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.

Figure 1

World map with the most common LGMD forms represented in colors. Grey color indicates countries with no known cohort. In Spain, Italy, England, Turkey, Russia, China, Brazil and Australia, the most common type was calpainopathy. LGMD2I was more frequent than other forms in the Scandinavian Peninsula. However, dysferlinopathy was the most frequent in US, Japan and Mexico. In India, sarcoglycanopathies had the highest incidence, whereas in Finland, anoctaminopathy ranked the first (25%) amongst other forms.

Figure 2

Disease spectrum for rapid recall of LGMD subtypes. Note: green color represents slow progression, yellow color represents moderate progression, red color represents rapid progression and mixed color represents variable progression depending upon either type of the mutation or gender factor (see text).