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Clinical assessment of a patient presenting with a neuromuscular disorder follows a standardised path, hallowed by clinical practice. Symptomatic history, family history and physical examination are followed by the development of a plan for further investigation, usually involving a blood creatine kinase level, other biochemical tests and, perhaps, an immunological assessment. Clinical neurophysiological studies and muscle biopsy are also nearly always used, although, increasingly, especially in suspected Duchenne muscular dystrophy and limb-girdle muscular dystrophies, genetic investigations not only supplement but may even replace this diagnostic test sequence. This clinical protocol, based on research developments during the past 50 years, progresses from syndromic recognition to more precise molecular and genetic diagnoses. The assumptions underlying this classical approach are seldom critically considered but may themselves imply a need for a modified approach. For example, the current diagnostic categories represent an uneasy synthesis of classical syndromic terminology and modern molecular biology.1 Current research emphasises precise, even molecular, diagnosis. However, there is an evident need for more intensive research around the practical management of people with muscle disease, ideas additional to possible technical developments that may lead to the holy grail of ‘genetic therapy’. For example, what are the mechanisms underlying onset and progression of these disorders, and are they generalisable? The assumptions underlying some of the accepted basic concepts of neuromuscular disease that currently define clinical practice raise issues that form the basis of this review. Six major issues are highlighted.
Clinical syndromes of myopathies: specificity and variability?
It has often been remarked that the pattern of weakness in muscular disorders is relatively limited. Typically, there is a predominantly proximal pattern of weakness. Hilton-Jones and Kissel2 suggested that “for reasons that are entirely unknown ……there are six basic patterns of muscular weakness” (box 1). Some of these patterns are closely associated with particular syndromes, for example oculopharyngeal …