Werdnig-Hoffmann disease: myosin isoform expression not arrested at prenatal stage of development

It has been suggested, on the basis of mostly morphological and some biochemical evidence, that defective innervation of muscle of patients with Werdnig-Hoffmann (WH) disease results in maturational arrest of the fibers at a stage comparable to 20-week gestational muscle. Therefore, with the use of recently developed and characterized, myosin-isoform-specific monoclonal antibodies (McAbs), an immunocytochemical study of muscle of 6 children with Werdnig-Hoffmann disease was done to determine if the pattern of expression of myosin heavy chain isoforms (MHC) in these fibers was similar to that of 20-week gestation muscle. This work showed that the MHC isoform expression in the muscle of the children with WH did not mimic that seen in 20-week gestation muscle since only a few fibers (less than 1-11%) in each specimen expressed prenatal MHC as detected by reactivity to McAb, ALD 180 (specific for a prenatal MHC) whereas virtually all of the fibers from 20-week gestation muscle were strongly reactive with ALD 180. The majority of the fibers expressed either adult fast MHC or adult slow MHC similar to that seen in normal muscle, although some co-expressed multiple MHC isoforms. Our results indicate that the difference of adult MHC isoforms in the muscle fibers of WH patients either proceeds in the absence of innervation or that denervation of muscle fibers is subsequent to the neural input required to initiate myosin isoform transitions to the adult isoforms.