52VP Muscle ultrasound as a potential biomarker in patients with LAMA2-related dystrophy under 6 years of age

LAMA2-related dystrophy (LAMA2-RD) is one of the most common forms of congenital muscular dystrophy (CMD). The severe phenotype, which manifests congenitally with muscle weakness and hypotonia, accounts for one-third of all CMD cases. Establishing disease-relevant biomarkers that can help monitor disease severity and progression beginning in infancy is crucial for clinical trial readiness. While muscle imaging remains a potential biomarker in CMDs, muscle MRI is not ideal given the requirement of sedation in infants and young children and its associated risks and discomfort. Muscle ultrasound (MUS) offers better sensitivity than MRI in capturing early muscle changes, does not require sedation, and can be performed conveniently at the bedside. However, MUS may reach a ceiling in reflecting fibroadipose muscle replacement relatively early in dystrophic muscle disorders. Here, we present findings from 27 muscle ultrasound studies performed in a cohort of 17 patients with LAMA2-RD (ages 5-71 months; males: 13; females: 4, 186 images total). The mean age at which examined muscle groups reached maximum echogenicity on the modified Heckmatt scale (grade 3, severely increased muscle echogenicity with loss of bone echo) was 34 months of age. Maximum echogenicity was demonstrated as early as 8 months for the hip adductors, hamstrings, and gastrocnemius, while certain proximal muscles of the upper extremities (triceps and deltoid) showed a persistence of bone echo in the majority of patients through 71 months of age. These results justify further investigation into MUS as a potential imaging biomarker for LAMA2-RD, particularly for the muscles of the proximal upper extremities. Overall, MUS remains an accessible, non-invasive way to monitor disease progression and may serve as an imaging biomarker to evaluate the potential efficacy of future therapies in very young patients with LAMA2-RD.