Practice Guideline American Association of Neuromuscular & Electrodiagnostic Medicine EVIDENCE-BASED GUIDELINE: DIAGNOSIS AND TREATMENT OF LIMB-GIRDLE AND DISTAL DYSTROPHIES Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine Pushpa Narayanaswami, MBBS, DM, FAAN1; Michael Weiss, MD, FAAN2; Duygu Selcen, MD3; William David, MD, PhD4; Elizabeth Raynor, MD1; Gregory Carter, MD5; Matthew Wicklund, MD, FAAN6; Richard J. Barohn, MD, FAAN7; Erik Ensrud, MD8,10; Robert C. Griggs, MD, FAAN9; Gary Gronseth, MD, FAAN7; Anthony A. Amato, MD, FAAN10 (1) Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA (2) Department of Neurology, University of Washington Medical Center, Seattle, WA (3) Department of Neurology, Mayo Clinic, Rochester, MN (4) Department of Neurology, Massachusetts General Hospital, Boston, MA/Harvard Medical School, Boston, MA (5) St Luke's Rehabilitation Institute, Spokane, WA (6) Department of Neurology, Penn State Hershey Medical Center, Hershey, PA (7) Department of Neurology, University of Kansas Medical Center, Kansas City, KS (8) Neuromuscular Center, Boston VA Medical Center, Boston, MA (9) Department of Neurology, University of Rochester Medical Center, Rochester, NY 1 (10) Department of Neurology, Brigham and Women’s Hospital, Boston, MA/Harvard Medical School, Boston, MA Correspondence to American Academy of Neurology: [email protected] Approved by the AAN Guideline Development Subcommittee on July 13, 2013; by the AAN Practice Committee on February 3, 2014; by the AANEM Board of Directors on July 10, 2014; and by the AANI Board of Directors on July 7, 2014. STUDY FUNDING Funding for this publication was made possible (in part) by grant DD10-1012 from the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The remaining funding was provided by the American Academy of Neurology. This guideline was endorsed by the American Academy of Physical Medicine and Rehabilitation on April 17, 2014; by the Child Neurology Society on July 11, 2014; by the Jain Foundation on March 14, 2013; and by the Muscular Dystrophy Foundation on August 27, 2014. 2 3 AUTHOR CONTRIBUTIONS Pushpa Narayanaswami: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content, study supervision. Michael Weiss: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. Duygu Selcen: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. William David: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. Elizabeth Raynor: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. Gregory Carter: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. Matthew Wicklund: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. 4 Richard J. Barohn: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. Erik Ensrud: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. Robert C. Griggs: study concept and design. Gary Gronseth: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content. Anthony A. Amato: study concept and design, acquisition of data, analysis or interpretation of data, drafting/revising the manuscript, critical revision of the manuscript for important intellectual content, study supervision. 5 DISCLOSURE Dr. Narayanaswami has received honoraria from the American Academy of Neurology (AAN) and the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). Dr. Weiss has served as a speaker for the AAN, AANEM, American Academy of Physical Medicine & Rehabilitation (AAPM&R), Athena Diagnostics, Nufactor, Walgreens, and Grifols Inc.; serves on speakers’ bureaus for Athena Diagnostics and Walgreens; has consulted for Genzyme Corporation, CSL Behring, Questcor Pharmaceuticals, and Washington State Labor and Industries; and has received research funding support from the ALS Therapy Alliance and Northeast ALS Consortium. Dr. Selcen has served as an editorial board member for Neuromuscular Disorders and has received funding for research from the National Institutes of Health (NIH). Dr. David reports no relevant disclosures. Dr. Raynor reports no relevant disclosures. Dr. Carter has served as the senior associate editor for Muscle & Nerve, has received honoraria from the AANEM and the Canadian Association of Physical Medicine and Rehabilitation, has received funding for research from the National Institutes on Aging and the National Institute on 6 Disability and Rehabilitation Research, and has testified on a case regarding the use of marijuana in pain. Dr. Wicklund has served on a scientific advisory board for Sarepta Therapeutics, has served on a speakers’ bureau for Genzyme, has received grant funding from Eli Lilly, and has collaborated on research without compensation with Athena Diagnostics.. Dr. Barohn has served as a consultant or on a scientific advisory board for Genzyme, Grifols, MedImmune, and Novartis; has received honoraria from Alexion, Isis, Baxter, Sarepta, and CSL Behring; and has received funding for research from the US Food and Drug Administration (FDA) and the NIH. Dr. Ensrud reports no relevant disclosures. Dr. Gronseth serves as an editorial advisory board member of Neurology Now, is an associate editor of Neurology, and receives honoraria from the AAN. Dr. Griggs consults for PTC Therapeutics (Chair of DSMB), Novartis (DSMB), Marathon Pharmaceuticals, Taro Pharmaceuticals, and Viromed (DSMB); receives funding from the NIH, the Italian Telethon (DSMB Chair), the Muscular Dystrophy Association, the Parent Project for Muscular Dystrophy, and the AAN; and receives royalties from Elsevier (for Cecil Essentials and Cecil Textbook of Medicine). 7 Dr. Amato has served as a consultant or on scientific advisory boards for MedImmune, Amgen, Biogen, DART, and Baxter; serves as an associate editor for Neurology and Muscle & Nerve; has received royalties from publishing from Neuromuscular Disorders; has received honoraria from the AAN and AANEM; and has received funding for research from Amgen, MedImmune, Novartis, the FDA, and the NIH. 8 ABBREVIATIONS AAN = American Academy of Neurology AD = autosomal dominant AE = adverse event ALS = amyotophic lateral sclerosis AR = autosomal recessive BMD = Becker muscular dystrophy CDC = Centers for Disease Control and Prevention CHF = congestive heart failure CI = confidence interval CK = creatine kinase CMD = congenital muscular dystrophy CMT = Charcot-Marie-Tooth syndrome CyA = cyclosporine A DMD = Duchenne muscular dystrophy EDB = extensor digitorum brevis EDMD = Emery-Dreifuss muscular dystrophy EF = ejection fraction EM = electron microscopy fALS = familial amyotophic lateral sclerosis FCMD = Fukuyama congenital muscular dystrophy FVC = forced vital capacity GH = growth hormone hIBM = hereditary inclusion body myopathy hIBMPFD = hereditary inclusion body myopathy with Paget disease and frontotemporal dementia HMERF = hereditary myopathy with early respiratory failure LDM = Laing distal myopathy LGMD = limb-girdle muscular dystrophyLVEF = left ventricular ejection fraction MEB = muscle-eye-brain disease MFM = myofibrillar myopathy MM3= Miyoshi myopathy type III MR = mental retardation PDB = Paget disease of bone PIRCs = percussion-induced rapid contractions RAE = right atrial enlargement ULN = upper limit of normal VO2 max = maximal oxygen uptake Wmax = maximal workload WWS = Walker-Warburg syndrome 9 ABSTRACT Objective: To review the current evidence and make practice recommendations regarding the diagnosis and treatment of limb-girdle muscular dystrophies (LGMDs). Methods: Systematic review and practice recommendation development using the American Academy of Neurology guideline development process. Results: Most LGMDs are rare, with estimated prevalences ranging from 0.07 per 100,000 to 0.43 per 100,000. The frequency of some muscular dystrophies varies based on the ethnic background of the population studied. Some LGMD subtypes have distinguishing features, including pattern of muscle involvement, cardiac abnormalities,