The Natural History and Muscle Fatigability of Patients With Congenital Myopathies.

Change of 6-minute walk test (6MWT) (5 years and older)

How far the patient can walk in 6 minutes. The first and last minute will be compared to each other.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Accelerometry - change of extent and intensity of physical activity in daily life (all ages)

Physical activity in daily life will be assessed by wearing an wrist worn accelerometer (GENEActiv original devices) for 7 days.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Change of bone density (DEXA scan) (6 years and older)

The bone density of the spine and hip will be measured by a DEXA scan.

Time frame: Change from baseline at 24 months

Change of graded and timed rise from floor (5 years and older)

The time it takes to rise from the floor

Time frame: Change from baseline at 6, 12, 18 and 24 months

Handheld dynamometry (5 years and older)

Maximal voluntary isometric contraction will be measured by handheld dynamometry (m. biceps brachii, m. quadriceps, grip strength, all bilaterally)

Time frame: Change from baseline at 6, 12, 18 and 24 months

Creatine Kinase

Blood level of Creatine Kinase

Time frame: At baseline

Vitamin D3

Blood level of Vitamin D3

Time frame: At baseline

Calcium

Blood level of calcium

Time frame: At baseline

Liver function panel

Blood level of bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase GGT, albumin, bile acids and full blood count.

Time frame: At baseline

Manual muscle testing (MMT) (5 years and older)

Muscle power of individual muscle groups can be assessed by muscle power measurements and graded in correspondence with the Medical Research Council (MRC) scale.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Change in muscle fattening by quantitative lower extremity muscle MRI (10 years and older)

A lower extremity muscle MRI will be performed in participants who are able to lie supine and still for 20 minutes and who are not dependent on respiratory equipment. Muscle fattening will be assessed by Regions of Interest (ROIs) (quantitative) and modified Mercuri score (semi-quantitative).

Time frame: Change from baseline at 24 months

Change of muscle atrophy by quantitative lower extremity muscle MRI (10 years and older)

A lower extremity muscle MRI will be performed in participants who are able to lie supine and still for 20 minutes and who are not dependent on respiratory equipment. Atrophy will be assessed by muscle volume score (semi-quantitative).

Time frame: Change from baseline at 24 months

Change in muscle atrophy (cm) assessed by muscle ultrasound (all ages)

Muscle atrophy of the leg, arm, back, abdominal muscles and diaphragm will be assessed by muscle ultrasound.

Time frame: Change from baseline at 24 months

Change in muscle fattening (echo-intensity) assessed by muscle ultrasound (all ages)

Muscle fattening of the leg, arm, back, abdominal muscles and diaphragm will be assessed by muscle ultrasound.

Time frame: Change from baseline at 24 months

Range of motion (all ages)

The range of motion of the elbows, fingers, knees and ankles is noted bilaterally by goniometry.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Pulmonary function - change of forced vital capacity (percentage predicted) (5 years and older)

Obtained with handheld spirometry in sit and supine.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Pulmonary function - change of forced expiratory volume in the first second (5 years and older)

Obtained with handheld spirometry in sit and supine.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Pulmonary function - change of maximal expiratory pressure (cmH2O) (5 years and older)

Obtained with handheld device.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Pulmonary function - change of maximal inspiratory pressure (cmH2O) (5 years and older)

Obtained with handheld device.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Pulmonary function - change of sniff nasal inspiratory pressure (5 years and older)

Obtained with handheld device.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Vignos and Brooke scale (all ages)

The Brooke (score 1-6) and Vignos (score 1-10) scales provide ordinal data to assess the upper and lower extremity functions. A lower score indicates more functionality.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Isokinetic dynamometry (quadriceps and hamstrings or biceps and triceps) (8-60 years old) - fatigability part

Peak torque, time to peak torque, change in torque from first third to last third, acceleration time and deceleration time for 3, 5 and 30 repetitions at a set speed. For the 30 repetitions how many repetitions until failure is also noted.

Time frame: At assessment 1 or 2 of the fatigability part of the study. Which day is dependent on the preference of the patient and planning possibilities.

Change in surface electromyography (EMG) amplitude and median frequency during isokinetic dynamometry with surface EMG (quadriceps and hamstrings or biceps and triceps) (8-60 years old) - fatigability part

On the quadriceps/hamstrings or biceps/triceps surface EMG amplitude and median frequency will be measured.

Time frame: At assessment 1 or 2 of the fatigability part of the study. Which day is dependent on the preference of the patient and planning possibilities.

Repetitive nerve stimulation (RNS) (8-60 years old) - fatigability part

We will stimulate the n. ulnaris, n. accesorius and n. facialis at 3 Hz to measure the m abductor digiti minimi, m. trapezius and m nasalis. The decrement/increment will be determined by the compound muscle action potential amplitude and area. The RNS will be performed before and after 60 seconds of voluntary contraction.

