Dissociation of echogenicity of the flexor digitorum profundus (FDP) and flexor carpi ulnaris (FCU) on neuromuscular ultrasound has been reported to be a useful sign to differentiate inclusion body myositis (IBM) from more common disease mimics, but it is not clear that this finding is pathognomonic of IBM. Our study aimed to evaluate whether this sign may be present in certain muscular dystrophies. This case series included 6 genetically confirmed muscular dystrophy patients (2 Becker muscular dystrophy [BMD], 2 myotonic dystrophy type 2 [DM2], 1 myotonic dystrophy type 1 [DM1], and 1 facioscapulohumeral muscular dystrophy type 1 [FSHD1]), whose clinical picture was notable for selective deep finger flexor weakness. Neuromuscular ultrasound had been used to image the proximal medial forearm, where echointensity (EI) of the FDP and FCU was visually graded according to the Heckmatt scale and an FDP/FCU EI ratio was generated from quantitative grayscale analysis. The FDP had a higher EI-by Heckmatt grade and quantitative grayscale-than the FCU in all 6 patients, indicating preferential ultrasonographic involvement of the FDP in these muscular dystrophy cases. Ultrasonographic FDP-FCU dissociation of echogenicity confirms selective deep finger flexor involvement. The differential diagnosis of this imaging sign includes IBM but also certain muscular dystrophies (BMD, DM1, DM2, and FSHD), which should be considered in uncommon presentations of suspected IBM or when additional supportive diagnostic findings thereof are lacking.

Muscular dystrophy (MD) comprises a class of genetic conditions characterized by the progressive degeneration and weakness of skeletal muscle. Genetic etiologies differ among the major muscular dystrophies: myotonic dystrophy type 1 (DM1) is linked to CTG repeat expansion in DMPK whereas DM2 is linked to CCTG repeat expansion in CNBP; facioscapulohumeral muscular dystrophy (FSHD1) is linked to contraction of the D4Z4 repeat to cause inappropriate DUX4 expression whereas FSHD2 is linked to mutations in chromatin modifier SMCHD1 that derepress DUX4 expression. Despite advancements in investigations into the molecular mechanisms, effective treatments for MD remain limited. This review study aims to elaborate on the pathogenesis of each type of MD, including the underlying genetic mutations, cellular dysfunction, and pathway deregulation. We also conduct comprehensive research on various breakthroughs in treatment strategies, including protein replacement therapies, stem-cell-based, exon skipping, gene therapy, and recently discovered drugs for MD. Furthermore, this study focuses on the artificial intelligence (AI)-based improvement in the diagnosis, management, and treatment of MD. The AI-based discovery of compounds has provided novel treatment modalities that hold potential for managing MD conditions.

Endogenous circadian rhythm sleep disorders through the lens of nonparametric variables of actigraphy: an exploratory study in myotonic dystrophy type 1.

Myotonic Dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder. Gastrointestinal (GI) symptoms significantly impact quality of life, but remain under-assessed. Currently, no DM1 specific GI questionnaire is available. The Gastrointestinal Symptoms Rating Scale (GSRS) is widely used but lacks validation with modern clinimetric methods. To evaluate the GSRS using Rasch analysis in DM1 patients and develop a disease-specific, interval-level GI symptom measure. Rasch analysis evaluated item fit, threshold ordering, differential item functioning (DIF), local dependency, and unidimensionality. Model fit was evaluated using chi-square statistics, item and person fit residuals, and the Person Separation Index (PSI). Four hundred and three DM1 patients (206 women, mean age 48.3 years) completed the GSRS questionnaire. The GSRS initial data did not meet Rasch model expectations. Three items (hard stools, heartburn, diarrhea) were removed and the item nausea was split by age category. The item constipation had misfit exceeding the Bonferroni threshold, but was retained due to its clinical relevance. The final model did not fulfill Rasch requirements (item fit residuals: -0.23, SD 1.29; person fit residuals: mean -0.27, SD 1.15; item-trait Chi-square: p-value < 0.001; degrees of freedom: 60). Acceptable person separation index (0.76) was obtained. This study highlights the challenges of measuring GI symptoms in DM1. Although this research is an important first step, more research is needed for developing a questionnaire that reflects the patient experience whilst simultaneously considering measurement accuracy.

