Neonatal Cerebellar Ataxia in Coton de Tulear Dogs

Abstract

A neonatal ataxia syndrome was observed in Coton de Tulear dogs. Seven affected pups (32%; 7/22) of both genders came from 5 different litters with phenotypically normal parents. Neurologic examination revealed normal mental status, head titubation, intention tremors, and severe gait, stance, and ocular ataxia beginning at 2 weeks of age. One of the pups was able to walk with assistance, but most of the affected pups were unable to stand and used propulsive movements (''swimming'') for goal-oriented activities. They frequently would fall to lateral recumbency with subsequent decerebellate posturing and paddling. Ocular motor abnormalities included fine vertical tremors at rest and saccadic dysmetria. The condition was nonprogressive at least until 4 months of age. No specific abnormalities were identified in routine laboratory screening of blood and urine. Cerebrospinal fluid (CSF) analysis was normal in 1 dog, and a mild increase in protein concentration was observed in a second dog. CSF organic and amino acid concentrations were within normal limits. Magnetic resonance imaging and computed tomography of the brain, electromyography, motor nerve conduction studies, and brain stem auditory-evoked potentials were within normal limits. Postmortem examinations were performed on 5 affected dogs between 2 and 4 months of age. Routine light microscopic and immunocytochemical examination of brain, spinal cord, peripheral nerve, and muscle did not disclose any gross or histologic lesions. Compared with the cerebellum from an age-matched normal dog, the cerebellum from an affected dog showed synaptic abnormalities, including loss of presynaptic terminals and organelles associated with parallel fiber varicosities within the molecular layer and increased numbers of lamellar bodies in Purkinje cells. An autosomal recessive trait affecting development of the cerebellum is suspected.

A Truncated Retrotransposon Disrupts the GRM1 Coding Sequence in Coton de Tulear Dogs with Bandera's Neonatal Ataxia

“…21,22 Similar pathology may explain the subtle ultrastructural abnormalities reported in the cerebellar molecular layer from a 4-month-old puppy with BNAt. 1 Electrophysiologic experiments with brain sections from Grm1 knockout mice have demonstrated deficiencies in long-term depression in the cerebellum and deficiencies in long-term potentiation in the hippocampus. 6,7,23 Longterm depression and long-term potentiation are widely believed to be the bases for learning and memory.…”

“…Pedigree analysis suggested an autosomal recessive mode of inheritance for BNAt. 1 An apparently distinct, later-onset cerebellar ataxia of Coton de Tulear puppies with granule cell degeneration also has been described. We here report that a genome-wide association study (GWAS) found strong associations between the BNAt phenotype and single-nucleotide polymorphisms (SNPs) on canine chromosome 1 (CFA1).…”

“…Repeated neurologic examinations failed to show either progression or remission of clinical signs. 1 Analysis of affected puppies by CBC, serum biochemistry, and urinalysis produced normal results. 1 Brain images produced by computed tomography and magnetic resonance imaging also were normal, as were electromyography results, motor nerve conduction parameters, and auditory brainstem-evoked responses.…”

“…1 Analysis of affected puppies by CBC, serum biochemistry, and urinalysis produced normal results. 1 Brain images produced by computed tomography and magnetic resonance imaging also were normal, as were electromyography results, motor nerve conduction parameters, and auditory brainstem-evoked responses. Cerebrospinal fluid samples from 2 affected pups were analyzed and 1 had slightly increased protein concentrations.…”

“…1 The ataxia of affected Coton de Tulear puppies became apparent as soon as their littermates developed coordinated movements. The affected puppies exhibited titubation of the head and intention tremors.…”