RYR1-related congenital myopathy with fatigable weakness,responding to pyridostigimine |
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| Affiliation: | 1. Dubowitz Neuromuscular Centre, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK;2. Department of Clinical Neurophysiology, Great Ormond Street Hospital, London, UK;3. Wolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry, UK;4. Department of Radiology, Great Ormond Street Hospital, London, UK;5. Department of Paediatrics, Gloucester Royal Hospital, Gloucester, UK;6. Weatherall Institute, John Radcliffe Hospital, Oxford, UK;1. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands;2. Department of Medical Sciences, University of Ferrara, Ferrara, Italy;3. United Parent Project Muscular Dystrophy, The Netherlands;1. Program in Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe (CIPF), CIPF and IBV-CSIC Associated Unit at CIPF, Valencia, Spain;2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain;3. Neurology Department, Hospital Universitario La Paz, Madrid, Spain;4. Pediatric Neurology Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain;5. Program in Computational Medicine, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain;1. Krankenanstalt Rudolfstiftung, Vienna, Austria;2. Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090 Vienna, Austria;3. 2nd Medical Department with Cardiology and Intensive Care Medicine Krankenanstalt Rudolfstiftung, Vienna, Austria;4. Centre for Medical Research, University of Western Australia and Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia 6009, Australia;1. Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK;2. Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK;3. Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, UK;4. Department of Neurological Sciences, University of Bologna, Bologna, Italy;1. Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China;2. Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China;3. Neurology Department, First People’s Hospital of Yunnan Province, Kunming 650032, China |
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| Abstract: | ![]()
The spectrum of RYR1 mutation associated disease encompasses congenital myopathies, exercise induced rhabdomyolysis, malignant hyperthermia susceptibility and King-Denborough syndrome. We report the clinical phenotype of two siblings who presented in infancy with hypotonia and striking fatigable ptosis. Their response to pyridostigimine was striking, but genetic screening for congenital myasthenic syndromes was negative, prompting further evaluation. Muscle MRI was abnormal with a selective pattern of involvement evocative of RYR1-related myopathy. This directed sequencing of the RYR1 gene, which revealed two heterozygous c.6721C>T (p.Arg2241X) nonsense mutations and novel c.8888T>C (p.Leu2963Pro) mutations in both siblings. These cases broaden the RYR1-related disease spectrum to include a myasthenic-like phenotype, including partial response to pyridostigimine. RYR1-related myopathy should be considered in the presence of fatigable weakness especially if muscle imaging demonstrates structural abnormalities. Single fibre electromyography can also be helpful in cases like this. |
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| Keywords: | Congenital fibre type disproportion Fatigability Muscle MRI Electrophysiology |
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