Neuromuscular disorders (NMDs) comprise a group of conditions affecting the muscles and/or the nerves controlling them, resulting in progressive muscle weakness. Beyond the physical limitations, NMDs can significantly impact quality of life (QoL), including sexuality. Sexuality, as defined by the World Health Organization, encompasses physical, psychological, and social dimensions. However, research exploring the multifaceted impact of NMDs on sexual well-being remains limited, despite the potential influence of physical impairments, psychological distress, and social stigma. This scoping review aims to synthesize the existing literature on sexuality in individuals with NMDs, identifying the interplay of physical, psychological, and social factors affecting sexual QoL, highlighting research gaps, and informing future research and clinical practice. A scoping review was conducted using PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases (up to May 15, 2025) to identify studies examining sexuality in individuals with NMDs. Studies addressing physical, psychological, and social factors influencing sexual health in NMD patients were included. Data were extracted using a standardized form and synthesized narratively. The review was registered on Open OSF (DOI https://doi.org/10.17605/OSF.IO/RP9U2). Fourteen studies with various conditions such as Duchenne muscular dystrophy, amyotrophic lateral sclerosis (ALS), myotonic dystrophy type 1, myasthenia gravis, and Charcot-Marie-Tooth disease were included, from interviews to surveys. One key theme that emerged was the extent to which personal narratives reveal the emotional weight of stigma, the struggle with body image, and how intimacy is peripheral in medical institutions. In surveys, many said their sexual activity had declined, particularly among people with progressive diseases like ALS and myotonic dystrophy. Many of these studies also pointed to how sexual health was directly associated with QoL, a good reminder that it's an important aspect of well-being that we need to pay more attention to in care and support. This scoping review highlights a significant gap in research regarding sexuality in individuals with NMDs. The limited number of studies identified underscores the need for further research to understand the complex interplay of physical, psychosocial, and social factors affecting sexual well-being in this population.

Role of Cardiovascular Magnetic Resonance in Diagnosis and Management of Muscular Dystrophies.

287th ENMC international workshop: Harmonization and federated analysis of myotonic dystrophy registries to model heterogeneous disease trajectories. Hoofddorp, the Netherlands, 28-30 March 2025.

Pathological mechanism in Fuchs endothelial corneal dystrophy and myotonic dystrophy type 1: more than meets the eye.

Neural damage and inflammation in myotonic dystrophy type 1: Longitudinal analysis of serum NFL, GFAP, and IL-6.

Clinical features, quality of life, and fatigue in children with myotonic dystrophy type 1: A cross-sectional study.

Transcriptome-wide isoform and promoter remodeling in DM1 fibroblasts uncovered by long-read RNA sequencing.

Purpose: To report two cases of myotonic dystrophy type 1 presenting with binocular horizontal diplopia as an initial symptom.Case summary: The first patient was a 49-year-old woman with a one-month history of diplopia. Examination revealed mild nuclear cataracts and exotropia of 16 prism diopters (PD) at distance and 30 PD at near, without gaze limitation. Neurologic assessment showed distal-dominant weakness, generalized atrophy, and myotonia. The second patient was a 50-year-old woman with a 10-year history of diplopia. Examination showed bilateral cataracts, retinal pigment epithelium depigmentation, and exotropia of 20 PD at distance and 30 PD at near, notably accompanied by limitation of movement in all directions. She exhibited proximal weakness, grip myotonia, and a positive family history. Genetic analysis confirmed more than 90 CTG repeats in the DMPK gene, confirming the diagnosis of myotonic dystrophy type 1 in both patients.Conclusions: Clinicians should include myotonic dystrophy type 1 in the differential diagnosis of unexplained diplopia and perform thorough neurologic and genetic evaluations.

