Search Results (641)

Background and Objectives: Assessing knee extensor (KE) strength is important for detecting muscle weakness in older adults, yet dynamometry is often impractical in community settings. This study examined whether smartphone-derived kinematics during the Five Times Sit-to-Stand Test (FTSST) could predict seated isometric KE strength. Materials and Methods: A cross-sectional study included 105 community-dwelling older adults (68.19 ± 5.85 years). A smartphone application extracted rising time, vertical velocity, and smartphone-estimated relative vertical power during the FTSST. KE strength was measured as maximum voluntary isometric contraction (MVIC) using fixed-frame dynamometry with a Lafayette dynamometer head. Bioelectrical impedance-derived body composition variables were reported descriptively but excluded from the primary prediction models to maintain a transparent movement-based model independent of device-specific body-composition estimates. Hierarchical regression models used smartphone-derived variables and transparent non-BIA covariates. Agreement was examined using Bland–Altman analysis. Results: Smartphone-estimated relative vertical power showed the strongest correlation with MVIC (r = 0.787, p < 0.001). The combined model including sex, age, femur length, and smartphone-estimated relative vertical power explained 71.6% of MVIC variance (adjusted R² = 0.716, SEE = 3.276 kg), outperforming vertical velocity, rising time, and total FTSST time models. Internal validation using repeated 10-fold cross-validation showed CV-R² = 0.701, CV-adjusted R² = 0.689, CV-RMSE = 3.343 kg, and CV-MAE = 2.739 kg. Bland–Altman analysis showed minimal mean bias (0.00 kg), 95% limits of agreement from −6.296 to 6.296 kg, and significant proportional bias (slope = −0.172, p = 0.002), indicating overestimation in weaker individuals and underestimation in stronger individuals. Conclusions: Consistent with our hypothesis, smartphone-estimated relative vertical power was the strongest kinematic predictor of seated isometric KE strength among the evaluated FTSST-derived variables. This approach may support community screening and monitoring, but it should not replace standardized dynamometry for precise individual-level strength quantification. Full article

Background/Objectives: Diabetic cardiomyopathy (DCM) is largely driven by severe oxidative stress and calcium dyshomeostasis. We examined the targeted antioxidant and therapeutic effects of zinc sulfate (ZnSO₄) on contractile dynamics, oxidative damage, calcium turnover, and apoptosis/fibrosis in aged female rats with type 2 diabetes. Methods: Thirty-two aged female Wistar rats were divided into Control, Control + ZnSO₄, Diabetes (DM), and DM + ZnSO₄ groups. DM was induced via high-fat diet and 30 mg/kg streptozotocin. After a 4-week complication period, treatment groups received 10 mg/kg/day ZnSO₄ (i.p.) for 6 weeks. Left ventricular papillary muscle contraction, oxidative/antioxidant markers (MDA/GSH), and gene expressions (SIRT1, GLUT4, SERCA2a, RyR2, Cav1.2, PLN) were evaluated. Myocardial architecture, fibrosis, and apoptosis were analyzed immunohistochemically. In DM rats, contractile force (CF) and velocities (±dF/dtmax) significantly declined. Results: Concurrently, SIRT1, GLUT4, SERCA2a, RyR2, Cav1.2, and antioxidant GSH decreased, while oxidative lipid damage (MDA), PLN, Caspase-3 activity, Collagen I, and fibrosis increased (p < 0.001). ZnSO₄ treatment in diabetic rats acted as a potent antioxidant modulator; it restored redox balance, activated the SIRT1/GLUT4 pathway, protected calcium-handling proteins from oxidative degradation, and significantly improved contractile dynamics. It also preserved myocardial architecture by reducing apoptosis and fibrosis. In healthy rats, ZnSO₄ caused mild stress and early fibrosis. Conclusions: In conclusion, while inducing mild stress in healthy myocardium, zinc supplementation provides robust antioxidant protection in diabetic hearts. It activates SIRT1, suppresses oxidative damage, maintains calcium homeostasis, and restores contractile dynamics, demonstrating strong antioxidant therapeutic potential against DCM. Full article

