Centronuclear Myopathies in Dogs

The centronuclear myopathies are a group of congenital myopathies characterized by histopathological abnormalities affecting type II muscle fibers. Causative genetic mutations affecting the HACD1 (previously named PTPLA), MTM1, and BIN1 genes have been identified in several different dog breeds. A mutation of HACD1 is associated with centronuclear myopathy in Labrador Retrievers (1). Mutations in MTM1 were shown to cause centronuclear myopathy in Labrador Retrievers, Rottweilers, and Boykin Spaniels. A BIN1 mutation is linked to centronuclear myopathy in Great Danes (2, 3, 4, 5).An autosomal dominant DNM2 mutation causing centronuclear myopathy has been reported in a male Border Collie (6).

Clinical signs of centronuclear myopathy and the time of their onset vary by breed. In Labrador Retrievers, the condition is typically diagnosed between the ages of 6 weeks and 7 months, and the most obvious clinical signs appear by age 3–4 months. The condition stabilizes by age 6–12 months.

Clinical signs in Labrador Retrievers can include the following:

• short, stilted gait with "bunny-hopping" in the pelvic limbs

• cervical ventroflexion and/or kyphosis

• abnormal joint postures, such as carpal hyperextension and valgus, splayed digits, and a "cow-hocked" pelvic limb stance

• decreased or absent tendon reflexes (particularly patellar and triceps)

• atrophy of the proximal limb, head, and epaxial muscles

Cold weather, stress, and excitement can exacerbate these clinical signs. Megaesophagus occurs rarely. Labrador Retrievers with centronuclear myopathy can have a normal lifespan.

Great Danes can begin to show clinical signs of centronuclear myopathy any time from age 6 months to age 3 years (median age of onset: 7 months). Clinical signs in Great Danes may be mild and progress slowly, and can include the following:

• generalized weakness that worsens with exercise

• muscular atrophy

• short-strided gait with "bunny-hopping"

• tremors while standing

Most Great Danes with centronuclear myopathy progress and require euthanasia within months of the initial diagnosis.

Diagnosis is confirmed with genetic testing in Labrador Retrievers and Great Danes and can also be confirmed by muscle biopsy. Electromyographic findings are frequently abnormal. Serum CK activity may be normal to elevated.

There is no specific treatment for centronuclear myopathy. Warm housing and lifelong supplementation with L-carnitine, coenzyme Q₁₀, and B vitamins can improve the condition in some dogs. Controlled studies using these supplements to treat centronuclear myopathies in small animals have not been undertaken. Thus, use of these supplements at the following dosages to treat centronuclear myopathies in small animals is anecdotal:

• L-carnitine: 50–200 mg, PO, every 8–12 hours

• coenzyme Q₁₀: 200 mg, PO, every 12 hours

• vitamin B complex: comes in many different forms (injectable, oral); dosing should be based on concentration and manufacturer recommendations

The clinical features of centronuclear myopathy differ from those of exercise-induced intolerance and collapse in Labrador Retrievers.

For other degenerative/developmental myopathies in dogs, see the Overview for this chapter.