Hereditary myotonia in American Bulldog associated with a novel frameshift mutation in the CLCN1 gene
Myotonia is a clinical sign resulting from delayed relaxation of skeletal muscles after voluntary contraction and electrical or mechanical stimulation [1]. Hereditary myotonia (HM) is the main disease resulting from dysfunction of the chloride channel CLC-1 [2]. Clinically, HM is characterized by the appearance of myotonia after the onset of movement and tends to improve after repeated movement, a phenomenon known as "warm-up". The development of muscle hypertrophy is observed in most patients. HM results from mutations in the CLCN1 gene, which encodes the selective channel for chloride ions in skeletal muscle ti...
Source: Neuromuscular Disorders - October 24, 2020 Category: Neurology Authors: Daiane de Jesus Rodrigues, Adilson Donizeti Damasceno, C ésar Erineudo Tavares de Araújo, Sandra Regina Torelli, Luine Gabriela Hilário Fonseca, Diego José Zanzarini Delfiol, José Paes de Oliveira-Filho, João Pessoa Araújo, Alexandre Secorun Borges Source Type: research

Clinical and molecular evidence of possible true digenic inheritance for mfn2/gdap1 genes in charcot-marie-tooth disease
Charcot-Marie-Tooth disease (CMT) has an extensive molecular basis and is characterized by a progressive motor and sensory polyneuropathy, either of demyelinating, axonal or intermediate type [1]. The mitofusin 2 (MFN2) gene encodes a key protein involved in the mitochondrial fusion process [2] and energy metabolism [3], its pathogenic variants are associated with CMT of autosomal dominant (AD) inheritance, although autosomal recessive (AR) cases have been described [4,5]. The GDAP1 gene codes for the ganglioside-induced differentiation associated protein 1, which is also involved in the mitochondrial dynamics and bioenerg...
Source: Neuromuscular Disorders - October 19, 2020 Category: Neurology Authors: Ren ée Barreda Fierro, Patricia Herrera Mora, Juan Carlos Zenteno, Camilo E. Villarroel Cortés Tags: Case report Source Type: research

Impact of a national population-based carrier-screening program on spinal muscular atrophy births
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by progressive muscle atrophy and weakness. It is the most common genetic neurodegenerative disease, leading to infant death due to respiratory insufficiency. The estimated incidence is 1 in 11,000 births, and the carrier frequency is 1 in 40 to 1 in 67 people [1]. The time of onset ranges from the intrauterine period to adolescence or young adulthood. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 19, 2020 Category: Neurology Authors: Sharon Aharoni, Yoram Nevo, Naama Orenstein, Lina Basel-Salmon, Shay Ben-Shachar, Huda Mussaffi, Lena Sagi-Dain, Rony Cohen, Amihood Singer Source Type: research

Adolph Seeligm üller's contribution to myotonia congenita Thomsen
The papers by Thomsen and Seeligm üller were not the first studies describing the symptoms of the disease later called myotonia congenita. This has already been mentioned by Thomsen himself in 1876 and later by Strümpell in 1881 [1, 3]. Seeligmüller also reported earlier descriptions of “muscle tension” by Benedict [2, 4]. In the introduction of his paper Thomsen quoted Charles Bell (1774-1842) [1]. In his opinion Bell has found an “approximate” description of symptoms of a nearly similar disease to the one Thomsen described in more detail in his paper [1]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 19, 2020 Category: Neurology Authors: Carolin Arendt, Stephan Zierz Tags: Historical article Source Type: research

Presynaptic congenital myasthenic syndrome due to three novel mutations in SLC5A7 encoding the sodium-dependent high-affinity choline transporter
Congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited neuromuscular disorders caused by mutations in genes encoding proteins that are essential for neuromuscular transmission. There are currently more than 30 subtypes of CMS and they can be classified according to the location of the encoded protein into presynaptic, synaptic and postsynaptic disorders [1]. Until recently, most of the CMS described were postsynaptic in origin with a few being located to the synaptic space or the presynaptic terminal. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 19, 2020 Category: Neurology Authors: Pedro M Rodr íguez Cruz, Imelda Hughes, Adnan Manzur, Pinki Munot, Sithara Ramdas, Ronnie Wright, Catherine Breen, Mathew Pitt, Alistair T. Pagnamenta, Jenny C. Taylor, OxClin WGS, Jacqueline Palace, David Beeson Source Type: research