Spinal cord injury (SCI) is frequently accompanied by abnormal muscle tone and spasticity, which impair voluntary motor control, mobility, and quality of life. Although classically defined as velocity-dependent hyperreflexia, tone abnormalities after SCI encompass a broader spectrum, including sustained muscle activation, co-contraction, clonus, and non–velocity-dependent resistance to movement. These manifestations arise from distributed changes across spinal and supraspinal motor systems. At the segmental level, SCI induces maladaptive plasticity involving motoneurons, interneurons, sensory afferents, and muscle, including dysregulated persistent inward currents, altered inhibitory neurotransmission, afferent hyperexcitability, synaptic reorganization, and structural muscle remodeling. In parallel, supraspinal adaptations—including cortical motor map reorganization, reduced intracortical inhibition, corticospinal–reticulospinal imbalance, loss of monoaminergic modulation, and altered brainstem and cerebellar regulation—further amplify spinal circuit gain and impair inhibitory control of tone. Current pharmacologic treatments largely suppress symptoms without addressing these underlying circuit changes, while invasive neuromodulatory strategies are limited by surgical risk or state-dependent effects. This review synthesizes emerging insights into the multilevel mechanisms regulating abnormal tone after SCI and examines neuromodulatory approaches targeting spinal and supraspinal networks. Particular attention is given to transcutaneous spinal cord stimulation (TcSCS), a non-invasive method capable of modulating segmental reflex circuits and descending control pathways. Advances in transcriptomic and epigenetic profiling may further enable mechanism-based therapies and biomarker-guided strategies for treating spasticity. Full article

Background: Isokinetic strength of the knee joint represents a significant determinant of athletic performance and injury prevention; however, its relationship with explosive performance in young female athletes remains insufficiently explored. The aim of the study was to analyze the relationships between isokinetic strength of the knee joint at different angular velocities and explosive jumping performance in young female athletes. Methods: The research sample consisted of 13 young female athletes enrolled in sport-oriented educational programs specializing in athletics. Explosive lower-limb power was assessed using performance tests for countermovement jump (CMJ), countermovement jump free arms (CMJ FAs) and squat jump (SJ) administered with the Chronojump system. Isokinetic strength of the knee flexors and extensors was assessed using the Humac Norm dynamometer in the concentric mode at angular velocities of 60°/s, 180°/s, and 300°/s. Peak torque, the ipsilateral H:Q ratio, and bilateral asymmetries were evaluated. Pearson’s correlation coefficient was used to analyze the relationships between the investigated parameters. Results: The strongest relationships with explosive performance were observed for hamstring strength at an angular velocity of 180°/s, where significant high correlations were identified with performance in the CMJ (r = 0.693), CMJ FA (r = 0.754), and SJ (r = 0.713). In contrast, quadriceps strength demonstrated predominantly low to moderate associations with jumping performance, while no significant correlations were confirmed at an angular velocity of 300°/s. Bilateral asymmetries of the knee extensors and flexors were generally low, ranging approximately between 7 and 10%, whereas the values of the ipsilateral H:Q ratio were within the physiological range of approximately 50–55%. Conclusions: The results suggest that the ability to generate force at higher contraction velocities, particularly in the hamstrings, is significantly associated with explosive performance in young female athletes. At the same time, isokinetic strength assessment appears to be an appropriate tool for evaluating muscular strength, muscle balance, and potential asymmetries in youth sports. However, explosive performance cannot be explained solely by the level of maximal muscular strength, but rather by a complex interaction of neuromuscular and biomechanical factors. Full article

Objective: This study aimed to examine the associations of morphological variables, maximal isometric handgrip strength (MIHS), and static postural balance with self-esteem, motivational climate, school climate, and health-related quality of life (HRQoL) in early adolescents. Methods: A cross-sectional study was conducted in 235 Chilean adolescents, in whom morphological variables, MIHS, and static postural balance were assessed using center-of-pressure (CoP) parameters under eyes-open (EO) and eyes-closed (EC) conditions. Psychosocial variables, including self-esteem, motivational climate, school climate, and HRQoL, were evaluated via validated questionnaires. Multiple linear regression analyses were performed to determine associations between physical and psychosocial variables. Results: Reduced CoP sway area and lower CoP velocity under eyes-closed conditions were significantly associated with higher self-esteem (R² = 0.168; p < 0.001). Greater non-dominant MIHS and younger age were associated with more favorable perceptions of a task-involving motivational climate (R² = 0.438; p < 0.001). Higher HRQoL scores were associated with male sex and better postural balance performance. Conclusions: Better static postural balance and greater muscle strength were associated with more favorable psychosocial outcomes, particularly self-esteem and HRQoL. However, these findings should be interpreted as associative rather than causal relationships due to the cross-sectional design. Full article

