Muscular Dystrophies: What the Radiologist Should Know
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A Schematic Approach to Hypotonia in Infancy
Leyenaar.qxd 8/26/2005 4:03 PM Page 397 NEUROLOGY SUBSPECIALTY ARTICLE A schematic approach to hypotonia in infancy JoAnna Leyenaar MD MPH, Peter Camfield MD FRCPC, Carol Camfield MD FRCPC J Leyenaar, P Camfield, C Camfield. A schematic approach Une démarche schématique envers l’hypotonie to hypotonia in infancy. Paediatr Child Health 2005; pendant la première enfance 10(7):397-400. L’hypotonie peut être le signe révélateur de nombreuses maladies Hypotonia may be the presenting sign for many systemic diseases and systémiques ou du système nerveux. Le présent article traite d’une diseases of the nervous system. The present paper discusses a rational, démarche diagnostique rationnelle, simple et précise envers l’hypotonie simple and accurate diagnostic approach to hypotonia in infancy, pendant la première enfance, illustrée par le cas d’une fillette de cinq mois illustrated by the case of a five-month-old infant girl recently referred récemment aiguillée vers le IWK Health Centre de Halifax, en Nouvelle- to the IWK Health Centre in Halifax, Nova Scotia. Key points in the Écosse. Les principaux points de l’anamnèse et de l’examen physique sont history and physical examination are outlined to allow a tailored exposés afin de permettre une exploration personnalisée de la patiente et investigation both for the patient and for other hypotonic infants. A des autres nourrissons hypotoniques. Un exposé sur une importante discussion of an important neuromuscular disease, diagnosed in the maladie neuromusculaire, diagnostiquée chez la patiente, conclut l’article. present patient, concludes the paper. Key Words: Hypotonia; Infant; Spinal muscular atrophy nfants with hypotonia pose challenges for clinicians respiratory syncytial virus-positive bronchiolitis. -
The Role of Z-Disc Proteins in Myopathy and Cardiomyopathy
International Journal of Molecular Sciences Review The Role of Z-disc Proteins in Myopathy and Cardiomyopathy Kirsty Wadmore 1,†, Amar J. Azad 1,† and Katja Gehmlich 1,2,* 1 Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK; [email protected] (K.W.); [email protected] (A.J.A.) 2 Division of Cardiovascular Medicine, Radcliffe Department of Medicine and British Heart Foundation Centre of Research Excellence Oxford, University of Oxford, Oxford OX3 9DU, UK * Correspondence: [email protected]; Tel.: +44-121-414-8259 † These authors contributed equally. Abstract: The Z-disc acts as a protein-rich structure to tether thin filament in the contractile units, the sarcomeres, of striated muscle cells. Proteins found in the Z-disc are integral for maintaining the architecture of the sarcomere. They also enable it to function as a (bio-mechanical) signalling hub. Numerous proteins interact in the Z-disc to facilitate force transduction and intracellular signalling in both cardiac and skeletal muscle. This review will focus on six key Z-disc proteins: α-actinin 2, filamin C, myopalladin, myotilin, telethonin and Z-disc alternatively spliced PDZ-motif (ZASP), which have all been linked to myopathies and cardiomyopathies. We will summarise pathogenic variants identified in the six genes coding for these proteins and look at their involvement in myopathy and cardiomyopathy. Listing the Minor Allele Frequency (MAF) of these variants in the Genome Aggregation Database (GnomAD) version 3.1 will help to critically re-evaluate pathogenicity based on variant frequency in normal population cohorts. -
Current and Emerging Therapies in Becker Muscular Dystrophy (BMD)
Acta Myologica • 2019; XXXVIII: p. 172-179 OPEN ACCESS © Gaetano Conte Academy - Mediterranean Society of Myology Current and emerging therapies in Becker muscular dystrophy (BMD) Corrado Angelini, Roberta Marozzo and Valentina Pegoraro Neuromuscular Center, IRCCS San Camillo Hospital, Venice, Italy Becker muscular dystrophy (BMD) has onset usually in child- tients with a deletion in the dystrophin gene that have nor- hood, frequently by 11 years. BMD can present in several ways mal muscle strength and endurance, but present high CK, such as waddling gait, exercise related cramps with or with- and so far their follow-up and treatment recommenda- out myoglobinuria. Rarely cardiomyopathy might be the pre- senting feature. The evolution is variable. BMD is caused by tions are still a matter of debate. Patients with early cardi- dystrophin deficiency due to inframe deletions, mutations or omyopathy are also a possible variant of BMD (4, 5) and duplications in dystrophin gene (Xp21.2) We review here the may be susceptible either to specific drug therapy and/or evolution and current therapy presenting a personal series of to cardiac transplantation (6-8). Here we cover emerging cases followed for over two decades, with multifactorial treat- therapies considering follow-up, and exemplifying some ment regimen. Early treatment includes steroid treatment that phenotypes and treatments by a few study cases. has been analized and personalized for each case. Early treat- ment of cardiomyopathy with ACE inhibitors is recommended and referral for cardiac transplantation is appropriate in severe cases. Management includes multidisciplinary care with physi- Pathophysiology and rationale of otherapy to reduce joint contractures and prolong walking. -
