Clinical History
This 7 month-old male Labrador Retriever was presented for pre-neutering blood work. The dog was clinically normal with no detectable muscle weakness, exercise intolerance or muscle atrophy. The serum creatine kinase (CK) activity was markedly elevated at >40,000 (reference <200 IU/L), ALT was elevated at 441 (5-107 IU/L) and AST at 938 (reference 5-55 IU/L). The serum CK was repeated 1 week later and was still elevated at >30,000 IU/L. A muscle biopsy was suggested to determine the cause of this markedly elevated muscle enzyme.

Diagnostic Procedures
A muscle biopsy was performed and evaluated in frozen sections. Although not severe, a pattern of myonecrosis and regeneration was found consistent with a muscular dystrophy.  To further define which form of muscular dystrophy was present, immunostaining and immunoblotting for detection of dystrophy associated proteins was performed (See July 2007 Case of the Month). A mosaic staining pattern was identified using monoclonal antibodies against the rod (DYS1) and carboxy terminus (DYS2) of dystrophin (Fig. 1). Staining for utrophin (DRP2) was increased. Staining for sarcoglycans was appropriate (γ-SG shown). Immuoblotting confirmed a truncated form of dystrophin with an approximately 200 kDa protein fragment using the DYS1 antibody and no staining with the DYS2 antibody (Fig. 2). These findings confirm a dystrophin deficient muscular dystrophy in this asymptomatic dog.  

Figure 1

Figure 2

Conclusions
Dystrophin deficient muscular dystrophy has been reported in the Labrador Retriever breed (Bergman et al, JAAHA 2002;38:255-261).  In most cases of canine muscular dystrophy, a myopathic clinical presentation is obvious with gait abnormalities, muscle wasting and exercise intolerance. A markedly elevated serum CK activity is a hallmark of muscular dystrophy.  As in the dog of this report, a recent publication describes a 6 year old boy ( Dubowitz V, Neuromuscul Disord 2006;16:865-866) who did not show a typical myopathic phenotype but was dystrophin deficient. Similar to the Labrador reported here,  the serum CK concentration was markedly elevated. What are the compensatory factors that allow the normal clinical phenotype despite dystrophin deficiency? Perhaps the size of the dystrophin fragment present in this case is enough to ameliorate the clinical signs. Perhaps utrophin may be a modifying factor. Study of dystrophic “variants” may have important implications for muscular dystrophy therapies.