Background/Objectives: Rigidity has been defined as an increase in muscle tone that is independent of the velocity of the stretch in Parkinson’s disease (PD). However, there is an ongoing debate about this non-velocity-dependent nature of rigidity in PD. To investigate the behaviour of axial muscle tone at different examination velocities using isokinetic dynamometry, and to determine whether trunk muscle resistance is velocity-dependent in people with PD compared with healthy controls (HCs). Methods: A cross-sectional study was conducted with HC and people with PD (I–III stages of Hoehn and Yahr and assessed by the UPDRS, Section III: motor aspects) by a senior neurologist. The trunk extension–flexion component of an isokinetic dynamometer measured axial muscle tone over a range of 50° (S: 30-50-80). The continuous passive mode with three angular speeds (30°/s, 45°/s and 60°/s) was used to assess muscle tone. Peak torque (N), work (J) and work recorded in the first and in the last third of the explored trunk range of motion were calculated (J) were registered. All these outcomes were performed within 1–3 h of the administration of anti-Parkinsonian medication (ON phase) in the PD sample. Results: People with PD (N = 36) and healthy controls (N = 20) completed the study. Our results showed largely similar behaviour in work and peak torque registered in both groups, by which, resistance measures, like peak torque, weakly increased with mobilisation speed from 30°/s to 45°/s, without reaching statistical significance, but increased from 45°/s to 60°/s, only in the flexors. No clear increase was observed in the work. Furthermore, greater torque measures in PD than controls were only observed for peak torque at 30°/s. Conclusions: Peak torque of trunk flexors–extensors tends to increase as the angular speed increases in both PD and controls. This may suggest that the (relatively slow) tested speeds were likely evaluating the non-neural component of muscle tone. This has implications for the clinical assessment of axial rigidity in PD. Full article

Background/Objectives: The suboccipital muscles (SOMs) are rich in muscle spindles and play a critical role in proprioceptive input and postural control. However, the relationship between SOM tone, head posture, and balance performance remains unclear. Therefore, this study aimed to investigate the association between SOM tone and postural balance, including the craniovertebral angle (CVA), static balance, and dynamic balance, in healthy adults. Methods: A total of 112 healthy adults participated in this study. SOM, cervical extensor muscle (CEM), and upper trapezius muscle (UTM) tones were assessed. Head posture was evaluated by measuring the CVA. Static balance was assessed through the trajectory of the center of pressure (COP), whereas dynamic balance was evaluated using gait parameters. Results: Participants with a higher SOM tone exhibited a significantly smaller CVA, increased COP path length and velocity, and narrower step width during walking than did those with a lower tone. The regression analysis showed that SOM tone was significantly associated with CVA (β = −0.219, p = 0.020), COP path length (β = 0.308, p = 0.001) and velocity (β = 0.296, p = 0.002), and step width (β = −0.242, p = 0.014), whereas CEM and UTM tone were not significantly associated with these variables. Conclusions: These findings suggest that SOM tone may be associated with postural control characteristics among healthy adults. Full article

Research on human motion representation commonly investigates portable, wearable, and ergonomic sensing systems. Cameras, infrared sensors, and inertial measurement units (IMUs) are widely used to reproduce and validate human movement. Known limitations persist, including increased error during slow movements, the gimbal lock effect in Euler space, and the requirement for one sensor per joint. The objective of this work is twofold: first, to characterize the measurement accuracy of a commercial IMU sensor (BWT901BLE) under controlled conditions using a fixed-arm pendulum model that replicates the single-degree-of-freedom planar kinematics of elbow flexion–extension, comparing angular position, angular velocity, and angular acceleration outputs against a video-based reference system; and second, to describe and publish a complete data processing pipeline—from raw sensor readings to real-time biomechanical motion visualization within OpenSim—demonstrated through upper limb motion recordings from 6 participants, whose data were used to generate motion files and estimate muscle fiber lengths and activation patterns within OpenSim. Regarding sensor characterization, experiments compared sensor data against the video-based reference. The inter-sensor angular position mean error was 0.765° (100 Hz) and 0.445° (200 Hz); angular velocity mean error was 0.124°/s (100 Hz) and 0.277°/s (200 Hz). Direct Euler angle measurements outperformed quaternion-to-Euler conversion (mean RMSE 5.69° vs. 53.1° at 100 Hz; 5.08° vs. 41.8° at 200 Hz). Angular velocity showed the highest agreement with the video-based reference (mean RMSE 0.60 rad/s at 100 Hz and 0.43 rad/s at 200 Hz; mean R = 0.982 and 0.991). Raw accelerometer output showed negligible correlation with the video-based angular acceleration reference (mean R ≈ 0.00–0.05); however, acceleration derived from angular velocity differentiation achieved high accuracy (mean RMSE 4.43 rad/s² at 100 Hz and 3.06 rad/s² at 200 Hz; mean R = 0.976 and 0.989). Regarding the OpenSim integration, the real-time visualization pipeline achieved an effective frame rate of 40–50 fps with an estimated end-to-end latency of 35–50 ms, and the recorded motion data were used to estimate muscle fiber lengths and activation patterns through OpenSim’s analysis tools. These findings confirm that angular velocity is the most reliable output of this sensor class. Full article

