Authors: Hernan D. Gonorazky, Carsten G. Bӧnnemann, James J. Dowling
Congenital myopathies are a clinically and genetically heterogeneous group of conditions that most commonly present at or around the time of birth with hypotonia, muscle weakness, and (often) respiratory distress. Historically, this group of disorders has been subclassified based on muscle histopathologic characteristics. There has been an explosion of gene discovery, and there are now at least 32 different genetic causes of disease. With this increased understanding of the genetic basis of disease has come the knowledge that the mutations in congenital myopathy genes can present with a wide variety of clinical phenotypes and can result in a broad spectrum of histopathologic findings on muscle biopsy. In addition, mutations in several genes can share the same histopathologic features. The identification of new genes and interpretation of different pathomechanisms at a molecular level has helped us to understand the clinical and histopathologic similarities that this group of disorders shares. In this review, we highlight the genetic understanding for each subtype, its pathogenesis, and the future key issues in congenital myopathies.