Natural History Study for Patients With Nemaline Myopathy in Spain

A standardized muscle ultrasound protocol of assessment is performed (whole body). Muscle images are scored using the Heckmatt scale (score 1-4):

• Heckmatt grade 1 represents a normal muscle image.
• Heckmatt grade 2 shows an increased echogenicity without attenuation of the deeper image regions.
• Heckmatt grade 3 indicates a larger increase in echogenicity with some visible loss of normal muscle architecture.
• Heckmatt grade 4 shows a strongly increased echogenicity with complete loss of recognizable muscle architecture.

The CHOP-INTEND assesses a child's ability to move their body in a lying down position, supported sitting, and assisted rolling through 16 items. Scores range from 0 to 64, with higher scores indicating better motor function.

Change in motor function assessed using age-appropriate validated motor scales and dependent on patient's ability.

This is a 37-item measure of infant developmental motor milestones that will be performed in participants aged 0-24months. Scores are interpreted in relation to optimality scores and cut-off scores for the participant's age. Higher scores represented higher function.

Change in motor function assessed using age-appropriate validated motor scales and dependent on patient's ability. PDMS-3 measures various motor abilities in young children. Four types of normative scores are yielded: age equivalents, percentile ranks, subtest scaled scores, and composite index scores. Higher scores indicate higher level of function.

Change in motor function assessed using age-appropriate validated motor scales and dependent on patient's ability. This motor function assessment consists of 32 items organized in three dimensions: standing position and transfers, axial and limb proximal motor function, and limb distal motor function. Total scores are given between 0-100, with 0 indicating severe functional impairment and 100 indicating no functional impairment.

Change in motor function assessed using age-appropriate validated motor scales and dependent on patient's ability. Scores in the NSAA scale range from 0 to 34, with higher scores indicating better motor function.

Change in upper limb function assessed using the Performance of Upper Limb (PUL) scale. Higher scores indicate better function.

Respiratory function will be assessed longitudinally using age-appropriate measures depending on patient ability. Respiratory status will include ventilatory support requirements (none, non-invasive ventilation, or invasive ventilation) and time on/off ventilator, when feasible. Forced vital capacity (FVC), expressed as percent predicted for age and sex, will be used when spirometry is possible.

Assessment of nutritional status over time through indicators such as feeding method (oral versus enteral feeding) and need for nutritional support. Swallowing status and dietary modifications will be recorded when applicable. Changes from baseline will be analyzed to evaluate nutritional progression and feeding outcomes.

Assessment of patient or caregiver-reported quality of life using validated questionnaires appropriate for age and functional status, including standardized health-related quality of life instruments (the Clinical Global Impression-Severity [CGI-S], the Clinical Global Impression-Change [CGI-C], Patient Global Impression of Change [PGI-C], and Patient Global Impression of Severity [PGI-S]). Total scores and domain-specific scores will be analyzed. Changes from baseline will be evaluated to assess perceived health status and daily functioning.