Introduction: An apoptotic mode of cell death has been identified in the developing skeletal muscle of invertebrates. It has been also involved in the pathogenesis of muscle degeneration in the dystrophin-deficient mdx mouse. This has raised an interest on the possible role of apoptosis in human neuromuscular disorders, but the existing studies have offered conflicting results.
Objective: To analyze the presence of apoptosis in several pediatric neuromuscular disorders.
Patients and methods: Identification of cells with apoptotic morphology, detection of DNA fragmentation in situ by means of the TUNEL assay and study of the pattern of DNA fragmentation by agarose gel electrophoresis and Southern blot hybridization in muscle biopsies of 29 patients and three normal controls.
Results: No morphological features of apoptosis were found in any of the samples examined. The TUNEL method did not label the myonuclei from any of the biopsies, though some mastocytes stained positively. Agarose gel electrophoresis of extracted DNA and Southern blot hybridization with a genomic DNA probe did not show oligonucleosomal fragmentation. However, smearing of DNA was observed in samples from three patients affected with Duchenne's muscular dystrophy, one with Becker's muscular dystrophy and one with infantile spinal muscular atrophy.
Conclusions: The present results do not favor the hypothesis of persistent apoptosis in some of the pediatric neuromuscular disorders, although they do not exclude that some sort of programmed cell death occurs either excessively or anachronically at other stages of the pathogenesis of these diseases.