Test Detail
X-linked myotubular myopathy (XL-MTM)
Musculoesquelético · Dog
Severe congenital myopathy of the skeletal muscles due to a defect of myotubularin 1, a phosphatase involved in the maturation of muscle fibres. It appears in males as severe neonatal hypotonia («floppy puppy») with progressive respiratory weakness and early death. The canine form of the Labrador Retriever and the Rottweiler is a natural model of human X-linked myotubular myopathy (MTM1) and has been used in preclinical gene therapy trials.
Incidence
Labrador Retriever and Rottweiler are the breeds in which the X-linked form has been described. In the Labrador, the variant was found in affected males and was not detected in healthy dogs or in other breeds of the original study (Beggs 2010). No reliable figures on carrier frequency in the breeding population are published.
Breeder management
- Genotype females of lines with a history before mating
- A carrier female must not be mated: mating with a free male produces 50% carrier daughters and 50% hemizygous affected sons
- Affected males must not be used as breeding animals
- In breeding lines with confirmed carriers, prioritise free females and replace progressively
- Confirm the diagnosis with muscle biopsy (type I fibres with central nuclei) and genetic test before retiring valuable breeding animals
- A carrier female must not be mated: mating with a free male produces 50% carrier daughters and 50% hemizygous affected sons
- Affected males must not be used as breeding animals
- In breeding lines with confirmed carriers, prioritise free females and replace progressively
- Confirm the diagnosis with muscle biopsy (type I fibres with central nuclei) and genetic test before retiring valuable breeding animals
Specialist notes
Differential diagnosis with other congenital myopathies of the puppy (nemaline myopathy, congenital muscular dystrophy, congenital myasthenia) and with neonatal polyneuropathies. The biopsy shows small type I fibres with central nuclei; immunohistochemistry for myotubularin and the molecular study confirm. It is a model of gene therapy (AAV-MTM1) in preclinical trials.
References
1. Beggs AH et al. (2010) MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proc Natl Acad Sci USA 107(33):14697-14702. PMID: 20682747
2. Shelton GD et al. (2015) X-linked myotubular myopathy in Rottweiler dogs is caused by a missense mutation in Exon 11 of the MTM1 gene. Skelet Muscle 5:1. PMID: 25664165
3. Snead EC et al. (2015) Clinical phenotype of X-linked myotubular myopathy in Labrador Retriever puppies. J Vet Intern Med 29(1):254-260. PMID: 25581576
2. Shelton GD et al. (2015) X-linked myotubular myopathy in Rottweiler dogs is caused by a missense mutation in Exon 11 of the MTM1 gene. Skelet Muscle 5:1. PMID: 25664165
3. Snead EC et al. (2015) Clinical phenotype of X-linked myotubular myopathy in Labrador Retriever puppies. J Vet Intern Med 29(1):254-260. PMID: 25581576