Gene Therapy in Duchenne muscular dystrophy: Identifying and preparing for the challenges ahead
There is considerable interest, excitement and anticipation for the development of adeno-associated virus (AAV) gene-therapy as a treatment for Duchenne muscular dystrophy (DMD). Much of this expectation is based on promising pre-clinical data as well as success in other neuromuscular conditions, such as spinal muscular atrophy (SMA). However, it is also important to take an objective view of the realistic possibilities and limitations of AAV gene-therapy for DMD as well as considering the likely barriers to clinical trials and the development of gene-therapy as an approved and accessible treatment. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 15, 2020 Category: Neurology Authors: Emma Heslop, Cathy Turner, Anna Irvin, Francesco Muntoni, Volker Straub, Michela Guglieri, workshop participants Tags: Workshop report Source Type: research

Electrophysiological study of neuromuscular junction in congenital myasthenic syndromes, congenital myopathies, and chronic progressive external ophthalmoplegia
Congenital myasthenic syndrome (CMS) comprises inherited diseases in which the safety margin of neuromuscular transmission is impaired [1]. It is characterized by fatigue and fluctuating or fixed weakness in extraocular, facial, bulbar, truncal, respiratory, or limb muscles [1,2]. Weakness typically begins in young children but can also appear in teens or adults. The clinical severity of CMS ranges from mild to disabling weakness, sometimes with respiratory insufficiency and premature death [2,3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 13, 2020 Category: Neurology Authors: Vitor Marques Caldas, Carlos Otto Heise, Jo ão Aris Kouyoumdjian, Antônio Alberto Zambon, André Macedo Serafim Silva, Eduardo de Paula Estephan, Edmar Zanoteli Source Type: research

Tasks and interfaces in primary and specialized palliative care for Duchenne muscular dystrophy – a patients’ perspective.
In the last two decades, advances in pediatric medicine have led to significantly higher survival rates in children with chronic life-limiting conditions. The prolonged life expectancies introduce new challenges for families and caregivers since the increased survival rates are associated with new morbidities, diverse psychosocial requirements and the need for novel concepts of care and quality of life. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 3, 2020 Category: Neurology Authors: Maria Janisch, Kristin Boehme, Simone Thiele, Annette Bock, Janbernd Kirschner, Ulrike Schara, Maggie C. Walter, Silke Nolte-Buchholtz, Maja von der Hagen Source Type: research

Homozygous intronic variants in TPM2 cause recessively inherited Escobar variant of multiple pterygium syndrome and congenital myopathy
Tropomyosins are regulatory proteins located on the thin muscle filaments. They stabilise the thin filaments and control muscle contraction. Four distinct genes, TPM1, TPM2, TPM3 and TPM4, express different isoforms of tropomyosin at a level that varies depending on muscle and fibre type. TPM2, located at 9p13.3, encodes beta-tropomyosin. This gene consists of 9 exons and expresses four isoforms (TPM2.1, TPM2.2, TPM2.3, TPM2.4) through alternative splicing [1]. TPM2 expression is enriched in slow type 1 striated muscle fibres, although, it is expressed in all muscles of the body. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2020 Category: Neurology Authors: Schaida Schirwani, Anna Sarkozy, Rahul Phadke, Anne-Marie Childs, Rachael Mein, Azzam Ismail, Audrey Smith, Francesco Muntoni, Hobson Emma, Karen Pysden Source Type: research

Editorial Board
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2020 Category: Neurology Source Type: research

Author index
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Source Type: research

New genes in neuromuscular diseases
Distal myopathies are a clinically, histopathologically and genetically heterogeneous group of inherited skeletal muscle diseases with muscle weakness predominantly observed in the distal muscles. Despite advancements in high throughput sequencing, a number of patients remain without a molecular diagnosis. Especially sporadic distal myopathy cases, often due to lack of additional family history, usually cannot progress beyond candidate gene approaches. Taking advantage of deep phenotyping and histopathological evidence, we have identified the small muscle protein X gene (SMPX) as a novel disease gene causing the first X-li...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Johari, M. Savarese, A. Vihola, M. Jokela, A. Torella, G. Piluso, P. Jonson, H. Luque, A. Magot, F. Magri, C. Kornblum, T. Stojkovic, N. Romero, P. Lahermo, K. Donner, V. Nigro, P. Hackman, B. Udd Source Type: research

New genes in neuromuscular diseases
DnaJ homolog, subfamily B, member 4 (DNAJB4) is a member of the heat shock protein 40 chaperone family, and it is highly expressed in striated muscles. Although DNAJB6 is known to cause LGMDD1, no human disease related to DNAJB4 has been reported so far. Here, we report one family including six affected individuals. The initial symptom was hand grip weakness from around 30 years of age, then they developed lower limb weakness from their 40 ’s. Muscle imaging showed a characteristic pattern of involvement with rectus femoris and hamstrings affected. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Inoue, A. Iida, K. Watanabe, Y. Hosoi, H. Miyajima, S. Hayashi, Y. Inoue, T. Inoue, S. Noguchi, I. Nishino Source Type: research

New genes in neuromuscular diseases
Malignant hyperthermia (MH) and Exertional Heat Stroke (EHS) present hypermetabolic states leading to rhabdomyolysis and muscle rigidity with progressive hyperthermia; MH is triggered by volatile inhaled anesthetics, while EHS is triggered by exercise in hot/humid environment. Given the similarity of clinical features and the fact that a portion of EHS cases were diagnosed as MH susceptible by the in vitro contracture test, MH and EHS are believed to share common etiology. Mutations in RYR1 and CACNA1S have been found to be associated with MH; however the genetic cause remains to be identified in approximately 30% of MH ca...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: Y. Endo, L. Groom, N. Kraeva, A. Celic, P. Hopkins, S. Riazi, R. Dirksen, J. Dowling Source Type: research

New genes in neuromuscular diseases
Disrupting pathogenic variants in RNA-binding proteins such as TDP-43, hnRNPA2B1, FUS, TIA-1 are known to cause a spectrum of diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, inclusion body myopathy, and/or distal myopathy. Using deep clinical phenotyping and exome sequencing, we identified six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: P. Mohassel, S. Donkervoort, H. Kim, A. Foley, X. Lornage, hnRNPA2B1 Study Group, N. Foulds, S. Hammans, T. Haack, J. B öhm, M. Tarnopolsky, V. Straub, J. Laporte, F. Muntoni, J. Taylor, C. Bönnemann Source Type: research

OMICs AND AI APPROACHES FOR MUSCLE DISEASES
Joint contractures are recurrent and sometimes prominent features in neuromuscular disorders, most notably in extracellular matrix (ECM)-related myopathies, such as COL6-related disorders (COL6-RD). Here, we report a patient with an atypical clinical presentation of congenital arthrogryposis, associated with distal hyperlaxity, proximal muscle deficit, dysphonia, dysphagia, mild ptosis and preserved respiratory function. At age 15, a COL6-RD was evoked and immunostaining of cutaneous fibroblasts from the patient revealed a subtle impairment of COLVI secretion; however, no mutation in the COL6A1-3 genes was identified. (Sou...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. Cohen, I. Nelson, C. Gartioux, M. Beuvin, Z. Mezdari, F. Roth, R. Ben Yaou, S. Quijano-Roy, T. Stojkovic, R. Carlier, G. Bonne, V. Allamand Source Type: research

OMICs AND AI APPROACHES FOR MUSCLE DISEASES
Molecular genetic analysis of large genes is demanding although high-throughput sequencing (HTS) has facilitated the task immensely. Ultra-rare or novel missense variants in large genes such as nebulin and titin are very common in the general population, which makes variant interpretation difficult in sporadic cases. The interpretation of rare heterozygous variants is especially difficult when samples from family members are lacking and thus, segregation analysis is not possible. Short-read HTS collapses a diploid genome to a single sequence, but the linked-read technology provides phase information of continuous DNA fragm...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Lehtonen, M. Johari, H. Almusa, A. Lehesjoki, K. Wartiovaara, J. Saarela, P. Hackman, C. Wallgren-Pettersson, B. Udd, V. Lehtokari, K. Pelin, M. Savarese Source Type: research

