Characteristic findings of skeletal muscle MRI in caveolinopathies.

Caveolinopathies, caused by CAV3 mutations, can include several phenotypes such as rippling muscle disease, limb-girdle muscular dystrophy type 1C, distal myopathy, familial hypertrophic cardiomyopathy, and idiopathic hyperCKemia. Here we present characteristic skeletal muscle imaging findings in four patients with genetically defined childhood-onset RMD caused by CAV3 mutations and in one patient with congenital generalized lipodystrophy type 4 with muscular dystrophy due to polymerase I and transcript release factor (PTRF) mutations, which may have caused secondary deficiency of caveolin-3. Muscle MRI revealed that the rectus femoris and semitendinosus muscles were most commonly affected in the rippling muscle disease patients. Peripheral changes in the rectus femoris were specific and observed even in one of the younger patients in this study. Furthermore, muscle involvement extended to the semitendinosus muscles, biceps femoris, and gracilis with disease progression or increase in its severity. Similar patterns of involvement were observed on reviewing skeletal muscle images of various previously reported phenotypes of caveolinopathy; interestingly, patients with secondary deficiency of caveolin due to PTRF mutations revealed the same pattern. Thus, primary caveolinopathies and secondary deficiency of caveolin demonstrated specific findings on skeletal muscle imaging, regardless of the broad phenotypic spectrum of these two conditions.

Congenital fiber type disproportion myopathy caused by LMNA mutations.

A boy, who had shown muscle weakness and hypotonia from early childhood and fiber type disproportion (FTD) with no dystrophic changes on muscle biopsy, was initially diagnosed as having congenital fiber type disproportion (CFTD). Subsequently, he developed cardiac conduction blocks. We reconsidered the diagnosis as possible LMNA-myopathy and found a heterozygous mutation in the LMNA gene. This encouraged us to search for LMNA mutations on 80 patients who met the diagnostic criteria of CFTD with unknown cause. Two patients including the above index case had heterozygous in-frame deletion mutations of c.367_369delAAG and c.99_101delGGA in LMNA, respectively. Four of 23 muscular dystrophy patients with LMNA mutation also showed fiber type disproportion (FTD). Importantly, all FTD associated with LMNA-myopathy were caused by hypertrophy of type 2 fibers as compared with age-matched controls, whereas CFTD with mutations in ACTA1 or TPM3 showed selective type 1 fiber atrophy but no type 2 fiber hypertrophy. Although FTD is not a constant pathological feature of LMNA-myopathy, we should consider the possibility of LMNA-myopathy whenever a diagnosis of CFTD is made and take steps to prevent cardiac insufficiency.