Myopathy with lobulated muscle fibers: evidence for heterogeneous etiology and clinical presentation.

The clinico-pathological features of 17 patients displaying a myopathy with lobulated (trabeculated) fibers are reported. All these patients had a limb girdle phenotype and at least 20% of lobulated fibers in their muscle biopsies. There were ten females and seven males. The onset of symptoms ranged from 2 to 55 years (mean 24). The average age at the time of muscle biopsy was 39 (range 3-63). Interestingly, in six patients, high prevalence of lobulated fibers was observed at the second biopsy only, performed on average 11 years after the first or in another muscle. Six patients had a suggestively positive family history. Facial weakness was noted in two patients (genetic study confirmed FSH dystrophy). The course and the severity of weakness varied from one patient to another. Immunohistochemistry and Western blot analyses revealed one Duchenne carrier, one alpha-sarcoglycanopathy, no dysferlinopathy and four calpain deficiencies (including one patient with FSH dystrophy), but SSCP revealed mutation in the calpain gene in only one of the patients. These results show that (1) myopathies with lobulated fibers are clinically and genetically heterogeneous, (2) lack of calpain expression by Western blot analysis is not always associated with null mutation, (3) a molecular diagnosis is made in less than 40% of myopathy with lobulated fibers, (4) when observed, lobulated fibers are most prominent in proximal muscles and require time to appear.