Search Results (104)

Background: Temporomandibular disorders are a generic term referred to clinical conditions involving the jaw muscles and temporomandibular joint with multifactorial pattern and genetic background. The aim of this observational study was to investigate the correlation between craniomandibular disorders and the presence of occlusal alterations. A clinical evaluation of the occlusal and articular status of the patients was carried out, integrating the latter with the electromyographic recording the activity of the masseter and temporalis muscles. Methods: A clinical observational study on 20 adults assessed temporomandibular disorders using DC/TMD criteria, anamnesis, clinical exams, occlusal and electromyographic analyses. Occlusion was evaluated morphologically and functionally. Electromyography tested static/dynamic muscle activity. Data were statistically analyzed using t-tests and Pearson correlation (p < 0.05). Results: Electromyographic analysis revealed significant differences between subjects with and without visual correction, suggesting that visual input influences masticatory muscle activity. Correlations emerged between occlusal asymmetries and neuromuscular parameters. These findings highlight clinical implications for mandibular function, muscle symmetry, and the potential for therapeutic rebalancing through targeted interventions. Conclusions: The study demonstrates a significant correlation between visual–motor integration and masticatory muscle efficiency. It emphasizes lateralized neuromuscular activation’s influence on occlusal contact distribution. Moreover, it identifies mandibular torsion–endfeel inverse correlation as a potential diagnostic marker for craniomandibular dysfunctions via surface electromyography. Full article

Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disorder and a leading genetic cause of infant mortality. Advances in disease-modifying therapies have significantly improved outcomes when treatment is initiated early, underscoring the importance of timely diagnosis. With the growing availability of prenatal genetic screening and high-resolution molecular diagnostics, opportunities for early detection, and potentially in utero intervention, are rapidly expanding. This narrative review synthesizes current evidence on the prenatal management of SMA, focusing on diagnostic strategies, the clinical application of fetal genetic testing, and the emerging potential of fetal therapy. We explore both invasive and non-invasive diagnostic approaches and evaluate experimental prenatal treatment modalities, while critically addressing the associated ethical, regulatory, and economic considerations. As the field progresses, integrating in utero strategies into clinical care may reshape perinatal medicine and offer transformative potential for genetic neurodegenerative disorders diagnosed before birth. The convergence of early diagnosis, fetal intervention, and personalized genetic counseling will be central to optimizing care pathways and outcomes in the era of precision medicine. Although significant challenges remain, the translation of fetal therapy into routine clinical practice is approaching feasibility. Future clinical trials, anchored in definitive prenatal diagnosis, will be essential, with benefits potentially outweighing the inherent procedural risks. Full article

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder primarily affecting motor neurons. Emerging evidence suggests it also involves multiple organs, including potential cardiac manifestations. This study aimed to evaluate cardiac abnormalities in pediatric SMA patients compared to age-matched healthy controls, providing insight into underlying cardiomyopathy in this population. A total of 126 children were included in the study, with 63 SMA patients and 63 age-matched controls. We conducted clinical examinations, standard electrocardiography (ECG), and cardiac ultrasound (CUS) in all patients. Electrocardiographic analysis revealed a higher prevalence of sinus tachycardia in the SMA group and significantly deeper Q waves, indicating possible myocardial involvement. Echocardiographic findings demonstrated a significant reduction in left ventricular mass and left ventricular mass index in SMA patients compared to controls, despite normal systolic function. Statistical analysis confirmed that SMA diagnosis was an independent predictor of reduced myocardial mass, suggesting a distinct cardiac phenotype in SMA patients. This study provides new evidence of subclinical cardiac involvement in SMA, characterized by reduced myocardial mass, altered electrocardiographic parameters, and increased sinus tachycardia. These findings suggest a previously unrecognized form of cardiomyopathy in SMA that differs from cardiac manifestations typically seen in other neuromuscular disorders. Full article

Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by the progressive loss of motor neurons and consequent muscle atrophy. Although SMN-targeted therapies have significantly improved survival and motor outcomes, residual muscle weakness remains a major clinical challenge, particularly in patients treated later in the disease course. Myostatin, a potent negative regulator of skeletal muscle mass, has emerged as a promising therapeutic target to address this gap. This review summarizes the preclinical and clinical evidence supporting the modulation of the myostatin pathway in SMA. Preclinical studies have demonstrated that inhibiting myostatin, especially when combined with SMN-enhancing agents, can increase muscle mass, improve motor function, and enhance neuromuscular connectivity in SMA mouse models. These findings provide a strong rationale for translating myostatin inhibition into clinical practice as an adjunctive strategy. Early clinical trials investigating myostatin inhibitors have shown favorable safety profiles and preliminary signs of target engagement. However, large-scale trials have yet to demonstrate widespread, robust efficacy across diverse patient populations. Despite this, myostatin pathway inhibition remains a compelling approach, particularly when integrated into broader treatment paradigms aimed at enhancing motor unit stability and function in individuals with SMA. Further clinical research is essential to validate efficacy, determine optimal timing, and define the patient subgroups most likely to benefit from myostatin-targeted therapies. Full article

