Lethal Acrodermatitis affects puppies from birth. Affected puppies show characteristic skin lesions on the feet and on the face, diarrhoea, bronchopneumonia, and a failure to thrive. The skin on the feet becomes hard and cracked and crusted skin lesions and cracks develop on the footpads. Affected puppies typically die before they reach an age of two years, either due to infections such as bronchopneumonia or because they are euthanized when their paw pad lesions become very severe and painful. They grow slower than their non-affected littermates and at the age of one year have about half the body weight and size of an unaffected dog.
The single nucleotide substitution in the gene called MKLN1 that causes lethal acrodermatitis (LAD) in Miniature Bull Terriers and Bull Terriers is recessive. This means that dogs that carry two copies of the mutation (homozygotes) will almost certainly be affected with LAD when they are born. Dogs that carry a single copy of the mutation (also known as carriers or heterozygotes) will not develop LAD as a result of the MKLN1 mutation, but they will pass the mutation onto about half of any offspring they have. Breeding dogs that are not affected with LAD should be the breeder’s priority, with a reduction in mutation frequency within the whole breed being the secondary, longer-term target.
Carriers can be bred from safely, provided they are mated to a dog that has also been tested and is clear of the MKLN1mutation (i.e. carry no copies of the mutation). If a carrier is mated to a clear dog approximately half of the resulting puppies will also be carriers, so should be tested themselves prior to breeding. Breeding carriers to tested, clear dogs is safe, in terms of avoiding dogs affected with LAD, and will help to maintain the genetic diversity of a breed. It is therefore encouraged, particularly in the first few generations following the availability of a new genetic test, so that other desirable characteristics and traits can be preserved before the frequency of the disease mutation within the breed is gradually reduced.