Time frame: At assessment 1 or 2 of the fatigability part of the study. Which day is dependent on the preference of the patient and planning possibilities.

Checklist individual strength (CIS) questionnaire fatigue subscale (18 years and older)

The CIS is a questionnaire rating four subscales: subjective tiredness, concentration, motivation and physical activity. It consists of 20 items on a 7-point scale. We will use the Fatigue subscale. A CIS fatigue scale ≥ 35 points to severe fatigue.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Fatigue severity scale questionnaire (12 years and older)

Nine-questions scale about the impact of fatigue on the patient's life. Each item is scored on a 7 point scale. A higher score indicates greater fatigue/greater impact of fatigue on daily life.

Time frame: Change from baseline at 6, 12, 18 and 24 months

PedsQL multidimensional fatigue scale (MFS) (2-17 years old)

The PedsQL MFS assesses subjective fatigue in three domains with 6 items each, namely General Fatigue Scale, Sleep/Rest Fatigue Scale, and Cognitive Fatigue Scale. Each item is scored on a three point scale ranging from not at all to a lot for children aged 5-7 and a five point scale from never to almost always for the others. Higher scores indicates less symptoms.

Time frame: Change from baseline at 6, 12, 18 and 24 months

PROMIS Fatigue Short Form questionnaire (all ages)

Consists of 8 items representing the most informative items from the PROMIS item bank. The PROMIS Fatigue item banks assess a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. For patients younger than 18 a parent proxy is also available. The items are scored form 1-5 with a higher score indicating more fatigue.

Time frame: Change from baseline at 6, 12, 18 and 24 months

McGill pain questionnaire (MPQ) (12 years and older)

The MPQ consists of 4 components: a pain word list to state the type and intensity of the pain, questions about the effect on daily life, a visual-analogue scale for pain intensity and questions about the location and course of the pain.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Wong-Baker Faces Pain Scale (2-11 years old)

The Wong-Baker Faces Pain Scale was originally created for children to help them communicate about their pain. It has six types of faces ranging from no hurt (0) tot hurts worst (10).

Time frame: Change from baseline at 6, 12, 18 and 24 months

PedsQL generic quality of life (2-17 years old)

The PedsQL generic quality of life questionnaire consists of 8 items on physical functioning, 5 items on emotional functioning, 5 items on social functioning, and 5 items on school functioning. Each item is scored on a 0-4 scale. The items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate a better outcome.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Short Form 36 (SF36) quality of life scale (18 years and older)

The adult Quality of Life is measured by the SF36/RAND36 questionnaire. The SF36/RAND36 addresses eight concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. It has a total of 36 items.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Activlim questionnaire (7-17 years old)

ACTIVLIM assesses the ability to perform 22 activities of daily life on a 3-point scale from impossible to easy. The questionnaires will be answered by the parents of the patient.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Impact on participation and autonomy (18 years and older)

Questionnaire about participation and autonomy in daily life with 41 questions on a ordinal 3- or 5-point likert scale. Higher scores indicate more obstacles in participation and autonomy.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P) (18 years and older)

USER-P Restrictions scale is a patients-reported outcome measures with 32 questions focusing on daily activities including school and work. Each item is scored on a 4-, 5-, and 6-point Likert scale. A higher score indicates more participation.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Borg rating scale of perceived exertion (5 years and older)

Borg Rating Scale of Perceived Exertion is a way of measuring physical activity intensity level. Perceived exertion is based on the physical sensations a person experiences during physical activity. It is scored 6-20 with a higher score indicating a greater perceived exertion. Participants will be asked to score the intensity level at the beginning and at the end of the 6MWT.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Hospital anxiety and depression scale (18 years and older)

Questionnaire about the main complaints of anxiety and depression with 7 items each on a 4-point Likert scale. A higher score indicates more complaints.

Time frame: Change from baseline at 6, 12, 18 and 24 months

PedsQL neuromuscular module (NMM) (2-17 years old)

The PedsQL NMM questionnaire consists of 25 questions in three domains: Neuromuscular disease, communication and family resources. Each item is scored on a 0-4 scale. The items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate a better outcome.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Resilience evaluation scale (18 years and older)

9-Item questionnaire on psychological resilience with each item being scored from 0-4, higher scores indicating greater resilience.

Time frame: Change from baseline at 6, 12, 18 and 24 months

Effects of pyridostigmine and/or salbutamol (8-60 years old) - fatigability part

We will ask patients if they use pyridostigmine and/or salbutamol. If they use it we will ask how often, what the effects are and how long those effects last.

Time frame: At baseline of the fatigability part of the study