Objectives of the Presentation

 To provide an example of a complex disease where some of the genetic component has been determined.

Overview of the Issue

 Addison's disease is caused by insufficient production of two types of hormones by the adrenal gland. It is thought to be caused by an auto-immune destruction of the hormone producing cells in the adrenal glands.

 Addison's disease is more common in some breeds than in others indicating a genetic component to the disease.

 The disease occurs in the Nova Scotia Duck Tolling Retriever with an incidence of approximately 1.4% (14 times more common than in other breeds). It also occurs at a younger average age of onset (2.6 years compared to 5.5 years) in this breed.

 The underlying genes predisposing dogs to this disease are beginning to be understood and highlight the complex genetic influence on the disease.

 Additional immune mediated diseases occur in this breed and share SOME but not all of the same genetic loci.

Additional Detail

The NSDTR appears susceptible to a number of immune mediated diseases. One is hypoadrenocorticism or Addison's disease, which is caused by a deficiency of mineralocorticoid and glucocorticoid hormones. The clinical presentation of this disease in Tollers is unusual since they seem to get the disease at a younger age (earliest 7 weeks) and they are often (33%) not mineralocorticoid deficient. Unlike other breeds many never become mineralocorticoid deficient. The clinical signs of Addison's disease include lethargy, vomiting, anorexia and weakness. The gold standard of diagnosis for this disease is an ACTH stimulation test and in the case of the Toller this is mandatory since routine blood work can be completely normal.

European Tollers seem more susceptible to two other immune mediated diseases. One is sterile meningitis referred to as Steroid responsive meningitis arteritis (SRMA). These diseases also presents in young dogs (~ 1 year) and the clinical signs are lethargy, neck pain and fever. Ideally a CSF tap would be performed to rule out infectious meningitis. Affected dogs respond to steroid therapy although 33% may have relapse of clinical signs. The third disease is immune mediated polyarthritis (IMPA) or Immune mediated rheumatic disease (IMRD). The clinical signs of this disease include stiffness and joint pain. Many dogs have positive ANA titers. Joint taps show neutrophils in multiple joints and can be used to characterize response to therapy which includes corticosteroids.

Summary

 Selection against complex genetic diseases, while maintaining genetic diversity, will be a challenge for breeders.

References/Suggested Reading

1.  Burton S, DeLay J, Holmes A, Somerville C, Eye J, Shaw D, Wack O, Hanna P: Hypoadrenocorticism in young related Nova Scotia duck tolling retrievers. Can Vet J 1997, 38(4):231-234.

2.  Anfinsen K, Berendt M, Liste F, Haagensen T, Indrebo A, Lingaas F, Stigen O, Alban L: A retrospective epidemiological study of clinical signs and familial predisposition associated with aseptic meningitis in the Norwegian population of Nova Scotia duck tolling retrievers born 1994-2003. Can J Vet Res 2008, 72(4):350-355.

3.  Hughes AM, Nelson RW, Famula TR, Bannasch DL. Clinical features and heritability of hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers: 25 cases (1994-2006). J Am Vet Med Assoc. 2007 Aug 1;231(3):407-12.

4.  Hansson-Hamlin H, Lilliehöök I. A possible systemic rheumatic disorder in the Nova Scotia duck tolling retriever. Acta Vet Scand. 2009 Mar 30;51:16.