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An Urban Experience
Pinschers and Boxers are also screened with 24-hour (Holter) recordings because a single ECG trace only corresponds to a small fraction of the dog’s rhythm
over a 24 hour period, and identification of intermittent abnormalities may be entirely fortuitous. Evidence of ventricular arrhythmia may precede echocardiographic evidence of DCM in the Doberman Pinscher by some months or even years. In Doberman Pinschers and Boxer dogs, therefore, Holter monitoring is of proven value
in the identification of dogs destined to develop DCM and guidelines have been produced for these breeds
for acceptable number of ventricular depolarizations over a 24 hour period. The echocardiographic diagnosis of DCM is based on the identification of myocardial (predominantly but not solely) systolic dysfunction with the active exclusion of other acquired or congenital cardiac diseases.
Genetic aspects of DCM
Dilated cardiomyopathy has been described to be inherited as an autosomal dominant trait in most breeds where it has been studied, the exceptions being Great Danes and Portuguese Water dogs (see below). At present date, only two causative mutations have been suggested, one in Dobermann Pinschers, mitochondrial enzyme pyruvate dehydrogenase kinase 4 (PDK4), and one in Boxer dogs, striatin. The mutation in the PDK4 gene was tested in a cohort of European dogs from Germany and the UK, but the association could not be replicated in this population of dogs. This is suggestive of other causative genes in European dogs and/or geographic stratification of the breed. A genome-wide significant association to DCM was recently found in German Doberman Pinschers, classified according to both echocardiographic and 24-hour (Holter) findings) on chromosome 5 (praw = 3.54 x 10-8). The association was replicated in an independent cohort collected in
the UK. There is no currently known DCM candidate gene under the association signal. For the Boxer dogs, an attempt has been made to replicate the association between the Striatin mutation and ARVC in UK Boxer dogs,(19) but failed to do so. The results showed that the Striatin mutation was very common in this population of UK Boxer. However, the proportion of dogs in the phenotypically normal and phenotypically affected dogs was not significantly different. Furthermore, in contrast to the Boxers from USA, the genotype was not correlated to the number of VPCs recorded over 24 hours in the UK population. However, genome wide association analyses have also been performed in Irish Wolfhounds, Newfoundlands and Great Dane dogs, and preliminary results of significant genome wide associations have been presented, but no candidate genes have yet been brought forward in these breeds. In people, mutations
in the genes encoding the thick filament components myosin heavy chain and myosin binding protein C together explain 75% of inherited cases of hypertrophic
cardiomyopathy (HCM) (which is a rare disease in dogs, but not in cats), which is suggestive of that HCM is a disease of the sarcomere. In contrast, DCM in people appears to be far more genetically heterogeneous, with mutations in genes encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. Private mutations account for most DCMs, with few hotspots
or recurring mutations. More than 50 single genes are linked to inherited DCM in people, including many genes that also link to HCM. There are still many human DCM forms, where the causative mutation remains unknown.
Selected References
Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation. 1996;93:841-2.
Egenvall A, Bonnett BN, Haggstrom J. Heart disease as a cause of death in insured Swedish dogs younger than 10 years of age. J Vet Intern Med. 2006;20(4):894-903.
Vollmar AC. The prevalence of cardiomyopathy in the Irish wolfhound: a clinical study of 500 dogs. J Am Anim Hosp Assoc. 2000;36(2):125-32.
Dukes-McEwan J, Borgarelli M, Tidholm A, et al. Proposed guidelines for the diagnosis of canine idiopathic dilated cardiomyopathy. J Vet Cardiol. 2003;5(2):7- 19
Wess G, Schulze A, Butz V, et al. Prevalence of dilated cardiomyopathy in Doberman Pinschers in various age groups. J Vet Intern Med;24(3):533-8.
Motskula PF, Linney C, Palermo V, et al. Prognostic Value of 24-Hour Ambulatory ECG (Holter) Monitoring in Boxer Dogs. J Vet Intern Med;27(4):904-12.
Meurs KM, Lahmers S, Keene BW, et al. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher. Hum Genet.;131(8):1319-25.
Meurs KM, Mauceli E, Lahmers S, et al. 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(3):315-24.
Owczarek-Lipska M, Mausberg TB, Stephenson H, et al. A 16-bp deletion in the canine PDK4 gene is not associated with dilated cardiomyopathy in a European cohort of Doberman Pinschers. Anim Genet. Apr;44(2):239.

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