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Clinical Features of the Myasthenic Syndrome Arising From Mutations in Gmppb Publisher Pubmed



Rodriguez Cruz PM1, 2 ; Belaya K1 ; Basiri K3 ; Sedghi M4 ; Farrugia ME5 ; Holton JL6 ; Liu WW1 ; Maxwell S1 ; Petty R4 ; Walls TJ7 ; Kennett R1 ; Pitt M8 ; Sarkozy A8 ; Parton M8 Show All Authors
Authors
  1. Rodriguez Cruz PM1, 2
  2. Belaya K1
  3. Basiri K3
  4. Sedghi M4
  5. Farrugia ME5
  6. Holton JL6
  7. Liu WW1
  8. Maxwell S1
  9. Petty R4
  10. Walls TJ7
  11. Kennett R1
  12. Pitt M8
  13. Sarkozy A8
  14. Parton M8
  15. Lochmuller H9
  16. Muntoni F10
  17. Palace J2
  18. Beeson D1, 2
Show Affiliations
Authors Affiliations
  1. 1. Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom
  2. 2. Neurology Department, Neuroscience Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, United Kingdom
  5. 5. Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom
  6. 6. MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom
  7. 7. Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom
  8. 8. Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
  9. 9. Institute of Genetic Medicine, John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne, United Kingdom
  10. 10. Dubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, UCL Institute of Child Health, London, United Kingdom

Source: Journal of Neurology, Neurosurgery and Psychiatry Published:2016


Abstract

Background: Congenital myasthenic syndrome (CMS) due to mutations in GMPPB has recently been reported confirming the importance of glycosylation for the integrity of neuromuscular transmission. Methods: Review of case notes of patients with mutations in GMPPB to identify the associated clinical, neurophysiological, pathological and laboratory features. In addition, serum creatine kinase (CK) levels within the Oxford CMS cohort were retrospectively analysed to assess its usefulness in the differential diagnosis of this new entity. Results: All patients had prominent limb-girdle weakness with minimal or absent craniobulbar manifestations. Presentation was delayed beyond infancy with proximal muscle weakness and most patients recall poor performance in sports during childhood. Neurophysiology showed abnormal neuromuscular transmission only in the affected muscles and myopathic changes. Muscle biopsy showed dystrophic features and reduced α-dystroglycan glycosylation. In addition, myopathic changes were present on muscle MRI. CK was significantly increased in serum compared to other CMS subtypes. Patients were responsive to pyridostigimine alone or combined with 3,4-diaminopyridine and/or salbutamol. Conclusions: Patients with GMPPB-CMS have phenotypic features aligned with CMS subtypes harbouring mutations within the early stages of the glycosylation pathway. Additional features shared with the dystroglycanopathies include myopathic features, raised CK levels and variable mild cognitive delay. This syndrome underlines that CMS can occur in the absence of classic myasthenic manifestations such as ptosis and ophthalmoplegia or facial weakness, and links myasthenic disorders with dystroglycanopathies. This report should facilitate the recognition of this disorder, which is likely to be underdiagnosed and can benefit from symptomatic treatment. © 2016 Published by the BMJ Publishing Group Limited.
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