OMICs AND AI APPROACHES FOR MUSCLE DISEASES
Dermatomyositis (DM) is a rare and systemic autoimmune disease belonging to the idiopathic inflammatory myopathies, primarily affecting skeletal muscle and skin. However, other organs might be affected, like the lung, heart or arteries, and development of cancer might also be associated with DM. For diagnostic and prognostic management, the detection of one of the associated autoantibodies (aAB, e.g. Mi-2, NXP-2, MDA5 TIF1 γ and rarely SAE) is of outmost importance, since associations between these antibodies and interstitial lung disease (ILD) or cancer (e.g. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: C. Preusse, A. Ross, D. Hathazi, A. Hentschel, H. Goebel, W. Stenzel Source Type: research

OMICs AND AI APPROACHES FOR MUSCLE DISEASES
This study aims to establish the algorithm to assist muscle pathology diagnosis using deep convolutional neural networks (CNNs), which can differentiate major muscle diseases only by hematoxylin and eosin (H&E)-stained pathological images. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: Y. Kabeya, M. Okubo, S. Yonezawa, H. Nakano, M. Inoue, M. Ogasawara, Y. Saito, J. Tanboon, L. Indrawati, T. Kumutpongpanich, Y. Chen, R. Tokumasu, T. Iwamori, A. Takano, I. Nishino Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Pompe disease is a genetic neuromuscular disorder caused by loss of acid alpha-glucosidase (GAA) expression, leading to glycogen accumulation, muscle tissue degeneration, progressive muscle weakness and cardiac insufficiency. Enzyme replacement therapy (ERT) is currently the only approved treatment for Pompe. Uptake of circulating, synthetic GAA by the muscle tissue is limited, however, with corresponding impacts on efficacy of ERT. AT845 is an investigational, AAV-based gene therapy designed to reconstitute human GAA synthesis and activity directly in skeletal muscles and heart. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Eggers, C. Vannoy, J. Huang, P. Purushottoman, J. Brassard, J. Gray, M. Lawlor, C. Sadhu, F. Mavilio Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Long-term safety/efficacy of avalglucosidase alfa is being assessed in LOPD in NEO-EXT (NCT02032524), an ongoing NEO1 (NCT01898364) extension. NEO1 patients (pts), treatment-na ïve (Naïve, n=10) or had received alglucosidase alfa for ≥9mo (Switch, n=14), received avalglucosidase alfa (5, 10, or 20 mg/kg qow) for 6mo; 8 Naïve/11 Switch pts then entered NEO-EXT, continuing their NEO1 dose until switched to 20 mg/kg qow in 2016. Avalglucosidase alfa was generally well-to lerated; the safety profile in NEO-EXT was consistent with NEO1. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: B. Schoser, R. Barohn, B. Byrne, O. Goker-Alpan, P. Kishnani, S. Ladha, P. Laforet, E. Mengel, L. Pena, S. Sacconi, V. Straub, J. Trivedi, P. Van Damme, A. van der Ploeg, J. Vissing, P. Young, K. Haack, I. Ivanina, Y. Wang, M. Dimachkie Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Enzyme replacement therapy (ERT) has substantially improved the prognosis in classic-infantile Pompe patients. Different dosing regimens have been reported in the literature, but no study comparing the effects of different dosing regimens in a larger cohort of classic-infantile Pompe patients has been published. The aim of this study was to obtain an overview of dosing regimens and treatment outcome within the European Pompe Consortium (EPOC). A retrospective, multicentre study was conducted, including 116 confirmed classic-infantile patients treated with ERT from France, Germany, Italy and the Netherlands. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: I. Ditters, H. Huidekoper, M. Kruijshaar, A. Hahn, T. Mongini, F. Labarthe, M. Tardieu, J. van den Hout, A. van der Ploeg Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Pompe disease is caused by mutations of the acid α-glucosidase gene (GAA) that result in reduced activity of the lysosomal enzyme GAA. Pompe disease can be divided into infantile-onset (IOPD) and late-onset (LOPD) type. Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). This is a ret rospective observational study of 4 patients with IOPD that have been followed up for 10 years. All the patients presented at the neonatal period severe hypotonia and hypertrophic myocardiopathy. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: C. Ortez, L. Carrera, J. Exposito, D. Natera, S. Zambudio, J. Colomer, A. Baz án, A. Pareja, E. Bobadilla, V. Sáez, J. Medina, C. Jou, A. Codina, J. Corbera, D. Yubero, L. Martorell, C. Jimenez-Mallebrera, A. Nascimento Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
First longitudinal studies showed that enzyme replacement therapy (ERT) effects in late-onset Pompe disease (LOPD) seem to peak at 2-3 y often followed by a secondary decline. We aimed to examine long-term ERT effects in an elderly cohort of LOPD. Main inclusion criteria were age at diagnosis and onset of ERT> 50 y and ERT duration> 7 y. Outcome parameters included MRC sum-score (% of max.), 6-minute walk test 6MWT (% predicted), Quick Motor Function Test QMFT (% of max.), forced vital capacity FVC sitting and supine (% predicted), CK levels, and IgG antibody titers against alglucidase alfa. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Winkler, C. von Landenberg, K. Kuchenbecker, J. Reimann, C. Kornblum Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Pompe disease (PD), a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and resulting accumulation of lysosomal glycogen, presents as a broad clinical spectrum. In late-onset PD (LOPD), signs/symptoms present at any age and without the cardiomyopathy seen in infantile-onset PD. Progressive respiratory function loss due to weakened diaphragm and resp iratory muscles leads to considerable morbidity and early mortality. Avalglucosidase alfa is an investigational enzyme replacement therapy designed for enhanced receptor targeting and enzyme uptake, aimed at increased glycogen clear...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: P. Clemens, The  COMET Study Group, The COMET Study Group Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