This Letter Is for Families with Variant(S) in the Titin Gene, Also
This letter is for families with variant(s) in the Titin gene , also abbreviated as TTN . Changes in the Titin protein may cause muscle weakness as well as heart problems . You will need to discuss with your doctor if and how your Titin variant affects your health. What is Titin? Titin is a very large protein. It’s huge! In fact, Titin is the largest protein in the human body. The Titin protein is located in each of the individual muscle cells in our bodies. It is also found in the heart, which is a very specialized muscle. Muscles need Titin in order to work and move. You can learn more about Titin here: http://titinmyopathy.com . What is a Titin Myopathy? In medical terms, “Myo” refers to muscle and “-opathy” at the end of a word means that the word describes a medical disease or condition. So “myopathy” is a medical illness involving muscles. Myopathies result in muscle weakness and muscle fatigue. “Titin Myopathy” is a specific category of myopathy where the muscle problem is caused by a change in the Titin gene and subsequently the protein. What is a Titin-related Dystrophy? A Titin dystrophy is a muscle disorder where muscle cells break down. Dystrophies generally result in weakness that gets worse over time. A common heart problem caused by variants in the Titin gene is known as dilated cardiomyopathy. Sometimes other heart issues are also present in people with changes in their Titin gene. It is a good idea to have a checkup from a heart doctor if you have even a single variant in the Titin gene. -
Nemaline MYOPATHY Myopathy
NEMALINENemaline MYOPATHY Myopathy due to chest muscle weakness, feeding and swallowing What is nemaline myopathy? problems, and speech difficulties. Often, children with the condition have an elongated face and a Nemaline myopathy (NM) is a group of high arched palate. rare, inherited conditions that affect muscle tone and strength. It is also What causes nemaline myopathy? The condition can be caused by a mutation in one known as rod body disease because of several different genes that are responsible for at a microscopic level, abnormal making muscle protein. Most cases of nemaline rod-shaped bodies (nemalines) can myopathy are inherited, although there are some- be seen in affected muscle tissue. times sporadic cases. People with a family history may choose to undergo genetic counseling to help At various stages in life, the muscles of understand the risks of passing the gene on to their the shoulders, upper arms, pelvis and children. thighs may be affected. Symptoms usually start anywhere from birth to What are the types of nemaline myopathy? There are two main groups of nemaline myopathy: early childhood. In rare cases, it is ‘typical’ and ‘severe.’ Typical nemaline myopathy diagnosed during adulthood. NM is the most common form, presenting usually in affects an estimated 1 in 50,000 infants with muscle weakness and floppiness. It may people -- both males and females. be slowly progressive or non progressive, and most adults are able to walk. Severe nemaline myopathy is characterized by absence of spontaneous movement What are the symptoms? or respiration at birth, and often leads to death in Symptoms vary depending on the age of onset of the first months of life. -
Myasthenia and Related Disorders of the Neuromuscular Junction Jennifer Spillane, David J Beeson, Dimitri M Kullmann
Myasthenia and related disorders of the neuromuscular junction Jennifer Spillane, David J Beeson, Dimitri M Kullmann To cite this version: Jennifer Spillane, David J Beeson, Dimitri M Kullmann. Myasthenia and related disorders of the neuromuscular junction. Journal of Neurology, Neurosurgery and Psychiatry, BMJ Publishing Group, 2010, 81 (8), pp.850. 10.1136/jnnp.2008.169367. hal-00557404 HAL Id: hal-00557404 https://hal.archives-ouvertes.fr/hal-00557404 Submitted on 19 Jan 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Myasthenia and related disorders of the neuromuscular junction Jennifer Spillane1, David J Beeson2 and Dimitri M Kullmann1 1UCL Institute of Neurology 2Weatherall Institute for Molecular Medicine, Oxford University Abtract Our understanding of transmission at the neuromuscular junction has increased greatly in recent years. We now recognise a wide variety of autoimmune and genetic diseases that affect this specialised synapse, causing muscle weakness and fatigue. These disorders greatly affect quality of life and rarely can be fatal. Myasthenia Gravis is the most common disorder and is most commonly caused by auto‐antibodies targeting postsynaptic acetylcholine receptors (AChRs). Antibodies to muscle‐specific kinase (MuSK) are detected in a variable proportion of the remainder. -
