Acral Mutilation Syndrome (AMS)

 

Gene: GDNF-AS

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, GDNF-AS; Chr. 4 g.70875561 C>T, last exon

Medical system: Neurological

Breeds: American Cocker Spaniel, American Staffordshire Terrier/Amstaff, Beagle, Boston Terrier, Boxer, Cavalier King Charles Spaniel, Chihuahua, Cirneco dell'Etna, Coton de Tulear, Dachshund Miniature Longhair/Shorthair, English Cocker Spaniel, English Springer Spaniel, French Spaniel, German Shepherd, German Shorthaired Pointer, Golden Retriever, Irish Terrier, Labrador Retriever, Miniature Pinscher, Newfoundland, Old English Sheepdog, Pointer (English), Pomeranian, Rottweiler, Scandinavian Hound

Age of onset of symptoms: between 3 to 12 months of age

Acral mutilation syndrome (AMS) is a neurological disorder that is characterised by a progressive degeneration of sensory nerves in the paws of affected animals that develops into an insensitivity to pain.   This can result in excessive licking of the paws, self mutilation, painless fractures, ulcerations and infections.  Motor nerves are normal.  Clinical treatment of symptoms are of temporary value, but there are no cures for AMS.   Dogs affected by AMS are often euthanized for humanitarian reasons.

 

References:

OMIA link: [1514-9615]

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]

Correard S, Plassais J, Lagoutte L, Botherel N, et al. (2019) Canine Neuropathies: Powerful Spontaneous Models for Human Hereditary Sensory Neuropathies. Hum Genet. (5):455-466. [pubmed/30955094]

Plassais J, Lagoutte L, Paradis M, et al. (2016)  Point mutation in the upstream region of the neurotrophic factor GNDF linked to a canine insensitivity to pain: a spontaneous model for human sensory neuropathies.  PLOS Genetics 12(12):e1006482. [pubmed/28033318]

Paradis M, de Jaham C, Page N, Sauve F, Helie P. (2005) Acral mutilation and analgesia in 13 French spaniels. Vet Dermatol. [pubmed/15842538]