A Novel SPEG mutation causing congenital myopathy with fiber size disproportion and dilated cardiomyopathy with heart transplantation
In this report, we describe two Brazilian siblings, aged 13 and 6 years, with a novel homozygous mutation (c.8872 C>T:p.Arg2958Ter) in the SPEG gene leading to a congenital myopathy. In the older sibling, the muscle biopsy showed fiber size disproportion. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 21, 2021 Category: Neurology Authors: Juliana Gurgel-Giannetti, Lucas Santos Souza, Guilherme Ferraz Messina de P ádua Andrade, Maria de Fátima Derlene, Zilda Maria Alves Meira, Beatriz Vilela Morais Azevedo, Wilson Campos Jr, Sabrina Stephanie Lana Diniz, Marina Belisario Carvalhais, Julia Tags: Case report Source Type: research

WMS 2021 Author index
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Source Type: research

Clinical trial highlights
We present updated results from ASPIRO (NCT03199469), investigating gene replacement therapy with AT132 for XLMTM patients. XLMTM, an ultra-rare, life-threatening myopathy caused by mutations in the MTM1 gene, leads to impaired neuromuscular and respiratory function, and early death. Patients enrolled required ventilator support and had no clinically significant underlying liver disease at baseline, defined as>5x ULN ALT or AST, or hepatic peliosis by imaging. As of Jul2020, efficacy data were analysed for 16 patients (n=6, 1  × 1014 vg/kg (age 0.8–4.1 years at dosing); n=10, 3 × 1014 vg/kg (ag...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: P. Shieh, N. Kuntz, J. Dowling, W. M üller-Felber, A. Blaschek, C. Bönnemann, R. Foley, D. Saade, A. Seferian, L. Servais, M. Lawlor, M. Noursalehi, S. Prasad, S. Rico, W. Miller Source Type: research

Clinical trial highlights
IGNITE DMD is an ongoing, multicenter, first-in-human open-label Phase I/II ascending dose study of the safety and efficacy of a single intravenous infusion of SGT-001, an AAV9 microdystrophin gene therapy, in DMD patients. DMD is caused by mutations that result in the absence of dystrophin in skeletal and cardiac muscle, which leads to muscle fiber deterioration, progressive decline in motor function, and premature death. SGT-001 microdystrophin is a five-repeat dystrophin surrogate that includes the critical actin, dystroglycan, and nNOS binding domains. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: V. Rao, B. Byrne, P. Shieh, S. Salabarria, J. Berthy, M. Corti, S. Redican, J. Lawrence, K. Brown, C. Shanks, S. Spector, P. Gonzalez, J. Schneider, C. Morris, C. Clary Source Type: research

Clinical trial highlights
Vamorolone is a first-in-class steroidal anti-inflammatory drug with novel structure/activity relationships with glucocorticoid and mineralocorticoid receptor targets compared to deflazacort or prednisone.   Published open-label dose-finding studies (0.25–6.0 mg/kg/day) in DMD showed significant motor function improvement over 24 weeks for 2.0 and 6.0 mg/kg/day dose groups (n=48; age 4 to (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: E. Hoffman, U. Dang, P. Clemens, H. Gordish-Dressman, B. Schwartz, L. Mengle-Gaw, M. Leinonen, E. Smith, D. Castro, N. Kuntz, R. Finkel, M. Tulinius, Y. Nevo, M. Ryan, R. Webster, J. van den Anker, L. Ward, J. Damsker, C. McDonald, M. Guglieri, J. Mah Source Type: research

Clinical trial highlights
SMA is a severe neuromuscular disease in which motor neuron degeneration may occur in the first months of life, often before symptoms appear. Risdiplam (EVRYSDI ™) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier that has been approved by the FDA for the treatment of patients with SMA, aged 2 months and older. RAINBOWFISH (NCT03779334) is an open-label, single-arm, multicenter study to investig ate efficacy, safety, and pharmacokinetics (PK)/pharmacodynamics of risdiplam in infants with genetically diagnosed presymptomatic SMA. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: L. Servais, M. Al-Muhaizea, M. Farrar, L. Nelson, A. Prufer, R. Finkel, Y. Wang, E. Zanoteli, M. El-Khairi, M. Gerber, K. Gorni, H. Kletzl, L. Palfreeman, R. Scalco, E. Bertini Source Type: research