Objectives: Karting imposes high neuromuscular demands on the forearm during dynamic steering, gripping and braking. This study examined whether a single high-velocity, low-amplitude (HVLA) manipulation of the elbow acutely modified surface EMG_RMS amplitude and EMG median frequency responses during standardized isometric forearm testing after simulated karting load, rather than EMG activity during dynamic driving itself. Methods: In this randomized, sham-controlled, within-subject trial, 15 drivers completed a single-session within-participant protocol in which one upper limb was randomly allocated to receive elbow HVLA manipulation (manipulated limb) and the contralateral limb received a standardized sham procedure (sham limb) involving therapist contact and low-grade oscillatory movement without end-range pre-tension or thrust. Drivers completed two 8 min simulated races separated by the allocated manual procedure. Surface electromyography (EMG) from four forearm muscles was collected outside the karting task during standardized laboratory-based isometric forearm contractions at baseline, after race 1, post-intervention, and after race 2. EMG was not recorded during real-time steering, braking, vibration exposure or competitive driving. The extensor carpi radialis (ECR) was specified as the principal muscle of interest because the HVLA technique pre-tensioned the common extensor origin and radial wrist extensors. The primary outcome was ECR mean EMG_RMS amplitude, expressed in µV, across the four measurement time points; the primary statistical test was the condition × time interaction. ECR maximal EMG_RMS amplitude and ECR median frequency were treated as secondary outcomes, whereas ECU, FCR, and FCU outcomes were treated as exploratory anatomical specificity outcomes. Mixed-model ANOVAs compared maximal and mean EMG amplitudes and median frequency between manipulated and sham limbs, treating limb condition and time as repeated within-participant factors. Results: For the primary outcome, ECR mean EMG_RMS amplitude showed a main effect of condition (p = 0.023) and a condition × time interaction (p < 0.001). As a secondary amplitude outcome, ECR maximal EMG_RMS amplitude showed a main effect of time (p = 0.009) and a condition × time interaction (p < 0.001), with higher post-manipulation values in the manipulated limb. No consistent limb-condition effects were found for the other muscles, and EMG median frequency showed only modest time-related changes (p = 0.031) without between-condition differences. Conclusions: A single-elbow manipulation produced short-lived, muscle-specific increases in ECR activation after simulated racing, whereas broader neuromuscular changes were not evident. These findings indicate only transient modulation of ECR surface EMG amplitude in a small sample of screened karting drivers and do not demonstrate improved recovery, neuromuscular efficiency, sport performance, or injury prevention. Because EMG was assessed during standardized isometric contractions rather than during dynamic steering, braking, vibration exposure or competitive racing, the findings should not be interpreted as direct evidence of altered neuromuscular behaviour during actual kart driving. Larger studies including force, performance, clinical, fatigue-specific and dynamic driving EMG outcomes are required. Full article

Background/Objectives: Transradial access (TRA) is the preferred route for coronary catheterization, yet its consequences for radial artery vasoreactivity and hemodynamic parameters remain incompletely characterized. We prospectively quantified TRA-induced functional impairment, its clinical determinants, and the association of baseline parameters with post-procedural outcomes. Methods: Ninety-four consecutive patients undergoing elective TRA were assessed at baseline, 24 h, and one month using high-resolution Doppler ultrasound. Nine vascular parameters were measured: flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), peak systolic velocity (PSV), resistive index (RI), pulsatility index (PI), resting and hyperemic velocity-time integral, hyperemic blood flow volume, and lumen diameter. Non-parametric methods were applied throughout. Results: FMD declined at 24 h (−31.2%; p < 0.001) and showed no significant recovery at one month (p = 0.08 vs. 24 h). NMD showed a greater acute decline (−36.6%; p < 0.001) with partial but statistically significant recovery at one month (p < 0.001). PSV recovered fully by one month; RI fell below baseline, consistent with compensatory microvascular vasodilation. Radial artery lumen diameter remained significantly below baseline at one month. Radial artery occlusion occurred in 4 patients (4.3%), all with spontaneous recanalization. Female sex was selectively associated with greater NMD reduction (ΔNMD −8.3% vs. −5.8%; p = 0.005) without a statistically significant FMD difference (p = 0.40). Older age correlated with impaired FMD recovery at one month (ρ = −0.62; p < 0.001) but not with NMD outcomes. Baseline PSV demonstrated the highest discriminatory performance for significant FMD decline (AUC = 0.73). Conclusions: TRA causes multidomain, persistent radial artery functional impairment at one month, with distinct recovery trajectories for endothelial and smooth muscle function. Female sex and advanced age are selective determinants of injury and recovery, respectively. A pre-procedural phenotype comprising baseline diameter, PSV, RI, and age is associated with post-procedural outcomes and supports further investigation of pre-procedural phenotyping as a candidate framework for risk stratification. Full article

