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Canine Acral Mutilation Syndrome (AMS)
| Acronym: | AMS |
| Gene: | GDNF |
| Mutation: | g.70875561C>T |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Acral mutilation syndrome (AMS) is an inherited canine disorder, which is part of a wider group of disorders, known as Hereditary Sensory Autonomic Neuropathies (HSN). The disorder causes insensitivity to pain and progressive self-mutilation of the distal extremities. AMS is known to affect several dog breeds, including English Cocker Spaniel, French Spaniel, English Springer Spaniel, English Pointer, and German Shorthaired Pointer. AMS is a canine equivalent to Human Hereditary Sensory Autonomic Neuropathies (HSANs), which share the same symptoms. Affected puppies appear smaller than healthy pups in the litter. The age of the onset of the symptoms varies from 2 to 12 months of age. Clinical symptoms include sudden intense licking, biting, and severe self-mutilation of the feet. Wounds developed on paws are a common source of infections, with fungi, E. coli, and Staphylococcus sp. identified as the source of infection. Severe self-mutilation can lead to auto-amputation of the claws, digits, and footpads. Acral changes include swollen reddened paws, soft tissue infection around a fingernail (paronychia), palmar and plantar ulceration, nail loss, painless fractures, and digit amputation. Examination shows no impairment of proprioceptive, somatic motor, or autonomic impairment. Clinical findings confirm that the pathologic process affects primary sensory neurons. Necropsy reveals a reduction in the size of the spinal ganglia.
Acral mutilation syndrome (AMS) is caused by a mutation within a regulatory region of GDNF. Mutation results in decreased levels of GDNF protein. GDNF or Glial cell-derived neurotrophic factor is a small protein that potently promotes the axon development and the survival of many types of neurons. AMS causative mutation disturbs the expression of GDNF, causing the decreased number of sensory neurons and their death. This process could occur during the first months of life, which is in accordance with the early age of onset of AMS-specific insensitivity to pain. AMS is inherited in an autosomal recessive pattern. Healthy parents of affected puppies are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of acral mutilation syndrome (AMS). At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Cummings JF et al (1983): Hereditary sensory neuropathy. Nociceptive loss and acral mutilation in pointer dogs: canine hereditary sensory neuropathy. Am J Pathol 112(1):136-138.
Paradis M et al (2005): Acral mutilation and analgesia in 13 French spaniels. Vet Dermatol 16(2):87-93.
Plassais J, Lagoutte L, Correard S, Paradis M, Guaguère E, HeÂdan B, et al. (2016): A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies. PLoS Genet 12(12): e1006482. doi:10.1371/journal.pgen.1006482.