Clinical research
The main objective is to evaluate the efficacy of losmapimod in inhibiting the aberrant expression of DUX4, the root cause of FSHD. Secondary objectives are to evaluate the safety, tolerability, PK, and TE in blood and muscle, and muscle health with MRI. FSHD is caused by aberrant expression of DUX4 due to loss of repression at the D4Z4 locus. DUX4 activates a downstream transcriptional program that causes myofiber death, maladaptive tissue remodeling characterized by replacement of muscle with fat ultimately resulting in progressive motor disability. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: R. Tawil, K. Wagner, Behalf of the ReDUX4 Study Grp Source Type: research

Clinical research
Malignant hyperthermia (MH) is a life-threatening reaction triggered by volatile anaesthetics and succinylcholine (SC) characterized by hypercapnia, hypermetabolism and muscle breakdown. MH is commonly caused by mutations in RYR1, as is rhabdomyolysis triggered by exertion and/or pyrexia. The discrepancy between risk genotypes and actual MH incidence remains unexplained. We hypothesized that MH is a compound event, reflecting a synergistic effect of predisposing genotype, triggering anaesthetic, and exercise and/or pyrexia as modifying factors. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: S. Riazi, L. van den Bersselaar, G. Islander, L. Heytens, M. Snoeck, A. Bjorksten, R. Gillies, G. Dranitsaris, A. Hellblom, S. Treves, N. Voermans, H. Jungbluth Source Type: research

Clinical research
The main objective of this natural history study was (i) to understand the disease course of patients with Duchenne muscular dystrophy (DMD) presenting deletions in dystrophin that make them eligible for exon 53-skipping therapy and (ii) to identify sensitive outcomes by using functional and strength assessments as well as quantitative magnetic resonance imaging (qMRI). Furthermore, this prospective and longitudinal study enabled to explore prognostic factors of loss of ambulation and upper limb weakness progression over a period of three years. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. Lilien, H. Reyngoudt, A. Seferian, T. Gidaro, M. Annoussamy, V. Ch ê, V. Decostre, I. Ledoux, J. Le Louër, E. Guemas, F. Muntoni, J. Hogrel, P. Carlier, L. Servais Source Type: research

Clinical research
Valosin-containing protein (VCP) disease is an adult autosomal dominant disorder caused by mutations in the VCP gene which leads to disabling weakness, Paget Disease of the Bone and Fronto Temporal Dementia among other multisystemic clinical features. This audit aimed to describe the clinical and genetic features of a large international cohort of patients with mutations in the VCP gene and investigate genotype - phenotype correlations. Clinical and genetic data from patients with confirmed mutations in the VCP gene, from 23 centres in 12 countries, was collected. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: M. Schiava, C. Ikenaga, T. Stojkovic, M. Caballero, I. Nishino, C. Paradas, A. Alonso-Jimenez, A. Kostera-Pruszczyk, F. Miralles Morell, J. De Bleecker, C. Dom ínguez-Gonzalez, G. Papadimas, K. Claeys, P. Laforet, A. Toscano, E. Pál, M. Farrugia, G. Tas Source Type: research

Autoimmune & inflammatory nmd
We report 2 patients with onset in the first years of life. Both received corticosteroids, immunoglobulins, methotrexate, hydroxychloroquine and tacrolimus. Patient 1 has clearly improved. Patient 2 was misdiagnosed as muscular dystrophy for 15 years; nevertheless, after 4 months of therapy there was mild motor improvement. Patient 1. A 6-year-old girl presented with weakness, but her parents could not recall the beginning. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: A. Camacho, D. Ghandour, J. De Inocencio, A. Hern ández Laín, O. Toldos, S. Vila, N. Núñez, R. Simón Source Type: research

Autoimmune & inflammatory nmd
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of progressive autoimmune muscle disorders of unknown etiology. It is postulated that mitochondrial dysfunction and protein aggregation in skeletal muscle lead to myofiber degeneration. However, molecular pathways that contribute to protein aggregation in skeletal muscle are not well defined. Here we have isolated membrane-bound organelles (e.g., nuclei, mitochondria, endoplasmic reticulum (ER), Golgi apparatus and plasma membrane) from muscle biopsies of normal (n=3), IIM (n=10), and mitochondrial myopathy (MM) (n=1) patients for global proteomic analysis ...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: J. Peterson, R. Zahedi, M. Alamr, V. Leclair, J. DiBattista, K. Nagaraju, M. Hudson Source Type: research