This study examined the anthropometric, lower-limb flexibility, power, and kinematic correlates of 5 m and 7.5 m post-entry passive underwater glide performance during forward-weighted (FW) and rear-weighted (RW) swim starts in adolescent female swimmers. Twenty-three trained female swimmers aged 14–16 years completed FW and RW starts in a randomized within-subject repeated-measures design. Anthropometry, ankle dorsiflexion range of motion, lower-limb muscle extensibility, vertical jump performance, and start kinematics were assessed. FW starts produced shorter block exit time (mean difference = −0.06 s; p < 0.001; Cohen’s dz = −1.63), shorter water-entry time (mean difference = −0.07 s; p < 0.001; Cohen’s dz = −1.65), and higher average water-entry velocity (mean difference = 0.17 m·s⁻¹; p < 0.001; Cohen’s dz = 1.36) compared with RW starts. FW also yielded a faster 5 m post-entry passive underwater glide completion time (mean difference = −0.04 s, approximately 40 ms; p = 0.005; Cohen’s dz = −0.66), whereas 7.5 m post-entry passive underwater glide completion time did not differ between techniques (p = 0.725). Exploratory regression models accounted for 29.0–64.4% of the adjusted variance across outcomes, but these models were not externally validated and should be interpreted as exploratory, hypothesis-generating associations. Technique-related differences were specific to the block exit and early post-entry passive glide phases; selected physical characteristics may complement kinematic assessment in this population but should not be used as stand-alone criteria for start-technique selection. Full article

Tropomyosins (Tpm) are the family of actin-binding proteins encoded by four genes in humans. Missense mutations in the TPM1 gene associated with cardiomyopathies have been studied in the sarcomeric isoform Tpm1.1. The cardiomyopathy-causing mutations E40K and E54K are located in exon 2b of the TPM1 gene and may be expressed in non-muscle cytoplasmic Tpm isoforms, including Tpm1.7, which is associated with early tissue development. In the present work, we investigate the effects of mutations E40K and E54K on the properties of Tpm1.7. The E40K and E54K mutations caused destabilization of the Tpm1.7 molecule at the N- and C-termini parts. Neither mutation affected the Tpm1.7 affinity for filamentous actin (F-actin). The bending stiffness of F-actin/Tpm1.7 E40K filaments was lower compared to F-actin/Tpm1.7 WT (wild-type). The interplay of Tpm1.7 and motor proteins was studied in an in vitro motility assay with skeletal myosin. Tpm1.7 WT reduced the sliding velocity of F-actin by half; the velocity of F-actin with Tpm1.7 E54K did not differ from that of bare F-actin; and Tpm1.7 E40K decreased the F-actin velocity by approximately threefold. While Tpm1.7 E40K did not affect the protective effect of Tpm1.7 against F-actin severing by cofilin-1, the E54K mutation enhanced protection against cofilin-1. Thus, cardiomyopathic mutations in the TPM1 gene can affect the properties of non-muscle Tpm isoforms, which indicates that this should be taken into account when studying the molecular mechanisms of the pathogenesis of these diseases. Full article

