G.P.57: Novel MYH7-mutations in Norwegian patients with distal myopathy

Abstract

Distal myopathies are a group of inherited diseases affecting mainly the distal limb muscles. As a group, these are outnumbered by the Limb Girdle muscular dystrophies, and less is known about the prevalence of relevant mutations in our population. We found novel mutations in the MYH7 gene in two Norwegian kindreds with a dominantly inherited, distal myopathy starting in childhood. MYH7-mutations have been previously associated with three different clinical manifestations: Laing distal myopathy, myosin storage myopathy and cardiomyopathy. In our families, one mutation is situated in exon 32, within the region generally associated with Laing myopathy. The clinical picture is also similar; selective affection of anterior calf muscles and finger extensors, and a slow, relatively non-progressive course. The other mutation is in exon 28, which is outside the region associated with Laing myopathy, and has only been reported once, in a Norwegian patient with hypertrophic cardiomyopathy. Nevertheless, the phenotype is still similar, albeit more severe, with clear proximal affection as disease progresses. One patient in this family has also developed a cardiomyopathy. Patients from both kindreds demonstrate the characteristic radiological features and fibre type specific pathology that support the clinical relevance of these novel mutations with regards to skeletal myopathy.