ABSTRACT
INTRODUCTION The diagnosis of neuromuscular disorders is continuing its dramatic development of recent years. The main reasons behind this progress are related not only to improvements in protein-based assays that can directly or indirectly point towards a specific condition, but also the wider application of techniques such as magnetic resonance (MR) imaging and the molecular genetic revolution brought about by techniques such as next-generation sequencing. Indeed, following the identification of the gene responsible for Duchenne muscular dystrophy (DMD), which initiated a revolution in molecular diagnosis in the field, the defective genes of numerous neuromuscular disorders are now known, and the list is extending almost on a weekly basis (see the gene table of neuromuscular disorders at www. musclegenetable.fr). The genetic diversity of these disorders is far greater than appreciated before the 1990s, as exemplified by the number of genes responsible for the muscular dystrophies. For a few conditions, molecular analysis is now so reliable that muscle pathology often contributes little additional diagnostic information, so muscle biopsy is rarely performed. In particular, molecular analysis is now the test of choice for the diagnosis of spinal muscular atrophy (SMA), myotonic muscular dystrophies (DM1 and often DM2) and facioscapulohumeral muscular dystrophy (FSHD), and also for conditions in which there is no specific muscle pathology, such as disorders associated with mutations in the lamin A/C gene and the limb-girdle muscular dystrophy (LGMD) due to mutations in the gene encoding anoctamin 5 (ANO5). Similarly, muscle pathology may be absent, minimal or non-specific in myasthenic syndromes, where the combination of careful clinical and electrophysiological studies often provides the diagnosis.
