wrist score (MWS, 64.3 to 81.9), and Disabilities of the Arm, Shoulder, and Hand (DASH) score (37.1 to 12.7) were improved postoperatively (p < 0.001). There were no surgery-related complications. On multivariable analysis, longer symptom duration (p = 0.031) and positive ulnar variance (p = 0.045) were associated with lower MWS; model fit was modest (R2=0.224). Arthroscopic-assisted en Masse repair for peripheral TFCC tears was associated with improved clinical outcomes at one year or more after surgery, and postoperative ballottement testing revealed no detectable DRUJ laxity. Within this cohort, one-year follow-up precluded assessment of long-term durability; also, applicability to degenerative/chronic peripheral TFCC tears remains undetermined.

Canine hip dysplasia (CHD) is a common orthopedic condition characterized by joint laxity, abnormal femoral head development, and osteoarthritis. Radiography remains the gold standard in diagnosis; however, ultrasonography (US) can detect changes in bone and periarticular soft tissue earlier in CHD progression. Forty-four hips from twenty-two adult dogs of various breeds were graded according to the Fédération Cynologique Internationale (FCI) grading system, and grouped as normal (A, B) or dysplastic (C, D, E). Canine hip US evaluation, using the ventral femoral head-neck approach, included the following: capsule thickness at the femoral head index (CTFHi) and capsule thickness at the femoral head-neck index (CTFHNi), both measured in mm/body weight × 100; femoral head shape score (FHSs) and femoral head-neck transition score (FHNTs); and osteophyte score (Os). These findings were evaluated qualitatively and then converted into numerical scores. Twenty-three hips were graded on the FCI system as being normal, and twenty-one as dysplastic. Median values of the US parameters CTFHi, CTFHNi, FHSs, FHNTs, and Os were 2.02, 7.79, 1.00, 1.00, and 0.00 in the normal-hips group, and 3.11, 9.32, 3.00, 2.00, and 1.00 in the dysplastic-hips group. Significant differences were observed between most US parameters evaluated. Strong associations were found between CTFHi, FHNTs, and Os, indicating progressive bone remodeling. These findings support US usage as a potential tool for CHD diagnosis and monitoring.

IntroductionFemoro-Acetabular Impingement (FAI) is characterized by abnormal interaction between the femoral head and acetabulum, often resulting in pain, restricted motion, and arthritis. Hip arthroscopy is an effective management intervention, but outcomes can be influenced by the degree of hip laxity. Currently, hip laxity assessment relies on physical exams and intra-operative imaging. Identifying a reliable, preoperative indicator of hip laxity could enhance surgical strategies and patient outcomes.AimThis study aims to investigate the relationship between hip capsule thickness and hip laxity in patients diagnosed with FAI. Specifically, it aims to investigate whether there is a correlation between hip capsule thickness measured by preoperative magnetic resonance arthrogram (MRA) and hip laxity through intraoperative x-rays.MethodA retrospective analysis was conducted on 100 patients aged 18-35 with FAI treated at The Hip Preservation Institute, UPMC Whitfield, Waterford, between January 2019 and January 2021. Data was gathered from an institutional hip arthroscopy register, electronic health records, and imaging databases. Capsule thickness was measured using preoperative magnetic resonance arthrogram (MRA) scans, while hip laxity was evaluated using intraoperative x-rays (no traction(NT), manual traction(MT), full traction(FT)), both via the InteleViewer software. Descriptive statistics, correlation analysis and multivariable linear regression was performed using SPSS.Results85 male, 15 females were included, mean age 25.8±4.6 years. Mean capsular thickness measurement was 3.7±0.96mm. Mean traction measurements: NT 3.6±0.72cm, MT 9.4±3.0cm, 12.3±3.1cm. Pearson’s correlation revealed a significant inverse relationship between capsular thickness and MT (r=0.349, p<0.001) and FT (r=0.360, p<0.001). Multivariable linear regression revealed that increased capsular thickness and increased alpha angle reduced the measurable traction distance: For MT: for every 1mm increase in capsular thickness and 1degree increase in alpha angle, manual traction decreased by 0.997cm (p<0.001) and 0.053cm (p=0.017) respectively. For FT: for every 1mm increase in capsular thickness and 1degree increase in alpha angle, manual traction decreased by 1.077cm (p<0.001) and 0.063cm (p=0.006) respectively.ConclusionA preoperative MRA measurement of capsular thickness correlates with joint laxity (as the capsule thickens the laxity decreases) and therefore may assist in decision making around capsulotomy technique and capsular repair for those with increased likelihood of a lax joint.