Endurance training camps are well established in elite sports, but one-week camps for recreational endurance athletes have recently gained popularity despite limited scientific evidence. This study investigated the effects of a one-week endurance training camp on body composition, endurance performance, and markers of metabolic stress and mitochondrial adaptation in recreational athletes. Female and male endurance athletes (≥18 years) participated in a professionally guided one-week endurance training camp. Assessments included body composition, running diagnostics, sleep-quality/recovery-stress questionnaires, nutrition/energy balance diaries, blood profiling, and mitochondrial biogenesis markers. Measurements were conducted before (pre), during (camp), and after the camp (post). A total of 35 participants (18 male/17 female) were included. Body mass and body fat decreased from pre- to post-camp. Lactate concentrations at threshold levels changed, while velocities at fixed lactate concentrations and maximal oxygen uptake did not significantly improve. Post-camp, lactate dehydrogenase, klotho, and vitamin D increased, whereas interferon-γ, kynurenine, cortisol, creatinine, and ferritin decreased. Plasma mitochondrial and nuclear DNA abundance, as well as PGC1-α expression, increased, while vascular endothelial growth factor decreased. A one-week endurance training camp in a holiday-like setting induces measurable physiological, metabolic, and mitochondrial adaptations in recreational athletes and is associated with reduced systemic and psychological stress. However, the concurrent increase in muscle- and cell-stress markers indicates a substantial physiological load. Full article

Muscle wasting contributes substantially to inflammatory bowel disease (IBD)-related disability, but its association with colitis severity across disease stages remains poorly characterized. We therefore assessed skeletal muscle mass, fiber morphology, and voluntary wheel-running performance in Winnie mice—a spontaneous Muc2 mutant model of chronic colitis—in separate female and male homozygous mutant and WT littermate cohorts. Assessments were performed at 5 weeks, before overt colitis, and at 15 weeks, in a cohort with more pronounced colitis. Outcomes included disease activity index (DAI), fecal lipocalin-2 (LCN-2), wheel-running metrics, soleus and tibialis anterior mass, and minimal Feret’s diameter distributions. At 5 weeks, Winnie mice showed no overt disease activity and no consistent structural muscle deficit. In contrast, the 15-week cohort exhibited marked colitis in both sexes, with increased DAI and LCN-2, reduced voluntary wheel-running performance, lower soleus and tibialis anterior mass, and smaller muscle fiber diameters with left-shifted size distributions. Correlation analyses identified associations between fecal LCN-2, skeletal muscle mass and size, and wheel-running distance and velocity, supporting a link between intestinal inflammation and muscle impairment in this model. These cross-sectional data are consistent with reduced voluntary activity and structural myopathy during progression of spontaneous colitis. The Winnie mouse model therefore provides a clinically relevant preclinical platform to study IBD-associated muscle wasting and its association with intestinal inflammation. Full article

Background/Objectives: Titin (TTN; OMIM 188840) is the largest known human sarcomeric protein, and pathogenic variants in the TTN gene cause a broad spectrum of inherited myopathies and cardiomyopathies. The extent to which TTN variants may also involve the peripheral nervous system remains poorly defined. We aimed to describe two pediatric patients carrying heterozygous truncating TTN variants with neurophysiological evidence of peripheral nerve involvement, and to review the existing literature on this underrecognized association. Pathogenic variants in the TTN gene are associated with a wide spectrum of inherited myopathies and cardiomyopathies. To date, peripheral neur opathy has not been recognized as a defining feature of TTN-related disorders, and neurophysiological investigations in affected individuals typically demonstrate normal or myopathic findings without evidence of a primary neuropathic process. Here, we report two pediatric patients with heterozygous truncating TTN variants and neurophysiological evidence of bilateral axonal involvement of the deep peroneal nerve. Methods: This case report was structured and reported according to the CARE guidelines. Genetic testing was performed using whole-exome sequencing (Blueprint Genetics Whole Exome Family Test). Nerve conduction studies and needle electromyography were performed using the Galileo NT system. Variant classification followed current ACMG guidelines. Results: The first patient, a 10-year-old girl, presented with a symptomatic distal motor phenotype characterized by bilateral pes cavus, anterior compartment muscle atrophy, areflexia, and steppage gait with onset in early childhood. The second patient, an 8-year-old boy, had subclinical bilateral axonal neuropathy identified during neurophysiological evaluation prompted by intermittent lower limb pain; his father, carrying the same variant, showed concordant neurophysiological abnormalities. In both cases, nerve conduction studies demonstrated reduced compound muscle action potential amplitudes with preserved conduction velocities and distal latencies, consistent with axonal neuropathy. Whole-exome sequencing excluded other established genetic causes of inherited neuropathy in both probands. Conclusions: Although a causal relationship cannot be established, these observations raise the possibility that peripheral nerve involvement may represent an underrecognized feature of the titinopathy spectrum. Prospective studies in larger cohorts of TTN variant carriers are needed to clarify the prevalence and pathophysiological basis of neuropathy in this context. Full article