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Research paper
Clinical features of congenital myasthenic syndrome due to mutations in DPAGT1
  1. Sarah Finlayson1,2,
  2. Jacqueline Palace2,
  3. Katsiaryna Belaya1,
  4. Timothy J Walls3,
  5. Fiona Norwood4,
  6. Georgina Burke5,
  7. Janice L Holton6,
  8. Samuel I Pascual-Pascual7,
  9. Judith Cossins1,
  10. David Beeson1
  1. 1Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
  2. 2Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK
  3. 3Department of Neurology, Regional Neurosciences Centre, Newcastle General Hospital, Newcastle upon Tyne, UK
  4. 4Department of Neurology, King's College Hospital NHS Foundation Trust, London, UK
  5. 5Wessex Neurological Centre, Southampton General Hospital, Southampton, UK
  6. 6Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
  7. 7Servicio de Neurologia Pediátrica, Hospital Universitario La Paz, Departamento de Pediatria, Universidad Autónoma de Madrid, Madrid, Spain
  1. Correspondence to Dr Sarah Finlayson, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford OX3 9DU, UK; sarah.finlayson{at}clneuro.ox.ac.uk

Abstract

Background A newly defined congenital myasthenic syndrome (CMS) caused by DPAGT1 mutations has recently been reported. While many other CMS-associated proteins have discrete roles localised to the neuromuscular junction, DPAGT1 is ubiquitously expressed, modifying many proteins, and as such is an unexpected cause of isolated neuromuscular involvement.

Methods We present detailed clinical characteristics of five patients with CMS caused by DPAGT1 mutations.

Results Patients have prominent limb girdle weakness and minimal craniobulbar symptoms. Tubular aggregates on muscle biopsy are characteristic but may not be apparent on early biopsies. Typical myasthenic features such as pyridostigmine and 3, 4- diaminopyridine responsiveness, and decrement on repetitive nerve stimulation are present.

Conclusions These patients mimic myopathic disorders and are likely to be under-diagnosed. The descriptions here should facilitate recognition of this disorder. In particular minimal craniobulbar involvement and tubular aggregates on muscle biopsy help to distinguish DPAGT1 CMS from the majority of other forms of CMS. Patients with DPAGT1 CMS share similar clinical features with patients who have CMS caused by mutations in GFPT1, another recently identified CMS subtype.

  • Myasthenia
  • Genetics
  • Neuropathology, Muscle
  • Myopathy
  • Molecular Biology

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