The Myotonic Dystrophies: Diagnosis and Management Chris Turner,1 David Hilton-Jones2
Review J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2008.158261 on 22 February 2010. Downloaded from The myotonic dystrophies: diagnosis and management Chris Turner,1 David Hilton-Jones2 1Department of Neurology, ABSTRACT asymptomatic relatives as well as prenatal and National Hospital for Neurology There are currently two clinically and molecularly defined preimplantation diagnosis can also be performed.7 and Neurosurgery, London, UK 2Department of Clinical forms of myotonic dystrophy: (1) myotonic dystrophy Neurology, The Radcliffe type 1 (DM1), also known as ‘Steinert’s disease’; and Anticipation Infirmary, Oxford, UK (2) myotonic dystrophy type 2 (DM2), also known as DMPK alleles greater than 37 CTG repeats in length proximal myotonic myopathy. DM1 and DM2 are are unstable and may expand in length during meiosis Correspondence to progressive multisystem genetic disorders with several and mitosis. Children of a parent with DM1 may Dr C Turner, Department of Neurology, National Hospital for clinical and genetic features in common. DM1 is the most inherit repeat lengths considerably longer than those Neurology and Neurosurgery, common form of adult onset muscular dystrophy whereas present in the transmitting parent. This phenomenon Queen Square, London WC1N DM2 tends to have a milder phenotype with later onset of causes ‘anticipation’, which is the occurrence of 3BG, UK; symptoms and is rarer than DM1. This review will focus increasing disease severity and decreasing age of onset [email protected] on the clinical features, diagnosis and management of in successive generations. The presence of a larger Received 1 December 2008 DM1 and DM2 and will briefly discuss the recent repeat leads to earlier onset and more severe disease Accepted 18 December 2008 advances in the understanding of the molecular and causes the more severe phenotype of ‘congenital’ pathogenesis of these diseases with particular reference DM1 (figure 2).8 9 A child with congenital DM 1 to new treatments using gene therapy. -
Combined Web 759..782
Movement Disorders Vol. 24, No. 5, 2009, pp. 759–782 Ó 2009 Movement Disorder Society Brief Reports Clinical Characteristics of Psychogenic movement disorders (PMDs) are not uncommon in movement disorder clinics.1 PMDs may 49 Patients with Psychogenic phenomenologically mimic almost all movement disor- Movement Disorders in a Tertiary ders. The most common movement disorder is tremor, followed by dystonia and others.2–5 Clinic in Turkey Diagnostic criteria for PMDs was first identified by Fahn and Williams, based on atypical and common Sibel Ertan, MD,1 Derya Uluduz, MD,1 clinical clues.6 Later, other authors described additional 1* 1 Sibel O¨ zekmekc¸i, MD, Gu¨nes Kiziltan, MD, features to distinguish PMD patients from those with 2 1 1 Turan Ertan, MD, Cengiz Yalc¸inkaya, MD, , and neurogenic movement disorders.7–9 ¨ 1 and C¸ igdem Ozkara, MD Because there is no study written in English on any 1Department of Neurology, Cerrahpasa Faculty of Medicine, hospital-based data of PMDs in Turkey, we aimed to Istanbul University, Istanbul, Turkey; 2Department of identify the frequency and phenomenological features Psychiatry, Cerrahpasa Faculty of Medicine, Istanbul of PMDs in our patient population with movement dis- University, Istanbul, Turkey orders. Abstract: Patients admitted to movement disorders outpa- tient unit at a university hospital between January 2002 and June 2007 were screened for psychogenic movement PATIENTS AND METHODS disorders (PMDs). Out of 1,743 patients, 49 patients Patients admitted to our Movement Disorders Unit (2.8%), including four children, were diagnosed to have between January 2002 and June 2007, were screened PMDs. Women to men ratio was 34/15. -
Diagnosis and Treatment of Facioscapulohumeral Muscular Dystrophy: 2015 Guidelines Steven Karceski Neurology 2015;85;E41-E43 DOI 10.1212/WNL.0000000000001865
