The unfolding spectrum of inherited distal myopathies

Abstract

Distal myopathies are a group of rare muscle diseases characterized by distal weakness at onset. Although acquired myopathies can occasionally present with distal weakness, the majority of distal myopathies have a genetic etiology. Their age of onset varies from early-childhood to late-adulthood while the predominant muscle weakness can affect calf, ankle dorsiflexor, or distal upper limb muscles. A spectrum of muscle pathological changes, varying from nonspecific myopathic changes to rimmed vacuoles to myofibrillar pathology to nuclei centralization, have been noted. Likewise, the underlying molecular defect is heterogeneous. In addition, there is emerging evidence that distal myopathies can result from defective proteins encoded by genes causative of neurogenic disorders, be manifestation of multisystem proteinopathies or the result of the altered interplay between different genes. In this review, we provide an overview on the clinical, electrophysiological, pathological, and molecular aspects of distal myopathies, focusing on the most recent developments in the field. Muscle Nerve, 2018.

Actininopathy: A new muscular dystrophy caused by ACTN2 dominant mutations

“…Distal myopathies, also called distal muscular dystrophies, are rare genetic diseases, characterized by predominant weakness in the feet and/or hands, due to dystrophic degeneration of distal muscles in the lower, and less frequently, upper extremities . Although >20 different genes have been identified so far, a large number of patients do not harbor mutations in previously known disease genes …”

A Promising Future for Stem-Cell-Based Therapies in Muscular Dystrophies—In Vitro and In Vivo Treatments to Boost Cellular Engraftment

“…The majority of distal myopathies are genetically determined, although acquired myopathies can occasionally manifest with distal weakness (e.g., sporadic inclusion body myositis, sarcoid myopathy, or focal myositis [52]). Mutations in many different genes encoding for proteins such as caveolin-3, dysferlin, α-actin-1, myotilin, desmin, and many others lead to distal muscular dystrophy (reviewed in Reference [53]). In both CMD and distal muscular dystrophy, palliative approaches address the alleviation of symptoms and there is no cure.…”

Myopathies with finger flexor weakness: Not only inclusion‐body myositis

“…Although the pathophysiological underpinnings of this phenomenon are poorly understood, the various patterns of muscle weakness can provide helpful clues regarding the identity of the underlying muscle disease. Myopathies most commonly affect proximal muscles but can also involve distal muscles at disease onset (distal myopathies), 1 or in the setting of more widespread weakness. Distal myopathies frequently cause weakness of foot dorsiflexor and finger extensor muscles 1 .…”

“…Myopathies most commonly affect proximal muscles but can also involve distal muscles at disease onset (distal myopathies), 1 or in the setting of more widespread weakness. Distal myopathies frequently cause weakness of foot dorsiflexor and finger extensor muscles 1 . Myopathies presenting with or eventually developing predominant finger flexor weakness are less numerous.…”