Distal femoral derotational osteotomy (DFDO) is widely performed to correct excessive femoral anteversion in patients with patellofemoral instability. However, unintended changes in coronal alignment can occur depending on the orientation of the cutting plane. We present a case of unintentional femoral valgization after DFDO in a patient with a recurrent patellar dislocation. A 23-year-old female presented with multiple episodes of recurrent patellar dislocation of her right knee. Physical examination revealed a positive apprehension test, positive J-sign, and generalized joint laxity. An effusion was observed in the right knee. Radiologic findings included increased femoral anteversion (30.3°), ruptured medial patellofemoral ligament (MPFL), mild varus alignment (hip-knee-ankle angle 0.4°), mechanical lateral distal femur angle (mLDFA) of 86.6°, patella alta, and increased tibial tuberosity-trochlear groove (TT-TG) distance. The patient underwent MPFL reconstruction and DFDO with target correction of femoral anteversion of 15°. Osteotomy was performed perpendicular to the real anatomical shaft axis. Postoperative imaging revealed an unintended valgus malalignment (HKA angle -3.0°) and decrease of mLDFA (83.6°). Despite the altered alignment, no recurrence of dislocation was noted during the 18-month follow-up period, and the clinical outcome was satisfactory. Unintentional valgus alignment may result from osteotomies oriented perpendicular to the real anatomical shaft axis. Surgeons should consider using the virtual anatomical shaft axis to determine the cutting plane and minimize the risk of iatrogenic malalignment during DFDO.

Preservation of posterior cruciate ligament in cruciate-retaining total knee arthroplasty with a cruciate-substituting insert does not affect postoperative clinical outcomes, including Forgotten Joint Score 12.

Fibulin-4, an extracellular matrix protein, is indispensable for elastic fiber assembly. Fibulin-4 null mice show bilateral forelimb contracture and patients with EFEMP2/FBLN4 mutations demonstrate similar defects, besides joint laxity, vascular and pulmonary abnormalities. Here we report that limb tendons in fibulin-4 null mice developed normally until E17.5-18.5, but thereafter thinner tendons showed abnormalities, suggesting that fibulin-4 maintains the integrity of certain tendons. Tendon/ligament specific conditional knockout mice of Efemp2/Fbln4 (ScxCre-H;Fbln4flox/- mice) were generated in order to elucidate its role of collagen fibril organization, collagen cross-linking and mechanical features of tendons. Curiously, however, the conditional Fbln4 knockout mice did not show forelimb contractures or other obvious morphological defects. We could detect small amounts of fibulin-4 in tendon extracts, but isolated tenocytes from the conditional knockout mice did not secrete fibulin-4, confirming that the Efemp2/Fbln4 gene was properly deleted in tenocytes. Electron microscopic analyses revealed an enhanced proportion of thinner fibrils in tendons from the conditional knockout mice. Furthermore, mechanical stress tests of patellar tendons of the conditional knockout mice revealed strongly reduced strain resistance compared to the tendons of control mice, although cross-link formation and thermal stability of tendon collagen were not affected. These finding indicate that fibulin-4 has an important role in the organization and stability of collagen fibrils in tendons.

The impact of meniscal tears on anterior tibial translation and rotatory instability in anterior cruciate ligament-deficient knees: Retrospective analysis of 306 cases.

Background: This pilot study aimed to examine postural control characteristics in adolescents with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), who often show atypical postural regulation due to sensory integration challenges. While sensory factors have received increasing attention, few studies have investigated postural sway under different environmental conditions, particularly auditory stimulation. The primary objective was to compare the center of pressure (COP) sway between adolescents with and without NDDs under open-eye, closed-eye, and auditory conditions. Secondary objectives included evaluating directional sway (X- and Y-axis) and the specific effects of auditory input.Methods: This cross-sectional pilot study included nine adolescents with NDDs and 37 typically developing (TD) peers. Physical measurements (height, weight, BMI, joint laxity, grip strength, knee extension strength) and postural control were assessed. Static standing balance was measured barefoot for 30 seconds in three conditions (open eyes, closed eyes, auditory stimulation with a non-rhythmic piano composition) using a force plate. Each condition was measured once for 30 seconds. COP parameters included total path length, path length per unit area, and directional displacement. Between- and within-group comparisons were analyzed using the Mann-Whitney U and Wilcoxon signed-rank tests, with exact p-values, effect sizes (r), and 95% confidence intervals reported.Results: Adolescents with NDDs exhibited significantly lower grip and knee extension strength than TD peers (p < 0.001, r = 0.47-0.68). COP sway was significantly greater in the NDD group under auditory stimulation (p < 0.001, r = 0.71). Within both groups, sway increased significantly under auditory stimulation compared to the open-eyes condition (p < 0.001, r = 0.25-0.52).Conclusion: This pilot study provides preliminary evidence that adolescents with NDDs demonstrate increased postural sway under auditory stimulation, which may reflect sensory integration difficulties and reduced muscular control. Given the small and heterogeneous sample, these findings should be interpreted with caution. Larger and more homogeneous studies are needed to confirm the observed associations and to clarify the role of auditory input in postural stability among youth with developmental disorders.

