Sixty-one members of a large Spanish kindred with autosomal dominant limb-girdle muscular dystrophy (LGMD), spanning 5 generations, were examined at the Hospital Vail d’Hebron, Barcelona and other centers. Characteristic proximal muscle weakness involving pelvic and shoulder girdle muscles was found in 32 patients (15 men, 17 women) between the ages of 7 and 66 years (mean 34 years). Age at onset ranged from less than 1 to 58 years (mean 16 years). A juvenile form (onset before 15 years) and an adult-onset form (30-40 year onset) were identified in 72 and 28%, respectively. Weakness extended to distal muscles late in the course in adult cases, but generalized weakness occurred at initial presentation in severely affected juvenile cases. Progression was slow in adult cases and relatively faster in juvenile-onset cases. Severity worsened in successive generations (anticipation) among 26 parent-child pairs. None had ptosis, ophthalmoplegia, dysphagia, speech disorders, calf hypertrophy, myalgia, or mental deterioration. Muscle biopsy on 5 patients showed nonspecific findings compatible with MD; rimmed vacuoles were present in 3. Linkage analysis findings were distinct from previously reported forms of LGMD (1A - E), and chromosomes 5q31, lqll, 3p25, 6q23, and 7q linkages were identified. [1]

COMMENT. A genetically distinct form of autosomal dominant limb-girdle muscular dystrophy (LGMD) is added to the previously described 5 types of AD-LGMD (1 A-E). Characteristic features of LGMD include: slowly progressive proximal symmetric weakness with predominantly pelvic onset, normal to mildly elevated CK, myopathic EMG and muscle biopsy, and negative immuno-histochemical stains for dystrophin and sarcoglycans. Extraocular, facial, and bulbar muscles are unaffected. Two clinical types are identified (juvenile and adult-onset), according to age at onset, severity of muscle involvement, and rate of progression. In almost two-thirds, onset is in childhood or adolescence. Earlier onset in children than in parents suggests genetic anticipation, but disease severity is unrelated to the parent’s gender.