OMIA 000878-9615 : Arrhythmogenic right ventricular cardiomyopathy in Canis lupus familiaris

In other species: chimpanzee , domestic cat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 107970

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: no

Species-specific name: Arrhythmogenic right ventricular cardiomyopathy

Species-specific symbol: ARVC

Species-specific description: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by monomorphic ventricular arrhythmias, syncope, and sudden cardiac death in Boxer dogs. Because the presenting sign can be sudden death, many dogs die without a diagnosis. Pathologic changes in the heart include dilation of the right ventricle and replacement of myocardial tissue with fibrous and fatty infiltrates. The mode of inheritance appears to be autosomal dominant with incomplete penetrance. A causative mutation has been identified in STRN.

Edited by Meg Sleeper, VMD and Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

Inheritance: Meurs et al. (2010) and Cattanach et al. (2015) reported autosomal dominance with mostly low penetrance, which means, in effect, that this disorder is multifactorial.

Mapping: By conducting a GWAS on 46 affected and 43 control Boxers, each genotyped with the Affymetrix Canine Genome 2.0 Array “Platinum Panel” (comprising 49,663 SNPs), Meurs et al. (2010) highlighted a region on chromosome CFA17. By fine-mapping and sequencing within the CFA17 candidate region, these authors identified an 8bp deletion in the 3’ UTR of STRN in strong (but not complete) association with ARVC in the Boxer.

Meurs et al. (2013) reported that the above STRN deletion is strongly associated with a closely related disorder, namely dilated cardiomyopathy (DCM) in Boxers.

A pedigree analysis by Cattanach et al. (2015) confirmed the result of Meurs et al. (2010), namely that the STRN deletion is strongly but not completely associated with the disease. In other words, the STRN deletion is a marker for a QTL for liability to ARVC in Boxers.

Clinical features: Signs include monomorphic ventricular arrhythmias, syncope, and sudden cardiac death. Magnetic resonance imaging (MRI) demonstrates right ventricular dilation and aneurysms, reduced right ventricular ejection fraction, and bright anterolateral and/or infundibular ventricular signals corresponding with an infiltration of fatty tissue (Meurs et al, 2010). Dogs homozygous for the STRN mutation had, on average, more ventricular premature contractions (VPCs) than heterozygous dogs (Meurs et al., 2010). Although STRN is also highly expressed in neural tissue, affected dogs have no apparent neurologic deficits (Meurs et al., 2010).

Pathology: Frequent left bundle branch block morphology ventricular premature complexes cause the clinical signs (Meurs et al., 2010). The disorder causes a gradual and progressive right (and sometimes left) ventricular loss of muscle which is replaced with fat and fibrous tissue. Lesions include a thin right ventricular free wall, aneurysms, and myocyte loss starting at the epicardium (Basso et al., 2004).

Prevalence: Prevalence is thought to be very high in the USA, and it may also be prevalent in the Netherlands. True prevalence is unknown because many dogs likely die without a diagnosis.

Control: Breeding of affected dogs is not recommended.

Genetic testing: In assessing the results of Cattanach et al. (2015), Sargan (2015) discussed the pitfalls of basing a DNA test on "a mutation that has been thought to be the cause of a monogenic disease and has been treated as such in two commercial genetic testing laboratories [but which] is in fact not causal, but simply linked to the disease". DNA testing laboratories should heed this advice.

Breed: Boxer.

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Arrhythmogenic right ventricular cardiomyopathy STRN deletion, small (<=20) CanFam2.0 17 g.32373916_32373923del8 2010 20596727