Robotic-assisted surgery has become an increasingly attractive option for orthopaedic surgeries, specifically in its use for total knee replacement (TKR). Despite the allure, characterization of the outcomes of robotic-assisted surgery against conventional manual methods remains to be investigated. Therefore, this study aims to characterize kinematics of TKR knees following robotic-assisted and conventional arthroplasty through loaded laxity testing. We hypothesize that robotic-assisted TKR will result in less variable kinematic behavior at end range of motion than its conventional counterparts. Seven pairs of TKR knees were used in this study. For each pair, one surgery was performed using conventional manual methods, while the contralateral side utilized a VELYS robotic-assisted solution (DePuy Synthes). All TKRs were performed by the same surgeon and used a cruciate retaining rotating platform (CR RP) implant system. The knees were mounted onto a VIVO joint motion simulator (Advanced Mechanical Technologies Inc.). Once installed, specimens were pre-conditioned via a baseline loading protocol that involved cycling though the flexion arc from 15 to 90 degrees, while reducing the joint with 30 N of compression. Next, laxity was assessed via applied isolated (1) 4 Nm internal/ external (IE) rotation torques, (2) 8 Nm varus/ valgus (VV) rotation torques, and (3) 40 N anterior, and 80 N posterior forces. Each was performed at discrete positions of 15, 30, 60 and 90 degrees of knee flexion. Laxity outputs were adjusted for joint behavior during baseline to mitigate and mounting biases and account for specimen-specific joint behavior, and conventional TKR and robotic-assisted TKR knees were compared via paired two-tailed t-tests for each combination of flexion angle and tested degree of freedom. At 90° flexion, external rotation laxity was significantly different between the groups (P=0.04), with conventional TKR knees exhibiting greater rotation (26.5° ± 9.1°) than robotic- assisted TKR knees (18.3° ± 3.5°). This is complemented by the observed trend of the difference between conventional and robotic TKR knee external rotation laxity limits increasing with each flexion angle”: 15.8° ± 8.1° [conventional] and 14.1° ± 4.1° [robotic-assisted] at 15 degrees, 20.2° ± 7.2° [conventional] and 18.5° ± 5.6° [robotic-assisted] at 30 degrees, and 21.9° ± 7.2° [conventional] and 19.0° ± 5.2° [robotic-assisted] at 60 degrees. No other statistically significant differences were identified. The results of the current study suggest that while conventionally done TKR may result in comparable joint laxity than those done using conventionally methods, through most of the flexion arc, the latter provides greater stability in external rotation in high flexion (namely 90°). However, observed laxity differences may be compensated for in the opposite direction, resulting in a balanced total laxity envelope. These findings could provide a greater understanding of patient outcomes and inform surgical decision making to cater to a patient's desired functional outcome.

