Linssen et al. (1998) reported a Dutch family with Miyoshi myopathy not caused by dysferlin mutations (DYSF; 603009) and not linked to the MMD2 locus (613318) on chromosome 10. Age at onset ranged from 39 to 51 years, ... Linssen et al. (1998) reported a Dutch family with Miyoshi myopathy not caused by dysferlin mutations (DYSF; 603009) and not linked to the MMD2 locus (613318) on chromosome 10. Age at onset ranged from 39 to 51 years, and the presenting symptom was inability to stand on tiptoe due to asymmetric distal muscle weakness of the lower limbs. Jaiswal et al. (2007) reported 2 Finnish brothers with Miyoshi myopathy. The 41-year-old proband reported discomfort of the calf muscles since age 20 years. In his late twenties, he had difficulty running, and was unable to run after age 30. He remained ambulatory with a waddling gait. Physical examination showed mild weakness of the calf muscles, hypertrophy of the extensor digitorum brevis muscles, weakness of the proximal lower limb muscles, and increased serum creatine kinase. MRI showed fatty infiltration of affected muscles. His 46-year-old brother was clinically asymptomatic, but he had increased serum creatine kinase and showed fatty infiltration of the distal lower limb muscles on MRI. Among 16 male patients, most of Finnish origin, with recessive ANO5 mutations, Penttila et al. (2012) found that only 3 had distal lower limb weakness consistent with Miyoshi myopathy. One patient had proximal and distal lower limb weakness. The rest of the patients had proximal muscle weakness more consistent with the LGMD2L phenotype. There were no particular genotype/phenotype correlations. - Clinical Variability Penttila et al. (2012) observed that female patients with ANO5 mutations had consistently milder phenotypes than males with similar mutations. In a cohort of 25 mutation carriers, including 9 females and 16 males, most of Finnish origin, none of the females had clinically detectable muscle weakness despite increased serum creatine kinase and myopathic findings in muscle biopsy samples. They also had less severe fatty degenerative changes on MRI and less severely increased serum creatine kinase compared to males. Females presented with myalgia, exercise intolerance, calf hypertrophy, or isolated hyperCKemia. These gender differences were evident even among sibs in the same family, and there were no particular genotype/phenotype correlations.
In affected members of a Dutch family with MMD3 (Linssen et al., 1998), Bolduc et al. (2010) identified a homozygous mutation in the ANO5 gene (191dupA; 608662.0004). Two Finnish brothers with Miyoshi myopathy (Jaiswal et al., 2007) were ... In affected members of a Dutch family with MMD3 (Linssen et al., 1998), Bolduc et al. (2010) identified a homozygous mutation in the ANO5 gene (191dupA; 608662.0004). Two Finnish brothers with Miyoshi myopathy (Jaiswal et al., 2007) were found to be homozygous for another mutation in the ANO5 gene (R758C; 608662.0006). The 191dupA mutation was also observed in the heterozygous state in a family with LGMD2L (611307), confirming that the 2 disorders are allelic. Electron microscopy of a patient's muscle biopsy showed disruption of the sarcolemmal membrane, and Bolduc et al. (2010) postulated a defect in membrane repair.