Genetic neuromuscular disease.

The clinical practice of neuromuscular disease is currently undergoing enormous change as a direct result of the wealth of recent molecular genetic discoveries. Indeed, the majority of gene discoveries in the area of neurological disease relate to neuromuscular disorders. The immediate impact of these discoveries is that a precise DNA based diagnosis is possible. This often gives patients accurate prognostic and genetic counselling information. It will also facilitate rational screening programmes for recognised complications such as cardiac or respiratory involvement. Unfortunately, at present many eligible patients do not benefit from or have access to such diagnostic precision, although this is changing. The discovery of new genes and proteins has opened up unexplored avenues of research into therapies for neuromuscular patients. While therapeutic trials in genetic neuromuscular diseases remain in their infancy, it seems clear that a precise DNA based diagnosis will be essential. Eligibility for such trials and indeed for future proven therapies will be contingent upon DNA based diagnosis. For example, it is no longer acceptable to make “limb-girdle muscular dystrophy” based on simple histochemistry, a final diagnosis. Detailed immunocytochemistry and protein chemistry in combination with DNA analysis offer the patient the best chance of a precise diagnosis from which accurate prognostication, screening, and genetic counselling will follow. In this review we describe some of the more common genetic nerve and muscle diseases encountered by adult neurologists. We have elected not to include the spinal muscular atrophies or the neuromuscular junction disorders (see web review for references on these diseases). Our aim is not to give a detailed description of each disorder, but to inform the reader about the latest genetic information and particularly about the availability of DNA based diagnosis. We will describe how DNA based diagnosis may accelerate and simplify the diagnostic process, thereby providing the most accurate information for patients with these diseases.