DOCSLIB.ORG

Hereditary Muscle Diseases and the Heart: the Cardiologist's Perspective

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Hereditary Muscle Diseases and the Heart: the Cardiologist's Perspective European Heart Journal Supplements (2020) 22 (Supplement E), E13–E19 The Heart of the Matter doi:10.1093/eurheartj/suaa051 Hereditary muscle diseases and the heart: the cardiologist’s perspective Lorenzo Giuliani1, Alessandro Di Toro1, Mario Urtis1, Alexandra Smirnova1, Monica Concardi1, Valentina Favalli2, Alessandra Serio1, Maurizia Grasso1, and Eloisa Arbustini1* 1Centre for Inherited Cardiovascular Diseases, IRCCS Foundation University Hospital Policlinico San Matteo, Pavia, Italy; and 2Ingenomics Srls, Polo Tecnologico, Pavia, Italy KEYWORDS Hereditary muscle disease; Cardiomyopathy; Heart failure Introduction patients in a way to collect data useful in accelerating tar- geted treatment development. Cardiac manifestations in hereditary muscle diseases in- clude cardiomyopathies, defects of cardiac conductions Dilated and hypokinetic phenotypes (DCM) with or without primary myocardial muscle involvement, 1,2 and arrhythmias. Symptoms and signs of these diseases The most common heritable muscle diseases affecting the 3 may exhibit in paediatric as well as in adult age, and in heart and leading to dilated and hypokinetic cardiac phe- many cases only a multidisciplinary clinical approach can notype include dystrophinopathies, limb girdle muscular 4,5 ensure correct diagnosis and management. Cardiologists dystrophies (LGMD), and Emery–Dreifuss Muscular might be the first to recognize an apparently lone cardiac Dystrophies (EDMD). involvement as an important clinical marker of an heredi- tary muscle disease or be the first in line in a multidiscipli- nary team when cardiac involvement represents the major Dystrophinopathies clinical manifestation affecting evolution and prognosis of Mutations in the DMD gene encoding for dystrophin cause the disease.6 dystrophinopathies, a group of rare X-linked recessive The actual classifications of hereditary muscle disorders (XLR) muscle diseases. Dystrophin is a large sarcolemmal are based on phenotype, aetiology, and pathology and may protein that is essential for structural and functional integ- result complex and potentially impractical for a cardiologic rity of the myocyte membranes. Patients affected by dys- clinical approach. For this reason, we are proposing the trophin defects manifest DCM as unique and often fatal grouping of most common cardiac manifestations observed cardiac phenotype. Muscle and cardiac phenotypes are in hereditary muscle diseases on the basis of the cardiac clinically heterogeneous and classified according to the se- phenotypes. A new way of describing the complexity of car- verity of the dystrophy [from the severe Duchenne Muscle diac phenotype and genotype together with extra-cardiac Dystrophy (DMD) to the milder Becker Muscular Dystrophy clinical manifestations, as represented by MOGES nosology (BMD)] or the exclusive involvement of the heart, when for cardiomyopathies,7 is the possible solution for nosology skeletal muscle is clinically spared (i.e. in XLR-DCM). assignment and deep phenotype description of these • DMD (1:4000–1:6000 live male birth)8 is a severe mus- cle dystrophy clinically and genetically diagnosed in *Corresponding author. Email: [email protected] paediatric age. In most of the cases (>70%), the Published on behalf of the European Society of Cardiology. VC The Author(s) 2020. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] E14 L. Giuliani et al. genetic defects are large rearrangements in DMD autosomal recessive (AR, type 2, LGMD2) diseases. gene. The pathologic hallmark is the total absence of Alphabetic letters indicating the mutated protein/gene dystrophin in the skeletal myocyte sarcolemma.9 complement the description.23 Currently, eight AD LGMDs Regular cardiology care is needed since initial diagno- (LGMD1) and more than 25 AR LGMDs are known. sis in all DMD patients and annual echocardiograms The prevalence of LGMDs is estimated to be ranging from represent the minimum follow-up.4,5,8 The prevalence 1:14 500 to 2.27:100 000.24,25 Cardiac and respiratory im- of DCM is age-dependent and in nearly all young–adult pairment is common. The most represented cardiac