A number sign (#) is used with this entry because of evidence that autosomal recessive myosin storage congenital myopathy-7B (CMYO7B) is caused by homozygous or compound heterozygous mutation in the MYH7 gene (160760) on chromosome 14q11.

Autosomal dominant myosin storage congenital myopathy-7A (CMYO7A; 608358) is caused by heterozygous mutation in the MYH7 gene.

Autosomal recessive myosin storage congenital myopathy-7B (CMYO7B) is a skeletal muscle disorder characterized by the onset of scapuloperoneal muscle weakness in early childhood or young adulthood. Affected individuals have difficulty walking, steppage gait, and scapular winging due to shoulder girdle involvement. The severity and progression of the disorder is highly variable, even within families. Most patients develop respiratory insufficiency, nocturnal hypoventilation, and restrictive lung disease; some develop hypertrophic cardiomyopathy. Additional features include myopathic facies, high-arched palate, scoliosis, and muscle wasting with thin body habitus. Serum creatine kinase may be normal or elevated. Skeletal muscle biopsy shows variable findings, including myosin storage disease, type 1 fiber predominance, centralized nuclei, and multiminicore disease (Onengut et al., 2004; Tajsharghi et al., 2007; Beecroft et al., 2019).

For a discussion of genetic heterogeneity of congenital myopathy, see CMYO1A (117000).

Onengut et al. (2004) reported 2 brothers with congenital 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 1 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 1 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. The brothers carried a homozygous missense mutation in the MYH7 gene (R1820W; 160760.0047).

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. The proband was found to carry a homozygous mutation in the MYH7 gene (E1883K; 160760.0035).

Beecroft et al. (2019) reported 3 patients from 2 unrelated families with CMYO7B. Two sibs, born of consanguineous parents of Middle Eastern ancestry in Australia (family AUS1), presented in early childhood with hypotonia and delayed motor milestones. At age 21 years, the older sib was ambulatory, but used a wheelchair for long distances. She also had progressive scoliosis, winged scapulae, weakness of neck extension and flexion, thin body habitus, myopathic facies, and restrictive lung disease requiring nocturnal noninvasive ventilation in the second decade. Her younger brother had mild truncal weakness and difficulty running. At age 13, he had spinal rigidity without scoliosis and required nocturnal ventilation. Cardiac function and serum creatine kinase were normal in both sibs. The only affected patient in the second family (family UK) was a 30-year-old woman with mild motor delay, progressive scoliosis, poor weight gain and thin body habitus requiring gastrostomy until age 18, and progressive nocturnal hypoventilation. She demonstrated proximal weakness of the shoulder and hip girdles; deep tendon reflexes were diminished. Creatine kinase levels were normal. Muscle biopsy in 1 sib in the first family showed variation in fiber size and hyaline bodies, whereas muscle biopsy in the patient from the second family showed features consistent with multiminicore disease. Affected members of both families carried homozygous or compound heterozygous mutations in the MYH7 gene (e.g., R1712W, 160760.0032).

The transmission pattern of CMYO7B in the family reported by Onengut et al. (2004) was consistent with autosomal recessive inheritance.

In a 44-year-old man, born of consanguineous British parents, with CMYO7B, 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 CMYO7B 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.

In 3 patients from 2 unrelated families with CMYO7B, Beecroft et al. (2019) identified homozygous or compound heterozygous mutations in the MYH7 gene. Two sibs from a consanguineous family (AUS1) carried a homozygous missense mutation (R1712W; 160760.0032), and an unrelated woman (UK1) was compound heterozygous for a nonsense and a missense mutation (Q1567X, 160760.0049 and E1555G, 160760.0050). The mutations, which were found by next-generation sequencing and confirmed by Sanger sequencing, were each inherited from an unaffected parent in both families. None were present in the gnomAD database.