G.P.32 Progressive core myopathy with dilated cardiomyopathy, respiratory failure and severe scoliosis caused by a novel mutation in the MYH7 gene

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Heterozygous mutations in the MYH7 gene, encoding for the slow/beta-cardiac myosin heavy chain, are responsible for a wide spectrum of myopathies variably affecting cardiac or skeletal muscle, such as hypertrophic cardiomyopathy, Laing distal myopathy (MPD1), congenital fibre type disproportion, scapuloperoneal myopathy and myosin storage myopathy. Occurrence of both skeletal myopathy and cardiomyopathy has so far been described only in a few families. Here we report about a family with a novel MYH7 mutation, presenting with a progressive phenotype affecting both skeletal and cardiac muscles. The index case, aged 28years at time of last assessment, showed first symptoms at 1year of age. The phenotype was characterized by progressive proximal and distal weakness, severe scoliosis requiring spinal fixation at 9years of age, joint contractures and significant involvement of neck flexors and extensors. The patient lost ambulation at the age of 16years and subsequently developed respiratory insufficiency, dilated cardiomyopathy and seizures. His daughter showed first symptoms at the age of 3years, with mild proximal weakness, tiredness, joint hypermobility and a progressive scoliosis. CK values were normal and muscle biopsy showed type 1 fibre atrophy in both patients. The index case also showed feature of a core myopathy in his biopsy. Analysis of the MYH7 gene identified a heterozygous c.4823G>C (p.Arg1608Pro) variant in exon 34. Interestingly the unaffected father of the index case was mosaic for the c.4823G>C mutation. The degree of somatic mosaicism was not assessed and no other family members were found to carry the MYH7 variant. Missense mutations to proline disrupting the ability of the myosin tail to form a coiled coil are known to cause MPD1. Our findings expand the severe end of the phenotypic spectrum of conditions associated with MYH7 mutations.