Muscular Hypertrophy (double muscling)

Gene: MSTN (myostatin)

Transmission: Autosomal co-dominant

Mutation: Deletion, MSTN gene; c.939_940 del. TG, p.(C313 STOP)

Medical system: Muscular

Breeds: Greyhound, Whippet

Age of onset of symptoms: Variable, from birth to 23 months.

Whippet Muscle Hypertrophy Syndrome is a genetic condition whose most striking clinical sign is the excessive size of a dog’s muscles.  The myostatin (MSTN) gene codes for a growth factor that regulates muscle growth; a mutation in the MSTN gene leads to an exaggerated increase in the size and number of muscle fibers as seen in the muscle hypertrophy syndrome.  Affected dogs are often referred to as “Bully Whippets”, hence the origin of the more common name for the condition, “Bully Whippet Syndrome”. Muscular hypertrophy syndrome is transmitted in an autosomal co-dominant fashion: the homozygous dominant individual for the mutated MSTN has excessive muscularity, so much so that it is referred to as “double musculed”.  The exaggerated musculature of the Bully Whippet is to the detriment of the animal’s mobility, and these animals can suffer from muscle cramps in the shoulder and thigh as well as have a jaw overbite. Whippets heterozygous (carriers) for mutated myostatin have a more modestly increased musculature and retain their physical mobility.  These carrier animals can run faster than non-mutated or double-mutated animals, making this heterozygous mutation valuable for Whippet dog racing. Interestingly, the MSTN mutation is selected in racing Whippits, who run short distances, but less so in racing Greyhounds, who must run longer distances.  Mutations in the same MSTN gene are responsible for the double muscling seen in Belgian Blue cattle.

References:

OMIA link: [0683-9615]

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]

Omosule CL, Phillips CL. (2021) Deciphering myostatin’s regulatory, metabolic, and developmental influence in skeletal diseases. Front Genet 12:662908.  [pubmed/33854530]

Aiello D, Patel K, Lasagna E. (2018) The myostatin gene: an overview of mechanisms of action and its relevance to livestock animals. Anim Genet 49:505-19.  [pubmed/30125951]

Mosher DS, Quignon P, Bustamante CD, et al. (2007) A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet 3:e79. [pubmed/17530926]

Contributed by: Giang Mai-Vo, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).