Autoimmune & inflammatory nmd
Anti-mitochondrial M2 antibody (AM2A) has been associated with myositis although it is unknown whether it is an independent subtype of myositis. To characterize the clinicopathological features, we reviewed the clinical information and muscle pathology slides of 226 patients (160 women) with AM2A whose pathological diagnosis was made at National Center of Neurology and Psychiatry. The age at muscle biopsy was 58.6 ±12.9 years and disease duration before biopsy was 52.4±75.3 months. Serum CK level was 1,585±2,319 U/L. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: Y. Nishimori, S. Hayashi, S. Noguchi, I. Nishino Source Type: research

Autoimmune & inflammatory nmd
Sporadic inclusion body myositis (sIBM) is a slowly progressive inflammatory myopathy developing in the elderly. Though there is distinct evidence of coexisting inflammatory and degenerative mechanisms in sIBM, its true pathogenesis remains unknown. On electromyography (EMG), both myogenic and neurogenic changes are often detected in sIBM; however, again, the mechanism remains unknown. Therefore, this study addressed this question pathologically. We extracted sIBM cases based upon the European Neuromuscular Centre criteria (2011) among patients who underwent a muscle biopsy from 2008 to 2020. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: N. Eura, T. Mano, A. Yamanaka, Y. Nishimori, T. Shiota, H. Nanaura, K. Sugie Source Type: research

Autoimmune & inflammatory nmd
Anti-transcription intermediary factor 1 γ (TIF1γ) antibodies are one of the myositis-specific antibodies frequently detected in dermatomyositis (DM). To elucidate the characteristics of anti-TIF1γ antibody-positive myositis, we extracted cases with anti-TIF1γ antibodies from idiopathic inflammatory myopathy (IIM) patients who underwen t muscle biopsy from 2008 to 2019, and analyzed the clinicopathological findings. We found 87 cases of IIM (40 DM, 3 polymyositis, 25 immune-mediated necrotizing myopathy, 14 antisynthetase syndrome, and 5 nonspecific myositis), among which anti-TIF1γ antibodies...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: A. Yamanaka, N. Eura, M. Yamaoka, M. Ozaki, T. Shiota, H. Nanaura, K. Sugie Source Type: research

Autoimmune & inflammatory nmd
A 72-year-old woman presented with a 6-month history of anorexia, weight loss (-14kg) and myalgia in upper limbs. Clinical examination showed moderate proximal muscle weakness in upper limbs and crepitation at lung auscultation, but no skin rash nor joint involvement. Biological assessment disclosed increased C-reactive protein (68 µM) and creatine-kinase (3800 U/l) serum levels and anti-nuclear and -PL7 autoantibodies at immunological screening. Thoracic CT-scan showed abnormalities consistent with interstitial pneumonia. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: S. Souvannanorath, F. Cohen-Aubart, J. Authier Source Type: research

Autoimmune & inflammatory nmd
Systemic sclerosis (SSc) is a multisystemic fibrotic autoimmune disease that involves the muscles. Two muscular forms were described: the SSc myositis and myopathy. The SSc myopathy is characterized by three main histopathological findings: fibrosis, microangiopathy and type-II fiber atrophy. Quantifying these features is important to enable staging the disease, establishing a prognostic tool and linking it with systematic involvement. Muscle biopsies from 22 SSc patients and seven controls (patients with histologically normal muscle) were sectioned and stained for the pathological features of SSc myopathy. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: L. Zaidan, N. Le Gouellec, N. Dognon, E. Hachulla, L. Mouthon, J. Authier Source Type: research

Autoimmune & inflammatory nmd
Inclusion body myositis (IBM) belongs to the family of dysimmune inflammatory myopathies (DIMs). It is characterized by T-cells infiltrates and abnormal expression of major histocompatibility complex (MHC)-II by myofibers. Notably, MHC-II expression is induced in response to IFN γ binding and T-cells are major producers of IFNγ. Our aim was to dissect the pathogenic role of IFNγ in IBM. First, we showed that IFNγ signaling was upregulated in IBM patients’ muscles compared with muscles from DIMs patients and healthy controls. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. Hou, B. Periou, M. Gervais-Taurel, Y. Baba-Amer, F. Relaix, M. Bencze, J. Authier Source Type: research

