Hereditary spinal muscular atrophy

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Hereditary spinal muscular atrophy is a rare autosomal-dominant genetic neurological disease characterized by progressive hindlimb muscular atrophy.

A number of breeds appear predisposed, including the Brittany Spaniel, English Pointer, German Shepherd, Rottweiler and Cairn Terrier[1].

With this motor neuron disease, homozygous-affected dogs display muscle motor unit dysfunction before motor terminal or axonal degeneration appear[2][3] and this dysfunction is an important determinant of weakness in affected animals[4]. The most important form of dysfunction is an inability to sustain motor unit force during repetitive activity. Interestingly, this dysfunction occurs to a significant extent in the absence of any electromyographic evidence of denervation[5].

Affected dogs are also predisposed to developing complement-3 deficiency[6] and familial juvenile glomerulonephropathy[7][8].

Clinical symptoms include a progressive and profound hindleg weakness and hemiparesis which usually develops within the first 12 weeks of age with tetraparesis evident by 6 months of age. Clinical progression may develop slower in heterozygous dogs and these dogs may not develop tetraparesis until 1 - 2 years of age. Typically, the first signs of weakness appear in the tail extensor muscles, with neck extensor and paravertebral muscles exhibiting signs of weakness soon thereafter. Hindlimb reflexes are usually reduced although sensory reflexes are normal[9].

Radiographic, CT and MRi imaging are usually unrewarding and myographic studies and histological testing are required to definitely diagnose this condition[10].

Spinal cord lesions include chromatolysis, axonal swelling filled with neurofilaments and eventually motor neurone death. Abnormalities in glutamate metabolism are also reported with this condition[11].

Neurological examination, electrodiagnostic testing, and histologic studies indicates that the disease results from motor horn cell degeneration.

A differential diagnosis would include centronuclear myopathy and myasthenia gravis.

There is no known treatment for this condition which is unresponsive to medical therapy such as prednisolone.

Palliative responses may be observed with fampridine.

References

  1. LIDA
  2. Rich MM et al (2002) Reduced endplate currents underlie motor unit dysfunction in canine motor neuron disease. J Neurophysiol 88(6):3293-3304
  3. Rich MM et al (2002) Reduced neuromuscular quantal content with normal synaptic release time course and depression in canine motor neuron disease. J Neurophysiol 88(6):3305-3314
  4. Balice-Gordon, RJ et al (2000) Functional motor unit failure precedes neuromuscular degeneration in canine motor neuron disease. Ann Neurol 47:596–605
  5. Pinter, MJ et al (2001) Canine motor neuron disease: a view from the motor unit. In: Motor Neurobiology of the Spinal Cord, edited by T. C. Cope. Boca Raton, FL: CRC. pp:231–250
  6. Lorenz MD et al (1979) Hereditary spinal muscular atrophy in Brittany Spaniels: clinical manifestations. J Am Vet Med Assoc 175(8):833-839
  7. Cork, LC et al (1991) Membranoproliferative glomerulonephritis in dogs with a genetically determined deficiency of the third component of complement. Clin Immunol Immunopathol 60:455
  8. Blum, JR et al (1985) The clinical manifestations of a genetically determined deficiency of the third component of complement in the dog. Clin Immunol Immunopathol 34:304
  9. Cork LC et al (1990) Hereditary canine spinal muscular atrophy: canine motor neuron disease. Can J Vet Res 54:77–82
  10. Carrasco DI et al (2004) Activity-driven synaptic and axonal degeneration in canine motor neuron disease. J Neurophysiol 92(2):1175-1181
  11. Blazej RG et al (1998) Hereditary canine spinal muscular atrophy is phenotypically similar but molecularly distinct from human spinal muscular atrophy. J Hered 89(6):531-537