The elucidation of pathomechanisms leading to the manifestation of neuromuscular diseases represents an important step toward the molecular understanding of the respective disease and might help to define starting points for therapeutic intervention concepts. Very often these studies are limited by the availability of human biomaterial especially regarding the fact that nowadays muscle and nerve biopsies become less common in the diagnostic work-up. To systematically analyse if fibroblasts might serve as a valuable source of biomaterial toward functional studies of neuromuscular diseases, utilizing liquid chromatography co...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: A. Hentschel, O. Pogoryelova, A. Sickmann, U. Schara, H. Lochm üller, A. Roos Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Chloroquine (CQ) and hydroxychloroquine (HCQ) are used in the treatment of malaria and various connective tissue diseases (CTD). They have been associated with muscle toxicity, mostly described as a proximal myopathy with evidence of lysosomal dysfunction on muscle biopsy. As patients with CTD may have muscle weakness due to myositis or steroid myopathy, the diagnosis can be missed or delayed. In this retrospective study, we aimed to define the clinical phenotype, laboratory features and treatment outcomes of CQ/HCQ-myopathy. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. Naddaf, P. Pritikanta Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
The phenotypic spectrum associated with autosomal dominant SPTAN1 variants has evolved since the initial 2008 description of infantile epileptic encephalopathy due to non-truncating mutations. Loss of function variants were reported in association with a central nervous system phenotype without epilepsy in 2018, and with a juvenile onset hereditary motor neuropathy in 2019. Here we report novel SPTAN1 variants in two patients seen in our clinic. The first presented at 9 years old with a history of mild motor and cognitive delays, dysmorphic features and abnormal gait. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: A. Meyer, W. Arnold, M. Waldrop, K. Flanigan Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
In Pompe disease (glycogen storage disease type II), the lysosomal α-glucosidase deficiency leads to pathological glycogen accumulation in muscle, but also in other tissues such as the peripheral nervous system. Since chronic pain has been reported in late onset Pompe disease (LOPD), we aimed to investigate the pain characteristics and whether small fiber affectio n may play a role in the mediation of pain. 32 patients with LOPD under enzyme replacement therapy (56% females; age 52.8 ±13.5 years, with duration from Pompe symptom onset 15.94± 10.19 years) were enrolled. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. Enax- Krumova, J. G örlach, A. Rosenbohm, K. Claeys, F. Montagnese, I. Schneider, D. Sturm, T. Nicoletto, T. Fangerau, A. Roth, J. Wanschitz, W. Löscher, A. Güttsches, S. Vielhaber, L. Zunk, H. Krämer-Best, B. Schoser, A. Hahn, A. Schänzer Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
We have identified four patients with a childhood/adolescence onset of a myopathy from two unrelated consanguineous families. The patients have a wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures as characteristic features. All patients showed increased levels of serum creatine kinase but no or minor muscle weakness. Mild cardiac manifestations were observed. Light and electron microscopical investigations revealed a structural myopathy with numerous lobulated muscle fibers and considerable myofibrillar alterations with a coarse and irregular intermyofibrillar network. (Sou...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: C. Hedberg-Oldfors, Supervillin Study Group, Supervillin Study Group Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
A subgroup of autophagic vacuolar myopathies (AVMs) is characterized by unusual autophagic vacuoles with sarcolemmal features (AVSFs) and includes Danon disease and X-linked myopathy with excessive autophagy (XMEA). We suggest referring to this subgroup as ‘AVSF myopathy’ as a new clinical entity. However, the features of AVSF myopathy have not been well established. Therefore, to evaluate the clinical features, we reviewed the clinical histories, muscle specimens, and genetic analyses of Japanese patients with AVSF myopathy. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: K. Sugie, H. Komaki, T. Kurashige, D. Kaneda, N. Eura, T. Shiota, Y. Nishimori, N. Iguchi, H. Nanaura, T. Kiriyama, E. Mori, I. Nonaka, I. Nishino Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Immune-mediated necrotizing myopathy (IMNM) belongs to the group of idopathic inflammatory myopathies. Affected patients present with severe proximal lower-limb-predominant muscle weakness and strong elevation of the creatine kinase. The presence of anti-HMGCR- or anti-SRP- autoantibodies or the absence of known myositis specific antibodies is diagnostically essential and divides IMNM into three subgroups. Treatment with immune modulators can be effective, but escalation of therapy is often necessary. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: N. Fischer, C. Preusse, Y. Allenbach, O. Benveniste, A. Roos, H. Goebel, W. Stenzel Source Type: research

