Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology最新文献

Objective: Thymidine kinase 2 (TK2) deficiency is a rare mitochondrial disease with variable phenotypes and emerging treatments. Prompt diagnosis is essential to optimize patient outcomes and management. To assess the current awareness, diagnostic approaches, and readiness to include TK2 screening in Italian neuromuscular clinical practice.

Methods: A nationwide survey was distributed to AIM-affiliated clinicians. The questionnaire assessed TK2 awareness, diagnostic pathways, gene panel content, and attitudes towards screening in unresolved cases.

Results: while awareness of TK2 deficiency was almost universal, inclusion of TK2 in genetic panels varied: 85% in metabolic myopathy panels, 56% in LGMD panels. Screening for TK2 in genetically unsolved SMA, FSHD, and OPMD phenotypes was inconsistent.

Conclusions: Although awareness of TK2 deficiency is widespread, diagnostic strategies are inconsistent. Standardizing TK2 inclusion in NGS panels and promoting differential screening are key steps toward earlier diagnosis in the view of future treatment options.

Objectives: Collagen 6-related Bethlem myopathy and LDLR-related familial hypercholesterolemia are presumed to be quite rare in the general population.

Case report: Here, we present the clinical findings from a 65-year-old man with comorbid Bethlem myopathy and familial hypercholesterolemia to highlight some important molecular diagnostic considerations and clinical management implications.

Introduction: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease linked to the X chromosome caused by the lack of functional dystrophin. About 10-15% of cases are caused by nonsense mutations, and their natural history is thought to be similar to DMD by other causes. Ataluren is a new therapeutic option that promotes the readthrough of nonsense mutations leading to the production of functional dystrophin proteins.

Objective: To describe the natural history of patients with nonsense mutations DMD (nmDMD) and evaluate the impact of corticosteroids and ataluren on disease progression.

Methods: It is a retrospective, longitudinal case-series study of all male patients with nmDMD treated at Sant Joan de Déu Hospital in Barcelona, Spain, since 2007.

Results: 28 patients from 3.7 to 22 years old were included. The mean age at symptom onset was 3.5 years, and at genetic diagnosis was 4.5 years. All patients were treated with corticosteroids, and 17 patients also received ataluren. Patients treated with ataluren delayed the loss of ambulation by three years (14 vs 10.9 years). No patients treated with ataluren required non-invasive ventilation.

Conclusions: Patients with DMD caused by nonsense mutations present a similar phenotype to those with DMD with other types of mutations. Patients treated with ataluren delayed the loss of ambulation and appeared to maintain upper limb and respiratory function better than those not treated with ataluren.

Artificial Intelligence (AI) is the ability of machines to perform tasks that typically require human intelligence, such as learning, problem-solving, and decision-making. Its integration into healthcare may revolutionize many areas of medicine, including the diagnosis and management of neuromuscular disorders (NMDs).

These disorders, characterized by their clinical and genetical complexity and heterogeneity, demand innovative approaches to improve patient outcomes. Among these approaches, AI-driven solutions hold immense potential. However, the success of these solutions depends on preparing a new generation of clinicians equipped to harness the multifaceted power of AI.

One remarkable initiative addressing this need is the CoMPaSS-NMD project, which pioneers an interdisciplinary framework for developing AI-driven strategies to stratify patients using multiple clinical, histopathological, MRI e genetic datasets. By fostering a shared working language and integrating diverse competencies, the project aims to advance knowledge dissemination and bridge gaps between traditional disciplines. This approach is vital for addressing the challenges posed by NMDs, where early diagnosis and personalized treatment plans are critical.

To support this mission, the Young Investigator Training (YIT) initiative within CoMPaSS-NMD fosters education and scientific exchange among early-career researchers. By promoting high-quality clinical assessments and multidisciplinary training, YIT prepares a new generation to meet the evolving challenges in NMD care and research.

Objectives: Some muscular dystrophies, such as myotonic dystrophy type 1 and 2 (DM1 and DM2), facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD), are caused by genetic mutations that may affect the expression and function of various cancer-related genes. We assessed the frequency and type of cancers and benign tumors in patients with DM1, DM2, FSHD, and OPMD.

Methods: We conducted a single-center, retrospective, cross-sectional study on patients with DM1, DM2, FSHD, and OPMD at our institution from January 2000 to September 2023.

Results: Seventy seven (46 female) DM1, 20 (15 female) DM2, 40 (18 female) FSHD, and 46 (22 female) OPMD patients were included, among which 22 (28.57%), 9 (45%), 7 (17.5%), and 15 (32.61%) patients had at least one cancer, respectively. Median age (range) of patients where presence or absence of cancer was ascertained was 65 (18-87), 63.5 (45-86), 61 (27-83), and 71.5 (40-82) years, respectively (P < 0.0001). Overall, non-sex-related cancers were more frequent than sex-related cancers among all patients together. Independent to sex and age, DM1 patients had an increased risk of non-sex-related cancers compared to non-DM cases. Melanoma (P < 0.01) and testicular (P < 0.05) cancers were significantly more frequent in DM2 and OMPD patients, respectively. DM patients had also increased risk of non-sex related benign tumors (including skin and thyroid benign tumors) compared to non-DM patients.

