Megaesophagus Research Aims To Shed Light On Disease In Great Danes

A search for a Great Dane puppy for her daughter led Sabrina Wowdzia of Red Deer, Alberta, Canada, to a 4-month-old mantle female, the last in a litter of nine to go to a home. Recently diagnosed with megaesophagus, the puppy would need special care and attention to survive. Wowdzia proved to be the right person for the job. When Wowdzia first met “Magic,” she recalls the puppy weighed 14 pounds compared to a normal weight of about 60 pounds at 4 months of age. The veterinarian did not expect Magic to live to be 2 years old even if she received proper care and nutrition. Undaunted, Wowdzia was determined to help the puppy. Megaesophagus is caused when the esophagus, the long tube connecting the pharynx to the stomach, fails to move food into the stomach.

When normal dogs eat, their food is pushed into the stomach by a process known as peristalsis. As the muscular walls of their esophagus progressively contract from the upper esophagus, food is worked downward to the stomach. The swallowing sequence is completed when the sphincter muscle relaxes to allow food to enter the stomach. Great Danes are among more than 30 breeds genetically predisposed to the potentially fatal neuromuscular disease. Although there are no statistics available on the prevalence of the condition in the breed, it is considered one of the top health concerns. Neil O’Sullivan, PhD, chair of the Health and Research Committee of the Great Dane Club of America, estimates that one puppy in 20 percent of litters is affected. “In some bloodlines, the disease occurs in every litter,” he says. “It is a heartbreaking disease because affected puppies often must be euthanized. Breeders are highly motivated to find a solution.” Research is soon to begin at Clemson University to identify a genetic marker for megaesophagus in Great Danes. The study, which is supported by the Great Dane Club of America, will tap into work already completed in German Shepherd Dogs that identified a region likely to contain a gene(s) involved in the disorder. Leigh Anne Clark, PhD, assistant professor in the Department of Genetics and Biochemistry, says, “We found in German Shepherd Dogs that mega­esophagus is not a simple autosomal disorder. There may be multiple genes and environmental factors at play because not all dogs with genetic markers for this disease show clinical signs.” 

The goal is to develop a genetic test that will identify affected dogs and those that carry the gene(s) for megaesophagus. “This will enable breeders to plan matings that will not produce affected dogs,” Clark says. Clark will study DNA from blood samples of healthy and affected Great Danes using single nucleotide polymorphism (SNP) chip analysis. A genome-wide analysis will help her identify candidate genes that could possibly contain the mutation. Comparing the SNP profiles of healthy and affected dogs will help her identify the location of disease genes. “It appears the disease is inherited differently among different breeds, thus it may be caused by mutations in different genes or by different mutations in the same gene,” adds Clark. “Once a marker is known, learning the inheritance pattern should come easily.” Megaesophagus is a congenital condition usually diagnosed during weaning, when puppies are 6 to 8 weeks old, as solid food is introduced. Coughing and regurgitation of food and water are common. Since ingested food moves into the stomach only as a result of gravity, it often stays in the esophagus from several minutes to hours. This causes the tube to dilate or stretch, which explains why the condition is named “megaesophagus.” Megaesophagus also occurs secondary to other conditions such as myasthenia gravis, a neuromuscular disease that causes muscle weakness and fatigue, and Addison’s disease, a disorder caused by insufficient production of adrenal hormones.

It can be confused with geriatric onset laryngeal paralysis polyneuropathy, a progressive nerve disease that causes regurgitation. A definitive diagnosis usually is made from radiographs taken after a dog has undergone a barium swallow test containing a contrast agent to help make the abnormality easy to recognize. Radio­graphs of the esophagus help to distinguish the condition from diseases that mimic megaesophagus and require different therapies. Mildly affected dogs may not show signs other than occasional regurgitation or coughing. Moderately to severely affected dogs may suffer from malnutrition, excessive salivation and physical wasting, with frequent coughing or wheezing. Regurgitation is the most common clinical sign, though owners sometimes mistake regurgitation for vomiting. Regurgitation is a passive expulsion of undigested food, whereas vomiting is the forceful ejection of stomach contents. The primary life-threatening effect of megaesophagus is aspiration pneumonia, the leakage of food, water or saliva into the lungs. Treatment consists of trying to help food reach the dog’s stomach. Owners usually first try small, frequent feedings from an elevated position to take advantage of gravity. Moistening kibble or pureeing food to help it pass through the esophagus to the stomach can be helpful. In some cases, a gastrostomy tube can be inserted through the skin and wall of the abdomen to get nutrition into the stomach. Many dogs diagnosed with megaesophagus die or are euthanized within weeks or months. Even with proper care, it is challenging to help affected dogs receive proper nutrition and gain weight. In the beginning, Wowdzia carefully prepared meals for Magic by soaking one-half cup kibble in warm water until it was soft, and then she blended the mixture.

She gently held Magic in an upright position as she fed the dog, patting her sides for 30 minutes to ensure the food moved to the stomach. No matter how hard she worked, the Great Dane frequently regurgitated. Next, Wowdzia tried feeding Magic with the dog’s front feet propped on the edge of the bathtub. She worked with the dog for an hour, holding the dog’s legs while patting her sides and massaging her neck in a downward motion. She repeated this eight times a day. After much trial and error, Magic, now 5 years old, weighs 75 pounds and can eat from a bowl on the floor. The dog even sits tall on her own to help settle her food. “Breeders and owners should keep trying new things until they find a feeding routine that works for their megasesophagus-affected dogs,” Wowdzia says. “This condition is challenging, but dogs can live long, happy lives if their megaesophagus is properly managed.” Purina appreciates the support of the Great Dane Club of American and particularly Neil O’Sullivan, PhD, chair of the GDCA Health and Research Committee, in helping to identify topics for the Purina Pro Club Great Dane Update newsletter. Great Dane Owners Can Help Advance Megaesophagus Research Breeders and owners of Great Danes, particularly puppies, affected by mega­esophagus are encouraged to submit blood samples for genetic research underway at Clemson University. The Great Dane Club of America is helping to fund the study. For information about participating in the research, please contact Leigh Anne Clark, PhD, assistant professor in the Department of Genetics and Biochemistry, at lclark4@clemson.edu. GDCA Charitable Trust Donations Can Be Earmarked for Megaesophagus Research The Great Dane Club of America Charitable Trust allows Great Dane enthusiasts who make tax-deductible charitable donations to designate them for megaesophagus research. The funding will be used to help collect DNA samples for the genetics study at Clemson University.