Myotubular, centronuclear or peri-centronuclear myopathy?

Abstract

A female child who died at the age of 27 months from an intercurrent pulmonary infection secondary to severe generalised hypotonia, muscular atrophy and weakness, showed clinical and pathological features previously described in patients with myotubular or centronuclear myopathy. She was noted to have multiple extra-ocular palsies and facial asymmetry at 5 months of age. No myotonia or other features of myotonic dystrophy were found. The histological findings in a muscle biopsy obtained from the quadriceps muscle at 19 months of age were first that 95% of muscle fibres were abnormally small and of these more than 85% had centrally-placed nuclei with a surrounding sarcoplasm-sparse zone. The remaining 5% of fibres were abnormally large and were of two types. One group resembled Wohlfart B fibres, the others were larger multi-nucleated fibres of apparently unique structure. No evidence of dystrophic muscle changes or inflammation were seen either in biopsy or autopsy sections. No abnormality was found in the brain or spinal cord. Electron microscopic studies on the small fibres showed that the perinuclear zone consisted of a focal area of myofibrillar degeneration with myofilamentous debris, mitochondria, myelin figures and empty vesicular structures. The degeneration sometimes extended so as to occupy the whole width of the cell with total loss of sarcomere structure. Although there are certain clinical and pathological resemblances between this condition and infantile myotonic dystrophy the reported cases have not shown the other associated features of the latter disease with the exception of the electrical demonstration of myotonia in 1 case; a family history of myotonic dystrophy has not been reported in any of the cases. External ocular muscle weakness has been a distinctive feature in several of the cases and although this may infrequently occur as a late feature in myotonic dystrophy, it has not been reported in such cases in childhood. The aetiology of this condition is unknown but because of the distinctive histopathological changes in our case we would like to suggest the descriptive term peri-centronuclear myopathy.