Canine Scott Syndrome (CSS)

Gene: ANO6 (TMEM16F)

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, ANO6 gene; c.1934+1 G>A (splicing error)

Medical system: Blood

Breeds: American Staffordshire Terrier/Amstaff, Australian Cattle Dog, Beagle, Belgian Malinois, Chinese Crested, German Shepherd, Great Pyrenees, Labrador Retriever, Presa Canario, Siberian Husky

Age of onset of symptoms: Throughout the animal’s life, often after surgery.

Scott syndrome is an inherited coagulation disorder that causes abnormal bleeding in affected animals. This bleeding can take the form of non-traumatic bleeding into soft tissues or joints, nasal bleeding (epistaxis), and post-surgical bruising and hematomas.  In affected dogs, platelets do not express phosphatidylserine on their membrane surface and are unable to catalyze prothrombin to thrombin, resulting in impaired platelet procoagulant activity.  However, platelet secretion and aggregation remain normal, making the diagnosis of Scott syndrome more complex.  The mutation was first identified in the German Shepherd breed, but a survey of pathological DNA mutations (Donner et al., 2023) demonstrated that the mutation is present in many breeds of dog.  A DNA test for the mutation is now available.

References:

OMIA link: [1353-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Brooks MB, Catalfamo JL, MacNguyen R, et al. (2015) A TMEM16F point mutation causes an absence of canine platelet TMEM16F and ineffective activation and death-induced phospholipid scrambling. J Thromb Haemost 13:2240-52.  [pubmed/26414452]

Jandrey KE, Norris JW, Tucker M, Brooks MB. (2012) Clinical characterization of canine platelet procoagulant deficiency (Scott syndrome). J Vet Intern Med 26:1402-7. [pubmed/22306]

Brooks M, Etter K, Catalfamo J, et al. (2010) A genome-wide linkage scan in German shepherd dogs localizes canine platelet procoagulant deficiency (Scott syndrome) to canine chromosome 27. Gene 450:70-5.  [pubmed/19854246]

Contributed by:  Sara Gauvin and Rosalie Lacasse, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).