Polioencephalopathy in Eurasier dogs

Abstract

Background: Polioencephalopathies secondary to inborn errors of metabolism have been described in dogs, but few genetically characterized.

Objectives: Clinically and genetically characterize polioencephalopathy in a family of Eurasier dogs.

Animals: Three Eurasier dogs (littermates) presented with early onset movement disorders (9 weeks in 2, 4-6 months in 1). Progressive gait abnormalities were detected in 2 of the dogs, persistent divergent strabismus in 1, whereas consciousness and behavior remained intact in all dogs. One dog was euthanized at 25 months.

Methods: Video footage was assessed in all dogs, and Dogs 1 and 2 had examinations and investigations performed. Whole genome sequencing of Dog 1 and further genetic analyses in the family were performed. A cohort of 115 Eurasier controls was genotyped for specific variants.

Results: Episodes were characterized by generalized ataxia, as well as a hypermetric thoracic limb gait, dystonia, and irregular flexion and extension movements of the thoracic limbs. Magnetic resonance imaging of the brain in Dogs 1 and 2 identified symmetrical, bilateral T2 and fluid attenuated inversion recovery hyperintense, T1 hypo to isointense, nonenhancing lesions of the caudate nucleus, lateral and medial geniculate nuclei, thalamus, hippocampus, rostral colliculus and mild generalized brain atrophy. Genetic analyses identified a homozygous mitochondrial trans-2-enoyl-CoA reductase (MECR) missense variant in all 3 dogs, and a homozygous autophagy-related gene 4D (ATG4D) missense variant in Dogs 1 and 2.

Conclusions and clinical importance: We describe a presumed hereditary and progressive polioencephalopathy in a family of Eurasier dogs. Further research is needed to establish the role of the MECR gene in dogs and the pathogenic effects of the detected variants.

Keywords: canine; movement disorder; neurodegenerative; polioencephalopathy.

FIGURE 1

Selected MR images of the brain of Dog 1 in T2w (A), FLAIR (B), T1w (C), and T1w post contrast (D) sequences. The caudate nuclei are shown in the first column (arrows); the thalamus in the second column (arrows); the medial geniculate nuclei (arrows) and lateral geniculate nuclei (arrowheads) in the third column; the hippocampi (arrows) and rostral colliculi (arrowheads) in the fourth column. These areas are symmetrically bilaterally T2/FLAIR hyperintense, T1 hypo to isointense, and noncontrast enhanced. The thalamus and hippocampus are more affected in Dog 1 compared to Dog 2.

FIGURE 2

Selected MR images of the brain of Dog 2 in T2w (A), FLAIR (B), T1w (C), and T1w post contrast (D) sequences. The caudate nuclei are shown in the first column (arrows); the thalamus in the second column (arrows); the medial geniculate nuclei (arrows) and lateral geniculate nuclei (arrowheads) in the third column; the hippocampi (arrows) and rostral colliculi (arrowheads) in the fourth column. These areas are symmetrically bilaterally T2/FLAIR hyperintense, T1 hypo to isointense, and noncontrast enhanced. Dog 2 has milder abnormal signal at these locations; in particular the thalamus and hippocampus are less affected compared to Dog 1. The rostral colliculus is more affected in Dog 2 compared to Dog 1.

FIGURE 3

Pedigree of the Eurasier family showing the expected cosegregation of the genotypes at the 2 variants for the more severe phenotype in Dog 1 and 2, and the milder phenotype in Dog 3 assuming autosomal recessive inheritance.