Centronuclear myopathy (CNM) of the Labrador Retriever: congenital myopathy due to an exonic SINE insertion in the PTPLA gene (now HACD1), which alters splicing and produces progressive muscle weakness from the first months of life, with exercise intolerance, abnormal postures and muscle atrophy. It is inherited in an autosomal recessive manner. The test detects the Labrador founder variant; it is complementary to neurological examination and muscle biopsy.

Labrador Retriever worldwide (disseminated founder mutation; Mauri et al. 2012). In an Italian sample the allele frequency was 1.8% (0.47% excluding cases; ~1 case per 20,000 dogs). The test is also offered for Great Dane and German Terrier, but the variant is the Labrador one: a negative result in those breeds does not rule out their own myopathies (limited data).

- Generalised muscle weakness with onset between 8 weeks and 6 months\n- Abnormal gait with short stride, bunny hopping and swaying of the hindquarters\n- Exercise intolerance with rapid fatigue after short efforts\n- Muscle atrophy of trunk and limbs\n- Hunched postures (arched back) and extended neck\n- Fine muscle tremors at rest or after exercise\n- Worsening with cold and overexertion; many stabilise partially as they mature

Centronuclear myopathy of the Labrador was described clinically as an entity distinct from hereditary myopathy due to type II fibre deficiency (HMLR, of unresolved molecular basis). Pelé et al. (2005) identified an exonic SINE insertion in PTPLA that segregates with the autosomal recessive form. The 2012 study showed that it is a recent founder mutation rapidly disseminated throughout the world. It must not be confused either with HMLR (type II, no known gene) or with exercise-induced collapse (EIC, a distinct DNM1 variant).

- Test Labrador Retriever breeding animals before mating.\n- Do not mate two carriers: 25 %% risk of affected homozygotes.\n- A carrier may be mated with a clear dog; test offspring intended for breeding.\n- In Great Dane and German Terrier, interpret a negative result with caution (it only rules out the Labrador variant).\n- In the face of juvenile muscle weakness, include CNM in the differential diagnosis together with HMLR, EIC and acquired causes.

Differential diagnosis: hereditary myopathy due to type II fibre deficiency (HMLR, no known gene), exercise-induced collapse (EIC, DNM1), congenital/acquired myasthenia gravis, polymyositis and neuropathies. Muscle biopsy with nuclear centralisation points to CNM; the PTPLA test confirms it. No curative treatment: supportive management and physiotherapy.

1. Pelé M et al. 2005, inserción SINE exónica en PTPLA y miopatía centronuclear autosómica recesiva (PMID 15829503)
2. Maurer M et al. 2012, la miopatía centronuclear del Labrador es una mutación fundadora reciente diseminada mundialmente (PMID 23071563)
3. Gentilini F et al. 2011, frecuencia del alelo PTPLA en Labrador Retriever de Italia (PMID 21217042)
4. OMIA:001374 Miopatía centronuclear (PTPLA) del Labrador Retriever