pheno- patients cardiac involvement is demonstrated.10–13 type in LGMD is DCM26 having a prevalence that varies ECG changes like right axis deviation, Q wave in the between the different subgroups of patients; in sarcoglyca- left precordial leads, and conduction defects may ex- nopathies (a-, b-, d-, c-) more than 30% of patients develop hibit an early onset.10 DCM is diagnosed through trans- DCM.27 The risk of sudden death (SD) is also variable, being thoracic echocardiogram and when feasible, CMR may particularly high in LGMD1B (laminopathy) where is also as- add information on adipose and fibrous replacement sociated with DCM and conduction defects.28 Disease- of left ventricle (LV) wall structure and LV trabecular specific biomarkers exist but hyperCKemia represent a anatomy.11 Patients have to be treated for cardiac common finding in all LGMDs. Functional studies of cardiac manifestations according to heart failure (HF) guide- (echocardiography and CMR) and skeletal muscle (electro- lines and disease-specific recommendations4,5 with myography, muscle ultrasound, and magnetic resonance ACE-I and ARBs as cornerstone therapy. Multiple con- imaging) are useful to characterize the involvement of the tributors to cardio-respiratory failure determine end- heart and skeletal muscles.29,30 Patients usually need a stage evolution of the disease13 precluding indication scheduled monitoring in multidisciplinary settings and the to heart transplantation (HTx). In recent years, life actual therapeutic options include steroids with variable expectancy has increased from the late 20s12 to early effectiveness.30 Since actionable targeted therapies cur- 40s14 thanks to steroid treatment, spinal stabilization rently does not exist, DCM, arrhythmias and, conduction surgery, nocturnal ventilation, and physiotherapy. defects have to be treated according to contemporary • In patients with BMD [1:18 000 live male birth15] DCM guidelines4,5,19,26 fully manifests in the second to fourth decade of life but it can be recognized even earlier when BMD is clinically suspected.16 Skeletal muscle involvement is Emery–Dreifuss muscle dystrophy milder than in DMD and variable, depending on the se- Contractures of elbows, ankles, and cervical spine associ- verity of the loss of protein expression.17 Patients usu- ated with slowly progressive muscle weakness are the ma- ally remain ambulatory until advanced adult age.8,9,15 jor traits in EDMD.31 The cardiac phenotype is DCM may be the first clinically overt manifestation of characterized by LV dilation and dysfunction often pre- the disease18 but hyperCKemia is common and by it- ceded by conduction disease that requires PM implanta- self may represent a reason for neurological consulta- tion. HyperCKemia is common. The disease is genetically tion. The most common cause of end-stage disease is heterogeneous and is caused by mutations in genes that HF.4,5,19 Patients with BMD-DCM have to be treated code for nuclear envelope protein. Half of the patients di- according to HF guidelines and HTx may be indicated. agnosed with EDMD are carriers of mutations in genes that Post-transplant outcome is similar to that of (non- code for emerin, lamin A/C, nesprin-1, and nesprin-2.31 BMD) idiopathic DCM.4,5,19 Depending upon the disease gene, the pattern of inheri- • XLR-DCM can be the unique overt manifestation in tance is either X-Linked or autosomal, both dominant patients with dystrophin defects. The prevalence (common) or recessive (rare). ranges from 3% to 7% in consecutive male patients In XLR emerinopathies, patients are usually referred to with familial, non-paternally inherited DCM.20,21 cardiologists for arrhythmia consultation and consideration Patients have no history or symptoms of muscular dys- of possible pacemaker (PM) placement; AV conduction trophy but almost always present hyperCKemia. defects and arrhythmias, mostly of atrial origin, may ap- Clinical management is based on HF guidelines; trans- pear before LV systolic dysfunction.32,33 In AD EDMD caused plantation is the elective treatment for patients with by mutations in LMNA gene,33 the risk of ventricular end-stage HF and has the same outcome as in BMD- arrhythmias is high. DCM, arrhythmias and conduction dis- DCM.22 ease should be treated according to HF guidelines. However, the