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

Background: Xp21 contiguous gene deletion syndrome is a rare X-linked disorder involving deletions of DMD, GK, and NR0B1 (DAX1), leading to a combination of Duchenne muscular dystrophy, glycerol kinase deficiency, and congenital adrenal hypoplasia. Diagnosis can be delayed due to overlapping symptoms, especially in critically ill infants.

Case reports: We describe two male infants presenting in early life with adrenal insufficiency, electrolyte imbalance, hyperpigmentation, and hypotonia. Biochemical findings included elevated ACTH, low cortisol, high CK, and pseudo-hypertriglyceridemia. In the first case, delayed diagnosis led to sudden death at 7 months. In the second case, early clinical suspicion enabled timely genetic testing and family screening. MLPA revealed DMD gene deletion in both cases. In the second case, molecular karyotyping confirmed deletion at Xp21.3-p21.1; the mother and sister were also carriers.

Conclusion: Clinicians should consider Xp21 syndromes in male infants with adrenal insufficiency and neuromuscular or metabolic signs. Early recognition and genetic testing are crucial for accurate diagnosis, effective management, and informed family counseling.

Objectives: This case report explores the feasibility and effects of long-term physical exercise (PE) in a patient with TRPV4-related scapuloperoneal spinal muscular atrophy (SPSMA).

Methods: We describe a 26-year-old male who regularly engaged in supervised PE since age 21. He underwent annual clinical evaluations and laboratory assessments every 25 months to monitor maximal oxygen consumption (V̇O₂max), muscle strength, body composition, and emotional well-being.

Results: Over five years, the clinical condition remained stable. The patient showed V̇O₂max and handgrip strength values comparable to athletic cohorts; body composition aligned with reference values for age- and sex-matched healthy individuals; and limb muscle strength was preserved over time. Additionally, he maintained an active working life and consistently reported positive emotional well-being throughout the follow-up period.

Conclusions: This report provides preliminary data supporting the feasibility and potential benefits of long-term PE in the management of TRPV4-related SPSMA.

Congenital myopathies are a heterogeneous group of rare inherited muscle disorders. Despite the good sensitivity of whole-exome sequencing in detecting pathogenic variants, many cases remain molecularly unsolved. Here, we present the case of a woman with congenital myopathy that remained unsolved for many years, in which the application of whole-genome sequencing enabled the identification of a novel deep intronic mutation in the MYH7 gene.

A 22-year-old woman developed muscle weakness since infancy, with frequent falls, toe-walking, and difficulty climbing stairs. Muscle biopsy revealed atrophy of type 1 fibers relative to type 2, consistent with fiber-type disproportion. After a long "molecular odyssey," whole-genome sequencing performed on the patient-parents trio identified a de novo deep intronic variant in MYH7.

This case further underscores the importance of pursuing the search for the causative gene to enable more accurate clinical monitoring and tailored health care.

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.