Centronuclear myopathy (CNM) of the Labrador retriever is a hereditary disease of skeletal muscle with autosomal recessive inheritance. It is characterised by weakness, hypotonia and progressive muscle atrophy appearing from the first month of life. The cause is an insertion of a SINE element in exon 2 of the HACD1 gene (formerly PTPLA), which drastically reduces the amount of normal transcript. There is no curative treatment; management is supportive. In the Labradoodle the test is offered as screening by Labrador ancestry.

The variant is documented in the Labrador retriever (OMIA:001374-9615). In the Labradoodle the test is offered as screening by Labrador ancestry, without breed-specific studies (limited data). Carrier frequencies described in Labrador: around 19% in the United Kingdom (Maurer 2012), ~13% in the USA and ~11.5% in Canada.

- Weakness and reduced exercise tolerance\n- Hypotonia and altered tendon reflexes\n- Progressive muscle atrophy with onset around one month of life\n- Abnormal gait\n- In severe cases, difficulty swallowing due to oesophageal involvement and risk of sudden death\n- Worsening with cold; signs usually stabilise around one year of age

Clinically described in Labradors as congenital myopathy in the 1980s-90s; in 2005 Pelé and colleagues identified the causal mutation in PTPLA (now HACD1) and established the canine model of autosomal recessive CNM. In 2012, Maurer and colleagues demonstrated, by genotyping more than 7,000 Labradors, that the mutation comes from a single recent founder disseminated worldwide through popular stud dogs.

- Test breeding animals with the specific HACD1/PTPLA test\n- Do not mate two carriers (25% affected offspring)\n- A carrier may be mated with a clear dog; test offspring intended for breeding\n- In the Labradoodle, the test only has value as screening by Labrador ancestry, since the disease is documented in the Labrador; interpret with caution\n- Avoid intensive use of carrier stud dogs and record the results

The differential diagnosis includes other early-onset myopathies (muscular dystrophy, congenital myotonia) and myelopathies. Muscle biopsy shows an increase in internalised nuclei and fibre size variation. Confirmation is genetic. CNM is documented in the Labrador retriever; in the Labradoodle the indication for the test comes from ancestry and not from a breed-specific study, so caution is advisable when communicating results.

1. Pelé 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. PMID: 15829503
2. Maurer M et al. 2012. Centronuclear myopathy in Labrador retrievers: a recent founder mutation in the PTPLA gene has rapidly disseminated worldwide. PLoS One. PMID: 23071563
3. OMIA:001374-9615.