Autophagic myopathies / myofibrillar myopathies / distal myopathies / pompe disease
Pompe disease (PD) is an autosomal recessive glycogen storage disease due to deficiency of acid alpha-glucosidase (GAA). As enzyme replacement therapy is available, any patient should not be overlooked. However, late-onset PD (LOPD) cases can often clinically show nonspecific limb-girdle phenotype and sometimes pathologically lack pathognomonic vacuolar changes. Although we have reported acid-phosphatase-positive globular inclusion in myofibers as a diagnostic marker, still PD cases may be overlooked on routine muscle pathology diagnosis as the inclusion may not always be obvious. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: Y. Saito, K. Nakamura, T. Fukuda, H. Sugie, S. Hayashi, S. Noguchi, I. Nishino Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy type 6 (NEM6) is a rare congenital myopathy characterized by muscle weakness, exercise intolerance and muscle slowness, linked to autosomal dominant KBTBD13 gene mutations. Mutated KBTBD13 interacts improperly with thin filaments/actin provoking impaired muscle-relaxation kinetics. We performed a deep muscle phenotyping including immunohistochemistry and electron microscopy in 18 muscle biopsies of Dutch NEM6 patients in order to correlate muscle morphology with clinical phenotype and pathophysiological mechanisms. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: K. Bouman, B. K üsters, J. De Winter, C. Gllet, E. Van Kleef, L. Eshuis, G. Brochier, A. Madelaine, C. Labasse, C. Boulogne, B. Van Engelen, C. Ottenheijm, M. Olive, N. Romero, N. Voermans, E. Malfatti Source Type: research

Congenital myopathies 1 – nemaline
Actinopathies are congenital myopathies resulting from mutations in the ACTA1 gene encoding skeletal α-actin. ACTA1 mutations are the etiology for 15-30% of nemaline myopathies and approximately 50% of severe cases. The phenotypic spectrum is wide, with the most severely affected patients presenting with evidence of prenatal onset of disease and mildly affected subjects presenting first symptoms i n adulthood. This retrospective study of patients with causative mutations in the ACTA1 gene was performed at a single center. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: A. Foley, S. Ferranti, D. Saade, P. Mohassel, S. Donkervoort, L. Medne, J. Dastgir, D. Bharucha-Goebel, K. Meilleur, M. Leach, M. Scavina, S. Yum, G. Tennekoon, C. B önnemann Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy (NM) is a genetically and clinically heterogenous neuromuscular disorder that can cause death or lifelong disability. Essentially all genes associated with NM are related to the sarcomeric thin filament. Therefore, studies of weakness in NM have focused primarily on issues of skeletal muscle structure and contractility. However, the genetic variability seen does not explain the significant phenotypic heterogeneity observed in NM patients or mouse models, suggesting that additional factors determine disease phenotype. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Tinklenberg, R. Slick, J. Sutton, M. Prom, E. Ott, S. Danielson, M. Vanden Avond, M. Beatka, H. Meng, M. Grzybowski, J. Heisner, J. Ross, J. Ochala, K. Nowak, L. Zhang, A. Geurts, D. Stowe, F. Montanaro, M. Lawlor Source Type: research

