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BACKGROUND: Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes. METHODS AND RESULTS: We retrospectively collected 3138 echocardiographic measurements of left ventricular ejection fraction (EF), shortening fraction (SF), and end-diastolic volume (EDV) from 819 DMD participants, 541 from an Italian multicentric cohort and 278 from the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS). Using generalized estimating equation (GEE) models, we estimated the yearly rate of decrease of EF (-0.80%) and SF (-0.41%), while EDV increase was not significantly associated with age. Utilizing a multivariate generalized estimating equation (GEE) model we observed that mutations preserving the expression of the C-terminal Dp71 isoform of dystrophin were correlated with decreased EDV (-11.01 mL/m2, p = 0.03) while for dp116 were correlated with decreased EF (-4.14%, p =

The document discusses a rare case of focal epilepsy followed by rapidly progressive frontotemporal dementia in a 58-year-old woman with a VCP gene mutation. The patient experienced cognitive decline, behavioral changes, and seizures, leading to a diagnosis of probable behavioral variant frontotemporal dementia (bvFTD). Genetic testing revealed a mutation in the VCP gene, and treatment with antidepressants and antipsychotics showed cognitive and behavioral improvements. The study highlights the importance of genetic testing and FDG-PET scans in diagnosing complex neurological disorders like frontotemporal dementia. [Extracted from the article]

Background: Becker muscular dystrophy (BMD) is an X-linked neuromuscular disease due to mutations in the DMD gene, leading to a deficient and less functional dystrophin mainly in skeletal and cardiac muscle. Understanding the natural history of BMD is crucial for optimizing patient care and developing targeted treatments., Materials and Methods: Retrospective data were collected from 943 patients diagnosed with BMD based on a combination of clinical, biochemical and genetic criteria followed by 17 Italian neuromuscular centers. Patients' demographics, main signs and symptoms at BMD onset, neuropsychiatric comorbidities, age at loss of ambulation (LoA), cardiac left ventricular ejection fraction (LVEF), pulmonary forced vital capacity (FVC), and DMD mutations were collected. Disease milestones were analysed in specific DMD mutational groups., Results: the median age at the last assessment was 26.0 (16.6-41.9) years, with a median age at diagnosis of 7.5 (4.0-14.0) years. In 55% of patients, the diagnosis was prompted by the incidental finding of hyperCKemia. At the last assessment, 13.5% of patients had lost the ability to walk at a median age estimated by Kaplan-Meier analysis of 69 years. Thirty percent of patients exhibited left ventricular impairment and 2.7% respiratory involvement. Ten percent of patients carried out-of-frame mutations, 4% nonsense mutations, and 86% in-frame deletions/duplications. The subset of in-frame deletions was further classified based on the specific mutations. Patients carrying del45-49 compared to del45-47 were associated with an earlier LoA (P=1×10-4), where patients with del45-55 (P=.005), del48 (P=.02), and del48-49 (P=.02) correlated with a later LoA compared to del45-47. del45-55 (P=.002) and del48 (P=.003) were significantly associated with decreased odds of developing a pathological LVEF% compared to del45-47., Conclusion: Our results contribute to the better understanding of the natural history of BMD and capture precious data in the era of the emerging therapies. The knowledge of the specific DMD mutation may help to define a prognosis in a subset of BMD patients and will serve as a model for the design of future therapies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)