HEART DISEASE IN THE GREAT DANE: Cardiomyopathy and Congenital Disease.

A variety of heart diseases are reported in the Great Dane. Among them are dilated cardiomyopathy (DCM)--a progressive, life-threatening disease unfortunately not uncommon in the Dane, and then a variety of congenital heart defects, to include: mitral valve defects, typically stenosis--which is another serious and potentially fatal disorder, triscuspid valve dysplasia--another potentially fatal valvular defect, subaortic stenosis (SAS)--another potentially fatal defect of structure, patent ductus arteriosus (PDA)--a common congenital defect in dogs that is usually correctable, and persistent right aortic arch (PRAA or VRA)--another congenital, correctable defect. 

Congenital heart defects, as Patterson (JSAP; 1989: Hereditary congenital heart defects in dogs) noted "comprise probably the most common class of malformations found in dogs, occurring with a frequency approaching 1% in animals presented to veterinary clinics. The frequency is significantly higher among purebred dogs than in dogs of mixed breeding and specific anatomical malformations occur with highest frequency in certain breeds. Genetic studies of patent ductus arteriosus, pulmonic stenosis, subaortic stenosis, ventricular septal defect, tetralogy of Fallot and persistent aortic arch have confirmed that these are specific heritable defects, the genes for which are concentrated in a number of different breeds. Each of these defects is inherited in a complex manner consistent with a polygenic basis." 

The last two congenital defects listed above (PRAA & PDA) are reported sporadically in the dog, with PDA being the most common canine congenital heart defect. Both are the result of fetal structures which persist after birth, resulting in problems for the growing pup, so both are thought to be "timing gene" defects. Both are correctable by surgery as noted. PDA shows a female predominance in some breeds; in PRAA the persistent fetal structure essentially "strangles" the esophagus, causing constriction of the esophagus with regurgitation, aspiration pneumonia and dysphagia (poor eating ability), so can be confused with non-heart diseases such as megaesophagus. Congenital valve defects result in reduced heart efficiency, and if severe are typically fatal in the first year of life with the puppy likely demonstrating lethargy, poor appetite, even syncope (fainting) and sudden death. SAS is a narrowing of a major area of blood flow, and although mild cases may go undetected, a diagnosis of SAS often requires careful treatment & death may occur regardless. All these congenital heart conditions can be the cause of "unthrifty" puppies and/or sudden inexplicable death. All can have a "graded expression," meaning the defects of structure can be mild, moderate, or severe, resulting in more or less obvious symptoms of disease. All are considered to be inherited diseases. Generally all are associated with heart murmurs (of various sorts), and an expert auscultation (exam with a stethoscope by a cardiologist or internist) can often offer a preliminary diagnosis of congenital heart disease. The OFA Cardiac clearance exam and registry is a suitable screening method for congenital heart disease. 

HCM (hypertrophic cardiomyopathy) is exceeding rare in dogs & typically not a primary disease (i.e. it results from other disease). DCM and ACM (arrhythmogenic cardiomyopathy) are primary heart diseases that are heritable in nature and involve the heart muscle. For a precise discussion of DCM and it's relationship to ACM, another form of "cardio" that does occur in dogs and may occur in the Great Dane, see: http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00034.htm

Dilated cardiomyopathy (DCM) is in a different category. This is typically an adult-onset disease and is progressive in nature, so signs of disease are not obvious for months and even years. In an earlier paper in the JAVMA (Meurs, et al, Mar2001) concerning DCM, Dr. Meurs outlined the clinical features of DCM and offered some comments on potential inheritance of the disease. In our breed the preliminary data has suggested that DCM is typically inherited in an X-linked recessive fashion. This means that usually unaffected, but carrier, dams pass on the defective X chromosome to statistically 50% of their offspring. When this is a bitch pup, she will also be an unaffected carrier like her dam. When this is a dog pup, he will suffer from DCM as an adult dog. This is because male dogs only have one X chromosome; the other sex chromosome being the Y chromosome inherited from their sire (which made them male). Affected males will produce 100% carrier daughters, as they give this defective X chromosome to all their female offspring. Then these carrier daughters produce again affected sons. However, when a disease is X-linked, the sons of an affected sire are NOT at risk, as they do not inherit an X chromosome from their sires. Females can also be affected (i.e. develop DCM), although this is more rare. With an X-linked recessive disease females have TWO defective X-chromosomes. If used in a breeding program, such a bitch would produce 100% affected sons and 100% carrier daughters bred to a clear dog. If an affected dog was used on a carrier bitch, then 50% of the male pups would be affected, 25% of the female pups would also have DCM, with the other 25% would be DCM carriers. So to summarize, X-linked recessive disorders are: seen with much more frequency in males than in females, are a trait never transferred directly from father to son, and have the appearance of skipping a generation because it's transmitted through carrier females typically. DCM is obviously a serious enough disease that it's wise for breeders to learn about the method of inheritance and they should track its progression through various generations, thereby attempting to predict carrier status and thus reducing the number of potentially affected dogs. To read a non-technical "walk thru" of how recessive X-linkage DCM works in the Great Dane, click on the following links:

http://ginnie.com/DaDane301.shtml
http://ginnie.com/DaDane300.shtml
http://ginnie.com/DaDane299.shtml
http://ginnie.com/DaDane298.shtml

Currently there are two seperate research projects on dilated cardiomyopathy (DCM) that are being supported by the Great Dane Club of America. The first is a recent addition (2006) that involves using a new technique to scan the genome looking for alterations in gene function between a healthy heart and a heart suffering from DCM. This work is being conducted by Dr. Mark Oyama at the University of Pennsylvania, and he is currently in need of healthy older Danes as well as Danes diagnosed with DCM. Dogs would have to travel to the facility at UPenn to participate. Email Dr. Oyama for more information: maoyama@vet.upenn.edu

The other current research project into DCM in the Great Dane is being conducted at Texas A&M University (TAMU) and is a "two-pronged" approach with a clinical and genetic aspect. DNA buccal (cheek) swabs and/or blood only are needed from the dog (along with medical records and pedigree information) to participate and more Danes are actively sought at this time (2006). For more information, please contact the following:

Stephanie Herbst, Canine Genetics Lab:
sherbst@cvm.tamu.edu
Lab phone: 979-845-5634
Cell phone: 979-575-6895
FAX: 979-845-9231

The Great Dane is the second most common breed of dog afflicted with DCM. So it's important that our dogs, especially our breeding stock, be examined for signs of DCM. Although it might be the case that a simple auscultation by an expert would be able to offer a preliminary diagnosis of DCM, it's generally thought that an ultrasound is required for a cardiomyopathy breeding clearance. This exam ideally should include a full physical and a history, and be done by a competent cardiologist. This generally takes up to an hour; the dog is examined, then the ultrasound performed & taped (audio & visual) and the results interperlated. Radiographs (xrays) or other further tests may be deemed necessary, particularly if the initial cardiac testing is for suspected illness &/or any anomalies come up on the ultrasound/physical exams. A thorough exam screens for all gross heart diseases & anomalies. Regular (annual?) screening exams on adult dogs are recommended for breeding stock in breeds like ours where DCM is found. So a one-time OFA Cardiac clearance is not an effective screening tool for DCM.

Cardiovascular diseases generally have their origin in the reduced effectiveness of the heart to function as a blood pump. This requires of course muscle. In DCM, the smooth muscle of the heart, the myocardium, fails to maintain it's contractility, and essentially gets "stretched out" so that the heart enlarges. DCM literally means enlarged heart muscle disease. The details of why and how exactly this occurs are currently unknown. However Dr. Meur's research on dystrophin points the way to one potential explanation. Dystrophin is a membrane-associated protein that helps regulate the integrity of the muscle cells; it fails to function properly in such diseases as muscular dystrophy, and when dystrophin is absent, the muscle cells die. Duchenne muscular dystrophy (DMD) is an X-linked disorder in humans. In DMD typically there are frame-shift & in-frame mutations (i.e. via deletion) in the DNA. The result is a defective protein as the DNA made is a "nonsense" strand or has portions that don't code for a useful dystrophin protein. Dr. Meurs will be speaking at our 2002 National Specialty on DCM and her research on our breed and will provide us with an update of the evaluation of DCM in the Great Dane. All are encouraged to attend. Also Purina has recently initiated a pamphlet on health and welfare issues in our breed. The first issue of this GREAT DANE REVIEW (Jan2002) was devoted to the topic of DCM. It gives a nice overview of the disease, it's diagnosis and treatment. With the cooperation of Purina, I have arranged to have this pamphlet made available as a free handout in the educational room at the 2002 GDCA National Specialty. Dr. Meurs email is: meurs.1@osu.edu. Her phone number at OSU (page her or leave a msg) is: (614) 292-3551 at Ohio State. 

Permission to reprint as submitted for educational purposes is given. 
Submitted by JP Yousha, Chair, H&W Committee, GDCA 2004.

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