We report a patient who presented an adult onset form of quadriceps myopathy, with increased CPK and slowly progressive atrophy of vastus medialis. A muscle biopsy revealed a prominent pathology of the type 1 fibers with reduced diameter and slight predominance. Oxidative enzymes reactions demonstrated multiple or single regions of decrease/loss activity in most type 1 fibers and in scattered type 2. Ultrastructural examination showed myofibrillar degeneration, with Z-band streaming and mitochondrial depletion in the same regions. A diagnosis of Multi/minicore disease (MmD) was made on the basis of the morphological aspects of the muscle biopsy. In particular, the features characterizing the minicores, such as their short length, their poorly-defined boundaries and their presence in both type 1 and type 2 fibres, are typical of this kind of pathology. Screening for mutations of the RYR1 gene revealed a C to T transition at nucleotide 1201 which resulted in a R401C substitution in exon 12. According to our observation, clinical, morphologic and genetic boundaries between MmD and Central Core Disease (CCD) could be less distinct than so far considered. In addition, we underline that the R401C mutation in RYR1 can be associated with a benign phenotype of adult onset MmD. It remains to be determined the functional relevance of this RYR1 modification.
Adult onset multi/minicore myopathy associated with a mutation in the RYR1 gene / PIETRINI V.; MARBINI A.; GALLI L.; SORRENTINO V.. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - 251(2004), pp. 102-104. [10.1007/s00415-004-0220-y]