Seminars in Pediatric Neurology RSS feed: Current Issue. Seminars in Pediatric Neurology is a topical journal that focuses on subjects of current importance in the field of pediatric neurology. The journal is devoted to making the status of such topics and the results of new investigations readily available to the practicing physician. Seminars in Pediatric Neurology is of special interest to pediatric neurologists, pediatric neuropathologists, behavioral pediatricians, and neurologists who treat all ages. 2010 Topics , Volume 17, Issues 1-4 March Controversies in the Management of Headache in Children David Rothner, MD June Case Studies in Pediatric Neurology John B. Bodensteiner, MD September Status Epilepticus Kevin Chapman, MD December Recent Developments in Pharmacotherapuetics Jong M. Rho, MD http://www.sempedneurjnl.com/?rss=yesElsevier Inc.en © 2011 Elsevier Inc. All rights reserved. Seminars in Pediatric Neurology1071-9091184December 2011 © 2011 Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.sempedneurjnl.com/article/PIIS1071909111000866/abstract?rss=yesWhen, 5 years ago, I edited an earlier issue of Seminars in Pediatric Neurology, we updated our knowledge on hereditary childhood neuromuscular diseases, subsequent to a previous one, which, likewise, covered hereditary neuromuscular disorders in children. In 2006, I reported 11 gene loci known to contain mutations responsible for several congenital myopathies. Then, the group of congenital myopathies was only scantily discussed among the protein aggregate myopathies. This edited issue of Seminars in Pediatric Neurology, now comprising congenital myopathies as the sole subject, emphasizes our increased knowledge on the molecular background of congenital myopathies and addresses several groups of individual entities among the congenital myopathies. Furthermore, the number of gene loci, the mutations of which are associated with congenital myopathies, has now approached more than 20 (), and new congenital myopathies have been reported (). While in the last decade of the past century molecular investigations among the hereditary neuromuscular diseases focused on muscular dystrophies, the first decade of this new century may be remembered as the one in which molecular discoveries in the congenital myopathies dominated the nosography of hereditary neuromuscular diseases. Taken the vast recently emerged information on molecular aspects in congenital myopathies and their nosologic implication for individual congenital myopathies, the essential and early diagnostic approach to congenital myopathies, ie, history taking and clinical examination, will be discussed by Kathryn North.IntroductionHans H. Goebel10.1016/j.spen.2011.10.001Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0213215http://www.sempedneurjnl.com/article/PIIS1071909111000878/abstract?rss=yes In this issue of Seminars in Pediatric Neurology, each chapter will focus on the features and management of individual congenital myopathies. This introductory chapter will provide an overview of the clinical features that alert the clinician to the likely diagnosis of a congenital myopathy, and specific features on history and examination that are characteristic of a specific genetic subtype. Most congenital myopathies share a common pattern of clinical features, which makes it difficult to predict the genetic cause in a patient by clinical assessment alone. Although no single feature is specific for the congenital myopathies, the presence of this common pattern highlights patients in whom a muscle biopsy is likely to provide important diagnostic information. The diagnosis of a specific congenital myopathy should only be made when the defining morphologic feature is the predominant pathologic change, other possible causes have been excluded, and the clinical course is nonprogressive or only slowly progressive. Clinical Approach to the Diagnosis of Congenital MyopathiesKathryn N. North10.1016/j.spen.2011.10.002Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0216220http://www.sempedneurjnl.com/article/PIIS107190911100088X/abstract?rss=yes Congenital myopathies are a genetically heterogeneous group of early-onset myopathies classified according to the predominant histopathological findings in skeletal muscle. During the past years, considerable overlap between different pathological and genetic forms of congenital myopathies has been discovered. In contrast, the pattern of involved muscles seen on muscle imaging is often more specific, providing useful additional