Donner et al. (2002) reported a woman with nemaline myopathy who presented at age 12 years with difficulty in walking. She had a mild form of the disorder with asymmetric limb involvement and mild facial and neck flexor ... Donner et al. (2002) reported a woman with nemaline myopathy who presented at age 12 years with difficulty in walking. She had a mild form of the disorder with asymmetric limb involvement and mild facial and neck flexor weakness. She used a wheelchair beginning at age 48 years and died of respiratory causes at age 51. In a second affected family, of Bosnian origin, the proband was a 4-year-old boy who had feeding difficulties and severe hypotonia from birth. He had delayed motor development, but achieved ambulation. His affected mother had never been able to run. She had asymmetric limb involvement, myopathic facies, high-arched palate, and weak neck flexor muscles. One muscle biopsy from the son showed type 1 fiber predominance consistent with nemaline myopathy, but the finding of nemaline rods was equivocal; however, Donner et al. (2002) noted that the quantity of nemaline rods can vary substantially in affected patients. Tajsharghi et al. (2007) reported a 66-year-old woman and her 35-year-old daughter with congenital, slowly progressive muscle weakness. Both had neonatal hypotonia, with respiratory insufficiency and feeding difficulties, respectively, delayed motor milestones, and moderate proximal muscle weakness at onset, which later progressed to distal muscle weakness. Other features included facial diplegia with ptosis, long narrow face, high-arched palate, micrognathia, and restricted ventilatory capacity with nocturnal hypoventilation. Serum creatine kinase was normal in both. Muscle biopsy in the daughter at age 2.5 years and the mother at age 32 years showed small type 1 fibers and fiber size variation with no inclusions. Muscle biopsy in the daughter at 26 years showed cap-like structures composed of disorganized myofibrils and thickened Z bands sharply demarcated from the rest of the fiber. There were no nemaline rods. Repeat biopsy in the mother at age 57 years showed numerous subsarcolemmal nemaline rods within cap-like structures and numerous ragged red fibers with accumulation of abnormal mitochondria. - Cap Myopathy 2 Fidzianska et al. (1981) first described cap myopathy in a 7-year-old boy with congenital myopathy. He never walked and showed generalized muscle wasting and weakness. Other features included high-arched palate, narrow face, elongated funnel chest, lordosis, and kyphoscoliosis. Skeletal muscle biopsy showed fiber size variability with about 70% of fibers containing a PAS-positive substance forming a partial ring around the fibers in the peripheral part of the fiber: so-called 'caps.' ATPase staining of the caps was negative. Electron microscopy showed abnormally arranged myofibrils with an abnormal sarcomere pattern and irregular or streaming Z lines. Fidzianska et al. (1981) postulated a defect in the fusion and synthesis of muscle protein. Lehtokari et al. (2007) reported a 36-year-old man with muscle weakness since childhood. He had delayed motor development and was never able to run. At age 11 years, he showed myopathic facies, dysarthria, hyperlordosis, small muscle bulk, and generalized muscle weakness. At age 33 years, he developed acute respiratory insufficiency with pneumonia. Other features included high-arched palate and ptosis. Skeletal muscle biopsies as a child and adult showed fiber type disproportion with hypotrophy of type I fibers, hypertrophy of type II fibers, absence of type IIb fibers, and cap-like myofibrillar lesions mostly in type I fibers that stained positive for tropomyosin. Electron microscopy showed modified subsarcolemmal areas, disoriented myofibrils, and thickened Z line extensions with some short, rod-like structures. Lehtokari et al. (2007) noted the similarities of cap myopathy to nemaline myopathy. Ohlsson et al. (2008) reported 3 unrelated patients with cap myopathy. Although the phenotypic severity was variable, all had hypotonia in infancy and showed difficulty in walking and running in childhood. Other features included kyphoscoliosis, Gowers sign, winged scapulae, and decreased pulmonary vital capacity. Skeletal muscle biopsies showed uniformity of type 1 fibers, cap structures, and a coarse irregular intermyofibrillar network. Nemaline rods were not identified. The authors noted that cap structures were only identified by electron microscopy in 1 patient and only on a second biopsy in adulthood in another. Clarke et al. (2009) reported a 14-year-old Australian girl who had a history of hypotonia since infancy, delayed motor development, and slow running. She had generalized muscle wasting and weakness, particularly in the proximal muscles, and hyporeflexia. Other features included mild facial weakness, nasal voice, high-arched palate, long thin face, and mild micrognathia. Cardiac examination showed decreased systolic function, with an ejection fraction of 42%, mild mitral valve prolapse, and borderline aortic root dilatation. She also had central hypoventilation and restrictive lung disease with decreased forced vital capacity. Skeletal muscle biopsy at age 10 showed fiber type variability, and she received an initial diagnosis of congenital fiber-type disproportion (CFTD; 255310), a diagnosis of exclusion. However, about 4% of fibers were later noted to have caps, leading to a final histologic diagnosis of cap myopathy. There was type 1 fiber predominance. Electron microscopy showed irregular and thickened Z-lines, and the caps contained disorganized thin filaments. No classic nemaline rods were observed. Clarke et al. (2009) noted that the cardiac involvement in this patient was an unusual finding.
In a woman with childhood-onset nemaline myopathy, Donner et al. (2002) identified a heterozygous mutation in the TPM2 gene (190990.0002). In another family, of Bosnian origin, they identified a heterozygous mutation in the TPM2 gene (190990.0003) in both ... In a woman with childhood-onset nemaline myopathy, Donner et al. (2002) identified a heterozygous mutation in the TPM2 gene (190990.0002). In another family, of Bosnian origin, they identified a heterozygous mutation in the TPM2 gene (190990.0003) in both mother and son. Donner et al. (2002) commented that mutations in the TPM2 gene are an uncommon cause of nemaline myopathy. Tajsharghi et al. (2007) identified a heterozygous TPM2 mutation (190990.0005) in a mother and daughter with nemaline myopathy. Lehtokari et al. (2007) identified a heterozygous deletion in the TPM2 gene (415delGAG; 190990.0006) in a patient with cap myopathy. In 3 unrelated patients with cap myopathy, Ohlsson et al. (2008) identified 3 different de novo heterozygous mutations in the TPM2 gene (see, e.g., 190990.0007 and 190990.0008). The findings confirmed that TPM2 mutations can cause cap myopathy. In a girl with cap myopathy, Clarke et al. (2009) identified a heterozygous 415delGAG mutation in the TPM2 gene.