CNS hypomyelination in Rat Terrier dogs with congenital goiter and a mutation in the thyroid peroxidase gene.

Arrested physical development and neurologic abnormalities were identified in 3 of 5 Rat Terrier puppies at 9 weeks of age. Bilaterally firm symmetrical masses were palpated in the region of the thyroid glands. Low serum total (T4) and free thyroxine (FT4, by equilibrium dialysis) and markedly elevated thyroid stimulating hormone (TSH) concentrations supported the diagnosis of hypothyroidism. At necropsy, the thyroid gland was grossly enlarged and histologically exhibited severe, diffuse hyperplasia of the follicular epithelium. Gross examination of the central nervous system revealed a myelin deficiency, most evident in the corpus callosum. Regional distribution of hypomyelination was confirmed histologically, affecting the corpus callosum and, to a lesser degree, the corona radiata, the longitudinal fibers of the pons, the pyramids, and the lateral funiculi of the spinal cord. Myelin reduction was paralleled by axon reduction, suggesting that hypomyelination was a consequence of reduced axonal formation. A homozygous nonsense mutation in the thyroid peroxidase gene was identified in the affected puppies. The dam and a clinically normal litter mate were heterozygous for this mutation, confirming simple autosomal recessive inheritance of the disease trait. The same mutation, causing congenital hypothyroidism with a goiter was previously described in the Toy Fox Terrier breed. Given the ongoing practice of introducing the Toy Fox Terrier genetic background into some Rat Terrier breeding programs to obtain a smaller stature and the apparent relative incidence of the disorder in the 2 breeds, it is likely that this mutation crossed into the Rat Terrier breed from Toy Fox Terriers fairly recently.

Oligodendroglial dysplasia in two bullmastiff dogs.

Leukodystrophies are inherited neurological disorders involving central nervous system white matter. They are uncommon in animals but a few, breed-specific entities have been described. In 2002, two young-adult, purebred Bullmastiff dogs from central New York State presented to their referring veterinarians displaying moderate to severe ataxia of all limbs, spastic tetraparesis that was worse in the pelvic limbs, and a diffuse, action-related, whole-body tremor. Clinical signs were insidious in onset and slowly progressive. Anatomic diagnoses considered were a C1-C5 lesion or, based on the whole-body tremor, a diffuse central nervous system disorder. No gross lesions were apparent in the brain or spinal cord. Histopathologically, numerous, multifocal, sharply demarcated, small, ovoid to angular areas of myelin pallor (plaques) were present throughout the major white matter tracts of the brainstem and spinal cord. These plaques, which often were traversed by axons, did not stain with luxol fast blue for myelin and were associated with minimal astrocytosis. Ultrastructural findings include occasional hypertrophic glia in white matter, rare unmyelinated segments of axons, and focal proliferation of tubule-containing cytoplasmic glial cell processes (oligodendroglial). The described clinical and morphological findings and age of onset are similar to the well-characterized, presumably hereditary, bovine syndrome known as Charolais ataxia or oligodendroglial dysplasia. This article presents the first description of a leukodystrophy in the Bullmastiff breed and the first report of oligodendroglial dysplasia in animals other than Charolais cattle.