Congenital myopathies (CM) are a group of rare hereditary muscle diseases defined by characteristic abnormalities on muscle biopsy. The most prominent clinical features are generalized muscle weakness often pronounced axially, variable cardiorespiratory and bulbar impairment, and skeletal and joint involvement. Currently, no curative therapies are available for CMs, however, a few phase I-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 patient-reported outcomes, clinical and functional outcome measures, and blood and imaging biomarkers is necessary. In collaboration with patient representatives, a natural history study has been designed. We are performing a prospective, longitudinal cohort study with five 6 monthly visits over a 2-year-period in patients with Centronuclear myopathy, Core myopathy, and Nemaline myopathy at the Radboudumc in the Netherlands. 45 patients aged ≥2 years old will be included. At each visit, the participants will undergo several measurements; neurological exam, functional tests, hand-held dynamometry, pulmonary function tests, and receive questionnaires. At the first and last visit, they will also undergo muscle imaging; muscle ultrasound bilaterally, muscle MRI of the lower extremities bilaterally, and a Dual-energy X-ray absorptiometry scan. The study is ongoing and the baseline measurements will have been performed at the end of spring 2025. This study will provide important natural history data of CM patients. Preliminary results of the baseline measurements will be presented at the conference.