Hereditary and acquired myopathies

Abstract

Congenital myopathies (CMs) are rare heterogeneous neuromuscular disorders characterized by early-onset muscle weakness. They are distinguished from muscular dystrophies as the former are characterized by distinct developmental and morphologic abnormalities in skeletal muscle that may be observed on light and/or electron microscopy, while muscular dystrophy is characterized by progressive degeneration and destruction of muscle fibers [1]. The onset of CMs was traditionally regarded as occurring at birth or soon thereafter, hence the name [2]. However, there have been reports of patients with onset of muscle weakness and/or motor difficulties later in childhood or sometimes even in adulthood whose muscle tissue samples bear histological findings that meet criteria for various types of CMs. In addition, as the genetic etiologies of various subtypes are increasingly delineated, numerous patients with later-onset muscle disease have been found to have mutations in genes that were first associated with CMs. Thus, some patients with CMs may have later onset disease, belying the explicit suggestion of uniform congenital onset in the name. The nomenclature systems for various inherited diseases are being modified to take into account these new discoveries, and someday it is expected that the nomenclature of this category of disease will be modified. For example, autosomal recessive mutations of SCN4A (which encodes the α-subunit of the skeletal muscle voltage-gated Na+ channel (NaV1.4)) were identified in patients with severe congenital myopathy (CM) [3]. The CMs have traditionally been classified according to classic muscle histological features. This classification system has been supplemented in recent years with the description of causative mutations in various genes (Table 43.1).