Autoimmune & inflammatory nmd
Dermatomyositis is a systemic idiopathic inflammatory disease affecting skeletal muscle and skin, clinically characterized by symmetrical proximal muscle weakness and typical skin lesions. Recently, myositis-specific autoantibodies (MSA) became of utmost importance because they strongly correlate with distinct clinical manifestations and prognosis. Antibodies against transcription intermediary factor 1 γ (TIF-1γ) are frequently associated with increased risk of malignancy, a specific cutaneous phenotype and limited response to therapy in adult DM patients. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. Preusse, P. Eede, L. Heinzerling, K. Freitag, R. Koll, W. Froehlich, U. Schneider, Y. Allenbach, O. Benveniste, A. Sch änzer, H. Goebel, W. Stenzel, J. Radke Source Type: research

Autoimmune & inflammatory nmd
The diagnosis of dermatomyositis had been relied on the combination of the typical skin lesions, perifascicular atrophy (PFA) and myositis. The discoveries of dermatomyositis-specific antibodies (DMSA i.e. TIF1- γ, Mi-2, MDA5, NXP2, and SAE) and type 1 interferon signature and its surrogate immunohistochemical marker, Myxovirus resistant protein A (MxA), in dermatomyositis has started the new era of the disease classification. We believe that dermatomyositis could be sero-pathologically defined using a com bination of DMSA and MxA. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: J. Tanboon, M. Inoue, Y. Saito, S. Hayashi, S. Noguchi, N. Okiyama, M. Fujimoto, I. Nishino Source Type: research

Autoimmune & inflammatory nmd
This study assesses skin tone representation in images of dermatomyositis rashes. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: S. Babool, S. Bhai, L. Christopher-Stine Source Type: research

Autoimmune & inflammatory nmd
Immune mediated necrotizing myopathies (IMNM) are part of the idiopathic inflammatory myopathies, precisely defined by international consensus recently. The main characteristics include proximal muscle weakness, substantially increased serum CK levels and detection of the myositis-specific auto-antibodies -SPR54 or -HMGCR in many patients, while 1/3 of IMNM patients do not present those. Notably, both antibodies target proteins of the endoplasmic reticulum (ER)/sarcoplasmic reticulum (SR) and are involved in protein processing. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. Preusse, T. Marteau, N. Fischer, A. Hentschel, S. Lang, C. Dittmayer, U. Schneider, U. Schara-Schmidt, Y. Allenbach, O. Benveniste, H. Goebel, W. Stenzel, A. Roos Source Type: research

Autoimmune & inflammatory nmd
Polymyositis is a term that has been less commonly used during the last decades, with the parallel rise of newer possibilities to identify and classify subtypes of myositis more precisely. Polymyositis with mitochondrial pathology (PM-Mito) has been defined as a relatively rare entity within the spectrum of idiopathic inflammatory myopathies. Although no consensus-driven definition of PM-Mito is available, the diagnosis can be made if a muscle biopsy shows T cell infiltrates in the endomysium surrounding or invading myofibres, a diffuse sarcolemmal MHC cl. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: F. Kleefeld, C. Preusse, H. Goebel, K. Hahn, C. Dittmayer, W. Stenzel, A. Uruha Source Type: research

Autoimmune & inflammatory nmd
Sporadic late-onset nemaline myopathy (SLONM) is characterized by the presence of nemaline bodies in skeletal muscle biopsies. SLONM is a non-hereditary myopathy usually affecting adults in 5th-7th decade and the most common clinical presentation is proximal muscle weakness. SLONM can be classified into 2 major subtypes considering its association with monoclonal gammopathy (1) SLONM without MGUS (SLONM-noMGUS) and (2) with MGUS (SLONM-MGUS) association. SLONM-MGUS has been shown to be associated with poorer prognosis and required aggressive treatment including high dose melphalan and autologous stem cell transplantation. ...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: J. Tanboon, A. Uruha, Y. Arahata, C. Dittmayer, L. Schweizer, H. Goebel, I. Nishino, W. Stenzel Source Type: research

Autoimmune & inflammatory nmd
We report a severe nelarabine related neuropathy with quadriparesis and respiratory failure and excellent recovery. Diagnosis of stage III biphenotypic lymphoblastic lymphoma was made at 11 years of age in a previously healthy male who presented with supraclavicular lymphadenopathy. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: I. Hughes, E. Whitehouse, R. Wynn Source Type: research

