Generalized myokymia, or neuromyotonia, or both in dogs with or without spinocerebellar ataxia

J Vet Intern Med. 2023 Nov-Dec;37(6):2310-2314. doi: 10.1111/jvim.16892. Epub 2023 Oct 31.

Abstract

Background: KCNJ10 and CAPN1 variants cause "spinocerebellar" ataxia in dogs, but their association with generalized myokymia and neuromyotonia remains unclear.

Objective: To investigate the association between KCNJ10 and CAPN1 and myokymia or neuromyotonia, with or without concurrent spinocerebellar ataxia.

Animals: Thirty-three client-owned dogs with spinocerebellar ataxia, myokymia neuromytonia, or a combination of these signs.

Methods: Genetic analysis of a cohort of dogs clinically diagnosed with spinocerebellar ataxia, myokymia or neuromyotonia. KCNJ10 c.627C>G and CAPN1 c.344G>A variants and the coding sequence of KCNA1, KCNA2, KCNA6, KCNJ10 and HINT1 were sequenced using DNA extracted from blood samples.

Results: Twenty-four Jack Russell terriers, 1 Jack Russell terrier cross, 1 Dachshund and 1 mixed breed with spinocerebellar ataxia were biallelic (homozygous) for the KCNJ10 c.627C>G variant. Twenty-one of those dogs had myokymia, neuromyotonia, or both. One Parson Russell terrier with spinocerebellar ataxia alone was biallelic for the CAPN1 c.344G>A variant. Neither variant was found in 1 Jack Russell terrier with ataxia alone, nor in 3 Jack Russell terriers and 1 Yorkshire terrier with myokymia and neuromyotonia alone. No other causal variants were found in the coding sequence of the investigated candidate genes in these latter 5 dogs.

Conclusion: The KCNJ10 c.627C>G variant, or rarely the CAPN1 c.344G>A variant, was confirmed to be the causal variant of spinocerebellar ataxia. We also report the presence of the KCNJ10 c.627C>G variant in the Dachshund breed. In dogs with myokymia and neuromyotonia alone the reported gene variants were not found. Other genetic or immune-mediated causes should be investigated to explain the clinical signs of these cases.

Keywords: EAST syndrome; canine; hereditary ataxia; peripheral nerve hyperexcitability.

MeSH terms

  • Animals
  • Ataxia / veterinary
  • Breeding
  • Dog Diseases* / genetics
  • Dogs
  • Humans
  • Isaacs Syndrome* / genetics
  • Isaacs Syndrome* / veterinary
  • Kv1.6 Potassium Channel
  • Myokymia* / genetics
  • Myokymia* / veterinary
  • Nerve Tissue Proteins
  • Spinocerebellar Ataxias* / veterinary

Substances

  • HINT1 protein, human
  • Nerve Tissue Proteins
  • KCNA6 protein, human
  • Kv1.6 Potassium Channel