IntroductionJoint injuries, a major type of human musculoskeletal disorder, are often accompanied by soft tissue damage, and restoring ligament integrity is a key strategy for reconstructing joint function. However, existing artificial ligaments face a critical challenge: reconciling robust biomechanical performance with intrinsic self-healing capability, especially under cyclic loading and accidental overload conditions. Conventional materials like polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) struggle with long-term durability, while emerging self-healing designs are limited by poor mechanical robustness and slow healing kinetics.MethodsThis study developed a self-healing artificial ligament via 3D braiding of shape memory alloy (SMA, Ni50.71Ti49.29) wires and polyethylene (PE) fishing lines, mimicking the hierarchical structure of natural ligaments. The ligament was fabricated with a 1-over-1-under interlock configuration (6 carriers, 180° braid angle) and pre-tensioned (5% strain at 60 °C for 12 h) for structural stabilization. Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA), and mechanical tests (hysteresis, stress relaxation, cyclic loading) were conducted to characterize its thermal and mechanical properties. Electrothermal recovery tests (3–5.5 W power input) evaluated self-healing performance, and a 3D-printed artificial hip joint was used to validate in-situ functionality.ResultsDSC showed the SMA had a thermal hysteresis window of 24.8 °C (Ms=46.5 °C, Mf=27.2 °C, As=58.3 °C, Af=71.3 °C), and DMA revealed an “S”-type storage modulus curve during heating . After 1,000 s of cyclic loading, the self-healing ligament retained ∼73% of initial stress (vs. 37% for conventional ligaments) and had a lower energy dissipation ratio due to SMA’s low damping. Electrothermal tests showed maximum contraction rate increased with pre-strain, and 3–5.5 W power input enabled proportional contraction strain. In artificial hip tests, SMA activation restored ∼95% of initial joint laxity, reducing excessive rotational/translational motion by 26% and 12% respectively.DiscussionThe hybrid SMA-PE design resolves the trade-off between biomechanical performance and self-healing: PE provides foundational tensile strength, while SMA enables electrothermal self-healing via phase transformation. The 3D braided structure replicates natural ligaments’ J-shaped stress-strain behavior, ensuring adaptability to dynamic joint movements. Compared to piezoelectric nanomaterial (PENM)-based designs (focused on proprioception), this ligament prioritizes mechanical stability and rapid self-healing, making it suitable for clinical rehabilitation and assistive devices. Future work will address limitations like wired power supply (via wireless modules) and long-term stability (via anti-degradation coatings).

Disclosure: R.C. Williams: None. S.S. Dahir: None. C.R. Lichtenfeld: None. L.T. Drake: None. L.R. Rehm: None. K.M. Dahir: Alexion Pharmaceuticals, Inc., Ultragenyx, Kyowa Kirin.Background: Osteogenesis Imperfecta (OI) is a group of rare inherited connective tissue disorders with low bone mass and fragility. In most cases, there is a reduction in the production or synthesis of normal type I collagen most commonly due to mutations in the COL1A1/COL1A2 genes. OI type VII is an autosomal recessive form of severe or lethal OI characterized by fractures at birth, bluish sclerae, early deformity of lower extremities, coxa vara, and osteopenia. Clinical manifestations of OI type VII include recurrent fractures that decrease after puberty and increased bone turnover. Affected individuals commonly exhibit below-average height and shortened upper arm and thigh bones. OI Type VII is caused by a homozygous or compound heterozygous mutation in the CRTAP gene on chromosome 3p22. Case Description: A 24-year-old Hispanic male presented for consultation of transition of care from pediatrics for a diagnosis of OI established at 8 days of age. The patient had no family history of the condition. Genetic screening for COL1A1 and COL1A2 gene mutations revealed no OI-associated abnormalities. At birth, he had bilateral femur fractures in both legs and broke his humerus and femur at ages 1 and 5 months, respectively. In his first 8 years of life, he had repeated breaks to both femurs as well as a left humerus and vertebral fracture. All fractures have been without trauma, such as reaching for an object. His last fracture was at age 14 which resulted in intermedullary rod placed. Prior medical management was IV Pamidronate initiated at the age of 7 and continued until the age of 16. Evaluation at age 24 was remarkable for marked joint laxity, opalescent dentin with brownish discoloration of malformed teeth, short stature with shortened upper arms, normal hearing and DXA scan normal. Genetic testing results revealed homozygous likely pathogenic variants in CRTAP c.471+4A>G and a variant of uncertain significance in the ANO5 c.1606A>C9. Conclusions: The diagnosis of osteogenesis imperfecta (OI) type VII was confirmed through a combination of genetic testing for CRTAP mutations and clinical history. While most OI cases (approximately 90%) result from COL1A1/COL1A2 mutations, distinguishing OI type VII relies on identifying pathogenic variants in CRTAP, a gene critical for collagen type I biosynthesis. A homozygous CRTAP mutation leads to OI due to a deficiency in cartilage-associated protein (CRTAP), impairing collagen modification. Expanded genetic testing panels play a crucial role in facilitating earlier diagnosis and intervention, particularly for individuals presenting with OI-consistent features but lacking COL1A1 and COL1A2 mutations. Incorporating CRTAP and other rare OI-related genes into routine diagnostic workflows enhances the detection of atypical OI subtypes, allowing for timely management and tailored treatment strategies that can improve patient outcomes.Presentation: Sunday, July 13, 2025

