Hyaline body myopathy is a rare congenital myopathy characterized by subsarcolemmal hyalinized bodies in type I muscle fibers.
Cancilla et al. (1971) described a brother and sister with a congenital myopathy in which they noted probable ... Hyaline body myopathy is a rare congenital myopathy characterized by subsarcolemmal hyalinized bodies in type I muscle fibers. Cancilla et al. (1971) described a brother and sister with a congenital myopathy in which they noted probable lysis of type I myofibrils. A fine granular material that stained intensely with the myosin ATPase reaction had accumulated within the fibers. Dye et al. (2006) stated that the disease progressed over the years in the patients reported by Cancilla et al. (1971). The sister developed joint contractures of her limbs, severe scoliosis, and required ventilatory assistance. She died at age 25 years from bronchopneumonia after exploratory abdominal surgery for appendicitis. Her younger brother had scoliosis with fusion rod and tracheotomy at the age of 30 years. Sahgal and Sahgal (1977) reported a patient with sporadic nonprogressive congenital myopathy with weakness and atrophy of the scapuloperoneal muscles. Muscle biopsy showed preferential atrophy of type I muscle fibers and subsarcolemmal bodies composed of an acid protein with ATPase activity. Goebel et al. (1981) reported a 15-year-old girl with proximal muscle weakness since infancy. Milder distal muscle weakness was also present. Quadriceps muscle biopsy showed a predominance of type I muscle fibers with 'cytoplasmic bodies.' There was no family history. Ceuterick et al. (1993) reported a 10-year-old boy with nonprogressive myopathy. Muscle biopsy showed hyaline bodies in type I fibers that stained with the myosin ATPase reaction at pH 4.2 and with polyclonal antiskeletal myosin. Immunoreactive deposits to antidesmin were observed at the border of some hyaline bodies. Ultrastructurally, the hyaline bodies were not surrounded by a limiting membrane and were only localized in subsarcolemmal areas. Periodic acid Schiff (PAS) staining for polysaccharides was negative. Barohn et al. (1994) reported 2 patients with sporadic hyaline body myopathy since infancy: a 40-year-old male and a 3-year-old female. Both had numerous subsarcolemmal glassy, hyaline bodies in 20 to 30% of type I muscle fibers. The hyaline bodies stained negative for PAS and oxidative enzymes, contained amorphous granular material, but were not contained within a membrane. Masuzugawa et al. (1997) reported a family in which 7 members over 4 generations developed slowly progressive scapuloperoneal muscle weakness and atrophy with an age at onset ranging from the first to fifth decade. Muscle biopsy of 2 patients showed subsarcolemmal hyaline bodies in approximately 20% of type I fibers. The hyaline bodies showed myofibrillar ATPase activity and stained intensely with antibodies to slow myosin heavy chain. Ultrastructurally, the hyaline bodies consisted of granules in linear array, filaments, or amorphous materials. Bohlega et al. (2003) reported a Saudi Arabian kindred in which 11 members, including a mother, her father, and 8 of her 13 children, were affected with hyaline body myopathy inherited in an autosomal dominant pattern. Muscle biopsies showed subsarcolemmal hyaline bodies in type I fibers that were positive for ATPase and heavy chain slow myosin. Ultrastucturally, the hyaline bodies were granular and filamentous or amorphous, surrounded by disorganized sarcomeres. There were also many signs of myopathy, including fiber-type grouping, angulated fibers, fiber necrosis, fibrosis, and central nucleation. Bohlega et al. (2003) noted 2 distinct disease patterns in the family: a nonprogressive minimal generalized muscle wasting and weakness since childhood, and a relentlessly progressive weakness starting at age 2 years with proximal arm and hand weakness, scapular winging, and severe functional impairment resulting in loss of ambulation around age 20 years. Goebel and Warlo (2001) suggested that hyaline body myopathy may be related to a surplus of proteins present in a granular or filamentous form. Tajsharghi et al. (2003) reported a patient with slowly progressive muscle weakness since childhood, when his gait was affected by hip weakness, but he was able to climb stairs and even run. He also had shoulder girdle weakness, bilateral winging of the scapulae, and pseudohypertrophy of the calves. By age 71 years, he was severely weak in the proximal muscles and moderately weak in the distal muscles. Lung vital capacity was 57% of normal, serum creatine kinase was elevated, and EMG findings were consistent with a myopathy. There were no signs of cardiomyopathy clinically or by imaging, although he did have atrial fibrillation. His mother had had similar symptoms, with hip and shoulder girdle weakness, as well as atrial fibrillation. One of 3 children (a daughter) of the proband was also affected. Tajsharghi et al. (2003) also reported an unrelated 33-year-old woman with a similar phenotype, including waddling gait, winging of the scapulae, pseudohypertrophy of the calves, and normal cardiac findings. None of her family members was affected. Muscle biopsy in the proband of the first family showed type 1 fiber predominance and increased interstitial fat and connective tissue. Inclusion bodies consisting of the beta cardiac myosin heavy chain were present in the majority of type 1 fibers, but not in type 2 fibers. The authors termed the disorder 'myosin storage myopathy.'
In affected members of a family and in an unrelated patient with myosin storage myopathy, Tajsharghi et al. (2003) identified a heterozygous mutation in the MYH7 gene (160760.0028).
In affected members of a Saudi Arabian family ... In affected members of a family and in an unrelated patient with myosin storage myopathy, Tajsharghi et al. (2003) identified a heterozygous mutation in the MYH7 gene (160760.0028). In affected members of a Saudi Arabian family with autosomal dominant hyaline body myopathy reported by Bohlega et al. (2003), Bohlega et al. (2004) identified a mutation in the MYH7 gene (160760.0031). In a Belgian patient with myosin storage myopathy originally reported by Ceuterick et al. (1993), Laing et al. (2005) identified a mutation in the MYH7 gene (160760.0028). In 1 of the affected sibs originally reported by Cancilla et al. (1971), Dye et al. (2006) identified a heterozygous mutation in the MYH7 gene (L1793P; 160760.0037), confirming that the disease in that family was autosomal dominant myosin storage myopathy. Dye et al. (2006) noted that contact with the family had been lost and DNA studies were performed on archival postmortem sections from the affected sister who died at age 25 years. The sibs presumably had the disease because of gonadal mosaicism in 1 of the unaffected parents, although this could not be confirmed. In a mother with myosin storage myopathy, who later developed hypertrophic cardiomyopathy (CMH1; 192600), and in her daughter, who had early-symptomatic left ventricular noncompaction (LVNC5; 613426), Uro-Coste et al. (2009) identified heterozygosity for the L1793P mutation in MYH7. The mother presented at age 30 years with proximal muscle weakness, which progressed to the point of her being wheelchair-bound by 48 years of age. At age 51, CMH was diagnosed. Skeletal muscle biopsy at 53 years of age showed subsarcolemmal accumulation of hyaline material in type 1 fibers. Her 24-year-old daughter presented with heart failure at 3 months of age and was diagnosed with early-onset cardiomyopathy. Angiography revealed a less-contractile, irregular 'spongiotic' wall in the inferior left ventricle, and echocardiography confirmed the diagnosis of LVNC. The daughter did not complain of muscle weakness, but clinical examination revealed bilateral wasting of the distal leg anterior compartment and she had some difficulty with heel-walking.