Muscular Dystrophy

Limb-girdle muscular dystrophy (LGMD) has been described both as a heterogeneous group of disorders and as a diagnosis of exclusion. Any patient who has weakness of the shoulder and hip-girdle muscles and who otherwise has been excluded from the other MDs will be diagnosed with LGMD. Using the patterns of inheritance that exist within LGMD, a classification system has been created to simplify the heterogeneity: Both autosomal dominant (LGMD1) and recessive families (LGMD2) are well recognized. The number of LGMD genes that have already been identified has further improved the classification.

The frequency of LGMD in the general population is reported to be one in twenty-five thousand. The age at onset may vary widely. In some individuals, onset is in early childhood and in others it occurs in the forties and fifties, but most commonly it occurs in the teens to early adulthood. The characteristic pattern of muscle involvement is symmetric weakness, beginning initially in the hip and shoulder girdle, but usually noticed in the hips before the shoulders. Thus slowness in running, difficulty rising from a low seat, and difficulty ascending stairs are all common complaints from affected individuals. As LGMD progresses, it will involve upper-leg and arm muscles and may eventually affect the muscles that extend the feet and wrists. Lower-extremity weakness may become severe enough to require a wheelchair.

Among the LGMD1 types, five have chromosomal linkages, but only in one is the protein product of the gene known. LGMD2 is better characterized, with nine chromosomal localizations, five with known proteins. Almost all these proteins are membrane-associated proteins (just as dystrophin is). When they are abnormal in structure or deficient in quantity, they affect the stability of the muscle membrane, resulting in the same pathological process that was described for DMD. Commercial testing in the United States is only available for some of the LGMD2 types and is performed using muscle tissue.