Long QT Syndrome (KCNQ1-linked)

Gene: KCNQ1

Transmission: Autosomal dominant

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutation: Substitution, KCNQ1 gene; c.770 C>A, p.(257K), chr.18

Medical system: Cardiac

Breeds: English Springer Spaniel, Rottweiler

Age of onset of symptoms: Variable, from young to adult animal.

A 5-year-old English Sringer Spaniel female gave birth to a litter of seven puppies, then died suddenly four months later following activity.  Two of her puppies also died suddenly after activity, at five months and at seven months of age.  Four surviving littermates were examined, and an electrocardiogram (ECG) revealed long QT waves in three of them.  Long QT waves can be responsible for cardiac arrhythmias and sudden death in humans and are often the result of mutations in the KCNQ1 gene.  The KCNQ1 gene codes for a potassium channel protein that is involved in repolarizing cardiac cells.  Molecular analysis of the four littermates revealed a heterologous mutation within the KCNQ1 gene in the three littermates exhibiting long QT ECGs.  The remaining littermate plus eleven related dogs did not have the mutation.  It is suggested that a novel mutation occurring in the dame was passed on to five out of seven of her puppies, resulting in the long QT syndrome and the sudden deaths observed.  The fact that this mutation was not observed in a commercial screening of 751 English Springer Spaniels suggests that this mutation was incidental and is not a concern to the breed.  The same survey detected a very low incidence of carriers for the mutation (M/N = 0.02%) in a population of 4718 Rottweiler dogs tested, the significance of which is not known.

References:

OMIA link: [2332-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Rivas VN, Stern JA, Ueda Y. (2023) The role of personalized medicine in companion animal cardiology. Vet Clin North Am Small Anim Pract 53:1255-1276.  [pm/37423841]

Ware WA, Reina-Doreste Y, Stern JA, Meurs KM. (2015) Sudden death associated with QT interval prolongation and KCNQ1 gene mutation in a family of English Springer Spaniels. J Vet Intern Med 29:561-8.  [pubmed/25779927]

With contributions by: Lea Fathallah and Marie-Elise Sotrea, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).