Inherited Myopathy in a 7 month old M Great Dane
Contributed by Dr. Eithne Comerford
University of Bristol
Bristol , UK
Clinical History
The dog presented with a recent history of muscle tremor, reluctance to exercise and collapse upon walking only a few steps.
Figure 1. 7 month old M Great Dane dog with centronuclear myopathy. Click here to play video.
Physical and Neurological Examination
When walking, the dog was very tentative on the pelvic limbs with a crouched stance. Generalized muscle atrophy was evident most notably in the pelvic limbs. Neurological examination was within normal limits and no pain was elicited upon palpation of the vertebral column. All other clinical parameters including heart rate and body temperature were within normal limits. Given the age, breed and clinical signs, the inherited myopathy of Great Danes, another myopathy, or possibly a cervical spondylopathy were considered.
Diagnostic Tests
CBC: Unremarkable Serum Chemistry: Creatine kinase was elevated at 1519 IU/L (reference 75-230) and total protein was mildly Radiographs of cervical spine: Within normal limits Electrophysiology: Electromyography revealed fibrillation potentials in the quadriceps muscle group, triceps, gluteal and hamstring muscles. The motor nerve conduction velocity was 42.9 m/sec. Muscle and nerve biopsies: Fresh and fixed specimens were collected from the quadriceps and triceps muscles, and the common peroneal nerve. The predominant pathological change within both muscle biopsies was the presence of large central zones that were basophilic on H&E staining (Fig. 2A) and darkly stained with the oxidative reactions SDH (Fig. 2B) and cytochrome C oxidase (not shown). No abnormalities were identified within resin embedded peripheral nerve sections.
Figure 2A. H&E stain frozen muscle biopsy
Figure 2B. SDH reaction
Clinical Course and Outcome
This dog was proven to have centronuclear myopathy by mutational analysis of the BIN1 gene. The histopathological changes (Fig. 2A and 2B) were consistent with this diagnosis. This myopathy was originally described as a "central core" myopathy (Targett et al 1994) and later as an "inherited myopathy" in Great Dane Dogs (Lujan Feliu-Pascual et al 2006). It is important not to confuse this myopahy with Central Core Disease described in humans (Fardeau and Tome 1994). Histochemical stainings of muscle biopsies from human patients show important differences from that of the Great Dane dogs. Core-like structures stain intensely with oxidative enzymes in the dogs but are unstained in muscles from human patients. EM studies by Targett et al described accumulations of normal appearing mitochondria and glycogen within the cores, which are also absent in human patients.
References
Bohm J, Vasli N, Maurer M, Cowling BS, Shelton GD et al. Altered splicing of the BIN1 muscle specific exon in humans and dogs with highly progressive centronuclear myopathy. PLoS Genet 9:e1003430. doi: 10.137/journal.pgen1003430.
Fardeau M, Tome’ FMS. Congenital Myopathies. In : Myology (Engel AG, Franzini-Armstron C eds). McGraw-Hill , New York 1994, pp 1487-1532.
Lujan Feliu-Pascual A, Shelton GD, Targett MP, Long SN, Comerford EJ et al. Inherited myopathy of Great Danes. J Small Anim Pract 47:249-254, 2006.
Targett MP, Franklin RJM, Olby NJ , Dyce J, Anderson JR, Houlton JEF. Central core myopathy in a great dane. J Small Anim Pract 35:100-103, 1994.