Von Willebrand Disease, type 1 (vWD 1)

 

Gene: VWF

Transmission: Autosomal

Mutation: Substitution, VWF gene; c.7437 G>A; p.(S2479S, fs)

Medical system: Blood

Breeds: American Cocker Spaniel, American Eskimo Dog, American Staffordshire Terrier/Amstaff, Australian Cattle Dog, Australian Kelpie, Australian Shepherd, Barbet, Beagle, Belgian Malinois, Bernese Mountain Dog, Boerboel, Border Collie, Boston Terrier, Boxer, Cairn Terrier, Cardigan Welsh Corgi, Chihuahua, Coton de Tulear, Dachshund Miniature Longhair/Shorthair, Dalmatian, Doberman Pinscher, Dutch Shepherd, English Springer Spaniel, French Bulldog, German Pinscher, German Shepherd, German Shorthaired Pointer, German Spitz, Golden Retriever, Great Dane, Havanese, Keeshond, Kerry Blue Terrier, Labrador Retriever, Lacy Dog, Maltese Terrier, Manchester Terrier, Miniature American Shepherd, Papillon / Continental Toy Spaniel, Pembroke Welsh Corgi, Pomeranian, Poodle - Miniature (Dwarf), Poodle - Standard, Prague Ratter, Pug, Puli, Rottweiler, Schipperke, Schnauzer - Miniature, Shar Pei, Shih Tzu, Siberian Husky, Silky Terrier, Stabyhoun, Staffordshire Bull Terrier, Volpino Italiano, Yorkshire Terrier

Age of onset of symptoms: Following a bleeding injury, regardless of age (average age of diagnosis = 4 years)

Von Willebrand factor (vWF) is a blood glycoprotein that is involved in blood coagulation as it is required for normal platelet adhesion.  Type 1 von Willebrand disease (vWD1) results in a reduction in the quantity of vWF protein due to a specific genetic mutation (c.7437 G>A) within the VWF gene.  Dogs with this mutation can have variable bleeding tendencies that are mild to moderate.  For example, affected dogs may experience excessive, prolonged bleeding after a minor injury, tooth eruption, heat or surgery.  They may also experience sudden bleeding from the gums, nosebleeds, blood in the stool or urine, bruising, and petechiae (small hemorrhages within the skin).  In affected animals the buccal mucosal bleeding time (BMBT) is prolonged while platelet counts and prothrombin times remain normal.  The genetics of canine vWD1 is not fully characterized, and the identified VWF c.7437 G>A mutation, although involved, is only partially responsible for the disease.  Furthermore, the heredity of vWD1 is reported to be dominant (with variable penetration) in some breeds, notably the Doberman Pincher, while recessive in other breeds.  Thus DNA testing for the mutation cannot be counted on to control the disease within a breed.  A recent survey of pathological mutations (Donner et al. 2023) reported the presence of the VWF c.7437 G>A mutation in a large number of dog breeds.

Note the different clinical presentations of von Willebrand Disease, caused by different mutations in the VWF gene:

vWD1     (mild to moderate clinical symptoms)

vWD2     (moderate to severe clinical symptoms)

vWB3     (severe clinical symptoms)

 

References:

OMIA link: [1057-9615]

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]

Haginoya S, Thomovsky EJ, Johnson PA, Brooks AC. (2023) Clinical assessment of primary hemostasis: A review. Top Companion Anim Med :100818.  [pubmed/37673175]

Segert JH, Seidel JM, Wurzer WJ, Geretschlaeger AM. (2019) vWDI is inherited in an autosomal dominant manner with incomplete penetrance, in the Kromfohrländer breed. Canine Genet Epidemiol 6:3. [pubmed/31131110]

Crespi JA, Barrientos LS, Giovambattista G. (2018) von Willebrand disease type 1 in Doberman Pinscher dogs: genotyping and prevalence of the mutation in the Buenos Aires region, Argentina. J Vet Diagn Invest 30:310-314. [pubmed/29271313]

Boudreaux MK. (2012) Inherited platelet disorders. J Vet Emerg Crit Care (San Antonio) 22:30-41. [pubmed/22316339]

 

Contributed by: Emy Beaudoin and Lélia Voyer, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).