PATIENT PAGE Section Editors Diagnosis and treatment of DavidC.Spencer,MD Steven Karceski, MD facioscapulohumeral muscular dystrophy 2015 guidelines Steven Karceski, MD WHAT DID THE AUTHORS STUDY? Dr. Tawil led a in people with FSHD. However, a person with committee of doctors who specialize in diagnosing FSHD could develop heart problems unrelated to and treating facioscapulohumeral muscular dystrophy FSHD. If a person with FSHD developed heart prob- (FSHD). Together, they reviewed published articles lems, he or she would need to see a doctor for an eval- and research in FSHD and similar muscular dystro- uation and treatment. phies. They assembled detailed recommendations Although rare, patients with a low number of about the diagnosis and treatment of people with copies of D4Z4 may develop problems with their FSHD.1 vision. They develop Coats disease, which can be de- tected by an ophthalmologist using special equip- HOW IS FSHD DIAGNOSED? The initial step to the ment called indirect ophthalmoscopy. In short, a diagnosis of FSHD is taking a careful medical history. person who has a low number of copies should be This starts in the doctor’s office. The doctor will ask screened and evaluated for this possibility by a many questions about the person’s weakness: how it trained eye specialist. started, where it is most noticeable, how quickly it is Pain is common in people with FSHD. The pain worsening, and whether there is a family history of occurs in the muscles and bones. It often responds to the same kind of problem. If there is a family history several medications and physical therapy. -
X-Linked Myotubular Myopathy and Chylothorax
ARTICLE IN PRESS Neuromuscular Disorders xxx (2007) xxx–xxx www.elsevier.com/locate/nmd Case report X-linked myotubular myopathy and chylothorax Koenraad Smets * Department of Neonatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium Received 10 August 2007; received in revised form 4 October 2007; accepted 24 October 2007 Abstract X-linked myotubular myopathy usually presents at birth with hypotonia and respiratory distress. Phenotypic presentation, however, can be extreme variable. We report on a newborn baby, who presented with the severe form of the disease. In the second week of life, he developed a clinically relevant chylothorax, needing drainage and treatment with octreotide acetate. Pleural effusions are frequently described in patients with congenital myotonic dystrophy. To our knowledge, the association of chylothorax and X-linked myotubular myopathy has not been described to date. As chylothorax could not be attributed to any evident condition in this child, perhaps it may be added to the clinical spectrum of X-linked myotubular myopathy. Ó 2007 Elsevier B.V. All rights reserved. Keywords: X-linked myotubular myopathy; Chylothorax 1. Introduction drainage (Fig. 1). Laboratory examination was compatible with chylothorax (5230 white blood cells/ll, 98% lympho- Congenital myopathies often present with hypotonia cytes; chylomicrons were present; triglycerides 746 mg/dl). and respiratory distress from birth, although their expres- There were no central venous catheters in place who could sion may be delayed. In most cases muscle biopsy is war- have caused thrombosis, impairing lymphatic flow, neither ranted for definitive diagnosis. In some instances could any other risk factor for chylothorax be identified. -
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]. -
Consensus-Based Care Recommendations for Adults with Myotonic Dystrophy Type 1
Consensus-based Care Recommendations for Adults with Myotonic Dystrophy Type 1 I Consensus-based Care Recommendations for Adults with Myotonic Dystrophy Type 1 Due to the multisystemic nature of this disease, the studies and rigorous evidence needed to drive the creation of an evidence-based guideline for the clinical care of adult myotonic dystrophy type 1 (DM1) patients are not currently available for all affected body systems and symptoms. In order to improve and standardize care for this disorder now, more than 65 leading myotonic dystrophy (DM) clinicians in Western Europe, the UK, Canada and the US joined in a process started in Spring 2015 and concluded in Spring 2017 to create the Consensus-based Care Recommendations for Adults with Myotonic Dystrophy Type 1. The project was organized and supported by the Myotonic Dystrophy Foundation (MDF). A complete list of authors and an overview of the process is available in Addendum 1. A complete reading list for each of the study area sections is available in Addendum 2. An Update Policy has been adopted for this document and will direct a systematic review of literature and appropriate follow up every three years. Myotonic Dystrophy Foundation staff will provide logistical and staff support for the update process. A Quick Reference Guide extrapolated from the Consensus-based Care Recommendations is available here http://www.myotonic.org/clinical-resources For more information, visit myotonic.org. Myotonic Dystrophy Foundation 1 www.myotonic.org Table of Contents Life-threatening symptoms