Characterization of the natural history of Italian LAMA2-RD patients and identification of novel disease biomarkers

Laminin-related muscular dystrophy (LAMA2-RD), previously known as merosin-deficient congenital muscular dystrophy- MDC1A, is a genetic disorder caused by mutations in the LAMA2 gene, encoding the alpha2 subunit of the laminin-211 protein. The clinical manifestations of LAMA2-RD range from severe, early-onset congenital muscular dystrophy, to a milder, childhood onset limb-girdle type muscular dystrophy. Despite its prevalence, there's a paucity of comprehensive studies on the natural history of the disease, especially focusing on adult patients and specific organ involvement like the heart or peripheral nervous system. Moreover, the lack of surrogate biomarkers to detect sub-clinical progression of muscle damage and/or response to treatment inpatients is a significant obstacle in view of incoming treatments. Our study aims to fill these gaps by describing the natural history of LAMA2-RD in a large cohort of Italian patients. Specifically, we aim to understand the prevalence and severity of cardiac involvement and correlate this with age and muscular phenotype; to explore the respiratory, nutritional, peripheral neuropathy, and cognitive impairment; to refine the classification of disease severity to improve clinical trial inclusion criteria; to investigate how quality of life is impacted and the transition to adulthood performed in this population; to collect biological samples for future research. This will be a comprehensive study involving 10 expert centers, combining retrospective and prospective data collection. Patients will undergo regular evaluations covering various aspects of the disease, including cardiac MRI in sub-population. We will analyse how different subgroups of LAMA2-RD patients are affected. Through this study, we aim to provide a detailed overview of LAMA2-RD in our country. By focusing on adult patients and specific organ complications like cardiac involvement, we hope to improve patient care and trial readiness.