The differential diagnosis of the human dystrophinopathies and related disorders

In addition to the now well recognized dystrophinopathies, recent investigation of the dystrophin-associated proteins has revealed a new group of disorders referred to as the 'sarcoglycanopathies'. These autosomal recessive muscle diseases are results of mutations of alpha-, beta-, or gamma-sarcoglycans and may be severe (Duchenne muscular dystrophy-like) or mild (limb girdle muscular dystrophy) depending upon whether there is a 'null' mutation with no gene product formed or a 'missense' mutation in which reduced amounts of the protein product are made. The relationship between the severe Duchenne muscular dystrophy-like phenotype and the milder limb girdle muscular dystrophy phenotype is therefore similar to that of Duchenne muscular dystrophy to Becker muscular dystrophy, where there is absence of dystrophin in Duchenne muscular dystrophy and reduced amounts in Becker muscular dystrophy. Not all of the limb girdle muscular dystrophies have been identified in molecular terms and, as yet, no disorder has been associated with mutations of the syntrophin or the dystroglycan genes. Nevertheless, progress in this field has been so rapid and of such practical importance that the clinical neurologist should become aware of these developments.