Background/Objectives: Rhabdomyolysis is a potentially life-threatening condition characterized by acute skeletal muscle breakdown. In addition to well-described external triggers, a genetic contribution is increasingly recognized. We aimed to (I) review the genetic diagnostic approach of rhabdomyolysis, (II) evaluate the clinical characteristics indicative of a genetic susceptibility with the ‘RHABDO’ acronym, and (III) assess the predictive value of the presence RHABDO features for identifying genetic variants. Methods: In this retrospective two-center study, 122 patients underwent genetic testing for rhabdomyolysis since the introduction of whole exome sequencing (WES) in 2013. The presence of RHABDO features was compared between those with (likely) pathogenic variants and those with benign or no identified variants or variants of uncertain significance. Results: The testing methods included panel-based WES (82%), Sanger sequencing (49%), and full WES (24%), of which 52 patients (43%) underwent multiple methods. A (likely) pathogenic variant was identified in 13 patients (11%), in all of whom ≥2 RHABDO features were present. The positive predictive value for ≥2 features was 14%, while the negative predictive value was 100%. Conclusions: These results highlight the relevance of WES in further elucidating the genetic basis of rhabdomyolysis and demonstrated that RHABDO is a valuable tool for selecting patients who should undergo genetic testing.

Nemaline myopathy (NM) is a congenital myopathy with generalised muscle weakness, most pronounced in neck flexor, bulbar and respiratory muscles. The aim of this cross-sectional study was to assess the Dutch NM patient cohort. We assessed medical history, physical examination, quality of life (QoL), fatigue severity, motor function (MFM), and respiratory muscle function. We included 18 of the 28 identified patients (13 females (11-67 years old); five males (31-74 years old)) with typical or mild NM and eight different genotypes. Nine patients (50 %) used a wheelchair, eight patients (44 %) used mechanical ventilation, and four patients (22 %) were on tube feeding. Spinal deformities were found in 14 patients (78 %). The median Medical Research Council (MRC) sum score was 38/60 [interquartile range 32-51] in typical and 48/60 [44-50] in mild NM. The experienced QoL was lower and fatigue severity was higher than reference values of the healthy population. The total MFM score was 55 % [49-94] in typical and 88 % [72-93] in mild NM. Most of the patients who performed spirometry had a restrictive lung function pattern (11/15). This identification and characterisation of the Dutch NM patient cohort is important for international collaboration and can guide the design of future clinical trials.

Introduction: Congenital myopathies (CMYO) are a group of rare hereditary muscle diseases defined by characteristic abnormalities on muscle biopsy. Several types, including the core myopathies central core disease and multi-minicore disease, nemaline myopathy and centronuclear myopathy, have been identified based on the characteristic histopathological changes and attributed to various genetic backgrounds. The most prominent clinical features are generalised muscle weakness often pronounced axially, variable cardiorespiratory and bulbar impairment, and skeletal and joint involvement. Currently, no curative therapies are available for CMYOs; however, a few phase I and II trials have been performed or are expected in the near future. To reach trial readiness, an informed understanding of the disease course and a selection of relevant and sensitive clinical and functional outcome measures, and blood and imaging biomarkers is necessary. Furthermore, additional symptoms such as muscle fatigability have been recognised but not investigated systematically yet. The lack of understanding muscle fatigability in CMYO in particular calls for a cross-sectional study as this feature may be a treatment target. Methods and analysis: In collaboration with patient representatives, two studies have been designed: (1) a prospective cohort study with five 6-monthly visits over a 2-year period; and (2) a cross-sectional study on muscle fatigability. For both studies, patients from the same study population will be included. We aim to include 45 patients in study 1 and 75 in study 2. Patients are invited to participate in both studies. In study 1, we will perform a range of assessments covering patient-reported outcomes, clinical and functional outcome measures, and blood and imaging biomarkers. For study 2, we will assess the muscle fatigability and neuromuscular junction transmission. Baseline data will be analysed using descriptive statistics and correlation analysis. To assess disease progression, mixed models will be used. Multiple linear regressions will be used to explore the relationship between potential disease-modifying variables and disease severity. Ethics and dissemination: This study was approved by the Central Committee on Research Involving Human Subjects (CCMO, registration number NL83069.000.23). Findings will be shared with the participating patients and the funder. It will be presented at conferences and shared through peer-reviewed publications. Trial registration number: NCT06157268 .

Background and objective: RYR1 -related diseases ( RYR1 -RD) are a group of genetic conditions characterized by early-onset muscle weakness, causing functional impairments. An increasing number of clinical trials is on the horizon. This study aims to improve trial readiness by characterizing the patient perspective on clinical trial participation. Methods: In collaboration with RYR1 -RD patients and patient representatives we adapted an existing facioscapulohumeral muscular dystrophy (FSHD) survey and conducted the resulting international patient survey in 2025. We used descriptive statistics to analyze the patient characteristics and personal experiences and expectations in clinical trials. Results: In total 146 participants (of whom 30 with previous trial experiences), residing mainly in the Netherlands or the United States, completed the survey. Symptoms that caused the greatest difficulties in daily life, including muscle weakness, fatigue, and impaired mobility, were seen as important outcomes for future trials. The possibility to receive the trial drug and results when published were reported as facilitators of trial participation. There was a strong demand for receiving updates on ongoing and upcoming trials. Fear of side effects and travel time were reported as barriers. Conclusion: A clear understanding of patients’ expectations and preferences is important for relevant future clinical trials to better align with patients’ needs.