Autoimmune & inflammatory nmd
Idiopathic inflammatory myopathies are a heterogenous group of diseases with prominent muscle inflammation and/or necrosis. Myositis is diagnosed through a combination of clinical, serologic, pathologic, and/or imaging findings, though these tools do not always yield clear diagnoses. A variety of neuromuscular conditions can mimic myositis, including muscular dystrophies, metabolic, endocrine, and toxic myopathies, and infectious myopathies. Through a series of four illustrative cases misdiagnosed as and treated for myositis, we highlight pitfalls and lessons to properly diagnosis myositis mimics to avoid immunosuppressant...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. Sanderson, S. Bhai Source Type: research

Autoimmune & inflammatory nmd
Inclusion body myositis (IBM) is a slowly progressive myopathy with unique clinical and pathological features. So far, there are several case reports of patients with IBM and HTLV-I infection. However, there is no study that investigated clinical features of IBM associated with HTLV-I infection. We investigated the clinical differences between the IBM patients with and without anti-HTLV-I antibodies. In 402 patients enrolled into the study, 250 patients fulfilled the ENMC2011 criteria for diagnoses of IBM. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: S. Yamashita, K. Hara, N. Tawara Source Type: research

Autoimmune & inflammatory nmd
Our objective is to describe two genetically confirmed Oculopharyngeal Muscular Dystrophy (OPMD) patients with HMGCoARdase-antibody positive autoimmune necrotic myopathy (AINM) responsive to immunosuppressive treatment. Although clinicians have suspected muscular dystrophy patients are at increased risk of statin side-effects, to date no patients with genetically confirmed muscular dystrophy have been reported with HMGCoRdase-antibody positive AINM. Here we describe the clinical presentation, serology, muscle pathology and response to treatment in two patients with genetically confirmed OPMD who developed statin-associated...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: K. Alrasheed, B. Brais, J. Schulz, T. Wein, J. Karamchandani, E. O'Ferrall Source Type: research

Covid-19 and neuromuscular diseases
We present a case diagnosed with facial onset acute inflammatory demyelinating polyneuropathy after being infected with SARS-CoV-2. A 51-year-old man presented with facial diplegia to the emerge ncy room. Then he developed bilateral ascending paralysis. He noticed that for one month he had smell and taste disturbances. SARS-CoV-2 infection was suspected. Nasopharyngeal swab polymerase chain reaction test was negative but anti-SARS-CoV-2 antibody found to be positive. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: A. Alaamel, R. Şahin, M. Hashal, T. Taşkınoğlu, T. Özel, N. Şimşek Erdem, H. Uysal Source Type: research

Covid-19 and neuromuscular diseases
Assessment of the change in the trend of weight gain in children affected by DMD during the first twelve months of the coronavirus pandemic in one paediatric neuromuscular centre. We noted that a number of children affected by Duchenne muscular dystrophy appeared to have had significantly accelerated weight gain during the first year of the pandemic; potentially greater than weight gain in previous years and that expected for age. To evaluate this, the body mass index BMI change and centiles during this year will be compared to that in the two years preceding the pandemic for each patient. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: Z. Alhaswani Source Type: research

Covid-19 and neuromuscular diseases
The unexpected Coronavirus disease 2019 (Covid 19) worldwide crisis induced a lockdown of the whole population in Belgium from 18th March 2020 to 4th May 2020 first and then from 2nd November to 1st December 2020. During this period, patients could not continue to come to hospital for their follow-up except for emergency situations. The Neuromuscular Reference Center of Liege (NMRC) takes care of adults and child patients suffering from neuromuscular disorders. The pluridisciplinary team ensures a follow-up of patients according to international standard of care. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: S. Delstanche, C. Bernar, L. Buscemi, C. Dubois, M. Duclos, L. Medard, L. Servais Source Type: research

Covid-19 and neuromuscular diseases
Children with neuromuscular disorders have been assumed to be a particularly vulnerable population since the beginning of COVID-19. Although this is a plausible hypothesis, there is no evidence that complications or mortality rates in neuromuscular patients are higher than in the general population. The aim of this study is to describe the clinical characteristics and outcome of COVID-19 in children with neuromuscular disorders. A registry of children with neuromuscular conditions and laboratory-confirmed-SARS-CoV-2 infection was set up by the Neuromuscular Working Group of the Spanish Pediatric Neurology Society (SENEP). ...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: D. Natera-de Benito, S. Aguilera-Albesa, L. Costa-Comellas, M. Garc ía-Romero, C. MirandaHerrero, C. Ortez, L. Carrera-García, J. Expósito-Escudero, J. Rúbies Olives, O. GarcíaCampos, E. Martínez del Val, J. Martinez Garcia, I. Medina Martinez, R. C Source Type: research

