Review: Limb-girdle muscular dystrophies (LGMDs) existing registries and natural history studies: Where do we stand?

Introduction: Limb-Girdle Muscular Dystrophies (LGMDs) are heterogeneous inherited disorders with no cure, including 29 recessive (LGMDR) and 5 dominant forms (LGMDD), characterized by proximal muscle weakness. Finding a cure for LGMD is difficult due to the their slow evolution for which comprehensive data collection through registries, network, and natural history studies is pivotal.

Methods: We conducted a review following PRISMA guidelines searching in PubMed, Scopus, and Web of Science for articles published between 2000-2025, focusing on LGMD registries, networks, and natural history studies. We included observational studies, cohort designs, and registry-based studies.

Results: Among 443 records, 38 studies were included, 10 registries, 4 networks, and 17 natural history studies respectively. Registries varied in scope, with many focused on specific LGMD subtypes. Natural history studies were predominantly subtype-specific, poorly linked to registries. Only 12 studies were connected to registries or networks, and most performed in Europe and North America.

Discussion: Registries, networks, and natural history studies showed considerable design variability, leading to challenges with data interoperability and underscoring the need for standardization. Despite regional coverage, low-income countries are underrepresented in the data. The limited linkage between natural history studies and registries presents a missed opportunity to leverage well-characterized cohorts. Many registries and networks remain unpublished, limiting available data for global research.

Conclusion: Registries are crucial, benefiting patients, clinicians, researchers, and industries. The scarcity of natural history studies hinders the development of centralized datasets. Standardizing registry design, improving data interoperability, and enhancing patient diversity are critical to boost LGMD research.