There is a large group of patients with muscular dystrophy who do not fit into the Duchenne/Becker, facioscapulohumeral, or scapuloperoneal categories. Children of both sexes in this group lack the hypertrophy of calves and other muscles; adults with late-onset forms have either pelvic or shoulder girdle involvement or both, and their facial muscles are spared. Because Wilhelm Erb first called attention to these types of dystrophy, they were classified by Walton and Nattrass as the “limb-girdle dystrophies of Erb.” This clinically based grouping has been problematic from the time it was proposed because, like the scapuloperoneal group, it is heterogeneous, the only unifying feature being the presence of limb-girdle weakness with sparing of the facial muscles. The inheritance is variable, but the autosomal recessive forms are the most common. Either the shoulder girdle or pelvic girdle muscles may be first affected (traditionally these forms had been referred to as the Erb juvenile atrophic and Leyden-Möbius types, respectively). Weakness and atrophy may become evident during either late childhood or early adult life and spread from shoulders to hips or vice versa.
The status of this group of limb-girdle muscular dystrophies (LGMDs) as a clinical–genetic entity is being steadily revised. The delineation of the progressive spinal muscular atrophies and the congenital and metabolic myopathies has considerably narrowed the category of limb-girdle dystrophies as originally described. During the past decade, with the application of molecular genetic techniques, progress in this direction has accelerated greatly. The now well-populated class of limb-girdle dystrophies is classified as LGMD1 for the autosomal dominant types, and LGMD2 for the recessive types, and further subclassified based on the specific genotype. At the time of this writing, at least 19 forms of autosomal recessive (LGMD type 2A-2S) and 6 forms of autosomal dominant (LGMD type 1A-1E) limb-girdle dystrophies have been defined, most with an identifiable mutation and a protein that in most cases is a constituent of the sarcolemmal, sarcomeric, or nuclear membrane structural protein (Bushby). The later the onset of these disorders, the more likely that the course will be benign. In these lesser-affected patients the EMG is myopathic and the CK values are only moderately elevated and may be normal. More severe cases can have greatly elevated CK levels. Cardiac involvement occurs but is infrequent (mainly in the group classified as myofibrillar dystrophies), and mental function is normal, but there are exceptions including in cases of laminin A/C mutations (type 1B), FKRP (fukutin-related protein mutation) mutations (type 2I), and in the sarcoglycanopathies.
This information is summarized in Table 45-2 and discussion of the better-characterized types follows.
Limb-Girdle Muscular Dystrophy 2I (FKRP, Fukutin Mutation)