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2015 Cattanach, B.M., Dukes-McEwan, J., Wotton, P.R., Stephenson, H.M., Hamilton, R.M. :
A pedigree-based genetic appraisal of Boxer ARVC and the role of the Striatin mutation. Vet Rec 176:492, 2015. Pubmed reference: 25661582. DOI: 10.1136/vr.102821.
Sargan, D. :
Inherited disease in boxer dogs: a cautionary tale for molecular geneticists. Vet Rec 176:490-1, 2015. Pubmed reference: 25953873. DOI: 10.1136/vr.h2371.
2013 Meurs, K.M., Stern, J.A., Sisson, D.D., Kittleson, M.D., Cunningham, S.M., Ames, M.K., Atkins, C.E., DeFrancesco, T., Hodge, T.E., Keene, B.W., Reina Doreste, Y., Leuthy, M., Motsinger-Reif, A.A., Tou, S.P. :
Association of dilated cardiomyopathy with the striatin mutation genotype in boxer dogs. J Vet Intern Med 27:1437-40, 2013. Pubmed reference: 24033487. DOI: 10.1111/jvim.12163.
2010 Hariu, C.D., Carpenter, D.H. :
Arrhythmogenic right ventricular cardiomyopathy in boxers. Compend Contin Educ Vet 32:E3, 2010. Pubmed reference: 21882165.
Meurs, KM., Mauceli, E., Lahmers, S., Acland, GM., White, SN., Lindblad-Toh, K. :
Genome-wide association identifies a deletion in the 3' untranslated region of Striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy. Hum Genet 128:315-24, 2010. Pubmed reference: 20596727. DOI: 10.1007/s00439-010-0855-y.
Winter, RL., Hariu, CD., Saunders, AB. :
ECG of the month. Arrhythmogenic right ventricular cardiomyopathy in a Boxer. J Am Vet Med Assoc 236:961-3, 2010. Pubmed reference: 20433394. DOI: 10.2460/javma.236.9.961.
2009 Scansen, BA., Meurs, KM., Spier, AW., Koplitz, S., Baumwart, RD. :
Temporal variability of ventricular arrhythmias in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy. J Vet Intern Med 23:1020-4, 2009. Pubmed reference: 19678888. DOI: 10.1111/j.1939-1676.2009.0366.x.
2008 Baumwart, RD., Meurs, KM., Raman, SV. :
Magnetic resonance imaging of right ventricular morphology and function in boxer dogs with arrhythmogenic right ventricular cardiomyopathy. J Vet Intern Med 23:271-4, 2008. Pubmed reference: 19192154. DOI: 10.1111/j.1939-1676.2008.0266.x.
Oyama, MA., Reiken, S., Lehnart, SE., Chittur, SV., Meurs, KM., Stern, J., Marks, AR. :
Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency. J Vet Cardiol 10:1-10, 2008. Pubmed reference: 18515204. DOI: 10.1016/j.jvc.2008.04.003.
2007 Meurs, KM., Ederer, MM., Stern, JA. :
Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular cardiomyopathy. Am J Vet Res 68:1338-41, 2007. Pubmed reference: 18052738. DOI: 10.2460/ajvr.68.12.1338.
2006 Nelson, OL., Lahmers, S., Schneider, T., Thompson, P. :
The use of an implantable cardioverter defibrillator in a Boxer Dog to control clinical signs of arrhythmogenic right ventricular cardiomyopathy. J Vet Intern Med 20:1232-7, 2006. Pubmed reference: 17063723.
2004 Basso, C., Fox, PR., Meurs, KM., Towbin, JA., Spier, AW., Calabrese, F., Maron, BJ., Thiene, G. :
Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model of human disease. Circulation 109:1180-5, 2004. Pubmed reference: 14993138. DOI: 10.1161/01.CIR.0000118494.07530.65.
1999 Meurs, K.M., Spier, A.W., Miller, M.W., Lehmkuhl, L., Towbin, J.A. :
Familial ventricular arrhythmias in boxers Journal of Veterinary Internal Medicine 13:437-439, 1999. Pubmed reference: 10499727.
1995 Bright, J.M., Mcentee, M. :
Isolated right ventricular cardiomyopathy in a dog Journal of the American Veterinary Medical Association 207:64-66, 1995. Pubmed reference: 7601695.
1994 Simpson, K.W., Bonagura, J.D., Eaton, K.A. :
Right Ventricular Cardiomyopathy in a Dog Journal of Veterinary Internal Medicine 8:306-309, 1994. Pubmed reference: 7983631.
1991 Harpster, NK. :
Boxer cardiomyopathy. A review of the long-term benefits of antiarrhythmic therapy. Vet Clin North Am Small Anim Pract 21:989-1004, 1991. Pubmed reference: 1949503.

Edit History


  • Created by Frank Nicholas on 22 Aug 2010
  • Changed by Martha MaloneyHuss on 06 Sep 2011
  • Changed by Frank Nicholas on 29 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Frank Nicholas on 25 Sep 2013
  • Changed by Frank Nicholas on 17 May 2015
  • Changed by Frank Nicholas on 22 Oct 2015