Genetic Test for Primary Hyperparathyroidism in the Keeshond

Primary Hyperparathyroidism (PHPT) is the 1st or 2nd most common cause of pathologic hypercalcemia in dogs. It is caused by an inappropriate secretion of parathyroid hormone (PTH) in the presence of ionized and total hypercalcemia (elevated calcium level) . This results in most cases (80-85%) from a solitary parathyroid adenoma but may also be caused by malignant parathyroid neoplasia (very rare) or parathyroid hyperplasia. The disease is especially concerning from a breed perspective because of the adult to geriatric onset of this condition and our inability to recognize affected dogs prior to breeding. The breed that is by far the most common in large surveys of dogs with PHPT is the Keeshond. In 2001, a review of cases of canine PHPT was published based on samples submitted to the Diagnostic Endocrinology Section, Animal Health Diagnostic Laboratory, Michigan State University. In this review the number of positive cases was reported for each breed, and was compared to the average number of dogs of each breed registered with the American Kennel Club over the years of the study. This data provided the basis for an estimation of an odds ratio for a positive result for each breed. The Keeshond was by far the most likely breed to be affected by PHPT with 214 positive samples and an average registration of 4,375 dogs, yielding an odds ratio of 50.764.

Mild to moderate hypercalcemia may cause no clinical signs obvious to the owner, so this is commonly an incidental finding on geriatric or pre-anesthetic screening blood work. Other signs closely associated with hypercalcemia in dogs and cats include: muscle weakness and lethargy, excessive drinking and urinating, calcium oxalate bladder stones, reduced appetite, weight loss, constipation and vomiting. The treatment of PHPT involves surgical removal or ultrasound guided chemical ablation or heat ablation of the affected parathyroid gland. When performed early in the disease, prior to the onset of renal failure and with appropriate post operative care and monitoring, treatment is typically very successful with a relatively low percentage of reoccurrence. 

The mode of transmission of PHPT in the Keeshond is autosomal dominant. An abnormal gene from one parent is all that is necessary to potentially pass on the disease to the offspring, regardless of whether or not the other parent also carries the PHPT gene.  PHPT affects older Keeshonden with what is known as "age dependent penetrance." This means that the test does not identify clinical disease at the time of testing; it indicates the presence of the defective gene, or the genetic potential to develop the disease later in life. The vast majority of Keeshonden with the defective gene will develop PHPT if they live long enough.

While the PHPT genetic test is beneficial to breeders, a positive test result allows the Keeshond owner to use this knowledge to give their dog the best care possible. Owners should begin to monitor the calcium level of a gene positive dog on a regular schedule, preferably twice a year starting around the age of six.  This will allow their vet to diagnose the disease in its earliest stages, before potential complications occur. Owners should talk with their vet about specialists in their area that treat the disease.

For more information about PHPT or the PHPT genetic test for Keeshonden, visit http://www.vet.cornell.edu/labs/goldstein/ or call (607) 253-4480.