G.P.260: Clinical diversity in patients with nemaline myopathy

Abstract

Nemaline myopathy (NM) is a clinically heterogeneous congenital myopathy characterized by the presence of nemaline rods in the skeletal muscle fibers. We investigated the clinical variation and pathological features in Korean patients with NM. Thirteen patients were diagnosed through muscle biopsy. Six patients had the typical congenital type, which showed the motor development delay and hypotonia at birth. Six patients showed the mild childhood type with the gait disturbance. One patient had the intermediate congenital type, who needed mechanical ventilation. Regarding the distribution of weakness, five patients presented distal dominant weakness across the clinical type. High arched palates and feet deformity were observed. Equino varus deformity was identified in two patients. But, we could not find the cardiac muscle involvement. Typical nemaline rods were recognized on light microscopy with muscle biopsy from 11 patients. However, we could identify the nemaline filamentous aggregation in electro microscope (EM) from 2 patients. One of them showed a mitochondrial abnormality in EM. Type 1 fiber predominance was in all patients. The causative mutation form 8 patients was investigated, we found a missense heterozygous mutation in exon 1 of <i>TPM3</i> gene (c.32T>A, p.Met11Lys). Seven patients showed negative results in <i>ACTA1</i> gene. The thirteen patients in this study did not share much common feature except the dysmorphic appearance. The clinical diversity was prominent with the distribution of muscle weakness and the severity of respiratory dysfunction. This study showed the phenotypic heterogeneity of NM is not only with clinical features but also with pathological findings in our patient pool. Wider application of whole exome sequencing may help overcome the phenotypic and genotypic diversity in the diagnosis of NM.