Disclosure: M.C. Duarte: None. R. Mattos: None. T.R. Costa: None. I.S. Freitas: None. J.B. Drummond: None. B.S. Soares: None.Introduction: Marfan Syndrome (MFS) is an autosomal hereditary disorder with skeletal, ocular, and cardiovascular manifestations, while acromegaly results from excess growth hormone (GH), leading to skin thickening, extremity enlargement, and macroglossia. Both conditions are individually described, but their coexistence is rare. This case presents a unique instance of both MFS and acromegaly in one patient.Case: A 56-year-old male with classic features of MFS, including joint laxity, pectus carinatum, arm span-to-height ratio of 1.06, and positive thumb and wrist signs, also had significant cardiovascular involvement, having undergone aortic valve replacement and aneurysmectomy of the descending aorta. Despite a negative family history, his clinical features met MFS diagnostic criteria. Ten years after diagnosis, he noticed progressive changes in his hands, feet, and facial features, including a prominent nose, lips, and jaw.He sought endocrinological evaluation, and during the physical examination, signs of joint swelling and severe heart failure symptoms, including dyspnea, bilateral leg edema, and a grade V systolic murmur, were noted.Laboratory tests showed elevated IGF-1 (346 ng/mL) and GH (11 ng/mL) levels after an oral glucose tolerance test. MRI revealed a macroadenoma (1.2x0.8x0.8 cm). Due to his decompensated heart condition, surgery was postponed, and he began monthly lanreotide injections (120 mg), which reduced IGF-1 to 256 ng/mL and improved symptoms of aortic insufficiency and heart failure. One year later, cabergoline (1.5 mg/week) was added, and MRI showed tumor shrinkage (1.0x0.8x0.7 cm), though IGF-1 remained elevated at 296 ng/mL. After stabilizing his cardiac condition, the patient underwent transsphenoidal surgery. One month post-surgery, IGF-1 levels normalized, and he reported relief from swelling and pain.Whole exome sequencing (NGS) revealed no pathogenic variants linked to MFS, Multiple Endocrine Neoplasia type 1 and/or Isolated Familial Acromegaly. However, several potential pathogenic variants were identified in heterozygous form across six genes: WDR87 (p.Arg131Ter), POLR3A (c.1909+22G>A), CTNS (48 kb deletion), DUOX (p.Ser205Ter), FLG (p.Arg501Ter), and HFE (p.Cys282Tyr), though their clinical relevance is uncertain.Discussion:. In patients with Marfan-like phenotypes, fewer than 10% show pathogenic variants in the FBN1 gene, possibly due to complex genetic alterations. The identification of potential pathogenic variants in multiple genes highlights the complexity of genetic contributions to the patient’s condition, warranting further investigation. The coexistence of MFS and acromegaly in a single patient raises significant considerations about the diagnostic process, treatment strategies, and genetic evaluation for complex diseases.Presentation: Monday, July 14, 2025

Skeletal dysplasia is an ensemble of hereditary conditions that impact bone and cartilage formation, leading to aberrant skeletal growth and proportions. Such illnesses can affect the limbs, spine, and skull, and they can produce a wide range of symptoms, from minor to severe. Filamin A and B are functionally analogous proteins, exhibiting structural resemblance and playing crucial role in the formation of cellular cytoskeleton. Objective of the research was to employ experimental and computational approaches to investigate the contribution of Filamins in skeletal dysplasias. Whole exome sequencing lead to the identification of two mutations involved in a spectrum of skeletal dysplasias with predominant spine and articular association. Here we report two families from Pakistan with distinct mutations in FLNA protein (R196W) causing otopalatodigital syndrome-1 or metaepishyseal dysplasia with short stature, prominent facial dysmorphism including hypertelorism, frontal bossing, down-slanting parpebral fissures and depressed nasal bridge. While novel, homozygous, nonsense FLNB mutation (p.C1081*) is causing Spondylocarpotarsal synostosis syndrome (SCT), an exceptionally rare skeletal disorder marked by disproportionate short stature, spinal deformities, and other associated features like dental enamel hypoplasia, joint laxity, and conductive hearing loss. In silico structural and functional analysis of mutant filamins provide compelling proof for their role in the progression of skeletal dysplasias. Screened variants have not only affected the protein’s three-dimensional structure dramatically but also resulted in loss of functional domains, leading to aberrant interactions with binding proteins and progression of disease.

Shear wave elastography ultrasound assessment of the ulnar collateral ligament in the elbow of college baseball players.

Assessment of joint laxity following total knee arthroplasty: A comparison of tensioner device, navigation, and robot evaluation.