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Congenital myasthenic syndromes: an update
  1. Sarah Finlayson1,2,
  2. David Beeson2,
  3. Jacqueline Palace1
  1. 1Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK
  2. 2Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
  1. Correspondence to Dr Sarah Finlayson, Department of Clinical Neurology, John Radcliffe Hospital, Oxford, OX3 9DU, UK; sarah.finlayson{at}clneuro.ox.ac.uk

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The last 20 years has seen significant advances in our understanding and treatment of the congenital myasthenic syndromes. This article discusses individual syndromes, their management and how to distinguish the subtypes from each other as well as from other conditions that commonly mimic them.

Background

What are congenital myasthenic syndromes?

Congenital myasthenic syndromes result from gene mutations affecting the neuromuscular junction structure and function. Unlike autoimmune myasthenia gravis, the immune system is not involved and there is no association with antibodies to the acetylcholine receptor (AChR) or muscle specific kinase. Although all congenital myasthenic syndromes share the feature of fatiguable muscle weakness, they are discrete syndromes each with their own, often distinct, phenotype. Significant advances in the last 20 years, mainly in molecular genetics, have enabled identification of at least 15 genes implicated in congenital myasthenic syndromes (table 1). About 80%–90% of patients with congenital myasthenia in the UK now have a confirmed genetic diagnosis. Thus, there are likely to be many unidentified associated genes.

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Table 1

Congenital myasthenic syndromes subtypes, associated genes and main pathology

The delineation of these different genetic syndromes has enabled the development of a range of effective symptomatic treatments. The choice of treatment is governed by the underlying pathogenic mechanism. Importantly, the treatments routinely used for some subtypes can cause significant deterioration in others. In addition, a range of conditions can mimic congenital myasthenic syndromes and these too require different therapy. Therefore, a definitive genetic diagnosis is important and guides treatment, prognosis and genetic counselling.

Most patients with congenital myasthenia present with symptoms at birth or early infancy, although in some subtypes, particularly those predominantly affecting proximal muscles such as downstream of kinase-7 (DOK7), onset is typically in childhood with walking difficulties. Patients with the slow channel syndrome may have symptom onset well into their second or third decades. While many patients are now identified …

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