Myopathy, Myosin Storage, Autosomal Recessive

A number sign (#) is used with this entry because of evidence that autosomal recessive myosin storage myopathy (MSMB) is caused by homozygous mutation in the MYH7 gene (160760) on chromosome 14q12.

An autosomal dominant form of myosin storage myopathy (MSMA; 608358) is caused by heterozygous mutation in the MYH7 gene.

Clinical Features

Onengut et al. (2004) reported 2 brothers with hyaline body myopathy; 1 of the brothers recalled weakness from childhood, but did not become severely symptomatic until age 28, whereas the other brother was asymptomatic until age 33 years. Both patients showed scapuloperoneal weakness and atrophy with an elevated creatine kinase (2- to 3-fold increase). The brother with earlier onset also had a long face, high-arched palate, and decreased cardiac systolic function. Muscle biopsies of both patients showed variation in fiber size with marked type I fiber predominance. Approximately 15 to 20% of the fibers had central nuclei. The most striking finding was the presence of subsarcolemmal hyalinized structures, which were present in 25 to 30% of type I fibers. The hyalinized structures lacked reactivity for periodic acid Schiff (PAS) and oxidative enzymes, and stained positive for ATPase at pH 4.3. Yuceyar et al. (2015) reported follow-up of the 2 brothers studied by Onengut et al. (2004), who were born of consanguineous Turkish parents. The older brother developed severe progressive dilated cardiomyopathy and respiratory insufficiency in his forties. Scapuloperoneal muscular atrophy and weakness was slowly progressive, and he had scapular winging. The younger brother had milder progression of the muscle weakness and mild symptoms of cardiac involvement.

Tajsharghi et al. (2007) reported 3 adult sibs, born of second-cousin British parents, with myosin storage myopathy associated with hypertrophic cardiomyopathy and respiratory failure. Muscle biopsies from all 3 sibs showed findings typical for myosin storage myopathy, with hyaline bodies seen in type 1 fibers. All patients had mildly increased serum creatine kinase as well as onset of cardiac symptoms as young adults. The proband was a 44-year-old man with short stature, myopathic facies, high-arched palate, scoliosis, and proximal muscle weakness and wasting. He had leg weakness and hypercapnic respiratory failure necessitating ventilatory support. Investigation revealed hypertrophic cardiomyopathy and heart failure. His sister had progressive muscle weakness, required a wheelchair by age 45, and died of cardiac failure at age 57. His brother had mild proximal muscle weakness and wasting and died of cardiac failure at age 32. Postmortem examination of affected cardiac muscle from 1 patient showed fibrosis, loss of myocytes, and hyaline bodies in the remaining myocytes.

Inheritance

The transmission pattern of hyaline body myopathy in the family reported by Onengut et al. (2004) was consistent with autosomal recessive inheritance.

Molecular Genetics

In a 44-year-old man, born of consanguineous British parents, with autosomal recessive myosin storage myopathy, Tajsharghi et al. (2007) identified a homozygous missense mutation in the MYH7 gene (E1883K; 160760.0035). He had 2 similarly affected sibs who died of cardiac failure, but their DNA was unavailable for study.

In 2 Turkish brothers, born of consanguineous parents, with autosomal recessive myosin storage myopathy, who were originally reported by Onengut et al. (2004), Yuceyar et al. (2015) identified a homozygous missense mutation in the MYH7 gene (R1820W; 160760.0047). The mutation, which was found by linkage analysis and candidate gene sequencing, segregated with the disorder in the family. Functional studies of the variant were not performed.