The differentiation of dystrophic diseases of muscle from those secondary to neuronal degeneration was an achievement of neurologists of the second half of the nineteenth century. Isolated cases of muscular dystrophy had been described earlier, but no distinction was made between neuropathic and myopathic disease. In 1855, Duchenne described the progressive muscular atrophy of childhood that now bears his name. However, it was not until the second edition of his monograph in 1861 that the “hypertrophic paraplegia of infancy” was recognized as a distinct syndrome. By 1868, he was able to write a comprehensive description of 13 cases and recognized that the disease was muscular in origin and restricted to males. Gowers in 1879 gave a masterful account of 21 personally observed cases and called attention to the characteristic way in which such patients arose from the floor (Gowers sign). Erb, in 1891, crystallized the clinical and histologic concept of a group of diseases caused by primary degeneration of muscle, which he named muscular dystrophies. The first descriptions of facioscapulohumeral dystrophy were published by Landouzy and Dejerine in 1894; of progressive ocular myopathy by Fuchs in 1890; of myotonic dystrophy by Steinert and by Batten and Gibb in 1909; of distal dystrophy by Gowers in 1888, Milhorat and Wolff in 1943, Welander in 1951, and Miyoshi and colleagues in 1986; and of oculopharyngeal dystrophy by Victor and associates in 1962. References to these and other writings of historical importance can be found in the works of Kakulas and Adams, of Walton and colleagues, and of Engel and Franzini-Armstrong, and most recently of Amato and Russell.
In the more recent history of the dystrophies, the most notable event was the discovery by Kunkel, in 1986, of the dystrophin gene and its protein product. Since then there has been an extraordinary accumulation of molecular-genetic, ultrastructural, and biochemical information about the muscular dystrophies, which has broadened our understanding of their mechanisms. It has also clarified a number of uncertainties as to their clinical presentations and has necessitated a revision of an older classification.
This is the most frequent and prototypic early-onset muscular dystrophies. It begins in early childhood and runs a relatively rapid, progressive course. The incidence is in the range of 13 to 33 per 100,000 yearly or about 1 in 3,300 live male births. There is a strong familial liability as the disease is transmitted as an X-linked recessive trait, occurring almost exclusively in males, and involving the DMD gene and the protein dystrophin. Careful examination of the mothers of affected boys shows slight muscle involvement in as many as half of them, as pointed out by Roses and coworkers (a frequency higher than in our limited experience). Approximately 30 percent of patients have no family history of the disease and these represent spontaneous mutations.
Rarely, a severe proximal Duchenne-type muscular dystrophy occurs in young girls. This may have several explanations. The female may have only 1 X chromosome, as occurs in the Turner (XO) syndrome, and that chromosome carries the Duchenne gene, or the Lyon principle may be operative; that is, there is inactivation of the unaffected paternal X chromosome allowing expression of the mutated Duchenne protein from the maternal chromosome in a large proportion of embryonic cells (mosaicism). It so happens that most childhood dystrophies in girls prove to be of an entirely different type that is caused by an autosomal recessive mutation causing a limb-girdle dystrophy as discussed further on.