Congenital myopathies 1 – nemaline
Ovine congenital progressive muscular dystrophy (OCPMD) was first described in Merino sheep flocks in Queensland and Western Australia (WA) in the 1960s and 70s. The most prominent feature of the disease is a distinctive gait with stiffness of the hind limbs that can be seen as early as three weeks after birth. The disease is progressive. Histopathological examination had revealed dystrophic changes specifically in slow myofibres, while electron microscopy had demonstrated abundant nemaline bodies. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Clayton, E. McNamara, H. Goullee, S. Conijn, K. Muthsam, G. Musk, D. Coote, J. Kijas, A. Testa, R. Taylor, M. O'Hara, D. Groth, C. Ottenheijm, G. Ravenscroft, N. Laing, K. Nowak Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy (NM) is a genetically and clinically heterogeneous disease that is diagnosed based on the presence of nemaline rods on skeletal muscle biopsy. Despite multiple genes and known mutations, the genetic heterogeneity of NM is not predictive of disease course, which suggests that unidentified secondary mechanisms exist that impact disease severity. We hypothesize that currently undetermined biological processes play a role in the muscle weakness of NM patients and that these can be revealed by examining disease signatures of NM mouse models. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: R. Slick, J. Tinklenberg, H. Meng, M. Beatka, M. Prom, E. Ott, F. Montanaro, L. Zhang, H. Granzier, E. Hardeman, A. Geurts, M. Lawlor Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy (NM) constitutes a clinically and genetically heterogeneous spectrum of muscle disorders. Until very recently, little or no scientific attention has been paid to the lived experience and functioning of people with neuromuscular disorders. The same is true for the impact of eating and nutrition on the daily life of these patients. Persons with NM often have weakness of the facial and bulbar muscles and secondary structural abnormalities of the oral region, complicating eating and swallowing, and likely affecting their nutritional state. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: V. Lehtokari, M. Tammepuu, M. Simil ä, S. Strang-Karlsson, S. Hiekkala, C. Wallgren-Pettersson Source Type: research

Congenital myopathies 1 – nemaline
Respiratory failure can be the initial presenting feature and is the most common cause of death in patients with nemaline myopathy. Surprisingly, data on respiratory muscle weakness, specifically diaphragm function, is scarce in these patients. Therefore, we performed a comprehensive characterization of respiratory muscle function, including diaphragm function, in patients with different nemaline myopathy mutations. We recruited children and adults with genetically confirmed nemaline myopathy with different mutations in the Netherlands. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. van Kleef, C. Ottenheijm, M. Gaytant, W. de Weerd, B. Vosse, B. van Engelen, N. Voermans, J. Doorduin Source Type: research

Congenital myopathies 1 – nemaline
Congenital myopathies are a heterogeneous group of hereditary primary muscle disorders that are present from birth, although their onset may be delayed until later in infancy or early childhood. The most common of these rare disorders are nemaline myopathy, central core disease, centronuclear (myotubular) myopathies, and congenital fiber type disproportion. Among them, nemaline myopathy, a rare congenital myopathy, is characterized by generalized muscle weakness, respiratory insufficiency, and the presence of rod structures on muscle biopsy, which is caused by mutations in at least 13 known genes. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: J. Lee, H. Park, Y. Choi Source Type: research

Congenital myopathies 1 – nemaline
We report the case of a 6 yo boy, born from consanguineous parents with typical phenotypic presentation for nemaline myopathy, proven on muscle biopsy. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: N. Chrestian, N. Laflamme, Y. Labrie, N. Rioux, M. Dugas, S. Rivest, B. Lace Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathies (NM) are clinically and genetically heterogeneous muscle disorders characterized by the presence of nemaline rods on muscle biopsies. Depending on the causative gene and the type of mutation, the clinical presentation of affected individuals can range from severe prenatal and neonatal muscle weakness with poor prognosis to milder childhood and adult-onset forms. Despite the discovery of 13 causative NM genes, a significant number of patients still await for molecular diagnosis. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: X. Lornage, H. Amthor, S. Quijano-Roy, R. Carlier, N. Monnier, N. Romero, J. Laporte, J. B öhm Source Type: research

