The muscular dystrophies.

In 1879 William Gowers, the eminent British neurologist, painted a remarkably lucid word picture of Duchenne muscular dystrophy in his series of lectures on pseudohypertrophic muscular paralysis, published in the Lancet.' This disease, he said, is one of the most interesting, and at the same time most sad, of all those with which we have to deal; interesting because of its peculiar features and mysterious nature; sad on account of our powerlessness to influence its course. Almost exactly a century later Duchenne dystrophy found itself at the centre of one of the most exciting breakthroughs in the modern science of molecular genetics. It was the first genetic disorder in which a previously unknown biochemical abnormality was resolved by the process of reversed genetics, with initial location, isolation and cloning of the gene and then identifying the protein it encodes. Moreover, we now seem to be on the verge of treating the disease by one or other of the potential routes of gene therapy. This would certainly have delighted Gowers. At the same time molecular genetics has generated a most complex and almost totally incomprehensible new jargon of its own, which must surely have turned Gowers in his grave. The muscular dystrophies, a term first coined by Erb in 1891, are a group of genetically determined disorders characterized by degeneration of skeletal muscle and no associated structural abnormality in the central or peripheral nervous system. They have been subdivided into various clinical types on the basis of the clinical distribution and severity of muscle weakness, and the mode of inheritance. The rate of progression of the disease is also variable and some, such as congenital muscular dystrophy, may remain relatively static or even show functional improvement over time. Some of the animal models of the dystrophies may be devoid of any clinical weakness as may some of the milder variants of, for example, Becker dystrophy, which can present solely with cramps on exercise.1'2 The main breakthrough has been in Duchenne and Becker muscular dystrophy, or the Xp2l dystrophies as some would now have us call them. The location of the gene for the X-linked Emery-Dreifuss muscular dystrophy on the long arm of the X chromosome at Xq28 was discovered a few years back3 but there has as yet been no further progress in its resolution. The locus for the dominantly inherited facioscapulohumeral dystrophy on the long arm of chromosome 4 has only recently been found4 and other dystrophies such as the autosomal recessive congenital dystrophy and limb girdle dystrophy will undoubtedly follow suit once sufficient collaborative clinical and laboratory effort is concentrated on them.