1. Background

• vimentin and desmin are filamentous proteins which act as cytoskeletal elements in developing fetal myotubes and serve to attach nuclei and mitochondria to the sarcolemma and preserve their central position.
• as fetal myotubes mature, vimentin and desmin decrease in amount and the nuclei and mitochondria are redistributed
• by term the vimentin in muscle cells has disappeared and desmin remains in trace amounts

2. Genetic Defect

• genetic defect -> ? persistence of vimentin and desmin -> matur-ational arrest of fetal muscle at myotubular stage (8-15 weeks gestational age) -> central nuclei and mitochondria -> clinical manifestations

1. Muscle Biopsy

• all muscles affected and 50-90% of fibres within a biopsy will be abnormal
• central nuclei
  • lie in a core of cytoplasm surrounded by a cylinder of contractile myofibrils (nuclei surrounded by a clear halo)
  • arranged in rows with the spaces between the nuclei filled with mitochondria
• stains
  • vimentin and desmin detected by immunohistochemistry
  • central distribution of stains for glycolysis and oxidative phosphorylation
  • mature ATPase stain for cylinder of myofibrils
    • central cores are devoid of ATPase
    • structured - myofibrils are normal in appearance
    • unstructured - myofibrils randomly arranged
• others
  • type 1 fibres predominantly affected and are smaller (atrophied)
  • type 2 fibres appear to be spared
  • on EM, clusters of mitochondria, lipopigments, glycogen, autophagic vacuoles, rER, and Golgi complexes are observed in the perinuclear central zone

1. Neurological Manifestations

• decreased fetal movements +/- polyhydramnios
• generalized infantile hypotonia and diffuse muscle weakness
  • facial, mastication, neck, axial, limb-girdle, distal
  • poor cough, cry, suck, swallow
  • respiratory distress
  • myopathic facies
  • gavage feeds
• thin tongue
• undescended testicles

1. Serum

• normal or slightly elevated CPK

2. EMG

• myopathic - brief, small amplitude, polyphasic motor potentials

3. Nerve Conduction Studies

• usually normal but somtimes slow

1. Supportive

• multidisciplinary approach
  • Paediatrics - promote ambulation and physiotherapy, moniter deformities
  • Surgery - moniter and correct deformities
  • Genetics - genetic counselling, prenatal diagnosis

2. Prognosis

• 75% die within first few weeks or months of life
• survivors have significant handicaps, are never ambulatory, and and remain severely hypotonic