Longitudinal Psychometric Properties of the Myotonic Dystrophy Health Index in a Large Multicenter Cohort of People Living With Myotonic Dystrophy Type 1 Valeria A. Sansone, Andrea Lizio, Carola R. Ferrari Aggradi, Lucia C. Greco, Cynthia Gagnon, et al. Muscle and Nerve, 2026 Introduction/Aim The Myotonic Dystrophy Health Index (MDHI) is a patient‐reported outcome measure assessing disease burden in DM1. In prior cross‐sectional studies, the MDHI correlated with disability status and with several functional measures and activities of daily living. To aid its use and interpretation, we investigated the longitudinal performance of MDHI. Methods Patients with genetically confirmed DM1 were enrolled as part of an observational longitudinal study within the Myotonic Dystrophy Clinical Research Network (DMCRN). Internal consistency and construct validity were evaluated to confirm previous findings. Both the Minimal Detectable Change (MDC) and the Minimal Clinically Important Difference (MCID) were calculated using distribution‐ and anchor‐based methods, respectively. Sensitivity to change and responsiveness were also investigated, along with potential factors associated with the progression of overall burden. Results 451 DM1 patients were assessed, with 147 completing 24‐month follow‐up. The MDHI showed excellent internal consistency ( α = 0.95) and confirmed construct validity. MDC for the total score ranged from ±4.24 (effect size change‐based approach) to ±9.72 (Standard Error Method‐based approach) points, while MCID ranged from small changes (−0.12 improvement/+1.25 worsening) to large changes (−2.17 improvement/+4.71 worsening). Changes in MDHI total and subscale scores were statistically significant at individual‐ or subgroup‐levels and consistently mirrored changes in corresponding clinical measures. Discussion The MDHI demonstrates robust sensitivity and responsiveness to individual and subgroup‐level changes in disease burden, offering valuable insights into patient‐perceived progression. These findings support MDHI use over time and as a potential additional outcome measure at subgroup levels in clinical trials.
Development and Validation of a Deep Learning-Based Facial Weakness Score for Objective Assessment in Facioscapulohumeral Muscular Dystrophy T. G. J. Loonen, T. C. ten Harkel, S. C. C. Vincenten, C. G. C. Horlings, C. H. G. Beurskens, et al. Muscle and Nerve, 2026 Introduction/Aims Facioscapulohumeral muscular dystrophy (FSHD) is a muscle disease that leads, among other manifestations, to facial weakness. This weakness can severely impact communication and quality of life, yet it remains under‐researched with limited objective clinical measures. Current manual scoring methods are subjective and exhibit suboptimal inter‐observer agreement. This study aimed to develop and validate a deep learning‐based facial weakness score (DLFWS) as an objective clinical outcome measure for facial weakness in FSHD. Methods One hundred and twenty‐two genetically confirmed FSHD patients and 56 controls were recruited. Sixty‐four patients had a 5‐year follow‐up visit. Video recordings of participants performing seven facial exercises, each repeated three times, were analyzed using a convolutional neural network. The deep learning‐based facial weakness score (DLFWS) was trained by comparing start and end frames from these exercises with the manual facial weakness scores (MFWS) assigned by three experienced observers. Pearson correlation coefficients and intraclass correlation coefficients (ICC) were used to evaluate the DLFWS's performance and reliability. Results The DLFWS showed a strong correlation with the MFWS across exercises, with a mean Pearson correlation of 0.79 and a maximum of 0.85 for individual exercises. The DLFWS demonstrated excellent test–retest reliability, with an ICC of 0.90. Over a 5‐year follow‐up period, no significant progression of facial weakness was detected. Discussion The DLFWS provides a reliable and objective assessment of facial weakness in FSHD patients. This automated tool holds potential for widespread clinical and research applications, enabling standardized assessment of facial weakness in FSHD.