Conclusions: Our study highlights the differences in the prevalence of cancers and benign tumors among patients with DM1, DM2, FSHD, and OPMD, underscoring the potential need for regular screening for specific cancers.

Introduction: Bethlem myopathy (BM) is a collagen-VI-related myopathy caused by mutations in the COL6A1, COL6A2, and COL6A3 genes. It is characterized by proximal muscle weakness, distal joint laxity, and contractures, with symptoms appearing during childhood and progressing slowly. Muscle ultrasound, using tools like the Heckmatt scale, complements genetic analysis and provides noninvasive insights into muscle pathology, particularly in atypical presentations.

Case report: An 8-year-old male presented with muscle weakness since birth, delayed motor milestones, toe walking, and frequent falls. Family history revealed maternal-line neuromuscular disorders. Clinical examination showed hyporeflexia, thoracic hypotrophy, and decreased proximal muscle strength, alongside joint hypermobility and keratosis pilaris. Electromyography indicated a myopathic pattern in proximal upper limb muscles. Genetic analysis confirmed a pathogenic COL6A1 variant (c.788G > A, p.Gly263Asp). Ultrasound findings revealed advanced structural compromise with Heckmatt grade IV echogenicity in the deltoid, iliopsoas, and rectus femoris, indicating fatty infiltration and fibrosis. Functional tests, including Motor Function Measurement (MFM), showed adequate performance despite significant structural abnormalities.

Discussion: This case illustrates the diagnostic challenges of BM, characterized by phenotypic variability and the complexity of correlating structural and functional findings. Muscle ultrasound findings demonstrated advanced echogenic changes, but functional performance remained preserved, highlighting a mismatch between structural changes and functional outcomes.

Conclusion: This case highlights the diagnostic challenges of BM, where a patient with a COL6A1 gene mutation exhibited significant muscle abnormalities on ultrasound but maintained relatively preserved motor function according to the MFM scale. This discrepancy emphasizes the limitations of functional assessments like MFM in capturing the extent of muscle weakness. Ultrasound and dynamometry provided a more comprehensive evaluation, underscoring the importance of integrating structural and functional assessments for accurate diagnosis and management. This case stresses the need for an individualized approach in managing BM, considering both genetic and clinical findings.

Case presentation: A 34-year-old male with congenital clubfoot, post-exertional rhabdomyolysis, and a family history of sudden cardiac death in mid-life was evaluated for a severe rhabdomyolysis requiring multiple hemodialyses. Clinical evaluation showed mild distal myopathy signs, with CK levels around 3000 IU/L and muscle biopsy revealing desmin- and dystrophin-positive cytosolic protein aggregates/fibre splitting. After a minor SARS-CoV-2 infection at 55, modest signs of cardiomyopathy were observed via cardiac MRI, without patterns indicative of myocarditis. Subsequently, NGS analysis identified a variant in the LDB3 gene, potentially correlated with the clinical-histological-radiological picture, thus broadening the phenotypic spectrum of LDB3-related distal myopathies. Additionally, a possible link was suggested between the viral infection and the exacerbation of the otherwise subtle cardiomyopathy. In the context of hyperCKemia and positive family history for unexplained cardiac abnormalities, broad-spectrum NGS testing, and cardiac MRI in selected cases, should be considered for timely diagnosis and interventions.

The management of patients with neuromuscular diseases requires a multidisciplinary approach that integrates medical care with targeted psychological support. Respiratory difficulties, often treated with non-invasive ventilation (NIV) are accompanied by mood disorders such as anxiety and depression, which can compromise treatment adherence and quality of life. In our Unit, we performed psychological assessment from the first visit, using the Beck Depression Inventory-II (BDI-II) scale to evaluate the patients, and initiate where necessary, psychological support, also via telemedicine.

We present four representative clinical cases including Giovanni, with Bethlem myopathy who exhibited resistance to NIV linked to feelings of anger and frustration; Luisa, with Steinert's disease who experienced relational rejection that undermined her self-esteem; Maria, also with Steinert's disease who expressed anticipatory anxiety over the loss of autonomy; and Lorenzo, with Duchenne muscular dystrophy who faced social isolation and resistance to ventilation by finding confort in music.

In all cases, psychological support led to reduced BDI scores and an improvement in treatment adherence. These results highlight the clinical efficacy of structured psychological integration within multidisciplinary teams. However, scientific literature still needs more controlled studies to confirm these results. We emphasize the importance of a holistic approach that equally takes into account the physical and psychological health of patients with neuromuscular diseases.

Emery-Dreifuss Muscular Dystrophy type 2 (EDMD2) and LMNA-related congenital muscular dystrophy (L-CMD) are caused by mutations in LMNA gene. Both pathologies are characterized by joint contractures, muscle weakness and wasting and cardiac involvement. In the last few years, circulating factors have been proposed to play a critical role in the pathogenesis of these diseases. Based on this consideration, we studied the effect of laminopathic serum on the myogenic differentiation in healthy human myoblasts in culture. We observed impaired myogenesis and increased fibrosis in myoblast cultures conditioned with laminopathic serum and a dramatic increase in the level of profibrotic and proinflammatory cytokines in the cell culture supernatants. These results strongly support the pathogenic role of circulating factors in muscular laminopathies and pave the way to a possible therapeutic strategy.