MYOTUBULAR MYOPATHY - MORPHOLOGICAL, IMMUNOHISTOCHEMICAL AND CLINICALVARIATION

Myotubular myopathy frequently presents in male infants with severe ge neralised muscular hypotonia and weakness associated with ventilatory insufficiency, and is diagnosed on biopsy by the presence of many fibr es with central nuclei and mitochondrial aggregation. In a 6-year peri od, we have investigated five unrelated patients with clinical and pat hological features suggesting an X-linked myotubular myopathy, includi ng one female patient. In one male infant, a biopsy of vastus laterali s showed less than 2% centrally-nucleated fibres, while biceps brachii showed up to 15% centrally-nucleated fibres. Immunohistochemical expr ession of the neural cell adhesion molecule (CD56) was more intense in the biceps muscle than in vastus lateralis, while expression of desmi n and vimentin was similar. Morphometric evaluation of tissue from eac h of the patients revealed a wide spread of values for the number of c entrally-nucleated fibres per microscopic field, and variation in the extent of immunohistochemical expression of NCAM, utrophin, laminin al pha 5 chain, vimentin and HLA1 antigen. These variations in the manife stations of myotubular myopathy have not been previously described, an d will need to be correlated with the increasing knowledge of the muta tions in the MTM1 gene coding for myotubularin. (C) 1998 Elsevier Scie nce B.V.