information in the differential diagnosis of these diseases. Therefore, muscle imaging can help to target the most appropriate genetic investigations. The aim of this review is to give a comprehensive up-to-date overview of the muscle imaging findings that have recently been described in different genetic congenital myopathies. Muscle Imaging in Congenital MyopathiesSusana Quijano-Roy, Robert Y. Carlier, Dirk Fischer10.1016/j.spen.2011.10.003Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0221229http://www.sempedneurjnl.com/article/PIIS1071909111000891/abstract?rss=yes Nemaline myopathy constitutes a continuous spectrum of primary skeletal muscle disorders named after the Greek word for thread, nema. The diagnosis is based on muscle weakness, combined with visualization of nemaline bodies on muscle biopsy. The patients' muscle weakness is usually generalized, but there may be a selective pattern of more pronounced weakness, and, most importantly, respiratory muscles may be especially weak. Histologically, additional features may coexist with the nemaline bodies. There are 7 known causative genes. The function of the most recently identified gene is unknown, but the other 6 encoded proteins are associated with the muscle thin filament. The 2 most common causes of nemaline myopathy are recessive mutations in nebulin and de novo dominant mutations in skeletal muscle α-actin. At least 1 further gene remains to be identified. Patient care is based on managing the clinical symptoms. Animal models are helping to gain insight into pathogenesis, and a variety of therapeutic approaches are being investigated. Nemaline MyopathiesCarina Wallgren-Pettersson, Caroline A. Sewry, Kristen J. Nowak, Nigel G. Laing10.1016/j.spen.2011.10.004Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0230238http://www.sempedneurjnl.com/article/PIIS1071909111000908/abstract?rss=yes The core myopathies, Central Core Disease and Multiminicore Disease, are heterogeneous congenital myopathies with the common defining histopathological feature of focally reduced oxidative enzyme activity (central cores, multiminicores). Mutations in the gene encoding for the skeletal muscle ryanodine (RyR1) receptor are the most common cause. Mutations in the selenoprotein N (SEPN1) gene cause a less common variant. Pathogenic mechanisms underlying dominant RYR1 mutations have been extensively characterized, whereas those associated with recessive RYR1 and SEPN1 mutations are emerging. Identifying a specific genetic defect from the histopathological diagnosis of a core myopathy is complex and ought to be informed by a combined appraisal of histopathological, clinical, and, increasingly, muscle magnetic resonance imaging data. The present review aims at giving an overview of the main genetic and clinicopathological findings, with a major emphasis on features likely to inform the diagnostic process, as well as current treatments and perspectives for future research. Core MyopathiesHeinz Jungbluth, Caroline A. Sewry, Francesco Muntoni10.1016/j.spen.2011.10.005Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0239249http://www.sempedneurjnl.com/article/PIIS107190911100091X/abstract?rss=yesCentronuclear myopathies (CNM) are inherited disorders characterized by a high incidence of nuclei usually placed in rows in the central part of the muscle fibers. Three main forms of CNM have been identified according to the mode of inheritance and clinical presentation: (1) the X-linked recessive form, also named myotubular myopathy, presenting as a severe prenatal or neonatal myopathy in the large majority of cases, caused by mutations in the MTM1 gene; (2) the classical autosomal dominant and sporadic forms, associated with mild, moderate, or severe phenotypes caused by mutations in the DNM2 gene; and (3) an autosomal recessive form presenting with severe and moderate phenotypes caused by mutations in BIN1 gene. The 3 CNM genes are involved in membrane remodeling and membrane trafficking, and impairment of these processes could be a common CNM pathomechanism. In addition, recent data gained in human biopsies or animal models highlighted a possible dysfunction of the T-tubule system in CNM.Centronuclear MyopathiesNorma B. Romero, Marc Bitoun10.1016/j.spen.2011.10.006Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0250256http://www.sempedneurjnl.com/article/PIIS1071909111000921/abstract?rss=yes During the past 2 years, considerable progress in the field of four and a half LIM domain protein 1 (FHL1)-related myopathies has led to the identification