What are the probable congenital myopathies?

Updated: Mar 11, 2019
  • Author: Matthew Harmelink, MD; Chief Editor: Amy Kao, MD  more...
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Probable congenital myopathies

  • Fingerprint body myopathy: Patients present with hypotonia from infancy, proximal muscle weakness, and a delay in attaining motor milestones. Weakness progresses slowly or is nonprogressive. Additional features can include pectus excavatum and intellectual disability. Inheritance is likely autosomal recessive or sporadic. Small inclusions can be seen on H&E section in a subsarcolemmal distribution. On electron microscopy (EM), the fingerprint inclusions consist of nonmembrane-bound perinuclear collections of convoluted lamellae, most often in type-1 muscle fibers.

  • Cylindrical spirals myopathy: Onset occurs in late childhood to adulthood. Phenotypes are variable, and manifestations can include weakness (at times facioscapular), abnormal gait, myotonia, cramps, and scoliosis. Inheritance is autosomal dominant or sporadic. Light microscopy shows subsarcolemmal or intermyofibrillar clusters that stain blue on H&E, red-purple on modified GT stain, and negatively for myosin ATPase and SDH, most often in type-2 fibers. EM reveals the cylindrical spirals to appear as concentrically wrapped lamellae merging into tubular structures that resemble tubular aggregates.

  • Myopathy with tubular aggregates

    • These myopathies fall into the following 4 groups: (1) Childhood or adulthood onset of exercise-induced cramps, pain, and stiffness is the most common phenotype. Males are most commonly affected. Inheritance is sporadic, autosomal dominant, or autosomal recessive. (2) The onset occurs during childhood or adulthood and is a slowly progressive proximal weakness that may be accompanied by myalgias, cramps, or stiffness. Inheritance is sporadic, autosomal dominant, or autosomal recessive. (3) The onset occurs during infancy or childhood and includes myasthenic features of limb weakness and fatigability. Inheritance is autosomal recessive. (4) The onset occurs during late childhood and includes gyrate atrophy of the choroids and retina, resulting in progressive blindness. Inheritance is autosomal recessive and due to a deficiency in ornithine aminotransferase.

    • Tubular aggregates are collections of 50- to 80-nm tubules that originate in the SR. They are best visualized on NADH, where they stain a dark blue, as shown below.

      Tubular aggregates, nicotinamide adenine dinucleot Tubular aggregates, nicotinamide adenine dinucleotide (NADH) stain. Cytoplasmic collections of membranous tubules (derived from the sarcoplasmic reticulum) can be present in various myopathies, including myopathy with tubular aggregates, hypokalemic periodic paralysis, malignant hyperthermia, myotonia congenita, and ceratin toxic myopathies.
    • They stain negatively with myosin ATPase and SDH. Aggregates are usually present in type 2 muscle fibers but also can be seen in type 1 fibers. They contain calsequestrin, heat shock proteins, SR ATPase, and SR calcium-pump proteins. Tubular aggregates also commonly occur in hypokalemic periodic paralysis and myotonia congenita, as well as less commonly in malignant hyperthermia, inflammatory myopathies, and alcoholic myopathy. Certain drugs, toxins, or hypoxia can also induce them. The tubular aggregates have been hypothesized to be an adaptive response to genetic or functional abnormalities affecting intracellular calcium flux, excitation-contraction coupling, or muscle fiber excitation.

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