Inherited Neuromuscular Disease


Inherited neuromuscular disease encompasses a broad array of diseases afflicting people at all stages of life. The main categories of inherited neuromuscular disease are diseases of peripheral nerve (neuropathy), neuromuscular junction (myasthenia), diseases of muscle (myopathy and dystrophy) and diseases of spinal cord motor neurons (motor neuron disease). The number of genes underlying such disorders has expanded greatly in the past 10 years. The discovery of such genes has allowed development of specific therapeutic approaches based on genetic diagnosis, as well as the ability to tackle pathways involved in multiple disorders. It has also complicated diagnosis, with mutations in single genes causing multiple clinical phenotypes. Research is starting to have concrete benefits, with treatments beginning to emerge from basic science research with the hope that many more will show efficacy over the next decade.

Key Concepts

  • Expanded genetic testing has led to the identification of dozens of new genes implicated in neuromuscular disorders.
  • Single genes can cause a wide spectrum of neuromuscular disease, and multiple genes can cause very similar clinical phenotypes.
  • Identification of pathways involved in neuromuscular disease may allow for therapies that are not specific to a single gene or mutation.
  • Pathways involved in inherited neuromuscular disorder are also involved in sporadic and acquired disease.
  • Geneā€specific therapy is being developed for multiple inherited neuromuscular disorders, including antisense oligonucleotides and gene therapy.

Keywords: neuropathy; myopathy; amyotrophic lateral sclerosis; spinal muscular atrophy; muscular dystrophy

Figure 1. Illustration of some proteins mutated in Charcot–Marie–Tooth disease. The cellular localisation of the proteins is indicated as well as their general function. Reproduced from Jerath and Shy (2014) © Elsevier.
Figure 2. Illustration of proteins involved in myopathy and muscular dystrophy. (a) Multiple proteins have been shown to be involved in muscular dystrophy, primarily related to the dystrophin complex and the cell membrane integrity. (b) Mutations within proteins of the sarcomere, directly affecting the contractile apparatus, more frequently cause congenital myopathies. Reproduced with permission from Rahimov and Kunkel (2013) © Rockefeller University Press.
Figure 3. Illustration of some proteins mutated in motor neuron disease. The cellular localisation of the proteins is indicated along with the disorders and particular genes implicated. Reproduced with permission from Patten et al. (2014) ©. The Company of Biologists Ltd distributed under the terms of the Creative Commons Attribution 4.0 International License.


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Further Reading

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Peters OM, Ghasemi M and Brown RH (2015) Emerging mechanisms of molecular pathology in ALS. Journal of Clinical Investigation 125 (5): 1767–1779.

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Kichula, Elizabeth A, Ferguson, Toby A, and Lynch, David R(Jan 2017) Inherited Neuromuscular Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005513.pub2]