Limb-girdle muscular dystrophies: Where next after six decades from the first proposal (Review)

Abstract

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of disorders, which has led to certain investigators disputing its rationality. The mutual feature of LGMD is limb-girdle affection. Magnetic resonance imaging (MRI), perioral skin biopsies, blood-based assays, reverse-protein arrays, proteomic analyses, gene chips and next generation sequencing are the leading diagnostic techniques for LGMD and gene, cell and pharmaceutical treatments are the mainstay therapies for these genetic disorders. Recently, more highlights have been shed on disease biomarkers to follow up disease progression and to monitor therapeutic responsiveness in future trials. In this study, we review LGMD from a variety of aspects, paying specific attention to newly evolving research, with the purpose of bringing this information into the clinical setting to aid the development of novel therapeutic strategies for this hereditary disease. In conclusion, substantial progress in our ability to diagnose and treat LGMD has been made in recent decades, however enhancing our understanding of the detailed pathophysiology of LGMD may enhance our ability to improve disease outcome in subsequent years.

Perceptions of the transition from receiving the diagnosis recessive limb-girdle muscular dystrophy to becoming in need of human support and using a wheelchair: an interview study

“…The diagnosis was perceived to be a relief as it helped to make sense of the symptoms and meant contact with healthcare professionals with knowledge about neuromuscular diseases. LGMD2 has previously been diagnosed by exclusion [22] and it was not until 1995 that more precise criteria for the diagnosis and the classification of different forms of LGMD2 based on genetics were established [23]. This means that some of the young adults in this study had their first symptoms before techniques to establish a precise diagnosis were available.…”

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients

“…S1). The dominant forms (LGMD1A to LGMD1G) are less common than the recessive forms, representing fewer than 10% of LGMD cases 1, 4. Defects in a wide variety of muscle‐related genes, including ones associated with severe congenital muscular dystrophy, are responsible for the 23 recessive forms (LGMD2A to LGMD2W) 1, 4, 5, 6.…”

“…The dominant forms (LGMD1A to LGMD1G) are less common than the recessive forms, representing fewer than 10% of LGMD cases 1, 4. Defects in a wide variety of muscle‐related genes, including ones associated with severe congenital muscular dystrophy, are responsible for the 23 recessive forms (LGMD2A to LGMD2W) 1, 4, 5, 6. Even though each of the individual LGMD subtypes is relatively rare, they are estimated to affect 1 in 14,500 to 1 in 123,000 individuals causing them to collectively affect many people (60,000 to 500,000 individuals) worldwide and is one of the most common muscular dystrophies 3…”

Concise Review: Mesoangioblast and Mesenchymal Stem Cell Therapy for Muscular Dystrophy: Progress, Challenges, and Future Directions

“…LGMD is a descriptive term applied to muscular dystrophies with a common pattern of weakness in the scapular, pelvic girdle, and trunk muscles that result from a mutation in up to 31 different loci in the genome, including genes encoding calpain 3, dysferlin, a-, b-, d-, or g-sarcoglycan, desmin, caveolin 3, and many others [2][3][4]. The LGMD incidence varies by region, but some prevalence rates have been as high as 5-15 per 100,000 individuals [4].…”