Abstract:

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.

日本語要旨:

成人期発症の還元小体ミオパチー(reducing body myopathy; RBM)症例の臨床像を報告した。本症例は32歳女性で、FHL1遺伝子に変異を有し、胸鎖乳突筋と僧帽筋の非対称性萎縮が特徴的であった。FHL1遺伝子変異のある成人発症のRBM症例では、これまで胸鎖乳突筋、僧帽筋の非対称性萎縮は報告されておらず、貴重な報告である。