DNA triplet repeat expansion causes several primarly neurological disorders like Huntington’s disease, myotonic dystrophy type 1, and fragile-X related disorders. There is general consensus that recognition of extrahelical extrusions or hairpin-loop structures (formed by strand slippage) by the DNA mismatch repair protein MutSβ leads to repeat expansion by a mutagenic process. By contrast, the FAN1 nuclease attenuates triplet repeat expansion, the molecular basis of which was explained by our recent finding that FAN1 nuclease cleaves and initiates removal of extrahelical extrusions. Here we show that extrusions containing two or more triplet repeats are subject to recognition and processing by either FAN1 or MutSβ. However, extrusions containing a single triplet escape FAN1 cleavage and are preferentially processed by a MutSβ-dependent process, leading to repeat expansion. Thus, extrahelical extrusion size determines the ultimate fate of the repeat element, the protective role of FAN1 being limited to removal of extrusions containing two or more triplets. Therefore, repeat expansion is a net consequence of MutSβ-dependent processing of single triplet extrusions and competition between MutSβ and FAN1 for extrusions containing two or more triplets. These findings provide new insights into the role of DNA structural dynamics in determining pathway choice in DNArepair.

Myotonic dystrophy type 1 is a multisystemic disorder that has been extensively studied for decades, yet our understanding of its neuropathological aspect remains rudimentary. Building on an established Drosophila model, we study the neuropathological features of the disease by expressing untranslated expanded CUG repeats at the Drosophila larval neuromuscular junction. In this model, we show that both pre- and postsynaptic expressions of CUG repeats participate in inducing phenotypes in synaptic boutons, arbors, transmission and larval locomotor activity. Furthermore, expression of CUG repeats in either motorneurons or body wall muscles induces upregulation of the cell adhesion molecule FasII (NCAM1 in mammals), and the knockdown of fasII is sufficient to rescue the phenotypes. Overexpression of FasII-C, a FasII isoform with no cytoplasmic domain, mimics the phenotypes of expanded CUG expression at the neuromuscular junction. In contrary, overexpression of FasII-A-PEST+ rescues the synaptic and behavioral defects. Our study provides insights into the fundamental mechanisms underlying synapse dysregulation in myotonic dystrophy type 1.

Background/Objectives: Myotonic dystrophy type 1 (DM1) is a rare, multisystemic disorder caused by an expanded (CTG)n repeat in the DMPK gene. Although DM1 has been studied in several populations, access to molecular diagnosis and comprehensive care remains limited in many low- and middle-income countries. This study provides an updated overview of DM1 in Mexico, from diagnostic implementation to patient management, describing key clinical and genetic findings. Methods: We conducted a nationwide, 15-year prospective study at Mexico's National Reference Center for neuromuscular diseases. A total of 853 individuals at risk were subjected to clinical and molecular evaluation using PCR, TP-PCR, and SP-PCR, encompassing symptomatic, pre-symptomatic, prenatal, and preimplantation genetic diagnosis. Socioeconomic, clinical, and molecular variables were analyzed. Results: A total of 488 individuals were confirmed as DM1 carriers, with the most prevalent phenotypes being classic (36.5%) and juvenile (28.5%). Genomic analysis revealed a correlation between CTG tract sizes and phenotypes. Intriguingly, interrupted CTG repeat tracts were identified in 2.8% of DM1 carriers, who exhibited milder clinical phenotypes and a reduced degree of somatic and intergenerational instability. Survival analysis revealed a reduction in symptom-free survival in patients with larger expansions, while interrupted CTG tracts were associated with delayed onset. Conclusions: The centralization of diagnostic services in Mexico resulted in regional disparities, impacting early diagnosis and family planning. This study highlights the clinical and molecular diversity of DM1 in a Latin American population and underscores the urgent need for decentralized diagnostic services, integrated care models, and tailored prognostic tools in underserved settings.

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy and severely affects multiple organ systems, including the brain, heart, skeletal muscle, and gastrointestinal (GI) tract. Despite 80% of individuals with DM1 experiencing GI dysfunction that affects their daily life, the mechanisms of GI dysmotility in DM1 remain an understudied aspect of the disease. DM1 is caused by a CTG repeat expansion in the DMPK gene that, when expressed as an expanded CUG repeat RNA, sequesters and reduces the activity of the muscleblind-like (MBNL) RNA-binding protein family. We developed a mouse line with conditional, smooth muscle-specific knockout of Mbnl1 and Mbnl2 to model and investigate myogenic mechanisms contributing to GI dysmotility in DM1. Mice with Mbnl knockout exhibited delayed GI transit of small and large bowel in vivo and increased smooth muscle contractile tone of jejunum and colon segments ex vivo. Smooth muscle from the jejunum and colon showed no histopathology suggesting an intrinsic defect and contained increased phosphorylation of the 20 kDa myosin light chain (Mlc20), consistent with increased contraction. RNA sequencing of mouse and human DM1 GI samples enriched for smooth muscle revealed conserved misregulated alternative splicing of transcripts associated with the regulation of Mlc20 phosphorylation and smooth muscle contraction. These findings demonstrate that Mbnl knockout disrupts the regulation of contraction dynamics and causes GI smooth muscle hyperactivity, suggesting that therapeutics that reduce GI contractile activity may improve DM1 GI symptoms.