Congenital myopathies 1 – nemaline
Inherited nemaline myopathies (iNM) are a genetically heterogeneous group of disorders characterized by accumulation of Z-disc derived nemaline rods in muscle fibres and presenting from infancy to adulthood. Nemaline rods are also a pathological feature of sporadic late onset nemaline myopathy (SLONM), an acquired myopathy sometimes associated with monoclonal gammopathies or HIV infection. We sought to identify pathological parameters distinguishing these two myopathies. This distinction has significant implications, as SLONM may respond to pharmacological therapy. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: S. Nicolau, A. Dasgupta, D. Selcen, A. Engel, J. Doles, M. Milone Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy is one of the most common congenital myopathies. The hallmarks of this disorder are early onset muscular weakness, hypotonia, pectus carinatum and rod-like inclusions in muscle cells. The severity spectrum of nemaline myopathy is broad, but early respiratory failure and death are the inevitable outcomes in most of the cases. Several gene mutations have been identified in nemaline myopathy, including a non-sense mutation in exon 11 of TNNT1 gene, encoding for the slow skeletal muscle isoform of troponin T (TnT), which results in selective atrophy of slow-twitch (type I) myofibers and in a unique form of Ne...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: E. D'Ambrosio, M. Sena-Esteves, H. GrayEdwards, M. Otero Source Type: research

Congenital myopathies 1 – nemaline
Nemaline myopathy (NM) is a non-dystrophic congenital myopathy which currently has no therapy. The gene Nebulin (NEB) accounts for 50% of all cases of NM, with most patients being compound heterozygous for two different mutations in NEB. Patients with NM have significantly reduced levels of nebulin. Nebulin is a giant protein that is mainly expressed in the skeletal muscle, specifically in the sarcomeres. Most of the protein consists of repetitive repeats that help nebulin bind to the thin filament. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: S. Viththiyapaskaran Source Type: research

Myasthenia & related disorders
Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of inherited disorders caused by defective synaptic transmission at the neuromuscular junction (NMJ) and characterized by fluctuation of muscle weakness and fatigability. Recently, many mutations encoding presynaptic proteins have been identified as responsible for increasingly complex CMS phenotypes of CMS. Among them, the autosomal dominant mutations in Synaptotagmin2 (SYT2) C2B domain that have been linked to described as responsible for presynaptic CMS combined to Lambert-Eaton myasthenic syndromes and motor neuropathy forms. (So...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: S. Bauch é, A. Sureau, D. Sternberg, J. Rendu, C. Buon, J. Messéant, M. Boëx, D. Furling, J. Fauré, X. Latypova, A. Bernabe Gelot, M. Mayer, F. Laffargue, M. Nougues, B. Fontaine, B. Eymard, A. Isapof, L. Strochlic Source Type: research

Myasthenia & related disorders
We report our case, along with the relevant literature. The patient is a 70-year-old man. Twelve years ago, he was diagnosed with anti-acetylcholine receptor antibody (anti-Ach-R Ab)-positive systemic MG. He underwent thymectomy and was treated with oral steroids. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: A. Ishii, M. Yokoyama, H. Tsuji, Y. Fujii, A. Tamaoka Source Type: research

Myasthenia & related disorders
Myasthenia Gravis (MG), an autoimmune neurological disease, is more frequently found amongst adults than amongst children. Our research provides data on the clinical symptoms, forms of MG, effective treatment, the presence of thymoma and the effect of thymectomy in children with MG in Israel. The database of a tertiary pediatric medical center was retrospectively reviewed for patients under 18 years of age diagnosed between the years 2000-2020 with either ocular or systemic acquired myasthenia gravis. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: A. Kuzminsky, Y. Nevo, S. Aharoni, M. Rabie Source Type: research

Myasthenia & related disorders
We present two siblings, a boy, P1, and a girl, P2, born to consanguineous Egyptian healthy parents. One brother died at 5 yrs of a respiratory infection, another one was healthy. P1 had ptosis, ophthalmoplegia, weak cry and nasal regurgitations from 8 months. He developed fatigable weakness, frequent respiratory infections and he lost walk at 6 yrs. EMG showed a decremental response. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Gomez Garcia de la Banda, N. Fahmi, D. Sternberg, P. Blondy, S. Quijano-Roy, E. Malfatti Source Type: research