Neuromuscular disorders (NMDs), such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and muscular dystrophies (e.g., Duchenne muscular dystrophy, DMD), are primarily driven by genetic mutations but are critically modulated by epigenetic mechanisms such as DNA methylation, histone modifications, and noncoding RNA activity. These epigenetic processes contribute to phenotypic variability and disease progression, and emerging evidence suggests that environmental factors, particularly nutrition and exercise, may further influence the molecular pathways that modulate these diseases. Dietary bioactive compounds (e.g., polyphenols and omega-3 fatty acids) exhibit epigenetic modulatory properties, which could mitigate oxidative stress, inflammation, and muscle degeneration in NMDs. For example, the inhibition of DNMTs and HDACs by curcumin in ALS models and the promyogenic effects of green tea catechins in DMD suggest plausible, though still requiring investigation, therapeutic avenues. However, the clinical application of nutriepigenetic interventions is preliminary and requires further validation. This review examines the interaction of genetic and epigenetic factors in ALS, SMA, and muscular dystrophies, highlighting their combined role in the heterogeneity of these diseases. Integrative therapeutic strategies combining gene therapies, epigenetic modulators, and lifestyle interventions may offer a multidimensional approach to the management of NMD. A deeper understanding of these interactions will be essential for advancing precision medicine and improving patient outcomes. Full article

Background/Objectives: Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disorder characterized by respiratory dysfunction that significantly impacts quality of life and longevity. This study aimed to explore the outcomes of pulmonary function tests and sleep-disordered breathing (SDB) workups in children with DM1 and to identify the factors contributing to SDB. Methods: A retrospective study examined patients’ medical records, including genetic analyses, clinical characteristics, and noninvasive pulmonary function testing (PFT), when possible. The Pediatric Sleep Questionnaire (PSQ), arterial blood gases, polygraphy, and overnight transcutaneous capnometry (PtcCO₂) were used to assess SDB. Results: The size of CTG expansion in the DMPK gene directly correlated with the severity of respiratory complications and the need for early tracheostomy tube insertion in 7/20 (35%) patients. A total of 13/20 (65%) children were available for respiratory evaluation during spontaneous breathing. While moderate/severe obstructive sleep apnea syndrome (OSAS) and hypoventilation were confirmed in 4/13 (31%) children, none of the patients had mixed or dominantly central sleep apnea syndrome. There was no correlation between apnea–hypopnea index (AHI) or PtcCO₂ and the presence of SDB-related symptoms or the PSQ score. Although a significant correlation between AHI and PtcCO₂ was not confirmed (p = 0.447), the oxygen desaturation index directly correlated with PtcCO₂ (p = 0.014). Conclusions: While SDB symptoms in children with DM1 may not fully correlate with observed respiratory events or impaired gas exchange during sleep, a comprehensive screening for SDB should be considered for all patients with DM1. Further research into disease-specific recommendations encompassing the standardization of PFT, as well as overnight polygraphic and capnometry recordings, could help to guide timely, personalized treatment. Full article

The BCS1L gene encodes a mitochondrial chaperone which inserts the Fe₂S₂ iron–sulfur Rieske protein into the nascent electron transfer complex III. Variants in the BCS1L gene are associated with a spectrum of mitochondrial disorders, ranging from mild to severe phenotypes. Björnstad syndrome, a milder condition, is characterized by sensorineural hearing loss (SNHL) and pili torti. More severe disorders include Complex III Deficiency, which leads to neuromuscular and metabolic dysfunctions with multi-systemic issues and Growth Retardation, Aminoaciduria, Cholestasis, Iron Overload, and Lactic Acidosis syndrome (GRACILE). The severity of these conditions varies depending on the specific BCS1L mutation and its impact on mitochondrial function. This study describes a 27-month-old child with SNHL, proximal renal tubular acidosis, woolly hypopigmented hair, developmental delay, and metabolic alterations. Genetic analysis revealed a homozygous BCS1L variant (c.38A>G, p.Asn13Ser), previously reported in a patient with a more severe phenotype that, however, was not functionally characterized. In this work, functional studies in a yeast model and patient-derived fibroblasts demonstrated that the variant impairs mitochondrial respiration, complex III activity (CIII), and also alters mitochondrial morphology in affected fibroblasts. Interestingly, we unveil a new possible mechanism of pathogenicity for BCS1L mutant protein. Since the interaction between BCS1L and CIII is increased, this suggests the formation of a BCS1L-containing nonfunctional preCIII unable to load RISP protein and complete CIII assembly. These findings support the pathogenicity of the BCS1L c.38A>G variant, suggesting altered interaction between the mutant BCS1L and CIII. Full article

