Centronuclear myopathy

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Centronuclear myopathy (CNM; Labrador muscular myopathy) is an autosomal-recessive genetic disease of dogs characterized by early-onset muscular atrophy.

This disease is caused by a missense mutation in the PTPLA gene[1].

Breeds which are affected include the Labrador Retriever, Border Collie[2] and Labradoodle.

Centronuclear myopathy is a recessively inherited muscular disease. At birth, affected puppies are indistinguishable from their control littermates but as from two weeks of age, a progressive significant weight loss is observed. At one month of age, the absence of tendon reflexes is noticed and used as an early and reliable diagnosis. The age of onset of the disabling phenotype varies between 2 to 5 months, with an awkward gait and a decreased exercise tolerance and difficulty eating associated with a generalized muscle weakness. The pup will never recover from this disabling disease.

Clinical signs become apparent within the first year of life (usually from 6 weeks to 7 months) and are variable degrees of exercise-induced weakness and collapse, particularly the hindlimbs, as well as neurological deficits such as ataxia, bunny-hopping and ventroflexion of the neck. As the condition progresses, generalized atrophy of the skeletal muscles develops.

Megaesophagus is a common sequela, which present with regurgiation and coughing. Secondary aspiration pneumonia may complicate the clinical picture.

Blood tests, CSF analysis and electromyography are usually unrewarding and serology should be performed to exclude infectious causes such as Neospora caninum and Toxoplasma gondii.

A tentative diagnosis can be established based on muscle tissue biopsy, with histopathology showing centronuclear myopathy in type II muscle fibres, but a definitive diagnosis requires molecular testing using PCR-based DNA assays[3]. This also allows for identification of asymptomatic heterozygous carrier dogs. This information is particularly relevant for breeders, enabling them to produce healthy litters[4].

A differential diagnosis would include Duchenne muscular dystrophy, Golden Retriever Muscular Dystrophy, Myasthenia gravis, myotubular myopathy, myotonia congenita and nemaline myopathy.

Some dogs may respond to supportive medications such as L-carnitine, co-enzyme Q10 and vitamin B compounds.

References

  1. Gentilini F et al (2011) Frequency of the allelic variant of the PTPLA gene responsible for centronuclear myopathy in Labrador Retriever dogs as assessed in Italy. J Vet Diagn Invest 23(1):124-126
  2. Eminaga S et al (2012) Centronuclear myopathy in a Border collie dog. J Small Anim Pract 53(10):608-612
  3. Pele´ M et al (2005) SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs. Hum Mol Genet 14:1417–1420
  4. Pfeiffer I & Brenig B (2005) Frequency of the canine leucocyte adhesion deficiency (CLAD) mutation among Irish red setters in Germany. J Anim Breed Genet 122:140–142