Covid-19 and neuromuscular diseases
The development of e-health technologies for teleconsultation and exchange of knowledge is within the mission of European Reference Networks (ERN), including Euro-NMD, the ERN for rare neuromuscular diseases. The Clinical Patient Management System (CPMS) is a web-based platform promoting active collaboration within and across ERNs to discuss patient cases. “Telegenetics” represents an attractive alternative to traditional on-site genetic counseling in light of the non-homogeneous availability of genetic services among countries and the increasing demand of high-level expertise. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: F. Fortunato, M. Farn è, F. Bianchi, M. Neri, G. Siciliano, V. Sansone, A. Barp, E. Albamonte, G. Vita, A. Atalaia, T. Evangelista, F. Gualandi, A. Ferlini Source Type: research

Covid-19 and neuromuscular diseases
Functional motor performance outcome measures (OM), assessed by Physiotherapists, are commonly used as primary or secondary endpoints in clinical trials, natural history studies and within clinics for children and adults with neuromuscular disorders (NMD). The impact of COVID-19 globally on the ability to assess patients within the clinic, especially those considered clinically vulnerable and advised to shield at home, necessitated rapid development of COVID-19 mitigation strategies. Here we explore the feasibility of adapting current standard outcomes to remote testing, considerations for a remote assessment, methods util...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: M. James, L. Alfano, K. Rose, L. Lowes, M. Eagle Source Type: research

Congenital myopathies – centronuclear myopathies
Myotubular and other centronuclear myopathies are congenital neuromuscular conditions characterised by the central location of the nucleus in muscle cells. The presumably most common form is the ultra-rare X-linked myotubular myopathy (XLMTM) with an estimated incidence of 1 in 50,000 male births. The Myotubular and Centronuclear Myopathy Patient Registry ("the registry") collects demographic, genetic and clinical data on affected individuals and female carriers of XLMTM from all over the world. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: J. Bullivant, B. Porter, L. Murphy, L. Render, M. Bellgard, A. Lennox, M. Spring, A. Hollander, C. B önnemann, H. Jungbluth, A. Buj-Bello, J. Dowling, C. Marini-Bettolo Source Type: research

Congenital myopathies – centronuclear myopathies
Clinical trial designs in rare and ultra-rare diseases yield multiple challenges due to restricted sample sizes. In the context of an ongoing investigation of centronuclear myopathies (CNMs), a group of congenital neuromuscular diseases whose most severe and most common incident form is X-linked, affecting approximately 1 in 50,000 newborn boys, this feature holds especially true. In such settings, innovative Bayesian methods can often pay dividends, allowing the sensible incorporation of auxiliary data and other relevant information to bolster that collected by the trial itself. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: A. Monseur, B. Carlin, B. Boulanger, A. Seferian, L. Servais, C. Freitag, L. Thielemans Source Type: research

Congenital myopathies – centronuclear myopathies
A 42-year-old male presented with the complaint of acute onset double vision in our emergency room. Examination revealed a tall stature, impaired eye movements in all directions, in particular upwards and left side abduction, the latter likely the cause of the acute complaints, and mild symmetrical ptosis compensated by permanent frontalis muscle contraction. As no evidence for myasthenic variability was found and CK was elevated 300 – 550 U/l (ULN 190), vastus lateralis muscle biopsy was performed under suspicion of atypical chronic progressive external ophthalmoplegia (CPEO). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. von Landenberg, M. Winkler, A. Abicht, D. Wolf, C. Kornblum, J. Reimann Source Type: research

Congenital myopathies – centronuclear myopathies
In this study, we investigated whether DYN101-m could also reverse disease phenotypes in Dnm2RW/+ mice in a dose-dependent manner. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: M. Depla, A. Rob é, S. Buono, C. Koch, M. Bitoun, S. Colombo, B. Cowling Source Type: research

Congenital myopathies – centronuclear myopathies
Congenital myopathies are progressive muscle disorders affecting children and adults in all populations and can be distinguished by the predominance of particular histopathologic anomalies on muscle biopsies. They are mainly caused by mutations in MTM1, DNM2 or BIN1, encoding proteins implicated in membrane trafficking and organelle positioning. MTM1 and BIN1 are negative regulators of DNM2, and the downregulation of DNM2 in mice was shown to be an efficient pre-clinical therapy for all three CNM forms. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: S. Djeddi, D. Reiss, A. Menuet, S. Freismuth, J. de Carvalho Neves, S. Djerroud, X. Massana-Mu ñoz, A. Sosson, C. Kretz, W. Raffelsberger, C. Keime, O. Dorchies, J. Thompson, J. Laporte Source Type: research