disease-causing gene and the type of muta- tion should be taken into account in the stratification of Limb girdle muscle dystrophy arrhythmogenic risk.2 The LGMD phenotype includes genetically heterogeneous group of more than 30 disorders in which skeletal, respira- Hypertrophic phenotypes tory, gastrointestinal, and nervous systems may be variably involved. They are characterized by weakness and wasting HCM represents the cardiac phenotype in a large group of of pelvic and shoulder girdle muscles. Recently, a novel clinically and genetically heterogeneous hereditary muscle gene-based nosology23 has classified LGMDs using the clini- disorders caused by impaired synthesis and utilization of cal descriptor (LGMD) followed by a number that distin- energy substrates with proliferation of abnormal
Load more

Recommended publications
  • Mitochondrial Trnaleu(Uur) May Cause an MERRF Syndrome
    J7ournal ofNeurology, Neurosurgery, and Psychiatry 1996;61:47-51 47 The A to G transition at nt 3243 of the J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.1.47 on 1 July 1996. Downloaded from mitochondrial tRNALeu(uuR) may cause an MERRF syndrome Gian Maria Fabrizi, Elena Cardaioli, Gaetano Salvatore Grieco, Tiziana Cavallaro, Alessandro Malandrini, Letizia Manneschi, Maria Teresa Dotti, Antonio Federico, Giancarlo Guazzi Abstract Two distinct maternally inherited encephalo- Objective-To verify the phenotype to myopathies with ragged red fibres have been genotype correlations of mitochondrial recognised on clinical grounds: MERRF, DNA (mtDNA) related disorders in an which is characterised by myoclonic epilepsy, atypical maternally inherited encephalo- skeletal myopathy, neural deafness, and optic myopathy. atrophy,' and MELAS, which is defined by Methods-Neuroradiological, morpholog- stroke-like episodes in young age, episodic ical, biochemical, and molecular genetic headache and vomiting, seizures, dementia, analyses were performed on the affected lactic acidosis, skeletal myopathy, and short members of a pedigree harbouring the stature.2 Molecular genetic studies later con- heteroplasmic A to G transition at firmed the nosological distinction between the nucleotide 3243 of the mitochondrial two disorders, showing that MERRF is strictly tRNAI-u(UR), which is usually associated associated with two mutations of the mito- with the syndrome of mitochondrial chondrial tRNALYs at nucleotides 83443 and encephalomyopathy, lactic
    [Show full text]
  • When Should MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic
    DOI: 10.1590/0004-282X20150154 VIEW ANDARTICLE REVIEW When should MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) be the diagnosis? Quando o diagnóstico deveria ser MELAS (Miopatia mitocondrial, encefalopatia, acidose lática, e episódios semelhantes a acidente vascular cerebral)? Paulo José Lorenzoni, Lineu Cesar Werneck, Cláudia Suemi Kamoi Kay, Carlos Eduardo Soares Silvado, Rosana Herminia Scola ABSTRACT Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a rare mitochondrial disorder. Diagnostic criteria for MELAS include typical manifestations of the disease: stroke-like episodes, encephalopathy, evidence of mitochondrial dysfunction (laboratorial or histological) and known mitochondrial DNA gene mutations. Clinical features of MELAS are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALeu(UUR) gene of the DNAmt, mainly A3243G, are responsible for more of 80% of MELAS cases. Morphological changes seen upon muscle biopsy in MELAS include a substantive proportion of ragged red fibers (RRF) and the presence of vessels with a strong reaction for succinate dehydrogenase. In this review, we discuss mainly diagnostic criterion, clinical and laboratory manifestations, brain images, histology and molecular findings as well as some differential diagnoses and current treatments. Keywords: MELAS, mitochondria, myopathy, stroke, encephalopathy, genetics. RESUMO Miopatia mitocondrial, encefalopatia, acidose lática, e episódios semelhantes a acidente vascular cerebral (MELAS) é uma rara doença mitocondrial. Os critérios diagnósticos para MELAS incluem as manifestações típicas da doença: episódios semelhantes a acidente vascular cerebral, encefalopatia, evidência de disfunção mitocondrial (laboratorial ou histológica) e mutação conhecida em genes do DNA mitocondrial.
