Importance of immunohistochemical evaluation of developmentally regulated myosin heavy chains in human muscle biopsies.

Our retrospective immunohistochemical study of normal quadriceps muscle biopsies shows that embryonic myosin heavy chains are down-regulated by, or soon after, birth. Fetal myosin heavy chains are down-regulated by 4-6 months. Thus the presence of an appreciable number of fibres with embryonic myosin heavy chains at birth or of fetal myosin heavy chains after 6 months of age suggests a delay in maturation or an underlying abnormality. Regenerating fibres in dystrophic muscle often co-express both embryonic and fetal myosin heavy chains but more fibres with fetal than embryonic myosin heavy chains can occur. Embryonic myosin heavy chains are a useful marker of regeneration but effects of denervation, stress, disuse, and fibre maintenance also have to be taken into account. In neurogenic disorders fibres with embryonic myosin heavy chains are rare but fetal myosin heavy chain expression is common, particularly in 5q spinal muscle atrophy. Nuclear clumps in denervated muscle show fetal and sometimes embryonic myosin heavy chains. Developmentally regulated myosins are useful for highlighting the perifascicular atrophy in juvenile dermatomyositis. Our studies highlight the importance of baseline data for embryonic and fetal myosin heavy chains in human muscle biopsies and the importance of assessing them in a spectrum of neuromuscular disorders.