Background and Objectives: Spinal muscular atrophy (SMA) is a progressive, autosomal recessive, rare neuromuscular disorder caused by a genetic defect in the SMN1 gene, where the SMN2 gene cannot sufficiently compensate. Patients experience progressive and predominantly proximal muscular weakness and atrophy. Oculomotor disorders are currently not regarded as a typical feature of SMA. The aim of this study was to determine whether oculomotor abnormalities are present in subjects with SMA and to assess a potential relationship between the oculomotor parameters and disease duration. Materials and Methods: An analysis of 15 patients with SMA type 2 and type 3 and 15 age-matched healthy controls was conducted. The oculomotor performance, including the analysis of smooth pursuit velocity gain and saccades parameters (latency, velocity, accuracy) in the horizontal and vertical directions, was compared between both groups. Results: The analysis of smooth pursuit gain in the participants revealed a marginally significant reduction between the SMA patients and the healthy controls in the horizontal direction at a frequency of 0.2 Hz (p = 0.051), but no significant differences were observed at any other frequency or direction. The vertical velocity of the saccade eye movements of the SMA patients was increased compared with the healthy subjects, which was statistically significant for the amplitude of ±10° (p = 0.030), but not for the amplitude of ±16.5° (p = 0.107). The horizontal saccade latency, saccade velocity and saccade accuracy did not differ significantly between the SMA patients and the controls. None of the oculomotor parameters were associated with disease duration. Conclusions: While certain oculomotor abnormalities, such as increased vertical saccade velocity, were observed in the SMA patients, these findings do not indicate a defining role of oculomotor impairment in SMA pathology or its clinical characteristics. Full article

The DEAD/DExD/H-box RNA helicases are a group of RNA-binding proteins involved in the metabolism of mRNAs. They coordinate gene expression programs and play a role in cellular signaling, fate, and survival. We describe a case of a 36-year-old female with neuromuscular disease, sensorineural hearing loss, retinitis pigmentosa, and primary ovarian insufficiency harboring a heterozygous de novo missense pathogenic variant in the DEAH-box helicase 16 (DHX16) gene. This is the first case exhibiting a high intellectual level and the highest survival outcome so far. Eight previous cases of DHX16 disease-causing variant carriers have been described with common features, including muscle weakness with hypotonia, myopathy or peripheral neuropathy, sensorineural hearing loss, abnormal retinal findings, and infantile spasms or epilepsy. Increasing evidence associates RNA-binding proteins, including the DEAD/DExD/H-box helicase family genes, with neuropsychiatric or neurodevelopmental disorders. DHX16 genetic analysis should be considered early when diagnosing a child or young adult with muscular disease, severe hearing loss, and ocular anomalies. Full article

Neuromuscular diseases (NMDs) encompass various hereditary conditions affecting motor neurons, the neuromuscular junction, and skeletal muscles. These disorders are characterized by progressive muscle weakness and can manifest at different stages of life, from birth to adulthood. NMDs, such as Duchenne and Becker muscular dystrophies, myotonic dystrophy, and limb–girdle muscular dystrophies, often involve cardiac complications, including cardiomyopathies and arrhythmias. Underlying genetic mutations contribute to skeletal and cardiac muscle dysfunction, particularly in the DMD, EMD, and LMNA genes. The progressive nature of muscle deterioration significantly reduces life expectancy, mainly due to respiratory and cardiac failure. The early detection of cardiac involvement through electrocardiography (ECG) and cardiac imaging is crucial for timely intervention. Pharmacological treatment focuses on managing cardiomyopathies and arrhythmias, with an emerging interest in gene therapies aimed at correcting underlying genetic defects. Heart transplantation, though historically controversial in patients with muscular dystrophies, is increasingly recognized as a viable option for individuals with advanced heart failure and moderate muscle impairment, leading to improved survival rates. Careful patient selection and management are critical to optimizing outcomes in these complex cases. Full article

