The objective of this natural history study is to comprehensively characterize the disease progression and clinical features of nemaline myopathies. The study aims to establish a well-defined cohort of patients in Spain, enabling long-term follow-up and facilitating recruitment for future clinical trials.
Patients with a confirmed clinical and genetic diagnosis of MN (mutations in ACTA1, NEB, TPM2, TPM3, KBTBD13, CFL2, KLHL40, KLHL41, LMOD3, MYPN, TNNT1, TNNT3), or under discussion if they only have a compatible biopsy.
Signed informed consent by the patient or Legal Authority Responsible, and/or assent by the subject (in pediatric population).
None
Patients with a confirmed clinical and genetic diagnosis of MN (mutations in ACTA1, NEB, TPM2, TPM3, KBTBD13, CFL2, KLHL40, KLHL41, LMOD3, MYPN, TNNT1, TNNT3), or under discussion if they only have a compatible biopsy.
Cohort
Prospective
Muscle Ultrasound
Diagnostic testUltrasound guided evaluation of 28 muscles evaluated accross different body regions, assessed using the Heckmatt gradinf system (semiquantitative scale).
Motor function scales
Diagnostic testEvaluation of patients motor function using motor scales (CHOP-INTEND, MFM32, HINE-2, NSAA, PDSM-3, RFF, 10m walk, PUL)
Complete physical examination
Other interventionComplete physical evaluations including muscle power and goniometry measurements
Ventilatory/ respiratory, Cardiac and other support assessment
Other interventionAssessment of ventilatory, cardiac, nutritional, and other support needs
QOL assessment, Neuropsychological
Other interventionAssessment of quality of life
Digital Biomarkers
DeviceVideo/photos with the aim is to record actions such as lifting a glass, raising arms above the head, getting up from the floor or a chair, walking, or running, in order to later analyze in detail how these movements are performed.
Oromotor function and nutrition
Other interventionAssessment of bulbar funcionality: feeding devices, nutritional status.
Motor Milestone Assessments
Other interventionMotor milestones age of acquisition and loss (if applicable)
Observe changes in muscle echogenicity by muscle ultrasound.
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.
Observe natural history changes in motor function using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
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.
Observe natural history changes in motor function using the Hammersmith Infant Neurological Examination Section 2 (HINE-2)
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.
Observe natural history changes in Peabody Developmental Motor Scales (PDMS-3) Scale Score
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.
Observe the natural clinical progression in respiratory 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.
Observe changes in Nutritional Status
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.
Observe changes in Quality of Life
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.
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