title: Polymyositis without Beneficial Response to Steroid Therapy: Should Miyoshi Myopathy be a Differential Diagnosis?
abstract: BACKGROUND Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. CASE REPORT We report the case of a 16-year-old male who presented with severe bilateral calf pain and elevated CK levels (15 000 IU/l) who was on prolonged steroid therapy prompted by the clinical suspicion of inflammatory myopathy. Three years into his illness, he was referred for neuromuscular evaluation presenting with untreatable muscle pain and progressive weakness. The diagnosis of "refractory polymyositis" was revisited. Targeted exome sequencing revealed homozygous pathogenic mutations in the DYSF gene, confirming a diagnosis of Miyoshi myopathy. CONCLUSIONS Our case illustrates that severe muscle pain may be the initial feature of Miyoshi myopathy and should be considered in the differential diagnosis of inflammatory myopathies. Although the described patient reported partial clinical improvement in muscle pain, steroid treatment is not an effective therapy for dysferlinopathy patients and it did not prevent disease progression. In addition, we confirm the utility of next-generation sequencing approaches to myopathies, particularly in complex or unusual cases when muscle biopsy is not available.
authors.affiliation: MRC Centre for Neuromuscular Diseases and Division of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, United Kingdom.|Department of Neurology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.|Capes Foundation, Ministry of Education, Brasilia, Brazil.
authors.forename: Renata Siciliani
authors.initials: RS
authors.lastname: Scalco
authors.affiliation: Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
authors.forename: Paulo José
authors.initials: PJ
authors.lastname: Lorenzoni
authors.affiliation: MRC Centre for Neuromuscular Diseases and Division of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, United Kingdom.
authors.forename: David S
authors.initials: DS
authors.lastname: Lynch
authors.affiliation: Department of Neurology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: William Alves
authors.initials: WA
authors.lastname: Martins
authors.affiliation: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London (KCL), London, United Kingdom.|Department of Paediatric Neurology, Evelina Children's Hospital, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom.|Randall Division for Cell and Molecular Biophysics, Muscle Signalling Section, King's College London, London, United Kingdom.
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
authors.affiliation: MRC Centre for Neuromuscular Diseases and Division of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, United Kingdom.
authors.forename: Ros
authors.initials: R
authors.lastname: Quinlivan
authors.affiliation: Department of Neurology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Becker
authors.affiliation: MRC Centre for Neuromuscular Diseases and Division of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, United Kingdom.
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D003937:Diagnosis, Differential; D018450:Disease Progression; D049310:Distal Myopathies / Q000175:diagnosis* / Q000235:genetics*; D000073939:Dysferlin; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D063806:Myalgia / Q000235:genetics; D017285:Polymyositis / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins