Advances in the diagnosis of inherited neuromuscular diseases and implications for therapy development

Lancet Neurol. 2020 Jun;19(6):522-532. doi: 10.1016/S1474-4422(20)30028-4. Epub 2020 May 26.


Advances in DNA sequencing technologies have resulted in a near doubling, in under 10 years, of the number of causal genes identified for inherited neuromuscular disorders. However, around half of patients, whether children or adults, do not receive a molecular diagnosis after initial diagnostic workup. Massively parallel technologies targeting RNA, proteins, and metabolites are being increasingly used to diagnose these unsolved cases. The use of these technologies to delineate pathways, biomarkers, and therapeutic targets has led to new approaches entering the drug development pipeline. However, these technologies might give rise to misleading conclusions if used in isolation, and traditional techniques including comprehensive neurological evaluation, histopathology, and biochemistry continue to have a crucial role in diagnostics. For optimal diagnosis, prognosis, and precision medicine, no single ruling technology exists. Instead, an interdisciplinary approach combining novel and traditional neurological techniques with computer-aided analysis and international data sharing is needed to advance the diagnosis and treatment of neuromuscular disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Interdisciplinary Research / methods
  • Interdisciplinary Research / trends*
  • Neuromuscular Diseases / diagnosis*
  • Neuromuscular Diseases / genetics*
  • Neuromuscular Diseases / therapy
  • Precision Medicine / trends
  • Prognosis
  • Sequence Analysis, DNA