A 5-year Natural History Study in LAMA2-related Muscular Dystrophy and SELENON-related Myopathy.

Rationale: A long-term prospective natural history study in an unselected group of patients including clinical and functional outcome measures is lacking in both SELENON-related myopathy (SELENON-RM) and LAMA2-related muscular dystrophy (LAMA2-MD). Due to the promising ongoing preclinical trials, there is a high need to obtain natural history data in order to reach trial readiness for both diseases. With the extended LAST STRONG study, we aim to further analyze and expand our 1.5-year natural history data on SELENON-RM and LAMA2-MD to provide a detailed clinical description of the Dutch and Flemish cohort. This will enable a smooth transition towards implementation into clinical care and clinical trials that are expected to start within 5 years.

Objective: (1) To collect 3- and 5-year natural history data in patients with SELENON-RM and LAMA2-MD. (2) Implementation of natural history data collection into clinical care and international guidelines, and reach trial readiness.

Study design: This is an observational study. A variety of tests will be performed to get a full impression of the patient's abilities and disabilities (standard medical history, neurological examination, functional measurements, questionnaires, imaging, pulmonary assessment and accelerometry). The tests that the patient undergoes depend on the age/abilities/wishes. The tests are selected based on our previously performed 1.5-year natural history study in LAMA2-MD and SELENON-RM. Each participant will perform these measurements during the two scheduled visits at 3- and 5-year after the first visit during the LAST STRONG Study.

Risk and benefit assessment: This study does not concern any product (medicinal product, food product or medical device). There is a small risk for minor injury, e.g. when a participant falls. However since the investigators use all functional tests using movements to which most participants are familiar (i.e. walking, transfers, etc.), the participant will be able to estimate his/her own risk. The investigators don't include tests in which they push participants to their physical limits. the investigators conclude that this study has a negligible risk. A benefit includes the possibility for participants to get a detailed analysis on their own health. Additionally, participants will contribute to the design of future clinical trials on possible treatment options.

• Change of physical activity in daily life assessed by an accelerometer (GENEActiv original devices) for 7 days [Time frame: Change from baseline to 3 years and 5 years]
• Change of activity limitations assessed using ACTIVLIM (6 years and older) [Time frame: Change from baseline at 3 years and 5 years]
• Change of bone density assessed using DEXA-scan (2 years and older) [Time frame: Change from baseline at 3 years and 5 years]
• Change of The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score (children under the age of 2 years) [Time frame: Change from baseline at 3 years and 5 years]
• Change of fatigue (pediatric 2-17 years old) assessed by PedsQL Multidimensional Fatigue Scale (MFS) [Time frame: Change from baseline at 3 years and 5 years]
• Change of functional ability in daily life assessed by Egen klassification scale version 2 (EK2) (16 years and older) [Time frame: Change from baseline at 3 years and 5 years]
• Change of Functional Ambulation Category (FAC) (5 years and older) [Time frame: Change from baseline at 3 years and 5 years]
• Change of Graded and Timed function tests [Time frame: Change from baseline at 3 years and 5 years]
• Change of Hammersmith Infant Neurological Examination (HINE) (under the age of 2 years) [Time frame: Change from baseline at 3 years and 5 years]
• Change of Impact on Participation and Autonomy (IPA) (18 years and older) [Time frame: Change from baseline at 3 years and 5 years]
• Change of maximal voluntary isometric contraction (5 years and older) [Time frame: Change from baseline at 3 years and 5 years]
• Change of location, level and characteristics of pain assessed by McGill pain questionnaire (12 years and older) [Time frame: Change from baseline at 3 years and 5 years]