Congenital myopathies – centronuclear myopathies
Breakthrough advances have recently been achieved in therapy development in the neuromuscular disease field, based on promising preclinical data obtained in animal models. Generating reliable preclinical therapeutic data from validated animal models can significantly de-risk drug development by improving trust in the outcome from preclinical studies across study sites. Here we perform statistical analysis and a joint longitudinal-survival modelling of the progressive phenotype observed in Mtm1 −/y knock-out mice, a faithful model for myotubular myopathy, due to myotubularin 1 (MTM1) loss-of-function mutations. (Sourc...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: S. Buono, A. Monseur, A. Menuet, A. Rob é, C. Koch, J. Laporte, L. Thielemans, M. Depla, B. Cowling Source Type: research

Congenital myopathies – centronuclear myopathies
The mode of inheritance of X-linked myotubular myopathy (XL-MTM) is currently considered recessive and the proportion of manifesting carriers is assumed low. We aimed to characterize the spectrum of clinical signs and symptoms in a cohort of female XL-MTM carriers, including prevalence, genetic features and associated disease burden. We performed a cross-sectional online questionnaire study among XL-MTM carriers, recruiting from patient associations, medical centres and registries in the United Kingdom, Germany and the Netherlands. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: F. Braun, S. Reumers, J. Spillane, J. Bohm, M. Pennings, M. Schouten, A. van der Kooi, A. Foley, C. B önnemann, E. Kamsteeg, C. Erasmus, U. Schara-Schmidt, H. Jungbluth, N. Voermans Source Type: research

Congenital myopathies – nemaline myopathies
Biallelic pathogenic variants in the troponin T type 1 (TNNT1) gene cause a severe form of congenital myopathy with nemaline rods. Typical features include severe motor delay, proximal contractures and weakness, pectus carinatum, chest wall rigidity and tremor. If left untreated, respiratory failure leads to early death at a median age of 18 months. Here we report on two non-Amish, unrelated patients harbouring four novel compound heterozygous TNNT1 variants (c.611+1dupG  + deletion of exons 7-14 and c.299dupA; p.(Glu101fs) + deletion of exons 12-14). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: A. Zambon, F. Abel, R. Phadke, L. Feng, A. Sarkozy, A. Manzur, F. Muntoni Source Type: research

Congenital myopathies – nemaline myopathies
We re-evaluated the muscle biopsies, clinical picture and molecular findings of 14 patients with severe forms of Congenital Nemaline myopathy (NM) due to ACTA1 mutations, with the aim of determining possible correlations between these findings. Muscle biopsy was performed between the ages of two days to three months. Eight children died in the first years of live, three died between the ages of 5-9 years old. Three patients are alive at the ages of 3, 12 and 18 years old in spite of the clinical severity; 2/3 follow normal schooling for their age. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. Labasse, G. Brochier, J. Rendu, J. Bohm, S. Monges, S. Quijano-Roy, H. Amthor, L. Servais, A. Madelaine, E. Lac ène, M. Bui, S. Coppens, V. Biancalana, F. Lubieniecki, N. Laing, A. Taratuto, A. Buj-Bello, T. Evangelista, J. Laporte, N. Romero Source Type: research

Congenital myopathies – nemaline myopathies
Nemaline myopathy 8 (NEM8) is typically a severe autosomal recessive disorder associated with variants in the kelch-like family member 40 gene (KLHL40). To date, patients with NEM8 have only been identified with coding pathogenic variants and almost all have presented with severe disease. Common features include fetal akinesia/hypokinesia, fractures, contractures, dysphagia, respiratory failure, and neonatal death (average age at death ∼5 months). Here, we describe a 26-year-old man with milder NEM8. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: L. Dofash, F. Faiz, E. Servi án-Morilla, E. Rivas, P. Sullivan, E. Oates, J. Clayton, R. Taylor, M. Davis, N. Laing, M. Cabrera-Serrano, G. Ravenscroft Source Type: research

