Dilated Cardiomyopathy, DCM

 

Gene: RBM20

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion, RBM20 gene; 22 bp deletion with frame shift, exon11

Medical system: Cardiac

Breeds: American Staffordshire Terrier/Amstaff, Australian Shepherd, Border Collie, German Shepherd, Great Pyrenees, Labrador Retriever, Saint-Bernard, Schnauzer - Giant, Schnauzer - Miniature, Schnauzer - Standard, Siberian Husky

Age of onset of symptoms: Variable, from 3 months to 3 years, with a mean age at diagnosis of 1.6 years

Dilated cardiomyopathy is a complex disease, with both genetic and environmental contributions.  A mutation in the RBM20 gene is the cause of a hereditary dilated cardiomyopathy seen in Schnauzers. This mutation disrupts the intracellular calcium utilization of cardiac muscles, and when present in two copies causes weakness of the cardiac muscle leading to dilation of the ventricles and reduced force of contraction. This results in reduced cardiac output as well as arrhythmias.  Clinical signs of dilated cardiomyopathy include difficulty breathing (dyspnea), coughing, exercise intolerance, weight loss, fluid accumulation in the abdomen (ascites), brief loss of consciousness (syncope) and loss of appetite. Affected dogs have an 80% shorter life expectancy, with increased risk of sudden death from heart failure or arrhythmia.  According to a study by Leach et al. (2022), 19.5% of medium-sized Schnauzers were carriers of a mutated allele of the RBM20 gene while 1.5% were double mutant and thus at risk of developing dilated cardiomyopathy.  For giant schnauzers, the prevalence of carrier animals was 8.7% while 1.1% of animals tested were double mutated and thus at risk of the disease.  According to a study by Donner et al. (2023), the mutated allele of the RBM20 gene is found in several additional breeds of dog even if the disease has not necessarily been documented.

Mutations in additional genes that can be risk factors or be responsible for DCM in the dog:

PLN gene, OMIA link: [2195-9615]

PDK4 gene, OMIA link: [0162-9615]

TTN gene, OMIA link: [0162-9615]

RBM20 gene, OMIA link: [2365-9615]

LMNA gene, OMIA link: [2796-9615]

ABCC9 gene, OMIA link: [2710-9615]

 

References:

OMIA link: [2365-9615]

Aherne M. (2023) Cardiac disease and screening in breeding dogs. Vet Clin North Am Small Anim Pract 53(5):985-1012.  [pubmed/37353418]

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]

Gaar-Humphreys KR, Spanjersberg TCF, Santarelli G, et al. (2022) Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model. Animals (Basel) 12(13):1679. [pubmed/35804579]

Leach SB, Briggs M, Hansen L, Johnson GS. (2022) Prevalence, geographic distribution, and impact on lifespan of a dilated cardiomyopathy-associated RNA-binding motif protein 20 variant in genotyped dogs. J Vet Cardiol 40:119-125. [34144877]

Leach SB, Johnson GS, Gilliam D, et al. (2014) Dilated cardiomyopathy in standard schnauzers with a homozygous 22 bp deletion in RBM20. Proceedings of the 32nd ACVIM Forum, 2014 June 4–7; Nashville, TN, USA. :1353. [https://onlinelibrary.wiley.com/doi/10.1111/jvim.12375]

 

Contributed by: Lara-Michèle Bellemare et Gabrielle Després, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).