Myotonic dystrophy type 1 is the most prevalent muscular dystrophy in adults, characterized by weakness, impaired functional abilities, and myotonia. However, little is known about the relationship between quantitative MRI measures (fat fraction and T2 relaxation time) and clinical findings of the upper extremity. This study assessed forearm muscle structure in patients with myotonic dystrophy using quantitative MRI and correlated these measures with strength, function, and handgrip myotonia. Eighteen adults with myotonic dystrophy type 1 underwent MRI using three-point Dixon and T2 spin echo imaging of the forearm. The average fat fraction and T2 relaxation time were greatest in the flexor digitorum profundus (26.7% and 55.6 ms, respectively). Correlations were found between quantitative MRI values and clinical tests of strength (r = -0.61 to -0.92, p < 0.01), function (r = -0.64 to -0.83, p < 0.01), and handgrip myotonia (r = 0.48, p < 0.05). Overall, the anterior forearm fat fraction values showed higher correlations with strength and function compared to those of the posterior forearm. Our results support the use of quantitative MRI measures to assess forearm disease pathology and show potential to monitor the effectiveness of therapeutic treatments in patients with myotonic dystrophy type 1.

Development of an AAV-delivered microRNA gene therapy for myotonic dystrophy type 1.

To evaluate the diagnostic yield of exome sequencing (ES) in isolated polyhydramnios. This retrospective study included 40 cases of isolated polyhydramnios. All patients underwent screening for gestational diabetes mellitus (GDM) and chromosomal microarray analysis (CMA). ES was performed in CMA-negative cases, along with targeted testing for spinal muscular atrophy, myotonic dystrophy type 1, and Prader-Willi syndrome. Pathogenic or likely pathogenic variants were identified in 7 cases, yielding a 17.5% diagnostic rate. Diagnostic yield was 12% (2/17) in mild cases and 22% (5/23) in moderate-severe cases. Diagnoses included Bartter syndrome (KCNJ1, BSND, MAGED2), Noonan syndrome (RIT1), Osteopathia Striata with Cranial Sclerosis (AMER1), and AUTS2-related neurodevelopmental disorder. In addition, one case was diagnosed postnatally with myotonic dystrophy 1. Two ES-positive cases had concurrent GDM. Postnatal follow-up showed normal development in 85% of live-born infants, with a few cases of global or speech delay. ES yields a substantial diagnostic benefit in isolated polyhydramnios, including mild cases and those with GDM. These findings support incorporating ES into the diagnostic approach for isolated polyhydramnios.

Myotonic dystrophy type 1 (DM1) is a genetic disease which affects multiple systems including the central nervous system. One of its key neuroimaging biomarkers are white matter hyperintensities (WMHs). The clinical relevance of WMHs remains unclear, and treating them as a uniform entity may overlook their heterogeneous composition and spatial distribution. To assess WMHs heterogeneity we applied intra-voxel incoherent motion (IVIM) modelling, an advanced magnetic resonance imaging technique, to a cohort of 23 patients with DM1 (age [mean ± std]: 44.1 ± 11.9 years; M/F = 8/15). WMHs were distinguished into periventricular (PWMHs) and deep (DWMHs) subtypes using criteria based on continuity and distance rules. A quantitative evaluation of their distribution among white matter tracts was conducted, together with correlation analysis between WMHs and clinical scales. Our research reveals that PWMHs have higher parenchymal diffusivity than DWMHs, consistently with their closeness to the ventricles. Significant positive correlation is identified between PWMH volumes and age, while DWMHs seem to be more strongly associated with an impairment of cognitive functions. Overall, these findings could have possible implications in clinics, highlighting the importance of considering WMHs heterogeneity and opening the door to a better comprehension of their role in the disease.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-26964-4.