Lethal Acrodermatitis (LAD) (Bull Terrier)

 

Gene: MKLN1

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, MKLN1 gene; c.400+3 A>C,p.(G105S fs STOP 10), intron 4-5, Chr 14

Medical system: Dermal

Breeds: American Staffordshire Terrier/Amstaff, Bull Terrier, Bull Terrier-Miniature

Age of onset of symptoms: At birth

Lethal acrodermatitis is a genetic disease of Bull Terriers and Miniature Bull Terriers that is characterized by skin lesions of the paws (acro), inflammation of the skin (dermatitis) and mortality (lethal).  Affected newborns will be smaller than their littermates.  The skin lesions consist of inflammation, scales, erosions and ulcerations on the muzzle, elbows and paws.  Puppies can have eating difficulties due to malformations of the head.  The immune system is compromised which makes affected animals more susceptible to infections of the pulmonary and digestive tracts and the skin.  By 8 to12 weeks of age, a thickening of the footpads (hyperkeratosis) can occur that affects the gait of the animal and can cause nail deformation.  Other symptoms include diarrhea as well as cardiac, renal and ocular problems.  Due to multiple infections, LAD dogs will rarely live past two years of age and euthanasia is often the humanitarian option.

 

References:

OMIA link: [2146-9615]

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]

Bauer A, Jagannathan V, Högler S, et al. (2018) MKLN1 splicing defect in dogs with lethal acrodermatitis. PLoS Genet. 14(3):e1007264. [pubmed/29565995]

McEwan NA, McNeil PE, Thompson H, McCandlish IA. (2000) Diagnostic features, confirmation and disease progression in 28 cases of lethal acrodermatitis of bull terriers. J Small Anim Pract. 41(11):501-7. [pubmed/29847795]

 

Contributed by: Marine Rullier, Class of 2020, Faculty of Veterinary Medicine, University of Montreal.