Cardiac and pulmonary findings in dysferlinopathy: A 3-year, longitudinal study

Ursula Moore, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Roberto Fernandez-Torron, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Marni Jacobs, Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, District of Columbia, USA.
Heather Gordish-Dressman, Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, District of Columbia, USA.
Jordi Diaz-Manera, Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Barcelona, Spain.
Meredith K. James, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Anna G. Mayhew, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Elizabeth Harris, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Michela Guglieri, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Laura E. Rufibach, The Jain Foundation, Seattle, Washington, USA.
Jia Feng, Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, District of Columbia, USA.
Andrew M. Blamire, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Pierre G. Carlier, University Paris-Saclay, CEA, DRF, Service Hospitalier Frederic Joliot, Orsay, France.
Simone Spuler, Charite Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.
John W. Day, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Kristi J. Jones, The Children's Hospital at Westmead, and The University of Sydney, Westmead, New South Wales, Australia.
Diana X. Bharucha-Goebel, Department of Neurology Children's National Health System, Washington, District of Columbia, USA.
Emmanuelle Salort-Campana, Service des maladies neuromusculaire et de la SLA, Hôpital de La Timone, Marseille, France.
Alan Pestronk, Department of Neurology Washington University School of Medicine, St. Louis, Missouri, USA.
Maggie C. Walter, Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany.
Carmen Paradas, Neuromuscular Unit, Department of Neurology, Hospital U. Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain.
Tanya Stojkovic, Centre de référence des maladies neuromusculaires, Institut de Myologie, AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France.
Madoka Mori-Yoshimura, Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Elena Bravver, Neuroscience Institute, Carolinas Neuromuscular/ALS-MDA Center, Carolinas HealthCare System, Charlotte, North Carolina, USA.
Elena Pegoraro, Department of Neuroscience, University of Padova, Padua, Italy.
Linda Pax Lowes, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Jerry R. Mendell, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Kate Bushby, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Document Type

Journal Article

Publication Date

2-18-2022

Journal

Muscle & nerve

DOI

10.1002/mus.27524

Keywords

Miyoshi myopathy; cardiac; dysferlin; limb girdle muscular dystrophy R2; respiratory

Abstract

INTRODUCTION/AIMS: There is debate about whether and to what extent either respiratory or cardiac dysfunction occurs in patients with dysferlinopathy. This study aimed to establish definitively whether dysfunction in either system is part of the dysferlinopathy phenotype. METHODS: As part of the Jain Foundation's International Clinical Outcome Study (COS) for dysferlinopathy, objective measures of respiratory and cardiac function were collected twice, with a 3-y interval between tests, in 188 genetically confirmed patients aged 11-86 y (53% female). Measures included forced vital capacity (FVC), electrocardiogram (ECG), and echocardiogram (echo). RESULTS: Mean FVC was 90% predicted at baseline, decreasing to 88% at year 3. FVC was less than 80% predicted in 44 patients (24%) at baseline and 48 patients (30%) by year 3, including ambulant participants. ECGs showed P-wave abnormalities indicative of delayed trans-atrial conduction in 58% of patients at baseline, representing a risk for developing atrial flutter or fibrillation. The prevalence of impaired left ventricular function or hypertrophy was comparable to that in the general population. DISCUSSION: These results demonstrate clinically significant respiratory impairment and abnormal atrial conduction in some patients with dysferlinopathy. Therefore, we recommend that annual or biannual follow-up should include FVC measurement, enquiry about arrhythmia symptoms and peripheral pulse palpation to assess cardiac rhythm. However, periodic specialist cardiac review is probably not warranted unless prompted by symptoms or abnormal pulse findings.

Department

Pediatrics

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