Pompe disease is a neuromuscular disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA), which leads to lysosomal glycogen accumulation and progressive development of muscle weakness. Two distinct isoforms have been identified. In the infantile form, the weakness is often severe and leads to motor difficulties from the first few months of life. In adult patients, the progression is slower but can still lead to significant loss of mobility. The current inherent difficulties of the disease lie in both early diagnosis and the use of biomarkers. Given that this is a multifactorial disease, a number of components may exert an influence on the disease process; from the degree of pre-ERT (enzyme replacement therapy) muscle damage to the damaged autophagic system and the different pathways involved. What methodology should be employed to study the complex characteristics of Pompe disease? Our approach relies on the application of genetic and epigenetic knowledge, with a progression from proteomics to transcriptomics. It is also becoming increasingly evident that artificial intelligence is a significant area of interest. The objective of this study is to conduct a comprehensive review of the existing literature on the known data and complications associated with the disease in patients with disorders attributed to Pompe disease. Full article

Stem cells are unique, undifferentiated cells that have the ability to both replicate themselves and develop into specialized cell types. This dual capability makes them valuable in the development of regenerative medicine. Current development in stem cell research has widened their application in cell therapy, drug discovery, reproductive cloning in animals, and cell models for various diseases. Although there are substantial studies revealing the treatment of human degenerative diseases using stem cells, this is yet to be explored in livestock animals. Many diseases in livestock species such as mastitis, laminitis, neuromuscular disorders, autoimmune diseases, and some debilitating diseases are not covered completely by the existing drugs and treatment can be improved by using different types of stem cells like embryonic stem cells, adult stem cells, and induced pluripotent stem cells. This review mainly focuses on the use of stem cells for disease treatment in livestock animals. In addition to the diseases mentioned, the potential of stem cells can be helpful in wound healing, skin disease therapy, and treatment of some genetic disorders. This article explores the potential of stem cells from various sources in the therapy of livestock diseases and also their role in the conservation of endangered species as well as disease model preparation. Moreover, the future perspectives and challenges associated with the application of stem cells in livestock are discussed. Overall, the transformative impact of stem cell research on the livestock sector is comprehensively studied which will help researchers to design future research work on stem cells related to livestock diseases. Full article

Background: This study presents a comprehensive investigation into the correlation between Rare Diseases and Syndromes (RDS) and the dysphagic disorders manifested during childhood and adulthood in affected patients. Dysphagia is characterized by difficulty or an inability to swallow food of any consistency, as well as saliva or medications, from the oral cavity to the stomach. RDS often present with complex and heterogeneous clinical manifestations, making it challenging to develop standardized diagnostic and therapeutic approaches. Dysphagia can arise from various etiologies, including those related to the central nervous system, inflammatory and neoplastic processes, anatomical or structural disorders, and neuromuscular conditions. These diverse etiologies can result in both structural and functional deficits or neurological impairments that compromise swallowing function. While RDS frequently leads to uncommon conditions, dysphagia remains an underrecognized complication. Objectives: The primary objective of this review is to illuminate the latest knowledge concerning the management of dysphagia in both pediatric and adult populations within the context of RDS, with a particular focus on current therapeutic approaches. To achieve this, the study provides a comprehensive analysis of existing strategies for managing dysphagia in RDS, highlighting recent advancements in therapy while identifying critical gaps in clinical knowledge and practice. By synthesizing available evidence, the review aims to deepen understanding of the unique challenges associated with dysphagia in these conditions and explore innovative interventions to enhance patient care and outcomes. Results: The integration of innovative therapeutic techniques into the speech-language pathology treatment of dysphagia augments traditional strategies, offering updated knowledge that can be applied to prognosis and therapeutic interventions across various ages and racial groups. This review also provides an overview of symptomatology, assessment techniques, and the specific characteristics of dysphagia associated with various genetic and acquired RDS. Full article

Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients’ quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot–Marie–Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb–Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn. Full article

The loss of one of the two copies of the 9 bp tandem repeat sequence (CCCCCTCTA) located in the small non-coding region between the cytochrome oxidase II (COII) and the lysine tRNA genes in human mtDNA has been reported to be polymorphic in Asian, Oceanian and Sub-Saharan African populations, but it has rarely been observed in Europe. In this study, we will evaluate the possible association between the MIC9D polymorphism and cognitive disorders. A genetic analysis of unrelated Sicilian patients with cognitive deficits was performed to identify the 9 bp deletion MIC9D polymorphism. The MIC9D polymorphism was found in six patients, whereas this variant was absent in control individuals without cognitive deficits. The patients with the MIC9D polymorphism exhibited more complex clinical presentations; in particular, all had neuromuscular disorders and five also presented with behavioral disorders. The present study suggests a potential association between the MIC9D polymorphism and cognitive impairment with concurrent neuromuscular and behavioral involvement. Full article