Congenital myopathies – nemaline myopathies
Nemaline myopathies (NM) are genetically and phenotypically heterogeneous congenital myopathies (CM), with NEB gene related NM being the most common. In this work, we provide phenotypic and genotypic data on a clinically and genetically heterogeneous cohort of NM patients seen or diagnosed at the Highly Specialised Service for CM at Great Ormond Street Hospital until March 2021. We identified 134 patients with a genetic diagnosis of NM. 60 patients had NEB, 39 ACTA1, 11 TPM3, 9 KLHL40, 8 TPM2, 3 LMOD3, 2 TNNT1 and 2 CFL2 related NM. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: L. Perry, R. Phadke, R. Mein, Y. Clinch, S. Robb, P. Munot, L. Feng, C. Sewry, A. Manzur, R. Quinlivan, M. Scoto, G. Baranello, F. Muntoni, A. Sarkozy Source Type: research

Congenital myopathies – nemaline myopathies
The molecular mechanisms of nemaline myopathy and related disorders (NMs) have been widely studied, whereas little scientific attention has been paid to the general health of the patients. We set out to study nutrition and food consumption and their correlation with self-experienced functioning and health in adult NM patients. We used food diaries and a food frequency questionnaire (D2D-FFQ) to study food consumption, internationally validated PROMIS ®-questionnaires to study functioning, and laboratory analyses of nutritional parameters. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: V. Lehtokari, M. Simil ä, M. Tammepuu, S. Hiekkala, S. Strang-Karlsson, C. Wallgren-Pettersson Source Type: research

Congenital myopathies – nemaline myopathies
We describe clinical and histopathologic features of 5 newborns (two girls) studied between 2013 and 2020 in Clinica Alemana de Santiago and Hospital Luis Calvo Mackenna. Genetic analysis was performed in Hospital Bambino Ges ú and Invitae (commercial laboratory USA). The first patient studied (2013) was a girl with fetal akinesia syndrome. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: R. Erazo-Torricelli, A. Gallardo, E. Bertini, F. Fattori, A. Zakharova, C. Arce, E. Alcalde, J. Carrasco, P. G ómez Source Type: research

Congenital myopathies – nemaline myopathies
Nemaline myopathy (NM) is a congenital myopathy characterized by muscle weakness and the presence of abnormal thread- or rod-like structures (nemaline bodies) in muscle fibres. Approximately 25% of NM cases worldwide are caused by mutations in the skeletal muscle alpha actin gene, ACTA1. We generated two induced pluripotent stem cell lines from lymphoblastoid cells of a 4-month-old female with severe NM harbouring a dominant mutation in ACTA1 (c.553C>A). The isogenic lines displayed characteristic iPSC morphology, expressed pluripotency markers, differentiated into cells of all three germ layers, and possessed normal ka...
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: J. Clayton, C. Scriba, N. Romero, E. Malfatti, S. Saker, T. Larmonier, K. Nowak, G. Ravenscroft, N. Laing, R. Taylor Source Type: research

Congenital myopathies – nemaline myopathies
The TNNT1 gene encodes troponin T type 1, expressed in type I skeletal myofibers. Recessive null mutations in TNNT1 are a rare cause of nemaline myopathy (MIM#605355) which leads to death during infancy due to respiratory failure. Recently, a milder phenotype has been described in 3 adults and 1 child that shared a missense homozygous variant in TNNT1. They developed very slowly progressive limb-girdle weakness, rigid spine, contractures and restrictive lung disease. Here we report an adult patient with a nemaline myopathy due to a novel homozygous causal variant in TNNT1. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. Fuenmayor-Fern ández de la Hoz, A. Hernández-Laín, A. Arteche López, A. Hernández Voth, M. Olivé, C. Domínguez-González Source Type: research

Congenital myopathies – nemaline myopathies
Nemaline myopathies (NMs) are a clinically heterogenous group of non-dystrophic congenital muscle diseases caused by mutations in at least 13 genes. NMs are characterised by muscle weakness, hypotonia and respiratory insufficiency, with presence of cytoskeletal protein aggregates (rods) in skeletal muscle fibers. In the present study we investigated whether neuromuscular junctions (NMJ) are affected in ACTA1-related nemaline myopathy, which accounts for about 50% of severe cases of NMs. For this purpose, we analysed the morphology and function of NMJs in the Acta1(H40Y) knock-in mouse model of the disease. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: C. Bogni, E. Girard, K. Poulard, G. Brochier, E. Errazuriz-Cerda, J. Cosette, C. Labasse, A. Madelaine, A. Lia Taratuto, N. Messaddeq, L. Schaeffer, N. Romero, A. Buj-Bello Source Type: research