    [Show full text]
  • Congenital Disorders of Glycosylation from a Neurological Perspective
    brain sciences Review Congenital Disorders of Glycosylation from a Neurological Perspective Justyna Paprocka 1,* , Aleksandra Jezela-Stanek 2 , Anna Tylki-Szyma´nska 3 and Stephanie Grunewald 4 1 Department of Pediatric Neurology, Faculty of Medical Science in Katowice, Medical University of Silesia, 40-752 Katowice, Poland 2 Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland; [email protected] 3 Department of Pediatrics, Nutrition and Metabolic Diseases, The Children’s Memorial Health Institute, W 04-730 Warsaw, Poland; [email protected] 4 NIHR Biomedical Research Center (BRC), Metabolic Unit, Great Ormond Street Hospital and Institute of Child Health, University College London, London SE1 9RT, UK; [email protected] * Correspondence: [email protected]; Tel.: +48-606-415-888 Abstract: Most plasma proteins, cell membrane proteins and other proteins are glycoproteins with sugar chains attached to the polypeptide-glycans. Glycosylation is the main element of the post- translational transformation of most human proteins. Since glycosylation processes are necessary for many different biological processes, patients present a diverse spectrum of phenotypes and severity of symptoms. The most frequently observed neurological symptoms in congenital disorders of glycosylation (CDG) are: epilepsy, intellectual disability, myopathies, neuropathies and stroke-like episodes. Epilepsy is seen in many CDG subtypes and particularly present in the case of mutations
    [Show full text]
  • Orphanet Report Series Rare Diseases Collection
    Marche des Maladies Rares – Alliance Maladies Rares Orphanet Report Series Rare Diseases collection DecemberOctober 2013 2009 List of rare diseases and synonyms Listed in alphabetical order www.orpha.net 20102206 Rare diseases listed in alphabetical order ORPHA ORPHA ORPHA Disease name Disease name Disease name Number Number Number 289157 1-alpha-hydroxylase deficiency 309127 3-hydroxyacyl-CoA dehydrogenase 228384 5q14.3 microdeletion syndrome deficiency 293948 1p21.3 microdeletion syndrome 314655 5q31.3 microdeletion syndrome 939 3-hydroxyisobutyric aciduria 1606 1p36 deletion syndrome 228415 5q35 microduplication syndrome 2616 3M syndrome 250989 1q21.1 microdeletion syndrome 96125 6p subtelomeric deletion syndrome 2616 3-M syndrome 250994 1q21.1 microduplication syndrome 251046 6p22 microdeletion syndrome 293843 3MC syndrome 250999 1q41q42 microdeletion syndrome 96125 6p25 microdeletion syndrome 6 3-methylcrotonylglycinuria 250999 1q41-q42 microdeletion syndrome 99135 6-phosphogluconate dehydrogenase 67046 3-methylglutaconic aciduria type 1 deficiency 238769 1q44 microdeletion syndrome 111 3-methylglutaconic aciduria type 2 13 6-pyruvoyl-tetrahydropterin synthase 976 2,8 dihydroxyadenine urolithiasis deficiency 67047 3-methylglutaconic aciduria type 3 869 2A syndrome 75857 6q terminal deletion 67048 3-methylglutaconic aciduria type 4 79154 2-aminoadipic 2-oxoadipic aciduria 171829 6q16 deletion syndrome 66634 3-methylglutaconic aciduria type 5 19 2-hydroxyglutaric acidemia 251056 6q25 microdeletion syndrome 352328 3-methylglutaconic
    [Show full text]
  • Haematological Abnormalities in Mitochondrial Disorders
    Singapore Med J 2015; 56(7): 412-419 Original Article doi: 10.11622/smedj.2015112 Haematological abnormalities in mitochondrial disorders Josef Finsterer1, MD, PhD, Marlies Frank2, MD INTRODUCTION This study aimed to assess the kind of haematological abnormalities that are present in patients with mitochondrial disorders (MIDs) and the frequency of their occurrence. METHODS The blood cell counts of a cohort of patients with syndromic and non-syndromic MIDs were retrospectively reviewed. MIDs were classified as ‘definite’, ‘probable’ or ‘possible’ according to clinical presentation, instrumental findings, immunohistological findings on muscle biopsy, biochemical abnormalities of the respiratory chain and/or the results of genetic studies. Patients who had medical conditions other than MID that account for the haematological abnormalities were excluded. RESULTS A total of 46 patients (‘definite’ = 5; ‘probable’ = 9; ‘possible’ = 32) had haematological abnormalities attributable to MIDs. The most frequent haematological abnormality in patients with MIDs was anaemia. 27 patients had anaemia as their sole haematological problem. Anaemia was associated with thrombopenia (n = 4), thrombocytosis (n = 2), leucopenia (n = 2), and eosinophilia (n = 1). Anaemia was hypochromic and normocytic in 27 patients, hypochromic and microcytic in six patients, hyperchromic and macrocytic in two patients, and normochromic and microcytic in one patient. Among the 46 patients with a mitochondrial haematological abnormality, 78.3% had anaemia, 13.0% had thrombopenia, 8.7% had leucopenia and 8.7% had eosinophilia, alone or in combination with other haematological abnormalities. CONCLUSION MID should be considered if a patient’s abnormal blood cell counts (particularly those associated with anaemia, thrombopenia, leucopenia or eosinophilia) cannot be explained by established causes.
