Juvenile Dilated Cardiomyopathy & Xanthinuria Type 2a

Juvenile Dilated Cardiomyopathy

Toy Manchester TerrierJuvenile dilated cardiomyopathy (JDCM) occurs in Toy Manchester Terriers. It results in sudden cardiac death at a young age, with dogs reported to have passed as early as 10 weeks of age and as late as 1 year of age. Affected dogs usually appear healthy with no signs of heart disease present before the sudden passing. The only external abnormality is that affected male puppies may have unilateral or bilateral cryptorchidism (undescended testicles on one or both sides). For a number of the puppies, their sudden passing occurred within a day of general anesthesia/surgery or exercise. Necropsy (post-mortem examination) may show mild enlargement and dilation of the heart. Microscopic changes include degeneration and scarring of heart tissue and varying degrees of inflammation. Death is presumed to be the result of a sudden fatal arrhythmia (abnormal heart rhythm).

Research performed at the University of Minnesota, in collaboration with University of Pennsylvania and the University of Prince Edward Island, has discovered that JDCM in Toy Manchester Terriers is caused by an autosomal recessive mutation in a cardiac potassium channel. To date, we have tested DNA from 14 Toy Manchester Terriers with JDCM, and all had two copies of the mutation. We have also tested nearly 100 adult healthy Manchester Terriers, and none have had two copies of the mutation. Thus, the disease may be fully penetrant, meaning that all dogs with two copies of the mutation develop JDCM.

We currently estimate that ~15-20% of Toy Manchester Terriers are carriers of the mutation. Carriers do not develop the disease but can produce affected puppies if bred to another carrier. However, this does not mean that carriers need to be taken out of the breeding pool, as that could rapidly reduce breed diversity. As long as carriers are only bred to clear dogs, there is no risk of producing affected puppies.

We do not currently know if the mutation exists in Standard Manchester Terriers. We also do not know the mutation frequency in English Toy Terriers. 

Please see the JDCM Result Interpretation document for details on expected outcomes in affected, carrier, and clear dogs as well as breeding guidelines.

 Three Toy Manchester TerriersScientific References

Legge CH, et al. Histological characterization of dilated cardiomyopathy in the juvenile Toy Manchester Terrier. Vet Pathol 2013;50:10431052.

Xanthinuria type 2a

Toy Manchester TerrierHereditary xanthinuria is an autosomal recessive genetic disorder that results in excessive xanthine (a metabolic byproduct) in the urine. This increases the risk for formation of xanthine bladder or kidney stones and can cause significant kidney disease.  Hereditary xanthinuria is a result of mutations in either xanthine dehydrogenase (XDH, type 1 xanthinuria) or molybdenum cofactor sulfurase (MOCOS, type 2 xanthinuria). Xanthinuria can also occur from non-genetic factors such as exposure to drugs that inhibit XDH (e.g. allopurinol). This is termed iatrogenic xanthinuria.

We have identified the causative mutation in Toy Manchester Terriers (Type 2a).  Genetic test results can be used to help guide medical management of affected dogs, identify dogs at risk even before they form stones, and to inform breeding decisions.

Please see the Xanithinuria Result Interpretation document for details on expected outcomes in affected, carrier, and clear dogs as well as breeding guidelines.

What are the clinical signs? 

Xanthinuria leads to the development of urinary stones. This causes irritation that may manifest as straining to urinate, frequent urination, urgency with urination, blood in the urine, or life-threatening urinary obstructions. Microscopic crystals can also accumulate in the kidney and cause kidney disease. Patients with xanthinuria can present at virtually any age from a few months onwards. Though many patients have serious consequences, some remain asymptomatic. Males appear to be more likely to form stones than females.   

How is it managed? 

Once diagnosed, stones can be treated surgically or with other removal techniques, but the disease tends to recur without additional intervention. High fluid intake is important, along with a low purine diet. Therapeutic veterinary low purine diets are available by prescription. Egg, nuts, and dairy are generally low purine sources of protein; foods with high purine content such as liver, kidney, bacon, and most seafood should be avoided. 

Toy Manchester TerrierScientific References

E. Furrow, N. Tate, K. Minor, J. Mickelson, K. Peterson, and J. Lulich. Three diverse mutations underlying canine xanthine urolithiasis. ACVIM Research Report, 2016.
N. Tate, K. Minor, J. Mickelson, K. Peterson, J.P. Lulich, and E. Furrow. Three diverse mutations underlying canine xanthine urolithiasis. ISAG Oral Abstract, 2016.

Canine Genetics Lab Home & Contact Info

Canine Genetics Lab Home & Contact Info


Canine Genetics Lab
University of Minnesota
1988 Fitch Ave
AS/VM 295
St. Paul, MN 55108



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