Electrical Impedance Myography Detects Disease Progression over 12 to 24 Months in Facioscapulohumeral Muscular Dystrophy Karlien Mul, Michael P. McDermott, Russell J. Butterfield, Bakri Elsheikh, Kate Eichinger, et al. Annals of Neurology, 2026 Objective Targeted therapies for facioscapulohumeral muscular dystrophy (FSHD) are progressing through clinical trials. Electrical impedance myography (EIM) provides a noninvasive biomarker of muscle composition that may be valuable especially in early phase trials. This study evaluated EIM data from a multicenter FSHD cohort over 24 months. Methods Adult patients with FSHD at 8 sites underwent EIM in 6 muscles bilaterally (deltoid, biceps, triceps, vastus lateralis, tibialis anterior, and medial gastrocnemius). EIM outcomes phase and reactance (50 and 100 kHz [kilohertz] frequencies) and 50 of 211 kHz phase ratio were evaluated for reliability, correlations with clinical measures, and sensitivity to change. Results One hundred fifty‐seven patients (53% male patients) were included. Test–retest reliability was excellent for all EIM outcomes (intraclass correlation coefficient [ICC] ≥0.94). Phase outcomes strongly correlated with the FSHD‐composite outcome measure (FSHD‐COM; r ≤ −0.69) and Motor Function Measure Domain 1 (MFM1; r ≥ 0.75); reactance outcomes exhibited moderate correlations with the FSHD‐COM ( r ≥ –0.41) and MFM1 ( r ≤ 0.44). Mean declines in phase and phase ratio were apparent at 12 months (eg, –0.25, 95% confidence interval [CI] = –0.45 to –0.05 at 50 kHz), and further progressed through 24 months (–0.66, 95% CI = –0.92 to –0.40] at 50 kHz and –0.65 [95% CI = –0.87 to –0.44] at 100 kHz; both p < 0.0001). Reactance changes were smaller and not significant: –0.21 (95% CI = –0.44 to 0.02) at 50 kHz and –0.13 (95% CI = –0.35 to 0.10) at 100 kHz. Interpretation EIM phase outcomes are reliable, valid, and sensitive to change over 12 to 24 months, supporting their potential utility as biomarkers in FSHD clinical trials. ANN NEUROL 2026
The blind men and the elephant: recognising the multisystem symptoms of myotonic dystrophy type 1 Kristofoor E. Leeuwenberg, Johanna E. Bruijnes, llse Karnebeek, Fran Smulders, Sandra Altena-Rensen, et al. Orphanet Journal of Rare Diseases, 2025 Although myotonic dystrophy type 1 (DM1) is named after its characteristic muscle symptoms, it is in fact a multisystem disorder that can affect many different organs. It is therefore not surprising that this disease can manifest with a myriad of symptoms, depending on the organs involved. The age of onset and severity of symptoms vary widely. Diagnostic delays of more than ten years are common and it’s not unusual for an entire family to be diagnosed only after the birth of a child with a severe phenotype. Knowledge of the spectrum of possible symptoms in DM1 can aid clinicians to recognise this disorder, thereby preventing unnecessary diagnostic delay and facilitating early treatment of disease complications. Here, we present an overview of the potential symptoms of DM1 at different ages, with the aim of raising awareness among healthcare professionals about the recognition of this disabling disease.
Establishing biomarkers and clinical endpoints in myotonic dystrophy type 1 (END-DM1): Protocol of an international natural history study Karlien Mul, Kate Eichinger, Man Hung, Valeria A. Sansone, Cynthia Gagnon, et al. Plos One, 2025 Background Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited multi-system disorder that affects skeletal muscles but also many other organ systems. Molecular targets have been identified and targeted therapies are being developed and tested in first-in-human clinical trials. However, insufficient knowledge of the phenotypic heterogeneity and natural course of the disease, together with a lack of reliable biomarkers, complicate the design of clinical trials. Methods The main objectives of this study are to 1) characterize the phenotypic heterogeneity and disease progression of DM1 in a large cohort; 2) identify baseline characteristics that predict subsequent progression; 3) validate RNA biomarkers of disease severity. This is a prospective, multi-site observational study with a follow-up period of 24 months including approximately 700 adult DM1 patients. Visits will occur at baseline, and months 12 and 24. All patients will undergo strength testing, myotonia assessment, a battery of functional outcome assessments, spirometry, and complete various questionnaires and cognitive tests. Blood and urine samples will be taken at each visit for biomarker studies. A subset of 60 patients will undergo a muscle biopsy at baseline and at an additional 3-month visit. The sensitivity to disease progression and minimally clinically important differences will be determined for the various clinical outcome measures. Associations between baseline patient characteristics and the rate of disease progression will be evaluated. Discussion The results of this large international study on DM1 will contribute to optimizing clinical trial design. Both data and biological samples will be collected for future research as well. Trial registration Clinicaltrials.gov NCT03981575