    [Show full text]
  • Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders
    Supplementary Online Content Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA. doi:10.1001/jama.2014.14604. eMethods 1. Sample acquisition and pre-test sample processing eMethods 2. Exome capture and sequencing eMethods 3. Sequence data analysis eMethods 4. Variant filtration and interpretation eMethods 5. Determination of variant pathogenicity eFigure 1. UCLA Clinical Exome Sequencing (CES) workflow eFigure 2. Variant filtration workflow starting with ~21K variants across the exome and comparing the mean number of variants observed from trio-CES versus proband-CES eFigure 3. Variant classification workflow for the variants found within the primary genelist (PGL) eTable 1. Metrics used to determine the adequate quality of the sequencing test for each sample eTable 2. List of molecular diagnoses made eTable 3. List of copy number variants (CNVs) and uniparental disomy (UPD) reported and confirmatory status eTable 4. Demographic summary of 814 cases eTable 5. Molecular Diagnosis Rate of Phenotypic Subgroups by Age Group for Other Clinical Exome Sequencing References © 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 This supplementary material has been provided by the authors to give readers additional information about their work. © 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eMethods 1. Sample acquisition and pre-test sample processing. Once determined by the ordering physician that the patient's presentation is clinically appropriate for CES, patients were offered the test after a counseling session ("pre-test counseling") [eFigure 1].
    [Show full text]
  • Migraines: Genetic Studies Pietro Cortelli Mirella Mochi and Some Practical Considerations
    J Headache Pain (2003) 4:47–56 DOI 10.1007/s10194-003-0030-0 EDITORIAL Pasquale Montagna The “typical” migraines: genetic studies Pietro Cortelli Mirella Mochi and some practical considerations Abstract Epidemiological genetic, in the inflammation cascade; etc.) family and twin studies show that the did not result in uniformely accepted typical migraines carry a substantial findings. Linkage and genome wide genetic risk; they are currently con- scans gave evidence for several ceptualized as complex genetic dis- genetic susceptibility loci, still how- ౧ P. Montagna ( ) • M. Mochi eases. Several genetic association ever in need of confirmation. Careful Department of Clinical Neurosciences, University of Bologna Medical School, and linkage studies have been per- dissection of the clinical phenotypes Via Ugo Foscolo 7, I-40123 Bologna, Italy formed in the typical migraines. and trigger factors shall greatly help e-mail: [email protected] Candidate gene studies based on “a future efforts in the quest for the Tel.: +39-051-6442179 priori” pathogenic models of genetic basis of the typical Fax: +39-051-6442165 migraine (migraine as a calcium migraines. P. Cortelli channelopathy; a mitochondrial Department of Neurology, DNA disorder; a disorder in the University of Modena and Reggio Emilia, metabolism of serotonin or Key words Migraine • Aura • Modena, Italy dopamine; in vascular risk factors or Genetics • Cardiovascular risk prove heritability, since it may result from shared envi- “Typical” migraine as a complex disease: genetic ronmental factors. It is therefore interesting to note that at epidemiology, twin and segregation analysis studies least one genetic epidemiology survey found an increased disease risk for migraine in first-degree relatives com- That migraine runs in families is an ancient observation.