of a growing number of FHL1 mutations. This genetic progress has uncovered crucial pathophysiological concepts, thus redefining clinical phenotypes. Important new characterizations include 4 distinct human myopathies: reducing body myopathy, X-linked myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy, and scapuloperoneal myopathy. Additionally, FHL1 mutations have been discovered in rigid spine syndrome and in a single family with contractures, rigid spine, and cardiomyopathy. In this review, we focus on the clinical phenotypes, which we correlate with the novel genetic and histological findings encountered within FHL1-related myopathies. This correlation will frequently lead to a considerably expanded clinical spectrum associated with a given FHL1 mutation. Reducing Body Myopathy and Other FHL1-Related Muscular DisordersJoachim Schessl, Sarah Feldkirchner, Christiana Kubny, Benedikt Schoser10.1016/j.spen.2011.10.007Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0257263http://www.sempedneurjnl.com/article/PIIS1071909111000933/abstract?rss=yes Congenital fiber-type disproportion is a form of congenital myopathy that may be best viewed as a syndrome rather than as a formal diagnosis. The central histologic abnormality is that type 1 fibers are consistently smaller than type 2 fibers by at least 35%-40%. Care is needed in diagnosing patients, as this histologic abnormality can occur in other congenital myopathies and in other neuromuscular disorders. Many of the genetic causes have been identified. Careful surveillance of respiratory function is required in all patients until the specific genetic cause is known and advice can be individualized. Congenital Fiber-Type DisproportionNigel F. Clarke10.1016/j.spen.2011.10.008Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0264271http://www.sempedneurjnl.com/article/PIIS1071909111000945/abstract?rss=yes Protein aggregation in congenital myopathies may be encountered among different myofibrillar myopathies such as granulofilamentous myopathy, cytoplasmic body myopathy, or spheroid body myopathy, which are designated as αB crystallinopathy, desminopathy, and myotilinopathy, respectively, according to the respective mutant proteins. Caps in cap disease and reducing bodies in reducing body myopathy were disclosed to contain numerous proteins. The multitude of diverse proteins aggregating within muscle fibers suggests impaired extralysosomal degradation of proteins, a disturbance of catabolism. The lack of different proteins accruing, but the mutant ones at an early age of affected patients in actin filament aggregating myopathy (AFAM) and hyaline body myopathy (HBM), suggests defects in maturation of sarcomeres and failure to integrate the possible mutant proteins, sarcomeric actin and heavy chain myosin in AFAM and HBM, a disturbance of anabolic metabolism. Protein Aggregation in Congenital MyopathiesHans H. Goebel, Astrid Blaschek10.1016/j.spen.2011.10.009Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0272276http://www.sempedneurjnl.com/article/PIIS1071909111000957/abstract?rss=yes Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous neuromuscular disorders with onset at birth or in infancy in which the muscle biopsy is compatible with a dystrophic myopathy. In the past 10 years, knowledge of neuromuscular disorders has dramatically increased, particularly with the exponential boost of disclosing the genetic background of CMDs. This review will highlight the clinical description of the most important forms of CMD, paying particular attention to the main keys for diagnostic approach. The diagnosis of CMDs requires the concurrence of expertise in multiple specialties (neurology, morphology, genetics, neuroradiology) available in a few centers worldwide that have achieved sufficient experience with the different CMD subtypes. Currently, molecular diagnosis is of paramount importance not only for phenotype-genotype correlations, genetic and prenatal counseling, and prognosis and aspects of management, but also concerning the imminent availability of clinical trials and treatments. Congenital Muscular Dystrophies: A Brief ReviewEnrico Bertini, Adele D'Amico, Francesca Gualandi, Stefania Petrini10.1016/j.spen.2011.10.010Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0277288http://www.sempedneurjnl.com/article/PIIS1071909111001239/abstract?rss=yesAuthor-Subject Index10.1016/S1071-9091(11)00123-9Seminars in Pediatric Neurology 18, 4 (2011)2011-12-01Seminars in Pediatric Neurology2011-12-01184S1071-9091(11)X0005-0e1e7