Congenital Muscular Dystrophies and Myopathies: An Overview and Update David C. Schorling 1 Janbernd Kirschner 1 Carsten G. Bönnemann 2 1 Division of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg, Freiburg, Germany 2 Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States Neuropediatrics Address for correspondence David C. Schorling, MD, Division of Neuropaediatrics and Muscle Disorders, Faculty of Medicine, University of Freiburg Medical Center, Mathildenstrasse 1, 79106 Freiburg, Germany (e-mail: [email protected]). Introduction While the phenotypes of congenital muscular dystrophies (CMDs), characterized by congenital muscular weakness and dystrophic changes in muscle biopsy, and congenital myopathies (CMs) have first been described over 100 and 70 years ago, respectively, significant progress in the under- standing of pathophysiological mechanisms has been made in the past 20 years, first and foremost attributable to the substantial advances in genetic research. A variety of pro- teins that are involved in mediating muscular function have been identified since the discovery of dystrophin in 1987. 1 Mutations in many of the encoding genes have been detected to be causative for the variety of phenotypes within the groups of CMDs, CMs, and limb-girdle muscular dystrophies (LGMDs); in some cases, mutations in the same gene are responsible for a whole spectrum of clinical heterogeneous phenotypes of varying severity (as in lamin A/C, where variable forms of CMD have been described, as well as an adult-onset LGMD, or even more impressively in fukutin-related protein, where the clinical spectrum ranges from milder late-onset LGMD to very severe phenotype of Walker –Warburg’s syndrome (WWS) with structural cen- tral nervous system [CNS] involvement). Furthermore, there is substantial clinical overlap between phenotypes, as in the group of α-dystroglycanopathies, where the severe clinical phenotype of muscle–eye–brain (MEB) disease is most frequently caused by mutations in in POMGnT1, but can also be seen with mutations in FKRP , POMT2, POMT1, FKTN, and LARGE. Lastly, the possibilities of next-generation sequencing enabled characterization of new genetic sub- types prevalent only in a minority of patients and made the distinction of the different entities, which was already confusing 10 years ago, 2 even more complicated. In this review, we give an overview of the broad spectrum of clinical phenotypes of CMDs and CMs, outline similarities and diagnostic/therapeutical considerations, and summar- ize recent advances in research for selected diseases. Additionally, we comment on the expanding genetic and phenotypic overlap of previously separated clinical entities. Keywords ► congenital muscular dystrophies ► congenital myopathies Abstract With continuous deciphering of the genetic background of congenital muscular dystrophies and congenital myopathies, some of the historic classifications based on clinical phenotypes or histopathological similarities have become blurred. With a growing number of associated genes, the general understanding of these disorders is shifting to a more genotype-based classification. Furthermore, establishing of the right genetic diagnosis involves new aspects of clinical care and therapeutic considerations for gene-specific phenotypes and pathology. In this review, we give an overview of the wide spectrum of clinical phenotypes of congenital muscular dystrophies and con- genital myopathies, outline diagnostic considerations, and summarize recent advances in research for selected diseases. received June 7, 2017 accepted June 10, 2017 Issue Theme Neuromuscular Disorders in Children and Adolescents; Guest Editor: Rudolf Korinthenberg, MD. © Georg Thieme Verlag KG Stuttgart · New York DOI https://doi.org/ 10.1055/s-0037-1604154. ISSN 0174-304X. Review Article Downloaded by: Cornell. Copyrighted material.