    [Show full text]
  • Veille Neuromusculaire / Neuromuscular Alert Sommaire Par
    Veille Neuromusculaire / Neuromuscular Alert Bibliographie sur les maladies neuromusculaires / Bibliography on neuromuscular disorders n° 2018-08-1 du 06 au 26 Août 2018 (August 6 to 26, 2018) Publiée tous les 15 jours par le service de documentation de l'AFM-Téléthon, la "Veille Neuromusculaire" contient les dernières références intégrées dans Pubmed. La liste des pathologies concernées par cette veille est celle de la Fiche Technique Savoir & Comprendre "Avancées médico-scientifiques neuromusculaires" publiée par l'AFM-Téléthon et mise à jour en octobre 2012. Vous trouverez les veilles précédentes sur notre portail documentaire dédié aux maladies neuromusculaires Myobase Every two weeks, you will find in the “Neuromuscular Alert” the latest references published in Pubmed. The list of covered diseases comes from the October 2012 publication "Avancées médico-scientifiques neuromusculaires", Fiche technique Savoir & Comprendre published by l'AFM-Téléthon. Previous alerts are available for consultation on Myobase, the AFM bibliographic database in the field of Neuromuscular Disorders Sommaire par maladies / diseases Amyotrophies spinales – Spinal muscular atrophies .................................................................................. 3 Amyotrophie spinale proximale liée à SMN1 – SMN1-related spinal muscular atrophy (SMA) .............. 3 Canalopathies musculaires – Muscular channelopathies........................................................................... 7 Maladie de Charcot-Marie-Tooth – Charcot-Marie-Tooth disease
    [Show full text]
  • The Role of Genetics in Cardiomyopaties: a Review Luis Vernengo and Haluk Topaloglu
    Chapter The Role of Genetics in Cardiomyopaties: A Review Luis Vernengo and Haluk Topaloglu Abstract Cardiomyopathies are defined as disorders of the myocardium which are always associated with cardiac dysfunction and are aggravated by arrhythmias, heart failure and sudden death. There are different ways of classifying them. The American Heart Association has classified them in either primary or secondary cardiomyopathies depending on whether the heart is the only organ involved or whether they are due to a systemic disorder. On the other hand, the European Society of Cardiology has classified them according to the different morphological and functional phenotypes associated with their pathophysiology. In 2013 the MOGE(S) classification started to be published and clinicians have started to adopt it. The purpose of this review is to update it. Keywords: cardiomyopathy, primary and secondary cardiomyopathies, sarcomeric genes 1. Introduction Cardiomyopathies can be defined as disorders of the myocardium associated with cardiac dysfunction and which are aggravated by arrhythmias, heart failure and sudden death [1]. The aim of this chapter is focused on updating and reviewing cardiomyopathies. In 1957, Bridgen coined the word “cardiomyopathy” for the first time and in 1958, the British pathologist Teare reported nine cases of septum hypertrophy [2]. Genetics has played a key role in the understanding of these disorders. In general, the overall prevalence of cardiomyopathies in the world population is 3%. The genetic forms of cardiomyopathies are characterized by both locus and allelic heterogeneity. The mutations of the genes which encode for a variety of proteins of the sarcomere, cytoskeleton, nuclear envelope, sarcolemma, ion channels and intercellular junctions alter many pathways and cellular structures affecting in a negative form the mechanism of muscle contraction and its function, and the sensi- tivity of ion channels to electrolytes, calcium homeostasis and how mechanic force in the myocardium is generated and transmitted [3, 4].
    [Show full text]
  • Cognitive Deficits in Myopathies
    International Journal of Molecular Sciences Review Cognitive Deficits in Myopathies Eleni Peristeri 1, Athina-Maria Aloizou 1, Paraskevi Keramida 1, Zisis Tsouris 1, Vasileios Siokas 1, Alexios-Fotios A. Mentis 2,3 and Efthimios Dardiotis 1,* 1 Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly, University Hospital of Larissa, PC 41110 Larissa, Greece; [email protected] (E.P.); [email protected] (A.-M.A.); [email protected] (P.K.); [email protected] (Z.T.); [email protected] (V.S.) 2 Public Health Laboratories, Hellenic Pasteur Institute, PC 11521 Athens, Greece; [email protected] 3 Department of Microbiology, Faculty of Medicine, University of Thessaly, University Hospital of Larissa, PC 41110 Larissa, Greece * Correspondence: [email protected]; Tel.: +30-241-350-1137 Received: 7 April 2020; Accepted: 25 May 2020; Published: 27 May 2020 Abstract: Myopathies represent a wide spectrum of heterogeneous diseases mainly characterized by the abnormal structure or functioning of skeletal muscle. The current paper provides a comprehensive overview of cognitive deficits observed in various myopathies by consulting the main libraries (Pubmed, Scopus and Google Scholar). This review focuses on the causal classification of myopathies and concomitant cognitive deficits. In most studies, cognitive deficits have been found after clinical observations while lesions were also present in brain imaging. Most studies refer to hereditary myopathies, mainly Duchenne muscular dystrophy (DMD), and myotonic dystrophies (MDs); therefore, most of the overview will focus on these subtypes of myopathies. Most recent bibliographical sources have been preferred. Keywords: myopathies; dystrophies; cognitive deficits; behavioral indices; brain imaging indices 1. Introduction Myopathies represent a wide spectrum of heterogeneous diseases mainly characterized by the abnormal structure or functioning of skeletal muscle [1]; they can be hereditary or acquired, and can also manifest during the course of endocrine, autoimmune or metabolic disorders.
