Congenital myopathies

The concept of congenital myopathies (CMs) as a group of genetically determined muscle disorders originally relied on clinical and histopathologic/histochemical criteria, pioneered and developed by Magee and Shy¹ and by Dubowitz and Pearse.² Clinical criteria of hypotonia and weakness, usually manifesting from birth, together with a static or slowly progressive course, are enduring concepts despite the major advances of molecular genetics in this area. These clinical criteria, together with electrophysiologic and histopathologic assessments, remain valuable tools in the differentiation of CMs from other congenital neuromuscular disorders, such as muscular dystrophies, myasthenic syndromes, and metabolic myopathies as well as polyneuropathies and neuronopathies. Nevertheless, genetic and pathogenetic criteria have recently added a few late infantile and adult-onset variants to this group of disorders and occasionally have blurred the borders between CMs and congenital neuromuscular transmission defects.^3,4 The relative use of histopathologic/histochemical criteria has diminished as we have learned that CMs with similar histopathology may be caused by mutations in more than one gene, and that mutations in the same gene can result in different muscle pathologies.^5,6 More recently, muscle MRI has offered additional support in the preliminary diagnostic assessment of these conditions.^5–7