    [Show full text]
  • Mitochondrial Diseases in North America an Analysis of the NAMDC Registry
    ARTICLE OPEN ACCESS Mitochondrial diseases in North America An analysis of the NAMDC Registry Emanuele Barca, MD, PhD, Yuelin Long, MS, Victoria Cooley, MS, Robert Schoenaker, MD, BS, Correspondence Valentina Emmanuele, MD, PhD, Salvatore DiMauro, MD, Bruce H. Cohen, MD, Amel Karaa, MD, Dr. Hirano [email protected] Georgirene D. Vladutiu, PhD, Richard Haas, MBBChir, Johan L.K. Van Hove, MD, PhD, Fernando Scaglia, MD, Sumit Parikh, MD, Jirair K. Bedoyan, MD, PhD, Susanne D. DeBrosse, MD, Ralitza H. Gavrilova, MD, Russell P. Saneto, DO, PhD, Gregory M. Enns, MBChB, Peter W. Stacpoole, MD, PhD, Jaya Ganesh, MD, Austin Larson, MD, Zarazuela Zolkipli-Cunningham, MD, Marni J. Falk, MD, Amy C. Goldstein, MD, Mark Tarnopolsky, MD, PhD, Andrea Gropman, MD, Kathryn Camp, MS, RD, Danuta Krotoski, PhD, Kristin Engelstad, MS, Xiomara Q. Rosales, MD, Joshua Kriger, MS, Johnston Grier, MS, Richard Buchsbaum, John L.P. Thompson, PhD, and Michio Hirano, MD Neurol Genet 2020;6:e402. doi:10.1212/NXG.0000000000000402 Abstract Objective To describe clinical, biochemical, and genetic features of participants with mitochondrial diseases (MtDs) enrolled in the North American Mitochondrial Disease Consortium (NAMDC) Registry. Methods This cross-sectional, multicenter, retrospective database analysis evaluates the phenotypic and molecular characteristics of participants enrolled in the NAMDC Registry from September 2011 to December 2018. The NAMDC is a network of 17 centers with expertise in MtDs and includes both adult and pediatric specialists. Results One thousand four hundred ten of 1,553 participants had sufficient clinical data for analysis. For this study, we included only participants with molecular genetic diagnoses (n = 666).
    [Show full text]
  • Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-Like Episodes—MELAS Syndrome
    CASE REPORT Ochsner Journal 17:296–301, 2017 Ó Academic Division of Ochsner Clinic Foundation Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes—MELAS Syndrome Caitlin Henry, MS,1 Neema Patel, MD,2 William Shaffer, MD,3 Lillian Murphy, MD,4 Joe Park, MD,4 Bradley Spieler, MD4 1Louisiana State University Health Sciences Center, School of Medicine, New Orleans, LA 2Department of Radiology, Mayo Clinic Hospital, Jacksonville, FL 3Department of Radiology, Slidell Memorial Hospital, Slidell, LA 4Department of Radiology, Louisiana State University Health Sciences Center, New Orleans, LA Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and waning nervous system and muscle dysfunction. MELAS syndrome may overlap with other neurologic disorders but shows distinctive imaging features. Case Report: We present the case of a 28-year-old female with atypical stroke-like symptoms, a strong family history of stroke- like symptoms, and a relapsing-remitting course for several years. We discuss the imaging features distinctive to the case, the mechanism of the disease, typical presentation, imaging diagnosis, and disease management. Conclusion: This case is a classic example of the relapse-remitting MELAS syndrome progression with episodic clinical flares and fluctuating patterns of stroke-like lesions on imaging. MELAS is an important diagnostic consideration when neuroimaging reveals a pattern of disappearing and relapsing cortical brain lesions that may occur in different areas of the brain and are not necessarily limited to discrete vascular territories. Future studies should investigate disease mechanisms at the cellular level and the value of advanced magnetic resonance imaging techniques for a targeted approach to therapy.
    [Show full text]